INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL

The present invention provides compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.

NOVEL PROLYLCARBOXYPEPTIDASE INHIBITORS

Compounds of structural formula I are inhibitors of prolylcarboxypeptidase (PrCP). The compounds of the present invention are useful for the prevention and treatment of conditions related to the enzymatic activity of PrCP such as abnormal metabolism, including obesity; diabetes; metabolic syndrome; obesity related disorders; and diabetes related disorders. 2. The compound of wherein [{'sup': '5', '(1) —NR, and'}, '(2) —CH—;, 'X is selected from the group consisting of [{'sup': '6', '(1) —NR, and'}, {'sub': '2', '(2) —CH—;'}], 'Y is selected from the group consisting of (1) —O—, and', {'sub': '2', '(2) —CH—,'}], 'Z is selected from the group consisting of{'sub': 2', '2', '2, 'sup': '5', 'provided that one of X and Y is —CH—, further provided that one of X, Y and Z is not —CH—, and further provided that if X is —NRor —O—, then Z is —CH—;'}or a pharmaceutically acceptable salt thereof.3. The compound of wherein Ris hydrogen; or a pharmaceutically acceptable salt thereof.4. The compound of wherein Ris heteroaryl claim 1 , wherein heteroaryl is unsubstituted or substituted with one to three substituents selected from R; or a pharmaceutically acceptable salt thereof.5. The compound of wherein Ris pyrimidine claim 4 , wherein pyrimidine is unsubstituted or substituted with one to three substituents selected from R; or a pharmaceutically acceptable salt thereof.8. The compound of wherein Ris aryl claim 1 , wherein aryl is unsubstituted or substituted with one to three substituents selected from R; or a pharmaceutically acceptable salt thereof.9. The compound of wherein Ris phenyl claim 8 , wherein phenyl is unsubstituted or substituted with one to three substituents selected from R; or a pharmaceutically acceptable salt thereof.14. The compound of wherein{'sup': '1', 'claim-text': (1) hydrogen,', '(2) oxo, and', {'sub': 2', 'm, '(3) —(CH)aryl,'}], 'Ris selected from the group consisting of{'sub': '2', 'sup': 'a', 'wherein each CH, and aryl is unsubstituted or substituted ...

Inhibitors of the renal outer medullary potassium channel

The present invention provides compounds of Formula I (I) and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.

Prolylcarboxypeptidase inhibitors

Compounds of structural formula I are inhibitors of prolylcarboxypeptidase (PrCP). The compounds of the present invention are useful for the prevention and treatment of conditions related to the enzymatic activity of PrCP such as abnormal metabolism, including obesity; diabetes; metabolic syndrome; obesity related disorders; and diabetes related disorders.

METALLO-BETA-LACTAMASE INHIBITORS

The present invention relates to metallo-β-lactamase inhibitor compounds of Formula I:

NOVEL CYCLIC BENZIMIDAZOLE DERIVATIVES USEFUL AS ANTI-DIABETIC AGENTS

Novel compounds of the structural formula (I) are activators of AMP-protein kinase and are useful in the treatment, prevention and suppression of diseases mediated by the AMPK-activated protein kinase. The compounds of the present invention are useful in the treatment of Type 2 diabetes, hyperglycemia, metabolic syndrome, obesity, hypercholesterolemia, and hypertension.

INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL

The present invention provides compounds of Formula I (I) and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.

Inhibitors of the Renal Outer Medullary Potassium Channel

The present invention provides compounds of Formula Ia and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and conditions associated with excessive salt and water retention.

Antagonists of gonadotropin releasing hormone

Antagonists of gonadotropin releasing hormone

Hydroisoindoline tachykinin receptor antagonists

The present invention is directed to certain hydroisoindoline compounds which are useful as neurokinin-1 (NK-1) receptor antagonists, and inhibitors of tachykinin and in particular substance P. The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including emesis, urinary incontinence, depression, and anxiety.

Metallo-beta-lactamase inhibitors

The present invention relates to compounds of formula (I) that are metallo-β-lactamase inhibitors, the synthesis of such compounds, and the use of such compounds for use with β-lactam antibiotics for overcoming resistance.

Inhibitors of the renal outer medullary potassium channel

The present invention provides compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure, kidney disease, edema, and conditions associated with excessive salt and water retention.

INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL

The present invention provides compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention. 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —H claim 1 , —F or —OH.3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein each of Rand Rare —H.4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —H or —Calkyl.5. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —H.6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —H claim 1 , —Cl claim 1 , —CHor cyclopropyl.7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —H.8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —CH.14. A compound which is:8-(2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,3,8-triazaspiro[4.5]decan-1-one;(R)-8-(2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,3,8-triazaspiro[4.5]decan-1-one;8-(2-(6-(1H-tetrazol-1-yl)pyridin-3-yl)-2-hydroxyethyl)-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,3,8-triazaspiro[4.5]decan-1-one;(R)-8-(2-(6-(1H-tetrazol-1-yl)pyridin-3-yl)-2-hydroxyethyl)-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,3,8-triazaspiro[4.5]decan-1-one;(S)-8-(2-(6-(1H-tetrazol-1-yl)pyridin-3-yl)-2-hydroxyethyl)-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,3,8-triazaspiro[4.5]decan-1-one;8-(2-(6-(1H-tetrazol-1-yl)pyridin-3-yl)-2-hydroxyethyl)-2-(4- ...

Metallo-beta-lactamase inhibitors

The present invention relates to metallo-β-lactamase inhibitor compounds of Formula I: and pharmaceutically acceptable salts thereof, wherein Z, RA, X1, X2and R1are as defined herein. The present invention also relates to compositions which comprise a metallo-β-lactamase inhibitor compound of the invention or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, optionally in combination with a beta lactam antibiotic and/or a beta-lactamase inhibitor. The invention further relates to methods for treating a bacterial infection comprising administering to a patient a therapeutically effective amount of a compound of the invention, in combination with a therapeutically effective amount of one or more β-lactam antibiotics and optionally in combination with one or more beta-lactamase inhibitor compounds. The compounds of the invention are useful in the methods described herein for overcoming antibiotic resistance.

INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIM CHANNEL

The present invention provides compounds of Formula (I) (Formula (I)) including pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.

SPIRO - FUSED PIPERIDINE DERIVATIVES FOR USE AS INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL

METALLO-BETA-LACTAMASE INHIBITORS

The present invention relates to compounds of formula (I) that are metallo-β-lactamase inhibitors, the synthesis of such compounds, and the use of such compounds for use with β-lactam antibiotics for overcoming resistance.

BIARYL MONOBACTAM COMPOUNDS AND METHODS OF USE THEREOF FOR THE TREATMENT OF BACTERIAL INFECTIONS

The present invention relates to biaryl monobactam compounds of Formula I: and pharmaceutically acceptable salts thereof, wherein X, Y, Z, A, Q, M, W, Rand Rare as defined herein. The present invention also relates to compositions which comprise a biaryl monobactam compound of the invention or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. The invention further relates to methods for treating a bacterial infection comprising administering to the patient a therapeutically effective amount of a compound of the invention, either alone or in combination with a therapeutically effective amount of a second beta-lactam antibiotic. 4. The compound of claim 3 , or a pharmaceutically acceptable salt thereof claim 3 , wherein Rand Rare independently hydrogen claim 3 , C-Calkyl claim 3 , tetrazolyl claim 3 , oxadiazolonyl or —C(O)OR; and Ris hydrogen.5. The compound of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein X is N.6. The compound of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein X is CR.8. The compound of any of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein Ais HetC or a 5- to 6-membered monocyclic aromatic ring with 1 claim 2 , 2 claim 2 , or 3 ring atoms independently selected from N claim 2 , N as a quaternary salt claim 2 , O and S claim 2 , optionally substituted with one to four R.10. The compound of any of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein M is —(CH)Ror R.11. The compound of any of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein M is C-Calkyl substituted with —NRR.12. The compound of any of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein Rand Rare methyl claim 2 , or Ris methyl and Ris hydrogen.14. A trifluoroacetic acid salt of the compound of .15. A trifluoroacetic acid salt of the compound of .16. A pharmaceutical composition comprising a ...

Cyclic benzimidazole derivatives useful as anti-diabetic agents

Novel compounds of the structural formula (I) are activators of AMP-protein kinase and are useful in the treatment, prevention and suppression of diseases mediated by the AMPK-activated protein kinase. The compounds of the present invention are useful in the treatment of Type 2 diabetes, hyperglycemia, metabolic syndrome, obesity, hypercholesterolemia, and hypertension.

Inhibitors of the renal outer medullary potassium channel

The present invention provides compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.

Hydroisoindoline tachykinin receptor antagonists

The present invention is directed to certain hydroisoindoline compounds which are useful as neurokinin-1 (NK-1) receptor antagonists, and inhibitors of tachykinin and in particular substance P. The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including emesis, urinary incontinence, depression, and anxiety.

Indazole derivatives useful as inhibitors of diacylglyceride O-acyltransferase 2

The present invention relates to a compound represented by formula I′: and pharmaceutically acceptable salts thereof. The compounds of formula I are inhibitors of diacylglyceride O-acyltransferase 2 (“DGAT2”) and may be useful in the treatment, prevention and suppression of diseases mediated by DGAT2. The compounds of the present invention may be useful in the treatment of hepatic steatosis, diabetes mellitus, obesity, hyperlipidemia, hypercholesterolemia, atherosclerosis, cardiorenal diseases such as chronic kidney diseases and heart failure and related diseases and conditions.

Inhibitors of the renal outer medullary potassium channel

The present invention provides compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.

Inhibitors of the renal outer medullary potassim channel

The present invention provides compounds of Formula (I) (Formula (I)) including pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.

