THERAPEUTICALLY ACTIVE ESTRATRIENTHIAZOLE DERIVATIVES AS HINIBITORS OF 17 B-HYDROXYSTEROID DEHYDROGENASE, TYPE 1

The invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof wherein R1 to R6 are as defined in the claims. The invention further relates to their use as inhibitors of 17β-HSD and in treatment or prevention of steroid hormone de-pendent diseases or disorders, such as steroid hormone dependent diseases or disorders requiring the inhibition of the 17β-HSD1 enzyme and/or requiring the lowering of the endogenous estradiol concentration. The present invention also relates to the preparation of the aforementioned compounds and to pharmaceutical compositions comprising as an active ingredient(s) one or more of the aforementioned compounds or pharmaceutically acceptable salts thereof.

THERAPEUTICALLY ACTIVE 17-NITROGEN SUBSTITUTED ESTRATREINTHIAZOLE DERIVATIVES AS INHIBITORS OF 17.BETA-HYDROXYSTEROID DEHYDROGENASE

The invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof wherein R2 to R7 are as defined in the claims. The invention further relates to their use as inhibitors of 17β-HSD and in treatment or prevention of steroid hormone de-pendent diseases or disorders, such as steroid hormone dependent diseases or disorders requiring the inhibition of the 17β-HSD1 enzyme and/or requiring the lowering of the endogenous estradiol concentration. The present invention also relates to the preparation of the aforementioned compounds and to pharmaceutical compositions comprising as an active ingredient(s) one or more of the afore-mentioned compounds or pharmaceutically acceptable salts thereof. 3. A compound as claimed in claim 2 , wherein R7′ is selected from the group consisting of H claim 2 , methyl claim 2 , ethyl claim 2 , allyl claim 2 , and carboxymethylenyl.4. A compound as claimed in claim 1 , wherein R5 and R6 are both H.8. A compound as claimed in claim 1 , wherein{'sub': 1-6', '1-3', '1-3', '2', '3', '2', '2', 'n', '2, '(i-a) R2 and R4 are each independently selected from the group consisting of H, halogen, C-alkyl, C-haloalkyl, C-perhaloalkyl, CN, NO, N, N(R′), (CH)(R′), C(═N—OH)R″, and C(═N—OMe)R″.'}9. A compound as claimed in claim 1 , wherein{'sub': 1-6', '1-3', '2', '3, 'R3 is selected from a group consisting of H, C-alkyl, C-perhaloalkyl, N(R′), N, and OR′.'}10. A compound as claimed in claim 9 , wherein R3 is H or OR′.11. A compound as claimed in claim 1 , wherein R2 and R3 or R3 and R4 claim 1 , together with the ring carbon atoms to which they are attached claim 1 , form an oxazolone or 1 claim 1 ,3-oxazole ring claim 1 , optionally substituted with methyl.12. A compound as claimed in claim 11 , wherein R4 or R2 claim 11 , respectively claim 11 , is selected from the group consisting of H claim 11 , F claim 11 , Cl claim 11 , Br claim 11 , and I.13. A compound as claimed in claim 1 , wherein{'sub': 1-6', '1-3', '1-3', '2', '3', ...

THERAPEUTICALLY ACTIVE ESTRATRIENTHIAZOLE DERIVATIVES AS INHIBITORS OF 17.BETA-HYDROXY-STEROID DEHYDROGENASE, TYPE 1

The invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof wherein R2, R3, R4, R7 and R8 are as defined in the claims. The invention further relates to their use as inhibitors of 17β-HSD1 and in treatment or prevention of steroid hormone dependent diseases or disorders, such as steroid hormone dependent diseases or disorders requiring the inhibition of the 17β-HSD1 enzyme and/or requiring the lowering of the endogenous estradiol concentration. The present invention also relates to the preparation of the aforementioned compounds and to pharmaceutical compositions comprising as an active ingredient(s) one or more of the aforementioned compounds or pharmaceutically acceptable salts thereof. 4. A compound as claimed in claim 2 , wherein R8 is selected from the group consisting of C-alkyl claim 2 , C-haloalkyl claim 2 , C-perhaloalkyl claim 2 , (CH)CN claim 2 , (CH)OH claim 2 , (CH)N(R′) claim 2 , (CH)C(O)OR′ claim 2 , C(O)N(R′) claim 2 , and (CH)C(O)NH.5. A compound as claimed in claim 3 , wherein R8 is selected from the group consisting of C-alkyl claim 3 , C-haloalkyl claim 3 , C-perhaloalkyl claim 3 , (CH)CN claim 3 , (CH)OH claim 3 , (CH)N(R′) claim 3 , (CH)C(O)OR′ claim 3 , C(O)N(R′) claim 3 , and (CH)C(O)NH.7. A compound as claimed in claim 1 , wherein R2 and R4 are each independently selected from the group consisting of H claim 1 , halogen claim 1 , C-alkyl claim 1 , C-haloalkyl claim 1 , C-perhaloalkyl claim 1 , CN claim 1 , NO claim 1 , N claim 1 , N(R′) claim 1 , (CH)N(R′) claim 1 , OR′ claim 1 , (CH)OR′ claim 1 , COR′ claim 1 , CONHR′ claim 1 , COR″ claim 1 , NHCOR″ claim 1 , SCOR′ claim 1 , or COR′″; and{'sub': 1-6', '1-3', '1-3', '2', '2', 'n', '2', '2', 'n', '3', '3', '3', '2', 'n', '2', '2', '2', '2', '2', '2', '2', 'n', '2, 'R3 is selected from the group consisting of H, halogen, C-alkyl, C-haloalkyl, C-perhaloalkyl, N(R′), (CH)NH, (CH)OR % N, and OR′, wherein R′ is selected from the group consisting of R′, benzyl, ...

