Patent CA-1337937-C (CA)
Title: Tricyclic 3-oxo-propanenitrile derivatives and process for their preparation
Inventor: DORIA GIANFEDERICO
IPC: A61P35/00
Filed: 1989-06-08
Granted: 1996-01-16
Abstract: The invention relates to compounds having the general formula (I) (I)   wherein X represents an oxygen atom or a -S(O)n- group, wherein n is zero, 1 or 2;        R represents C1-C6 alkyl, pyridyl or phenyl, the phenyl being unsubstituted or substituted by one or two substituents chosen independently from halogen, trifluoromethyl, C1-C6 alkyl, C1-C6 alkoxy, nitro, amino, formylamino and C2-C8 alkanoylamino;          R1 is a°) hydrogen, di(C1-C6 alkyl)-amino or a       group wherein R' and R", the same or different, is C1-C6 alkyl or R' and R", taken together with the nitrogen atom to which they are linked, form a heterocylic ring which is selected from N-pyrrolidinyl, N-piperazinyl, hexahydroazepin-1-yl, thiomorpholino, morpholino and piperidino and which is unsubstituted or substituted by C1-C6 alkyl; b°) CH2OH, CHO, COOH or C2-C7 alkoxycarbonyl; c°) a       group wherein Rd is hydrogen or C1-C6 alkyl and Rc is hydrogen, phenyl or the side-chain of an .alpha.-aminoacid;   d°) a      group, wherein Rc is as defined above;     e°) a           , a -CH2OCO(CH2)nCOORd or a -NHCO(CH2)nCOORd group wherein n and Rd are as defined above; f°) a -CH=N-OR'1 group wherein R'1 is hydrogen or a -CH2COOH group; g°) a -CH=N-NH-R'2 group wherein R'2 is hydrogen, -CH2CH2OH, C2 or C3 alkoxycarbonyl or a -(CH2)p-R'3 group wherein p is 1 or 2 and R'3 is COOH or C2-C7 alkoxycarbonyl;     h°) a           group wherein R' and R'' are as definded above; or k°) a              group wherein R' and R'' are as defined above; 1°) a C2-C7 alkoxycarbonyl group substituted by a   group, wherein R' and R'' are as defined above; each of R2 and R3 is independently: a) hydrogen, halogen or C1-C6 alkyl; b) hydroxy, C1-C6 alkoxy or C3 or C4 alkenyloxy; or c) nitro, amino, formylamino or C2-C8 alkanoylamino;          R4 represents hydrogen or C1-C6 alkyl; and Q represents hydrogen, carboxy, C2-C7 alkoxycarbonyl or a   group wherein Ra represents hydrogen or C1-C20 alkyl and Rb represents C1-C20 alkyl, a     group wherein Rc and Rd are as defined above or a -(A)m-R5 group wherein m is zero or 1, A is a C1-C6 alkylene chain and R5 is a') C5-C8 cycloalkyl; b') pyridyl, unsubstituted or substituted by one or two substituents chosen independently from halogen, C1-C6 alkyl and C1-C6 alkoxy; c') phenyl, unsubstituted or substituted by one or two substituents independently chosen from halogen, CF3, C1-C6 alkyl, C1-C6 alkoxy, amino, nitro, formylamino, C2-C8 alkanoylamino, di(C1-C6 alkyl)-amino, hydroxy, formyloxy and C2-C8 alkanoyloxy; d') phenyl substituted by a -CH2OH, COOH, C2-C7 alkoxycarbonyl or a            group wherein R' and R" are as defined above and optionally by another substituent chosen from halogen, C1-C6 alkyl, C1-C6 alkoxy, amino, nitro, formylamino, C2-C8 alkanoylamino, hydroxy, formyloxy and C2-C8 alkanoyloxy, or e') 2-thienyl, 2-furyl or 1-(C1-C6 alkyl)-pyrrol-2-yl; or f') a heterocyclic ring which is selected from 2-pyrimidyl, 2-thiazolyl and 3-isoxazolyl and which is unsubstituted or substituted by C1-C6 alkyl; and the pharmaceutically acceptable salts thereof;     and wherein, when R1 is hydrogen, then Q is only a       group in which Ra is as defined above and either Rb is a   group wherein Rc and Rd are as defined above or Rb is a'') a - (CH2)z -R'5 group wherein z is zero, 1 or 2 and R'5 is as R5 defined above under d'), e') or f') or b'') a    or -A'-R5 group, wherein A' is a C3-C6 alkylene chain and R5 is as defined above, which possess immunomodulating activity and are useful e.g. in the treatment of neoplastic diseases and acute and chronic infections of both bacterial and viral origin in mammals.