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US 7,678,787 B2Granted
Pyrrolobenzodiazepine pyridine carboxamides and derivatives as follicle-stimulating hormone receptor antagonists
AssigneeWyeth
InventorsAmedeo A. Failli, Gavin D. Heffernan, Arthur A. Santilli, Dominick A. Quagliato, Richard D. Coghlan, Patrick M. Andrae, Susan C. Croce, Emily S. Shen, Eugene J. Trybulski
Life of this patent
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Abstract
This invention provides pyrrolobenzodiazepine pyridine carboxamides selected from those of Formula (1), which act as follicle stimulating hormone receptor antagonists. The invention also provides pharmaceutical compositions and methods of treatment utilizing the compounds of Formulae (1) and (2).
Claims32
A compound having the Formula I:
- wherein
- R1 and R2 are selected independently from hydrogen, (C1-C6) alkyl, halogen, trifluoromethyl, hydroxyl, (C1-C6) alkoxy, OCF3, carboxy, —CONH[(C1-C6) alkyl], or —CON[(C1-C6) alkyl]2, amino, (C1-C6) alkylamino, —NHCO[(C1-C6) alkyl];
- R3 is selected from the group consisting of hydrogen, (C1-C6) alkyl, (C1-C6) alkoxy, hydroxyl, amino, (C1-C6) alkylamino, C(O)—(C1-C6) alkyl, and halogen;
- A is selected from the group consisting of C═O, CH2, SO2;
- and SO2;
- B is
- wherein R6, R7, R8, R9, R10, R101, and R102 are selected independently from the group consisting of hydrogen, alkyl, alkoxy, trihalomethyl, halogen, —C(O) alkyl, hydroxy, hydroxyalkyl, alkyloxyalkyl, —CH(OH)alkyl, —CH(alkoxy)alkyl, formyl, nitro, thioalkyl, —SO2alkyl, —SO2NHR11, —SO2N(R11)2, —(CH2)pCN, —(CH2)pCOOR12, —(CH2)pNR13R14, —(CH2)pCONR13R14, —CH═NOH, —CH═NO-alkyl,
- and —C(O)aryl optionally substituted by alkyl;
- wherein R5 and R100 are selected independently from the group consisting of hydrogen, alkyl, trihalomethyl, halogen, —C(O) alkyl, hydroxy, hydroxyalkyl, alkyloxyalkyl, —CH (OH)alkyl, —CH(alkoxy)alkyl, formyl, nitro, thioalkyl, —SO2alkyl, —SO2NHR11, —SO2N(R11)2, —(CH2)pCN , —(CH2)pCOOR12, —(CH2)pNR13R14, —(CH2)pCONR13R14, —CH═NOH, —CH═NO-alkyl,
- and —C(O)aryl optionally substituted by alkyl;
- R11 and R12 are each independently hydrogen or alkyl;
- R13 and R14 are each independently hydrogen or alkyl;
- or can be taken together with the nitrogen to which they are attached to form a 4-6 membered saturated ring optionally containing one or more additional O, S or N atoms;
- p is 0 or 1;
- R is a group consisting of
- wherein
- R15 is hydrogen or alkyl;
- X is selected independently from the group consisting of
- wherein
- R16 at each occurrence is independently selected from hydrogen or alkyl;
- R17 is one to three substituents independently selected from the group consisting of hydrogen, alkyl, halogen, hydroxy, aryloxy, or hydroxyalkyl;
- R18 is 5 or 6-membered saturated heterocycle containing one nitrogen atom;
- m is an integer from 1 to 4;
- q is an integer from 1 to 2;
- and
- r is 0 or 1;
- provided that:
- if A is C═O, m is 1 or 2, r is 0, R7 is methyl or methoxy and R5, R6, R8, R9, R10, R17, R100, and R101 are hydrogen, then R102 is not methyl or methoxy;
- if A is C═O, m is 2, r is 0, R6 is methoxy and R5, R7, R9, R10, R17, R100, R101, and R102 are hydrogen, then R8 is not methoxy;
