Claims for Patent: 7,452,996

Summary for Patent: 7,452,996

Title:	Substituted quinoline derivatives
Abstract:	The present invention relates to new substituted quinoline compounds and pharmaceutically acceptable salts, esters or prodrugs thereof, compositions of the new compounds together with pharmaceutically acceptable carriers, and uses of the new compounds. The compounds of the invention have the following general formula: ##STR00001##
Inventor(s):	Wang; Weibo (Moraga, CA), Constantine; Ryan N. (Salt Lake City, UT), Lagniton; Liana Marie (Berkeley, CA), Bair; Kenneth (Emeryville, CA)
Assignee:	Novartis Vaccines and Diagnostics, Inc. (Emmeryville, CA)
Application Number:	11/133,509
Patent Claims:	1. A compound of formula I: ##STR00027## wherein: m is an integer from 0 to 3; R.sup.1 is selected from the group consisting of acylamino, carboxyl ester, and C.sub.1 to C.sub.5 alkyl optionally substituted with hydroxy, or halo; R.sup.2 is hydrogen or C.sub.1 to C.sub.5 alkyl; R.sup.3 is --C(.dbd.X)-A, wherein A is selected from the group consisting of aryl, heteroaryl, heterocyclic, and cycloalkyl, all of which may be optionally substituted with 1 to 4 substituents selected from the group consisting of C.sub.1 to C.sub.4 alkyl, C.sub.1 to C.sub.4 alkoxy, halo, hydroxy, and nitro and X is oxygen or sulfur; R.sup.4 is -alkylene-heterocyclic or -alkylene-NR.sup.7R.sup.8 wherein alkylene is a C.sub.1 to C.sub.4 straight chained alkylene; R.sup.7 and R.sup.8 are independently selected from the group consisting of hydrogen, C.sub.1 to C.sub.4 alkyl, arylalkyl, heteroarylalkyl, cycloalkyl and cycloalkylalkyl; R.sup.5 is selected from the group consisting of L-A.sup.1, wherein A.sup.1 is selected from the group consisting of aryl, heteroaryl, heterocyclic, and cycloalkyl, all of which may be optionally substituted with 1 to 4 substituents selected from the group consisting of C.sub.1 to C.sub.4 alkyl, C.sub.1 to C.sub.4 alkoxy, halo, hydroxy, and nitro and wherein L is selected from the group consisting of oxygen, --NR.sup.9 where R.sup.9 is hydrogen or alkyl, --S(O).sub.q-- where q is zero, one or two, and C.sub.1 to C.sub.5 alkylene, optionally substituted with hydroxy, halo, or acylamino; and R.sup.6 is selected from the group consisting of C.sub.1 to C.sub.5 alkyl, C.sub.2 to C.sub.5 alkenyl, C.sub.2 to C.sub.5 alkynyl, --CF.sub.3, C.sub.1 to C.sub.5 alkoxy, halo, and hydroxy; or a pharmaceutically acceptable salt thereof. 2. The compound of claim 1, wherein the compound is represented by formula II: ##STR00028## wherein: A.sup.2 and A.sup.3 are independently selected from the group consisting of aryl, heteroaryl, heterocyclic, and cycloalkyl, all of which may be optionally substituted with 1 to 4 substituents selected from the group consisting of C.sub.1 to C.sub.4 alkyl, C.sub.1 to C.sub.4 alkoxy, halo, hydroxy, and nitro; each R.sup.6 is independently selected from the group consisting of C.sub.1 to C.sub.5 alkyl, C.sub.2 to C.sub.5 alkenyl, C.sub.2 to C.sub.5 alkynyl, -CF.sub.3, C.sub.1 to C.sub.5 alkoxy, halo and hydroxyl; R.sup.11 is C.sub.2 to C.sub.3 alkyl; R.sup.12 and R.sup.13 are independently selected from the group consisting of hydrogen, C.sub.1 to C.sub.4 alkyl, arylalkyl, heteroarylalkyl, cycloalkyl and cycloalkylalkyl; m is an integer equal to 0 to 2; n is an integer equal to 1 to 3; and p is an integer equal to 1 to 4; or a pharmaceutically acceptable salt thereof. 3. The compound of claim 1, wherein the compound is represented by formula III: ##STR00029## wherein: A.sup.2 and A.sup.3 are independently selected from the group consisting of aryl, heteroaryl, heterocyclic, and cycloalkyl, all of which may be optionally substituted with 1 to 4 substituents selected from the group consisting of C.sub.1 to C.sub.4 alkyl, C.sub.1 to C.sub.4 alkoxy, halo, hydroxy, and nitro; R.sup.12 and R.sup.13 are independently selected from the group consisting of hydrogen, C.sub.1 to C.sub.4 alkyl, arylalkyl, heteroarylalkyl, cycloalkyl and cycloalkylalkyl; p is an integer equal to 1 to 4; or a pharmaceutically acceptable salt thereof. 4. The compound of claim 1, wherein R.sup.1 is C.sub.1 to C.sub.5 alkyl. 5. The compound of claim 1, wherein R.sup.1 is isopropyl or t-butyl. 6. The compound of claim 1, wherein R.sup.2 is hydrogen or methyl. 7. The compound of claim 1, wherein X is oxygen. 8. The compound of claim 1, wherein A is aryl. 9. The compound of claim 1, wherein A is phenyl or naphthyl. 