- SUBSTITUTED IMIDAZO[1,2-a]PYRIDINE COMPOUNDS AS TROPOMYOSIN RECEPTOR KINASE A (TrkA) INHIBITORS
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The present application relates to a series of substituted imidazo[1,2-a]pyridine compounds of formula (I), pharmaceutically acceptable salts, pharmaceutically acceptable solvates or stereoisomers thereof, their use as tropomyosin receptor kinase (Trk) family protein kinase inhibitors, method of making and pharmaceutical compositions comprising such compounds.
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Paragraph 0632; 0633
(2016/01/15)
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- BIOMARKERS FOR DETERMINING EFFECTIVE RESPONSE OF TREATMENTS OF HEPATOCELLULAR CARCINOMA (HCC) PATIENTS
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This invention is directed to the use of one or more biomarkers defined as KRAS or NRAS gene for predicting the pharmaceutical efficacy or clinical response of MEK protein kinase inhibitor and/or Sorafenib or Regorafenib to be administred to a Hepatocellu
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Page/Page column 39; 40
(2014/01/07)
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- COMBINATIONS OF MEK INHIBITORS AND RAF KINASE INHIBITORS AND USES THEREOF
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This invention concerns combinations of inhibitors of MEK, Raf protein kinases, and other kinases including VEGFR1-3 and PDGFR-β. This invention also concerns pharmaceutical compositions comprising the compounds described herein and methods of use of the compounds and compositions described herein, including the use in the treatment and/or prevention of cancer and other hyperproliferative disorders.
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- NOVEL 6-ARYLAMINO PYRIDONE SULFONAMIDES AND 6-ARYLAMINO PYRAZINONE SULFONAMIDES AS MEK INHIBITORS
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The invention provides novel substituted 6-arylamino pyridone sulfonamides and 6 arylamino pyrazinone sulfonamides represented by Formula I, or a pharmaceutically acceptable salt, solvate, polymorph, ester, tautomer or prodrug thereof, and a composition comprising these compounds. The compounds provided can be used as inhibitors of MEK and are useful in the treatment of inflammatory diseases, cancer and other hyperproliferative diseases. The invention further provides a method of treatment for inflammatory diseases, cancer and other hyperproliferative diseases in mammals, especially humans
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Page/Page column 54-55
(2010/12/31)
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- N-(ARYLAMINO)-SULFONAMIDE INHIBITORS OF MEK
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This invention concerns N-(2-arylamino) aryl sulfonamides, which are inhibitors of MEK and are useful in treatment of cancer and other hyperproliferative diseases.
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Page/Page column 48; 49
(2008/06/13)
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- Cyclopropanesulfonyl Chloride: Its Mechanism of Hydrolysis and Reactions with Tertiary Amines in Organic Media
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Cyclopropanesulfonyl chloride (1) has been synthesized and its reactions examined to see if the three-membered ring leads to unusual reactions in either 1 or the corresponding sulfene, cyclopropanethione S,S-dioxide (2). pH-rate profiles, primary kinetic isotope effects (KIE's), and pH-product ratio experiments are in full agreement with mechanisms of hydrolysis of 1 like those of a simple alkanesulfonyl chlorides (J.Am.Chem.Soc.1992,114,1743-1749), specifically, (a) below pH 7.2 by SN2-S reaction with water and (b) above pH 7.3, elimination by hydroxide to form the sulfene (2) which is trapped by (i) water below pH 12.0 and (ii) hydroxide above pH 12.0.The products of the reaction of cyclopropanesulfonyl-1-d chloride (9) with triethylamine and 2-propanol in dichloromethane indicate that most of the reaction goes via 2; the analogous reaction with trimethylamine apparently proceeds by a direct formation of the sulfonylammonium chloride (14) which then yields the α-deuterated N,N-dimethyl sulfonamide (12, R=Me).The evident sulfene formation processes in the reaction of triethylamine with ethenesulfonyl, 2-propanesulfonyl, and cyclopropanesulfonyl chlorides show very low primary KIE's (1.5), pointing to highly product-like transition states.Reaction of 1 with an enamine (1-pyrrolidino-2-methylpropene, 20) in the presence of a base in either water or dichloromethane gave cyclopropanesulfonpyrrolidide (23) and an aldehyde adduct (24), but no four-membered cycloadduct (21).
- King, James F.,Lam, Joe Y. L.,Ferrazzi, Gabriele
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p. 1128 - 1135
(2007/10/02)
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