- if A is C═O, m is 1 or 2, r is 0, R6 is methyl or methoxy, and R5, R7, R8, R10, R17, R100, R101, and R102 are hydrogen, then R9 is not methoxy;
- if A is C═O, m is 1 or 2, r is 0 or 1, R7 is methyl, and R5, R6, R9, R10, R17, R100, R101, and R102 are hydrogen, then R8 is not trifluoromethyl;
- if A is C═O, m is 1, r is 0, R7 is methoxy, R5, R6, R9, R10, R17, R100, and R102 are hydrogen then R8 is not chlorine wherein R101 is hydrogen or R101 is not methoxy wherein R8 is hydrogen;
- if A is C═O, m is 2, r is 0, R7 is methyl, and R5, R6, R9, R10, R17, R100, R101, and R102 are hydrogen, then R8 is not methoxy;
- if A is C═O, m is 1 or 2, r is 0, R7 is methyl, and R5, R6, R8, R9, R10, R17, R100 and R102 are hydrogen, then R101 is not methoxy;
- if A is C═O, m is 1, r is 0 or 1, R6 is methoxy, R102 is trifluoromethyl, and R5, R7, R8, R9, R10, R17, and R101 are hydrogen, then R100 is not hydrogen;
- if A is C═O, m is 1 or 2, r is 0, R8 is methyl, and R5, R7, R9, R10, R17, R100, R101 and R102 are hydrogen, then R6 is not hydrogen or methyl;
- and
- if A is C═O, m is 1 or 2, r is 0, and R5, R6, R7, R9, R10, R17, R100, R101 and R102 are hydrogen, then R8is not methoxy;
- or
- a pharmaceutically acceptable salt thereof.
37 more elements
A compound of 1 claim wherein each R16 is hydrogen, m is 1 and r is 0, and at least one R17 is not hydrogen.
A compound of 1 claim wherein R16 is hydrogen, m is 1, r is 0, and no R17is hydrogen.
A compound of 1 claim wherein each R16 and R17 are hydrogen, q is 1 and r is 0, and R18 is a 5-membered saturated cycloalkylamine.
A compound having the Formula I:
- wherein
- R1 and R2 are selected independently from hydrogen, (C1-C6) alkyl, halogen, trifluoromethyl, hydroxyl, (C1-C6) alkoxy, OCF3, carboxy, —CONH[(C1-C6) alkyl], or —CON [(C1-C6) alkyl]2, amino, (C1-C6) alkylamino, —NHCO[(C1-C6) alkyl];
- R3 is selected from the group consisting of hydrogen, (C1-C6 ) alkyl, (C1-C6) alkoxy, hydroxyl, amino, (C1-C6) alkylamino, C(O)—(C1-C6) alkyl, and halogen;
- A is SO2;
- B is
- wherein R5, R6, R7, R8, R9, R10, R100, R101, and R102 are selected independently from the group consisting of hydrogen, alkyl, alkoxy, trihalomethyl, halogen, —C(O) alkyl, hydroxy, hydroxyalkyl, alkyloxyalkyl, —CH(OH)alkyl, —CH(alkoxy)alkyl, formyl, nitro, thioalkyl, —SO2alkyl, —SO2NHR11, —SO2N(R11)2, —(CH2)pCN , —(Ch2)pCOOR12, —(CH2)pNR13R14, —(CH2)pCONR13R14, —CH═NOH, —CH ═NO-alkyl,
- and —C(O)aryl optionally substituted by alkyl;
- R11 and R12 are each independently hydrogen or alkyl;
- R13 and R14 are each independently hydrogen or alkyl;
- or can be taken together with the nitrogen to which they are attached to form a 4-6 membered saturated ring optionally containing one or more additional O, S or N atoms;
- is 0 or 1;
- R is a group consisting of
- wherein
- R15 is hydrogen or alkyl;
- X is selected independently from the group consisting of
- wherein
- R16 at each occurrence is independently selected from hydrogen or alkyl;
- R17 is one to three substituents independently selected from the group consisting of hydrogen, alkyl, halogen, hydroxy, aryloxy, or hydroxyalkyl;
- R18 is 5 or 6-membered saturated heterocycle containing one nitrogen atom;
- m is an integer from 1 to 4;
- q is an integer from 1 to 2;
- and
- r is 0 or 1;
- or a pharmaceutically acceptable salt thereof.
