Bicyclic compounds capable of inhibiting tyrosine kinases of the epidermal growth factor receptor family

A compound of Formula Ia or Ib

• wherein X is NH or NR.sup.7, wherein R.sup.7 is selected from the group consisting of lower alkyl (1-4 carbon atoms), OH, NH.sub.2, lower alkoxy (1-4 carbon atoms) and lower monoalkylamino (1-4 carbon atoms);
• n is 0, 1 or 2;
• R.sup.1 is H or lower alkyl (1-4 carbon atoms);
• if n is 2, R.sup.1 is independently H or lower alkyl (1-4 carbon atoms) on either linking carbon atom;
• R.sup.2 is selected from the group consisting of lower alkyl (1-4 carbon atoms), cycloalkyl (3-8 carbon atoms), lower alkoxy (1-4 carbon atoms), cycloalkoxy (3-8 carbon atoms), nitro, halo (fluoro, chloro, bromo, iodo), lower perfluoroalkyl (1-4 carbon atoms), hydroxy, lower acyloxy (1-4 carbon atoms;
• --O--C(O)--R), amino, lower mono or dialkylamino (1-4 carbon atoms), lower mono or dicycloalkylamino (3-8 carbon atoms), hydroxymethyl, lower acyl (1-4 carbon atoms;
• --C(O)R), cyano, lower thioalkyl (1-4 carbon atoms), lower sulfinylalkyl (1-4 carbon atoms), lower sulfonylalkyl (1-4 carbon atoms), thiocycioalkyl (3-8 carbon atoms), sulfinyicycloalkyl (3-8 carbon atoms), sulfonylcycloalkyl (3-8 carbon atoms), sulfonamido, lower mono or dialkylsulfonamido (1-4 carbon atoms), mono or dicycloalkylsulfonamido (3-8 carbon atoms), mercapto, carboxy, carboxamido (--C(O)--NH.sub.2), lower mono or dialkylcarboxamido (1-4 carbon atoms), mono or dicycloalkoxycarboxamido (3-8 carbon atoms), lower alkoxycarbonyl (1-4 carbon atoms), cycloalkoxycarbonyl (3-8 carbon atoms), lower alkenyl (2-4 carbon atoms), cycloalkenyl (4-8 carbon atoms), lower alkynyl (2-4 carbon atoms), and two R.sup.2 taken together on contiguous carbon atoms form a carbocyclic ring of 5-7 members or a monounsaturated ring selected from the group consisting of 1,3-dioxolanyl, 1,4-dioxanyl, 1,4-dioxepinyl, pyranyl, furanal, pyrrolidyl, piperidinyl, thiolanyl, oxazolanyl, thiazolanyl, diazolanyl, piperazinyl, morpholino and thiomorpholino;
• m=0-3;
• and
• R.sup.3, R.sup.4, and R.sup.5 are independently selected from the group consisting of H, lower alkyl (1-4 carbon atoms), cycloalkyl (3-8 carbon atoms), lower alkoxy (1-4 carbon atoms), cycloalkoxy (3-8 carbon atoms), hydroxy, lower acyloxy (1-4 carbon atoms), amino, lower mono or dialkylamino (1-4 carbon atoms), lower mono or dicycloalkylamino (3-8 carbon atoms), carbonato (--OC(O)OR) where the R is lower alkyl of 1 to 4 carbon atoms or cycloalkyl of 3-8 carbon atoms;
• ureido or thioureido or N- or O-linked urethane any one of which is optionally substituted by mono or di-lower alkyl (1-4 carbon atoms) or cycloalkyl (3-8 carbon atoms);
• lower thioalkyl (1-4 carbon atoms), thiocycloalkyl (3-8 carbon atoms), mercapto, lower alkenyl (2-4 carbon atoms), hydrazino, N'-lower alkylhydrazino (1-4 carbon atoms), lower acylamino (1-4 carbon atoms), hydroxylamino, and lower O-alkylhydroxylamino (1-4 carbon atoms);
• or optionally R.sup.3 and R.sup.5 taken together on contiguous carbon atoms form a carbocyclic ring of 5-7 members or a monounsaturated ring selected from the group consisting of 1,3-dioxolanyl, 1,4-dioxanyl, 1,4-dioxepinyl, pyranyl, furanyl, pyrrolidyl, piperidinyl, thiolanyl, oxazolanyl, thiazolanyl, diazolanyl, piperazinyl, morpholino and thiomorpholino;
• any lower alkyl group substituent on any of the substituents in R.sup.3 -R.sup.5 which moiety is optionally substituted with one or more groups selected from the group consisting of hydroxy, amino, lower monoalkylamino, lower dialkylamino, N-pyrrolidyl, N-piperidinyl, N-pyridinium, N-morpholino, N-thiomorpholino and N-piperazino;
• with the proviso that R.sup.3 -R.sup.5 on a neighboring C atom to one of the N atoms, cannot be either OH or SH;
• with the further proviso that at least one of the group R.sup.3 and R.sup.5 or R.sup.4 and R.sup.5 substituents must be other than hydrogen, lower alkyl (1-4 carbon atoms), or lower alkoxy (1-4 carbon atoms);
• optionally if any of the substituents R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 have chiral centers, then all stereoisomers thereof both separately and as racemic and/or diastereoisomeric mixtures are included;
• or a pharmaceutical salt or hydrate thereof.