NOVEL PROLYLCARBOXYPEPTIDASE INHIBITORS

Compounds of structural formula I are inhibitors of prolylcarboxypeptidase (PrCP). The compounds of the present invention are useful for the prevention and treatment of conditions related to the enzymatic activity of PrCP such as abnormal metabolism, including obesity; diabetes; metabolic syndrome; obesity related disorders; and diabetes related disorders.

Octahydropyrano[3,4-C]pyrrole tachykinin receptor antagonists

The present invention is directed to certain hydropyranopyrrolidine compounds which are useful as neurokinin-1 (NK-1) receptor antagonists, and inhibitors of tachykinin and in particular substance P. The invention is also concerned with pharmaceutical formations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including emesis, urinary incontinence, depression, and anxiety.

Inhibitors of the renal outer medullary potassium channel

The present invention provides compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and conditions associated with excessive salt and water retention.

HYDROXYMETHYL ETHER HYDROISOINDOLINE TACHYKININ RECEPTOR ANTAGONISTS

The present invention is directed to certain hydroxymethyl ether hydroisoindoline compounds which are useful as neurokinin-1 (NK-1) receptor antagonists, and inhibitors of tachykinin and in particular substance P. The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including emesis, urinary incontinence, LUTS, depression, and anxiety.

5-Phenyl-5,6,7,8-Hydroquinoline Tachykinin Receptor Antagonists

The present invention is directed to certain 5-phenyl-5,6,7,8-hydroquinoline compounds which are useful as neurokinin-1 (NK-1) receptor antagonists, and inhibitors of tachykinin and in particular substance P. The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including emesis, urinary incontinence, depression, and anxiety.

8-Phenyl-5,6,7,8-Hydroquinoline Tachykinin Receptor Antagonists

The present invention is directed to certain 8-phenyl-5,6,7,8-hydroquinolinecompounds which are useful as neurokinin-1 (NK-1) receptor antagonists, and inhibitors of tachykinin and in particular substance P. The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including emesis, urinary incontinence, depression, and anxiety.

Hydroisoindoline tachykinin receptor antagonists

The present invention is directed to certain hydroisoindoline compounds which are useful as neurokinin-1 (NK-1) receptor antagonists, and inhibitors of tachykinin and in particular substance P. The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including emesis, urinary incontinence, depression, and anxiety.

METALLO-BETA-LACTAMASE INHIBITORS AND METHODS OF USE THEREOF

The present invention relates to metallo-β-lactamase inhibitor compounds of Formula I: and pharmaceutically acceptable salts thereof, wherein R, R, and Z are as defined herein. The present invention also relates to compositions which comprise a metallo-β-lactamase inhibitor compound of the invention or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, optionally in combination with a beta lactam antibiotic and/or a beta-lactamase inhibitor. The invention further relates to methods for treating a bacterial infection comprising administering to a patient a therapeutically effective amount of a compound of the invention, in combination with a therapeutically effective amount of one or more β-lactam antibiotics and optionally in combination with one or more beta-lactamase inhibitor compounds. The compounds of the invention are useful in the methods described herein for overcoming antibiotic resistance. 5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris{'sub': 2', '4', '2, 'a) —N(H)—C-Calkyl, optionally substituted with 1, 2, or 3, substituents independently selected from: —NHand OH;'}{'sub': 2', '4', '2, 'b) —C-Calkyl, optionally substituted with 1, 2, or 3, substituents independently selected from —NHand OH; or'}c) —N(H)-HetB1, wherein HetB1 is azetidinyl, pyrrolidinyl, or piperidinyl;7. (canceled)9. A pharmaceutical composition which comprises a compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable carrier.10. The pharmaceutical composition according to claim 9 , which further comprises an effective amount of a beta-lactam antibiotic.11. The pharmaceutical composition according to which further comprises an effective amount of one or more beta-lactamase inhibitor compounds.12. The pharmaceutical composition according to claim 11 , wherein the beta-lactamase inhibitor compound is selected from the group consisting of: ...

Hydroisoindoline tachykinin receptor antagonists

The present invention is directed to certain hydroisoindoline compounds of formula I which are useful as neurokinin-1 (NK-1) receptor antagonists, and inhibitors of tachykinin and in particular substance P. The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including emesis, urinary incontinence, depression, and anxiety.

Cyclic azabenzimidazole derivatives useful as anti-diabetic agents

Novel compounds of structural formula (I) are activators of AMP-protein kinase and are useful in the treatment, prevention and suppression of diseases mediated by the AMPK-activated protein kinase. The compounds of the present invention are useful in the treatment of Type 2 diabetes, hyperglycemia, metabolic syndrome, obesity, hypercholesterolemia, and hypertension.

Hydroisoindoline tachykinin receptor antagonists

The present invention is directed to certain hydroisoindoline compounds which are useful as neurokinin-1 (NK-1) receptor antagonists, and inhibitors of tachykinin and in particular substance P. The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including emesis, urinary incontinence, depression, and anxiety.

INDOLE DERIVATIVES USEFUL AS INHIBITORS OF DIACYLGLYCERIDE O-ACYLTRANSFERASE 2

The present invention relates to a compound represented by formula I: and pharmaceutically acceptable salts thereof. The compounds of formula I are inhibitors of diacylglyceride O-acyltransferase 2 (“DGAT2”) and may be useful in the treatment, prevention and suppression of diseases mediated by DGAT2. The compounds of the present invention may be useful in the treatment of hepatic steatosis, diabetes mellitus, obesity, hyperlipidemia, hypercholesterolemia, atherosclerosis, nonalcoholic steatohepatitis (NASH), cardiorenal diseases such as chronic kidney diseases and heart failure and related diseases and conditions. 2. The compound of claim 1 , wherein Ris —(C)alkyl-O—(C)alkyl; a 5- to 7-membered heterocyclyl containing 1 or 2 heteroatoms independently selected from N claim 1 , O claim 1 , and S claim 1 , wherein the heterocyclyl is unsubstituted or substituted by 1-3 R; or —(C)alkyl-heterocyclyl containing 1 or 2 heteroatoms independently selected from N claim 1 , O claim 1 , and S claim 1 , and wherein the heterocyclyl is a 5- to 7-membered ring.9. A compound selected from the group consisting of(1) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1H-indole-6-carboxamide,(2) 3-(2-Chlorophenyl)-N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorophenyl)-1H-indole-6-carboxamide,(3) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-(1-methoxypropan-2-yl)-1H-indole-6-carboxamide,(4) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-(2-methyl-1-morpholinopropan-2-yl)-1H-indole-6-carboxamide,(5) (S)-3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-(2-hydroxy-1-(6-(trifluoromethyl)pyridin-3-yl)ethyl)-1H-indole-6-carboxamide,(6) (S)-3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-(1-(6-(trifluoromethyl)pyridin-3-yl)ethyl)-1H-indole-6-carboxamide(7) (R)-3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-(1-(6-(trifluoromethyl)pyridin-3-yl)ethyl)-1H-indole-6-carboxamide,(8) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-2-methyl-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1H-indole-6- ...

METALLO-BETA-LACTAMASE INHIBITORS

The present invention relates to metallo-beta-lactamase inhibitor compounds of Formula I: and pharmaceutically acceptable salts thereof, wherein Z, R, X, Xand Rare as defined herein. The present invention also relates to compositions which comprise a metallo-beta-lactamase inhibitor compound of the invention or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, optionally in combination with a beta-lactam antibiotic and/or a beta-lactamase inhibitor. The invention further relates to methods for treating a bacterial infection comprising administering to a patient a therapeutically effective amount of a compound of the invention, in combination with a therapeutically effective amount of one or more β-lactam antibiotics and optionally in combination with one or more beta-lactamase inhibitor compounds. The compounds of the invention are useful in the methods described herein for overcoming antibiotic resistance. 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Xand Xare CH.4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris AryA1.6. The compound of claim 4 , or a pharmaceutically acceptable salt thereof claim 4 , wherein AryA1 is 1) pyridyl optionally substituted with —NH claim 4 , 2) benzoimidazolyl substituted with 1 or 2 substituents independently selected from F claim 4 , —CHand —(CH)NH; or 3) benzothiazolyl substituted with 1 or 2 substituents independently selected from —CHand —(CH)NH.7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris:{'sub': '2', '1) —NH;'}{'sup': a', 'a', 'b', 'a', 'b', '+', 'a', 'b', 'a', 'a, 'sub': 1', '6', '3', '1', '6', '2', '2', '2', '1-2', '2', '3', '2', '2', '3', '2', '2-3', '2', '2', '2-3', '2, '2) —NR—C-Calkyl optionally substituted with 1, 2, 3 or 4 substituents independently selected from —F, —CF, C-Calkyl, —CH(NH)C(O)NH, —C(O)NRR, —C(O)OH, —(CH)NH, —NRR, —NRRCH, — ...

INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL

The present invention provides compounds of Formula I: (I) and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention. 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Xis —C(O)—.3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Xis —CH—.4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —H claim 1 , —F or —OH.5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein each of Rand Rare —H.6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —H or —Calkyl.7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —H.8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —H claim 1 , —Cl claim 1 , —CHor cyclopropyl.9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —H.10. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —CH.15. A compound which is:7-(2-hydroxy-2-(2-methyl-6-(1H-tetrazol-1-yl)pyridin-3-yl)ethyl)-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,7-diazaspiro[3.5]nonan-1-one;4-(2-(2-(6-(1H-tetrazol-1-yl)pyridin-3-yl)-2-hydroxyethyl)-2,7-diazaspiro[4.5]decan-7-yl)furan-2(5H)-one;8-(2-(5-(1H-tetrazol-1-yl)pyrazin-2-yl)-2-hydroxyethyl)-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.6]undecan-1-one;8-(2-hydroxy-2-(2-methyl-6-(1H-tetrazol-1-yl)pyridin-3-yl)ethyl)-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.6]undecan-1-one;8-(2-(5-(1H-tetrazol-1- ...

