Patent HU-9903370-A2 (HU)
Title: Beta-sulfonamido hydroxamic acids and pharmaceutical compositions containing them
Inventor: GU YANSONG
IPC: A61K31/16
Filed: 1997-10-08
Abstract: ~b-sulphonamide hydroxamic acid derivatives of formula (I) and their salts and optical isomers or diastereoisomers are new: A = 5-7 membered monocyclic, non-aromatic heterocycle containing 1-2 heteroatoms comprising N, O and/or S (optionally substituted by R1, R2, R3 and R4), 3-7C cycloalkyl containing 0-2 double bonds (optionally substituted by R1, R2, R3 and R4) or CHR5=CHR6; the hydroxamic acid and sulphonamido moieties are bonded to adjacent C on group A; Z = aryl, heteroaryl or heteroaryl fused to Ph; aryl = Ph or naphthyl (optionally substituted by R1, R2, R3 and R4); heteroaryl = 5-6 membered heteroaromatic ring containing 1-3 heteroatoms comprising N, O and/or S (optionally substituted by R1, R2, R3 and R4); when heteroaryl is fused to Ph either or both rings can be optionally substituted by R1, R2, R3 and R4; R1 - R4 = H, COR5, F, Br, Cl, I, C(O)NR5OR6, CN, OR5, 1-4C perfluoroalkyl, SOxR5, OPO(OR5)(OR6), PO(OR6)R5, OC(O)NR5R6, CO2R5, CONR5R6, SO3H, NR5R6, NR5COR6, NR5COOR6, SO2NR5R6, NO2, N(R5)SO2R6, NR5CONR5R6, NR5C(=NR6)NR5R6, 3-6C cycloalkyl (optionally having 1-2 double bonds and being optionally substituted by 1-3 R5), 3-6 membered cycloheteroalkyl (containing 1-4 heteroatoms comprising N, O and/or S optionally having 1-2 double bonds and being optionally substituted by 1-3 R5), aryl, heteroaryl, SO2NHCOR5, CONHSO2R5', tetrazol-5-yl, SO2NHCONR5R6 or SO2NHCN or 1-6C alkyl, 2-6C alkenyl or 2-6C alkynyl (optionally substituted by COR5, CN, 2-6C alkenyl, 2-6C alkynyl, OR5, 1-4C perfluoroalkyl, SOxR5, OC(O)NR5R6, CO2R5, CONR5R6, SO3H, NR5R6, NR5COR6, NR5CO2R6, SO2NR5R6, NO2, N(R5)SO2R6, NR5CONR5R6, 3-6C cycloalkyl, 3-6 membered cycloheteroalkyl, aryl, heteroaryl, biphenyl, SO2NHCOR5', CONHSO2R5', PO(OR5)OR6, PO(OR6)R5, tetrazol-5-yl, C(O)NR5OR6, NR5C(=NR6)NR5R6, SO2NHCONR5R6 or SO2NHCN); provided that when R1 and R2 are on adjacent C atoms then CR1CR2 = 5-7 membered optionally unsaturated 5-6 monocyclic membered heterocyclic or 5-6 membered heteroaryl ring (each containing 1-3 heteroatoms comprising O, S or N and being optionally substituted by 1-4 R4) or a 5-7 membered optionally unsaturated carbocycle (optionally substituted by 1-4 R4); x = 0-2; R5, R6 = H, aryl, heteroaryl, 3-6C cycloalkyl or 3-6C cycloheteroalkyl, 1-4C perfluoroalkyl or 1-6C alkyl, 2-6C alkenyl or 2-6C alkynyl (all optionally substituted by OH, COR8, CN, C(O)NR8OR9, 2-6C alkenyl, 2-6C alkynyl, OR8, 1-4C perfluoroalkyl, SOxR8, OPO(OR8)OR9, PO(OR8)R9, OC(O)NR8R9, CO2R8, CONR8R9, SO3H, NR8R9, NHCOR8R9, NR8CO2R9, SO2NR8R9, NO2, NR8SO2R9, NR8CONR8R9, SO2NHCOR8, CONHSO2R8, 3-6C cycloalkyl, 3-6C cycloheteroalkyl, aryl, heteroaryl, SO2NHCOR8', CONHSO2R8', tetrazol-5-yl, NR8C(=NR9)NR8R9, SO2NHCONR8R9 or SO2NHCN); R8' = a group R8 excluding H; R7 = (a) H, 1-6C alkyl, 2-6C alkenyl or 2-6C alkynyl (optionally substituted by OH, COR5, CN, 2-6C alkenyl, 2-6C alkynyl, OR5, 1-4C perfluoroalkyl, SOxR5, OPO(OR5)OR6, PO(OR5)R6, OC(O)NR5R6, COOR5, CONR5R6, SO3H, NR5R6, NR5COR6, NR5COOR6, SO2NR5R6, NO2, N(R5)SO2R6, NR5CONR5R6, 3-6C cycloalkyl, 3-6C cycloheteroalkyl, aryl, heteroaryl, SO2NHCOR5', CONHSO2R5', tetrazol-5-yl, NR5C(=NR6)NR5R6, CONR5OR6, SO2NHCONR5R6 or SO2NHCN; (b) Ph or naphthyl (optionally substituted by R1, R2, R3 and R4) or a 5-6 membered heteroaryl (containing 1-3 heteroatoms comprising N, O and/or S and optionally substituted by R1, R2, R3 and R4); or (c) 3-6C cycloalkyl or 3-6 membered cycloheteroalkyl; or R7CH2NA forms a non-aromatic 1,2-benzofused 7-10 membered heterocycle with the C bearing sulphonamido (optionally containing an additional heteroatom selected from O, S and N and being optionally fused to another benzene ring); R8, R9 = H, aryl, heteroaryl, 3-7C cycloalkyl, 3-6 membered cycloheteroalkyl, 1-4C perfluoroalkyl, 1-6C alkyl, 2-6C alkenyl or 2-6C alkynyl (optionally substituted by OH, alkoxy, aryloxy, 1-4C perfluoroalkyl, amino, mono- or di-(1-6C alkyl) amino, carboxylic acid, carboalkoxy or carboaryloxy), NO2, CN, carboxamido primary, mono- or di-(1-6C alkyl)carbamoyl; and R5' = R5 excluding H.