Heterocyclic aspartyl protease inhibitors

The invention discloses compounds of the formula (I) or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein W is a bond, -C(=S)-, -S(O)-, -S(O)2-, -C(=O)-, -O-, -C(R<6>)(R<7>)-, -N(R<5>)- or -C(=N(R<5>))-; X is -O-, -N(R<5>)- or -C(R<6>)(R<7>)-; provided that when X is -O-, U is not -O-, -S(O)-, -S(O)2-, -C(=O)- or -C(=NR<5>)-; U is a bond, -S(O)-, -S(O)2-, -C(O)-, -O-, -P(O)(OR<15>)-, -C(=NR<5>)-, -(C(R<6>)(R<7>))b- or -N(R<5>)-; wherein b is 1 or 2; provided that when W is -S(O)-, -S(O)2-, -O-, or -N(R<5>)-, U is not -S(O)-, -S(O)2-, -O-, or -N(R<5>)-; provided that when X is -N(R<5>)- and W is -S(O)-, -S(O)2-, -O-, or -N(R<5>)-, then U is not a bond; and R<1>, R<2>, R<3>, R<4>, R<5>, R<6>, and R<7> are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula (I). Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and ...

CYCLIC AMINE BASE-1 INHIBITORS HAVING A HETEROCYCLIC SUBSTITUENT

Disclosed are novel compounds of the formula (I)or a pharmaceutically acceptable salt or solvate thereof, wherein R is formula (I) X is -0-, -C(R)2- or -N(R)-; Z is -C(R)2- or -N(R)-; t is 0, 1, 2 or 3; each R and R is independently H, alkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, heterocycloalkylalkyl, alkenyl or alkynyl; each Ris H, alkyl, alkenyl, alkynyl, halo, -CN, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, heterocycloalkylalkyl, - OR35, N(R)(R) or -SR; Ris alkyl, cycloalkyl, -S0(alkyl), -C(O)-alkyl, - C(O)-cycloalkyl or -alkyl-NH-C(O)CH3; and the remaining variables are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I and methods of treating cognitive or neurodegenerative diseases with compounds of formula (I). Also disclosed are pharmaceutical compositions and methods of treatment comprising compounds ...

HETEROCYCLIC ASPARTYL PROTEASE INHIBITORS

Disclosed are compounds of the formula (I) or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of Human Immunodeficiency Virus, plasmepins, cathepsin D and protozoal enzymes. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula (I) in combination with a cholinesterase inhibitor or a muscarinic antagonist. © KIPO & WIPO 2007 ...

HETEROCYCLIC ASPARTYL PROTEASE INHIBITORS

Disclosed are compounds of the formula (I) or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein W is a bond,-C(=S)-,-S(O)-,-S(O)2-,-C(=O)-,-O-,-C(R6)(R7)-,-N(R5)-or-C(=N(R5))-; X is-O-,-N(R5)-or-C(R6)(R7)-; provided that when X is-O-, U is not-O-,-S(O)-,-S(O)2-,-C(=O)-or-C(=NR5)-; U is a bond,-S(O)-,-S(O)2-,-C(O)-,-O-,-P(O)(OR15)-,-C(=NR5)-,-(C(R6)(R7))b-or-N(R5)-; wherein b is 1 or 2; provided that when W is-S(O)-,-S(O)2-,-O-, or-N(R5)-, U is not-S(O)-,-S(O)2-,-O-, or-N(R5)-; provided that when X is-N(R5)-and W is-S(O)-,-S(O)2-,-O-, or-N(R5)-, then U is not a bond; and R1, R2, R3, R4, R5, R6, and R7 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula (I). Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of Human Immunodeficiency Virus, plasmepins ...

HETEROCYCLIC ASPARTYL PROTEASE INHIBITORS

Disclosed are compounds of the formula (I) a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein W is a bond,-C(=S)-,-S(O)-,-S(O)2-,-C(=O)-,-O-,-C(R6) (R7)-,-N(R5)-or-C(=N(R5))-; X is-O-,-N(R5)-or-C(R6)(R7)-; provided that when X is-O-, U is not-O-,-S(O)-,-S(O)2-,-C(=O)-or-C(=NR5)-; U is a bond,-S(O)-,-S(O)2-,-C(O)-,-O-,-P(O)(OR15)-,-C(=NR5)-,-(C(R6)(R7))b-or-N(R5)-; wherein b is 1 or 2; provided that when W is-S(O)-,-S(O)2-,-O-, or-N(R5)-, U is not-S(O)-,-S(O)2-,-O-, or-N(R5)-; provided that when X is-N(R5)-and W is-S(O)-,-S(O)2-,-O-, or-N(R5)-, then U is not a bond; and R1, R2, R3, R4, R5, R6, and R7 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula (I). Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of Human Immunodeficiency Virus, plasmepins ...

Cyclic amine BACE-1 inhibitors having a heterocyclic substituent

Disclosed are novel compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein R1 is X is -O-, -C(R14)2- or -N(R)-; Z is -C(R14)2- or -N(R)-; t is 0, 1, 2 or 3; each R and R2 is independently H, alkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, heterocycloalkylalkyl, alkenyl or alkynyl; each R14 is H, alkyl, alkenyl, alkynyl, halo, -CN, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, heterocycloalkylalkyl, -OR35, -N(R24)(R25) or -SR35; R41 is alkyl, cycloalkyl, -SO2(alkyl), -C(O)-alkyl, -C(O)-cycloalkyl or -alkyl-NH-C(O)CH3; and the remaining variables are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I and methods of treating cognitive or neurodegenerative diseases with compounds of formula I. Also disclosed are pharmaceutical compositions and methods of treatment comprising compounds ...

Macrocyclic heterocyclic aspartyl protease inhibitors

Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt, solvate or ester thereof, wherein U, W, X, L, Y, M, Z, c, d, e, f, g, h, s, t, R1, R2, R7, R8, R9, R10, R11, R12, R13, R14, R15, R16, R17 and R18 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic m1 agonist or m2 antagonist.

Substituted quinoxalines as inhibitors of fatty acid binding protein

The present invention relates to novel quinoxaline compounds of Formula I: as Fatty Acid Binding Protein (“FABP”) inhibitors, pharmaceutical compositions comprising the quinoxaline compounds and the use of the quinoxaline compounds for treating or preventing a cardiovascular disease, a metabolic disorder, obesity or an obesity-related disorder, diabetes, dyslipidemia, a diabetic complication, impaired glucose tolerance or impaired fasting glucose.

HETEROCYCLIC ASPARTYL PROTEASE INHIBITORS

Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein W is a bond, —C(═S)—, —S(O)—, —S(O) 2 —, —C(═O)—, —O—, —C(R 6 )(R 7 )—, —N(R 5 )— or —C(═N(R 5 ))—; X is —O—, —N(R 5 )— or —C(R 6 )(R 7 )—; provided that when X is —O—, U is not —O—, —S(O)—, —S(O) 2 —, —C(═O)— or —C(═NR 5 )—; U is a bond, —S(O)—, —S(O) 2 —, —C(O)—, —O—, —P(O)(OR 15 )—, —C(═NR 5 )—, —(C(R 6 )(R 7 )) b — or —N(R 5 )—; wherein b is 1 or 2; provided that when W is —S(O)—, —S(O) 2 —, —O—, or —N(R 5 )—, U is not —S(O)—, —S(O) 2 —, —O—, or —N(R 5 )—; provided that when X is —N(R 5 )— and W is —S(O)—, —S(O) 2 —, —O—, or —N(R 5 )—, then U is not a bond; and R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , and R 7 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of Human Immunodeficiency Virus, plasmepins, cathepsin D and protozoal enzymes. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic antagonist.

Macrocyclic beta-secretase inhibitors

Disclosed are novel compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein R1, R2, R3, n and X are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of treating cognitive or neurodegenerative diseases such as Alzheimer's disease. Also disclosed are methods of treating a cognitive or neurodegenerative disease comprising administering to a patient I need of such treatment a combination of at least one compound of formula I and at least one compound selected from the group consisting of -secretase inhibitors other than those of formula I, HMG-CoA reductase inhibitors, gamma-secretase inhibitors, non-steroidal anti-inflammatory agents, N-methyl-D-aspartate receptor antagonists, cholinesterase inhibitors and anti-amyloid antibodies.

Macrocyclic heterocyclic aspartyl protease inhibitors

Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt, solvate or ester thereof, wherein U, W, X, L, Y, M, Z, c, d, e, f, g, h, s, t, R 1 , R 2 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 and R 18 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic m 1 agonist or m 2 antagonist.

