Claims for Patent: 7,186,723

Summary for Patent: 7,186,723

Title:	Tyrosine kinase inhibitors
Abstract:	The present invention relates to compounds which inhibit, regulate and/or modulate tyrosine kinase signal transduction, compositions which contain these compounds, and methods of using them to treat tyrosine kinase-dependent diseases and conditions, such as angiogenesis, cancer, tumor growth, atherosclerosis, age related macular degeneration, diabetic retinopathy, inflammatory diseases, and the like in mammals.
Inventor(s):	Peckham; Jennifer P. (Cary, NC), Hoffman; William F. (Lansdale, PA), Arrington; Kenneth L. (Elkins Park, PA), Fraley; Mark E. (North Wales, PA), Hartman; George D. (Lansdale, PA), Kim; Yuntae (Harleysville, PA), Hanney; Barbara (Pennsburg, PA), Spencer; Keith L. (Hatfield, PA)
Assignee:	Merck & Co., Inc. (Rahway, NJ)
Application Number:	10/487,589
Patent Claims:	1. A compound selected from: 3-(5-{[(3S)-3-methylpiperazin-1-yl]methyl}-1H-indol-2-yl)quinolin-2(1H)-o- ne; 3-(5-{[(3R)-3-methylpiperazin-1-yl]methyl}-1H-indol-2-yl)quinolin-2(1H- )-one; 3-(5-{[(3S)-3-methyl-4-(methylsulfonyl)piperazin-1-yl]methyl}-1H-in- dol-2-yl) quinolin-2(1H)-one; 3-(5-{[(3R)-3-methyl-4-(methylsulfonyl)piperazin-1-yl]methyl}-1H-indol-2-- yl) quinolin-2(1H)-one; 2-(4-{[2-(2-oxo-1,2-dihydroquinolin-3-yl)-1H-indol-5-yl]methyl}piperazin-- 1-yl) acetamide; 3-{5-[(4-acetyl-4-hydroxypiperidin-1-yl)methyl]-1H-indol-2-yl}quinolin-2(- 1H)-one; 1-{[2-(2-oxo-1,2-dihydroquinolin-3-yl)-1H-indol-5-yl]methyl}piper- idine-4-sulfonamide; 4-{[2-(2-oxo-1,2-dihydroquinolin-3-yl)-1H-indol-5-yl]methyl}piperazine-1-- carboxamide; methyl 2-methyl-1-{[2-(2-oxo-1,2-dihydroquinolin-3-yl)-1H-indol-5-yl]methyl}pipe- ridine-2-carboxylate; methyl 2-methyl-1-{[2-(2-oxo-1,2-dihydroquinolin-3-yl)-1H-indol-5-yl]methyl}pipe- ridine-2-carboxylic acid; 3-(5-{[4-(aminomethyl)piperidin-1-yl]methyl}-1H-indol-2-yl)quinolin-2(1H)- -one; N-[(1-{[2-(2-oxo-1,2-dihydroquinolin-3-yl)-1H-indol-5-yl]methyl}pipe- ridin-4-yl)methyl]methanesulfonamide; 1-{[2-(2-oxo-1,2-dihydroquinolin-3-yl)-1H-indol-5-yl]methyl}piperazine-2-- carboxamide; 4-{[2-(2-oxo-1,2-dihydroquinolin-3-yl)-1H-indol-5-yl]methyl}piperazine-2-- carboxamide; 3-(5-{2-[4-(methylsulfonyl)piperazin-1-yl]ethyl}-1H-indol-2-yl)quinolin-2- (1H)-one; N-methyl-4-{2-[2-(2-oxo-1,2-dihydroquinolin-3-yl)-1H-indol-5-yl]- ethyl}piperazine-1-carboxamide; 3-{5-[2-(4-aminopiperidin-1-yl)ethyl]-1H-indol-2-yl}quinolin-2(1H)-one; 3-{6-[(4-methylpiperazin-1-yl)carbonyl]-1H-indol-2-yl}quinolin-2(1H)-one; 3-{4-[(4-methylpiperazin-1-yl)carbonyl]-1H-indol-2-yl}quinolin-2(1H)-one; and 3-(6-{[4-(methylsulfonyl)piperazin-1-yl]methyl}-1H-indol-2-yl)quinoli- n-2(1H)-one; and or a pharmaceutically acceptable salt or stereoisomer thereof. 2. A compound according to claim 1 selected from: 3-(5-{[(3S)-3-methylpiperazin-1-yl]methyl}-1H-indol-2-yl)quinolin-2(1H)-o- ne; 3-(5-{[(3R)-3-methylpiperazin-1-yl]methyl}-1H-indol-2-yl)quinolin-2(1H- )-one; 3-(5-{[(3S)-3-methyl-4-(methylsulfonyl)piperazin-1-yl]methyl}-1H-in- dol-2-yl) quinolin-2(1H)-one; 3-(5-{[(3R)-3-methyl-4-(methylsulfonyl)piperazin-1-yl]methyl}-1H-indol-2-- yl) quinolin-2(1H)-one; 3-(5-{[4-(1,1-dioxidotetrahydrothien-3-yl)piperazin-1-yl]methyl}-1H-indol- -2-yl) quinolin-2(1H)-one; 2-(4-{[2-(2-oxo-1,2-dihydroquinolin-3-yl)-1H-indol-5-yl]methyl}piperazin-- 1-yl) acetamide; 3-{5-[(4-acetyl-4-hydroxypiperidin-1-yl)methyl]-1H-indol-2-yl}quinolin-2(- 1H)-one; 1-{[2-(2-oxo-1,2-dihydroquinolin-3-yl)-1H-indol-5-yl]methyl}piper- idine-4-sulfonamide; 