21 more elements
A compound of 1 claim wherein R16 and R17 are hydrogen, m is 1, r is 0 and R6 is methyl.
A compound having the Formula I:
- wherein
- R1 and R2 are selected independently from hydrogen, (C1-C6) alkyl, halogen, trifluoromethyl, hydroxyl, (C1-C6) alkoxy, OCF3, carboxy, —CONH[(C1-C6) alkyl], or —CON[(C1-C6) alkyl]2, amino, (C1-C6) alkylamino, —NHCO[(C1-C6) alkyl];
- R3 is selected from the group consisting of hydrogen, (C1-C6) alkyl, (C1-C6) alkoxy, hydroxyl, amino, (C1-C6) alkylamino, C(O)—(C1-C6) alkyl, and halogen;
- A is selected from the group consisting of C═O, CH2, and SO2;
- B is
- wherein R5, R6, R8, R9, R10, R100, R101, and R102 are selected independently from the group consisting of hydrogen, alkyl, alkoxy, trihalomethyl, halogen, —C(O) alkyl, hydroxy, hydroxyalkyl, alkyloxyalkyl, —CH(OH)alkyl, —CH(alkoxy)alkyl, formyl, nitro, thioalkyl, —SO 2alkyl, —SO2NHR11, —SO2N(R11)2, —(CH2)pCN , —(CH2)pCOOR12, —(CH2)pNR13R14, —(CH2)pCONR13R14, —CH═NOH, —CH═NO-alkyl,
- and —C(O)aryl optionally substituted by alkyl;
- R11 and R12are each independently hydrogen or alkyl;
- R13 and R14 are each independently hydrogen or alkyl;
- or can be taken together with the nitrogen to which they are attached to form a 4-6 membered saturated ring optionally containing one or more additional 0, S or N atoms;
- p is 0 or 1;
- R7 is methyl or methoxy;
- R is a group consisting of
- wherein
- R15 is hydrogen or alkyl;
- X is selected independently from the group consisting of
- wherein
- R16 and R17 are hydrogen;
- R18 is 5 or 6-membered saturated heterocycle containing one nitrogen atom;
- m is 1;
- q is an integer from 1 to 2;
- and
- r is 0;
- provided that:
- if A is C═O, m is 1, r is 0, R7 is methyl or methoxy and R5, R6, R8, R9, R10, R17, R100, and R101 are hydrogen, then R102 is not methyl or methoxy;
- if A is C═O, m is 1, r is 0 , R7 is methyl, and R5, R6, R9, R10, R17, R100, R101, and R102 are hydrogen, then R8 is not trifluoromethyl;
- if A is C═O, m is 1, r is 0, R7 is methoxy, R5, R6, R9, R10, R17, R100, and R102 are hydrogen then R8 is not chlorine wherein R101 is hydrogen or R101 is not methoxy wherein R8 is hydrogen;
- if A is C═O, m is 1, r is 0, R7 is methyl, and R5, R6, R8, R9, R10, R17, R100 and R102 are hydrogen, then R101 is not methoxy;
- or
- a pharmaceutically acceptable salt thereof.
27 more elements
A compound of 1 claim wherein R16 and R17 are hydrogen, m is 1, r is 0, and R8 is selected from the group consisting of methyl, chlorine, hydroxy, methoxy, —COCH3, —CHO, —CH(OH)CH2CH3, —CH2OH, —CN, —CH(CH3)2, —CO(phenyl), —CH2OCH3, —CH2COOCH3, —OCH2CH3,—CH2CN, —SCH3, —CH2COOH, —CH(OH)CH3, —COCH(CH3)2, —SO2CH3, —COOCH3, —COOC(CH3)3, —COOH, —CH2CONH2, —CH2CONHCH3, —CH2CON(CH3)2, —CH2CONH(CH2CH3), —CH2CON(CH2CH3)2, —CH(OH)CH(CH3)2, —CON(CH3)2, —CH2N(CH3)2, —CH2NHCH3, —CH2C(NH2)═NOH, —CH2NH2, —SO2NH2, and —CONHCH3.