HETEROCYCLIC ASPARTYL PROTEASE INHIBITORS

Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein W is a bond, -C(-S)-, -S(O)-, -S(O)2-, -C(-O)-, -O-, -C(R6)(R7)-, -N(R5)- or -C(-N(R5))-; X is -O-, -N(R5)- or -C(R6)(R7)-; provided that when X is -O-, U is not -O-, -S(O)-, -S(O)2-, -C(-O)- or -C(-NR5)-; U is a bond, -S(O)-, -S(O)2-, -C(O)-, -O-, -P(O)(OR15)-, -C(-NR5)-, -(C(R6)(R7))b- or -N(R5)-; wherein b is 1 or 2; provided that when W is -S(O)-, -S(O)2-, -O-, or -N(R5)-, U is not -S(O)-, -S(O)2-, -O-, or -N(R5)-; provided that when X is -N(R5)- and W is -S(O)-, -S(O)2-, -O-, or -N(R5)-, then U is not a bond; and R1, R2, R3, R4, R5, R6, and R7 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of ...

Macrocyclic beta-secretase inhibitors

Disclosed are novel compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 , R 2 , R 3 , n and X are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of treating cognitive or neurodegenerative diseases such as Alzheimer's disease. Also disclosed are methods of treating a cognitive or neurodegenerative disease comprising administering to a patient I need of such treatment a combination of at least one compound of formula I and at least one compound selected from the group consisting of β-secretase inhibitors other than those of formula I, HMG-CoA reductase inhibitors, gamma-secretase inhibitors, non-steroidal anti-inflammatory agents, N-methyl-D-aspartate receptor antagonists, cholinesterase inhibitors and anti-amyloid antibodies.

SH2 domain binding inhibitors

Disclosed are compounds for SH2 domain binding inhibition. For example, disclosed is a compound of formula (I) wherein R₁ is a lipophile; R₂, in combination with the phenyl ring, forms a phenylphosphate mimic group or a protected phenylphosphate mimic group; R₃ is hydrogen, azido, amino, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, or alkylcarbonylamino, wherein the alkyl portion of R₃ may be optionally substituted with a substituent selected from the group consisting of halo, hydroxy, carboxyl, amino, aminoalkyl, alkyl, alkoxy, and keto; R₆ is a linker; AA is an amino acid; and n is 1 to 6; or a salt thereof. Also disclosed are a pharmaceutical composition, a method for inhibiting an SH2 domain from binding with a phosphoprotein and a method of treating breast cancer.

CYCLIC AMINE BACE-1 INHIBITORS HAVING A BENZAMIDE SUBSTITUENT

Disclosed are compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein R1 is R is C(O)N(R27)(R28) or and the remaining variables are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of treating cognitive or neurodegenerative diseases such as Alzheimer's disease. Also disclosed are pharmaceutical compositions and methods of treating cognitive or neurodegenerative diseases comprising the compounds of formula I in combination with a -secretase inhibitor other than those of formula I, an HMG-CoA reductase inhibitor, a gamma-secretase inhibitor, a non-steroidal anti-inflammatory agent, an N-methyl-D-aspartate receptor antagonist, a cholinesterase inhibitor or an anti-amyloid antibody.

Cyclic amine BACE-1 inhibitors having a benzamide substituent

Disclosed are compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein R1 is R is C(O)N(R27)(R28) or and the remaining variables are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of treating cognitive or neurodegenerative diseases such as Alzheimer's disease. Also disclosed are pharmaceutical compositions and methods of treating cognitive or neurodegenerative diseases comprising the compounds of formula I in combination with a -secretase inhibitor other than those of formula I, an HMG-CoA reductase inhibitor, a gamma-secretase inhibitor, a non-steroidal anti-inflammatory agent, an N-methyl-D-aspartate receptor antagonist, a cholinesterase inhibitor or an anti-amyloid antibody.

CYCLIC AMINE BACE-1 INHIBITORS HAVING A BENZAMIDE SUBSTITUENT

Disclosed are compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein R is- C(O)-N(R27)(R28) or and the remaining variables are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of treating cognitive or neurodegenerative diseases such as Alzheimer's disease. Also disclosed are pharmaceutical compositions and methods of treating cognitive or neurodegenerative diseases comprising the compounds of formula I in combination with a β-secretase inhibitor other than those of formula I, an HMG-CoA reductase inhibitor, a gamma-secretase inhibitor, a non-steroidal anti- inflammatory agent, and N-methyl-D-aspartate receptor antagonist, a cholinesterase inhibitor or an anti-amyloid antibody. © KIPO & WIPO 2007 ...

REDOX-STABLE, NON-PHOSPHORYLATED CYCLIC PEPTIDE INHIBITORS OF SH2 DOMAIN BINDING TO TARGET PROTEIN, CONJUGATES, THEREOF, COMPOSITIONS AND METHODS OF SYNTHESIS AND USE

A compound of formula: in which (i) aa¹ is Adi and aa⁴ is Glu or (ii) each of aa¹ and aa⁴ is Adi, L is sulfur, sulfoxide, oxygen or methylene, which compound (and its conjugates) bind to an SH2 domain in a protein comprising an SH2 domain, is non-phosphorylated, is redox-stable in vivo, is characterized by an IC₅₀ in vivo of less than about 4.0 muM with respect to the SH2 domain in Grb2, and, upon binding to the SH2 domain of Grb2, has a turn conformation. A conjugate comprising a compound as described above and a carrier agent, a composition comprising (i) a compound or a conjugate as described above and (ii) a carrier, a method of inhibiting binding of an SH2 domain in a protein comprising an SH2 domain to a target protein in an animal, wherein the SH2 domain is contacted with a target protein-binding inhibiting effective amount of a compound or a conjugate as described above, and a method of synthesizing such conjugates.

Compounds and uses thereof

The present invention relates to methods and compositions for treating BAF-related conditions, such as cancer and viral infections.

Macrocyclic beta-secretase inhibitors

Disclosed are novel compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein R¹, R², R³, n and X are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of treating cognitive or neurodegenerative diseases such as Alzheimer's disease. Also disclosed are methods of treating a cognitive or neurodegenerative disease comprising administering to a patient I need of such treatment a combination of at least one compound of formula I and at least one compound selected from the group consisting of beta-secretase inhibitors other than those of formula I, HMG-CoA reductase inhibitors, gamma-secretase inhibitors, non-steroidal anti-inflammatory agents, N-methyl-D-aspartate receptor antagonists, cholinesterase inhibitors and anti-amyloid antibodies.

INHIBITORS OF FATTY ACID BINDING PROTEIN (FABP)

The present invention relates to novel heterocyclic compounds as Fatty Acid Binding Protein (FABP) inhibitors, pharmaceutical compositions comprising the heterocyclic compounds and the use of the compounds for treating or preventing a cardiovascular disease, a metabolic disorder, obesity or an obesity-related disorder, diabetes, dyslipidemia, a diabetic complication, impaired glucose tolerance or impaired fasting glucose. An illustrative compound of the present invention is shown below:

MACROCYCLIC BETA-SECRETASE INHIBITORS

Disclosed are novel compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein R1, R2, R3, n and X are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of treating cognitive or neurodegenerative diseases such as Alzheimer's disease. Also disclosed are methods of treating a cognitive or neurodegenerative disease comprising administering to a patient I need of such treatment a combination of at least one compound of formula I and at least one compound selected from the group consisting of -secretase inhibitors other than those of formula I, HMG-CoA reductase inhibitors, gamma-secretase inhibitors, non-steroidal anti-inflammatory agents, N-methyl-D-aspartate receptor antagonists, cholinesterase inhibitors and anti-amyloid antibodies.

HETEROCYCLIC ASPARTYL PROTEASE INHIBITORS

Disclosed are compounds of the formula I 1. (canceled)2. A pharmaceutical composition comprising an effective amount of a compound of and a pharmaceutically effective carrier.3. A method of inhibiting aspartyl protease comprising administering to a patient in need of such treatment an effective amount of a compound of .4. A method of treating cardiovascular diseases claim 16 , cognitive and neurodegenerative diseases claim 16 , and the methods of inhibiting of Human Immunodeficiency Virus claim 16 , plasmepins claim 16 , cathepsin D and protozoal enzymes comprising administering to a patient in need of such treatment an effective amount of a compound of .5. The method of wherein a cognitive or neurodegenerative disease is treated.6. The method of wherein Alzheimer's disease is treated.7. A pharmaceutical composition comprising an effective amount of a compound of claim 16 , and an effective amount of a cholinesterase inhibitor or a muscarinic magonist or mantagonist in a pharmaceutically effective carrier.8. A method of treating a cognitive or neurodegenerative disease comprising administering to a patient in need of such treatment an effective amount of a compound of in combination with an effective amount of a cholinesterase inhibitor.9. The method of wherein Alzheimer's disease is treated.10. A method of treating a cognitive or neurodegenerative disease comprising administering to a patient in need of such treatment an effective amount of a compound of in combination with an effective amount of a gamma secretase inhibitor claim 16 , an HMG-CoA reductase inhibitor or non-steroidal anti-inflammatory agent.11. The method of wherein Alzheimer's disease is treated.12. The method of wherein said HMG-CoA reductase inhibitor is atorvastatin claim 10 , lovastatin claim 10 , simvistatin claim 10 , pravastatin claim 10 , fluvastatin or rosuvastatin.13. The method of wherein said non-steroidal anti-inflammatory agent is ibuprofen claim 10 , relafen or naproxen.14. A ...

