518035-83-1Relevant academic research and scientific papers
Structure-activity relationship, kinetic mechanism, and selectivity for a new class of ubiquitin C-terminal hydrolase-L1 (UCH-L1) inhibitors
Mermerian, Ara H.,Case, April,Stein, Ross L.,Cuny, Gregory D.
, p. 3729 - 3732 (2008/02/10)
3-Amino-2-keto-7H-thieno[2,3-b]pyridin-6-one derivatives were discovered as moderately potent inhibitors of ubiquitin C-terminal hydrolase-L1 (UCH-L1) utilizing an assay that measures hydrolysis of the fluorogenic substrate Ub-AMC. SAR studies revealed that both the carboxylate at the 5-position and the 6-pyridone ring were critical for inhibitory activity. Furthermore, activity was dependent on the nature of the ketone substituent at the 2-position, with 4-Me-Ph and 2-naphthyl being best. Kinetic mechanism studies revealed that these compounds were uncompetitive inhibitors of UCH-L1, binding only to the Michaelis-complex and not to free enzyme. The active compounds were selective for UCH-L1, exhibiting neither inhibition of other cysteine hydrolases (e.g., UCH-L3, papain, isopeptidase T, caspase-3, and tissue transglutaminase) nor cytotoxicity in N2A cells.
Anilinomethylidene derivatives of cyclic 1,3-dicarbonyl compounds in the synthesis of new sulfur-containing pyridines and quinolines
Dotsenko,Krivokolysko,Chernega,Litvinov
, p. 1556 - 1561 (2007/10/03)
Simple methods for the synthesis of previously unknown sulfur-containing pyridin-2-ones and 5,6,7,8-tetrahydroquinolines from cyanothioacetamide and anilinomethylidene derivatives of cyclic 1,3-dicarbonyl compounds were developed. Structures and chemical transformations of compounds obtained were studied.