NOVEL CYCLIC BENZIMIDAZOLE DERIVATIVES USEFUL ANTI-DIABETIC AGENTS

Novel compounds of the structural formula (I) are activators of AMP-protein kinase and are useful in the treatment, prevention and suppression of diseases mediated by the AMPK-activated protein kinase. The compounds of the present invention are useful in the treatment of Type 2 diabetes, hyperglycemia, metabolic syndrome, obesity, hypercholesterolemia, and hypertension. 4. The compound according to claim 1 , wherein Ris biphenyl claim 1 , wherein biphenyl is unsubstituted or substituted with 1 claim 1 , 2 or 3 substituents independently selected from R; or a pharmaceutically acceptable salt thereof.5. The compound according to claim 4 , wherein Ris halogen; or a pharmaceutically acceptable salt thereof.6. The compound according to claim 1 , wherein Y is —Ccycloalkyl claim 1 , wherein cycloalkyl is unsubstituted or substituted with 1 claim 1 , 2 claim 1 , 3 or 4 substituents selected from R; or a pharmaceutically acceptable salt thereof.9. The compound according to claim 1 , wherein RS is hydrogen; or a pharmaceutically acceptable salt thereof.11. The compound according to claim 10 , wherein Z is —COH; or a pharmaceutically acceptable salt thereof.13. The compound according to claim 12 , wherein Ris hydrogen or halogen claim 12 , and Ris hydrogen; or a pharmaceutically acceptable salt thereof.21. A composition comprising a compound according to and a pharmaceutically acceptable carrier.22. A composition comprising a compound according to and a compound selected from simvastatin claim 1 , ezetimibe claim 1 , taranabant and sitagliptin; and a pharmaceutically acceptable carrier.23. (canceled)24. (canceled)25. (canceled)26. (canceled)27. A method of treating a disorder claim 1 , condition or disease responsive to the activation of AMP-activated protein kinase in a patient in need thereof comprising administration of a therapeutically effective amount of a compound according to .28. The method of wherein the disorder claim 27 , condition claim 27 , or disease is selected ...

Bicyclic aryl monobactam compounds and methods of use thereof for the treatment of bacterial infections

The present invention relates to bicyclic aryl monobactam compounds of Formula (I), and pharmaceutically acceptable salts thereof, wherein A1, L, M, W, X, Y, Z, RXand Rzare as defined herein. The present invention also relates to compositions which comprise a bicyclic aryl monobactam compound of the invention or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. The invention further relates to methods for treating a bacterial infection comprising administering to the patient a therapeutically effective amount of a compound of the invention, either alone or in combination with a therapeutically effective amount of one or more beta-lactamase inhibitor compounds.

PREPARATION OF TETRAHYDROINDAZOLE DERIVATIVES AS NOVEL DIACYLGLYCERIDE O-ACYLTRANSFERASE 2 INHIBITORS

Invented are compounds of formula I and the pharmaceutically acceptable salts, esters, and prodrugs thereof, which are DGAT2 inhibitors. Also provided are methods of making compounds of Formula I, pharmaceutical compositions comprising compounds of Formula I, and methods of using these compounds to treat hepatic steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, type-2 diabetes mellitus, obesity, hyperlipidemia, hypercholesterolemia, atherosclerosis, cognitive decline, dementia, cardiorenal diseases such as chronic kidney diseases and heart failure and related diseases and conditions, comprising administering a compound of Formula I to a patient in need thereof.

Prolylcarboxypeptidase inhibitors

Compounds of structural formula I are inhibitors of prolylcarboxypeptidase (PrCP). The compounds of the present invention are useful for the prevention and treatment of conditions related to the enzymatic activity of PrCP such as abnormal metabolism, including obesity; diabetes; metabolic syndrome; obesity related disorders; and diabetes related disorders.

BIARYL MONOBACTAM COMPOUNDS AND METHODS OF USE THEREOF FOR THE TREATMENT OF BACTERIAL INFECTIONS

The present invention relates to biaryl monobactam compounds of Formula I 4. The compound of claim 3 , or a pharmaceutically acceptable salt thereof claim 3 , wherein Rand Rare independently hydrogen claim 3 , C-Calkyl claim 3 , tetrazolyl claim 3 , oxadiazolonyl or —C(O)OR; and Ris hydrogen.5. The compound of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein X is N.6. The compound of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein X is CR.8. The compound of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein Ais HetC or a 5- to 6-membered monocyclic aromatic ring with 1 claim 2 , 2 claim 2 , or 3 ring atoms independently selected from N claim 2 , N as a quaternary salt claim 2 , O and S claim 2 , optionally substituted with one to four R.9. (canceled)10. The compound of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein M is —(CH)Ror R.11. The compound of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein M is C-Calkyl substituted with —NRR.12. The compound of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein Rand Rare methyl claim 2 , or Ris methyl and Ris hydrogen.14. A trifluoroacetic acid salt of the compound of .15. A trifluoroacetic acid salt of the compound of .16. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable carrier.17. A pharmaceutical composition according to claim 16 , which further comprises a therapeutically effective amount of a beta-lactamase inhibitor compound.18. A pharmaceutical composition according to claim 17 , wherein the beta-lactamase inhibitor compound is selected from the group consisting of relebactam claim 17 , tazobactam claim 17 , clavulanic acid claim 17 , sulbactam claim 17 , and avibactam.19. A method for treating a bacterial infection ...

NOVEL CYCLIC AZABENZIMIDAZOLE DERIVATIVES USEFUL AS ANTI-DIABETIC AGENTS

Novel compounds of structural formula (I) are activators of AMP-protein kinase and are useful in the treatment, prevention and suppression of diseases mediated by the AMPK-activated protein kinase. The compounds of the present invention are useful in the treatment of Type 2 diabetes, hyperglycemia, metabolic syndrome, obesity, hypercholesterolemia, and hypertension. 2. The compound according to wherein:{'sup': '3', 'T is selected from the group consisting of: CR, N and N-oxide;'}{'sup': '1', 'U is selected from the group consisting of: CR, N and N-oxide;'}{'sup': '2', 'V is selected from the group consisting of: CR, N and N-oxide;'}{'sup': '4', 'W is selected from the group consisting of: CR, N and N-oxide,'}provided that at least one of T, U, V and W is N or N-oxide; [{'sub': '2', '(1) —CH—,'}, '(2) —CHF—,', {'sub': '2', '(3) —CF—,'}, '(4) —S—,', '(5) —O—,', {'sub': '2', '(6) —O—CH—,'}, '(7) —NH—,', '(8) —C(O)—,', '(9) —NHC(O)—,', '(10) —C(O)NH—,', {'sub': '2', '(11) —NHSO—,'}, {'sub': '2', '(12) —SONH—, and'}, {'sub': '2', '(13) —CO—,'}], 'X is absent or selected from{'sub': 2', '2', '1-6', '2', '2', '1-6', '1-6', '2', '1-6', '2', '2', '1-6', '1-6', '2, 'wherein each CHis unsubstituted or substituted with 1 or 2 substituents selected from: hydroxy, halogen, NH, Calkyl, COH, COCalkyl, COCalkyl, phenyl and —CH-phenyl, and wherein each NH is unsubstituted or substituted with 1 substituent selected from: Calkyl, COH, COCalkyl, COCalkyl, phenyl and —CH-phenyl;'} [{'sub': '3-10', '(1) Ccycloalkyl,'}, {'sub': '3-10', '(2) Ccycloalkenyl,'}, {'sub': '2-10', '(3) Ccycloheteroalkyl,'}, {'sub': '2-10', '(4) Ccycloheteroalkenyl,'}, '(5) aryl, and', '(6) heteroaryl,, 'Y is selected from{'sup': 'b', 'wherein cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, aryl and heteroaryl are unsubstituted or substituted with 1, 2, 3 or 4 substituents selected from R;'} (1) oxo,', '(2) —CN,', {'sub': '3', '(3) —CF,'}, {'sub': '1-6', '(4) —Calkyl,'}, {'sub': 2', 't, '(5) —(CH)- ...

Inhibitors of the renal outer medullary potassium channel

Novel spirocyclic compounds of formula I: and pharmaceutically acceptable salts thereof are disclosed as inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention. Pharmaceutical compositions and methods of treatment are also included.

Inhibitors of the renal outer medullary potassium channel

The present invention provides compounds of Formula (I) and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.

Inhibitors of the renal outer medullary potassium channel

The present invention provides compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.

Hydroisoindoline tachykinin receptor antagonists

The present invention is directed to certain hydroisoindoline compounds which are useful as neurokinin-1 (NK-1) receptor antagonists, and inhibitors of tachykinin and in particular substance P. The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including emesis, urinary incontinence, depression, and anxiety.

INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL

The present invention provides compounds of Formula I 8. The compound of or a pharmaceutically acceptable salt thereof wherein:{'sup': 1', '2', '3', '4', '4', '1', '2', '3', '4, 'X, X, Xand Xare each independently selected from C(R) or N; provided that at least one and at most two of X, X, Xand Xis N;'}{'sup': '4', 'sub': '1-4', 'each Ris independently —H or —Calkyl optionally substituted with 1-3 of —F;'}{'sup': '2', 'sub': 1-3', '1-3, 'Ris —H, ═O, —OH, —Calkyl or —OCalkyl;'}{'sup': '2a', 'sub': 3-4', '1-3', '3, 'Ris —H, —Ccycloalkyl or —Calkyl optionally substituted with —OCHor 1 to 3 of —F;'}{'sup': 3b', '3b, 'sub': '1-3', 'Ris —H or —Calkyl, or Ris absent when the dashed bond is a double bond;'}{'sup': '5', 'sub': '3', 'Ris —H or —CH;'}{'sup': '6', 'sub': '3', 'Ris —H or —CH;'}{'sup': '7', 'sub': 3', '2, 'Ris —H, —CHor —CHOH;'}{'sup': '8', 'sub': '3', 'Ris —H or —CH;'}{'sup': '9', 'sub': 1-3', '1-3, 'Ris —H, —F, —OH, —Calkyl, —OCalkyl; and'}the dashed bond (“ - - - ”) represents a single or double bond provided that:(i) when m is 1, then the dashed bond is a single bond; and{'sup': '2', '(ii) when m is zero and Ris not ═O, then the dashed bond is a double bond.'}9. The compound of selected from:8-{(2R)-2-hydroxy-2-[6-(1H-tetrazol-1-yl)pyridin-3-yl]ethyl}-1-oxo-2-(5-oxo-2,5-dihydrofuran-3-yl)-2-aza-8-azoniaspiro[4.5]decane,8-{(2S)-2-hydroxy-2-[6-(1H-tetrazol-1-yl)pyridin-3-yl]ethyl}-1-oxo-2-(5-oxo-2,5-dihydrofuran-3-yl)-2-aza-8-azoniaspiro[4.5]decane, single isomer,8-{(2R)-2-hydroxy-2-[2-methyl-6-(1H-tetrazol-1-yl)pyridin-3-yl]ethyl}-1-oxo-2-(5-oxo-2,5-dihydrofuran-3-yl)-2-aza-8-azoniaspiro[4.5]decane,8-{(2S)-2-hydroxy-2-[2-methyl-6-(1H-tetrazol-1-yl)pyridin-3-yl]ethyl}-1-oxo-2-(5-oxo-2,5-dihydrofuran-3-yl)-2-aza-8-azoniaspiro[4.5]decane,8-{(2S)-2-hydroxy-2-[6-methyl-5-(1H-tetrazol-1-yl)pyridin-2-yl]ethyl}-1-oxo-2-(5-oxo-2,5-dihydrofuran-3-yl)-2-aza-8-azoniaspiro[4.5]decane,8-{(2R)-2-hydroxy-2-[4-methyl-5-(1H-tetrazol-1-yl)pyridin-2-yl]ethyl}-1-oxo-2-(5-oxo-2,5- ...

Hydroxymethyl ether hydroisoindoline tachykinin receptor antagonists

The present invention is directed to certain hydroxymethyl ether hydroisoindoline compounds which are useful as neurokinin-1 (NK-1) receptor antagonists, and inhibitors of tachykinin and in particular substance P. The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including emesis, urinary incontinence, LUTS, depression, and anxiety.

Packaging box

METALLO-BETA-LACTAMASE INHIBITORS

The present invention relates to metallo-β-lactamase inhibitor compounds of Formula I: (I) and pharmaceutically acceptable salts thereof, wherein Z, R, X, Xand Rare as defined herein. The present invention also relates to compositions which comprise a metallo-β-lactamase inhibitor compound of the invention or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, optionally in combination with a beta lactam antibiotic and/or a beta-lactamase inhibitor. The invention further relates to methods for treating a bacterial infection comprising administering to a patient a therapeutically effective amount of a compound of the invention, in combination with a therapeutically effective amount of one or more β-lactam antibiotics and optionally in combination with one or more beta-lactamase inhibitor compounds. The compounds of the invention are useful in the methods described herein for overcoming antibiotic resistance. 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Xand Xare CH.4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris AryA1.6. The compound of claim 4 , or a pharmaceutically acceptable salt thereof claim 4 , wherein AryA1 is 1) pyridyl optionally substituted with —NH claim 4 , 2) benzoimidazolyl optionally substituted with 1 or 2 substituents independently selected from F claim 4 , —CHand —(CH)NH; or 3) benzothiazolyl optionally substituted with 1 or 2 substituents independently selected from —CHand —(CH)NH.7. The compound of claim 1 , wherein Ris: HetB1 or C-Calkyl optionally substituted with 1 or 2 substituents independently selected from —NRR claim 1 , —OH claim 1 , and cyclopropyl.9. (canceled)11. A zwitterion of the compound of .12. A pharmaceutical composition which comprises a compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable carrier.13. The pharmaceutical ...

NOVEL SPIROPIPERIDINE PROLYLCARBOXYPEPTIDASE INHIBITORS

Compounds of structural formula (I) are inhibitors of prolylcarboxypeptidase (PrCP). The compounds of the present invention are useful for the prevention and treatment of conditions related to enzymatic activity of PrCP such as abnormal metabolism, including obesity; diabetes; metabolic syndrome; obesity related disorders; and diabetes related disorders. 3. The compound of wherein T is N and U claim 1 , V and W are CH; or wherein T claim 1 , U claim 1 , V and W are CH; or a pharmaceutically acceptable salt thereof.9. The compound of wherein Ris hydrogen; or a pharmaceutically acceptable salt thereof.11. The compound of wherein Ris hydrogen; or a pharmaceutically acceptable salt thereof.14. The compound of wherein (1) CH, and', '(2) N,, 'each T, U, V and W is independently selected from the group consisting ofprovided that at least three of T, U, V and W are CH; [{'sub': '2', '(1) —CH—,'}, {'sub': 2', '2, '(2) —CHCH—, and'}, {'sub': '2', '(3) —SO—,'}], 'each X is independently selected from the group consisting of{'sub': '2', 'sup': 'a', 'wherein each CHis unsubstituted or substituted with one or two substituents selected from R;'}{'sup': '1', 'claim-text': [{'sub': '3-7', '(1) —Ccycloalkyl,'}, '(2) -aryl, and', '(3) -heteroaryl,, 'each Ris independently selected from the group consisting of{'sup': 'b', 'wherein each cycloalkyl, aryl and heteroaryl is unsubstituted or substituted with one to three groups independently selected from R;'}{'sup': '2', 'claim-text': (1) hydrogen,', {'sub': '1-6', '(2) —Calkyl,'}, '(3) oxo, and', '(4) —OH;, 'each Ris independently selected from the group consisting of{'sup': '3', 'claim-text': (1) -aryl, and', '(2) -heteroaryl,, 'each Ris independently selected from the group consisting of{'sup': 'c', 'wherein each aryl and heteroaryl is unsubstituted or substituted with one to three groups independently selected from R;'}{'sup': '4', 'claim-text': (1) hydrogen,', '(2) halogen, and', {'sub': '1-6', '(3) —Calkyl,'}], 'each Ris ...

Octahydropyrano[3,4-C]Pyrrole Tachykinin Receptor Antagonists

The present invention is directed to certain hydropyranopyrrolidine compounds which are useful as neurokinin-1 (NK-1) receptor antagonists, and inhibitors of tachykinin and in particular substance P. The invention is also concerned with pharmaceutical formations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including emesis, urinary incontinence, depression, and anxiety.

INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL

The present invention provides compounds of Formula I 3. The compound of or a pharmaceutically acceptable salt thereof wherein: Ris —H or —CH; Ris ═O; Ris —H or —CH; Ris —H or CH; Ris —H claim 2 , —OH claim 2 , —OCHor —NH; and Ris —H or —CH.4. The compound of or a pharmaceutically acceptable salt thereof wherein Ris —OH; and Ris —CH.6. The compound of or a pharmaceutically acceptable salt thereof wherein: Ris —H or —CH; Ris ═O; Ris —H or —CH; Ris —H or CH; Ris —H claim 5 , —OH claim 5 , —OCHor —NH; and Ris —H or —CH.7. The compound of or a pharmaceutically acceptable salt thereof wherein Ris —OH; and Ris —CH.8. The compound of that is:8-(2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one;(S)-8-((R)-2-methoxy-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-3-methyl-2-(5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one;8-[2-(1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]-2-(5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one;(S)-3-methyl-8-(2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-2-(5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one;8-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]-2-(5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one;(R)-8-((R)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-3-methyl-2-(5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one;(S)-8-((R)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-3-methyl-2-(5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one:8-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one;8-[(2S)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one;9-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]-2-(4-methyl-5-oxo-2,5-dihydrofuran-3- ...

Inhibitors of the Renal Outer Medullary Potassium Channel

The present invention provides compounds of Formula I 16. A compound of which is:(R)-5-(1-Hydroxy-2-(2-(5-(methylsulfonyl)pyridin-2-yl)-2,8-diazaspiro[4.5]decan-8-yl)ethyl)-4-methylisobenzofuran-1(3H)-one;(R)-5-(1-Hydroxy-2-(2-(5-(methylsulfonyl)pyrazin-2-yl)-2,8-diazaspiro[4.5]decan-8-yl)ethyl)-4-methylisobenzofuran-1(3H)-one;(R)-8-(2-Hydroxy-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-2-(5-(methylsulfonyl)pyridin-2-yl)-2,8-diazaspiro[4.5]decan-3-one;(R)-8-(2Hydroxy-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-2-(5-(methylsulfonyl)pyrazin-2-yl)-2,8-diazaspiro[4.5]decan-3-one;(R)-6-(9-(2-Hydroxy-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)-4-methoxynicotinonitrile;(R)-8-(2-Hydroxy-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-3-(5-(methylsulfonyl)pyrazin-2-yl)-1-oxa-3,8-diazaspiro[4.5]decan-2-one;(R)-6-(8-(2-amino-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-2,8-diazaspiro[4.5]decan-2-yl)nicotinonitrile;(R)-5-(8-(2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-2, 8-diazaspiro[4.5]decan-2-yl)pyrazine-2-carbonitrile;(R)-6-(9-(2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-3,9-diazaspiro[5.5]undecan-3-yl)pyrimidine-4-carbonitrile;or a pharmaceutically acceptable salt thereof.17. A pharmaceutical composition comprising a therapeutically effective amount of a compound as defined in or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.18. The pharmaceutical composition as defined in claim 17 , which further comprises a therapeutically effective amount of at least one additional therapeutic agent selected from the group consisting of losartan claim 17 , valsartan claim 17 , candesartan claim 17 , olmesartan claim 17 , telmesartan claim 17 , eprosartan claim 17 , irbesartan claim 17 , amlodipine claim 17 , alacepril claim 17 , benazepril claim 17 , captopril claim 17 , ceronapril claim 17 , cilazapril claim 17 , ...