ESTRA-1,3,5(10)-TRIENE COMPOUNDS CONDENSED IN POSITION 16(17) WITH A PYRAZOLE RING AS INHIBITORS OF 17-HSD1

The invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof 3. The compound according to claim 1 , whereinR1 is selected from the group consisting of H, F and Cl,R2 is selected from the group consisting of H, F and Cl, and{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'R3, R4 and R5 are as defined in ,'}or a pharmaceutically acceptable salt thereof.4. The compound according to claim 1 , whereinR1 is selected from the group consisting of H, F and Cl,R2 is H or F, and{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'R3, R4 and R5 are as defined in ,'}or a pharmaceutically acceptable salt thereof.5. The compound according to claim 1 , whereinR1 is HR2 is F, and{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'R3, R4 and R5 are as defined in ,'}or a pharmaceutically acceptable salt thereof.7. The compound according to claim 1 , whereinthe 1 to 3 heteroatoms of the 5 membered unsubstituted unsaturated or aromatic heterocycle are independently selected from nitrogen and oxygen,the 1 to 3 heteroatoms of the 5 membered unsubstituted unsaturated or aromatic heterocycle are independently selected from 2 nitrogens and 1 sulphur, orthe 1 to 3 heteroatoms of the 5 membered unsubstituted unsaturated or aromatic heterocycle are independently selected from 2 nitrogens and 1 oxygen,or a pharmaceutically acceptable salt thereof.8. The compound according to claim 1 , whereinR3 is H,{'sub': '2', 'R4 is a 5 membered unsaturated or aromatic heterocycle with 1 to 3 heteroatoms selected from the group consisting of nitrogen, and oxygen, optionally substituted with one or two substituent(s) selected from the group consisting of CN, C1-4-alkyl, C1-3-alkoxy, halogen and C(O)N(C1-3-alkyl),'}or a pharmaceutically acceptable salt thereof.11. The compound according to claim 1 , whereinR1 is H,R2 is H or F,R3 is H,{'sub': '2', 'R4 is a 6 membered aromatic heterocycle with 1 to 3 heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur, ...

Prodrugs of 17.beta.-hsd1-inhibitors

The present invention accordingly provides novel compounds of formula (I) wherein R1, R2, R3 and R4 are as defined in the claims. The invention further relates to their in treatment or prevention of steroid hormone dependent diseases or disorders, such as steroid hormone dependent diseases or disorders requiring the inhibition of the 17β-HSD1 enzyme and/or requiring the lowering of the endogenous estradiol concentration.

THERAPEUTICALLY ACTIVE STEROIDAL DERIVATIVES

The invention relates to compounds of formula (II), 112-. (canceled)14. A compound as claimed in claim 13 , wherein R1 is selected from the group consisting of H and halogen claim 13 , and R2 is H claim 13 , or a pharmaceutically acceptable salt thereof.15. A compound as claimed in claim 13 , wherein R3 is H or methyl claim 13 , or a pharmaceutically acceptable salt thereof.16. A compound as claimed in claim 13 , or a pharmaceutically acceptable salt thereof claim 13 , wherein R4 is selected from the group consisting of:5-membered unsubstituted unsaturated or aromatic heterocycle comprising 1 nitrogen atom and 1 to 2 further heteroatom(s) independently selected from the group consisting of nitrogen, sulfur, and oxygen,{'sub': '2', '5-membered unsaturated or aromatic heterocycle comprising 1 nitrogen atom and optionally 1 to 2 further heteroatom(s) independently selected from the group consisting of nitrogen, and oxygen, and being optionally substituted with one or two substituent(s) independently selected from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, C1-3-alkoxy, C(O)N(C1-3-alkyl), and 6-membered saturated heterocycle containing 1 to 2 heteroatom(s) independently selected from the group consisting of nitrogen, oxygen and sulfur and being optionally substituted with one or two substituent(s) independently selected from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, and C1-3-alkoxy, and'}{'sub': '2', '6-membered unsaturated or aromatic heterocycle comprising 1 nitrogen atom and optionally 1 to 2 further heteroatom(s) independently selected from the group consisting of nitrogen, sulfur, and oxygen, and being optionally substituted with one or two substituent(s) independently selected from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, oxo, C1-3-alkoxy, C(O)N(C1-3-alkyl), and 6-membered saturated heterocycle comprising 1 to 2 heteroatom(s) independently selected from the group ...

Prodrugs of 17.BETA.-HSD1-inhibitors

The invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof wherein R1 to R4 are as defined in the claims. The invention further relates to their use as inhibitors of 17β-HSD1 and in treatment or prevention of steroid hormone dependent diseases or disorders, such as steroid hormone dependent diseases or disorders requiring the inhibition of the 17β-HSD1 enzyme and/or requiring the lowering of the endogenous estradiol concentration. The present invention also relates to the preparation of the aforementioned compounds and to pharmaceutical compositions comprising as an active ingredient(s) one or more of the aforementioned compounds or pharmaceutically acceptable salts thereof.

