| 摘要 |
A 3-cyanoquinoline derivative or a pharmaceutically acceptable salt thereof has the formula 1 wherein: X is an optionally substituted bicyclic aryl or bicyclic heteroaryl ring system of 8 to 12 atoms where the bicyclic heteroaryl ring contains 1 to 4 heteroatoms selected from N, O, and S with the proviso that the bicyclic heteroaryl ring does not contain O-O, S-S, or S-O bonds or X is -A-T-L- ; A is optionally substituted pyridinyl, pyrimidinyl, or phenyl ring; T is bonded to a carbon of A and is -NH(CH2)m-, -O(CH2)m-, - S(CH2)m-, -NR(CH2)m-, -(CH2)m-, -(CH2)m-NH-, -(CH2)m-O-, - (CH2)m-S- or -(CH2)m-NR-; L is an optionally substituted phenyl ring provided that L can be an unsubstituted phenyl ring only when m>0 and T is not -CH2NH- or -CH2O- or L is an optionally substituted 5- or 6-membered heteroaryl ring where the heteroaryl ring contains 1 to 3 heteroatoms selected from N, O, and S, with the proviso that the heteroaryl ring does not contain O-O, S-S, or S-O bonds; Z is -NH-, -O-, -S-, or -NR-; R is alkyl or carboalkyl; G1, G2, R1 and R4 are independently, hydrogen, halogen, alkyl, alkenyl, alkynyl, alkenyloxy, alkynyloxy, hydroxymethyl, halomethyl, alkanoyloxy, alkenoyloxy, alkynoyloxy, alkanoyloxymethyl, alkenoyloxymethyl, alkynoyloxymethyl, alkoxymethyl, alkoxy, alkylthio, alkylsulphinyl, alkylsulphonyl, alkylsulphonamido, alkenylsulphonamido, alkynylsulphonamido, hydroxy, trifluoromethyl, trifluoromethoxy, cyano, nitro, carboxy, carboalkoxy carboalkyl, phenoxy, phenyl, thiophenoxy, benzyl, amino, hydroxyamino, alkoxyamino, alkylamino, dialkylamino, N-alkylcarbamoyl, N,N-dialkylcarbamoyl, N- alkyl-N-alkenylamino, N,N-dialkenylamino, phenylamino, benzylamino, a group of formula (2), R8R9-CH-M-(C(R6)2)k-Y- , R7-(C(R6)2)g-Y-, R7-(C(R6)2)p-M-(C(R6)2)k-Y- or Het- (C(R6)2)q-W-(C(R6)2)k-Y- or R1 and R4 are as defined above and G1 or G2 or both are R2-NH- or if any of the substituents R1, G1, G2, or R4 are located on contiguous carbon atoms then they may be taken together as the divalent radical -O-(C(R6)2)-O-; Y is a divalent radical selected from the group consisting of -C(H2)a-, -O- or -NR6-; R2, R3, R6, R7, R8, R9, M, W and Het are as defined in the specification; a and n are independently 0 or 1; g and s are independently 1-6; k, u, v and q are independently is 0-4; m is 0-3; p is 2-4; r is 1-4 wherein the sum of u+v is 2-4 limited by the provisos listed in the specification. The compounds are useful for inhibiting the growth of or eradicating neoplasms or polycystic kidney disease.
|