ASPARTYL PROTEASE INHIBITORS

Disclosed are compounds of the formula (I) or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein j, k, U, W, R, R1, R2, R3, R4, R6, R7 and R7a are as described above in the specification. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula (I) in combination with a cholinesterase inhibitor or a muscarinic m1 agonist or m2 antagonist. © KIPO & WIPO 2008 ...

Gamma secretase modulators

In its many embodiments, the present invention provides a novel class of heterocyclic compounds as modulators of gamma secretase, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the central nervous system using such compounds or pharmaceutical compositions.

Aspartyl protease inhibitors

Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein j, k, U, W, R, R¹, R², R³, R⁴, R⁶, R⁷ and R^7a are as described above in the specification. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic m₁ agonist or m₂ antagonist.

CYCLIC AMINE BACE-1 INHIBITORS HAVING A HETEROCYCLIC SUBSTITUENT

Disclosed are novel compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein R1 is X is -O-, -C(R14)2- or -N(R)-; Z is -C(R14)2- or -N(R)-; t is 0, 1, 2 or 3; each R and R2 is independently H, alkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, heterocycloalkylalkyl, alkenyl or alkynyl; each R14 is H, alkyl, alkenyl, alkynyl, halo, -CN, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, heterocycloalkylalkyl, -OR35, -N(R24) (R25) or -SR35; R41 is alkyl, cycloalkyl, -SO2(alkyl), -C(O)-alkyl, -C(O)-cycloalkyl or -alkyl-NH-C(O)CH3; and the remaining variables are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I and methods of treating cognitive or neurodegenerative diseases with compounds of formula I. Also disclosed are pharmaceutical compositions and methods of treatment comprising compounds ...

INHIBITORS OF FATTY ACID BINDING PROTEIN (FABP)

The present invention relates to novel heterocyclic compounds as Fatty Acid Binding Protein (FABP) inhibitors, pharmaceutical compositions comprising the heterocyclic compounds and the use of the compounds for treating or preventing a cardiovascular disease, a metabolic disorder, obesity or an obesity-related disorder, diabetes, dyslipidemia, a diabetic complication, impaired glucose tolerance or impaired fasting glucose. An illustrative compound of the present invention is shown below: (I) ...

Macrocyclic Heterocyclic Aspartyl Protease Inhibitors

Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt, solvate or ester thereof, wherein U, W, X, L, Y, M, Z, c, d, e, f, g, h, s, t, R1, R2, R7, R8, R9, R10, R11, R12, R13, R14, R15, R16, R17 and R18 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic m1 agonist or m2 antagonist.

Heterocyclic aspartyl protease inhibitors

Disclosed are compounds of the formula (I) a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, and pharmaceutical compositions comprising the compounds of formula (I). Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of Human Immunodeficiency Virus, plasmepins, cathepsin D and protozoal enzymes. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula (I) in combination with a cholinesterase inhibitor or a muscarinic m1 agonist or m2 antagonist.

Heterocyclic aspartyl protease inhibitors

Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein W is a bond, C(S), S(O), S(O)2, C(O), O, C(R6)(R7), N(R5) or C(N(R5)); X is O, N(R5) or C(R6)(R7); provided that when X is O, U is not O, S(O), S(O)2, C(O) or C(NR5); U is a bond, S(O), S(O)2, C(O), O, P(O)(OR15), C(NR5), (C(R6)(R7))b or N(R5); wherein b is 1 or 2; provided that when W is S(O), S(O)2, O, or N(R5), U is not S(O), S(O)2, O, or N(R5); provided that when X is N(R5) and W is S(O), S(O)2, O, or N(R5), then U is not a bond; and R1, R2, R3, R4, R5, R6, and R7 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of Human Immunodeficiency Virus, plasmepins, cathepsin D and protozoal enzymes. Also ...

Heterocyclic aspartyl protease inhibitors

Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein W is a bond, -C(-S)-, -S(O)-, -S(O)₂-, -C(-O)-, -O-, -C(R⁶)(R⁷)-, -N(R⁵)- or -C(-N(R⁵))-; X is -O-, -N(R⁵)- or -C(R⁶)(R⁷)-; provided that when X is -O-, U is not -O-, -S(O)-, -S(O)₂-, -C(-O)- or -C(-NR⁵)-; U is a bond, -S(O)-, -S(O)₂-, -C(O)-, -O-, -P(O)(OR¹⁵)-, -C(-NR⁵)-, -(C(R⁶)(R⁷))_b- or -N(R⁵)-; wherein b is 1 or 2; provided that when W is -S(O)-, -S(O)₂-, -O-, or -N(R⁵)-, U is not -S(O)-, -S(O)₂-, -O-, or -N(R⁵)-; provided that when X is -N(R⁵)- and W is -S(O)-, -S(O)₂-, -O-, or -N(R⁵)-, then U is not a bond; and R¹, R², R³, R⁴, R⁵, R ^{Подробнее}

HETEROCYCLIC ASPARTYL PROTEASE INHIBITORS

Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein W is a bond, -C(-S)-, -S(O)-, -S(O)2-, -C(-O)-, -O-, -C(R6)(R7)-, -N(R5)- or -C(-N(R5))-; X is -O-, -N(R5)- or -C(R6)(R7)-; provided that when X is -O-, U is not -O-, -S(O)-, -S(O)2-, -C(-O)- or -C(-NR5)-; U is a bond, -S(O)-, -S(O)2-, -C(O)-, -O-, -P(O)(OR15)-, -C(-NR5)-, -(C(R6)(R7))b- or -N(R5)-; wherein b is 1 or 2; provided that when W is -S(O)-, -S(O)2-, -O-, or -N(R5)-, U is not -S(O)-, -S(O)2-, -O-, or -N(R5)-; provided that when X is -N(R5)- and W is -S(O)-, -S(O)2-, -O-, or -N(R5)-, then U is not a bond; and R1, R2, R3, R4, R5, R6, and R7 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of ...

Cyclic amine bace-1 inhibitors having a heterocyclic substituent

Disclosed are novel compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 is X is —O—, —C(R 14 ) 2 — or —N(R)—; Z is —C(R 14 ) 2 — or —N(R)—; t is 0, 1, 2 or 3; each R and R 2 is independently H, alkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, heterocycloalkylalkyl, alkenyl or alkynyl; each R 14 is H, alkyl, alkenyl, alkynyl, halo, —CN, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, heterocycloalkylalkyl, —OR 35 , —N(R 24 )(R 25 ) or —SR 35 ; R 41 is alkyl, cycloalkyl, —SO 2 (alkyl), —C(O)-alkyl, —C(O)-cycloalkyl or -alkyl-NH—C(O)CH 3 ; and the remaining variables are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I and methods of treating cognitive or neurodegenerative diseases with compounds of formula I. Also disclosed are pharmaceutical compositions and methods of treatment comprising compounds of formula I in combination with other agents useful in treating cognitive or neurodegenerative diseases.

Aspartyl protease inhibitors

Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein j, k, U, W, R, R1, R2, R3, R4, R6, R7 and R7a are as described above in the specification. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic m1 agonist or m2 antagonist.

INHIBITORS OF FATTY ACID BINDING PROTEIN

The present invention relates to novel heterocyclic compounds as Fatty Acid Binding Protein (FABP) inhibitors, pharmaceutical compositions comprising the heterocyclic compounds and the use of the compounds for treating or preventing a cardiovascular disease, a metabolic disorder, obesity or an obesity-related disorder, diabetes, dyslipidemia, a diabetic complication, impaired glucose tolerance or impaired fasting glucose.

Heterocyclic aspartyl protease inhibitors

Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein W is a bond, C(S), S(O), S(O)2, C(O), O, C(R6)(R7), N(R5) or C(N(R5)); X is O, N(R5) or C(R6)(R7); provided that when X is O, U is not O, S(O), S(O)2, C(O) or C(NR5); U is a bond, S(O), S(O)2, C(O), O, P(O)(OR15), C(NR5), (C(R6)(R7))b or N(R5); wherein b is 1 or 2; provided that when W is S(O), S(O)2, O, or N(R5), U is not S(O), S(O)2, O, or N(R5); provided that when X is N(R5) and W is S(O), S(O)2, O, or N(R5), then U is not a bond; and R1, R2, R3, R4, R5, R6, and R7 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of Human Immunodeficiency Virus, plasmepins, cathepsin D and protozoal enzymes. Also ...

