177956-45-5Relevant academic research and scientific papers
Optimizing glucokinase activator binding kinetics to lower in vivo hypoglycemia risk
Borzilleri, Kris A.,Pfefferkorn, Jeffrey A.,Guzman-Perez, Angel,Liu, Shenping,Qiu, Xiayang,Chrunyk, Boris A.,Song, Xi,Tu, Meihua,Filipski, Kevin J.,Aiello, Robert,Derksen, David R.,Bourbonais, Francis J.,Landro, James,Bourassa, Patricia,D'Aquila, Theresa,Baker, Levenia,Barrucci, Nicole,Litchfield, John,Atkinson, Karen,Rolph, Timothy P.,Withka, Jane M.
, p. 802 - 804 (2014/06/10)
Activation of glucokinase represents a promising strategy for the treatment of type 2 diabetes; however, drug candidates have failed in clinical trials due to narrow therapeutic index between glucose-lowering efficacy and hypoglycemia. Described herein is a novel strategy for the design of next generation glucokinase activators with increased therapeutic index, which involves the optimization of activator-enzyme binding kinetics (kon, k off). This approach is based on the idea that activator binding kinetics are relevant to pharmacodynamics since the affinity of activator binding to glucokinase is cooperative with glucose such that, the rate at which an activator dissociates may influence the enzyme's sensitivity to changes in physiological glucose concentrations. This study provides a compelling example of using fast-off binding kinetics for developing safe and effective activator drugs targeting glucokinase.
Total synthesis of (-)· and (+)-balanol
Lampe, John W.,Hughes, Philip F.,Biggers, Christopher K.,Smith, Shelley H.,Hu, Hong
, p. 4572 - 4581 (2007/10/03)
Two total syntheses of the potent protein kinase C inhibitory fungal metabolite balanol are described. In the first approach, the core aminohydroxyazepane subunit was prepared in racemic form by stereospecific functionalization of N-benzyl-∈-caprolactam.
Total Synthesis of (-)-Balanol
Lampe, John W.,Hughes, Philip F.,Biggers, Christopher K.,Smith, Shelley H.,Hu, Hong
, p. 5147 - 5148 (2007/10/02)
(-)-Balanol, a fungal metabolite with potent protein kinase C inhibitory properties, has been prepared in a total synthesis which makes use of an anionic homo-Fries rearrangement approach to the benzophenone subunit and in which the azepane subunit is obt