4-{[2-(2-oxo-1,2-dihydroquinolin-3-yl)-1H-indol-5-yl]methyl}piperazine-1-- carboxamide; and methyl 2-methyl-1-{[2-(2-oxo-1,2-dihydroquinolin-3-yl)-1H-indol-5-yl]methyl}pipe- ridine-2-carboxylate; methyl 2-methyl-1-{[2-(2-oxo-1,2-dihydroquinolin-3-yl)-1H-indol-5-yl]methyl}pipe- ridine-2-carboxylic acid; 3-(5-{[4-(aminomethyl)piperidin-1-yl]methyl}-1H-indol-2-yl)quinolin-2(1H)- -one; N-[(1-{[2-(2-oxo-1,2-dihydroquinolin-3-yl)-1H-indol-5-yl]methyl}pipe- ridin-4-yl)methyl]methanesulfonamide; 1-{[2-(2-oxo-1,2-dihydroquinolin-3-yl)-1H-indol-5-yl]methyl}piperazine-2-- carboxamide; 4-{[2-(2-oxo-1,2-dihydroquinolin-3-yl)-1H-indol-5-yl]methyl}piperazine-2-- carboxamide; or a pharmaceutically acceptable salt or stereoisomer thereof. 3. A compound according to claim 1 selected from: 3-(5-{2-[4-(methylsulfonyl)piperazin-1-yl]ethyl}-1H-indol-2-yl)quinolin-2- (1H)-one; N-methyl-4-{2-[2-(2-oxo-1,2-dihydroquinolin-3-yl)-1H-indol-5-yl]- ethyl}piperazine-1-carboxamide; 3-{5-[2-(4-aminopiperidin-1-yl)ethyl]-1H-indol-2-yl}quinolin-2(1H)-one; 3-{6-[(4-methylpiperazin-1-yl)carbonyl]-1H-indol-2-yl}quinolin-2(1H)-one; 3-{4-[(4-methylpiperazin-1-yl)carbonyl]-1H-indol-2-yl}quinolin-2(1H)-one; and 3-(6-{[4-(methylsulfonyl)piperazin-1-yl]methyl}-1H-indol-2-yl)quinoli- n-2(1H)-one; or a pharmaceutically acceptable salt or stereoisomer thereof. 4. A pharmaceutical composition which is comprised of a compound in accordance with claim 1 and a pharmaceutically acceptable carrier. 5. A method of treating cancer in accordance with claim 1 wherein the cancer is selected from cancers of the brain, genitourinary tract, lymphatic system, stomach, larynx and lung. 6. A method of treating cancer in accordance with claim 1 wherein the cancer is selected from histiocytic lymphoma, lung adenocarcinoma, small cell lung cancers, pancreatic cancer, gioblastomas and breast carcinoma. 7. A method of treating cancer wherein the cancer is selected from cancers of the brain, genitourinary tract, lymphatic system, stomach, larynx, lung, histiocytic lymphoma, lung adenocarcinoma, small cell lung cancers, pancreatic cancer, gioblastomas, and breast carcinoma which comprises administering a therapeutically effective amount of a compound of claim 1 in combination with radiation therapy and a compound selected from: 1) an estrogen receptor modulator, 2) an androgen receptor modulator, 3) retinoid receptor modulator, 4) a cytotoxic agent, 5) an antiproliferative agent, 6) a prenyl-protein transferase inhibitor, 7) an HMG-CoA reductase inhibitor, 8) an HIV protease inhibitor, 9) a reverse transcriptase inhibitor, and 10) another angiogenesis inhibitor. 8. A method of treating wherein the cancer is selected from cancers of the brain, genitourinary tract, lymphatic system, stomach, larynx, lung, histiocytic lymphoma, lung adenocarcinoma, small cell lung cancers, pancreatic cancer, gioblastomas, and breast carcinoma cancer which comprises administering a therapeutically effective amount of a compound of claim 1 and paclitaxel or trastuzumab. 9. A method of treating or preventing diabetic retinopathy which comprises administering a therapeutically effective amount of a compound of claim 1 in combination with a PPAR-.gamma. agonist.

Details for Patent 7,186,723

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	09/25/1998		2039-02-26
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	02/10/2017		2039-02-26
Genentech, Inc.	HERCEPTIN HYLECTA	trastuzumab and hyaluronidase-oysk	Injection	761106	02/28/2019		2039-02-26