149519-95-9Relevant academic research and scientific papers
Burkholderia cepacia lipase is an excellent enzyme for the enantioselective hydrolysis of β-heteroaryl-β-amino esters
Tasnadi, Gabor,Forro, Eniko,Fueloep, Ferenc
experimental part, p. 1771 - 1777 (2009/12/28)
The enantioselective (E >200) lipase PS-catalysed hydrolysis of β-heteroaryl-β-amino esters is described. The reactions were performed with H2O (0.5 equiv) in either diisopropyl ether or tert-butyl methyl ether at 25 °C. The resulting β-heteroaryl-substituted β-amino acid enantiomers were formed in high enantiomeric excess (ee ≥ 97%) and in good yield (≥40%).
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 (2007/10/03)
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.