Hydroisoindoline Tachykinin Receptor Antagonists

The present invention is directed to certain hydroisoindoline compounds of formula I which are useful as neurokinin-1 (NK-1) receptor antagonists, and inhibitors of tachykinin and in particular substance P. The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including emesis, urinary incontinence, depression, and anxiety.

Metallo-Beta-Lactamase Inhibitors and Methods of Use Thereof

The present invention relates to metallo-β-lactamase inhibitor compounds of Formula (I) and pharmaceutically acceptable salts thereof, wherein Z, R, X, Xand Rare as defined herein. The present invention also relates to compositions which comprise a metallo-β-lactamase inhibitor compound of the invention or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, optionally in combination with a beta lactam antibiotic and/or a beta-lactamase inhibitor. The invention further relates to methods for treating a bacterial infection comprising administering to a patient a therapeutically effective amount of a compound of the invention, in combination with a therapeutically effective amount of one or more β-lactam antibiotics and optionally in combination with one or more beta-lactamase inhibitor compounds. The compounds of the invention are useful in the methods described herein for overcoming antibiotic resistance. 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Xand Xare each CH.3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris:{'sub': '2', '1) —NH;'}{'sup': a', 'a', 'b', 'a', 'a', 'b', '+', 'a', 'b', 'a, 'sub': 1', '6', '3', '1', '6', '2', '2', '2', '1-2', '2', '2', '2-3', '2', '3', '2', '2', '3', '2', '2-3', '2, '2) —NR—C-Calkyl, optionally substituted with 1, 2, 3, or 4 substituents independently selected from: —F, —CF, —C-Calkyl, —CH(NH)C(O)NH, —C(O)NRR, —C(O)OH, —(CH)NH, —NR(CH)NH, —NRR, —NRRCH, —NHCHCHOCH, —OR, and —O(CH)NH;'}{'sub': 1', '6', '3', '1', '6', '2', '1-2', '2', '2', '2-3', '2, 'sup': a', 'a', 'b', 'a, '3) —C-Calkyl, optionally substituted with 1, 2, or 3 substituents independently selected from —F, —CF, —C-Calkyl, —(CH)NH, —NR(CH)NH, —NRR, and —OR;'}{'sup': 'a', 'sub': 2', 'n, '4) —NR—(CH)-HetB1; or'}5) HetB 1.4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris HetA1.6. The compound of ...

NOVEL CYCLIC BENZIMIDAZOLE DERIVATIVES USEFUL AS ANTI-DIABETIC AGENTS

Novel compounds of the structural formula (I) are activators of AMP-protein kinase and are useful in the treatment, prevention and suppression of diseases mediated by the AMPK-activated protein kinase. The compounds of the present invention are useful in the treatment of Type 2 diabetes, hyperglycemia, Metabolic Syndrome, obesity, hypercholesterolemia, and hypertension.

INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL

The present invention provides compounds of Formula (I) and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention. 4. The compound of wherein:{'sup': '1', 'Ris —H or halo;'}{'sup': '2', 'Ris —H;'}{'sup': '3a', 'sub': 1-3', '3, 'Ris —H or —Calkyl optionally substituted with —OCHor 1 to 3 of —F;'}{'sup': '4', 'sub': '1-4', 'Ris —H, halo, or —Calkyl;'}{'sup': '5', 'sub': '1-3', 'Ris —H or —Calkyl;'}{'sup': '6', 'Ris —H;'}{'sup': 7', '7, 'Ris —H, or Ris absent when n is zero;'}{'sup': 8', '8, 'Ris —H, or Ris absent when n is zero;'}{'sup': '9', 'sub': 1-3', '1-3', '2, 'Ris —H, —F, —OH, —Calkyl, —OCalkyl or —CHOH;'}{'sup': '10', 'Ris —H;'}{'sup': '11', 'Ris —H;'}{'sup': '12', 'sub': '1-4', 'Ris —H, cyclopropyl, or —Calkyl optionally substituted with 1-3 of —F;'}{'sup': '13', 'sub': '1-4', 'Ris —H, or —Calkyl optionally substituted with 1-3 of —F; and'}n is zero or one;or a pharmaceutically acceptable salt thereof.5. The compound of wherein Ris —OH; or a pharmaceutically acceptable salt thereof.6. The compound of wherein n is one; or a pharmaceutically acceptable salt thereof.11. A compound which is:8-(2-hydroxy-2-(5H-tetrazolo[5,1-a]isoindol-7-yl)ethyl)-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one;8-(2-(6-chloro-5H-tetrazolo[5,1-a]isoindol-7-yl)-2-hydroxyethyl)-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one;6-fluoro-8-(2-hydroxy-2-(5H-tetrazolo[5,1-a]isoindol-7-yl)ethyl)-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one;8-(2-(4,5-dihydrotetrazolo[1,5-a]quinolin-7-yl)-2-hydroxyethyl)-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one;8-(2-hydroxy-2-(6- ...

Biaryl monobactam compounds and methods of use thereof for the treatment of bacterial infections

The present invention relates to biaryl monobactam compounds of Formula I: and pharmaceutically acceptable salts thereof, wherein X, Y, Z, A1, Q, A2, M, W, RXand Rzare as defined herein. The present invention also relates to compositions which comprise a biaryl monobactam compound of the invention or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. The invention further relates to methods for treating a bacterial infection comprising administering to the patient a therapeutically effective amount of a compound of the invention, either alone or in combination with a therapeutically effective amount of a second beta-lactam antibiotic.

Quinoline Tachykinin Receptor Antagonists

The present invention is directed to certain quinoline compounds which are useful as neurokinin-1 (NK-1) receptor antagonists, and inhibitors of tachykinin and in particular substance P. The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including emesis, urinary incontinence, depression, and anxiety.

Metallo-beta-lactamase inhibitors and methods of use thereof

The present invention relates to metallo-β-lactamase inhibitor compounds of Formula (I) and pharmaceutically acceptable salts thereof, wherein Z, RA, X1, X2 and R1 are as defined herein. The present invention also relates to compositions which comprise a metallo-β-lactamase inhibitor compound of the invention or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, optionally in combination with a beta lactam antibiotic and/or a beta-lactamase inhibitor. The invention further relates to methods for treating a bacterial infection comprising administering to a patient a therapeutically effective amount of a compound of the invention, in combination with a therapeutically effective amount of one or more β-lactam antibiotics and optionally in combination with one or more beta-lactamase inhibitor compounds. The compounds of the invention are useful in the methods described herein for overcoming antibiotic resistance.

SPIRO - FUSED PIPERIDINE DERIVATIVES FOR USE AS INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL

INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL

Novel spirocyclic compounds of formula I: and pharmaceutically acceptable salts thereof are disclosed as inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention. Pharmaceutical compositions and methods of treatment are also included. 3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein R and R′ are independently H or CH.4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein m is 1 claim 1 , or 2.5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein each Ris independently halo claim 1 , Calkyl claim 1 , tetrazolyl claim 1 , CN claim 1 , or OCalkyl claim 1 , wherein alkyl substituents are further optionally substituted with 1-4 halogen substituents.7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein n is 1.8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Rand Rare each H claim 1 , or Rand Rtogether form oxo.9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Y is CH.10. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris CH claim 1 , CHCH claim 1 , or cyclopropyl.12. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris H claim 1 , F claim 1 , Cl claim 1 , CH claim 1 , cyclopropyl claim 1 , phenyl claim 1 , or pyridyl claim 1 , wherein CH claim 1 , cyclopropyl claim 1 , phenyl claim 1 , or pyridyl substituents are further optionally substituted with 1-3 halogen substituents.13. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris H claim 1 , CH ...

INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL

The present invention provides compounds of Formula (I) and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention. 3. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris hydrogen or methyl.4. The compound of or a pharmaceutically acceptable salt thereof wherein ring A is phenyl claim 1 , wherein the aryl ring is substituted by R.5. The compound of or a pharmaceutically acceptable salt thereof wherein ring A is 5- or 6-membered heteroaryl claim 1 , containing 1-3 heteroatoms independently selected from the group consisting of N claim 1 , O claim 1 , and S claim 1 , wherein the heteroaryl ring is substituted by R.6. The compound of or a pharmaceutically acceptable salt thereof claim 5 , wherein ring A is pyridinyl claim 5 , pyrazinyl claim 5 , pyridazinyl claim 5 , or thiazolyl claim 5 , wherein each ring is substituted by R.7. The compound of or a pharmaceutically acceptable salt thereof claim 4 , wherein Ris tetrazolyl.8. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein ring A is 1 claim 1 ,3-dihydroisobenzofuran.9. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein ring A is 5H-tetrazolo[5 claim 1 ,1-a]isoindole claim 1 , 4 claim 1 ,5-dihydrotetrazolo[1 claim 1 ,5-a]quinolone claim 1 , 8H-tetrazolo[1′ claim 1 ,5′:1 claim 1 ,2]pyrrolo[3 claim 1 ,4-b]pyridine claim 1 , or tetrazolo[1 claim 1 ,5-a]quinoline.12. A pharmaceutical composition comprised of a compound of or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.13. The pharmaceutical composition of further comprising an additional active agent selected from ...

Hydroisoindoline tachykinin receptor antagonists

The present invention is directed to certain hydroisoindoline compounds which are useful as neurokinin-1 (NK-1) receptor antagonists, and inhibitors of tachykinin and in particular substance P. The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including emesis, urinary incontinence, depression, and anxiety.

Inhibitors of the renal outer medullary potassium channel

The present invention provides compounds of Formula (I) and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.

Inhibitors of the renal outer medullary potassium channel

The present invention provides compounds of Formula Ia and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and conditions associated with excessive salt and water retention.

