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

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″, SCOR′, or COR″, and
• 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, saturated 5 to 6 membered heterocyclic ring comprising 1 or 2 heteroatoms independently selected from N and O, (CH2)nOH, SO2OH, SO2R″, tosyl, SO2N(R′)2, PO(OR′)2, C(O)N(R′)2, C(O)(CH2)nN(R)2, and C(O)R′″;
• 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;
• (ii-a) one of R7 and R8 is OR7′, wherein R7′ is selected from the group consisting of H or C1-6-alkyl
• and the other is selected from the group consisting of H, C1-6-alkyl, C1-3-haloalkyl, C1-3-perhaloalkyl, C2-6-alkenyl, C2-6-alkynyl, benzyl, (CH2)nCN, (CH2)nOH, N(R′)2, (CH2)nN(R′)2, C(O)OR′, (CH2)nC(O)OR′, C(O)N(R′)2, (CH2)nC(O)NH2, OR7′, COR′, NHCO—C1-6-alkyl, —COCH2O—P(O)(OH)2;
• or
• (ii-b) one of R7 and R8 is H and the other is selected from the group consisting of halogen, C1-3-haloalkyl, C1-3-perhaloalkyl, (CH2)nCN, OSO2OH, OSO2R″, O-tosyl, OC(O)R′″, OC(O)(CH2)nCOOR′, OC(O)(CH2)nN(R)2, OC(O)CH2NHC(O)OR′, OPO(OR′)2, N3, N(R′)2, NH(CH2)mOR′, NH(CH2)mSR′, NH(CH2)mNR′2, NHOR′, and NHC(O)R′;
• or
• (ii-c) R7 and R8 form together a group selected from the group consisting of ═CH2, ═CHR8′, and CHCOOR7′, wherein R8′ is C1-6-alkyl, C1-6-alkoxy, or phenyl;
• 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 0, 1 or 2;
• m is 1, 2 or 3;
• or a pharmaceutically acceptable salt thereof.