95204-52-7Relevant academic research and scientific papers
Synthesis, biological activity screening and molecular modeling study of acylaminoacetamide derivatives
Coban, Gunes,Kose, Fadime Aydin,Kirmizibayrak, Petek Ballar,Pabuccuoglu, Varol
, p. 3710 - 3729 (2015/09/07)
In this study, non-rigid analogs of thalidomide have been designed in order to develop potentially active, more effective and safer lead molecules for disorders caused or contributed by inflammation. Five different series of acylaminoacetamide compounds were synthesized, and the biological inhibitory potency of the title compounds has been determined by evaluating their effects on COX-2 isoenzyme expression and PGE2 production in A549 (human lung adenocarcinoma) cell lines. Among the studied series, N-[2-(isopropylamino)-2-oxoethyl]isonicotinamide is the most active inhibitory compound on COX-2 isoenzyme expression, and N-[2-oxo-2-(pyrolydine-1-yl)etyl]isonicotinamide is the most active inhibitory compound on the biosynthesis of PGE2. Molecular docking studies and molecular dynamics simulations were also applied to investigate non-covalent interactions of the most active compounds inside the active side of the crystal structure of murine cyclooxygenase 2 (mCOX-2) isoenzyme.
Acylated Gly-(2-cyano)pyrrolidines as inhibitors of fibroblast activation protein (FAP) and the issue of FAP/prolyl oligopeptidase (PREP)-selectivity
Ryabtsova, Oxana,Jansen, Koen,Van Goethem, Sebastiaan,Joossens, Jurgen,Cheng, Jonathan D.,Lambeir, Anne-Marie,De Meester, Ingrid,Augustyns, Koen,Van Der Veken, Pieter
body text, p. 3412 - 3417 (2012/06/18)
A series of N-acylated glycyl-(2-cyano)pyrrolidines were synthesized with the aim of generating structure-activity relationship (SAR) data for this class of compounds as inhibitors of fibroblast activation protein (FAP). Specifically, the influence of (1) the choice of the N-acyl group and (2) structural modification of the 2-cyanopyrrolidine residue were investigated. The inhibitors displayed inhibitory potency in the micromolar to nanomolar range and showed good to excellent selectivity with respect to the proline selective dipeptidyl peptidases (DPPs) DPP IV, DPP9 and DPP II. Additionally, selectivity for FAP with respect to prolyl oligopeptidase (PREP) is reported. Not unexpectedly, the latter data suggest significant overlap in the pharmacophoric features that define FAP or PREP-inhibitory activity and underscore the importance of systematically evaluating the FAP/PREP-selectivity index for inhibitors of either of these two enzymes. Finally, this study forwards several compounds that can serve as leads or prototypic structures for future FAP-selective-inhibitor discovery.
