224295-73-2Relevant academic research and scientific papers
OLEFIN SUBSTITUTED OXINDOLES HAVING AMPK ACTIVITY
-
Page/Page column 75, (2015/01/07)
The present invention relates to compounds of formula (I), which have valuable pharmacological properties, in particular are activators of AMPK and which are therefore useful in the treatment of certain disorders that can be prevented or treated by activation of this receptor. The compounds are suitable for treatment and prevention of diseases which can be influenced by this receptor, such as metabolic diseases, in particular diabetes type 2.
Synthesis, biological evaluation and molecular modelling of N-heterocyclic dipeptide aldehydes as selective calpain inhibitors
Jones, Matthew A.,Morton, James D.,Coxon, James M.,McNabb, Stephen B.,Lee, Hannah Y.-Y.,Aitken, Steven G.,Mehrtens, Janna M.,Robertson, Lucinda J.G.,Neffe, Axel T.,Miyamoto, Shigeru,Bickerstaffe, Roy,Gately, Karl,Wood, Jacqueline M.,Abell, Andrew D.
, p. 6911 - 6923 (2008/12/22)
A series of N-heterocyclic dipeptide aldehydes 4-13 have been synthesised and evaluated as inhibitors of ovine calpain 1 (o-CAPN1) and ovine calpain 2 (o-CAPN2). 5-Formyl-pyrrole 9 (IC50 values of 290 and 25 nM against o-CAPN1 and o-CAPN2, respectively) was the most potent and selective o-CAPN2 inhibitor, displaying >11-fold selectivity. The amino acid sequences of o-CAPN1 and o-CAPN2 have been determined. Because of the lack of available structural information on the ovine calpains, in silico homology models of the active site cleft of o-CAPN1 and o-CAPN2 were developed based on human calpain 1 (h-CAPN1) X-ray crystal structure (PDB code 1ZCM). These models were used to rationalise the observed SAR for compounds 4-13 and the selectivity observed for 9. The o-CAPN2 selective inhibitor 9 (CAT0059) was assayed in an in vitro ovine lens culture system and shown to successfully protect the lens from calcium-induced opacification.