A compound having the Formula 1-2:
- wherein
- R6′ is H or (C1-3)alkyl;
- R8′ is selected from the group consisting of H, (C1-3)alkoxy, halogen, (C1-3)alkyl, (C1-5) hydroxyalkyl, —C(O)R600, CN, (C1-3)alkoxyalkyl, CH2C(O)R601, CH2CN, HC═NOH, OH, S((C1-3) alkyl), SO2((C1-3)alkyl), CH2N(R602)(R603), CH2C(NH2)═NOH, and SO2NH2;
- R9′ is H, halogen or (C1-3)alkyl;
- R10′ is H, halogen, (C1-3)alkyl, or C(O)(C1-3)alkyl;
- R102′ is H or (C1-3)alkyl;
- R15 is hydrogen or alkyl;
- R500 is H, OH, halogen, (C1-3)alkyl, or O-phenyl;
- R501 and R502 are each independently H or OH;
- and
- k is 0 or 1;
- wherein
- R600 is H, OH, (C1-3)alkyl, phenyl, (C1-6)alkoxy, or NR602R603;
- R601 is OH, (C1-3)alkoxy, or NR602R603;
- and
- R602 and R603 are each independently H or (C1-3)alkyl, or
- R602 and R603 together form a 5-6 membered heterocycle with up to 3 additional N or 0 atoms;
- provided that:
- when R6′ is methyl, R8′ is not methoxy;
- when R6′ is methyl, and one of R8′ or R102′ is methyl, then either:
- (a) the other of R8′ or R102′ is not H;
- or
- (b) k=1;
- and
- if R6′, R9′, R10′, R102′, R500, R501, and R502 are all H, then R8 is not methyl or methoxy.
22 more elements
A compound having the structure of Formula II:
- wherein
- R1 and R2 are selected independently from hydrogen, (C1-C6) alkyl, halogen, trifluoromethyl, hydroxyl, (C1-C6) alkoxy, OCF3, carboxy, —CONH[(C1-C6) alkyl], or —CON[(C1-C6) alkyl]2, amino, (C1-C6) alkylamino, —NHCO[(C1-C6) alkyl];
- R3 is a substituent selected from the group consisting of hydrogen, (C1-C6) alkyl, (C1-C6) alkoxy, hydroxyl, amino, (C1-C6) alkylamino, C(O)—(C1-C6) alkyl, and halogen;
- A is selected from the group consisting of C═O, CH2, and SO2;
- C is selected from the group consisting of
- —Y and Z
- wherein
- R19 and R20 are selected independently from the group consisting of hydrogen, alkyl, alkoxy, halogen, trifluoromethyl, trifluoromethoxy, —COOR21, dialkylamino, nitro, cyano, aryloxy, aroyl, and —CH2NHC(O)O-alkyl;
- or R19 and R20 can be taken together with the phenyl moiety to which they are attached to form a structure of the formula —O(—CH2)n—O—wherein n is 1 or 2;
- R21 is hydrogen or alkyl;
- Y is selected from the group consisting of alkyl, cycloalkyl, naphthyl,
- wherein
- R22 is selected from the group consisting of hydrogen, alkyl, halogen, aralkyloxy-, alkylamino, hydroxyalkylamino, cycloalkylamino, N-alkyl piperazino, (pyridinoalkyl) amino, (N-alkyl) aralkyl amino and aralkyl amino wherein the aryl is optionally substituted with alkoxy;
- R23 and R24 are each independently hydrogen or halogen;
- R25 and R30 are each independently hydrogen or alkyl;
- R26, R27, R28, and R29 are selected independently from the group consisting of hydrogen, alkyl and halogen;
- R31 is hydrogen, alkyl, halogen or aryl;
- and
- R32 is each independently H, OH or taken together with the carbon to which they are attached form —C═O;
- Z consists of the moiety D-E, wherein
- D is an aryl optionally substituted by one or more substituents selected from the group consisting of hydrogen, alkyl, alkoxy, halogen, nitro, —SO2NH2, and trifluoromethyl;
- and
- E is selected from the group consisting of
- wherein R33 is hydrogen or alkyl;
- and
- R′ is a group consisting of
- wherein
- R150 is hydrogen or alkyl;
- X is selected independently from the group consisting of
- wherein
- R160 is hydrogen or alkyl;
- R170 is one to three substituents selected from the group consisting of hydrogen, alkyl, halogen, hydroxy, aryloxy, and hydroxyalkyl;
- R180 is 5 or 6-membered saturated cycloalkylamine;
- m′ is an integer from 1 to 4;
- q ′ is an integer from 1 to 2;
- r′ is 0 or 1;
- or a pharmaceutically acceptable salt thereof.
