MK-0974

MK-0974 is an orally bioavailable antagonist of the calcitonin gene-related peptide (CGRP) receptor complex (Ki = 0.77 µM), which is composed of the calcitonin receptor-like receptor (CRLR) and receptor activity modifying protein 1 (RAMP1). MK-0974 binds selectively to the human CGRP receptor complex, over the adrenomedullin receptor complexes, which are composed of CRLR and RAMP2 or RAMP3 (Kis = >100 and 29 µM, respectively, in HEK293 cells). MK-0974 also binds to rhesus, canine, and rat CGRP receptor complexes (Kis = 1.2, 1,204, and 1,192 nM, respectively). MK-0974 inhibits cAMP accumulation stimulated by CGRP (Cay-24405) with an IC50 value of 2.2 nM in HEK293 cells expressing the CGRP receptor complex. Ex vivo, MK-0974 (5 µM) reduces CGRP-induced vasodilation in isolated human meningeal arteries. MK-0974 also inhibits vasodilation induced by topical application of capsaicin (Cay-92350) in rhesus monkeys (EC50 = 127 nM).Formal Name: N-[(3R,6S)-6-(2,3-difluorophenyl)hexahydro-2-oxo-1-(2,2,2-trifluoroethyl)-1H-azepin-3-yl]-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-1-yl)-1-piperidinecarboxamide. CAS Number: 781649-09-0. Molecular Formula: C26H27F5N6O3. Formula Weight: 566.5. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMSO: 10 mM, Ethanol: 1 mg/ml. lambdamax: 293 nm. SMILES: O=C(N[C@@H]1CC[C@@H](C2=CC=CC(F)=C2F)CN(CC(F)(F)F)C1=O)N3CCC(N4C(NC5=C4C=CC=N5)=O)CC3. InChi Code: InChI=1S/C26H27F5N6O3/c27-18-4-1-3-17(21(18)28)15-6-7-19(23(38)36(13-15)14-26(29,30)31)33-24(39)35-11-8-16(9-12-35)37-20-5-2-10-32-22(20)34-25(37)40/h1-5,10,15-16,19H,6-9,11-14H2,(H,33,39)(H,32,34,40)/t15-,19-/m1/s1. InChi Key: CGDZXLJGHVKVIE-DNVCBOLYSA-N.