Indole derivatives useful as inhibitors of diacylglyceride O-acyltransferase 2

The present invention relates to a compound represented by formula I: and pharmaceutically acceptable salts thereof. The compounds of formula I are inhibitors of diacylglyceride O-acyltransferase 2 (“DGAT2”) and may be useful in the treatment, prevention and suppression of diseases mediated by DGAT2. The compounds of the present invention may be useful in the treatment of hepatic steatosis, diabetes mellitus, obesity, hyperlipidemia, hypercholesterolemia, atherosclerosis, nonalcoholic steatohepatitis (NASH), cardiorenal diseases such as chronic kidney diseases and heart failure and related diseases and conditions.

INDAZOLE DERIVATIVES USEFUL AS INHIBITORS OF DIACYLGLYCERIDE O-ACYLTRANSFERASE 2

The present invention relates to a compound represented by formula I′: and pharmaceutically acceptable salts thereof. The compounds of formula I are inhibitors of diacylglyceride O-acyltransferase 2 (“DGAT2”) and may be useful in the treatment, prevention and suppression of diseases mediated by DGAT2. The compounds of the present invention may be useful in the treatment of hepatic steatosis, diabetes mellitus, obesity, hyperlipidemia, hypercholesterolemia, atherosclerosis, cardiorenal diseases such as chronic kidney diseases and heart failure and related diseases and conditions.

NOVEL PROLYLCARBOXYPEPTIDASE INHIBITORS

Compounds of structural formula I are inhibitors of prolylcarboxypeptidase (PrCP). The compounds of the present invention are useful for the prevention and treatment of conditions related to the enzymatic activity of PrCP such as abnormal metabolism, including obesity; diabetes; metabolic syndrome; obesity related disorders; and diabetes related disorders.

INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL

The present invention provides compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention. 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —H claim 1 , —F or —OH.3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein each of Rand Rare —H claim 1 , or Rand Rare joined together to form —CHCH—.4. The compound of any of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein n is 1.5. The compound of any of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —H claim 1 , —Cl claim 1 , —CHor cyclopropyl.6. The compound of any of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —H.7. The compound of any of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —CH.8. The compound of any of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Xis —C(O)— claim 1 , Xis —O— and Xis —CHCH—.9. The compound of any of wherein n is 1.10. The compound of any of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Xis —CH— claim 1 , Xis —O— and Xis —CHCH—.11. The compound of wherein n is 1.15. A compound which is:9-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]-4-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-1,4,9-triazaspiro[5.5]undecan-5-one dihydrochloride;9-(2-hydroxy-2-(2-methyl-6-(1H-tetrazol-1-yl)pyridin-3-yl)ethyl)-4-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-1,4,9-triazaspiro[5.5]undecan-5-one;9-(2-(5-(1H-tetrazol-1-yl)pyrazin-2-yl)-2-hydroxyethyl)-4-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-1,4,9- ...

INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL

The present invention provides compounds of Formula I 3. The method of or a pharmaceutically acceptable salt thereof wherein: Ris —H or —CH; Ris ═O; Ris —H or —CH; Ris —H or —CH; Ris —H claim 2 , —OH claim 2 , —OCHor —NH; and Ris —H or —CH.4. The method of or a pharmaceutically acceptable salt thereof wherein Ris —OH; and Ris —CH.6. The method of or a pharmaceutically acceptable salt thereof wherein: Ris —H or —CH; Ris ═O; Ris —H or —CH; Ris —H or —CH; Ris —H claim 5 , —OH claim 5 , —OCHor —NH; and Ris —H or —CH.7. The method of or a pharmaceutically acceptable salt thereof wherein Ris —OH; and Ris —CH.8. The method of wherein the compound is:8-(2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one;(S)-8-((R)-2-methoxy-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-3-methyl-2-(5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one;8-[2-(1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]-2-(5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one;(S)-3-methyl-8-(2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-2-(5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one;8-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]-2-(5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one;(R)-8-((R)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-3-methyl-2-(5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one;(S)-8-((R)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-3-methyl-2-(5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one:8-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one;8-[(2S)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one;9-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]-2-(4-methyl-5-oxo-2,5- ...

INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL

The present invention provides compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure, kidney disease, edema, and conditions associated with excessive salt and water retention.

Cyclic benzimidazole derivatives useful as anti-diabetic agents

Novel compounds of the structural formula (I) are activators of AMP-protein kinase and are useful in the treatment, prevention and suppression of diseases mediated by the AMPK-activated protein kinase. The compounds of the present invention are useful in the treatment of Type 2 diabetes, hyperglycemia, metabolic syndrome, obesity, hypercholesterolemia, and hypertension.

Cyclic benzimidazole derivatives useful as anti-diabetic agents

Novel compounds of the structural formula (I) are activators of AMP-protein kinase and are useful in the treatment, prevention and suppression of diseases mediated by the AMPK-activated protein kinase. The compounds of the present invention are useful in the treatment of Type 2 diabetes, hyperglycemia, Metabolic Syndrome, obesity, hypercholesterolemia, and hypertension.

Biaryl monobactam compounds and methods of use thereof for the treatment of bacterial infections

The present invention relates to biaryl monobactam compounds of Formula I: and pharmaceutically acceptable salts thereof, wherein X, Y, Z, A1, Q, A2, M, W, RX and Rz are as defined herein. The present invention also relates to compositions which comprise a biaryl monobactam compound of the invention or a pharmaceutically acceptable salt therof, and a pharmaceutically acceptable carrier. The invention further relates to methods for treating a bacterial infection comprising administering to the patient a therapeutically effective amount of a compound of the invention, either alone or in combination with a therapeutically effective amount of a second beta-lactam antibiotic.

Novel cyclic benzimidazole derivatives useful anti-diabetic agents

Novel compounds of the structural formula (I) are activators of AMP-protein kinase and are useful in the treatment, prevention and suppression of diseases mediated by the AMPK- activated protein kinase. The compounds of the present invention are useful in the treatment of Type 2 diabetes, hyperglycemia, metabolic syndrome, obesity, hypercholesterolemia, and h ypertensiion.

Hydroisoindoline tachykinin receptor antagonists

The present invention is directed to certain hydroisoindoline compounds of formula I which are useful as neurokinin-1 (NK-1) receptor antagonists, and inhibitors of tachykinin and in particular substance P. The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including emesis, urinary incontinence, depression, and anxiety.

Inhibitors of the renal outer medullary potassium channel

The present invention provides compounds of Formula (I) and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir11) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.

Inhibitors of the renal outer medullary potassium channel

The present invention provides compounds of Formula (I) and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.

Antagonists of gonadotropin releasing hormone

2-aminoquinoline compounds

The present invention is concerned with compounds of the general Formula I : and pharmaceutically acceptable salts thereof, which are useful as melanin concentrating hormone receptor antagonists, particularly MCH-1R antagonists.As such, compounds of the present invention are useful for the treatment or prevention of obesity or eating disorders associated with excessive food intake and complications thereof, osteoarthritis, certain cancers, AIDS wasting, cachexia, frailty (particularly in elderly), mental disorders stress, cognitive disorders, sexual function, reproductive function, kidney function, locomotor disorders, attention deficit disorder (ADD), substance abuse disorders and dyskinesias, Huntington s disease, epilepsy, memory function, and spinal muscular atrophy. Compounds of formula I may therefore be used in the treatment of these conditions, and in the manufacture of a medicament useful in treating these conditions. Pharmaceutical formulations comprising one of the compounds of formula (I) as an active ingredient are disclosed, as are processes for preparing these compounds.

Hydroxymethyl ether hydroisoindoline tachykinin receptor antagonists

The present invention is directed to certain hydroxymethyl ether hydroisoindoline compounds which are useful as neurokinin-1 (NK-1) receptor antagonists, and inhibitors of tachykinin and in particular substance P. The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including emesis, urinary incontinence, LUTS, depression, and anxiety.

4-aminoquinoline compounds

The present invention is concerned with compounds of the general Formula I : and pharmaceutically acceptable salts thereof, which are useful as melanin concentrating hormone receptor antagonists, particularly MCH-1R antagonists. As such, compounds of the present invention are useful for the treatment or prevention of obesity or eating disorders associated with excessive food intake and complications thereof, osteoarthritis, certain cancers, AIDS wasting, cachexia, frailty (particularly in elderly), mental disorders stress, cognitive disorders, sexual function, reproductive function, kidney function, locomotor disorders, attention deficit disorder (ADD), substance abuse disorders and dyskinesias, Huntington s disease, epilepsy, memory function, and spinal muscular atrophy. Compounds of formula I may therefore be used in the treatment of these conditions, and in the manufacture of a medicament useful in treating these conditions. Pharmaceutical formulations comprising one of the compounds of formula (I) as an active ingredient are disclosed, as are processes for preparing these compounds.

3-tetrazolyl-benzene-1,2-disulfonamide derivatives as metallo-beta-lactamase inhibitors

Antagonists of gonadotropin releasing hormone

Novel cyclic azabenzimidazole derivatives useful as anti-diabetic agents

Novel compounds of structural formula (I) are activators of AMP-protein kinase and are useful in the treatment, prevention and suppression of diseases mediated by the AMPK-activated protein kinase. The compounds of the present invention are useful in the treatment of Type 2 diabetes, hyperglycemia, metabolic syndrome, obesity, hypercholesterolemia, and hypertension.

2-aminoquinoline compounds

The present invention is concerned with compounds of the general Formula I : and pharmaceutically acceptable salts thereof, which are useful as melanin concentrating hormone receptor antagonists, particularly MCH-1R antagonists.As such, compounds of the present invention are useful for the treatment or prevention of obesity or eating disorders associated with excessive food intake and complications thereof, osteoarthritis, certain cancers, AIDS wasting, cachexia, frailty (particularly in elderly), mental disorders stress, cognitive disorders, sexual function, reproductive function, kidney function, locomotor disorders, attention deficit disorder (ADD), substance abuse disorders and dyskinesias, Huntington s disease, epilepsy, memory function, and spinal muscular atrophy. Compounds of formula I may therefore be used in the treatment of these conditions, and in the manufacture of a medicament useful in treating these conditions. Pharmaceutical formulations comprising one of the compounds of formula (I) as an active ingredient are disclosed, as are processes for preparing these compounds.

