TRICYCLIC COMPOUNDS HAVING ACTIVITY AS Ras-FPT INHIBITORS

摘要

Compounds of formula (I), wherein: X<1> is hydrogen, halogen, CF3, nitro, NH2 or lower alkyl; each X<2> is independently selected from the group consisting of hydrogen, halogen, lower alkoxy and lower alkyl; n is 1 or 2; Y is selected from the group consisting of S(O)p, O, and NR<5>, wherein p is 0, 1 or 2, and R<5> is hydrogen, alkyl, aryl, cycloalkyl, loweralkoxycarbonyl, aminocarbonyl or acyl; R<1> and R<2>, which may be the same or different, are selected from the group consisting of hydrogen and lower alkyl groups, or taken together can form an oxygen atom when Y is NR<5>; A..... is C=, CH- or N-; R is -CZ-Y<1>-Y<2>-R<3>, wherein: Z is O, =CH-CN, or =N-CN; one of Y<1> and Y<2> is a bond, -CO-, O, S, or -NR<4>-, and the other is (CH2)m, where m is 0 or an integer of 1 to 4, and R<4> is H or alkyl, with the previso that when Z is O and m is 0 then Y<1> or Y<2> is selected form -CO-, O, S, or -NR<4>; R<3> is aryl, heteroaryl or heterocycloalkyl, with proviso that R<3> can also be lower alkyl when Z is =N-CN; and their pharmaceutically acceptable acid additions salts; have activity as Ras-FPT inhibitors. They can be used, e.g., in pharmaceutical compositions, for inhibiting the abnormal growth of cells and for inhibiting proliferative diseases. Processes for their preparation, and useful intermediates, are also disclosed.