Details for Patent: 7,417,148
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Title: | 4-anilino-3-quinolinecarbonitriles for the treatment of chronic myelogenous leukemia (CML) |
Abstract: | Compounds of the formula: ##STR00001## wherein: n is an integer from 1-3; X is N, CH, provided that when X is N, n is 2 or 3; R is alkyl of 1 to 3 carbon atoms; R.sup.1 is 2,4-diCl, 5-OMe; 2,4-diCl; 3,4,5-tri-OMe; 2-Cl, 5-OMe; 2-Me, 5-OMe; 2,4-di-Me; 2,4-diMe-5-OMe, 2,4-diCl, 5-OEt; R.sup.2 is alkyl of 1 to 2 carbon atoms, and pharmaceutically acceptable salts thereof. |
Inventor(s): | Boschelli; Frank (New City, NY), Arndt; Kim T. (Towaco, NJ), Golas; Jennifer M. (Hewitt, NJ) |
Assignee: | Wyeth (Madison, NJ) |
Filing Date: | Nov 03, 2004 |
Application Number: | 10/980,097 |
Claims: | 1. A method of treating or inhibiting the proliferation of CML comprising, providing to a patient in need thereof a therapeutically effective amount of a compound of the formula: ##STR00004## wherein: n is an integer from 1-3; X is N, CH, provided that when X is N, n is 2 or 3; R is alkyl of 1 to 3 carbon atoms; R.sup.1 is 2,4-diCl, 5-OMe; 2,4-diCl; 3,4,5-tri-OMe; 2-Cl, 5-OMe; 2-Me, 5-OMe; 2,4-di-Me; 2,4-diMe-5-OMe, 2,4-diCl, 5-OEt; R.sup.2 is alkyl of 1 to 2 carbon atoms, and pharmaceutically acceptable salts thereof. 2. The method of claim 1 wherein the compound is of the formula: ##STR00005## wherein: n is an integer from 2-3; X is N, CH, provided that when X is N, n is 2 or 3; R is alkyl of 1 to 3 carbon atoms; R.sup.1 is 2,4-diCl, 5-OMe; 2,4-diCl; 3,4,5-tri-OMe; 2-Cl, 5-OMe; 2-Me, 5-OMe; 2,4-di-Me; 2,4-diMe-5-OMe, 2,4-diCl, 5-OEt; R.sup.2 is alkyl of 1 to 2 carbon atoms, and pharmaceutically acceptable salts thereof. 3. The method of claim 1 wherein the compound is of the formula: ##STR00006## X is N, CH n is 3; R.sup.2 and R are methyl; and pharmaceutically acceptable salts thereof. 4. The method of claim 1 wherein R.sup.2 is methyl. 5. The method of claim 1 wherein X is N. 6. The method of claim 1 wherein X is CH. 7. The method of claim 1 wherein the compound is: 4-[(2,4-Dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(4-methyl-1-pipera- zinyl)propoxy]-3-quinolinecarbonitrile. 8. The method of claim 1 wherein the compound is: 4-[(2,4-Dichloro-5-methoxyphenyl)amino]-7-[3-(4-ethyl-1-piperazinyl)propo- xy]-6-methoxy-3-quinolinecarbonitrile; 4-[(2,4-Dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[2-(4-methyl-1-pipera- zinyl)ethoxy]-3-quinolinecarbonitrile; 4-[(2,4-Dichloro-5-methoxyphenyl)amino]-7-[2-(4-ethyl-1-piperazinyl)ethox- y]-6-methoxy-3-quinolinecarbonitrile; 4-[(2,4-Dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[(1-methylpiperidin-4- -yl)methoxy]-3-quinolinecarbonitrile; 4-[(2,4-Dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[2-(1-methylpiperidin- -4-yl)ethoxy]-3-quinolinecarbonitrile; 4-[(2,4-Dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(1-methylpiperidin- -4-yl)propoxy]quinoline-3-carbonitrile; 4-[(2,4-Dichloro-5-methoxyphenyl)amino]-7-[(1 -ethylpiperidin-4-yl)methoxy]-6-methoxyquinoline-3-carbonitrile; 4-[(2,4-Dichloro-5-methoxyphenyl)amino]-6-ethoxy-7-[3-(4-methylpiperazin-- 1-yl)propoxy]quinoline-3-carbonitrile; 4-[(2,4-Dichloro-5-methoxyphenyl)amino]-6-ethoxy-7-[(1-methylpiperidin-4-- yl)methoxy]quinoline-3-carbonitrile; 4-[(2,4-Dichloro-5-methoxyphenyl)amino]-6-ethoxy-7-[3-(4-ethylpiperazin-1- -yl)propoxy]quinoline-3-carbonitrile; 4-[(2,4-Dichloro-5-methoxyphenyl)amino]-6-ethoxy-7-[3-(1-methylpiperidin-- 4-yl)propoxy]quinoline-3-carbonitrile; 4-[(2,4-Dichloro-5-methoxyphenyl)amino]-6-ethoxy-7-[2-(4-methyl-1-piperaz- inyl)ethoxy]quinoline-3-carbonitrile; 4-[(2,4-Dichloro-5-methoxyphenyl)amino]-6-ethoxy-7-[2-(1-methylpiperidin-- 4-yl)ethoxy]quinoline-3-carbonitrile; or 4-[(2,4-Dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(4-propyl-1-pipera- zinyl)propoxy]-3-quinolinecarbonitrile; and pharmaceutically acceptable salts thereof. 9. The method of claim 1 wherein the compound is: 4-[(2,4-dichlorophenyl)amino]-6-methoxy-7-[(1 -methylpiperidin-4-yl)methoxy]-3-quinolinecarbonitrile; 6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]-4-[(3,4,5-trimethoxyphenyl)- amino]quinoline-3-carbonitrile; 4-[(2-chloro-5-methoxyphenyl)amino]-6-methoxy-7-[(1-methylpiperidin-4-yl)- methoxy]quinoline-3-carbonitrile; 6-methoxy-4-[(5-methoxy-2-methylphenyl)amino]-7-[(1-methylpiperidin-4-yl)- methoxy]quinoline-3-carbonitrile; 4-[(2,4-dimethylphenyl)amino]-6-methoxy-7-[(1-methylpiperidin-4-yl)methox- y]quinoline-3-carbonitrile; 6-methoxy-4-[(5-methoxy-2,4-dimethylphenyl)amino]-7-[(1-methylpiperidin-4- -yl)methoxy]quinoline-3-carbonitrile; and 4-[(2,4-dichloro-5-ethoxyphenyl)amino]-6-methoxy-7-[(1-methylpiperidin-4-- yl)methoxy]quinoline-3-carbonitrile. 10. The method of claim 1 wherein the compound is a Src inhibitor and a Abl Kinase inhibitor. 11. The method of claim 1 wherein the compounds are delivered alone or in combination with other compounds used to treat CML. 12. The method of claim 11 wherein the combination compound is (Imatinib) 4-[(4-methyl-1piperazinyl)methyl]-N-[4-methyl-3-[[4-(3-pyridinyl)-2pyrimi- dinyl]amino]phenyl]-Benzamide. |