Hydroisoindoline tachykinin receptor antagonists

The present invention is directed to certain hydroisoindoline compounds which are useful as neurokinin-1 (NK-1) receptor antagonists, and inhibitors of tachykinin and in particular substance P. The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including emesis, urinary incontinence, depression, and anxiety.

Inhibitors of the renal outer medullary potassium channel

The present invention provides compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.

Biaryl monobactam compounds for the treatment of bacterial infections

3-tetrazolyl-benzene-1,2-disulfonamide derivatives as metallo-beta-lactamase inhibitors

The present invention relates to metallo-beta-lactamase inhibitor compounds of Formula I: and pharmaceutically acceptable salts thereof, wherein Z, R

Quinoline tachykinin receptor antagonists

3-tetrazolyl-benzene-1,2-disulfonamide derivatives as metallo-beta-lactamase inhibitors

The present invention relates to metallo-beta-lactamase inhibitor compounds of Formula I: and pharmaceutically acceptable salts thereof, wherein Z, RA, X1, X 2 and R1are as defined herein. The present invention also relates to compositions which comprise a metallo-beta-lactamase inhibitor compound of the invention or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, optionally in combination with a beta-lactam antibiotic and/or a beta-lactamase inhibitor. The invention further relates to methods for treating a bacterial infection comprising administering to a patient a therapeutically effective amount of a compound of the invention, in combination with a therapeutically effective amount of one or more ß-lactam antibiotics and optionally in combination with one or more beta-lactamase inhibitor compounds. The compounds of the invention are useful in the methods described herein for overcoming antibiotic resistance.

Inhibitors of the renal outer medullary potassium channel

COMPOUND, TRIFLUOROACETIC ACID SALT, PHARMACEUTICAL COMPOSITION, METHOD FOR TREATING A BACTERIAL INFECTION, AND, USE OF A COMPOUND

A presente invenção refere-se a compostos de biaril monobactama de Fórmula I e sais farmaceuticamente aceitáveis dos mesmos, em que X, Y, Z, Al, Q, A2, M, W, Rx e Rz são como aqui definidos. A presente invenção também se refere a composições que compreendem um composto de biaril monobactama da invenção ou um sal farmaceuticamente aceitável dos mesmos, e um carreador farmaceuticamente aceitável. A invenção refere-se ainda a métodos para tratar uma infecção bacteriana compreendendo administrar ao paciente uma quantidade terapeuticamente eficaz de um composto da invenção, isoladamente ou em combinação com uma quantidade terapeuticamente eficaz de um segundo antibiótico de beta-lactama. The present invention relates to biaryl monobactam compounds of Formula I and pharmaceutically acceptable salts thereof, wherein X, Y, Z, Al, Q, A2, M, W, Rx and Rz are as defined herein. The present invention also relates to compositions comprising a biaryl monobactam compound of the invention or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. The invention further relates to methods of treating a bacterial infection comprising administering to the patient a therapeutically effective amount of a compound of the invention, alone or in combination with a therapeutically effective amount of a second beta-lactam antibiotic.

Novel cyclic benzimidazole derivatives useful anti-diabetic agents

3-tetrazolyl-benzene-1,2-disulfonamide derivatives as metallo-beta-lactamase inhibitors

<p>LA PRESENTE INVENCIÓN SE REFIERE A COMPUESTOS INHIBIDORES DE METALO-b- LACTAMASA COMPUESTOS DE FÓRMULA I, Y SALES FARMACÉUTICAMENTE ACEPTABLES DE LOS MISMOS, EN LA QUE Z, RA, X1, X2 Y R1 SON COMO SE DEFINEN EN EL PRESENTE DOCUMENTO. LA PRESENTE INVENCIÓN TAMBIÉN SE REFIERE A COMPOSICIONES QUE COMPRENDEN UN COMPUESTO INHIBIDOR DE METALO-b-LACTAMASA DE LA INVENCIÓN O UNA SAL FARMACÉUTICAMENTE ACEPTABLE DEL MISMO, Y UN VEHÍCULO FARMACÉUTICAMENTE ACEPTABLE, OPCIONALMENTE JUNTO CON UN ANTIBIÓTICO BETALACTÁMICO Y/O UN INHIBIDOR DE BETA-LACTAMASA. LA INVENCIÓN TAMBIÉN SE REFIERE A MÉTODOS PARA EL TRATAMIENTO DE UNA INFECCIÓN BACTERIANA QUE COMPRENDE ADMINISTRAR A UN PACIENTE UNA CANTIDAD TERAPÉUTICAMENTE EFICAZ DE UN COMPUESTO DE LA INVENCIÓN, JUNTO CON UNA CANTIDAD TERAPÉUTICAMENTE EFICAZ DE UNO O MÁS ANTIBIÓTICOS BETALACTÁMICOS Y OPCIONALMENTE JUNTO CON UNO O MÁS COMPUESTOS INHIBIDORES DE BETA-LACTAMASA. LOS COMPUESTOS DE LA INVENCIÓN SON ÚTILES EN LOS MÉTODOS DESCRITOS EN EL PRESENTE DOCUMENTO PARA SUPERAR LA RESISTENCIA A ANTIBIÓTICOS.</p> <p> THE PRESENT INVENTION REFERS TO METHALO-B-LACTAMASE COMPOUNDS OF FORMULA COMPOUNDS I, AND PHARMACEUTICALLY ACCEPTABLE SALES OF THE SAME, IN WHICH Z, RA, X1, X2 AND R1 ARE AS DEFINED IN THIS DOCUMENT . THE PRESENT INVENTION ALSO REFERS TO COMPOSITIONS THAT INCLUDE AN INHIBITING METALO-b-LACTAMASA COMPOUND OF THE INVENTION OR A PHARMACEUTICALLY ACCEPTABLE SALT OF THE SAME, AND A PHARMACEUTICALLY ACCEPTABLE UNITIONALLY UNBATCHED OPTIONAL OPTIONAL UNIT LACTAMASE. THE INVENTION ALSO REFERS TO METHODS FOR THE TREATMENT OF A BACTERIAL INFECTION THAT INCLUDES ADMINISTRATING TO A PATIENT A THERAPEUTICALLY EFFECTIVE AMOUNT OF AN INVENTION COMPOUND, TOGETHER WITH A THERAPEUTICALLY EFFECTIVE OR MOST BOTH OPTIMAL BETWEEN ONE OR BETTER OPTION BETA-LACTAMASA INHIBITING COMPOUNDS. THE COMPOUNDS OF THE INVENTION ARE USEFUL IN THE METHODS DESCRIBED IN THIS DOCUMENT TO EXCEED ANTIBIOTIC RESISTANCE. </p>

3-TETRAZOLYL-BENZENE-1,2-DISULFONAMIDE DERIVATIVES AS METALLO-BETA-LACTAMASE INHIBITORS

La présente invention concerne des composés inhibiteurs de métallo-bêta-lactamase représentés par la formule i, et leurs sels pharmaceutiquement acceptables. Dans ladite formule, z, ra, x1, x 2 et r1 sont tels que définis ici. La présente invention concerne également des compositions qui comprennent un composé inhibiteur de métallo-bêta-lactamase ou son sel pharmaceutiquement acceptable, et un support pharmaceutiquement acceptable, éventuellement associé à un antibiotique bêta-lactame et/ou un inhibiteur de bêta-lactamase. L'invention concerne également des procédés permettant de traiter une infection bactérienne qui consistent à administrer à un patient une quantité thérapeutiquement efficace d'un composé de l'invention, en l'associant à une quantité thérapeutiquement efficace d'un ou de plusieurs antibiotiques bêta-lactame et éventuellement en l'associant à un ou plusieurs composés inhibiteurs de bêta-lactamase. Les composés de l'invention sont utiles dans les procédés de l'invention pour surmonter la résistance aux antibiotiques.

Inhibitors of the renal outer medullary potassium channel

The present invention provides compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.

Novel cyclic benzimidazole derivatives useful anti-diabetic agents

Novel compounds of the structural formula (I) are activators of AMP-protein kinase and are useful in the treatment, prevention and suppression of diseases mediated by the AMPK- activated protein kinase. The compounds of the present invention are useful in the treatment of Type 2 diabetes, hyperglycemia, metabolic syndrome, obesity, hypercholesterolemia, and hypertension.

Quinoline tachykinin receptor antagonists

The present invention is directed to certain quinoline compounds which are useful as neurokinin-1 (NK-1) receptor antagonists, and inhibitors of tachykinin and in particular substance P. The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including emesis, urinary incontinence, depression, and anxiety.

Hydroisoindoline tachykinin receptor antagonists

The present invention is directed to certain hydroisoindoline compounds which are useful as neurokinin-1 (NK-1) receptor antagonists, and inhibitors of tachykinin and in particular substance P. The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including emesis, urinary incontinence, depression, and anxiety.

Biaryl monobactam compounds and methods of use thereof for the treatment of bacterial infections

Inhibitors of the renal outer medullary potassium channel

Biaryl monobactam compounds and methods of use thereof for the treatment of bacterial infections

The present invention relates to biaryl monobactam compounds of Formula I: and pharmaceutically acceptable salts thereof, wherein X, Y, Z, A1, Q, A2, M, W, RX and Rz are as defined herein. The present invention also relates to compositions which comprise a biaryl monobactam compound of the invention or a pharmaceutically acceptable salt therof, and a pharmaceutically acceptable carrier. The invention further relates to methods for treating a bacterial infection comprising administering to the patient a therapeutically effective amount of a compound of the invention, either alone or in combination with a therapeutically effective amount of a second beta-lactam antibiotic.

