Patent HU-0301490-A2 (HU)
Title: Condensed cyclyc compounds and their pharmaceutical use
Inventor: HASHIMOTO HIROMASA
IPC: C07D235/18
Filed: 2002-06-26
Abstract: Antihepatitis C agents comprise a fused cyclic compound (I). Antihepatitis C agents comprise a fused cyclic compound of formula (I) or its salt. [Image] G 1-G 4CR 1 or N; G 5, G 6, G 8, G 9C or N; G 7CR 7, O, S, N or NR 8; R 1H, COAlk, COOH, CN, NO 2, Alk 1, COOR a 1, CONR a 2R a 3, C(=NR a 4)NH 2, NHR a 5, OR a 6, SO 2R a 7, P(=O)(OR a 3 1) 2 or Het; Alk : 1-6C alkyl; Alk 1Alk (optionally substituted by 1-3 Q); Q : halo, OH, COOH, NH 2, OAlk, OAlkOAlk, COOAlk or NHAlk); R a 1Alk 1, AlkAr or glucuronic acid; Ar : 6-14C aryl; Ar 1Ar optionally substituted by 1-5 Q 1; Q 1halo, CN, NO 2, Alk, COAlk, (CH 2) rCOOR b 1, (CH 2) rCONR b 1R b 2, (CH 2) rNR b 1R b 2, (CH 2) rNR b 1COR b 2, (CH 2) rNHSO 2R b 1, (CH 2) rOR b 1, (CH 2) rS(O) zR b 1 or SO 2NR b 1R b 2; z : 0-2; R b 1, R b 2H or Alk; r : 0-6; R a 2, R a 3H, OAlk or Alk 1; R a 4H or OH; R a 5H, COAlk or SO 2Alk; R a 6H or Alk 1; R a 7OH, NH 2, Alk or NHAlk; R a 3 1H, Alk 1 or AlkAr 1; Het : heterocyclyl containing 1-4 O, N or S; R 7, R 8H or Alk 1; Cy : Cyc or a group of formula (i)-(iv); Cyc : 3-8C cycloalkyl or 3-8C cycloalkenyl both optionally substituted by 1-5 OH, halo, Alk or OAlk; u, v : 1-3; A : Ar, 3-8C cycloalkyl, 3-8C cycloalkenyl or Het all substituted by R 5, R 6 and X; R 5, R 6H, halo, Alk 1 or OR a 8; R a 8H, Alk or AlkAr; X : H, halo, CN, NO 2, NH 2, NHCOAlk, SO 2Alk, Alk 1, 2-6C alkenyl (optionally substituted by 1-3 Q), COOR b 1, CONH(CH 2) rR a 1 0, OR a 6 or YB; R a 1 0Alk 1, COOAlk or NHCOAlk; B : Ar, 3-8C cycloalkyl or Het all optionally substituted by 1-3 Z; Z : D or Ar, 3-8C cycloalkyl, AlkAr, Het or AlkHet all optionally substituted by 1-5 halo, CN, NO 2, Alk 1, (CH 2) rCOR a 1 8, (CH 2) rCOOR a 1 9, (CH 2) rCONR a 2 7R a 2 8, (CH 2) rC(=NR a 3 3)NH 2, (CH 2) rOR a 2 0, (CH 2) rO(CH 2) pCOR a 2 1, (CH 2) rNR a 2 2R a 2 3, (CH 2) rNR a 2 9R a 2 4, (CH 2) rNR a 2 9SO 2R a 1 8, (CH 2) rS(O) qR a 1 8, (CH 2) rSO 2NHR a 1 8 or Het; R a 1 8Alk 1, Ar 1 or Het 1; Het 1Het optionally substituted by 1-5 Q 1; R a 1 8H, Alk 1, Ar 1 or Het 1; R a 2 7, R a 2 8H, Alk 1, Ar 1, AlkAr 1, Het 1, AlkHet 1, Cyc 1, AlkCyc 1, OH or OAlk; Cyc 13-8C cycloalkyl optionally substituted by 1-5 Q 1; R a 3 3H, Alk, OH or OAlk; R a 2 0H, Alk 1, Alk 2, Ar 1, AlkAr 1, Het 1, AlkHet 1 or Cyc 1; Alk 22-6C alkenyl or 2-6C alkynyl both optionally substituted by 1-3 Q; R a 2 1NH 2, NHAlk or Het 1; p : 0-6; R a 2 2, R a 2 3H, Alk 1, Ar 1, AlkAr 1, Het 1 or AlkHet 1; R 2 9H, Alk or COAlk; R 2 4NH 2, NHAlk, Alk 1, Ar 1, Het 1 or AlkHet 1; Y : bond, 1-6C alkylene, 2-6C alkenylene, (CH 2) rO(CH 2) r, CO, CO(CH 2) r, CONH(CH 2) rNH, NHCO 2, NHCONH, O(CH 2) rCO, O(CH 2) rO, SO 2, (CH 2) rNR a 1 2, (CH 2) rNR a 1 2CO, CONR b 5(CH 2) r, CONHCHAr 1, O(CH 2) rCR a 1 5R a 1 6, (CH 2) rNR a 1 2CHR a 1 5, NHSO 2, NHAlkSO 2, S(O) q(CH 2) rCR a 1 5R a 1 6(CH 2) r or (CH 2) rCR a 1 5R a 1 6(CH 2) r; R a 1 2Alk 1, AlkAr 1, Ar 1, COR b 5 or COOR b 5; R b 5H, Alk 1 or AlkAr 1; R a 1 5, R a 1 6H, COOH, Alk, OAlk, OAlkAr or NR b 7; or R a 1 5(CH 2) rB; and R b 7H, Alk, COAlk COOAlkAr. [Image] An independent claim is also included for some new compounds (I). ACTIVITY : Virucide; Hepatotropic; Antiinflammatory MECHANISM OF ACTION : HCV-Polymerase-Inhibitor. In assays 2-{4-{2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-(4-tetrahydrothiopyranyl)benzimidazole-5-carboxylic acid (Ib) inhibited hepatitis C polymerase with an IC 5 0 of less than 0.01 MicroM.