Claims for Patent: 8,410,082

Summary for Patent: 8,410,082

Title:	Fluorinated diaryl urea derivatives
Abstract:	This invention relates to novel diaryl urea compounds, their derivatives, and pharmaceutically acceptable salts thereof. This invention also provides compositions comprising a compound of this invention and the use of such compositions in methods of treating diseases and conditions that are beneficially treated by administering an inhibitor of multiple kinases. ##STR00001##
Inventor(s):	Liu; Julie F. (Lexington, MA), Tung; Roger D. (Lexington, MA), Harbeson; Scott L. (Cambridge, MA)
Assignee:	Concert Pharmaceuticals, Inc. (Lexington, MA)
Application Number:	13/320,646
Patent Claims:	1. A compound of Formula IA: ##STR00015## or a pharmaceutically acceptable salt thereof, wherein: R.sup.1 is selected from CH.sub.3 and CD.sub.3; R.sup.2, R.sup.10 and R.sup.11 are simultaneously D or H; R.sup.3, R.sup.8 and R.sup.9 are simultaneously D or H; and R.sup.5, R.sup.6 and R.sup.7 are simultaneously D or H, wherein at least one R group comprises a deuterium atom. 2. The compound of claim 1 having the formula IA, wherein the compound is selected from any one of the compounds set forth in the table below: TABLE-US-00002 Compound R.sup.1 R.sup.2 R.sup.3 R.sup.5 R.sup.6 R.sup.7 R.sup.8 R.sup.9 R- .sup.10 R.sup.11 100 CH.sub.3 D D D D D D D D D 101 CH.sub.3 H D D D D D D H H 102 CH.sub.3 D H D D D H H D D 103 CH.sub.3 D D H H H D D D D 104 CH.sub.3 H H D D D H H H H 105 CH.sub.3 H D H H H D D H H 106 CH.sub.3 D H H H H H H D D 107 CD.sub.3 D D D D D D D D D 108 CD.sub.3 H D D D D D D H H 109 CD.sub.3 D H D D D H H D D 110 CD.sub.3 D D H H H D D D D 111 CD.sub.3 H H D D D H H H H 112 CD.sub.3 H D H H H D D H H 113 CD.sub.3 D H H H H H H D D 114 CD.sub.3 H H H H H H H H H or a pharmaceutically acceptable salt thereof. 3. The compound of claim 1, wherein any atom not designated as deuterium is present at its natural isotopic abundance. 4. A pyrogen-free pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier. 5. The composition of claim 4, additionally comprising a second therapeutic agent useful in the treatment of a disease or condition selected from renal cell carcinoma and other cancers including liver, non-small cell lung, lung, breast, ovarian, fallopian tube, peritoneal cavity, pancreatic, bladder, prostate metastatic, thyroid, uterine, gastrointestinal stromal, metastatic melanoma, prostate adenocarcinoma, soft tissue sarcoma, mesothelioma, glioblastoma multiforme, acute myeloid leukemia, non-Hodgkin's lymphoma, multiple myeloma, glioblastoma, lymphoma, anaplastic astrocytoma, squamous cell head and neck carcinoma, oligodendroglioma, solid tumor, and colorectal cancers, viral infections, inflammatory disorders, diabetic neuropathy, pulmonary hypertension, arterial restenosis, osteoporosis and transplant rejection. 6. The composition of claim 5, wherein the second therapeutic agent is selected from doxorubicin, dacarbazine, temozolomide, anastrozole, gemcitabine, topotecan, bicalutamide, RAD001, AMG 386, taxotere, bevacizumab, temsirolimus, erlotinib, tipifarnib, perifosine, pemetrexed, cetuximab, recombinant IL-21, paclitaxel, irinotecan hydrochloride, everolimus, abraxane, mitoxantrone, prednisone, etoposide, cisplatin and carboplatin. 7. A method of treating a disease or condition selected from renal cell carcinoma and other cancers including liver, non-small cell lung, lung, breast, ovarian, fallopian tube, peritoneal cavity, pancreatic, bladder, prostate metastatic, thyroid, uterine, gastrointestinal stromal, metastatic melanoma, prostate adenocarcinoma, soft tissue sarcoma, mesothelioma, glioblastoma multiforme, acute myeloid leukemia, non-Hodgkin's lymphoma, multiple myeloma, glioblastoma, lymphoma, anaplastic astrocytoma, squamous cell head and neck carcinoma, oligodendroglioma, solid tumor, and colorectal cancers, viral infections, inflammatory skin, eye and/or ear diseases, diabetic neuropathy, pulmonary hypertension, arterial restenosis, osteoporosis and transplant rejection, in a subject the method comprising the step of administering to the subject an effective amount of a composition of claim 4. 8. The method of claim 7, wherein the disease or condition is renal cell carcinoma. 9. The method of claim 7, comprising the additional step of co-administering to the subject a second therapeutic agent useful in the treatment of a disease or condition selected from renal cell carcinoma, hepatocellular carcinoma, breast cancer, bladder cancer, pancreatic cancer, small cell lung cancer, non-small cell lung cancer, prostate adenocarcinoma, kidney cancer, prostate cancer, brain and central nervous system tumors, colorectal cancer, intraocular melanoma, solid tumors, melanoma, lymphoma or multiple myeloma, viral infections, inflammatory skin, eye and/or ear diseases, diabetic neuropathy, pulmonary hypertension, arterial restenosis, osteoporosis and transplant rejection. 10. The method of claim 9, wherein: a. the second therapeutic reagent is selected from AMG 386, recombinant IL-21, perifosine, and RAD001; or b. the second therapeutic reagent is doxorubicin; or c. the second therapeutic reagent is anastrozole; or d. the second therapeutic reagent is selected from gemcitabine and carboplatin; or e. the second therapeutic reagent is gemcitabine; or f. the second therapeutic reagent is topotecan; or g. the second therapeutic reagent is selected from pemetrexed, carboplatin, gemcitabine, cisplatin, and etoposide; or h. the second therapeutic reagent is bicalutamide; or i. the second therapeutic reagent is selected from RAD001, bevacizumab, and temsirolimus; or j. the second therapeutic reagent is selected from taxotere, mitoxantrone, and prednisone; or k. the second therapeutic reagent is selected from erlotinib, tipifarnib, and temsirolimus; or l. the second therapeutic reagent is selected from cetuximab and irinotecan hydrochloride; or m. the second therapeutic reagent is selected from paclitaxel and carboplatin; or n. the second therapeutic reagent is selected from temsirolimus, erlotinib, and bevacizumab; or o. the second therapeutic reagent is selected from temsirolimus, abraxane, carboplatin, dacarbazine, and temozolomide; or p. the second therapeutic reagent is everolimus.

Details for Patent 8,410,082

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	02/12/2004		2029-05-22
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	03/28/2007		2029-05-22
Genentech, Inc.	AVASTIN	bevacizumab	Injection	125085	02/26/2004		2029-05-22