Jansen, Koen published the artcileExtended Structure-Activity Relationship and Pharmacokinetic Investigation of (4-Quinolinoyl)glycyl-2-cyanopyrrolidine Inhibitors of Fibroblast Activation Protein (FAP), Recommanded Product: 2-Chloroisonicotinic acid, the publication is Journal of Medicinal Chemistry (2014), 57(7), 3053-3074, database is CAplus and MEDLINE.
Fibroblast activation protein (FAP) is a serine protease related to dipeptidyl peptidase IV (DPPIV). It has been convincingly linked to multiple disease states involving remodeling of the extracellular matrix. FAP inhibition is investigated as a therapeutic option for several of these diseases, with most attention so far devoted to oncol. applications. The authors previously discovered the N-4-quinolinoyl-Gly-(2S)-cyanoPro scaffold as a possible entry to highly potent and selective FAP inhibitors. In the present study, the authors explore in detail the structure-activity relationship around this core scaffold. The authors report extensively optimized compounds that display low nanomolar inhibitory potency and high selectivity against the related dipeptidyl peptidases (DPPs) DPPIV, DPP9, DPPII, and prolyl oligopeptidase (PREP). The log D values, plasma stabilities, and microsomal stabilities of selected compounds were found to be highly satisfactory. Pharmacokinetic evaluation in mice of selected inhibitors demonstrated high oral bioavailability, plasma half-life, and the potential to selectively and completely inhibit FAP in vivo.
Journal of Medicinal Chemistry published new progress about 6313-54-8. 6313-54-8 belongs to chlorides-buliding-blocks, auxiliary class Pyridine,Chloride,Carboxylic acid, name is 2-Chloroisonicotinic acid, and the molecular formula is C6H4ClNO2, Recommanded Product: 2-Chloroisonicotinic acid.
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