17 Beta-hydroxysteroid dehydrogenase type 3 inhibitors for the treatment of androgen dependent diseases

A compound of the formula (I):

• a prodrug thereof, or a pharmaceutically acceptable salt or solvate of said compound or of said prodrug wherein,
• R1 and R2 are the same or different and are independently selected from the group consisting of aryl, heteroaryl, arylalkyl and heteroarylalkyl, each optionally substituted with one to six groups selected from the group consisting of:
• a) halogen;
• b) —OCF3 or —OCHF2;
• c) —CF3;
• d) —CN;
• e) alkyl or R18-alkyl;
• f) heteroalkyl or R18-heteroalkyl;
• g) aryl or R18-aryl;
• h) heteroaryl or R18-heteroaryl;
• i) arylalkyl or R18-arylakyl;
• j) heteroarylalkyl or R18-heteroarylalkyl;
• k) hydroxy;
• l) alkoxy;
• m) aryloxy;
• n) —SO2-alkyl;
• o) —NR11R12;
• p) —N(R11)C(O)R13,
• q) methylenedioxy;
• r) difluoromethylenedioxy;
• s) trifluoroalkoxy;
• t) —SCH3 or —SCF3;
• and
• u) —SO2CF3 or —NHSO2CF3;
• R3 is H, —OH, alkoxy or alkyl, provided that when X is N, R3 is not —OH or alkoxy;
• R4, R5, R7 and R8 are the same or different and are independently selected from the group consisting of H, OH, OR14, —NR11R12, —N(R11)C(O)R13, alkyl, heteroalkyl, aryl, cycloalkyl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl,
• provided that when Z and/or X is N, then R4, R5, R7 and R8 are not OH, OR14, —NR11R12, or —N(R11)C(O)R13;
• R6 is selected from the group consisting of —C(O)R15 and —SO2R15;
• R9 and R10 are the same or different and are independently selected from the group consisting of H, F, —CF3, alkyl, cycloalkyl, arylalkyl, heteroalkyl, heteroarylalkyl, heterocycloalkyl, hydroxy, alkoxy, aryloxy, —NR11R12 and —N(R11)C(O)R13, provided that when Z is N, then R9 and R10 are each not F, hydroxy, alkoxy, aryloxy, —NR11, R12 or —N(R11)C(O)R13;
• R11 is selected from the group consisting of H, alkyl, aryl and heteroaryl;
• R12 is selected from the group consisting of H, alkyl, aryl and heteroaryl;
• R13 is selected from the group consisting of alkyl, alkoxy and aryloxy;
• R14 is selected from the group consisting of H, alkyl, aryl and heteroaryl;
• R15 is selected from the group consisting of —NR16R17, —OR16, alkyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl and heteroarylalkyl, each optionally substituted with R18;
• R16 and R17 are the same or different and are independently selected from the group consisting of H, alkyl, aryl, arylalkyl, heteroalkyl and heteroaryl, each optionally substituted with R18, provided that when R15 is —OR16, R16 is not H;
• R18 is one to four substituents each independently selected from the group consisting of lower alkyl, halo, cyano, nitro, haloalkyl, hydroxy, alkoxy, alkoxy carbonyl, carboxy, carboxyalkyl, carboxamide, mercapto, amino, alkylamino, dialkylamino, sulfonyl, sulfonamido, cycloalkyl, heterocycloalkyl, heterocycloalkylalkyl, aryl and heteroaryl;
• and
• either X=Z=N, or X=Z=C or X is C and Z is N,
• wherein the term “heteroaryl” refers to 5- or 10-membered single or benzofused aromatic ring consisting of 1 to 3 heteroatoms independently selected from the group consisting of —O—, —S, and —N═, provided that the rings do not possess adjacent oxygen and/or sulfur atoms, wherein said heteroaryl can be unsubstituted or substituted with one, two, or three substituents independently selected from lower alkyl, halo, cyano, nitro, haloalkyl, hydroxy, alkoxy, carboxy, carboxyalkyl, carboxamide, mercapto, amino, alkylamino and dialkylamino;
• the term “heteroarylalkyl” refers to a heteroaryl group bonded through an alkyl group, the term “heterocycloalkyl” refers to a non-aromatic, heterocyclic ring of 3-7 atoms containing 1-3 heteroatoms selected from N, O and S;
• and the term “heteroalkyl” refers to an alkyl group which containing at least one heteroatom.