N-oxides of amino containing pyrido 2,3-D! pyrimidines
First Claim
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1. A compound of the formula ##STR42## wherein A and B are linkers which independently are C1 -C6 - alkylene, C1 -C6 - alkylenoxy, C1 -C6 - alkylenethio, or phenylene;
- X is NH, N--C1 -C6 alkanoyl, O, or S;
R2 is hydrogen, (CH2)n Ph, where Ph is phenyl or phenyl substituted by one, two or three groups selected from halo, C1 -C6 alkyl, C1 -C6 alkoxy, SH, C1 -C6 alkylthio, hydroxy, C1 -C6 alkanoyl, --CN, --NO2, C1 -C6 alkanoyloxy, --CF3 or NR5 R6, and n is 0, 1, 2, or 3,C3 -C6 -cycloalkyl, C1 -C6 alkanoyl, C2 -C6 alkenyl, and C2 -C6 alkynyl, where the alkyl, alkenyl, and alkynyl groups may be substituted by NR5 R6, phenyl, C1 -C6 alkylthio, C1 -C6 -alkyloxy, hydroxy, carboxy, halogen, C3 -C6 - cycloalkyl, or phenyl substituted by one, two or three groups selected from halo, C1 -C6 alkyl, C1 -C6 alkoxy, SH, C1 -C6 alkylthio, hydroxy, C1 -C6 alkanoyl, --CN, --NO2, C1 -C6 alkanoyloxy, --CF3 or NR5 R6, and where R5 and 6 are independently hydrogen, C1 -C6 alkyl, C2 -C6 alkenyl, C2 -C6 alkynyl, (CH2)n Ph where Ph is phenyl or phenyl substituted by one, two or three groups selected from halo, C1 -C6 alkyl, C1 -C6 alkoxy, SH, C1 -C6 alkylthio, hydroxy, C1 -C6 alkanoyl, --CN, --NO2, C1 -C6 alkanoyloxy, --CF3 or NR5 R6, and n is 0, 1, 2, or 3, C3 -C6 - cycloalkyl, or R5 and R6 taken together nitrogen to which they are attached can complete a ring selected from piperazine;
Ar is phenyl, phenyl substituted by one, two or three groups selected from halo, C1 C6 alkyl, C1 C6 alkoxy, SH, C1 C6 alkylthio, hydroxy, C1 C6 alkanoyl, --CN, --NO2, C1 -C6 alkanoyloxy, --CF3 or NR56, or the pharmaceutically acceptable salts thereof.
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Abstract
N-oxides of amino containing 6-aryl pyrido 2,3-d!-pyrimidine 7-imines, 7-ones, and 7-thiones have the formula ##STR1## where A and B are linkers, Ar is aryl, R2 is aklyl, X is O, S, or NH, or NAcyl, and R5 and R6 are alkyl. The compounds are inhibitors of protein tyrosine kinases and cyclin-dependent kinases, and are thus useful in treating cellular proliferation mediated thereby. The compounds are especially useful in treating cancer, atherosclerosis, restenosis, and psoriasis.
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Citations
15 Claims
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1. A compound of the formula ##STR42## wherein A and B are linkers which independently are C1 -C6 - alkylene, C1 -C6 - alkylenoxy, C1 -C6 - alkylenethio, or phenylene;
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X is NH, N--C1 -C6 alkanoyl, O, or S; R2 is hydrogen, (CH2)n Ph, where Ph is phenyl or phenyl substituted by one, two or three groups selected from halo, C1 -C6 alkyl, C1 -C6 alkoxy, SH, C1 -C6 alkylthio, hydroxy, C1 -C6 alkanoyl, --CN, --NO2, C1 -C6 alkanoyloxy, --CF3 or NR5 R6, and n is 0, 1, 2, or 3,C3 -C6 -cycloalkyl, C1 -C6 alkanoyl, C2 -C6 alkenyl, and C2 -C6 alkynyl, where the alkyl, alkenyl, and alkynyl groups may be substituted by NR5 R6, phenyl, C1 -C6 alkylthio, C1 -C6 -alkyloxy, hydroxy, carboxy, halogen, C3 -C6 - cycloalkyl, or phenyl substituted by one, two or three groups selected from halo, C1 -C6 alkyl, C1 -C6 alkoxy, SH, C1 -C6 alkylthio, hydroxy, C1 -C6 alkanoyl, --CN, --NO2, C1 -C6 alkanoyloxy, --CF3 or NR5 R6, and where R5 and 6 are independently hydrogen, C1 -C6 alkyl, C2 -C6 alkenyl, C2 -C6 alkynyl, (CH2)n Ph where Ph is phenyl or phenyl substituted by one, two or three groups selected from halo, C1 -C6 alkyl, C1 -C6 alkoxy, SH, C1 -C6 alkylthio, hydroxy, C1 -C6 alkanoyl, --CN, --NO2, C1 -C6 alkanoyloxy, --CF3 or NR5 R6, and n is 0, 1, 2, or 3, C3 -C6 - cycloalkyl, or R5 and R6 taken together nitrogen to which they are attached can complete a ring selected from piperazine; Ar is phenyl, phenyl substituted by one, two or three groups selected from halo, C1 C6 alkyl, C1 C6 alkoxy, SH, C1 C6 alkylthio, hydroxy, C1 C6 alkanoyl, --CN, --NO2, C1 -C6 alkanoyloxy, --CF3 or NR56, or the pharmaceutically acceptable salts thereof. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 10, 11, 12, 13, 14, 15)
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9. The compound which is
6-(2,6-Dichlorophenyl)-2- 4-diethylaminoethoxy)-phenylamino!-8-methyl-2-(pyridin-3-ylamino)-8H-pyrido 2,3-d!pyrimidin-7-one-N.sup.ω - -oxide;
6-(3,5-dimethoxyphenyl)-2- 4- 2-diethylamino)ethoxy!-phenylamino!-8-ethyl-pyrido 2,3-d!pyrimidin-7(8H)-one, N.sup.ω
-oxide;6-(3,5-dimethylthiophenyl)-2- 4-(methylethylamino)phenyl!methyl!amino!-8-cyclopropyl-pyrido 2,3-d!pyrimidin-7(8H)-thione, N.sup.ω
-oxide;6-(3-methoxy-5-ethoxyphenyl)-2- 2-(methylethylamino)ethyl!amino!-8-n-butyl-pyrido 2,3-d!pyrimidin-7(8H)-one, N.sup.ω
-oxide;6-(4-ethyl-5-methoxyphenyl)-2- 4- 4-methyl-1-piperazinyl!butyl!amino!-8-methyl-pyrido 2,3-d!-pyrimidin-7(8H)-one, N.sup.ω
-oxide.
- -oxide;
Specification