34 more elements
A compound that is:
- a. 10-{[2′-(1-Hydroxyethyl)-1,1′-biphenyl-4-yl]carbonyl}-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- b. 10-{[2′-(Hydroxymethyl)-1,1′-biphenyl-4-yl]carbonyl}-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- c. 10-{[2′-(Methoxymethyl)-1,1′-biphenyl-4-yl]carbonyl}-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- d. Methyl(4′-{[3-{[(pyridin-3-ylmethyl)amino]carbonyl}-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10(11H)-yl]carbonyl}-1,1′-biphenyl-2-yl)acetate;
- e. (−)-10-({2′-[1-Hydroxyethyl]-1,1′-biphenyl-4-yl}carbonyl)-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- f. 10-{[2′-(2-Amino-2-oxoethyl)-1,1′-biphenyl-4-yl]carbonyl}-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- or
- g. 10-({2′-[2-Amino-2-(hydroxyimino)ethyl]-1,1′-biphenyl-4-yl)carbonyl)-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- or
- a pharmaceutically acceptable salt thereof.
7 more elements
A compound that is:
- a) 10-(4-Iodo-3-methylbenzoyl)-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- b) 10-(4-Benzoylbenzoyl)-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- c) 10-Benzoyl-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- d) 10-(4-Methylbenzoyl)-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- e) 10-(3-Fluorobenzoyl)-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- f) N-(Pyridin-3-ylmethyl)-10-[4-(trifluoromethyl)benzoyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- g) 10-(4-tert-Butylbenzoyl)-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- h) 10-(3,4-Dichlorobenzoyl)-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- i) N-(Pyridin-3-ylmethyl)-10-[2-(trifluoromethyl)benzoyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- j) 10-(3-Methylbenzoyl)-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- k) 10-[4-(Dimethylamino)benzoyl]-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- l) N-(Pyridin-3-ylmethyl)-10-[4-(trifluoromethoxy)benzoyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- m) 10-(2,6-Difluorobenzoyl)-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- n) Methyl 4-{[3-{[(pyridin-3-ylmethyl)amino]carbonyl}-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10(11H)-yl]carbonyl}benzoate;
- o) 4-{[3-{[(Pyridin-3-ylmethyl)amino]carbonyl}-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10(11H)-yl]carbonyl}benzoic acid;
- p) 10-(4-Methoxybenzoyl)-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c](1,4]benzodiazepine-3-carboxamide;
- q) 10-(4-Cyanobenzoyl)-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- r) 10-(4-Chlorobenzoyl)-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- s) N-(Pyridin-3-ylmethyl)-10-[3-(trifluoromethyl)benzoyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- t) 10-(4-Fluorobenzoyl)-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- u) 10-(2-Methylbenzoyl)-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- v) 10-(3,5-Difluorobenzoyl)-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- w) 10-(1,3-Benzodioxol-5-ylcarbonyl)-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- x) 10-(2-Fluorobenzoyl)-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- y) 10-(4-Propylbenzoyl)-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- z) 10-(4-Nitrobenzoyl)-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- aa) 10-(3,4-Difluorobenzoyl)-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- bb) 10-(4-Phenoxybenzoyl)-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- cc) 10-[4-(Diethylamino)benzoyl]-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- dd) tert-Butyl(4-{[3-{[(pyridin-3-ylmethyl)amino]carbonyl}-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10(11H)-yl]carbonyl}benzyl)carbamate;
