Arylethenylene compounds which are useful as tyrosine kinase inhibitors
AssigneeFarmitalia Carlo Erba S r l
InventorsFranco Buzzetti, Antonio Longo, Maristella Colombo
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Abstract
The present invention provides compounds of the formula ##STR1## wherein Y is a naphthyl, tetrahydronaphthyl, pyridyl, quinolyl, isoquinolyl or indolyl ring system, R is a moiety which is an acrylic acid, a CN-substituted acrylic acid, acrylamide, acrylonitrile or thioacrylamide, or a group of formulae (e) to (j): ##STR2## wherein R.sub.3 is OH or NH.sub.2, R.sub.1 is H, alkyl or alkanoyl, R.sub.2 is H, halogen, CN or alkyl; and n is 0, 1, 2 or 3; and the pharmaceutically acceptable salts thereof are useful as tyrosine kinase inhibitors.
Claims8
A compound of the formula (I) ##STR11## wherein Y is a bicyclic ring system selected from the group consisting of (A) and (B):
- ##STR12## R is a group of formula (a), (b) or (c) ##STR13## in which R.sub.3 is --OH or --NH.sub.2 ;
- R.sub.1 is hydrogen, C.sub.1 -C.sub.6 alkyl or C.sub.2 -C.sub.6 alkanoyl;
- R.sub.2 is hydrogen, halogen, cyano or C.sub.1 -C.sub.6 alkyl;
- n is zero or an integer of 1 to 3;
- n is zero or an integer of 1 to 3 when Y is a ring system (A) or it is zero, 1 or 2 when Y is a ring system (B);
- or a pharmaceutically acceptable salt thereof;
- and wherein each of the substituents R, OR.sub.1 and R.sub.2 may be independently on either aryl moiety of the bicyclic ring system (A), whereas only the benzene moiety may be substituted in the bicyclic ring system (B);
- and with the proviso that when Y is a ring system (A), R is other than a group (a) or (b).
A compound selected from the group consisting of the following which, when appropriate, may be either Z- or E-diastereoisomers or Z,E-mixtures of said diastereoisomers:
- 2-cyano-3-(2-hydroxynaphth-1-yl)thioacrylamide;
- 2-cyano-3-(3-hydroxynaphth-1-yl)thioacrylamide;
- 2-cyano-3-(4-hydroxynaphth-1-yl)thioacrylamide;
- 2-cyano-3-(1-hydroxynaphth-2-yl)thioacrylamide;
- 2-cyano-3-(3-hydroxynaphth-2-yl)thioacrylamide;
- 2-cyano-3-(4-hydroxynaphth-2-yl)thioacrylamide;
- 2-cyano-3-(2-hydroxy-5,6,7,8-tetrahydronaphth-1-yl)acrylamide;
- 2-cyano-3-(3-hydroxy-5,6,7,8-tetrahydronaphth-1-yl)acrylamide;
- 2-cyano-3-(4-hydroxy-5,6,7,8-tetrahydronaphth-1-yl)acrylamide;
- 2-cyano-3-(1-hydroxy-5,6,7,8-tetrahydronaphth-2-yl)acrylamide;
- 2-cyano-3-(3-hydroxy-5,6,7,8-tetrahydronaphth-2-yl)acrylamide;
- 2-cyano-3-(4-hydroxy-5,6,7,8-tetrahydronaphth-2-yl)acrylamide;
- 2-cyano-3-(2-hydroxy-5,6,7,8-tetrahydronaphth-1-yl)acrylic acid;
- 2-cyano-3-(3-hydroxy-5,6,7,8-tetrahydronaphth-1-yl)acrylic acid;
- 2-cyano-3-(4-hydroxy-5,6,7,8-tetrahydronaphth-1-yl)acrylic acid;
- 2-cyano-3-(1-hydroxy-5,6,7,8-tetrahydronaphth-2-yl)acrylic acid;
- 2-cyano-3-(3-hydroxy-5,6,7,8-tetrahydronaphth-2yl)acrylic acid;
- 2-cyano-3-(4-hydroxy-5,6,7,8,-tetrahydronaphth-2-yl)acrylic acid;
- 2-cyano-3-(2-hydroxy-5,6,7,8-tetrahydronaphth-1-yl)thioacrylamide;
- 2-cyano-3-(3-hydroxy-5,6,7,8-tetrahydronaphth-1-yl)thioacrylamide;
- 2-cyano-3-(4-hydroxy-5,6,7,8-tetrahydronaphth-1-yl)thioacrylamide;
- 2-cyano-3-(1-hydroxy-5,6,7,8-tetrahydronaphth-2-yl)thioacrylamide;
- 2-cyano-3-(3-hydroxy-5,6,7,8-tetrahydronaphth-2-yl)thioacrylamide;
- 2-cyano-3-(4-hydroxy-5,6,7,8-tetrahydronaphth-2-yl)thioacrylamide;
- or, if the case, a pharmaceutically acceptable salt thereof.
A method of treating patient in need of a tyrosine kinase inhibitor, which method comprises the step of administering to said patient, in an amount effective to inhibit tyrosine kinase, a compound of the formula (I') ##STR14## wherein Y is a bicyclic ring system chosen from the group consisting of (A) and (B), ##STR15## R is a group of formula (a) , (b) or (c) ##STR16## in which R.sub.3 is --OH or --NH.sub.2 ;
- R.sub.1 is hydrogen, C.sub.1 -C.sub.6 alkyl or C.sub.2 -C.sub.6 alkanoyl;
- R.sub.2 is hydrogen, halogen, cyano or C.sub.1 -C.sub.6 alkyl;
- n is zero or an integer of 1 to 3;
- n is zero or an integer of 1 to 3 when Y is a ring system (A) or it is zero, 1 or 2 when Y is a ring system (B);
- or a pharmaceutically acceptable salt thereof;
- and wherein each of the substituents R, OR.sub.1 and R.sub.2 may be independently on either aryl moiety of the bicyclic ring system (A) whereas only the benzene moiety may be substituted in the bicyclic ring system (B).
Dependencies are inferred from the claim text.