58586-61-1Relevant academic research and scientific papers
Nonpeptide αvβ3 Antagonists. 8. In Vitro and in Vivo Evaluation of a Potent αvβ3 Antagonist for the Prevention and Treatment of Osteoporosis
Hutchinson, John H.,Halczenko, Wasyl,Brashear, Karen M.,Breslin, Michael J.,Coleman, Paul J.,Duong, Le T.,Fernandez-Metzler, Carmen,Gentile, Michael A.,Fisher, John E.,Hartman, George D.,Huff, Joel R.,Kimmel, Donald B.,Leu, Chih-Tai,Meissner, Robert S.,Merkle, Kara,Nagy, Rose,Pennypacker, Brenda,Perkins, James J.,Prueksaritanont, Thomayant,Rodan, Gideon A.,Varga, Sandor L.,Wesolowski, Greg A.,Zartman, Amy E.,Rodan, Sevgi B.,Duggan, Mark E.
, p. 4790 - 4798 (2003)
3(S)-(6-Methoxypyridin-3-yl)-3-{2-oxo-3-[3-(5,6,7,8-tetrahydro-[1,8] -naphthyridin-2-yl)propyl]-imidazolidin-1-yl}propionic acid 6 was identified as a potent and selective antagonist of the αvβ3 receptor. This compound has an excellent in vitro profile (IC50 = 0.08 nM), a significant unbound fraction in human plasma (12%), and good pharmacokinetics in rat, dog, and rhesus monkey. On the basis of the efficacy shown in three in vivo models of bone turnover, the compound was selected for clinical development. To support the ongoing metabolism and safety studies, a novel strategy was employed in which a series of oxidized derivatives of 6 were prepared by exposure of 6 (or the methyl ester) to chemical oxidizing agents. These products proved useful in the identification of active metabolites generated by either in vitro or in vivo metabolism.
Substituted phenylalkanoic acid derivatives and use thereof
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Page 59, (2008/06/13)
A compound represented by the formula (I) or a salt thereof: wherein n represents an integer of 1 to 3, R represents an alkyl group having 3 to 8 carbon atoms, a group represented by the following formula: R1(CH2)k— (wherein k represents 0 or an integer of 1 to 3; R1 represents a saturated cyclic alkyl group having 3 to 7 carbon atoms or a saturated condensed cyclic alkyl group having 6 to 8 carbon atoms, and the group R1 may be substituted with a lower alkyl group having 1 to 4 carbon atoms) and the like, and Ar represents a condensed bicyclic group such as naphthalen-1-yl group, which has suppressing action on prostaglandin and leukotriene production and is useful for prophylactic and/or therapeutic treatment of various inflammatory diseases and the like caused by these lipid mediators.
