BMS-927711
Names
[ CAS No. ]:
1289023-67-1
[ Name ]:
BMS-927711
[Synonym ]:
Rimegepant
1-Piperidinecarboxylic acid, 4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-1-yl)-, (5S,6S,9R)-5-amino-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-yl ester
BMS-927711
(5S,6S,9R)-5-nitro-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-yl 4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxylate
(5S,6S,9R)-5-amino-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-yl 4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxylate
(5S,6S,9R)-5-Amino-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-yl 4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)-1-piperidinecarboxylate
BMS 927711
Biological Activity
[Description]:
Rimegepant (BMS-927711) is a highly potent, oral calcitonin gene-related peptide (CGRP) receptor antagonist with a Ki value of 0.027 nM.
[Related Catalog]:
[Target]
Ki: 0.027 nM (CGRP receptor)[1] IC50: 0.14 nM (CGRP receptor)[1]
[In Vitro]
Rimegepant (BMS-927711) is a full, competitive CGRP receptor antagonist with IC50 of 0.14±0.01 nM[1].
[In Vivo]
Rimegepant (BMS-927711) has good oral bioavailability in rat and cynomolgus monkey, attractive overall preclinical properties, and shows dose-dependent activity in a primate model of CGRP-induced facial blood flow[1]. The ratios of the mean AUC (0-24 h) values for Rimegepant (BMS-927711) (60, 100, and 300 mg/kg) in the DBS matrix, compare with plasma, are 0.5-0.6 across all doses in rats. Results from this study suggest a strong correlation of Rimegepant concentrations between rat plasma and rat blood (DBS)[2].
[Animal admin]
Rats[2] Rats are treated with drug-free vehicle (control) or Rimegepant (BMS-927711) in vehicle at 60, 100, and 300 mg/kg once daily via oral gavage. There are 6 rats in each treatment group. For each treatment group, blood is collected at 1, 6, and 24 h from first three rats, and at 3 and 8 h from the second three rats on Day 1 and Day 14 from the tail vein following daily oral dosing of Rimegepant (BMS-927711) for two weeks. The mean hematocrits in the blood are 50.2±1.8%, 49.8±2.2%, 46.4±5.2% corresponding to the animal groups of 60, 100, and 300 mg/kg doses, respectively. For DBS evaluation, four 15 μL blood samples are spotted onto DBS cards (4 spots per card), dried at room temperature for at least 2 h, and each card is packaged separately in a ziplock bag with desiccant prior to shipment. The remaining blood in each sample tube is processed to plasma within 1 h of collection and stored at -70°C until analysis. Plasma samples are shipped on dry ice, and DBS cards are shipped at ambient temperature. Rimegepant (BMS-927711) concentrations in rat plasma are analyzed. Rimegepant in rat DBS is analyzed using the DBS method. The toxicokinetic (TK) parameters are calculated from blood concentration and time data using non-compartmental methods using Kinetica.
[References]
[1]. Luo G, et al. Discovery of (5S,6S,9R)-5-amino-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-yl 4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxylate (BMS-927711): an oral calcitonin gene-related peptide (CGRP) antagonist in clinical trials for treating migraine. J Med Chem. 2012 Dec 13;55(23):10644-51.
[2]. Zheng N, et al. Improved liquid-liquid extraction with inter-well volume replacement dilution workflow and its application to quantify BMS-927711 in rat dried blood spots by UHPLC-MS/MS. J Pharm Biomed Anal. 2014 Feb;89:240-50.
[Related Small Molecules]
Chemical & Physical Properties
[ Density]:
1.5±0.1 g/cm3
[ Molecular Formula ]:
C28H28F2N6O3
[ Molecular Weight ]:
534.557
[ Exact Mass ]:
534.219116
[ PSA ]:
119.39000
[ LogP ]:
1.73
[ Index of Refraction ]:
1.676
Synthetic Route
Precursor & DownStream
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