Inhibitors of fatty acid binding protein (FABP)

The present invention relates to novel heterocyclic compounds as Fatty Acid Binding Protein (FABP) inhibitors, pharmaceutical compositions comprising the heterocyclic compounds and the use of the compounds for treating or preventing a cardiovascular disease, a metabolic disorder, obesity or an obesity-related disorder, diabetes, dyslipidemia, a diabetic complication, impaired glucose tolerance or impaired fasting glucose. An illustrative compound of the present invention is shown below: ...

GAMMA SECRETASE MODULATORS

In its many embodiments, the present invention provides a novel class of heterocyclic compounds as modulators of gamma secretase, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the central nervous system using such compounds or pharmaceutical compositions.

Heterocyclic aspartyl protease inhibitors

Disclosed are compounds of the formula (I) or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of Human Immunodeficiency Virus, plasmepins, cathepsin D and protozoal enzymes. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula (I) in combination with a cholinesterase inhibitor or a muscarinic antagonist. The formula (I) is shown in the description.

Heterocyclic aspartyl protease inhibitors

Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein W is a bond, -C(-S)-, -S(O)-, -S(O)₂-, -C(-O)-, -O-, -C(R⁶)(R⁷)-, -N(R⁵)- or -C(-N(R⁵))-; X is -O-, -N(R⁵)- or -C(R⁶)(R⁷)-; provided that when X is -O-, U is not -O-, -S(O)-, -S(O)₂-, -C(-O)- or -C(-NR⁵)-; U is a bond, -S(O)-, -S(O)₂-, -C(O)-, -O-, -P(O)(OR¹⁵)-, -C(-NR⁵)-, -(C(R⁶)(R⁷))_b- or -N(R⁵)-; wherein b is 1 or 2; provided that when W is -S(O)-, -S(O)₂-, -O-, or -N(R⁵)-, U is not -S(O)-, -S(O)₂-, -O-, or -N(R⁵)-; provided that when X is -N(R⁵)- and W is -S(O)-, -S(O)₂-, -O-, or -N(R⁵)-, then U is not a bond; and R¹, R², R³, R⁴, R⁵, R ^{Подробнее}

Heterocyclic aspartyl protease inhibitors

Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein W is a bond, C(S), S(O), S(O)2, C(O), O, C(R6)(R7), N(R5) or C(N(R5)); X is O, N(R5) or C(R6)(R7); provided that when X is O, U is not O, S(O), S(O)2, C(O) or C(NR5); U is a bond, S(O), S(O)2, C(O), O, P(O)(OR15), C(NR5), (C(R6)(R7))b or N(R5); wherein b is 1 or 2; provided that when W is S(O), S(O)2, O, or N(R5), U is not S(O), S(O)2, O, or N(R5); provided that when X is N(R5) and W is S(O), S(O)2, O, or N(R5), then U is not a bond; and R1, R2, R3, R4, R5, R6, and R7 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of Human Immunodeficiency Virus, plasmepins, cathepsin D and protozoal enzymes. Also ...

Cyclic amine bace-1 inhibitors having a benzamide substituent

Disclosed are compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein R¹ is R is -C(O)-N(R²⁷)(R²⁸) or and the remaining variables are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of treating cognitive or neurodegenerative diseases such as Alzheimer's disease. Also disclosed are pharmaceutical compositions and methods of treating cognitive or neurodegenerative diseases comprising the compounds of formula I in combination with a beta-secretase inhibitor other than those of formula I, an HMG-CoA reductase inhibitor, a gamma-secretase inhibitor, a non-steroidal anti-inflammatory agent, an N-methyl-D-aspartate receptor antagonist, a cholinesterase inhibitor or an anti-amyloid antibody.

Cyclic amine BACE-1 inhibitors having a benzamide substituent

Disclosed are compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 is R is —C(O)—N(R 27 )(R 28 ) or and the remaining variables are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of treating cognitive or neurodegenerative diseases such as Alzheimer's disease. Also disclosed are pharmaceutical compositions and methods of treating cognitive or neurodegenerative diseases comprising the compounds of formula I in combination with a β-secretase inhibitor other than those of formula I, an HMG-CoA reductase inhibitor, a gamma-secretase inhibitor, a non-steroidal anti-inflammatory agent, an N-methyl-D-aspartate receptor antagonist, a cholinesterase inhibitor or an anti-amyloid antibody.

HETEROCYCLIC ASPARTYL PROTEASE INHIBITORS

Disclosed are compounds of the formula I 167-. (canceled)69. A pharmaceutical composition comprising a compound of claim 68 , or a tautomer thereof claim 68 , or a pharmaceutically acceptable salt of said compound or said tautomer claim 68 , and a pharmaceutically acceptable carrier.70. A pharmaceutical composition according to claim 69 , further comprising at least one additional active agent selected from:{'sub': 1', '2', 'A, 'b': '1', 'a cholinesterase inhibitor; a muscarinic magonist; a muscarinic mantagonist; a N-methyl-D-aspartate receptor antagonist; a beta secretase inhibitor other than a compound of claim ; a gamma secretase inhibitor; an HMG-CoA reductase inhibitor; a cholesterol absorption inhibitor; a non-steroidal anti-inflammatory agent; an anti-amyloid antibody; vitamin E; a nicotinic acetylcholine receptor agonist; a CB1 receptor inverse agonist; a CB1 receptor antagonist; an antibiotic; a growth hormone secretagogue; a histamine H3 antagonist; an AMPA agonist; a PDE4 inhibitor; a GABAinverse agonist;'}an inhibitor of amyloid aggregation; a glycogen synthase kinase beta inhibitor; and a promoter of alpha secretase activity; and a pharmaceutically acceptable carrier.71. A method of inhibiting aspartyl protease comprising administering to a patient in need thereof with an effective amount of a compound of claim 68 , or said tautomer thereof claim 68 , or a pharmaceutically acceptable salt of said compound or said tautomer.72. A method of treating cardiovascular disease claim 68 , cognitive or neurodegenerative disease claim 68 , a fungal infection claim 68 , or a protozoal infection claim 68 , said method comprising administering to a patient in need of such treatment an effective amount of a compound of claim 68 , or said tautomer thereof claim 68 , or a pharmaceutically acceptable salt of said compound or said tautomer.73. A method of treating a cognitive or neurodegenerative disease claim 68 , said method comprising administering to a patient in ...

Redox-stable, non-phosphorylated cyclic peptide inhibitors of SH2 domain binding to target protein, conjugates thereof, compositions and methods of synthesis and use

A compound of formula: in which (i) aa 1 is Adi and aa 4 is Glu or (ii) each of aa 1 and aa 4 is Adi, L is sulfur, sulfoxide, oxygen or methylene, which compound (and its conjugates) bind to an SH2 domain in a protein comprising an SH2 domain, is non-phosphorylated, is redox-stable in vivo, is characterized by an IC 50 in vivo of less than about 4.0 μM with respect to the SH2 domain in Grb2, and, upon binding to the SH2 domain of Grb2, has a turn conformation. A conjugate comprising a compound as described above and a carrier agent, a composition comprising (i) a compound or a conjugate as described above and (ii) a carrier, a method of inhibiting binding of an SH2 domain in a protein comprising an SH2 domain to a target protein in an animal, wherein the SH2 domain is contacted with a target protein-binding inhibiting effective amount of a compound or a conjugate as described above, and a method of synthesizing such conjugates.

Heterocyclic aspartyl protease inhibitors

Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein W is a bond, -C(-S)-, -S(O)-, -S(O)2-, -C(-O)-, -O-, -C(R6)(R7)-, -N(R5)- or -C(-N(R5))-; X is -O-, -N(R5)- or -C(R6)(R7)-; provided that when X is -O-, U is not -O-, -S(O)-, -S(O)2-, -C(-O)- or -C(-NR5)-; U is a bond, -S(O)-, -S(O)2-, -C(O)-, -O-, -P(O)(OR15)-, -C(-NR5)-, -(C(R6)(R7))b- or -N(R5)-; wherein b is 1 or 2; provided that when W is -S(O)-, -S(O)2-, -O-, or -N(R5)-, U is not -S(O)-, -S(O)2-, -O-, or -N(R5)-; provided that when X is -N(R5)- and W is -S(O)-, -S(O)2-, -O-, or -N(R5)-, then U is not a bond; and R1, R2, R3, R4, R5, R6, and R7 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of ...

Gamma secretase modulators

The present invention provides a novel class of heterocyclic compounds of Formula (I) as modulators of gamma secretase, wherein the definitions of the variables of Formula (I) are defined herein, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the central nervous system using such compounds or pharmaceutical compositions.

Heterocyclic aspartyl protease inhibitors

Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein W, U, X, R1, R2, R3, and R4 are as defined herein, and pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of using such compounds to inhibit aspartyl protease and to treat a variety of disease or disorders, including cardiovascular diseases, cognitive and neurodegenerative diseases. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic antagonist ...

