New diphenyl-benzocycloheptene derivatives, are tissue-selective estrogens and antiestrogens useful e.g. for treating osteoporosis or hormone-dependent tumors or in hormone replacement therapy

摘要

5-(4-Substituted phenyl)-6-phenyl-8,9-dihydro-7H-benzocycloheptene derivatives (I) are new. Benzocycloheptenes of formula (I) are new. R1, R2 = H or OH; or 1-10C alkoxy, 1-10C alkanoyloxy or 7-15C aroyloxy (all optionally substituted); A = direct bond or O; B' = alkylene, alkenylene or alkynylene (all having up to 10C and optionally substituted); Z' = -D-SOx-E-G, NR7R8 or G; D = direct bond or -N(R3)-R4-; R3 = alkyl, alkenyl or alkynyl of up to 10C; R4 = as for B'; or R3 + R4 = group completing a 4-7 membered N-containing ring system; x = 0-2; E = as for B'; G = partially or completely fluorinated 1-5C alkyl; aryl or heteroaryl (both optionally substituted); CONR5R6; halo; or H; R5, R6 = as R7, R8; R7, R8 = H; alkyl, alkenyl or alkynyl (all having up to 14C, optionally partially fluorinated and optionally interrupted by 1-3 of O, S and N(R9)); aryl, heteroaryl, 3-10C cycloalkyl, 4-15C cycloalkylalkyl, 7-20C aralkyl or heteroaryl-(1-8C) alkyl (all optionally mono- or disubstituted); optionally substituted aminoalkyl; biphenylene residue; or COR10; R9 = H or 1-3C alkyl; R10 = as R7, R8; or NR7R8 = 5- or 6-membered saturated or unsaturated heterocycle (optionally containing 1 or 2 further N, O or S heteroatoms and optionally substituted); provided that: (i) if A = O and Z' = G, then G cannot be H or halo; and (ii) if A = O and Z' = NMe2 or pyrrolidino, then B' has at least 3C.