CASOPITANT MESYLATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C30H35F7N4O2.CH4O3S
Molecular Weight	712.719
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CS(O)(=O)=O.C[C@@H](N(C)C(=O)N1CC[C@@H](C[C@@H]1C2=C(C)C=C(F)C=C2)N3CCN(CC3)C(C)=O)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F

InChI

InChIKey=YRFKYVWDPCOSTE-REWBLLDVSA-N

InChI=1S/C30H35F7N4O2.CH4O3S/c1-18-13-24(31)5-6-26(18)27-17-25(40-11-9-39(10-12-40)20(3)42)7-8-41(27)28(43)38(4)19(2)21-14-22(29(32,33)34)16-23(15-21)30(35,36)37;1-5(2,3)4/h5-6,13-16,19,25,27H,7-12,17H2,1-4H3;1H3,(H,2,3,4)/t19-,25+,27-;/m1./s1

HIDE SMILES / InChI

Molecular Formula	CH4O3S
Molecular Weight	96.106
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C30H35F7N4O2
Molecular Weight	616.6133
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	3 / 3
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24106886 | http://www.fiercebiotech.com/biotech/glaxosmithkline-announces-new-drug-application-and-phase-iii-results-for-rezonic-zunrisa
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/19445564 | http://adisinsight.springer.com/drugs/800018590

Casopitant (GW679769) is a novel substituted piperidine derivative that competitively binds with NK1 receptors. The full occupancy of the receptor by their piperidine compound inhibits its binding with tachykinin neurotransmitters, including SP. Casopitant, in a series of in vitro and in vivo experimentations, has exhibited a potent NK1 receptor antagonism. On 29 May 2008, GlaxoSmithKline announced the submission of a new drug application to the FDA for intravenous and oral formulations of casopitant mesylate. This drug was proposed for the prevention of chemotherapy-induced nausea and vomiting as an add-on therapy to the standard dual therapy of 5-HT3 receptor antagonists + dexamethasone. The submission also included a proposed indication for postoperative nausea and vomiting prevention. Rezonic™ is the proposed trade name for casopitant mesylate in the United States; Zunrisa™ is the proposed trade name for casopitant mesylate for GlaxoSmithKline’s global group of companies. In September 2009, GlaxoSmithKline decided to discontinue all regulatory filings for casopitant based on an estimate of the amount of additional safety data.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Neurokinin 1 receptor 35 Target ID: CHEMBL249 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24106886	Antagonist 2778		10.2 null [pKi]
Cytochrome P450 3A4 127 Target ID: CHEMBL340 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21149541	Inhibitor 8297		9.86 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Postoperative nausea and vomiting 29 Sources: http://adisinsight.springer.com/drugs/800018590 https://clinicaltrials.gov/ct2/show/NCT00334152	Palliative		Phase III 656	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Novel neurokinin-1 antagonists as antiemetics for the treatment of chemotherapy-induced emesis.	2006 Apr 1	18632487
Pharmacokinetics and brain penetration of casopitant, a potent and selective neurokinin-1 receptor antagonist, in the ferret.	2008 Sep	18556439
Disposition and metabolism of radiolabeled casopitant in humans.	2009 Aug	19420128
Antiemetic control: toward a new standard of care for emetogenic chemotherapy.	2009 Mar	19284365
Effect of casopitant, a novel NK-1 antagonist, on the pharmacokinetics of dolasetron and granisetron.	2009 Sep	19205754
Ketoconazole and rifampin significantly affect the pharmacokinetics, but not the safety or QTc interval, of casopitant, a neurokinin-1 receptor antagonist.	2010 Aug	20124517
Phase II study to evaluate the safety and efficacy of the oral neurokinin-1 receptor antagonist casopitant (GW679769) administered with ondansetron for the prevention of postoperative and postdischarge nausea and vomiting in high-risk patients.	2010 Jul	20526194
Effect of casopitant, a novel NK-1 receptor antagonist, on the pharmacokinetics and pharmacodynamics of steady-state warfarin.	2010 May	20220045
Casopitant improves the quality of life in patients receiving highly emetogenic chemotherapy.	2010 Nov	19882176
Management of chemotherapy-induced nausea and vomiting.	2010 Sep-Oct	21128556
A novel and integrated approach for the identification and characterization of drug-induced cardiac toxicity in the dog.	2011 Feb	21422262
Why receptor reserve matters for neurokinin1 (NK1) receptor antagonists.	2013 Dec	24106886

Patents

Sample Use Guides

In Vivo Use Guide

A single 100 or 150 mg dose schedule of casopitant, orally or intravenously

Route of Administration: Other

In Vitro Use Guide

Casopitant inhibited CYP3A4 activity in human liver microsomes with an IC50 lower than 10 uM.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:30:34 UTC 2023` Edited by `admin` on `Fri Dec 15 16:30:34 UTC 2023`
Record UNII	7VSV9BL497
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

CASOPITANT MESYLATE

Official Name

English

CASOPITANT MESYLATE [USAN]

Common Name

English

1-PIPERIDINECARBOXAMIDE, 4-(4-ACETYL-1-PIPERAZINYL)-N-((1R)-1-(3,5-BIS(TRIFLUOROMETHYL)PHENYL)ETHYL)-2-(4-FLUORO-2-METHYLPHENYL)-N-METHYL-, (2R,4S)-, MONOMETHANESULFONATE

Common Name

English

(2R, 4S)-4-(4-ACETYL-PIPERAZIN-1-YL)-2-(4-FLUORO-2-METHYL-PHENYL)-PIPERIDINE-1-CARBOXYLIC ACID ((1R)-1-(3,5-BIS-TRIFLUOROMETHYL-PHENYL)-ETHYL)-METHYLAMIDE METHANESULFONATE

Common Name

English

Casopitant mesilate [WHO-DD]

Common Name

English

GW-679769B

Code

English

CASOPITANT MESILATE

Common Name

English

REZONIC

Brand Name

English

CASOPITANT MESILATE [MART.]

Common Name

English

GW679769B

Code

English

(2R,4S)-4-(4-Acetylpiperazin-1-yl)-N-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl]-2-(4-fluoro-2-methylphenyl)-N-methylpiperidine-1-carboxamide methanesulfonate

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C265