HETEROCYCLIC ASPARTYL PROTEASE INHIBITORS

Disclosed are compounds of the formula I 167-. (canceled)69. The method of claim 68 , wherein said disease or disorder is cardiovascular disease claim 68 , cognitive or neurodegenerative disease claim 68 , a fungal infection claim 68 , or a protozoal infection.70. The method of claim 68 , wherein said disease or disorder is cognitive or neurodegenerative disease.71. The method of claim 68 , wherein said disease or disorder is Alzheimer's disease.85. The method according to any one of to claim 68 , further comprising administering claim 68 , simultaneously or sequentially claim 68 , at least one additional active agent selected from:{'sub': 1', '2', 'A, 'b': '1', 'a cholinesterase inhibitor; a muscarinic magonist; a muscarinic mantagonist; a N-methyl-D-aspartate receptor antagonist; a beta secretase inhibitor other than a compound of claim ; a gamma secretase inhibitor; an HMG-CoA reductase inhibitor; a cholesterol absorption inhibitor; a non-steroidal anti-inflammatory agent; an anti-amyloid antibody; vitamin E; a nicotinic acetylcholine receptor agonist; a CB1 receptor inverse agonist; a CB1 receptor antagonist; an antibiotic; a growth hormone secretagogue; a histamine H3 antagonist; an AMPA agonist; a PDE4 inhibitor; a GABAinverse agonist; an inhibitor of amyloid aggregation; a glycogen synthase kinase beta inhibitor; and a promoter of alpha secretase activity; and a pharmaceutically acceptable carrier.'} This application is a Divisional application of U.S. patent application Ser. No. 12/693,874, filed Jan. 26, 2010, pending, which is a Divisional application of U.S. patent application Ser. No. 11/710,582, filed Feb. 23, 2007, U.S. Pat. No. 7,763,609, incorporated herein by reference.This invention relates to heterocyclic aspartyl protease inhibitors, pharmaceutical compositions comprising said compounds, their use in the treatment of cardiovascular diseases, cognitive and neurodegenerative diseases, and their use as inhibitors of the Human Immunodeficiency Virus, ...

Macrocyclic beta-secretase inhibitors

Disclosed are novel compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein R<1>, R<2>, R<3>, n and X are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of treating cognitive or neurodegenerative diseases such as Alzheimer's disease. Also disclosed are methods of treating a cognitive or neurodegenerative disease comprising administering to a patient I need of such treatment a combination of at least one compound of formula I and at least one compound selected from the group consisting of beta-secretase inhibitors other than those of formula I, HMG-CoA reductase inhibitors, gamma-secretase inhibitors, non-steroidal anti-inflammatory agents, N-methyl-D-aspartate receptor antagonists, cholinesterase inhibitors and anti-amyloid antibodies.

COMPOUNDS AND USES THEREOF

The present invention relates to methods and compositions for the treatment of BAF-related disorders such as cancers and viral infections. 23-. (canceled)4. The compound of claim 1 , wherein Ris optionally substituted C-Calkyl.611-. (canceled)13. (canceled)14. The compound of claim 1 , wherein Zis CR.1516-. (canceled)18. The compound of claim 1 , wherein Xis N and Xis C—R″.1921-. (canceled)22. The compound of claim 18 , wherein R″ is optionally substituted C-Calkyl claim 18 , optionally substituted C-Cheteroalkyl claim 18 , optionally substituted carbocyclyl having 3 to 6 atoms claim 18 , or optionally substituted heterocyclyl having 3 to 6 atoms.2324-. (canceled)25. The compound of claim 22 , wherein R″ is optionally substituted C-Cheteroalkyl.2627-. (canceled)28. The compound of claim 25 , wherein R″ is —NRR.2938-. (canceled)39. The compound of claim 22 , wherein R″ is optionally substituted heterocyclyl having 3 to 6 atoms.4174-. (canceled)75. The compound of claim 1 , wherein G″ is optionally substituted C-Caryl.77. (canceled)78. The compound of claim 76 , wherein each of R claim 76 , R claim 76 , R claim 76 , R claim 76 , and Ris claim 76 , independently claim 76 , H claim 76 , halogen claim 76 , optionally substituted C-Calkyl claim 76 , optionally substituted C-Cheteroalkyl claim 76 , optionally substituted —O—C-Ccarbocyclyl claim 76 , or optionally substituted —C-Calkyl-C-Cheterocyclyl.80105-. (canceled)107115-. (canceled)117. (canceled)118. The compound of claim 1 , wherein the degradation moiety is a ubiquitin ligase binding moiety.119133-. (canceled)135140-. (canceled)143152-. (canceled)153. A pharmaceutical composition comprising the compound of and a pharmaceutically acceptable excipient.154164-. (canceled)165. A method of treating a cancer in a subject in need thereof claim 1 , the method including administering to the subject an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.166179-. (canceled)180. The method ...

COMPOUNDS AND USES THEREOF

The present invention relates to compositions and methods for the treatment of BAF-related disorders, such as cancers and viral infections. 6. The compound of any one of to , wherein Ris H , optionally substituted C-Calkyl , optionally substituted C-Calkenyl , or optionally substituted C-Ccarbocyclyl.7. The compound of claim 6 , wherein Ris H.8. The compound of claim 6 , wherein Ris optionally substituted C-Calkyl.10. The compound of claim 6 , wherein Ris optionally substituted C-Calkenyl.12. The compound of claim 6 , wherein Ris optionally substituted C-Ccarbocyclyl.15. The compound of any one of to claim 6 , wherein Zis N.16. The compound of any one of to claim 6 , wherein Zis CR.17. The compound of claim 16 , wherein Ris H claim 16 , halogen claim 16 , optionally substituted C-Calkyl claim 16 , optionally substituted C-Ccarbocyclyl claim 16 , or optionally substituted C-Caryl.18. The compound of claim 17 , wherein Ris H claim 17 , halogen claim 17 , or optionally substituted C-Calkyl.20. The compound of any one of to claim 17 , wherein X′ is a bond.21. The compound of any one of to claim 17 , wherein X′ is O claim 17 , NR′ claim 17 , or CR′R′.22. The compound of any one of to claim 17 , wherein X′ is NR′ or CR′R′.23. The compound of claim 22 , wherein X′ is NR′.24. The compound of any one of to claim 22 , wherein X′ is NR′ or CR′R′.25. The compound of any one of to claim 22 , wherein X′ is a bond.26. The compound of any one of to claim 22 , wherein X′ is O claim 22 , NR′ claim 22 , or CR′R′.27. The compound of any one of to claim 22 , wherein X′ is CR′R′; X′ is NR′; X′ is CR′R′; and X′ is CR′R′.28. The compound of any one of to claim 22 , wherein X′ is CR′R′; X′ is CR′R′; X′ is NR′; and X′ is CR′R′.29. The compound of any one of to claim 22 , wherein X′ is O or NR′; X′ is CR′R′; X′ is CR′R′; and X′ is O or NR′.30. The compound of any one of to claim 22 , wherein X′ is a bond; X′ is CR′R′; X′ is O or NR′; and X′ is CR′R′.31. The compound of any one of to claim 22 ...

COMPOUNDS AND USES THEREOF

The present disclosure features compounds useful for the treatment of BAF complex-related disorders. 9. A method of reducing the level and/or activity of BRD9 in a cell claim 1 , the method involving contacting the cell with an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.1016-. (canceled)17. A method of treating a BAF complex-related disorder claim 1 , an SS18-SSX-related disorder claim 1 , and/or a BRD9-related disorder in a subject in need thereof claim 1 , the method involving administering to the subject an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.1820-. (canceled)21. A method of treating a cancer in a subject in need thereof claim 1 , the method including administering to the subject an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.22. The method of claim 21 , wherein the cancer is a malignant claim 21 , rhabdoid tumor claim 21 , a CD8+ T-cell lymphoma claim 21 , endometrial carcinoma claim 21 , ovarian carcinoma claim 21 , bladder cancer claim 21 , stomach cancer claim 21 , pancreatic cancer claim 21 , esophageal cancer claim 21 , prostate cancer claim 21 , renal cell carcinoma claim 21 , melanoma claim 21 , colorectal cancer claim 21 , a sarcoma claim 21 , non-small cell lung cancer claim 21 , stomach cancer claim 21 , or breast cancer.23. The method of claim 22 , wherein the cancer is a sarcoma.24. The method of claim 23 , wherein the sarcoma is a soft tissue sarcoma claim 23 , synovial sarcoma claim 23 , Ewing's sarcoma claim 23 , osteosarcoma claim 23 , rhabdomyosarcoma claim 23 , adult fibrosarcoma claim 23 , alveolar soft-part sarcoma claim 23 , angiosarcoma claim 23 , clear cell sarcoma claim 23 , desmoplastic small round cell tumor claim 23 , epithelioid sarcoma claim 23 , fibromyxoid sarcoma claim 23 , gastrointestinal stromal tumor claim 23 , Kaposi sarcoma claim 23 , liposarcoma claim 23 , leiomyosarcoma claim 23 ...