THERAPEUTICALLY ACTIVE STEROIDAL DERIVATIVES

The invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof 3. A compound or pharmaceutically acceptable salt as claimed in claim 2 , wherein R1 is selected from the group consisting of H claim 2 , F and Cl.4. A compound or pharmaceutically acceptable salt as claimed in claim 1 , wherein R3 is H or methyl.5. A compound or pharmaceutically acceptable salt as claimed in claim 4 , wherein R3 is H.6. A compound or pharmaceutically acceptable salt as claimed in claim 1 , wherein R4 is selected from a group consisting of5 membered unsubstituted unsaturated or aromatic heterocycle comprising 1 nitrogen atom and 1 to 2 further heteroatom(s) independently selected from the group consisting of nitrogen, sulfur, and oxygen,{'sub': '2', '5 membered unsaturated or aromatic heterocycle comprising 1 nitrogen atom and optionally 1 to 2 further heteroatom(s) independently selected from the group consisting of nitrogen, and oxygen, and being optionally substituted with one or two substituent(s) independently selected from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, C1-3-alkoxy, C(O)N(C1-3-alkyl), and 6 membered saturated heterocycle containing 1 to 2 heteroatom(s) independently selected from the group consisting of nitrogen, oxygen and sulfur and being optionally substituted with one or two substituent(s) independently selected from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, and C1-3-alkoxy, and'}{'sub': '2', '6 membered unsaturated or aromatic heterocycle comprising 1 nitrogen atom and optionally 1 to 2 further heteroatom(s) independently selected from the group consisting of nitrogen, sulfur, and oxygen, and being optionally substituted with one or two substituent(s) independently selected from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, oxo, C1-3-alkoxy, C(O)N(C1-3-alkyl), and 6 membered saturated heterocycle comprising 1 to 2 heteroatom(s) independently ...

Therapeutically active derivatives of estratriene thiazole substituted in position 17 as 17beta.-hydroxysteroid dehydrogenase inhibitors

L'invention concerne des composés de formule (i) et des sel pharmaceutiquement acceptables de ceux-ci, dans laquelle r2 à r7 sont tels que définis dans les revendications. L'invention concerne en outre leur utilisation en tant qu'inhibiteurs de la 17ß-hsd et pour le traitement ou la prévention de maladies ou troubles dépendant des hormones stéroïdes, tels que des maladies ou troubles dépendant des hormones stéroïdiennes exigeant l'inhibition de l'enzyme 17ß-hsd1 et/ou exigeant la réduction de la concentration en estradiol endogène. La présente invention concerne également la préparation des composés susmentionnés et de compositions pharmaceutiques comprenant en tant que principe(s) actif(s) un ou plusieurs des composés susmentionnés ou leurs sels pharmaceutiquement acceptables. The invention relates to compounds of formula (i) and pharmaceutically acceptable salts thereof, wherein r2 to r7 are as defined in the claims. The invention further relates to their use as inhibitors of 17β-hsd and for the treatment or prevention of steroid hormone dependent diseases or disorders, such as steroid hormone dependent diseases or disorders requiring inhibition of steroid hormone. 17β-hsd1 enzyme and / or requiring reduction of endogenous estradiol concentration. The present invention also relates to the preparation of the abovementioned compounds and of pharmaceutical compositions comprising as active principle (s) one or more of the abovementioned compounds or their pharmaceutically acceptable salts.

NOVEL 17β HYDROXYSTEROID DEHYDROGENASE TYPE I INHIBITORS

The present invention relates to novel 3, 15 substituted estrone derivatives which represent inhibitory compounds of the 17β-hydroxysteroid dehydrogenase type I (17β-HSD1), to their salts, to pharmaceutical preparations containing these compounds and to processes for the preparation of these compounds. Furthermore, the invention concerns the therapeutic use of said novel 3, 15 substituted estrone derivatives, particularly their use in the treatment or prevention of steroid hor­mone dependent diseases or disorders, such as steroid hormone dependent diseases or disorders requiring the inhibition of 17β-hydroxysteroid dehydrogenase type I enzymes and/or requiring the lowering of the endogenous 17β-estradiol concentration. In addition, the present invention relates to the general use of selective 17β-hydroxysteroid dehydrogenase type 1 inhibitors which possess in addition no or only pure antagonistic binding affinities to the estrogen receptor for the treatment and prevention of benign gynaecological disorders, in particular endometriosis.

Novel 17.beta.-hydroxysteroid dehydrogenase type i inhibitors

The present invention relates to novel 3, 15 substituted estrone derivatives which represent inhibitory compounds of the 17.beta.-hydroxysteroid dehydrogenase type I (17.beta.-HSD1), to their salts, to pharmaceutical preparations containing these compounds and to processes for the preparation of these compounds. Furthermore, the invention concerns the therapeutic use of said novel 3, 15 substituted estrone derivatives, particularly their use in the treatment or prevention of steroid hor~mone dependent diseases or disorders, such as steroid hormone dependent diseases or disorders requiring the inhibition of 17.beta.-hydroxysteroid dehydrogenase type I enzymes and/or requiring the lowering of the endogenous 17.beta.-estradiol concentration. In addition, the present invention relates to the general use of selective 17.beta.-hydroxysteroid dehydrogenase type 1 inhibitors which possess in addition no or only pure antagonistic binding affinities to the estrogen receptor for the treatment and prevention of benign gynaecological disorders, in particular endometriosis.

stratrientiazole derivatives, their uses, and pharmaceutical composition

a invenção refere-se a compostos de fórmula (i) e sais farmaceuticamente aceitáveis dos mesmos em que r2 a r7 são como definidos nas reivindicações. a invenção também se refere a seu uso como inibidores de 17ß-hsd e em tratamento ou prevenção de doenças ou distúrbios dependentes de hormônio esteroide, tais como doenças ou distúrbios dependentes de hormônio esteroide requerendo a inibição da enzima 17ß-hsd1 e/ou requerendo a redução da concentração de estradiol endógeno. a presente invenção também se refere à preparação dos compostos anteriormente mencionados e às composições farmacêuticas compreendendo, como um ingrediente ativo, um ou mais dos compostos anteriormente mencionados ou sais farmaceuticamente aceitáveis dos mesmos. The invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof wherein R 2 to R 7 are as defined in the claims. The invention also relates to its use as 17ß-hsd inhibitors and in the treatment or prevention of steroid hormone dependent diseases or disorders, such as steroid hormone dependent diseases or disorders requiring inhibition of the 17ß-hsd1 enzyme and / or requiring reduction of endogenous estradiol concentration. The present invention also relates to the preparation of the aforementioned compounds and to pharmaceutical compositions comprising as an active ingredient one or more of the aforementioned compounds or pharmaceutically acceptable salts thereof.