Indazole derivatives useful as inhibitors of diacylglyceride o-acyltransferase 2

The present invention relates to a compound represented by formula I': and pharmaceutically acceptable salts thereof. The compounds of formula I are inhibitors of diacylglyceride O-acyltransferase 2 ("DGAT2") and may be useful in the treatment, prevention and suppression of diseases mediated by DGAT2. The compounds of the present invention may be useful in the treatment of hepatic steatosis, diabetes mellitus, obesity, hyperlipidemia, hypercholesterolemia, atherosclerosis, cardiorenal diseases such as chronic kidney diseases and heart failure and related diseases and conditions.

Inhibitors of the renal outer medullary potassium channel

The present invention provides compounds of Formula Ia and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and conditions associated with excessive salt and water retention.

Spiro-fused piperidine derivatives for use as inhibitors of the renal outer medullary potassium channel

The present invention provides compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and conditions associated with excessive salt and water retention.

Metallo-beta-lactamase inhibitors

The present invention relates to compounds of formula (I) that are metallo-β-lactamase inhibitors, the synthesis of such compounds, and the use of such compounds for use with β-lactam antibiotics for overcoming resistance.

Indole derivatives useful as inhibitors of diacylglyceride o-acyltransferase 2

METALO-BETA-LACTAMASA INHIBITORS

La presente invención se refiere a compuestos inhibidores de metalo-ß-lactamasa compuestos de Fórmula I: (I) y sales farmacéuticamente aceptables de los mismos, en la que Z, RA, X1, X2 y R1 son como se definen en el presente documento. La presente invención también se refiere a composiciones que comprenden un compuesto inhibidor de metalo-ß-lactamasa de la invención o una sal farmacéuticamente aceptable del mismo, y un vehículo farmacéuticamente aceptable, opcionalmente junto con un antibiótico betalactámico y/o un inhibidor de beta-lactamasa. La invención también se refiere a métodos para el tratamiento de una infección bacteriana que comprende administrar a un paciente una cantidad terapéuticamente eficaz de un compuesto de la invención, junto con una cantidad terapéuticamente eficaz de uno o más antibióticos betalactámicos y opcionalmente junto con uno o más compuestos inhibidores de beta-lactamasa. Los compuestos de la invención son útiles en los métodos descritos en el presente documento para superar la resistencia a antibióticos.

Composto, zwitterion, composição farmacêutica, e, uso de um composto

composto, zwitterion, composição farmacêutica, métodos para inibir betalactamase em um indivíduo e para tratamento de uma infecção bacteriana, e, uso de um composto. a presente invenção refere-se a compostos inibidores de metalo-lactamase de fórmula i e sais farmaceuticamente aceitáveis dos mesmos, em que z, ra, x1, x2 e r1 são como aqui definidos. a presente invenção também se refere a composições que compreendem um composto inibidor de metalo-beta-lactamase da invenção ou um sal farmaceuticamente aceitável do mesmo e um veículo farmaceuticamente aceitável, opcionalmente em combinação com um antibiótico beta-lactâmico e/ou um inibidor de betalactamase. a invenção refere-se ainda a métodos para tratar uma infecção bacteriana compreendendo administrar a um paciente uma quantidade terapeuticamente eficaz de um composto do invento, em combinação com uma quantidade terapeuticamente eficaz de um ou mais antibióticos beta-lactâmicos e opcionalmente em combinação com um ou mais compostos inibidores de betalactamase. os compostos da invenção são úteis nos métodos aqui descritos para superar a resistência aos antibióticos.

Preparation of tetrahydroindazole derivatives as novel diacylglyceride o-acyltransferase 2 inhibitors

Invented are compounds of formula I and the pharmaceutically acceptable salts, esters, and prodrugs thereof, which are DGAT2 inhibitors. Also provided are methods of making compounds of Formula I, pharmaceutical compositions comprising compounds of Formula I, and methods of using these compounds to treat hepatic steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, type-2 diabetes mellitus, obesity, hyperlipidemia, hypercholesterolemia, atherosclerosis, cognitive decline, dementia, cardiorenal diseases such as chronic kidney diseases and heart failure and related diseases and conditions, comprising administering a compound of Formula I to a patient in need thereof.

Hydroisoindolin-tachykininrezeptorantagonisten

Biaryl monobactam compounds and methods of use thereof for the treatment of bacterial infections

The present invention seeks to solve the the lack of antibiotics used to treat antibiotic resistant bacteria. The present invention relates to biaryl monobactam compounds of Formula I:

Παραγωγα 3-τετραζολυλ-βενζεν-1,2-δισουλφοναμιδιου ως αναστολεις μεταλλο-βητα-λακταμασης

Η παρούσα εφεύρεση σχετίζεται με ενώσεις αναστολέων μεταλλο-βήτα-λακταμάσης του Χημικού Τύπου Ι: και φαρμακευτικώς αποδεκτά άλατα εξ αυτών, όπου τα Ζ, RA, Χ1, Χ2 και R1 καθορίζονται ως εις το παρόν. Η παρούσα εφεύρεση σχετίζεται επίσης και με συνθέσεις οι οποίες συμπεριλαμβάνουν μια ένωση αναστολέα μεταλλο-βήτα-λακταμάσης της εφεύρεσης ή ένα φαρμακευτικώς αποδεκτό άλας εξ αυτής, και μία φαρμακευτικώς αποδεκτή ουσία-φορέας, προαιρετικώς σε συνδυασμό με ένα αντιβιοτικό βήτα-λακτάμης και/ή έναν αναστολέα της βήτα-λακταμάσης. Η εφεύρεση σχετίζεται περαιτέρω με μεθόδους για αγωγή μιας βακτηριακής λοίμωξης περιλαμβάνοντας χορήγηση σε έναν ασθενή μιας θεραπευτικώς αποτελεσματικής ποσότητας μιας ένωσης της εφεύρεσης, σε συνδυασμό με μια θεραπευτικώς αποτελεσματική ποσότητα ενός ή περισσότερων αντιβιοτικών βήτα-λακτάμης και προαιρετικώς σε συνδυασμό με μία ή περισσότερες ενώσεις αναστολέων βήτα-λακταμάσης. Οι ενώσεις της εφεύρεσης είναι χρήσιμες στις μεθόδους που περιγράφονται εις το παρόν για υπερκέραση αντίστασης αντιβιοτικών.

Inhibitors of the renal outer medullary potassium channel

The present invention provides compounds of Formula Ia and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and conditions associated with excessive salt and water retention.

5-phenyl-5,6,7,8-hydroquinoline tachykinin receptor antagonists

The present invention is directed to certain 5-phenyl-5,6,7,8-hydroquinoline compounds which are useful as neurokinin-1 (NK-1) receptor antagonists, and inhibitors of tachykinin and in particular substance P. The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including emesis, urinary incontinence, depression, and anxiety.

5-phenyl-5,6,7,8-hydroquinoline tachykinin receptor antagonists

The present invention is directed to certain 5-phenyl-5,6,7,8-hydroquinoline compounds which are useful as neurokinin-1 (NK-1) receptor antagonists, and inhibitors of tachykinin and in particular substance P. The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including emesis, urinary incontinence, depression, and anxiety.

5-phenyl-5,6,7,8-hydroquinoline tachykinin receptor antagonists

Preparacion de derivados de tetrahidroindazol como innovadores inhibidores de la diacilglicerido o-aciltransferasa 2.

Se inventan compuestos de Fórmula I y las sales, ésteres y profármacos farmacéuticamente aceptables de los mismos, que son inhibidores de DGAT2. También se proporcionan métodos para preparar compuestos de Fórmula I, composiciones farmacéuticas que comprenden compuestos de Fórmula I y métodos para usar estos compuestos para tratar esteatosis hepática, esteatohepatitis no alcohólica (NASH), fibrosis, diabetes mellitus tipo 2, obesidad, hiperlipidemia, hipercolesterolemia, aterosclerosis, deterioro cognitivo, demencia, enfermedades cardiorrenales tales como enfermedades renales crónicas e insuficiencia cardíaca y enfermedades y afecciones relacionadas, que comprenden administrar un compuesto de Fórmula I a un paciente que lo necesite.

Preparation of tetrahydroindazole derivatives as novel diacylglyceride o-acyltransferase 2 inhibitors

Inhibitors of the renal outer medullary potassium channel

The present invention provides compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.

油浴清洗装置

本实用新型涉及油浴清洗技术领域，是一种油浴清洗装置，包括油浴箱、滤网板、出油管、进油管和油泵，油浴箱为开口向上的箱体结构，箱体内设有滤网板，滤网板的前侧与油浴箱前侧板内侧右部固定安装在一起，滤网板的后侧与油浴箱后侧板内侧右部固定安装在一起，滤网板的右侧与油浴箱右侧板内侧固定安装在一起，滤网板的左侧与油浴箱左侧板内侧间设有油浴开口。本实用新型结构合理而紧凑，构思巧妙，通过油泵使油浴箱内的油剂循环往复的使用，避免油剂在静止状态下清洗效果差的问题，具有高效、快速和清洗效果好的特点。

Novel prolylcarboxypeptidase inhibitors

Compounds of structural formula I are inhibitors of prolylcarboxypeptidase (PrCP). The compounds of the present invention are useful for the prevention and treatment of conditions related to the enzymatic activity of PrCP such as abnormal metabolism, including obesity; diabetes; metabolic syndrome; obesity related disorders; and diabetes related disorders.

8-phenyl-5,6,7,8-hydroquinoline tachykinin receptor antagonists

Inhibitors of the renal outer medullary potassium channel

The present invention provides compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.

8-phenyl-5,6,7,8-hydroquinoline tachykinin receptor antagonists

The present invention is directed to certain 8-phenyl-5,6,7,8-hydroquinolinecompounds which are useful as neurokinin-1 (NK-1) receptor antagonists, and inhibitors of tachykinin and in particular substance P. The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including emesis, urinary incontinence, depression, and anxiety.

Inhibitors of the renal outer medullary potassium channel

Inhibitors of the renal outer medullary potassium channel

Inhibitors of the renal outer medullary potassium channel

The present invention provides compounds of Formula I (I) and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.