WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H319680
CAS#: 1289023-67-1 (free base)
Description: Rimegepant, also known as BMS-927711 and BHV-3000, is a potent, selective, competitive, and orally active calcitonin gene-related peptide (CGRP) antagonist in clinical trials for treating migraines. Rimegepant has shown in vivo efficacy without vasoconstriction effect. BMS-927711 is superior to placebo at several different doses (75 mg, 150 mg, and 300 mg) and has an excellent tolerability profile.
Hodoodo Cat#: H319680
Name: Rimegepant
CAS#: 1289023-67-1 (free base)
Chemical Formula: C28H28F2N6O3
Exact Mass: 534.22
Molecular Weight: 534.570
Elemental Analysis: C, 62.91; H, 5.28; F, 7.11; N, 15.72; O, 8.98
Related CAS #: 1289023-67-1 (free base) 1374024-48-2 (0.5 sulfate 1.5 hydrate) 1642783-82-1 (0.5 sulfate) 2377164-85-5 (0.5 sulfate 3 hydrate)
Synonym: BHV-3000; BHV 3000; BHV3000; BMS-927711; BMS 927711; BMS927711; Rimegepant
IUPAC/Chemical Name: (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
InChi Key: KRNAOFGYEFKHPB-ANJVHQHFSA-N
InChi Code: InChI=1S/C28H28F2N6O3/c29-20-6-1-4-17(23(20)30)18-8-9-22(25-19(24(18)31)5-2-12-32-25)39-28(38)35-14-10-16(11-15-35)36-21-7-3-13-33-26(21)34-27(36)37/h1-7,12-13,16,18,22,24H,8-11,14-15,31H2,(H,33,34,37)/t18-,22+,24-/m0/s1
SMILES Code: FC1=CC=CC([C@H]2[C@H](N)C(C=CC=N3)=C3[C@H](OC(N4CCC(N5C6=C(N=CC=C6)NC5=O)CC4)=O)CC2)=C1F
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info:
| Biological target: | Rimegepant (BMS-927711) is a calcitonin gene-related peptide (CGRP) receptor antagonist with a Ki of 0.027 nM and an IC50 of 0.14 nM for hCGRP receptor. |
| In vitro activity: | Rimegepant antagonized signaling through both the CGRP and AMY1 receptors but was approximately 30-fold more effective at blocking the CGRP receptor (p < 0.05; unpaired t-test, t = 13.32, df = 6). Interestingly, at the AMY1 receptor, rimegepant was approximately fourfold less effective at antagonizing amylin signaling than αCGRP signaling, with mean pKB values ± s.e.m of 7.48 ± 0.19 (n = 5, amylin) and 8.07 ± 0.11 (n = 4, αCGRP), respectively (p < 0.05; unpaired t-test, t = 2.57, df = 7). The ability of rimegepant to block AM signaling at the human AM1 and AM2 receptors was determined. Rimegepant (10 µM) did not significantly antagonize AM signaling at either the AM1 or AM2 receptors (Table 1). Reference: Front Pharmacol. 2020; 11: 1240. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468408/ |
| In vivo activity: | First, rimegepant (100mg/kg) was tested in the 60-minute MCAO model but encountered 75% (6/8) mortality compared with none (0/8) in the vehicle group (p = 0.007, Fisher exact test; Fig 3). The only 2 surviving mice in the rimegepant group had infarct volumes of 85 and 109mm3 and neurological deficit scores of 13 and 16, compared with a median infarct volume of 62mm3 and neurological deficit score of 11 in the vehicle group. Once again, the residual collateral CBF in rimegepant-treated animals was lower than in the vehicle group (p = 0.014, 2-way ANOVA for repeated measures). Reference: Ann Neurol. 2020 Oct; 88(4): 771–784. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540520/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 43.3 | 81.06 | |
| DMSO:PBS (pH 7.2) (1:4) | 0.2 | 0.37 | |
| DMF | 5.0 | 9.35 | |
| Ethanol | 3.7 | 6.83 |
The following data is based on the product molecular weight 534.57 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Pan KS, Siow A, Hay DL, Walker CS. Antagonism of CGRP Signaling by Rimegepant at Two Receptors. Front Pharmacol. 2020 Aug 20;11:1240. doi: 10.3389/fphar.2020.01240. PMID: 32973499; PMCID: PMC7468408. 2. Mulder IA, Li M, de Vries T, Qin T, Yanagisawa T, Sugimoto K, van den Bogaerdt A, Danser AHJ, Wermer MJH, van den Maagdenberg AMJM, MaassenVanDenBrink A, Ferrari MD, Ayata C. Anti-migraine Calcitonin Gene-Related Peptide Receptor Antagonists Worsen Cerebral Ischemic Outcome in Mice. Ann Neurol. 2020 Oct;88(4):771-784. doi: 10.1002/ana.25831. Epub 2020 Aug 7. PMID: 32583883; PMCID: PMC7540520. 3. Luo G, Chen L, Conway CM, Denton R, Keavy D, Signor L, Kostich W, Lentz KA, Santone KS, Schartman R, Browning M, Tong G, Houston JG, Dubowchik GM, Macor JE. 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. doi: 10.1021/jm3013147. Epub 2012 Nov 15. PMID: 23153230. |
| In vitro protocol: | 1. Pan KS, Siow A, Hay DL, Walker CS. Antagonism of CGRP Signaling by Rimegepant at Two Receptors. Front Pharmacol. 2020 Aug 20;11:1240. doi: 10.3389/fphar.2020.01240. PMID: 32973499; PMCID: PMC7468408. |
| In vivo protocol: | 1. Mulder IA, Li M, de Vries T, Qin T, Yanagisawa T, Sugimoto K, van den Bogaerdt A, Danser AHJ, Wermer MJH, van den Maagdenberg AMJM, MaassenVanDenBrink A, Ferrari MD, Ayata C. Anti-migraine Calcitonin Gene-Related Peptide Receptor Antagonists Worsen Cerebral Ischemic Outcome in Mice. Ann Neurol. 2020 Oct;88(4):771-784. doi: 10.1002/ana.25831. Epub 2020 Aug 7. PMID: 32583883; PMCID: PMC7540520. 2. Luo G, Chen L, Conway CM, Denton R, Keavy D, Signor L, Kostich W, Lentz KA, Santone KS, Schartman R, Browning M, Tong G, Houston JG, Dubowchik GM, Macor JE. 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. doi: 10.1021/jm3013147. Epub 2012 Nov 15. PMID: 23153230. |
1: Pan KS, Siow A, Hay DL, Walker CS. Antagonism of CGRP Signaling by Rimegepant at Two Receptors. Front Pharmacol. 2020 Aug 20;11:1240. doi: 10.3389/fphar.2020.01240. PMID: 32973499; PMCID: PMC7468408.