Therapeutically active 17-nitrogen substituted estratrienthiazole derivatives as inhibitors of 17.beta.-hydroxysteroid dehydrogenase

The invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof wherein R2to R7are as defined in the claims. The invention further relates to their use as inhibitors of 17β-HSD and in treatment or prevention of steroid hormone de- pendent diseases or disorders, such as steroid hormone dependent diseases or disorders requiring the inhibition of the 17β-HSD1 enzyme and/or requiring the lowering of the endogenous estradiol concentration. The present invention also relates to the preparation of the aforementioned compounds and to pharmaceutical compositions comprising as an active ingredient(s) one or more of the afore- mentioned compounds or pharmaceutically acceptable salts thereof.

17-HSD1 and STS inhibitors

Un compuesto de formula general I,**Fórmula**en la que -X-A-Y- juntos representan un grupo seleccionado entre(a) -CO-NR4-,(b) -CO-O-,(c) -CO-,(d) -CO-NH-NR4-,(e) -NH-CO-NH-,(f) -NH-CO-O-,(g) -NH-CO-,(h) -NH-CO-NH-SO2-,(i) -NH-SO2-NH-,(j) -NH-SO2-O-,(k) -NH-SO2-(I) -O-CO-NH-,(m) -O-CO-,(n) -O-CO-NH-SO2-NR4-, y(o) -O-;n representa 1, 2, 3, 4, 5 o 6, o, si -X-A-Y- representa -CO-NR4-, -CO-O-, -CO-, o -CO-NH-NR4-, entonces n tambienpuede representar 0;R1 se selecciona entre:(a) -H,(b) -alquilo (C1-C6), que esta opcionalmente sustituido con halogeno, nitrilo, -OR6, -SR6 o -COOR6; siendo elnumero de dichos sustituyentes 1, 2 o 3 para halogeno, y 1 o 2 para cualquier combinacion de dichos restoshalogeno, nitrilo, -OR6, -SR6 o -COOR6,(c) -fenilo, que esta opcionalmente sustituido con halogeno, nitrilo, -OR6, -SR6, -R6 o -COOR6, siendo el numerode dichos sustituyentes hasta perhalo para halogeno, y 1 o 2 para cualquier combinacion de dichos restoshalogeno, nitrilo, -OR6, -SR6, -R6 o -COOR6,(d) -alquil (C1-C4)-fenilo, en el que la porcion alquilo esta opcionalmente sustituida con hasta tres halogenos; y laporcion fenilo esta opcionalmente sustituida con halogeno, nitrilo, -OR6, -SR6, -R6 o -COOR6, siendo el numerode sustituyentes en dicha porcion fenilo hasta perhalo para halogeno, y 1 o 2 para cualquier combinacion dedichos restos halogeno, nitrilo, -OR6, -SR6, -R6 o -COOR6,(e) -SO2-NR3R3',(f) -CO-NR3R3',(g) -PO(OR16)-R3,(h) -PS(OR16)-R3,(1) -PO(OR16)-O-R3 (j) -SO2-R3, y(k) -SO2-O- R3; A compound of general formula I, ** Formula ** in which -XAY- together represents a group selected from (a) -CO-NR4 -, (b) -CO-O -, (c) -CO -, ( d) -CO-NH-NR4 -, (e) -NH-CO-NH -, (f) -NH-CO-O -, (g) -NH-CO -, (h) -NH-CO-NH -SO2 -, (i) -NH-SO2-NH -, (j) -NH-SO2-O -, (k) -NH-SO2- (I) -O-CO-NH -, (m) -O -CO -, (n) -O-CO-NH-SO2-NR4-, and (o) -O-; n represents 1, 2, 3, 4, 5 or 6, or, if -XAY- represents -CO -NR4-, -CO-O-, -CO-, or -CO-NH-NR4-, so n can also represent 0; R1 is selected from: ...

Benzo[4,5]thieno[2,3-d]pyrimidin-4-ones and their use in therapy

This invention relates to benzo (4, 5) thieno (2, 3-d) pyrimidin-4-one compounds, their 5,6-dihydro and 5, 6, 7, 8-tetrahydro derivatives and their use for the treatment of a steroid hormone dependent disease or disorder, preferably for a steroid hormone dependent disease or disorder requiring the inhibition of a 17-hydroxysteroid dehydrogenase enzyme, most preferably of the 17beta HSD type 1, type 2 or type 3 enzyme. The steroid hormone dependent disease of disorder is selected from the group consisting of breast cancer, prostate carcinoma, ovarioan cancer, uterine cancer, endometrial cancer and endometrial hyperplasia, endometriosis, uterine fibroids, uterine leiomyoma, adenomyosis, dysmenorrhea, menorrhagia, metrorrhagia, prostadynia, benign prostatic hyperplasia, prostatitis, acne, seborrhea, hirsutism, androgenic alopecia, precocious puberty, adrenal hyperplasia, polycystic ovarian syndrome, urinary dysfunction, osteoporosis, multiple sclerosis, rheumatoid arthritis, Alzheimer’s disease, colon cancer, tissue wounds, skin wrinkles and cataracts.

Thiophenepyrimidinones as 17-beta-hydroxysteroid dehydrogenase inhibitors

This invention relates to compounds useful in therapy, especially for use in the treatment and/or prevention of a steroid hormone dependent disorder, preferably a steroid hormone dependent disease or disorder requiring the inhibition of a 170.beta.-hydroxysteroid dehydrogenase (1 7.beta.-HSD) such as 17.beta.-HSD type 1, type 2 or type 3 enzyme.

