Patent HU-9902294-A2 (HU)
Title: Substituted imidazoles having anti-cancer and cytokine inhibitory activity and pharmaceutical compositions containing them
Inventor: CLAREMON DAVID A
IPC: C07D233/76
Filed: 1996-10-02
Abstract: Substd imidazoles of formula (I) and their salts are new. Ar = 6-10 atom aromatic gp; X, X' = -(CH2)m-Y-(CH2)n-; m, n = 0 to 4; m+n = 0 to 6; Y = bond, O, S(O)y, NRq', C(O), OC(O), C(O)O, SOxNRq', NRq'SOx, C(O)NRq' or NRq'C(O); y = 0 to 2; x = 1 or 2; V = 4-10 membered non-aromatic heterocycle (contg. 1-3 N and 0 or 1 O or S, and opt. substd. by 1-3 R'); Rx = H, T, OT or COT; T = 1-6C alkyl substd. by 1-3 Rq; R, R" = halo, OH, T, OT, 3-8C cycloalkyl( substd. by 1-3 Rq), CN, CONH2, CONHT, CON(T)2, NH2, NHT, N(T)2, CO2H, CO2T, C(O)T, Ar, Het, CF3, SH, NO2, SOyT, SO2NH2, SO2NHT, SO2N(T)2, NHSO2T, NHSO2Ar, NHSO2Het, N(Rq')C(O)T, NRq'C(O)NHT, 2-4C alkenyl or 2-4C alkynyl (both substd. by 1-3 Rq); Ar = aryl substd. by 1-3 Rq; Het = heteroaryl substd. by 1-3 Rq; R' = hydroxy, T, 3-8C cycloalkyl(substd. by 1-3 Rq), heterocyclyl(substd. by 1-3 Rq), CN, NH(Rq"), NHT, N(T)2, NH(3-8C cycloalkyl substd. by 1-3 Rq), N((3-8C cycloalkyl substd. by 1-3 Rq)2, CF3, SH, NO2, 2-4C alkenyl(substd. by 2-3 Rq), Ar, Het, 2-4C alkynyl(substd. by 1-3 Rq), -OC(O)(3-8C cycloalkyl substd. by 1-3 Rq), SO2NH2, SO2NHT, SO2N(T)2, NHSO2T, NHSO2Ar, NHSO2Het, -OC(O)Het, N(Rq')C(O)T, NRq'C(O)NHT, -OC(O)(1-6C alkyl)(Rq)3, -OC(O)Ar, -OC(O)Het, -C(=NRq')NH2, -C(=NRq')NHT, -C(=NRq')N(T)2, CONH2, -CONHT, CON(T)2, CONH(3-8C cycloalkyl substd. by 1-3 Rq), CON((3-8C cycloalkyl substd. by 1-3 Rq)2, CO2H, CO2T, C(O)T, CO2(3-8C cycloalkyl substd. by 1-3 Rq), C(O)(3-8C cycloalkyl substd. by 1-3 Rq), -(C(O)(CH2)j-CR5R)6-(CH2)k-NR7)p-R8, - C(O)(3-8C cycloalkyl substd. by 1-3 Rq), -C(O)Het, -CON(T)(3-8C cycloalkyl substd. by 1-3 Rq), -COAr, - COHet, O(CO-(CH2)jCR5R6-(CH2)k-NR7)p-R8 or (NR7-(CH2)kCR5R6-(CH2)j-CO)p-R9; j, k = 0 - 3; R5, R6 = H, aryl or T; or CR5R6 = V'; V' = 3-6-membered cycloalkyl or heterocyclyl, aryl or heteroaryl; p = 1-3; provided that p = 1, then CR5R6 = V' and j, k are not both 0; R7, R8 = H, 1-6C alkyl or aryl; R9 = H, a negative charge by a positively charged gp or a protecting gp; Rq = Rq', CN, CO2H, CO2(1-4C alkyl), C(O)(1-4C alkyl), NH(Rq"), aryl(Ra)3, heteroaryl(Ra)3, NH(1-4C alkyl), N(1-4C alkyl)2, CONH2, SH, S(O)y(1-6C alkyl)(Ra)3, C(O)NH(1-6C alkyl)(Ra)3, C(O)N(1-6C alkyl)(Ra)3)2, NHC(NH)NH2, heteroalkyl(Ra)3, -NHC(O)NH2, or (opt. N- linked) mono- or bicyclic, non-aromatic or partially aromatic, ring system (contg 5-10 ring atoms including 1 to 4 N and 0 or 1 O or S(O)y, opt. contg 1 or 2 carbonyl gps); Ra = H, 1-6C alkyl, O(1-6C alkyl), opt. substd aralkyl, opt. substd heteroaralkyl, opt. substd aralkoxy, halo, hydroxy, CN, CONH2, CONH(1-6C alkyl), (CON(1-6C alkyl)2, CO2H, CO2(1-6C alkyl), C(O)(1-6C alkyl), phenyl, CF3, SH, NO2, SOy(1-6C alkyl), SO2NH2, SO2NH(1-6C alkyl), NHSO2(substd aryl), NHSO2(substd heteroaryl), NHSO2(1-6C alkyl), NHSO2heteroaryl, NH2, NH(1-6C alkyl), N(1-6C alkyl)2, NHC(O)(1-6C alkyl), NHC(O)NH(1-6C alkyl), 2-4C alkenyl or 2-4C alkynyl; Rq' = H, OH, 1-4C alkyl, -O(1-4C alkyl), aryl or C(O)(1-4C alkyl); and Rq" = H, OH or 1-4C alkyl.