Patent HU-9601036-A2 (HU)
Title: Hydroxamic acid derivatives of aryl sulfonyl cyclic amines and pharmaceutical compositions containg them
Inventor: PISCOPIO ANTHONY D
IPC: A61K31/435
Filed: 1996-04-19
Abstract: 1-Arylsulphonyl-piperidine- 2-hydroxamic acids and analogues with related heterocycles, of formula (I), and their salts, are new. X = C, O, or S; Y = C, O, S, SO, SO2, or N; R1-R9 = H, 1-6C alkyl (opt. substd. by 1-6C alkylamino, 1-6C alkylthio, 1-6C alkoxy, CF3, 6-10C aryl, 5-9C heteroaryl, 6-10C arylamino, 6-10C aryloxy, 6-10C arylthio, 5-9C heteroaryl-amino, 5-9C heteroaryloxy, 5-9C heteroarylthio, 6-10C aryl(6-10C aryl), 3-6C cycloalkyl, 1-6C hydroxyalkyl, (1-6C alkyl)hydroxymethylene, piperazinyl, 6-10C aryl(1-6C alkoxy), 5-9C heteroaryl(1-6C alkoxy); 1-6C acylamino, acylthio, acyloxy, alkylsulphinyl, or alkylsulphonyl; 6-10C arylsulphinyl or arylsulphonyl; amino, or mono- or di- (1-6C alkyl)amino), 2-6C alkenyl or alkynyl, 6-10C aryl-(2-6C alkenyl or alkynyl), 5-9C heteroaryl(2-6C alkenyl or alkynyl); 1-6C alkylamino, alkoxy, or alkylthio; CF3, 1-6C alkyl(difluoromethylene), 1-3C alkyl-(difluoromethylene)(1-3C alkyl); or 6-10C aryl, aryloxy, arylthio, or arylamino; or 5-9C heteroaryl, heteroaryloxy, heteroarylthio, or heteroaryl-amino; 3-6C cycloalkyl, 2-7C alkyl-methanol, piperidyl, 1-6C alkylpiperidyl; 1-6C acylamino, acyloxy, or acylthio; (1-6C acyl)piperazino(1-6C alkyl), (6-10C aryl)piperazino, (5-9C heteroaryl)piperazino, (1-6C alkyl)piperazino, (6-10C aryl 1-6C alkyl)piperazino, (5-9C heteroaryl 1-6C alkyl)piperazino, morpholino, thiomorpholino, piperidino, pyrrolidino, piperidyl, (1-6C alkyl)piperidyl, (6-10C aryl)piperidyl, (5-9C heteroaryl)piperidyl, (1-6C alkyl)piperidyl(1-6C alkyl), (6-10C aryl)piperidyl(1-6C alkyl), (5-9C heteroaryl)piperidyl(1-6C alkyl), (1-6C acyl)piperidyl, or (CH2)n-CO-Z; or R1+R2, R3+R4, or R5+R6 = O; or R1+R2, R3+R4, R5+R6, or R7+R8 = 3-6C cycloalkyl, oxa-cyclohexyl, thia-cyclohexyl, indanyl, tetrahydronaphthyl, or (1-R24)-piperidyl; n = 1-6; Z = OH, 1-6C alkoxy, or NR14R15; R14, R15 = H, 1-6C alkyl (opt. substd. by (1-6C alkyl)piperidyl, (6-10C aryl)piperidyl, (5-9C heteroaryl)piperidyl, 6-10C aryl, 5-9C heteroaryl, 6-10C aryl(6-10C aryl), 3-6C cycloalkyl, R16-(2-6C alkyl), (1-5C alkyl)CHR16(1-6C alkyl), R17-(1-6C alkyl), (1-5C alkyl)CHR17(1-6C alkyl), or CHR18COR19; R16 = OH, piperazino; 1-6C acyloxy, acylamino, alkylthio, alkylsulphinyl, or alkylsulphonyl; 6-10C arylthio, alkylsulphinyl, or arylsulphonyl; amino, mono- or di-(1-6C alkyl)amino, (1-6C acyl)piperazino, (1-6C alkyl)piperazino, (6-10C aryl-1-6C alkyl)piperazino, (5-9C heteroaryl-1-6C alkyl)piperazino, morpholino, thiomorpholino, piperidino, or pyrrolidino; R17 = piperidyl or (1-6C alkyl)piperidyl; R18 = H, 1-6C alkyl, 6-10C aryl(1-6C alkyl), 5-9C heteroaryl(1-6C alkyl), 1-6C alkylthio(1-6C alkyl), 6-10C arylthio(1-6C alkyl), 1-6C alkylsulphinyl or alkylsulphonyl-(1-6C alkyl), 6-10C arylsulphinyl- or arylsulphonyl-(1-6C alkyl), 1-6C aminoalkyl or hydroxyalkyl, mono- or di (1-6C alkyl)amino(1-6C alkyl), R20R21NCO(1-6C alkyl), or R20OCO(1-6C alkyl); R19 = OR22 or NR22R23; R20-R23 = H, 1-6C alkyl, 6-10C aryl(1-6C alkyl), or 5-9C heteroaryl(1-6C alkyl); or R14+R15, R20+R21, or R22+R23 = azetidinyl, pyrrolidinyl, morpholinyl, thiamorpholinyl, indolinyl, isoindolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, (1-6C acyl)piperazinyl, (6-10C aryl)piperazinyl, (5-9C heteroaryl)piperazinyl, or a diaza-bicycloalkyl gp. (a)-(e); r = 1-3; m = 1 or 2; p = 0 or 1; Q = H, 1-3C alkyl, 1-6C acyl, or 2-7C alkoxycarbamoyl; R24 = H, 1-6C acyl, alkylsulphonyl, or alkyl, 6-10C aryl(1-6C alkyl), or 5-9C heteroaryl(1-6C alkyl); and Ar = 6-10C aryl or 5-9C heteroaryl (both opt. substd. by 1-6C alkyl, one or two 1-6C alkoxy, 6-12C aryloxy, or 5-9C heteroaryloxy); provided that; (i) in the pairs R1 and R2, R3 and R4, R5 and R6, and R7 and R8, either both or neither are H; (ii) when R1, R2, or R9 are substits. with a heteroatom, then the heteroatom is not bonded directly to the 2- or 6-positions; (iii) when X = N, then R4 is absent; (iv) when X = O, S, SO, SO2, or N, and when any of R1, R2, R5, R6 is a substit. with a heteroatom, then the heteroatom is not bonded directly at the 4- or 6-positions; (v) when Y = O, S,