134521-82-7Relevant articles and documents
Histone demethylase LSD1 (lysine specific demethylase 1) inhibitor
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Paragraph 0024; 0036, (2017/09/29)
The invention provides a histone demethylase LSD1 (lysine specific demethylase 1) inhibitor. The invention relates to piperazine-containing compounds and pharmacologically acceptable salts thereof and use of the piperazine-containing compounds and pharmacologically acceptable salts thereof as the LSD1 inhibitor; the general structural formula of the piperazine-containing compounds is described in the description. The invention belongs to the field of pharmaceutical chemistry. An in-vitro LSD1 activity inhibition test proves that the piperazine-containing compounds implemented by the invention have an obvious inhibiting effect for LSD1 activity, thus being used as active ingredients for preparing LSD1 inhibitor medicines.
Small molecule disruptors of the Glucokinase-Glucokinase regulatory protein interaction: 1. Discovery of a novel tool compound for in vivo proof-of-concept
Ashton, Kate S.,Andrews, Kristin L.,Bryan, Marion C.,Chen, Jie,Chen, Kui,Chen, Michelle,Chmait, Samer,Croghan, Michael,Cupples, Rod,Fotsch, Christopher,Helmering, Joan,Jordan, Steve R.,Kurzeja, Robert J. M.,Michelsen, Klaus,Pennington, Lewis D.,Poon, Steve F.,Sivits, Glenn,Van, Gwyneth,Vonderfecht, Steve L.,Wahl, Robert C.,Zhang, Jiandong,Lloyd, David J.,Hale, Clarence,St. Jean, David J.
, p. 309 - 324 (2014/02/14)
Small molecule activators of glucokinase have shown robust efficacy in both preclinical models and humans. However, overactivation of glucokinase (GK) can cause excessive glucose turnover, leading to hypoglycemia. To circumvent this adverse side effect, we chose to modulate GK activity by targeting the endogenous inhibitor of GK, glucokinase regulatory protein (GKRP). Disrupting the GK-GKRP complex results in an increase in the amount of unbound cytosolic GK without altering the inherent kinetics of the enzyme. Herein we report the identification of compounds that efficiently disrupt the GK-GKRP interaction via a previously unknown binding pocket. Using a structure-based approach, the potency of the initial hit was improved to provide 25 (AMG-1694). When dosed in ZDF rats, 25 showed both a robust pharmacodynamic effect as well as a statistically significant reduction in glucose. Additionally, hypoglycemia was not observed in either the hyperglycemic or normal rats.
Penicillin acylase-catalyzed peptide synthesis in aqueous medium: A chemo-enzymatic route to stereoisomerically pure diketopiperazines
Khimiuk, Andrei Y.,Korennykh, Alexei V.,Van Langen, Luuk M.,Van Rantwijk, Fred,Sheldon, Roger A.,Svedas, Vytas K.
, p. 3123 - 3128 (2007/10/03)
A range of non-natural dipeptides of the general formula D-(-)-phenylglycyl-L-X, where X is a natural α-amino acid, have been prepared by penicillin acylase-catalyzed synthesis in aqueous medium from D-(-)-phenylglycine amide and the corresponding amino acids. The conversion of the dipeptides to the corresponding dipeptide esters, followed by their subsequent spontaneous cyclization afforded the corresponding stereoisomerically pure diketopiperazines.
