Ezlopitant

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MedKoo CAT#: 206100

CAS#: 147116-64-1

Description: Ezlopitant, also known CJ-11,974; is NK1 receptor antagonist. It has antiemetic and antinociceptive effects. Pfizer was developing ezlopitant for the treatment of irritable bowel syndrome but it appears to have been discontinued.


Chemical Structure

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Ezlopitant
CAS# 147116-64-1

Theoretical Analysis

MedKoo Cat#: 206100
Name: Ezlopitant
CAS#: 147116-64-1
Chemical Formula: C31H38N2O
Exact Mass: 454.29841
Molecular Weight: 454.64622
Elemental Analysis: C, 81.89; H, 8.42; N, 6.16; O, 3.52

Price and Availability

This product is not in stock, which may be available by custom synthesis. For cost-effective reason, minimum order is 1g (price is usually high, lead time is 2~3 months, depending on the technical challenge). Quote less than 1g will not be provided. To request quote, please email to sales @medkoo.com or click below button.
Note: Price will be listed if it is available in the future.

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Synonym: Ezlopitant; CJ11974; CJ-11974; CJ 11974; CJ-11, 974; CJ 11, 974; CJ11, 974;

IUPAC/Chemical Name: (2S,3S)-2-benzhydryl-N-(5-isopropyl-2-methoxybenzyl)quinuclidin-3-amine

InChi Key: XPNMCDYOYIKVGB-CONSDPRKSA-N

InChi Code: InChI=1S/C31H38N2O/c1-22(2)26-14-15-28(34-3)27(20-26)21-32-30-25-16-18-33(19-17-25)31(30)29(23-10-6-4-7-11-23)24-12-8-5-9-13-24/h4-15,20,22,25,29-32H,16-19,21H2,1-3H3/t30-,31-/m0/s1

SMILES Code: COC1=CC=C(C(C)C)C=C1CN[C@@H]2[C@H](C(C3=CC=CC=C3)C4=CC=CC=C4)N5CCC2CC5

Appearance: white 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

Preparing Stock Solutions

The following data is based on the product molecular weight 454.64622 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.

Recalculate based on batch purity %
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

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1: Muñoz M, Coveñas R. Safety of neurokinin-1 receptor antagonists. Expert Opin Drug Saf. 2013 Sep;12(5):673-85. doi: 10.1517/14740338.2013.804059. Epub 2013 May 25. PubMed PMID: 23706125.

2: Sharp TR. Calculated carbon-hydrogen bond dissociation enthalpies for predicting oxidative susceptibility of drug substance molecules. Int J Pharm. 2011 Oct 14;418(2):304-17. doi: 10.1016/j.ijpharm.2011.04.063. Epub 2011 May 14. PubMed PMID: 21575693.

3: Steensland P, Simms JA, Nielsen CK, Holgate J, Bito-Onon JJ, Bartlett SE. The neurokinin 1 receptor antagonist, ezlopitant, reduces appetitive responding for sucrose and ethanol. PLoS One. 2010 Sep 1;5(9). pii: e12527. doi: 10.1371/journal.pone.0012527. PubMed PMID: 20824145; PubMed Central PMCID: PMC2931709.

4: Prakash C, O'Donnell J, Khojasteh-Bakht SC. Metabolism, pharmacokinetics, and excretion of a nonpeptidic substance P receptor antagonist, ezlopitant, in normal healthy male volunteers: characterization of polar metabolites by chemical derivatization with dansyl chloride. Drug Metab Dispos. 2007 Jul;35(7):1071-80. Epub 2007 Apr 12. PubMed PMID: 17431029.

5: Yamamoto S, Honda M, Tanabe M, Ono H. Spinal ventral root after-discharges as a pain index: involvement of NK-1 and NMDA receptors. Brain Res. 2006 Apr 12;1082(1):115-23. Epub 2006 Feb 28. PubMed PMID: 16507302.

6: Tsuchiya M, Sakakibara A, Yamamoto M. A tachykinin NK1 receptor antagonist attenuates the 4 beta-phorbol-12-myristate-13-acetate-induced nociceptive behaviour in the rat. Eur J Pharmacol. 2005 Jan 10;507(1-3):29-34. Epub 2004 Dec 8. PubMed PMID: 15659291.

7: Giardina GA, Gagliardi S, Martinelli M. Antagonists at the neurokinin receptors--recent patent literature. IDrugs. 2003 Aug;6(8):758-72. Review. PubMed PMID: 12917772.

