Mitomycin analogs

Details Mitomycin analogs Mitomycin analogs

C - Chemistry, Metallurgy

07

D

167/208, 260/272

C07D 487/14 (2006.01) A61K 31/40 (2006.01) A61K 31/435 (2006.01) C07D 519/00 (2006.01)

Patent

CA 1244412

ABSTRACT OF THE DISCLOSURE Compounds of the formula, II, Image wherein: Y is hydrogen or lower alkyl ; and X is a lower alkoxy substituted quinolinylamino radical, a cyano substituted pyrazolylamino radical or a mono- or di- lower alkyl substituted thiazolamino radical, or a nitrogen-containing heterocyclic radical selected from the group consisting of 1-pyrrolinyl, 1-indolinyl, N-thiazoladinyl and N-thiomorpholinyl radicals, or a cyano, phenyl, carboxamido or lower alkoxycarbonyl substituted 1-aziridinyl radical, or a lower alkyl, formyl or acetylphenyl substituted 1-piperazinyl radical, or an hydroxy or piperidyl substituted 1-piperidyl radical, or a lower alkoxy, amino or halo substituted pyridyl- amino radical, or a carboxamido, mercapto or methylenedioxy substituted anilino radical, or a radical of the formula, Image wherein R is hydrogen or lower alkyl and R' is a nitrogen-containing heterocyclic radical selected from the group consisting of quinuclidinyl, pyrazolyl, 1-triazolyl, isoquinolinyl, indazolyl, benzoxazolyl, thiadiazolyl and benzothiadiazolyl, and lower alkyl and halo substituted derivatives thereof, or a butyrolactonyl radical, or an adamantyl radical, or a substituted lower alkyl radical selected from the group consisting of mercapto lower alkyl, mono-, di- and tri-lower alkoxy lower alkyl, lower alkyl thio lower alkyl and lower alkoxycarbonyl substituted deriva- tives thereof, cyano lower alkyl, mono-, di- and tri-lower alkoxy phenyl lower alkyl, phenyl cyclo lower alkyl, 1-pyrrolidinyl lower alkyl, N-lower alkyl pyrrolidinyl lower alkyl, and N-morpholinyl lower alkyl. Novel methods for treatment of neoplastic disease states in animals, which methods comprise administering a therapeutically effective amount of a compound of the formula, IIa, Image IIa wherein: Y is hydrogen or lower alkyl; and Z is a lower alkoxy substituted quinolinylamino radical, a cyano substituted pyrazolylamino radical or a mono- or di- lower alkyl substituted thiazolamino radical, or a nitrogen-containing heterocyclic radical selected from the group consisting of 1-pyrrolinyl, 1-indolinyl, N-thiazoladinyl, N-morpholinyl, 1-piperazinyl and N-thiomor- pholinyl radicals, or a cyano, phenyl, carboxamido or lower alkoxycarbonyl substituted 1-aziridinyl radical or a lower alkyl, formyl or acetylphenyl substituted 1-piperazinyl radical, or an hydroxy or piperidyl substituted 1-piperidyl radical, or a lower alkoxy, amino or halo substituted pyridyl- amino radical, or a carboxamido, mercapto or methylenedioxy substituted anilino radical, or a radical of the formula, Image wherein R is hydrogen or lower alkyl and R" is a nitrogen-containing heterocyclic radical selected from the group consisting of quinuclidinyl, pyrazolyl, 1-triazolyl, isoquinolinyl, indazolyl, benzoxazolyl, thiadiazolyl and benzothiadiazolyl and lower alkyl, and halo substituted derivatives thereof, or a butyrolactonyl radical, or an adamantyl radical, or a mono- lower alkoxy substituted phenyl radical, or a substituted lower alkyl radical selected from the group consisting of mercapto lower alkyl, carboxy lower alkyl, mono-, di- and tri-lower alkoxy lower alkyl, lower alkyl thio lower alkyl and lower alkoxy- carbonyl substituted derivatives thereof, cyano lower alkyl, mono-, di- and tri-lower alkoxy phenyl lower alkyl, phenyl cyclo lower alkyl, 1-pyrrolidinyl lower alkyl, N-lower alkyl pyrrolidinyl lower alkyl, N-mor- pholinyl lower alkyl, and lower dialkylamino lower alkyl.

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