Heterocyclic aspartyl protease inhibitors

Disclosed are compounds of the formula (I) or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein W is a bond, -C(=S)-, -S(O)-, -S(O)2-, -C(=O)-, -O-, -C(R6)(R7)-, -N(R5)- or -C(=N(R5))-; X is -O-, -N(R5)- or -C(R6)(R7)-; provided that when X is -O-, U is not -O-, -S(O)-, -S(O)2-, -C(=O)- or -C(=NR5)-; U is a bond, -S(O)-, -S(O)2-, -C(O)-, -O-, -P(O)(OR15)-, -C(=NR5)-, -(C(R6)(R7))b- or -N(R5)-; wherein b is 1 or 2; provided that when W is -S(O)-, -S(O)2-, -O-, or -N(R5)-, U is not -S(O)-, -S(O)2-, -O-, or -N(R5)-; provided that when X is -N(R5)- and W is -S(O)-, -S(O)2-, -O-, or -N(R5)-, then U is not a bond; and R1, R2, R3, R4, R5, R6, and R7 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula (I). Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of Human Immunodeficiency Virus, plasmepins, cathepsin D and protozoal enzymes. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic m1 agonist or m2 antagonist.

HETEROCYCLIC ASPARTYL PROTEASE INHIBITORS

HETEROCYCLIC COMPOUNDS AS ASPARTILE PROTEASE INHIBITORS

SE REFIERE A COMPUESTOS DE FORMULA (I), EN DONDE W ES UN ENLACE, -C(=S)-, -S(O)(1-2)-, -C(=O)-, -O-, -C(R6)(R7)-, ENTRE OTROS; X ES -O-, -N(R5)- O -C(R6)(R7)-, CON LA CONDICION DE QUE CUANDO X ES -O- U NO SEA -O-, -S(O)(1-2)-, -C(=O)- O -C(=NR5)-; U ES -S(O)(1-2)-, -C(O)-,-O-, -(C(R6)(R7))b-, ENTRE OTROS; R1, R2 Y R5 SON INDEPENDIENTEMENTE, H, ALQUILO, ALQUENILO, ENTRE OTROS; R3 Y R4 SON INDEPENDIENTEMENTE, H, ALQUILO, CICLOALQUILO, ENTRE OTROS. SON COMPUESTOS PREFERIDOS: 5-ETILCICLOHEXIL-2-IMINO-3-METIL-5-({3-[(2-OXOETIL)AMINO]CICLOHEXIL}METIL)-IMIDAZOL-4-ONA, 5-ETILCICLOHEXIL-2-IMINO-3-METIL-5-({3-(PIRROLIDIN)-CICLOHEXIL}METIL)-IMIDAZOL-4-ONA, ENTRE OTROS. TAMBIEN SE REFIERE A UN COMPOSICION FARMACEUTICA. ESTOS COMPUESTOS SON INHIBIDORES DE LA ASPARTIL PROTEASA, POR LO QUE SON UTILES EN EL TRATAMIENTO DE ENFERMEDADES CARDIOVASCULARES, COGNITIVAS Y NEURODEGENERATIVAS REFERS TO COMPOUNDS OF FORMULA (I), WHERE W IS A LINK, -C (= S) -, -S (O) (1-2) -, -C (= O) -, -O-, - C (R6) (R7) -, AMONG OTHERS; X IS -O-, -N (R5) - O -C (R6) (R7) -, WITH THE CONDITION THAT WHEN X IS -O- U IT IS NOT -O-, -S (O) (1-2 ) -, -C (= O) - O -C (= NR5) -; U IS -S (O) (1-2) -, -C (O) -, - O-, - (C (R6) (R7)) b-, AMONG OTHERS; R1, R2 AND R5 ARE INDEPENDENTLY, H, ALKYL, ALKENYL, AMONG OTHERS; R3 AND R4 ARE INDEPENDENTLY, H, ALKYL, CYCLOALKYL, AMONG OTHERS. PREFERRED COMPOUNDS ARE: 5-ETHYL CYCLOHEXIL-2-IMINO-3-METHYL-5 - ({3 - [(2-OXOETHYL) AMINO] CYCLOHEXYL} METHYL) -IMIDAZOL-4-ONA, 5-ETHYL CYCLOHEXIL-2-IMINO-3 -METIL-5 - ({3- (PYRROLIDIN) -CYCLOHEXYL} METHYL) -IMIDAZOL-4-ONA, AMONG OTHERS. IT ALSO REFERS TO A PHARMACEUTICAL COMPOSITION. THESE COMPOUNDS ARE INHIBITORS OF ASPARTILE PROTEASE, SO THEY ARE USEFUL IN THE TREATMENT OF CARDIOVASCULAR, COGNITIVE AND NEURODEGENERATIVE DISEASES

Heterocyclic aspartyl protease inhibitors

Sh2 domain binding inhibitors

Disclosed are compounds for SH2 domain binding inhibition. For example, disclosed is a compound of formula (I) wherein R1 is a lipophile; R2, in combination with the phenyl ring, is a phenylphosphate mimic group or a protected phenylphosphate mimic group; R3 is hydrogen, azido, amino, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, or alkylcarbonylamino, wherein the alkyl portion of R3 may be optionally substituted with a substituent selected from the group consisting of halo, hydroxy, carboxyl, amino, aminoalkyl, alkyl, alkoxy, and keto; R6 is a linker; AA is an amino acid; and n is 1 to 6; or a salt thereof. The compounds of the present invention have the advantage that their conformation is constrained to provide enhanced binding affinity with SH2 domain protein. Also disclosed are a pharmaceutical composition comprising a pharmaceutically or pharmacologically acceptable carrier and a compound of the present invention, a method for inhibiting an SH2 domain from binding with a phosphoprotein comprising contacting an SH2 domain with a compound of the present invention, a method of preventing or treating a disease, state, or condition by the use of one or more of these compounds, and a method for preparing the compounds of the present invention. The present invention further provides intermediates useful in the preparation of the compounds.

Heterocyclic aspartyl protease inhibitors

Compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, and pharmaceutical compositions comprising the compounds of formula I. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of Human Immunodeficiency Virus, plasmepins, cathepsin D and protozoal enzymes. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic antagonist.

Macrocyclic heterocyclic aspartyl protease inhibitors

ABSTRACT Disclosed are compounds of the formula I (Chemical formula should be inserted here as it appears on abstract in final form) or a stereoisomer, tautomer, or pharmaceutically acceptable salt, solvate or ester thereof, wherein U, W, X, L, Y, M, Z, c, d, e, f, g, h, s, t, R1, R2, R7, R8, R9, R10, R11, R12, R13, R14, R15, R16 , R17 and R18 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic m1 agonist or m2 antagonist.

Compounds and uses thereof

The present disclosure features compounds useful for the treatment of BAF complex-related disorders.

Heterocyclic aspartyl protease inhibitors

Det er beskrevet forbindelser med formel (I) en stereoisomer, tautomer eller et farmasøytisk akseptabelt salt eller solvat derav, hvor W er en binding, -C(=S)-, -S(O)-, -S(O)2-, -C(=O)-, -O-, -C(R6)(R7), -N(R5)- eller -C(=N(R5))-; X er -O-, -N(R5)- eller -C(R6)(R7)-; forutsatt at når X er -O-, er U ikke -O-, -S(O)-, -S(O)2-, -C(=O)- eller -C(=NR5)-; U er en binding, -S(O)-, -S(O)2-, -C(O)-, -O-, -P(O)(OR15)-, -C(=NR5)-, -(C(R6)(R7))b- eller -N(R5)-, hvor b er 1 eller 2; forutsatt at når W er -S(O)-, -S(O)2-, -O- eller -N(R5)-, er U ikke -S(O)-, -S(O)2-, -O- eller -N(R5)-; forutsatt at når X er -N(R5) og W er -S(O)-, -S(O)2-, -O- eller -N(R5)-, er U ikke en binding; og R1, R2, R3, R4, R5, R6 og R7 er som definert i beskrivelsen; og farmasøytiske preparater som omfatter forbindelsene med formel (I). Det er også beskrevet en fremgangsmåte for hemming av aspartylprotease, og særlig fremgangsmåtene for behandling av kardiovaskulære sykdommer, kognitive og neurodegenerative sykdommer, og fremgangsmåtene for hemming av humant immunsviktvirus, plasmepiner, kathepsin D og protozoenzymer. Det er også beskrevet fremgangsmåter for behandling av kognitive eller neurodegenerative sykdommer under anvendelse av forbindelsene med formel I i kombinasjon med en kolinesteraseinhibitor eller en muskarin m1-agonist eller m2-antagonist.

Heterocyclic aspartyl protease inhibitors

Disclosed are compounds of the formula (I) or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, and pharmaceutical compositions comprising the compounds of formula (I). Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of Human Immunodeficiency Virus, plasmepins, cathepsin D and protozoal enzymes. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula (I) in combination with a cholinesterase inhibitor or a muscarinic m1 agonist or m2 antagonist.