- ee) 10-(3-Methyl-4-thien-2-ylbenzoyl)-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- ff) N-(Pyridin-3-ylmethyl)-10-(4-pyrimidin-2-ylbenzoyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- gg) N-(Pyridin-3-ylmethyl)-10-(4-pyrimidin-5-ylbenzoyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- hh) 10-(4-Pyridin-2-ylbenzoyl)-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- ii) 10-(4-Pyridin-3-ylbenzoyl)-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- jj) 10-[4-(3-Methylpyridin-2-yl)benzoyl]-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- kk) 10-(4-Pyridin-4-ylbenzoyl)-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- ll) N-(Pyridin-3-ylmethyl)-10-[4-(1,3-thiazol-2-yl)benzoyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- mm) 10-[4-(1H-Pyrazol-1-yl)benzoyl]-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- nn) 10-(4-Piperidin-1-ylbenzoyl)-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- oo) 10-[3-(Aminosulfonyl)-4-morpholin-4-ylbenzoyl]-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide hemihydrate;
- pp) N-(Pyridin-3-ylmethyl)-10-(thien-2-ylcarbonyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- qq) 10-(Pyridin-2-ylcarbonyl)-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- rr) 10-[(6-Chloropyridin-3-yl)carbonyl]-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- ss) 10-[(2,5-Dichlorothien-3-yl)carbonyl]-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- tt) 10-{[6-(Benzylamino)pyridin-3-yl]carbonyl}-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- uu) 10-({6-[(2-Methoxybenzyl)amino]pyridin-3-yl}carbonyl)-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- vv) 10-Isonicotinoyl-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- ww) 10-({6-[(4-Methoxybenzyl)amino]pyridin-3-yl}carbonyl)-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- xx) 10-(Pyrazin-2-ylcarbonyl)-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- yy) 10-(Pyridin-3-ylcarbonyl)-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- zz) 10-[(6-Piperidin-1-ylpyridin-3-yl)carbonyl]-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- aaa) 10-({6-[(2-Phenylethyl)amino]pyridin-3-yl}carbonyl)-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- bbb) 10-({6-[(3-Phenylpropyl)amino]pyridin-3-yl}carbonyl)-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- ccc) 10-{[6-(4-Methylpiperazin-1-yl)pyridin-3-yl]carbonyl}-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- ddd) 10-({6-[(3-Methoxybenzyl)amino]pyridin-3-yl}carbonyl)-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- eee) 10-({6-[Benzyl(methyl)amino]pyridin-3-yl}carbonyl)-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- fff) N-(Pyridin-3-ylmethyl)-10-({6-[(pyridin-3-ylmethyl)amino]pyridin-3-yl}carbonyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- ggg) 10-({6-[(2-Hydroxyethyl)amino]pyridin-3-yl}carbonyl)-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- hhh) 10-{[6-(Butylamino)pyridin-3-yl]carbonyl}-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- iii) 10-{[6-(Benzyloxy)pyridin-3-yl]carbonyl}-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- jjj) 10-[(4-tert-Butylphenoxy)acetyl]-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- kkk) 10-(Phenoxyacetyl)-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- lll) 10-(2-Phenoxypropanoyl)-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- mmm) 10-[(4-Chlorophenoxy)acetyl]-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- nnn) 10-[(4-Chloro-2-methylphenoxy)acetyl]-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- ooo) 10-{[(4-Bromophenyl)thio]acetyl}-N-{[5-hydroxy-4-(hydroxymethyl)-6-methylpyridin-3-yl]methyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- ppp) 10-{[(4-Bromophenyl)thio]acetyl}-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- qqq) 10-[(4-Chlorophenyl)acetyl]-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- rrr) 10-(1,1′-Biphenyl-4-ylacetyl)-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- sss) 10-[(2E)-3-Phenylprop-2-enoyl]-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- ttt) 10-(1-Naphthoyl)-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- uuu) 10-(2-Naphthoyl)-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- vvv) 10-(9H-Fluoren-2-ylcarbonyl)-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- www) 10-(3,3-Dimethylbutanoyl)-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- xxx) 10-(Cyclohexylcarbonyl)-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- or
- yyy) 10-Isobutyryl-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide;
- or
- a pharmaceutically acceptable salt thereof.