Novel compounds and their use in therapy

17ß-HSD1 and STS inhibitors

Therapeutically active steroidal derivatives

The invention relates to compounds of formula (II), and pharmaceutically acceptable salts thereof, wherein R1 to R4 are as defined in the claims. The invention further relates to their use as inhibitors of 17β-HSD1 and in treatment or prevention of steroid hormone dependent diseases or disorders, such as steroid hormone dependent diseases or disorders requiring the inhibition of the 17β-HSD1 enzyme and/or requiring the lowering of the endogenous estradiol concentration. The present invention also relates to the preparation of the aforementioned compounds and pharmaceutical compositions comprising as an active ingredient(s) one or more of the aforementioned compounds or pharmaceutically acceptable salts thereof.

17beta-HSD1 and STS inhibitors

THIOPHEN-PYRIMIDINONES IN QUALITY OF INHIBITORS OF 17-BETA-HYDROXIESTEROID-DEHYDROGENASE.

Uso de un compuesto de la fórmula (I) (Ver fórmula) en la cual R1 y R2 representan radicales alquilo iguales o distintos entre sí o uno es alquilo y otro es H, o R1 y R2 forman, junto con sus sitios de unión, un sistema de anillo cíclico de 5, 6, 7 u 8 miembros, que está saturado o que contiene uno o más dobles enlaces entre los átomos del anillo, conteniendo dicho anillo opcionalmente hasta dos heteroátomos además del átomo de nitrógeno al que está unido R1, siendo 0-2 el número de átomos de N y siendo 0-1 el número de átomos de O o S cada uno, y en donde dicho anillo está opcionalmente sustituido con hasta tres sustituyentes seleccionados independientemente del grupo que consiste en alquilo, alquilo sustituido, arilo o arilalquilo, en el que el grupo arilo está opcionalmente sustituido, alcoxi, ariloxi, aciloxi, ariltio, alquiltio, arilsulfonilo, alquilsulfonilo, hidroxilo, oxo, halógeno, amino, oxima, acilo, carboxilo, tiocarboxilo, y amido; R3 y R4 forman, junto con sus sitios de unión, un sistema de anillo cíclico hidrocarbonado de 5, 6, 7 u 8 miembros, que está saturado o que contiene uno más dobles enlaces entre los átomos de carbono y en donde dicho anillo está opcionalmente sustituido con hasta tres sustituyentes independientemente seleccionados del grupo que consiste en alquilo, alquilo sustituido, arilo, o arilalquilo, estando el grupo arilo opcionalmente sustituido, alcoxi, ariloxi, aciloxi, ariltio, alquiltio, arilsulfonilo, alquilsulfonilo, hidroxilo, oxo, halógeno, amino, oxima, acilo, carboxilo, tiocarboxilo, y amido; a condición de que dicho compuesto no sea el 1,2,7,8,9,10,11,13-octahidro-13-oxo-4-(feniltio)-[1]-benzotieno[2'',3'': 4,5]pirimido[1,2,-a]azepin-3-carboxialdehído; para la fabricación de un medicamento para el tratamiento y/o prevención de una enfermedad o afección dependiente de hormonas esteroides, en donde la enfermedad o afección dependiente de hormonas esteroides se selecciona del grupo que consiste en cáncer de ...

15.beta.-[3-propanamido]-substituted estra-1,3,5(10)-trien-17-one compounds and their 17-oximes for use in inhibition of 17.beta.-hydroxysteroid dehydro-genases

The invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof (see formula I) wherein R1 to R4 are as defined in the claims. I he inven-tion further relates to their use as inhibitors of 17.beta.-HSD1 and in treatment or prevention of steroid hormone de-pendent diseases or disorders, such as steroid hormone dependent diseases or disorders requiring the inhibition of the 17.beta.-HSD1 enzyme and/or requiring the lowering of the endogenous estradiol concentration. The present inven-tion also relates to the compounds of formula (II) which defines the 17 -ketone compounds corresponding to the 17¨ oximes of formula (I). The present invention further relates to the preparation of the aforementioned com-pounds and to pharmaceutical compositions comprising as an active ingredient(s) one or more of the aforementioned compounds or pharmaceutically acceptable salts thereof.

Methods of Making and Using Therapeutically Active Thiophenepyrimidinone Compounds

Thiopheneprymidinone compounds useful in therapy, especially for use in the treatment and/or prevention of a steroid hormone dependent disorder, preferably a steroid hormone dependent disease or disorder requiring the inhibition of a 17β-hydroxysteroid dehydrogenase (17β-HSD) such as 17β-HSD type 1, type 2 or type 3 enzyme.

Prodrugs of 17.beta.-hsd1 -inhibitors

Steroid derivatives with therapeutic activity.

LA INVENCIÓN SE RELACIONA CON COMPUESTOS DE FÓRMULA (I) Y SUS SALES FARMACÉUTICAMENTE ACEPTABLES, DONDE R1 A R4 CORRESPONDEN A LA DEFINICIÓN DE LAS REIVINDICACIONES. LA INVENCIÓN SE RELACIONA ADEMÁS CON SU USO COMO INHIBIDORES DE 17Β-HSD1 Y EN EL TRATAMIENTO O LA PREVENCIÓN DE ENFERMEDADES O TRASTORNOS DEPENDIENTES DE HORMONAS ESTEROIDEAS, COMO ENFERMEDADES O TRASTORNOS DEPENDIENTES DE HORMONAS ESTEROIDEAS QUE REQUIERAN LA INHIBICIÓN DE LA ENZIMA 17Β-HSD1 Y/O LA REDUCCIÓN DE LA CONCENTRACIÓN DE ESTRADIOL ENDÓGENO. LA PRESENTE INVENCIÓN SE RELACIONA ADEMÁS CON LA PREPARACIÓN DE LOS COMPUESTOS MENCIONADOS Y CON COMPOSICIONES FARMACÉUTICAS QUE COMPRENDE COMO INGREDIENTES ACTIVOS UNO O MÁS DE LOS COMPUESTOS MENCIONADOS O SUS SALES FARMACÉUTICAMENTE ACEPTABLES. THE INVENTION RELATES TO COMPOUNDS OF FORMULA (I) AND THEIR PHARMACEUTICALLY ACCEPTABLE SALTS, WHERE R1 TO R4 CORRESPOND TO THE DEFINITION OF THE CLAIMS. THE INVENTION IS FURTHER RELATED TO THEIR USE AS INHIBITORS OF 17 HS-HSD1 AND IN THE TREATMENT OR PREVENTION OF DISEASES OR DISORDERS DEPENDENT ON STEROID HORMONES, SUCH AS DISEASES OR DISORDERS DEPENDENT OF HORMONES / STERANEOUS INHIBITION 1 IN HORMONE REQUIREMENTS OR THE REDUCTION OF THE ENDOGENOUS ESTRADIOL CONCENTRATION. THE PRESENT INVENTION IS ALSO RELATED TO THE PREPARATION OF THE MENTIONED COMPOUNDS AND TO PHARMACEUTICAL COMPOSITIONS THAT INCLUDE AS ACTIVE INGREDIENTS ONE OR MORE OF THE MENTIONED COMPOUNDS OR THEIR PHARMACEUTICALLY ACCEPTABLE SALTS.