8: Margolis JM, Obach RS. Impact of nonspecific binding to microsomes and phospholipid on the inhibition of cytochrome P4502D6: implications for relating in vitro inhibition data to in vivo drug interactions. Drug Metab Dispos. 2003 May;31(5):606-11. PubMed PMID: 12695349.

9: Kamel AM, Zandi KS, Massefski WW. Identification of the degradation product of ezlopitant, a non-peptidic substance P antagonist receptor, by hydrogen deuterium exchange, electrospray ionization tandem mass spectrometry (ESI/MS/MS) and nuclear magnetic resonance (NMR) spectroscopy. J Pharm Biomed Anal. 2003 Apr 10;31(6):1211-22. PubMed PMID: 12667937.

10: Tsuchiya M, Fujiwara Y, Kanai Y, Mizutani M, Shimada K, Suga O, Ueda S, Watson JW, Nagahisa A. Anti-emetic activity of the novel nonpeptide tachykinin NK1 receptor antagonist ezlopitant (CJ-11,974) against acute and delayed cisplatin-induced emesis in the ferret. Pharmacology. 2002 Nov;66(3):144-52. PubMed PMID: 12372904.

11: Callahan MJ. Irritable bowel syndrome neuropharmacology. A review of approved and investigational compounds. J Clin Gastroenterol. 2002 Jul;35(1 Suppl):S58-67. Review. PubMed PMID: 12184141.

12: Evangelista S. Eziopitant. Pfizer. Curr Opin Investig Drugs. 2001 Oct;2(10):1441-3. Review. PubMed PMID: 11890362.

13: Obach RS. Mechanism of cytochrome P4503A4- and 2D6-catalyzed dehydrogenation of ezlopitant as probed with isotope effects using five deuterated analogs. Drug Metab Dispos. 2001 Dec;29(12):1599-607. PubMed PMID: 11717179.

14: Obach RS. Cytochrome P450-catalyzed metabolism of ezlopitant alkene (CJ-12,458), a pharmacologically active metabolite of ezlopitant: enzyme kinetics and mechanism of an alkene hydration reaction. Drug Metab Dispos. 2001 Jul;29(7):1057-67. PubMed PMID: 11408374.

15: Kamel A, Prakash C, Saverino C, Obach B, Fouda H. Narrow-bore high-performance liquid chromatography in combination with ionspray tandem mass spectrometry for the determination of the substance P receptor antagonist ezlopitant and its two active metabolites in plasma. J Chromatogr B Biomed Sci Appl. 2000 Oct 1;748(1):179-88. PubMed PMID: 11092597.

16: Diemunsch P, Grélot L. Potential of substance P antagonists as antiemetics. Drugs. 2000 Sep;60(3):533-46. Review. PubMed PMID: 11030465.

17: Reed-Hagen AE, Janiszewski JS, Cole RO, Obach RS. Assay of ezlopitant, a substance P receptor antagonist, and metabolites in biological matrices by gas chromatography with mass spectrometric detection: simultaneous analysis of a benzyl alcohol and alkene. J Chromatogr B Biomed Sci Appl. 2000 Jul 21;744(2):333-43. PubMed PMID: 10993522.

18: Reed-Hagen AE, Tsuchiya M, Shimada K, Wentland JA, Obach RS. Pharmacokinetics of ezlopitant, a novel non-peptidic neurokinin-1 receptor antagonist in preclinical species and metabolite kinetics of the pharmacologically active metabolites. Biopharm Drug Dispos. 1999 Dec;20(9):429-39. PubMed PMID: 10951432.

19: Obach RS. Metabolism of ezlopitant, a nonpeptidic substance P receptor antagonist, in liver microsomes: enzyme kinetics, cytochrome P450 isoform identity, and in vitro-in vivo correlation. Drug Metab Dispos. 2000 Sep;28(9):1069-76. PubMed PMID: 10950851.



Additional Information

Pfizer is developing ezlopitant , a neurokinin-1 antagonist, for the potential treatment of irritable bowel syndrome (IBS). The compound had undergone phase II trials in the US and Europe, and phase I in Japan for treatment of chemotherapy-induced emesis [290988], [320737], [329187]. A phase II, double-blind, randomized study was performed to assess the safety and efficacy of ezlopitant for the control of cisplatin-induced emesis. Treatment was well tolerated [290988]. Although the compound effectively controls emesis, it is less effective in controlling nausea, and development has been discontinued for the emesis indication [347367]. Ezlopitant has undergone a pilot study in 14 IBS patients [367631]. (source: Curr Opin Investig Drugs. 2001 Oct;2(10):1441-3.)