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

A compound of formula (I)

• wherein
• (i-a) R2 and R4 are each independently selected from the group consisting of H, halogen, C1-6-alkyl, C1-3-haloalkyl, C1-3-perhaloalkyl, CN, NO2, N3, N(R′)2, (CH2)nN(R′)2, OR′, (CH2)nOR′, CO2R′, CONHR′, NHCOR″, C(═NH)R″, C(═N—OH)R″ and COR″;
• R3 is selected from the group consisting of H, C1-6-alkyl, C1-3-haloalkyl, C1-3-perhaloalkyl, N(R′)2, N3, and OR3′, wherein
• R3′ is selected from the group consisting of R′, benzyl, succinyl, optionally acylated glucuronyl, (CH2)nOH, SO2OH, SO2R″, tosyl, SO2N(R′)2, PO(OR′)2, COOR′″, C(O)N(R′)2, C(O)(CH2)nN(R′)2, C(O)CH2NHC(O)R′, C(O)CH2NHC(O)OR″ and C(O)R′″;
• wherein
• R′ is H or C1-6-alkyl, C1-3-haloalkyl, or C1-3-perhaloalkyl, or when part of any N(R′)2 both R's together with the nitrogen they are attached to may form an 5 to 6 membered aliphatic or aromatic heterocyclic ring comprising 1 or 2 heteroatoms each independently selected from N and O;
• R″ is C1-6-alkyl, C1-3-haloalkyl, or C1-3-perhaloalkyl;
• R′″ is C1-18-alkyl, C2-18-alkenyl, —(CH2)n—C3-6-cycloalkyl, or optionally substituted phenyl;
• and
• n is 1 or 2;
• or
• (i-b) R2 and R3 or R3 and R4, together with the ring carbon atoms to which they are attached, form an unsaturated or aromatic 5-membered heterocyclic ring comprising 1 or 2 heteroatoms each independently selected from N and O, optionally substituted with methyl or oxo;
• and
• R4 or R2, respectively, is H and halogen;
• (ii-a) R5 and R6 are each H or R5 and R6 form together ═CH—OH;
• and
• R7 is selected from the group consisting of ureido, R′O—C1-3-alkylenyl, R′S—C1-3-alkylenyl, R′2N—C1-3-alkylenyl, and OR7′, wherein R7′ is selected from the group consisting of H, C1-6-alkyl, C3-6-alkenyl, and carboxy-C1-3-alkylenyl;
• or
• (ii-b) R5 and R6 and ═NR7 form together with the carbons they are attached to a structure
• which is selected from
• wherein X is O or NH;
• or a pharmaceutically acceptable salt thereof.