2: DeFalco AP, Lazim R, Cope NE. Rimegepant Orally Disintegrating Tablet for Acute Migraine Treatment: A Review. Ann Pharmacother. 2020 Sep 10:1060028020954800. doi: 10.1177/1060028020954800. Epub ahead of print. PMID: 32909437.
3: Rimegepant (Nurtec ODT) for Acute Treatment of Migraine. JAMA. 2020 Sep 1;324(9):890-891. doi: 10.1001/jama.2020.8493. PMID: 32870296.
4: Berman G, Croop R, Kudrow D, Halverson P, Lovegren M, Thiry AC, Conway CM, Coric V, Lipton RB. Safety of Rimegepant, an Oral CGRP Receptor Antagonist, Plus CGRP Monoclonal Antibodies for Migraine. Headache. 2020 Aug 16;60(8):1734–42. doi: 10.1111/head.13930. Epub ahead of print. PMID: 32799325; PMCID: PMC7496574.
5: Doty EG, Krege JH, Pohl G, Case M, Dowsett SA, Tepper SJ. Pain Freedom at 2 to 8 Hours With Lasmiditan: A Comparison With Rimegepant and Ubrogepant. Headache. 2020 Jul 22. doi: 10.1111/head.13899. Epub ahead of print. PMID: 32700321.
6: Gasparini S, Torino C, Branca D, Ferlazzo E, Aguglia U. Testing rimegepant for migraine-time to revise the trial design? Lancet. 2020 Jun 20;395(10241):1901. doi: 10.1016/S0140-6736(20)30241-5. PMID: 32563366.
7: Croop R, Goadsby PJ, Stock DA, Lipton RB. Testing rimegepant for migraine- time to revise the trial design? - Authors' reply. Lancet. 2020 Jun 20;395(10241):1901-1902. doi: 10.1016/S0140-6736(20)30231-2. PMID: 32563365.
8: Rimegepant (Nurtec ODT) for acute treatment of migraine. Med Lett Drugs Ther. 2020 May 4;62(1597):70-72. PMID: 32555113.
9: Scott LJ. Rimegepant: First Approval. Drugs. 2020 May;80(7):741-746. doi: 10.1007/s40265-020-01301-3. PMID: 32270407.
10: Gao B, Yang Y, Wang Z, Sun Y, Chen Z, Zhu Y, Wang Z. Efficacy and Safety of Rimegepant for the Acute Treatment of Migraine: Evidence From Randomized Controlled Trials. Front Pharmacol. 2020 Jan 24;10:1577. doi: 10.3389/fphar.2019.01577. PMID: 32038251; PMCID: PMC6992660.
11: McCarthy L. Oral rimegepant increased freedom from pain and from most bothersome symptom at 2 h in acute migraine. Ann Intern Med. 2019 Nov 19;171(10):JC59. doi: 10.7326/ACPJ201911190-059. PMID: 31739342.
12: McCarthy L. Orally disintegrating rimegepant increased freedom from pain and from most bothersome symptom at 2 h in acute migraine. Ann Intern Med. 2019 Nov 19;171(10):JC58. doi: 10.7326/ACPJ201911190-058. PMID: 31739341.
13: Ju C, Spiegel R, Radecki R, Swaminathan AK. Rimegepant in the Treatment of Migraine Headache: The Importance of Comparator Treatments: November 2019 Annals of Emergency Medicine Journal Club. Ann Emerg Med. 2019 Nov;74(5):721-723. doi: 10.1016/j.annemergmed.2019.09.014. PMID: 31668246.
14: Edvinsson L. Rimegepant oral disintegrating tablet for migraine. Lancet. 2019 Aug 31;394(10200):711-712. doi: 10.1016/S0140-6736(19)31611-3. Epub 2019 Jul 13. PMID: 31311675.
15: Croop R, Goadsby PJ, Stock DA, Conway CM, Forshaw M, Stock EG, Coric V, Lipton RB. Efficacy, safety, and tolerability of rimegepant orally disintegrating tablet for the acute treatment of migraine: a randomised, phase 3, double-blind, placebo-controlled trial. Lancet. 2019 Aug 31;394(10200):737-745. doi: 10.1016/S0140-6736(19)31606-X. Epub 2019 Jul 13. PMID: 31311674.
16: Lipton RB, Croop R, Stock EG, Stock DA, Morris BA, Frost M, Dubowchik GM, Conway CM, Coric V, Goadsby PJ. Rimegepant, an Oral Calcitonin Gene-Related Peptide Receptor Antagonist, for Migraine. N Engl J Med. 2019 Jul 11;381(2):142-149. doi: 10.1056/NEJMoa1811090. PMID: 31291516.
