905832-67-9Relevant academic research and scientific papers
Discovery and preclinical profile of saxagliptin (BMS-477118): A highly potent, long-acting, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes
Augeri, David J.,Robl, Jeffrey A.,Betebenner, David A.,Magnin, David R.,Khanna, Ashish,Robertson, James G.,Wang, Aiying,Simpkins, Ligaya M.,Taunk, Prakash,Huang, Qi,Han, Song-Ping,Abboa-Offei, Benoni,Cap, Michael,Xin, Li,Tao, Li,Tozzo, Effie,Welzel, Gustav E.,Egan, Donald M.,Marcinkeviciene, Jovita,Chang, Shu Y.,Biller, Scott A.,Kirby, Mark S.,Parker, Rex A.,Hamann, Lawrence G.
, p. 5025 - 5037 (2005)
Efforts to further elucidate structure-activity relationships (SAR) within our previously disclosed series of β-quaternary amino acid linked L-cis-4,5-methanoprolinenitrile dipeptidyl peptidase IV (DPP-IV) inhibitors led to the investigation of vinyl substitution at the β-position of α-cycloalkyl-substituted glycines. Despite poor systemic exposure, vinyl-substituted compounds showed extended duration of action in acute rat ex vivo plasma DPP-IV inhibition models. Oxygenated putative metabolites were prepared and were shown to exhibit the potency and extended duration of action of their precursors in efficacy models measuring glucose clearance in Zuckerfa/fa rats. Extension of this approach to adamantylglycine- derived inhibitors led to the discovery of highly potent inhibitors, including hydroxyadamantyl compound BMS-477118 (saxagliptin), a highly efficacious, stable, and long-acting DPP-IV inhibitor, which is currently undergoing clinical trials for treatment of type 2 diabetes.
Application of the ester enolate Claisen rearrangement in the synthesis of amino acids containing quaternary carbon centers
Kazmaier, Uli
, p. 3694 - 3699 (2007/10/03)
Ester enolate Claisen rearrangement of highly substituted amino acid allylic esters 4 allows for the synthesis of sterically demanding amino acids 5 with β-quaternary carbon centers. Because of enolate fixation by chelation, the rearrangement occurs in a highly diastereoselective fashion. The methodology is suitable not only for glycine derivatives but also for allylic esters of various amino acids. In this case amino acids with two vicinal quaternary carbon centers are created. With unsymmetrically substituted allylic esters like 4k-n the rearrangement proceeds with a high degree of diastereoselectivity.