77 more elements
A method of inhibiting fertility in a mammal, said method comprising administering an effective amount of at least one compound of Formula III:
- wherein
- R1 and R2 are selected independently from hydrogen, (C1-C6) alkyl, halogen, trifluoromethyl, hydroxyl, (C1-C6) alkoxy, OCF3, carboxy, —CONH[(C1-C6) alkyl], or —CON[(C1-C6) alkyl]2, amino, (C1-C6) alkylamino, —NHCO[(C1-C6) alkyl];
- R3 is selected from the group consisting of hydrogen, (C1-C6) alkyl, (C1-C6) alkoxy, hydroxyl, amino, (C1-C6) alkylamino, C(O)—(C1-C6) alkyl, and halogen;
- A is selected from the group consisting of C═O, CH2, and SO2;
- R′ is a group consisting of
- wherein
- R150 is hydrogen or alkyl;
- X is selected independently from the group consisting of
- wherein
- R160 is hydrogen or alkyl;
- R170 is one to three substituents selected from the group consisting of hydrogen, alkyl, halogen, hydroxy, aryloxy, and hydroxyalkyl;
- R180 is 5 or 6-membered saturated cycloalkylamine;
- m′ is an integer from 1 to 4;
- q′ is an integer from 1 to 2;
- r′ is 0or 1;
- B′ is selected independently from the group consisting of
- wherein
- R5, R6, R7, R8, R9, and R10, are selected independently from the group consisting of hydrogen, alkyl, alkoxy, trihalomethyl, halogen, —C(O) alkyl, hydroxy, hydroxyalkyl, alkyloxyalkyl, —CH(OH)alkyl, —CH(alkoxy)alkyl, formyl, nitro, thioalkyl, —SO2alkyl, —SO2NHR11, —SO2N(R11)2, —(CH2)pCN , —(CH2)pCOOR12, —(CH2)pNR13R14, 13(CH2)pCONR13R14, —CH═NOH, —CH═NO-alkyl,
- and —C(O)aryl optionally substituted by alkyl;
- R11 and R12 are each indedendently hydrogen or alkyl;
- R13 and R14 are each indedendently hydrogen or alkyl;
- or can be taken together with the nitrogen to which they are attached to form a 4-6 membered saturated ring optionally containing one or more additional O, S or N atoms;
- p is 0 or 1.
20 more elements
A method of preventing conception in a mammal, said method comprising administering an effective amount of at least one compound of Formula III:
- wherein
- R1 and R2 are selected independently from hydrogen, (C1-C6) alkyl, halogen, trifluoromethyl, hydroxyl, (C1-C6) alkoxy, OCF3, carboxy, —CONH[(C1-C6) alkyl], or —CON[(C1—C6) alkyl]2, amino, (C1-C6) alkylamino, —NHCO[(C1—C6) alkyl];
- R3 is selected from the group consisting of hydrogen, (C1-C6) alkyl, (C1-C6) alkoxy, hydroxyl, amino, (C1-C6) alkylamino, C(O)—(C1-C6) alkyl, and halogen;
- A is selected from the group consisting of C═O, CH2, and SO2;
- R′ is a group consisting of
- wherein
- R150 is hydrogen or alkyl;
- X is selected independently from the group consisting of
- wherein
- R160 is hydrogen or alkyl;
- R170 is one to three substituents selected from the group consisting of hydrogen, alkyl, halogen, hydroxy, aryloxy, and hydroxyalkyl;
- R180 is 5 or 6-membered saturated cycloalkylamine;
- m′ is an integer from 1 to 4;
- q′ is an integer from 1 to 2;
- r′ is 0 or 1;
- B′ is selected independently from the group consisting of
- wherein
- R5, R6, R7, R8, R9, and R10, are selected independently from the group consisting of hydrogen, alkyl, alkoxy, trihalomethyl, halogen, —C(O) alkyl, hydroxy, hydroxyalkyl, alkyloxyalkyl, —CH(OH)alkyl, —CH(alkoxy)alkyl, formyl, nitro, thioalkyl, —SO2alkyl, —SO2NHR11, —SO2N(R11)2, —(CH2)pCN , —(CH2)pCOOR12, —(CH2)pNR13R14, —(CH2)pCONR13R14, —CH═NOH, —CH═NO-alkyl,
- and —C(O)aryl optionally substituted by alkyl;
- R11 and R12 are each independently hydrogen or alkyl;
- R13 and R14 are each independently hydrogen or alkyl;
- or can be taken together with the nitrogen to which they are attached to form a 4-6 membered saturated ring optionally containing one or more additional O, S or N atoms;
- p is 0 or 1.
20 more elements
Dependencies are inferred from the claim text.