Therapeutically active estratrien-thiazole derivatives

本發明有關式（I）化合物以及其藥學上可接受鹽類□其中R2、R3、R4、R7以及R8是如同申請專利範圍中所定義。本發明更有關它們作為17β-HSD1抑制劑以及在治療或預防類固醇荷爾蒙依賴型疾病或失調的用途，例如需要抑制17β-HSD1酵素及/或需要降低內生性雌二醇濃度的類固醇荷爾蒙依賴性疾病或失調。本發明也有關前述化合物的製備以及有關包含前述化合物或其藥學上可接受鹽類作為活性成分的藥學組成物。

17-beta HSD1 and STS inhibitors

Substituted steroid compounds which represent selective inhibitors of 17β-hydroxysteroid dehydrogenase type I (17β-HSD1) and, in addition, which may represent inhibitors of the steroid sulfatase, salts thereof, pharmaceutical preparations containing these compounds, and a process for the preparation of these compounds. Also disclosed is a therapeutic method of using such substituted steroid compounds, particularly in the treatment, inhibition, prophylaxis or prevention of steroid hormone dependent diseases or disorders, such as steroid hormone dependent diseases or disorders requiring the inhibition of 17β-hydroxysteroid dehydrogenase type I and/or steroid sulfatase enzymes and/or requiring lowering of the endogenous 17β-estradiol concentration.

Novel 17beta-hydroxysteroid dehydrogenase type I inhibitors

Novel 17 hydroxysteroid dehydrogenase type 1 inhibitors

Novel substituted thiophenepyrimidinone derivatives as inhibitors of 17 ??-hydroxysteroid dehydrogenase.

Esta invencion se refiere a nuevos derivados de tiofenpirimidinona sustituida y a su uso en terapia, especialmente para su uso en el tratamiento y/o prevencion de una enfermedad o trastorno dependiente de hormonas esteroides, tal como enfermedades o trastornos dependientes de hormonas esteroides que requieren la inhibicion de encimas 17??-hidroxiesteroide deshidogenasas.

Novel substituted thiophenepyrimidinone derivatives as inhibitors of 17beta-hydroxysteroid dehydrogenase

NEW INHIBITORS OF 17BETA-HYDROXIESTEROID DEHYDROGENASE TYPE I.

Un compuesto de fórmula general I, (Ver fórmula) en la cual (i) X representa: (a) un enlace, (b) -NR 3 -, o (c) -O-; A representa: (a) -CO-, o (b) con la condición de X represente -NR 3 , A representa -SO2-; Y representa: (a) -NR 4 -, (b) -O-, con la condición de que X represente un enlace o -NR 3 -, (c) un enlace, (d) -NH-SO2-, con la condición de que X represente -NR 3 y A represente -CO-, (e) -NH-SO2-NR 4 , con la condición de que X represente -O-, o (f) -NH-NR 4 -, con la condición de que X represente un enlace, o (ii) -X-A-Y- conjuntamente representa -O-; y en donde... A compound of general formula I, (See formula) in which (i) X represents: (a) a bond, (b) -NR 3 -, or (c) -O-; A represents: (a) -CO-, or (b) with the condition of X represent -NR 3, A represents -SO2-; Y represents: (a) -NR 4 -, (b) -O-, with the proviso that X represents a bond or -NR 3 -, (c) a bond, (d) -NH-SO2-, with the provided that X represents -NR 3 and A represents -CO-, (e) -NH-SO2-NR 4, with the proviso that X represents -O-, or (f) -NH-NR 4 -, with the condition that X represents a link, or (ii) -XAY- jointly represents -O-; and where...

Estra-1,3,5(10)-triene compounds condensed in position 16(17) with a pyrazole ring as inhibitors of 17-hsd1

The invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof (I) wherein R1 to R4 are as defined in the claims. The invention further relates to their use as inhibitors of 17β-HSD1 and in treatment or prevention of steroid hormone dependent dis-eases or disorders, such as steroid hormone dependent dis-eases or disorders requiring the inhibition of the 17β-HSD1 enzyme and/or requiring the lowering of the endogenous estradiol concentration. The present invention also relates to the preparation of the aforementioned compounds and to pharmaceutical compositions comprising as an active ingredient(s) one or more of the aforementioned compounds or pharmaceutically acceptable salts thereof.

