Patent ID: 6759414
Filing Date: 2004-07-06
Classification: A61P,C07D

Abstract:
A compound of formula I or a pharmaceutically acceptable salt thereof wherein:A3, A4, A5 and A6, together with the two carbons to which they are attached, complete a substituted benzene in which A3 is CR3, A4 is CR4, A5 is CR5, and A6 is CR6; whereinR3 is hydrogen, methyl, methoxy, fluoro, chloro or carboxy; one of R4 and R5 is hydrogen, (1-4C)alkyl, halo, trifluoromethyl, trifluoromethoxy, RfOâ€”, RfO2CCH2Oâ€”, HO(CH2)aOâ€” (in which a is 2, 3 or 4), RfO2Câ€”, RfO2CCH2â€”, RgNHâ€”, RhSO2â€”, hydroxymethyl, formyl, cyano, acetyl, 1-hydroxyethyl, 1-(hydroxyamino)ethyl, 1-(methoxyimino)-ethyl, methylthio or RfO2C(CH2)2â€”; the other of R4 and R5 is hydrogen; and R6 is hydrogen, methyl, fluoro, chloro or methoxy; in which Rf is hydrogen, (1-4C)alkyl or benzyl; Rg is hydrogen or RhSO2â€”; and Rh is (1-4C)alkyl or dimethylamino; or each of R3, R4 and R6 is hydrogen; and R5 is vinyl, 2-cyanovinyl, 2-({(1-2C)alkoxy}carbonyl)vinyl or Ra in which Ra is phenyl (which is unsubstituted or bears one or more substituents independently selected from halo, methyl, methoxy and hydroxy) or heteroaryl (which heteroaryl is a 5-membered aromatic ring which has one to four heteroatoms selected from sulfur, oxygen and nitrogen or is a 6-membered aromatic ring which has one to three nitrogen atoms, wherein the heteroaryl is attached at carbon and may bear one or more methyl substituents on carbon or nitrogen); L1 is â€”COâ€”NHâ€” such that â€”L1â€”Q1 is â€”COâ€”NHâ€”Q1; Q1 is 3-pyridazinyl (which may bear a methyl, fluoro or chloro substituent at the 6-position); R2 is â€”L2â€”Q2 in which â€”L2â€” is â€”NHâ€”COâ€”, â€”NHâ€”COâ€”Xâ€”, â€”NHâ€”COâ€”Oâ€”Xâ€”, â€”NHâ€”COâ€”NHâ€”Xâ€”, â€”NHâ€”CH2â€”, â€”NHâ€”C(CH3)Hâ€”, â€”N(CH3)â€”CH2â€” or â€”Oâ€”CH2â€”; and Q2 is Q2A, Q2B, Q2C, Q2D, Q2E or Q2F wherein X is a single bond or methylene and the values of L2 and Q2 are together selected from â€”NHâ€”COâ€”Xâ€”Q2A, â€”NHâ€”COâ€”Oâ€”Xâ€”Q2A, â€”NHâ€”COâ€”NHâ€”Xâ€”Q2A, â€”NHâ€”CH2â€”Q2A, â€”NHâ€”C(CH3)Hâ€”Q2A, â€”N(CH3)â€”CH2â€”Q2A, â€”Oâ€”CH2â€”Q2A, â€”NHâ€”COâ€”Xâ€”Q2B, â€”NHâ€”COâ€”Q2C, â€”NHâ€”COâ€”Q2D, â€”NHâ€”COâ€”Q2E and â€”NHâ€”COâ€”Q2F in which: Q2A (showing the L2 to which it is attached) is in whicheach of m and n independently is 0 or 1, or m is 2 and n is 1, and R2A is hydrogen, t-butyl, methylsulfonyl, â€”CHRyRz, â€”CHRwRx, or 4-pyridinyl (which is unsubstituted or bears a substituent Rv at the 2- or 3-position) wherein Rv is methyl, hydroxymethyl, {(1-2C)alkoxy}carbonyl; cyano, carbamoyl, thiocarbamoyl, or N-hydroxyamidino; each of Rw and Rx independently is hydrogen or (1-3C)normal alkyl; or â€”CHRwRx is 2-indanyl or (showing the nitrogen to which it is attached) is â€ƒin which T is a single bond or methylene and U is methylene, ethylene, oxy, â€”S(O)qâ€” (wherein q is 0, 1 or 2) or imino (which may bear a methyl substituent), or T is ethan-1,1-diyl and U is a single bond or methylene; Ry is hydrogen or methyl; and Rz is isopropyl, t-butyl, (3-6C)cycloalkyl, phenyl (which is unsubstituted or bears one or more substituents independently selected from halo, methyl, methoxy and hydroxy), 4-quinolinyl or heteroaryl (which heteroaryl is a 5-membered aromatic ring which has one to four heteroatoms selected from sulfur, oxygen and nitrogen or is a 6-membered aromatic ring which has one to three nitrogen atoms, wherein the heteroaryl is attached at carbon and may bear one or more methyl substituents on carbon or nitrogen); or R2A is â€”Lbâ€”CH2â€”Rb in which â€”Lbâ€” is a direct bond, â€”CH2â€”, â€”C(CH3)Hâ€” or â€”CH2â€”CH2â€”; and Rb is carboxy, {(1-2C)alkoxy}carbonyl, cyano, carbamoyl or trifluoromethyl; or R2A is â€”COâ€”Rc in which Rc is hydrogen, (1-3C)alkyl, {(1-2C)alkoxy}carbonyl-(CH2)câ€” (in which c is 1 or 2), phenyl (which is unsubstituted or bears one or more substituents independently selected from halo, methyl, methoxy and hydroxy), heteroaryl (which heteroaryl is a 5-membered aromatic ring which has one to four heteroatoms selected from sulfur, oxygen and nitrogen or is a 6-membered aromatic ring which has one to three nitrogen atoms, wherein the heteroaryl is attached at carbon and may bear one or more methyl substituents on carbon or nitrogen) or â€”NRdRe in which each of Rd and Re is independently hydrogen, methyl or ethyl, or â€”NRdRe is pyrrolidino, piperidino, morpholino or thiomorpholino; Q2B is 1-piperazinyl which bears at the 4-position the group R2A (defined as above); Q2C is 3,4-didehydropiperidin-4-yl which bears at the 1-position the group R2A (defined as above); Q2D is cyclohexyl which bears at the 4-position the group â€”NRsRt in which each of Rs and Rt independently is hydrogen or methyl or Rs and Rt together are trimethylene or tetramethylene; Q2E is 1-piperidinyl which bears at the 4-position the group â€”NRsRt (defined as above); and Q2F (showing the L2 to which it is attached) is â€ƒin which Ro is hydrogen, halo, (1-6C)alkyl, hydroxy, (1-4C)alkoxy, benzyloxy or (1-4C)alkylthio; and Rp is acetylamino, 1-hydroxyethyl, 1-hydroxy-1-methylethyl, 1-methoxy-1-methylethyl, 4-piperidinyl, 4-pyridinyl, dimethylaminosulfonyl or â€”Jâ€”Rq in which J is a single bond, methylene, carbonyl, oxy, â€”S(O)qâ€” (wherein q is 0, 1 or 2), or â€”NRrâ€” (wherein Rr is hydrogen or methyl); and Rq is (1-6C)alkyl, phenyl, 3-pyridyl or 4-pyridyl; or â€”NRqRr is pyrrolidino.