Patent TW-404946-B (TW)
Title: Quinazoline derivatives
Inventor: ARNOLD LEE D
IPC: C07D403/14
Filed: 1995-02-06
Granted: 2000-09-11
Abstract: This invention relates to certain 4-aminoquinazolines useful for the treatment of hyperproliferative diseases. A compound of Formula I and the pharmaceutically acceptable salts and stereoisomers thereof wherein either A, B or C Formula IV wherein X is methylene, thio, -N(H)- or oxy; Y completes a 5 or 6 membered aromatic or partially saturated ring which may incorporate an oxygen or sulfur atom; T is methylene, -N(H)-, thio or oxy; Formula VI wherein D may be saturated carbon, oxy or thio; Formula VIII wherein A completes a 7 to 9 membered mono-unsaturated mono-aza ring; R' for each occurrence is independently (a) trifluoromethyl, nitro, hydroxy, amino, cyano, (C1-C4)alkyl, (C1-C4)alkoxy, (C1-C4)alkoxycarbonyl, (C1-C4)alkanoyloxy, (C1-C4)alkanoylamino, carboxy, phenoxy, benzoyloxy, carbamoyl, mono-N- or di-N-N-di-(C1-C4)alkylcarbamoyl, mono-N- or di-N, N-(C1-C4)alkylamino, mono-N or di-N, N-(hydroxy(C1-C4)alkyl)amino, mono-N or di-N,N-(C1-C4)alkoxy(C2-C4)alkyl)amino, anilino, pyrrolidin-1-yl, piperidin-1-yl, morpholino, piperazin-1-yl, 4-(C1-C4)alkylpiperazin-1-yl, (C1-C4)alkythio, phenylthio, or such groups substituted on (C1-C4)alkyl; (b) hydroxy(C2-C4)alkoxy(C1-C4)alkyl, (C1-C4)alkoxy-(C2-C4)alkoxy-(C1-C4)alkyl, hydroxy(C2-C4)alkylthio(C1-C4)alkyl, (C1-C4)alkoxy(C2-C4)alkylthio(C1-C4)alkyl, hydroxyamino, benzoylamino, mono-N or di- N,N-(C1-C4)alkylcarbamoylmethylamino, carbamoylmethylamino, (C1-C4)alkoxycarbonylamino, (C1-C4)alkanoylamino, carboxymethylamino, (C1-C4)alkoxycarbonylmethylamino, (C1-C4)alkoxyamino, (C2-C4)alkanoyloxyamino, phenyl(C1-C4)alkylamino, (C1-C4)alkylsulphonylamino, benzenesulphonamido, 3-phenylureido, 2-oxopyrrolidin-1-yl, 2,5-dioxopyrrolidin-1-yl, ureido, (C1-C4)alkoxy(C1-C4)alkylcarbonylamino, (C1-C4)alkylsulfinyl, (C1-C4)alkylsulfonyl, (C1-C4)alkoxy(C2-C4)alkylthio, mono-, di- or trifluoromethyloxy, (C1-C4)alkylenedioxy, benzyloxy, azido, guanidino, aminocarbonyl, mono-N- or di-N,N-(C1-C4)alkylaminocarbonyl, phenyl(C1-C4)alkoxy, carboxymethoxy, (C1-C4)alkoxycarbonylmethoxy, carbamoylmethoxy, mono-N or di-N,N-(C1-C4)alkyl carbamoylmethoxy, mono-N- or di-N,N-(hydroxy(C2-C4)alkyl)carboxamido, mono-N- or di-N,N((C1-C4)alkoxy(C2-C4)alkyl)carboxamido or bis((C1-C4)alkanesulfonyl)amido; or (c) (C2-C4)alkoxy, (C2-C4)alkylthio, (C2-C4)alkanoyloxy, (C2-C4)alkylamino, (C1-C4)alkyl(C1-C4)alkylenedioxy, or (C2-C4)alkanoylamino; each such group substituted with amino, halo, hydroxy, (C2-C4)alkanoyloxy, (C1-C4)alkoxy, mono-N- or di-N,N-(C1-C4)alkylamino, mono-N or di-N,N-(hydroxy(C2-C4)alkyl)amino, mono-N or di-N,N-(C1-C4)alkoxy(C2-C4)alkyl)amino, (C1-C4)alkanoylamino, phenoxy, anilino, imidazol-1-yl, phenylthio, piperidino, morpholino, pipeerazin-1-yl, 4-(C1-C4)alkylpiperazin-1-yl, carboxy, (C1-C4)alkoxycarbonyl, carbamoyl, mono-N- or di-N,N-(C1-C4)alkylcarbamoyl, carboxamido, mono-N- or di-N,N-(C1-C4)alkylcarboxamido or mono-N- or di-N,N-(hydroxy(C2-C4)alkyl)carboxamido; wherein any phenyl in a R1 substituent is optionally mono- or di- substituted wiht halo, nitro, trifluoromethyl, hydroxy, (C1-C4)alkoxy or (C1-C4)alkyl and said (C1-C4)alkylenedioxy is linked at both ends to the quinazoline moiety; R2 for each occurrence is independently mono-, di- or tri-fluoromethyl, halo, nitro, hydroxy, amino, azido, isothiocyano, (C1-C4)alkyl, phenyl, thienyl, (C1-C4)alkoxy, benzyloxy, phenoxy, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C4)alkylenedioxy, cyano, benzoylamino, trifluoromethylcarbonylamino, (C1-C4)alkanoylamino, (C1-C4)alkanoyl, N-mono- or N,N-di-(C1-C4)alkylamino, (C1-C4)alkylsulfonylamino, trifluoromethylsulfonylamino, (C1-C4)alkylthio, (C1-C4)alkylsulfinyl or (C1-C4)alkylsulfonyl, pyrrol-1-yl, peperidin-1-yl or pyrrolidin-1-yl, said phenyl, benzyloxy, phenoxy and benzoylamino optionally mono-substituted with halo, nitro, trifluoromethyl, hydroxy or (C1-C4)alkyl and said (C1-C4)alkylenedioxy is linked at both ends to adjacent carbons on the benzene moiety; R3 for each occurrence is independently hydroxy, amino, N-mono- or N,N-di-(C1C4)alkylamino, sulfo, or (C1-C4)alkoxy (provided that such groups are not attached to a ring carbon which is adjacent to an oxy, thio or -N-), or R3 for each occurrence is independently carboxy, hydroxy(C1-C4)alkyl, (C1-C4)alkoxy(C1-C4)alkyl, amino(C1-C4)alkyl, mono-N or di-N,N-(C1-C4)alkylamino(C1-C4)alkyl, morpholino (C1-C4)alkyl, 4-(C1-C4)alkyl-piperazin-1-yl(C1-C4)alkyl, carboxy(C1-C4)alkyl, (C1-C4)alkoxycarbonyl, sulfo(C1-C4)alkyl or (C1-C4)alkyl; where m is 0-3; n is 0-4; p is 0, 1 or 2; and q is 0, 1 or 2; with the proviso that 4-(3,4-dihydro-2H-quinolin-1-yl)-quinazoline is not included.