10. The compound of claim 1, wherein A is heteroaryl. 11. The compound of claim 1, wherein A is selected from the group consisting of pyridinyl, imidazolyl, furanyl, pyrazolyl, and thiazolyl. 12. The compound of claim 1, wherein A is cycloalkyl. 13. The compound of claim 1, wherein A is cyclohexyl. 14. The compound of claim 1, wherein A is substituted with 1 to 4 substituents selected from the group consisting of chloro, methyl, bromo, fluoro, nitro, -CF.sub.3, methoxy, and t-butyl. 15. The compound of claim 1, wherein --C(O)-A is selected from the group consisting of: (2-chloro-6-methylpyridin-4-yl)carbonyl; (5-methylimidazol-4-yl)carbonyl; (naphth-2-yl)carbonyl; (pyridin-3-yl)carbonyl; (pyridin-4-yl) carbonyl; 3,4-difluorobenzoyl; 3,4-dimethylbenzoyl; 3,5-dimethylpyrazol-3-ylcarbonyl; 2-(3-aminopropanamido)- 4-methylbenzoyl; 2,4-difluorobenzoyl; 2,6-difluorobenzoyl; 2-chlorobenzoyl; 2-chloropyridin-3-ylcarbonyl; 2-chloropyridin-5-ylcarbonyl; 2-fluorobenzoyl; 2-methoxybenzoyl; 3,4-dichlorobenzoyl; 3-chlorobenzoyl; 3-fluoro-4-methylbenzoyl; 4-bromobenzoyl; 4-chlorobenzoyl; 4-hydroxybenzoyl; 4-methoxybenzoyl; 4-methyl-3-fluorobenzoyl; 4-methylbenzoyl; 4-nitrobenzoyl; 4-t-butylbenzoyl; 4-trifluoromethylbenzoyl; benzoyl; cyclohexylcarbonyl; furan-3 -ylcarbonyl; pyridin-2-ylcarbonyl; and thiazol-4-ylcarbonyl. 16. The compound of claim 15, wherein --C(O)-A is selected from the group consisting of 4-methyl-3-fluorobenzoyl, 4-methylbenzoyl, and 3,4-dimethylbenzoyl. 17. The compound of claim 1, wherein R.sup.4 is selected from the group consisting of: 3-(benzylamino) propyl; 3-(cyclobutylamino) propyl; 3-(cyclohexylmethylamino) propyl; 3-(diethylamino)propyl; 3-(isopropylamino) propyl; 3- [(3 -trifluoromethylpyridin-6-yl)amino]propyl; 3 -aminopropyl; 2-aminoethyl; piperidin-3-ylmethyl; and pyrrolidin-3 -ylmethyl. 18. The compound of claim 1, wherein R.sup.4 is 3-aminopropyl. 19. The compound of claim 1, wherein R.sup.5 is alkylene-A.sup.1 and A.sup.1 is aryl. 20. The compound of claim 19, wherein R.sup.5 is selected from the group consisting of: benzyl; 2-methylbenzyl; 3,5-difluorobenzyl; 3-acetylaminobenzyl; 3-fluorobenzyl; 3-hydroxybenzyl; 4-chlorobenzyl; 4-difluorobenzyl; and 4-methylbenzyl. 21. The compound of claim 1, wherein R.sup.6 is selected from the group consisting of hydrogen, fluoro, chloro, methyl, bromo, ethyl, vinyl, methoxy, phenyl, ethynyl, and --CF.sub.3. 22. The compound of claim 2, wherein m is 1 and n is 1. 23. The compound of claim 2, wherein R.sup.11 is isopropyl. 24. The compound of claim 2, wherein p is 3. 25. The compound of claim 2, wherein R.sup.12 and R.sup.13 are hydrogen. 26. The compound of claim 2, wherein A.sup.2 is phenyl. 27. The compound of claim 3, wherein A.sup.2 is phenyl. 28. The compound of claim 3, wherein p is 3. 29. The compound of claim 3, wherein R.sup.12 and R.sup.13 are hydrogen. 30. A compound selected from the group consisting of: N-(3-aminopropyl)-N- [1-(3-benzylquinolin-2-yl)- 2-methylpropyl]-3-fluoro-4-methylbenzamide; N-(3-aminopropyl)-N-[1-(3-benzylquinolin-2-yl)-2-methylpropyl]-4-methylbe- nzamide; N-(3-aminopropyl)-N-[1-(3-benzylquinolin-2-yl)-2-methylpropyl]-3,- 4-dimethylbenzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-7-chloroquinolin-2-yl)- 2-methylpropyl]-4-methylbenzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-7-chloroquinolin-2-yl)- 2-methylpropyl]-3-fluoro-4-methylbenzamide; and a pharmaceutically acceptable salt thereof. 31. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier. 32. The composition of claim 31 further comprising at least one additional agent for the treatment of cancer. 33. The composition of claim 31, wherein the additional agent for the treatment of cancer is selected from the group consisting of irinotecan, topotecan, gemcitabine, imatinib, trastuzumab, 5-fluorouracil, leucovorin, carboplatin, cisplatin, docetaxel, paclitaxel, tezacitabine, cyclophosphamide, vinca alkaloids, anthracyclines, rituximab, and trastuzumab.

Details for Patent 7,452,996

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	RITUXAN	rituximab	Injection	103705	11/26/1997		2024-05-21
Idec Pharmaceuticals Corp.	RITUXAN	rituximab	Injection	103737	02/19/2002		2024-05-21
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	09/25/1998		2024-05-21
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	02/10/2017		2024-05-21