Aspartyl protease inhibitors

Disclosed are compounds of the formula (I) or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein j, k, U, W, R, R1, R2, R3, R4, R6, R7 and R7a are as described above in the specification. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula (I) in combination with a cholinesterase inhibitor or a muscarinic m1 agonist or m2 antagonist.

Heterocyclic aspartyl protease inhibitors

Aspartyl protease heterocyclic inhibitors

Un compuesto, o un tautomero del mismo, o una sal farmaceuticamente aceptable de dicho compuesto o dicho tautomero, en donde dicho compuesto se selecciona entre el grupo que consiste en:**Tabla** A compound, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein said compound is selected from the group consisting of: ** Table **

Compounds and uses thereof

The present disclosure features compounds useful for the treatment of BAF complex-related disorders.

heterocyclic aspartyl protease inhibitor compounds, compositions and said uses

COMPOSTOS INIBIDORES DE ASPARTIL PROTEASE HETEROCICLICOS, COMPOSIÇÕES E REFERIDOS USOS. São descritos os compostos da fórmula I ou um estereoisômero, tautômero, ou sal farmaceuticamente aceitável ou solvato deste, onde w é uma ligação, -C(=S)-, -S(0)-, -S(O)~ 2~-, -C(=O)-, -O-, -C(R^ 6^) (R^ 7^)-, -N(R^ 5^)- ou C(=N(R^ 5^))-; X é -O-, -N(R^ 5^)- or -C(R^ 6^)(R^ 7^)-; contanto que quando X for -O-, U não seja -O-, -S(O)-, -S(O)~ 2~-, -C(=O)- ou -C(NR^ 5^)-; U é uma ligação, -S(O)-, -S(O)~ 2~-, -C(O)-, -O-, -P(O)(OR^ 15^)-, -C (=NR^ 5^)-, -(C(R^ 6^)(R^ 7^))~ b~- ou -N(R^ 5^)-; onde b é 1 ou 2; contanto que quando W for -S(O)-, -S(O)~ 2~-, -O-, ou -N(R^ 5^)-, U não seja -S(O)-, -S(O)~ 2~-, -O-, ou - N(R^ 5^)-; contanto que quando X for -N(R^ 5^)- e W for -S(O)-, -S(O)~ 2~-, -O-, ou - N(R^ 5^)-, então U não seja uma ligação; e R¹, R², Rü R^ 4^, R^ 5^, R^ 6^, e R^ 7^ são como definido na especificação; e composições farmacêuticas compreendendo os compostos de fórmula (1). É também descrito o método de inibição de aspartil protease, e em particular, os métodos de tratar doenças cardiovasculares, doenças cognitivas e neurodegenerativas, e os métodos de inibição do Vírus da Imuno-deficiência Humana, plasmepinas, catepsina D e enzimas protozoárias. São também descritos métodos de tratar doenças cognitivas ou neurodegenerativas empregando-se os compostos de fórmula I, em combinação com um inibidor de colinesterase ou um agonista m~ 1~ ou antagonista m~ 2~ muscarínico. HYPEROCYCLIC ASPARTIL PROTEASE INHIBITORS, COMPOSITIONS, AND USES. The compounds of formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof are described, where w is a bond, -C (= S) -, -S (O) -, -S (O) -2 -, -C (= O) -, -O-, -C (R 6 R 6) (R 4 7 R) -, -N (R 5 R 5) - or C (= N (R 5 R 5)) ) -; X is -O-, -N (R 5 R 6) - or -C (R 6 R 6) (R 7 R 7) -; provided that when X is -O-, U is not -O-, -S (O) -, -S (O) ~ 2 ~ -, -C (= O) - or -C (NR ^ 5 ^) - ; U is a bond, -S (O) -, -S (O) - ...

Compounds and uses thereof

The present invention relates to compositions and methods for the treatment of BAF-related disorders, such as cancers and viral infections.

Cyclic amine BACE-1 inhibitors having a benzamide substituent

Sh2 domain binding inhibitors

Disclosed are compounds for SH2 domain binding inhibition. For example, disclosed is a compound of formula (I) wherein R1 is a lipophile; R2, in combination with the phenyl ring, is a phenylphosphate mimic group or a protected phenylphosphate mimic group; R3 is hydrogen, azido, amino, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, or alkylcarbonylamino, wherein the alkyl portion of R3 may be optionally substituted with a substituent selected from the group consisting of halo, hydroxy, carboxyl, amino, aminoalkyl, alkyl, alkoxy, and keto; R6 is a linker; AA is an amino acid; and n is 1 to 6; or a salt thereof. The compounds of the present invention have the advantage that their conformation is constrained to provide enhanced binding affinity with SH2 domain protein. Also disclosed are a pharmaceutical composition comprising a pharmaceutically or pharmacologically acceptable carrier and a compound of the present invention, a method for inhibiting an SH2 domain from binding with a phosphoprotein comprising contacting an SH2 domain with a compound of the present invention, a method of preventing or treating a disease, state, or condition by the use of one or more of these compounds, and a method for preparing the compounds of the present invention. The present invention further provides intermediates useful in the preparation of the compounds.

aspartyl protease inhibitors

INIBIDORES DA ASPARTIL PROTEASE. A presente invenção refere-se a compostos de acordo com a Fórmula I ou um estereoisómero, um tautómero, ou um sal ou um solvato farmaceuticamente aceitável do mesmo, em que j, k, U, W, R, R^ 1^, R^ 2^, R^ 3^, R^ 4^, R^ 6^, R^ 7^ e R^ 7a^ são tal como descritos na especificação acima. é descrito também o método para inibição da aspartil protease, e particularmente, os métodos para tratamento das doenças cardiovasculares, doenças cognitivas e neurodegenerativas. São descritos também os métodos de tratar doenças cognitivas ou neurodegenerativas usando os compostos da Fórmula 1 em combinação com um inibidor da colinesterase ou um agonista ml ou antagonista m2 muscarinico. ASPARTIL PROTEASE INHIBITORS. The present invention relates to compounds according to Formula I or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt or solvate thereof, wherein j, k, U, W, R, R 1, R 2 ^ 2 ^, R ^ 3 ^, R ^ 4 ^, R ^ 6 ^, R ^ 7 ^ and R ^ 7a ^ are as described in the above specification. Also described is the method for inhibiting aspartyl protease, and particularly methods for treating cardiovascular disease, cognitive and neurodegenerative disease. Also described are methods of treating cognitive or neurodegenerative disorders using the compounds of Formula 1 in combination with a cholinesterase inhibitor or a muscarinic m2 agonist or antagonist.

Cyclic amine base-1 inhibitors having a heterocyclic substituent

Disclosed are novel compounds of the formula (I)or a pharmaceutically acceptable salt or solvate thereof, wherein R1 is formula (I) X is -0-, -C(R14)2- or -N(R)-; Z is -C(R14)2- or -N(R)-; t is 0, 1, 2 or 3; each R and R2 is independently H, alkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, heterocycloalkylalkyl, alkenyl or alkynyl; each R14 is H, alkyl, alkenyl, alkynyl, halo, -CN, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, heterocycloalkylalkyl, -OR35, -N(R24)(R25) or -SR35; R41 is alkyl, cycloalkyl, -S02(alkyl), -C(O)-alkyl, -C(O)-cycloalkyl or -alkyl-NH-C(O)CH3; and the remaining variables are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I and methods of treating cognitive or neurodegenerative diseases with compounds of formula (I). Also disclosed are pharmaceutical compositions and methods of treatment comprising compounds of formula I in combination with other agents useful in treating cognitive or neurodegenerative diseases.

Heterocyclic aspartyl protease inhibitors

Disclosed are compounds of the formula (I) or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein W is a bond, -C(=S)-, -S(O)-, -S(O)2-, -C(=O)-, -O-, -C(R6)(R7)-, -N(R5)- or -C(=N(R5))-; X is -O-, -N(R5)- or -C(R6)(R7)-; provided that when X is -O-, U is not -O-, -S(O)-, -S(O)2-, -C(=O)- or -C(=NR5)-; U is a bond, -S(O)-, -S(O)2-, -C(O)-, -O-, -P(O)(OR15)-, -C(=NR5)-, -(C(R6)(R7))b- or -N(R5)-; wherein b is 1 or 2; provided that when W is -S(O)-, -S(O)2-, -O-, or -N(R5)-, U is not -S(O)-, -S(O)2-, -O-, or -N(R5)-; provided that when X is -N(R5)- and W is -S(O)-, -S(O)2-, -O-, or -N(R5)-, then U is not a bond; and R1, R2, R3, R4, R5, R6, and R7 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula (I). Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of Human Immunodeficiency Virus, plasmepins, cathepsin D and protozoal enzymes. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic m1 agonist or m2 antagonist.

