39635-02-4Relevant articles and documents
Selective androgen receptor modulators
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Page/Page column 62-63, (2009/10/18)
This invention provides compounds of formulas I, Ia, Ib, Ic, Id, Ie, and or salts thereof, pharmaceutical compositions comprising a compound of formulas I, Ia, Ib, Ic, Id, Ie, and a pharmaceutically acceptable excipient, methods of modulating the androgen receptor, methods of treating diseases beneficially treated by an androgen receptor modulator (e.g., sarcopenia, prostate cancer, contraception, type 2 diabetes related disorders or diseases, anemia, depression, and renal disease) and processes for making compounds of formulas I, Ia, Ib, Ic, Id, Ie, and intermediates useful in the preparation of same.
Optimization of alkylidene hydrazide based human glucagon receptor antagonists. Discovery of the highly potent and orally available 3-cyano-4-hydroxybenzoic acid [1-(2,3,5,6-tetramethylbenzyl)-1h-indol-4ylmethylene]hydrazide
Madsen, Peter,Ling, Anthony,Plewe, Michael,Sams, Christian K.,Knudsen, Lotte B.,Sidelmann, Ulla G.,Ynddal, Lars,Brand, Christian L.,Andersen, Birgitte,Murphy, Douglas,Teng, Min,Truesdale, Larry,Kiel, Dan,May, John,Kuki, Atsuo,Shi, Shenghua,Johnson, Michael D.,Teston, Kimberly Ann,Feng, Jun,Lakis, James,Anderes, Kenna,Gregor, Vlad,Lau, Jesper
, p. 5755 - 5775 (2007/10/03)
Highly potent human glucagon receptor (hGluR) antagonists have been prepared employing both medicinal chemistry and targeted libraries based on modification of the core (proximal) dimethoxyphenyl group, the benzyl ether linkage, as well as the (distal) benzylic aryl group of the lead 2, 3-cyano-4-hydroxybenzoic acid (3,5-dimethoxy-4-isopropylbenzyloxybenzylidene)hydrazide. Electron-rich proximal aryl moieties such as mono- and dimethoxy benzenes, naphthalenes, and indoles were found to be active. The SAR was found to be quite insensitive regarding the linkage to the distal aryl group, since long and short as well as polar and apolar linkers gave highly potent compounds. The presence of a distal aryl group was not crucial for obtaining high binding affinity to the hGluR. In many cases, however, the affinity could be further optimized with substituted distal aryl groups. Representative compounds have been tested for in vitro metabolism, and structure - metabolism relationships are described. These efforts lead to the discovery of 74, NNC 25-2504, 3-cyano-4-hydroxybenzoic acid [1-(2,3,5,6tetramethylbenzyl)-1H-indol-4-ylmethylene]hydrazide, with low in vitro metabolic turnover. 74 was a highly potent noncompetitive antagonist of the human glucagon receptor (IC50 = 2.3 nM, KB = 760 pM) and of the isolated rat receptor (IC50 = 430 pM, KB = 380 pM). Glucagonstimulated glucose production from isolated primary rat hepatocytes was inhibited competitively by 74 (Ki = 14 nM). This compound was orally available in dogs (Fpo = 15%) and was active in a glucagon-challenged rat model of hyperglucagonemia and hyperglycemia.
Identification of alkylidene hydrazides as glucagon receptor antagonists
Ling,Hong,Gonzalez,Gregor,Polinsky,Kuki,Shi,Teston,Murphy,Porter,Kiel,Lakis,Anderes,May,Knudsen,Lau
, p. 3141 - 3149 (2007/10/03)
High throughput screening of our small molecule combinatorial library identified a class of benzoylnaphthalenehydrazones with modest affinity for the human glucagon receptor. Optimization of this initial hit through a series of targeted libraries and traditional medicinal chemistry led to ligands with nanomolar affinities. Pharmacological evaluation demonstrated that these ligands were competitive glucagon receptor antagonists. Intravenous administration of a representative benzoylnaphthalenehydrazone into rats attenuated glucagon-stimulated glucose levels.
Mesomorphic compound, liquid crystal composition containing same and liquid crystal device using same
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, (2008/06/13)
A mesomorphic compound represented by the following formula (I): STR1 wherein R1 and R2 respectively denote a linear or branched alkyl group having 1-18 carbon atoms capable of including one or non-neighboring two or more methylene g