15.beta.-(3-propanamido)-substituted estra-1,3,5(10)-trien-17-one compounds and their 17-oximes for use in inhibition of 17.beta.-hydroxysteroid dehydrogenases

The invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof (I) wherein R1 to R4 are as defined in the claims. The invention further relates to their use as inhibitors of 17β-HSD1 and in treatment or prevention of steroid hormone de- pendent diseases or disorders, such as steroid hormone dependent diseases or disorders requiring the inhibition of the 17β-HSD1 enzyme and/or requiring the lowering of the endogenous estradiol concentration. The present invention also relates to the preparation of the aforementioned compounds and to pharmaceutical compositions comprising as an active ingredient(s) one or more of the afore mentioned compounds or pharmaceutically acceptable salts thereof.

17-oximes of 15.beta.-[3-propanamido]-substituted estra-1,3,5(10)-trien-17-ones for use in inhibition of 17.beta.-hydroxysteroid dehydrogenases

15.beta.-[3-propanamido]-substituted estra-1,3,5(10)-trien-17-one compounds and their 17-oximes for use in inhibition of 17.beta.-hydroxysteroid dehydrogenases

The invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof wherein Rl to R4 are as defined in the claims. The invention further relates to their use as inhibitors of 17P-HSD1 and in treatment or prevention of steroid hormone dependent diseases or disorders, such as steroid hormone dependent diseases or disorders requiring the inhibition of the 17P-HSD1 enzyme and/or requiring the lowering of the endogenous estradiol concentration. The present invention also relates to the compounds of formula (II) which defines the 17-ketone compounds corresponding to the 17- oximes of formula (I). The present invention further relates to the preparation of the aforementioned compounds and to pharmaceutical compositions comprising as an active ingredient(s) one or more of the aforementioned compounds or pharmaceutically acceptable salts thereof.

Estra-1,3,5(10)-triene compounds condensed in position 16(17) with a pyrazole ring as inhibitors of 17-hsd1

The invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof (I) wherein R1 to R4 are as defined in the claims. The invention further relates to their use as inhibitors of 17ß-HSD1 and in treatment or prevention of steroid hormone dependent dis-eases or disorders, such as steroid hormone dependent dis-eases or disorders requiring the inhibition of the 17ß-HSD1 enzyme and/or requiring the lowering of the endogenous estradiol concentration. The present invention also relates to the preparation of the aforementioned compounds and to pharmaceutical compositions comprising as an active ingredient(s) one or more of the aforementioned compounds or pharmaceutically acceptable salts thereof.

Benzoä4,5üthienoä2,3-düpyrimidin-4-one und ihre therapeutische verwendung

Estra-1,3,5(10)-triene compounds condensed in position 16(17) with a pyrazole ring as inhibitors of 17-HSD1

The invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof (I) wherein R1 to R4 are as defined in the claims. The invention further relates to their use as inhibitors of 17β-HSD1 and in treatment or prevention of steroid hormone dependent dis-eases or disorders, such as steroid hormone dependent dis-eases or disorders requiring the inhibition of the 17β-HSD1 enzyme and/or requiring the lowering of the endogenous estradiol concentration. The present invention also relates to the preparation of the aforementioned compounds and to pharmaceutical compositions comprising as an active ingredient(s) one or more of the aforementioned compounds or pharmaceutically acceptable salts thereof.

Estra-1,3,5(10)-triene compounds condensed in position 16(17) with a pyrazole ring as inhibitors of 17-hsd1

15-beeta-[3-propanamido]substituoitujen estra-1,3,5(10)-trien-17-onien 17-oksiimeja käytettäväksi 17-beeta-hydroksisteroididehydrogenaasien inhiboimisessa

NEUE SUBSTITUIERTE THIOPHENPYRIMIDINONDERIVATE ALS INHIBITOREN VON 17ß- HYDROXYSTEROIDDEHYDROGENASE

Thiophenepyrimidinone als 17-beta-hydroxysteroid dehydrogenase inhibitoren

Neue inhibitoren der 17beta hydroxysteroid- dehydrogenase typ i

17-oximer af 15.beta.-[3-propanamido]-substituerede estra-1,3,5(10)-trien-17-oner til anvendelse i inhibition af 17.beta.-hydroxysteroid-dehydrogenaser

Derivados esteroides terapeuticamente ativos, seus usos e seu método de preparação, e composição farmacêutica

A presente invenção refere-se a compostos de fórmula (I) e sais farmaceuticamente aceitáveis dos mesmos em que R1 a R4 são como definidos nas reivindicações. A invenção ainda se refere ao seu uso como inibidores da 17β-HSD1 e no tratamento ou prevenção de doenças ou distúrbios dependentes do hormônio esteroide, tais como doenças ou distúrbios dependentes do hormônio esteroide que requerem a inibição da enzima 17β-HSD1 e/ou que requerem a redução da concentração endógena de estradiol. A presente invenção também se refere à preparação dos compostos acima mencionados e a composições farmacêuticas compreendendo como um ingrediente (s) ativo(s) um ou mais dos compostos acima mencionados ou sais farmaceuticamente aceitáveis dos mesmos.

Terapeuttisesti vaikuttavat aineet ja niiden käyttö

17-oksimi od 15.beta.-(3-propanamido)-substituiranih estra-1,3,5(10)-trien-17-onov za uporabo pri zaviranju 17.beta.-hidroksisteroid dehidrogenaz

17-oksimi 15.beta.-[3-propanamido]-supstituisanih estra-1,3,5(10)-trien-17-ona za upotrebu u inhibiciji 17.beta.-hidroksisteroid dehidrogenaza

15.beta.-[3-propanamido]-pakeisti estra-1,3,5(10)-trien-17-onų 17-oksimai, skirti 17.beta.-hidroksisteroidų dehidrogenazių slopinimui

15beta-(3-PROPANAMIDO)-SUBSTITUTED ESTRA-1,3,5(10)-TRIEN-17-OXIMES FOR USE IN INHIBITION OF 17beta-HYDROXYSTEROID DEHYDROGENASES

NOVEL SUBSTITUTED THIOPHENEPYRIMIDINONE DERIVATIVES AS INHIBITORS OF 17ß-HYDROXYSTEROID DEHYDROGENASE

This invention relates to novel substituted thiophenepyrimidinone derivatives and their use in therapy, especially for use in the treatment and/or prevention of a steroid hormone dependent diseases or disorder, such as steroid hormone dependent diseases or disorders requiring inhibition of 17ß-hydroxysteroid dehydrogenase enzymes.

