Claims for Patent: 8,609,673

Summary for Patent: 8,609,673

Title:	Vandetanib derivatives
Abstract:	This invention relates to novel quinazoline derivatives of the formula: ##STR00001## wherein each variable is as defined herein, and their acceptable acid addition salts. The invention also provides compositions comprising a compound of this invention and the use of such compositions in methods of treating diseases and conditions beneficially treated by inhibitory activity against the VEGF receptor tyrosine kinase.
Inventor(s):	Tung; Roger (Lexington, MA)
Assignee:	Concert Pharmaceuticals, Inc. (Lexington, MA)
Application Number:	12/864,219
Patent Claims:	1. A compound of Formula I ##STR00019## or a pharmaceutical salt thereof; wherein: each Z is independently selected from hydrogen or deuterium; each R is selected from --CH.sub.3, --CH.sub.2D, --CHD.sub.2 and CD.sub.3; and when each R is --CH.sub.3 at least one Z is deuterium, wherein there is at least 50.1% incorporation of deuterium at any atom designated as D or deuterium. 2. A compound of Formula A ##STR00020## or a pharmaceutically acceptable salt thereof; wherein: each Z is independently selected from hydrogen and deuterium; each R is selected from --CH.sub.3, --CH.sub.2D, --CHD.sub.2 and CD.sub.3; and when each R is --CH.sub.3 at least one Z is deuterium, wherein there is at least 50.1% incorporation of deuterium at any atom designated as D or deuterium. 3. The compound of claim 2, wherein each Z.sup.1 is the same. 4. The compound of claim 3, wherein each Z.sup.2 is the same. 5. The compound of claim 4, wherein each Z.sup.3 is the same. 6. The compound of claim 5, wherein R.sup.1 is selected from CH.sub.3 and CD.sub.3. 7. The compound of claim 6, wherein R.sup.2 is selected from CH.sub.3 and CD.sub.3. 8. The compound of claim 7 wherein Z.sup.4 is hydrogen. 9. The compound of claim 8, selected from any one of the compounds set forth in the table: TABLE-US-00003 Cmpd R.sup.1 R.sup.2 Each Z.sup.3 Each Z.sup.1 Each Z.sup.2 100 CD.sub.3 CH.sub.3 H H H 101 CH.sub.3 CD.sub.3 H H H 102 CH.sub.3 CH.sub.3 D H H 103 CD.sub.3 CH.sub.3 D H H 104 CH.sub.3 CD.sub.3 D H H 105 CD.sub.3 CD.sub.3 H H H 106 CD.sub.3 CD.sub.3 D H H 107 CD.sub.3 CH.sub.3 H D H 108 CH.sub.3 CD.sub.3 H D H 109 CH.sub.3 CH.sub.3 D D H 110 CD.sub.3 CH.sub.3 D D H 111 CH.sub.3 CD.sub.3 D D H 112 CD.sub.3 CD.sub.3 H D H 113 CD.sub.3 CD.sub.3 D D H 114 CD.sub.3 CH.sub.3 H H D 115 CH.sub.3 CD.sub.3 H H D 116 CH.sub.3 CH.sub.3 D H D 117 CD.sub.3 CH.sub.3 D H D 118 CH.sub.3 CD.sub.3 D H D 118 CD.sub.3 CD.sub.3 H H D 119 CD.sub.3 CD.sub.3 D H D 120 CD.sub.3 CH.sub.3 H D D 121 CH.sub.3 CD.sub.3 H D D 122 CH.sub.3 CH.sub.3 D D D 123 CD.sub.3 CH.sub.3 D D D 124 CH.sub.3 CD.sub.3 D D D 125 CD.sub.3 CD.sub.3 H D D 126 CD.sub.3 CD.sub.3 D D D. 10. The compound of claim 7 wherein Z.sup.4 is deuterium. 11. The compound of claim 10 which is ##STR00021## 12. The compound of claim 1, wherein any atom not designated as deuterium is present at its natural isotopic abundance. 13. A pyrogen-free pharmaceutical composition comprising a compound of claim 2; and a pharmaceutically acceptable carrier. 14. The composition of claim 13 further comprising a second anti-cancer agent. 15. The composition of claim 14, wherein the second anti-cancer agent is selected from one or more of 5-fluorouracil, folinic acid, irinotecan, docetaxel, capecitabine, oxaliplatin, bevacizumab, cyclophosphamide, methotrexate, pemetrexed, cisplatin, carboplatin, irinotecan, cetuximab, vinorelbine, gemcitabine, paclitaxel, prednisolone, 13-cis retinoic acid, erlotinib, anastrozole, and leucovorin. 16. A method of inhibiting the activity of VEGFR-2/KDR tyrosine kinase in a cell, comprising the step of contacting the cell with a compound of claim 2. 17. A method of treating a patient suffering from thyroid cancer, comprising the step of administering to the patient in need thereof a composition of claim 13.

Details for Patent 8,609,673

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	02/12/2004		2039-02-26
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	03/28/2007		2039-02-26
Genentech, Inc.	AVASTIN	bevacizumab	Injection	125085	02/26/2004		2039-02-26