Gosogliptin

• CAT Number: I007016
• CAS Number: 869490-23-3
• Molecular Formula: C17H24F2N6O
• Molecular Weight: 366.41
• Purity: ≥95%
• Synonyms: (3,3-difluoropyrrolidin-1-yl)-[(2S,4S)-4-(4-pyrimidin-2-ylpiperazin-1-yl)pyrrolidin-2-yl]methanone
• InChI: InChI=1S/C17H24F2N6O/c18-17(19)2-5-25(12-17)15(26)14-10-13(11-22-14)23-6-8-24(9-7-23)16-20-3-1-4-21-16/h1,3-4,13-14,22H,2,5-12H2/t13-,14-/m0/s1
• InChIKey: QWEWGXUTRTXFRF-KBPBESRZSA-N
• SMILES: C1CN(CC1(F)F)C(=O)C2CC(CN2)N3CCN(CC3)C4=NC=CC=N4

Gosogliptin is a potent and selective inhibitor of dipeptidyl peptidase-IV (DPP-IV).
Gosogliptin (PF-00734200) is a potent, orally active, selective, and competitive inhibitor of DPP-IV, the enzyme mainly responsible for the degradation of the incretin peptides GLP-1 and glucose-dependent insulinotropic polypeptide. Gosogliptin demonstrates greater than 200-fold selectivity over other members of the DPP family (DPP-2, DPP-3, DPP-8, and DPP-9) and the related serine proteases, fibroblast activation protein, aminopeptidase P, and propyl oligopeptidase, enzymes that possess similar catalytic activities. Gosogliptin demonstrates rapid and reversible inhibition of plasma DPP-4 activity when administered orally to rats, dogs, and monkeys. In various nonclinical models, Gosogliptin stimulates insulin secretion and improves glucose tolerance[2].
The objectives of the present study are to characterize the metabolism, pharmacokinetics, and excretion of [14C] Gosogliptin in Sprague-Dawley (SD) rats, beagle dogs, and humans. A single dose of [14C] Gosogliptin is administered orally to intact SD rats (5 mg/kg), beagle dogs (5 mg/kg), and humans (20 mg). After a single oral dose of [14C] Gosogliptin to SD rats, an overall mean of 97.1% of the administered radioactivity is recovered in the urine, feces, and cage wash over a period of 168 h postdose. The mean cumulative dose recovered in feces is 66.0%. The mean cumulative excretion in the urine is 30.8%. Approximately 95% of the excreted radioactivity recovery occurred in the first 48 h. Mean total recoveries of dosed radioactivity from bile duct-cannulated rats are 29.5% in urine and 62.0% in bile. No gender-related differences are observed in the excretion pattern of radioactivity[2].

Reference

[1]. Dai H, et al. The pharmacokinetics of PF-734200, a DPP-IV inhibitor, in subjects with renal insufficiency. Br J Clin Pharmacol. 2011 Jul;72(1):85-91.
 [Content Brief]

[2]. Sharma R, et al. Metabolism, excretion, and pharmacokinetics of ((3,3-difluoropyrrolidin-1-yl)((2S,4S)-4-(4-(pyrimidin-2-yl)piperazin-1-yl)pyrrolidin-2-yl)methanone, a dipeptidyl peptidase inhibitor, in rat, dog and human. Drug Metab Dispos. 2012 Nov;40(11):2143-61.
 [Content Brief]