Aspartyl protease inhibitors

Cyclic amine BACE-1 inhibitors having a heterocyclic substituent

Heterocyclic aspartyl protease inhibitors

Disclosed are compounds of the formula (I) or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, and pharmaceutical compositions comprising the compounds of formula (I). Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of Human Immunodeficiency Virus, plasmepins, cathepsin D and protozoal enzymes. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula (I) in combination with a cholinesterase inhibitor or a muscarinic m1 agonist or m2 antagonist.

Cyclic amine bace-1 inhibitors having a benzamide substituent

Disclosed are compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein R is-C(O)-N(R27)(R28) or and the remaining variables are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of treating cognitive or neurodegenerative diseases such as Alzheimer~s disease. Also disclosed are pharmaceutical compositions and methods of treating cognitive or neurodegenerative diseases comprising the compounds of formula I in combination with a .beta.-secretase inhibitor other than those of formula I, an HMG-CoA reductase inhibitor, a gamma-secretase inhibitor, a non-steroidal anti-inflammatory agent, and N-methyl-D-aspartate receptor antagonist, a cholinesterase inhibitor or an anti-amyloid antibody.

HETEROCICLIC INHIBITORS OF ASPARTILE PROTEASE

SE REFIERE A COMPUESTOS HETEROCICLOS TALES COMO: 5-[4-(3-CLOROFENIL)-2-TIENIL]-2-IMINO-3-METIL-5-FENIL-4-IMIDAZOLIDINONA, 5-(3-BROMOFENIL)-2-IMINO-3-METIL-5-(1-METILCICLOPROPIL)-4-IMIDAZOLIDINONA, 5-[4-FLUORO-3-(3-PIRIDINIL)FENIL]-2-IMINO-3,5-DIMETIL-4-IMIDAZOLIDINONA, ENTRE OTROS, Y SALES FARMACEUTICAMENTE ACEPTABLES DE LOS MISMOS TALES COMO ACETATO, ALGINATO, CITRATO, FUMARATO, SUCCINATO, ENTRE OTROS. SE REFIERE TAMBIEN A UNA COMPOSICION FARMACEUTICA. DICHOS COMPUESTOS SON INHIBIDORES DE LA ASPARTIL PROTEASA SIENDO UTILES EN EL TRATAMIENTO DE HIPERTENSION, FALLA RENAL, ENFERMEDAD DE ALZHEIMER REFERS TO HETEROCICLOS COMPOUNDS SUCH AS: 5- [4- (3-CHLOROPHENYL) -2-THENYL] -2-IMINO-3-METHYL-5-PHENYL-4-IMIDAZOLIDINONE, 5- (3-BROMOPHENYL) -2- IMINO-3-METHYL-5- (1-METHYL CYCLOPROPYL) -4-IMIDAZOLIDINONE, 5- [4-FLUORO-3- (3-PYRIDINYL) PHENYL] -2-IMINO-3,5-DIMETHYL-4-IMIDAZOLIDINONE, BETWEEN OTHERS, AND PHARMACEUTICALLY ACCEPTABLE SALTS OF THE SAME SUCH AS ACETATE, ALGINATE, CITRATE, FUMARATE, SUCCINATE, AMONG OTHERS. IT ALSO REFERS TO A PHARMACEUTICAL COMPOSITION. SUCH COMPOUNDS ARE INHIBITORS OF ASPARTIL PROTEASE, BEING USEFUL IN THE TREATMENT OF HYPERTENSION, KIDNEY FAILURE, ALZHEIMER'S DISEASE

Compounds and uses thereof

The present disclosure features compounds and methods useful for the treatment of BAF complex-related disorders.

Triazolopyrimidinones and methods of use thereof

The present invention discloses a method of treating a cardiovascular disease or condition comprising administering therapeutically effective amounts of certain triazolopyrimidinones as Fatty Acid Binding Protein ("FABP") inhibitors. Examples of such disease or condition include metabolic disorder, obesity or an obesity-related disorder, diabetes, dyslipidemia, a diabetic complication, impaired glucose tolerance or impaired fasting glucose. An illustrative inventive method to treat the above-noted conditions uses the administration of the compound shown below: (I)

Heterocyclic aspartyl protease inhibitors

Compounds and uses thereof

The present disclosure features compounds useful for the treatment of BAF complex-related disorders.

Compounds and uses thereof

The present invention relates to compositions and methods for the treatment of BAF-related disorders, such as cancers and viral infections.

Compounds and uses thereof

The present disclosure features compounds useful for the treatment of BAF complex-related disorders.

Compounds and uses thereof

Pyrazine derivatives and uses thereof

The present disclosure features compounds of Formula I, or pharmaceutically acceptable salts thereof, and formulations containing the same. Methods of treating BAF complex-related disorders, such as cancer, are also disclosed.

Pyrazine derivatives and uses thereof

The present disclosure features compounds Formula I or II: or pharmaceutically acceptable salts thereof, and formulations containing the same. Methods of treating BAF complex-related disorders, such as cancer, are also disclosed.

Compounds and uses thereof

The present disclosure features compounds useful for the treatment of BAF complex-related disorders.

Compounds and uses thereof

The present disclosure features compounds useful for the treatment of BAF complex-related disorders.

Compuestos y usos de estos

La presente descripción presenta compuestos útiles para el tratamiento de trastornos relacionados con el complejo BAF.

Heterozyklische aspartyl-proteasehemmer

Compounds and uses thereof

The present invention relates to compositions and methods for the treatment of BAF-related disorders, such as cancers and viral infections.

Compounds and uses thereof

The present disclosure features compounds useful for the treatment of BAF complex-related disorders.

Compuestos y usos de estos

La presente descripción presenta compuestos útiles para el tratamiento de trastornos relacionados con el complejo BAF.

BRD9 degraders and uses thereof

The present invention relates to methods and compositions for the treatment of BAF-related disorders such as cancers and viral infections.

Compuestos y usos de estos.

La presente divulgación presenta compuestos útiles para el tratamiento de trastornos relacionados con el complejo BAF.

Compounds and uses thereof

The present disclosure features compounds and methods useful for the treatment of BAF complex-related disorders.

Compuestos y usos de estos.

La presente descripción presenta compuestos y métodos útiles para el tratamiento de trastornos relacionados con el complejo BAF.

Compounds and uses thereof

Compounds and uses thereof

The present disclosure features compounds and methods useful for the treatment of BAF complex-related disorders.

Compounds and uses thereof

The present disclosure features compounds and methods useful for the treatment of BAF complex-related disorders.

Compounds and uses thereof

The present disclosure features compounds useful for the treatment of BAF complex-related disorders.

Compuestos y usos de estos.

La presente descripción presenta compuestos útiles para el tratamiento de trastornos relacionados con el complejo BAF.

Compounds and uses thereof

The present disclosure features compounds useful for the treatment of BAF complex-related disorders.

Compounds and uses thereof

The present disclosure features compounds useful for the treatment of BAF complex-related disorders.

Brd9 degraders and uses thereof

The present invention relates to methods and compositions for the treatment of BAF-related disorders such as cancers and viral infections.

Compuestos y usos de estos

La presente descripción presenta compuestos útiles para el tratamiento de trastornos relacionados con el complejo BAF.

Inhibitors of fatty acid binding protein (fabp)

Compounds and uses thereof

The present invention relates to compositions and methods for the treatment of BAF-related disorders, such as cancers and viral infections.

Compounds and uses thereof

The present invention relates to compositions and methods for the treatment of BAF-related disorders, such as cancers and viral infections.

Compounds and uses thereof

The present invention relates to compositions and methods for the treatment of BAF-related disorders, such as cancers and viral infections.

Inhibitors of fatty acid binding protein (fabp)

The present invention relates to novel heterocyclic compounds as Fatty Acid Binding Protein (FABP) inhibitors, pharmaceutical compositions comprising the heterocyclic compounds and the use of the compounds for treating or preventing a cardiovascular disease, a metabolic disorder, obesity or an obesity-related disorder, diabetes, dyslipidemia, a diabetic complication, impaired glucose tolerance or impaired fasting glucose. An illustrative compound of the present invention is shown below:

Compuestos y usos de los mismos.

La presente descripción presenta compuestos útiles para el tratamiento de trastornos relacionados con el complejo BAF.

Compuestos y usos de estos

La presente descripción presenta compuestos útiles para el tratamiento de trastornos relacionados con el complejo BAF.

Compounds and uses thereof

The present disclosure features compounds useful for the treatment of BAF complex-related disorders.

Compounds and uses thereof

The present disclosure features compounds useful for the treatment of BAF complex-related disorders.

Compounds and uses thereof

The present disclosure features compounds and methods useful for the treatment of BAF complex-related disorders.

Compounds and uses thereof

The present disclosure features compounds useful for the treatment of BAF complex-related disorders.

Compounds and uses thereof

The present disclosure features compounds useful for the treatment of BAF complex-related disorders.

Compounds and uses thereof