Nye substituerte tiofenpyrimidinonderivater som inhibitorer for 17 β-hydroksysteroiddehydrogenase

Denne oppfinnelsen vedrører nye substituerte tiofenpyrimidinonderivater og deres anvendelse i terapi, spesielt for anvendelse ved behandling og/eller profylakse av en steroidhormonavhengig sykdom eller forstyrrelse, slik som steroidhormonavhengige sykdommer eller forstyrrelser som krever hemming av 17?-hydroksysteroiddehydrogenaseenzymer.

NOVEL SUBSTITUTED THIOPHENEPYRIMIDINONE DERIVATIVES AS INHIBITORS OF 17β-HYDROXYSTEROID DEHYDROGENASE

This invention relates to novel substituted thiophenepyrimidinone derivatives and their use in therapy, especially for use in the treatment and/or prevention of a steroid hormone dependent diseases or disorder, such as steroid hormone dependent diseases or disorders requiring inhibition of 17β-hydroxysteroid dehydrogenase enzymes.

17-oksymy 15.beta.-[3-propanamido]-podstawionych estra-1,3,5(10)-trien-17-onów do stosowania w hamowaniu aktywności 17.beta.-dehydrogenaz hydroksysteroidowych

17-oksimi 15.beta.-[3-propanamido]-supstituiranih etera-1,3,5(10)-trien-17-ona za uporabu u inhibiciji 17.beta.-hidroksisteroid dehidrogenaza

17-beta HSD1 and STS Inhibitors

Substituted steroid compounds which represent selective inhibitors of 17β-hydroxysteroid dehydrogenase type I (17β-HSD1) and, in addition, which may represent inhibitors of the steroid sulfatase, salts thereof, pharmaceutical preparations containing these compounds, and a process for the preparation of these compounds. Also disclosed is a therapeutic method of using such substituted steroid compounds, particularly in the treatment, inhibition, prophylaxis or prevention of steroid hormone dependent diseases or disorders, such as steroid hormone dependent diseases or disorders requiring the inhibition of 17β-hydroxysteroid dehydrogenase type I and/or steroid sulfatase enzymes and/or requiring lowering of the endogenous 17β-estradiol concentration.

15.beta.-[3-propanamido]-substituted estra-1,3,5(10)-trien-17-one compounds and their 17-oximes for use in inhibition of 17.beta.-hydroxysteroid dehydro-genases

The invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof (see formula I) wherein R1 to R4 are as defined in the claims. I he inven-tion further relates to their use as inhibitors of 17.beta.-HSD1 and in treatment or prevention of steroid hormone de-pendent diseases or disorders, such as steroid hormone dependent diseases or disorders requiring the inhibition of the 17.beta.-HSD1 enzyme and/or requiring the lowering of the endogenous estradiol concentration. The present inven-tion also relates to the compounds of formula (II) which defines the 17 -ketone compounds corresponding to the 17¨ oximes of formula (I). The present invention further relates to the preparation of the aforementioned com-pounds and to pharmaceutical compositions comprising as an active ingredient(s) one or more of the aforementioned compounds or pharmaceutically acceptable salts thereof.

Therapeutically active steroidal derivatives

The invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereofwherein R1 to R4 are as defined in the claims. The invention further relates to their use as inhibitors of 17β-HSD1 and in treatment or prevention of steroid hormone dependent diseases or disorders, such as steroid hormone dependent diseases or disorders requiring the inhibition of the 17β-HSD1 enzyme and/or requiring the lowering of the endogenous estradiol concentration. The present invention also relates to the preparation of the aforementioned compounds and to pharmaceutical compositions comprising as an active ingredient(s) one or more of the aforementioned compounds or pharmaceutically acceptable salts thereof.

15beta-(3-PROPANAMIDO)-SUBSTITUTED ESTRA-1,3,5(10)-TRIEN-17-OXIMES FOR USE IN INHIBITION OF 17beta-HYDROXYSTEROID DEHYDROGENASES

Therapeutically active estratrienthiazole derivatives as inhibitors of 17.beta-hydroxy-steroid dehydrogenase, type 1

The invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof wherein R2, R3, R4, R7 and R8 are as defined in the claims. The invention further relates to their use as inhibitors of 17β-HSD1 and in treatment or prevention of steroid hormone dependent diseases or disorders, such as steroid hormone dependent diseases or disorders requiring the inhibition of the 17β-HSD1 enzyme and/or requiring the lowering of the endogenous estradiol concentration. The present invention also relates to the preparation of the aforementioned compounds and to pharmaceutical compositions comprising as an active ingredient(s) one or more of the aforementioned compounds or pharmaceutically acceptable salts thereof.

Therapeutically active 17-nitrogen substituted estratreinthiazole derivatives as inhibitors of 17β-hydroxysteroid dehydrogenase

The invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof wherein R2 to R7 are as defined in the claims. The invention further relates to their use as inhibitors of 17β-HSD and in treatment or prevention of steroid hormone de-pendent diseases or disorders, such as steroid hormone dependent diseases or disorders requiring the inhibition of the 17β-HSD1 enzyme and/or requiring the lowering of the endogenous estradiol concentration. The present invention also relates to the preparation of the aforementioned compounds and to pharmaceutical compositions comprising as an active ingredient(s) one or more of the afore-mentioned compounds or pharmaceutically acceptable salts thereof.