| 摘要 |
0991f JAB 522 NOVEL (1H-IMIDAZOL-1-YLMETHYL) SUBSTITUTED BENZIMIDAZOLE DERIVATIVES Novel (1H-imidazol-1-ylmethyl) substituted benzimidazole derivatives, compositions containing the same, and methods of treating androgen dependent disorders in mammals. The present invention therefore is concerned with imidazole derivatives of formula <IMG> (I), the pharmaceutically acceptable acid addition, metal or amine substitution salts and the stereochemically isomeric forms thereof, wherein R is hydrogen; C1-10alkyl; C3-7cycloalkyl; Ar1 or Ar1-C1-6alkyl; R1 is hydrogen; C3-7cycloalkyl; Ar1; C1-10alkyl; C1-6alkyl substituted wlth Arl or C3-7cycloalkyl; hydroxy; C1-10alkyloxy; C1-6alkyloxy substituted with Ar1 or C3-7cycloalkyl; C3-6alkenyloxy optionally substituted with Ar2; C3-6alkynyloxy optionally substituted with Ar2; or Ar1-oxy; A is a bivalent radical having the formula -CR2=N- (a) or <IMG> (b), wherein the carbon atom in the bivalent radical (a) or (b) is connected to -NR1; said R2 being hydrogen; halo; C1-4alkyl substituted with up to 4 halo atoms; C3-7cycloalkyl; Ar1; quinolinyl; indolinyl; C1-10alkyl; C1-6alkyl substituted with Ar1, C3-7cycloalkyl. quinolinyl, indolinyl or hydroxy; C1-10alkyloxy; C1-6alkyloxy substituted with Ar1 or C3-7cycloalkyl: C3-6alkenyl optionally substituted with Ar1; Ar2-oxy; C1-6alkyloxycarbonyl; carboxyl; C1-6alkylcarbonyl; Ar1-carbonyl or Ar1-(CHOH)-; said X being O or S; said R3 being hydrogen. C1-6alkyl or Ar2-C1-6alkyl: Ar1 is phenyl, substituted phenyl, pyridinyl, aminopyridinyl, imidazolyl, thienyl, halothienyl, furanyl, halofuranyl or thiazolyl; Ar2 is phenyl or substituted phenyl; in Ar1 and Ar2 said substituted phenyl being phenyl substituted with 1, 2 or 3 substltuents each independently selected from halo, hydroxy, trifluoromethyl, C1-6alkyl, C1-6alkyloxy, cyano, amino, mono- and di(C1-6alkyl)amino. nitro. carboxyl. formyl and C1-6alkyl-oxycarbonyl.
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