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US 5,849,733 AGranted
2-thio or 2-oxo flavopiridol analogs
AssigneeBristol-Myers Squibb Company
InventorKyoung Soon Kim
Life of this patent
Estimating the term…
Abstract
Compounds of the formula I ##STR1## and pharmaceutically acceptable salts thereof, wherein X, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, m and n are as defined in the disclosure. The compounds of formula I are protein kinase inhibitors and are useful in the treatment of proliferative diseases.
Claims19
A compound of the formula ##STR34## or pharmaceutically acceptable salts thereof wherein:
- X is oxygen or sulfur;
- R.sup.1 is hydrogen, alkyl, aryl, arylalkyl, cycloalkyl, --(CH.sub.2).sub.q --NR.sup.7 R.sup.8, alkylcarbonyl, arylcarbonyl, arylalkylcarbonyl, alkyloxycarbonyl, arylalkyloxycarbonyl or aryloxycarbonyl;
- R.sup.2 is hydrogen, alkyl, arylalkyl, aryl, cycloalkyl, hydroxy, alkoxy, arylalkoxy, aryloxy, alkylcarbonyloxy, arylalkylcarbonyloxy, arylcarbonyloxy, carboxy, alkyloxycarbonyl, arylalkoxycarbonyl, aryloxycarbonyl, amino, --NR.sup.7 R.sup.8, thiol, alkylthio, arylalkylthio or arylthio;
- R.sup.3 is alkyl, cycloalkyl, aryl or substituted aryl, arylalkyl, -5 or 6 membered heterocycle or -5 or 6 membered heterocycloalkyl;
- R.sup.4 is hydrogen, alkyl, aryl, arylalkyl, nitro, amino, --(CH.sub.2).sub.p --NR.sup.7 R.sup.8, halogen, hydroxy, alkoxy, carboxy, -5 or 6 membered heterocycle or alkyloxycarbonyl;
- R.sup.5 is hydrogen, alkyl, arylalkyl, aryl, cycloalkyl, hydroxy, alkoxy, arylalkoxy, aryloxy, alkylcarbonyloxy, arylalkylcarbonyloxy, arylcarbonyloxy, carboxy, alkyloxycarbonyl, arylalkoxycarbonyl, cyano, nitro, --NR.sup.7 R.sup.8, halogen, alkylhalo, --CHO, alkylS(O).sub.m -- or --OC(O)NR.sup.7 R.sup.8 ;
- R.sup.6 is hydrogen, alkyl, arylalkyl, aryl, cycloalkyl, hydroxy, alkoxy, arylalkoxy, aryloxy, alkylcarbonyloxy, arylalkylcarbonyloxy, arylcarbonyloxy, carboxy, alkyloxycarbonyl, arylalkoxycarbonyl, aryloxycarbonyl, amino, --NR.sup.7 R.sup.8, thiol, alkylthio, arylalkylthio or arylthio;
- R.sup.7 and R.sup.8 are independently hydrogen, alkyl, aryl, arylalkyl, cycloalkyl, heterocycle or alkylcarbonyl;
- or R.sup.7 and R.sup.8 together with the nitrogen atom to which they are bonded can form a -5 or 6 membered heterocycle;
- m is an integer of 0 to 2;
- n is an integer of 0 to 3;
- p is an integer of 1 to 3;
- and
- q is an integer of 2 to 5.
11 more elements
A compound selected from the group consisting of
- cis-(.+-.)-2-(ethylthio)-5,7-dihydroxy-8-(3-hydroxy-1-methyl-4-piperidinyl) -4H-1-benzopyran-4-one;
- cis-(.+-.)-5,7-dihydroxy-8-(3-hydroxy-1-methyl-4-piperidinyl)-2-(phenylthio )-4H-1-benzopyran-4-one;
- cis-(.+-.)-2-(butylthio)-5,7-dihydroxy-8-(3-hydroxy-1-methyl-4-piperidinyl) -4H-1-benzopyran-4-one;
- cis-(.+-.)-2-(ethylthio)-5-hydroxy-8-(3-hydroxy-1-methyl-4-piperidinyl)-7-m ethoxy-4H-1-benzopyran-4-one;
- cis-(.+-.)-3-5,7-dihydroxy-8-(3-hydroxy-1-methyl-4-piperidinyl)-4-oxo-4H- 1-benzopyran-2-yl!thio!propanoic acid, methyl ester;
- cis-(.+-.)-2-(2-chlorophenyl)thio!-5,7-dihydroxy-8-(3-hydroxy-1-methyl-4-p iperidinyl)-4H-1-benzopyran-4-one;
- cis-(.+-.)-5,7-dihydroxy-8-(3-hydroxy-1-methyl-4-piperidinyl)-2-phenoxy-4H- 1-benzopyran-4-one;
- cis-(-)-2-(2-chlorophenyl)thio!-5,7-dihydroxy-8-(3-hydroxy-1-methyl-4-pipe ridinyl)-4H-1-benzopyran-4-one;
- cis-(+)-2-(2-chlorophenyl)thio!-5,7-dihydroxy-8-(3-hydroxy-1-methyl-4-pipe ridinyl)-4H-1-benzopyran-4-one;
- cis-(.+-.)-2-(2-chlorophenoxy)-5,7-dihydroxy-8-(3-hydroxy-1-methyl-4-piperi dinyl)-4H-1-benzopyran-4-one;
- cis-(-)-2-(2-chlorophenoxy)-5,7-dihydroxy-8-(3-hydroxy-1-methyl-4-piperidin yl)-4H-1-benzopyran-4-one;
- cis-(.+-.)-5,7-dihydroxy-8-(3-hydroxy-1-methyl-4-piperidinyl)-2-(phenylmet hyl)thio!-4H-1-benzopyran-4-one, trifluoroacetate;
- cis-(.+-.)-5,7-dihydroxy-8-(3-hydroxy-1-methyl-4-piperidinyl)-2-(4-methoxy phenyl)-thio!-4H-1-benzopyran-4-one, trifluoroacetate;
- cis-(.+-.)-5,7-dihydroxy-8-(3-hydroxy-1-methyl-4-piperidinyl)-2-(4-methox yphenyl)methyl!-thio!-4H-1-benzopyran-4-one, trifluoroacetate;
- cis-(.+-.)-N-2-5,7-dihydroxy-8-(3-hydroxy-1-methyl-4-piperidinyl)-4-oxo- 4H-1-benzopyran-2-yl!thio!ethyl!acetamide, trifluoroacetate;
- cis-(.+-.)-5,7-dihydroxy-2-(2-hydroxyethyl)thio!-8-(3-hydroxy-1-methyl-4-p iperidinyl)-4H-1-benzopyran-4-one, trifluoroacetate;
- or
- a pharmaceutically acceptable salt thereof.
15 more elements
Dependencies are inferred from the claim text.