ORVEPITANT MALEATE

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C31H35F7N4O2.C4H4O4
Molecular Weight	744.6962
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

SMILES

OC(=O)\C=C/C(O)=O.[H][C@@]12CCC(=O)N1CCN(C2)[C@H]3CCN([C@H](C3)C4=CC=C(F)C=C4C)C(=O)N(C)[C@H](C)C5=CC(=CC(=C5)C(F)(F)F)C(F)(F)F

InChI

InChIKey=IPACOHTZCSBGBV-WUXDIRCFSA-N

InChI=1S/C31H35F7N4O2.C4H4O4/c1-18-12-23(32)4-6-26(18)27-16-24(40-10-11-41-25(17-40)5-7-28(41)43)8-9-42(27)29(44)39(3)19(2)20-13-21(30(33,34)35)15-22(14-20)31(36,37)38;5-3(6)1-2-4(7)8/h4,6,12-15,19,24-25,27H,5,7-11,16-17H2,1-3H3;1-2H,(H,5,6)(H,7,8)/b;2-1-/t19-,24+,25+,27-;/m1./s1

HIDE SMILES / InChI

Molecular Formula	C31H35F7N4O2
Molecular Weight	628.624
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	4 / 4
E/Z Centers	0
Optical Activity	UNSPECIFIED

Molecular Formula	C4H4O4
Molecular Weight	116.0722
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

Description

Orvepitant is a novel generation brain penetrant, selective and potent, small molecule NK-1 receptor antagonist. Orvepitant’s (GW823296) mode of action and developability characteristics made it a suitable development candidate for the treatment of common anxiety disorders, posttraumatic stress disorder and major depressive disorder. It’s in phase II clinical trials as an effective inhibitor of itch-associated response.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Neurokinin 1 receptor 35	Antagonist 2,778	10.2 null [pKi]
Platelet activating factor receptor 20	Modulator 828	2.27 µM [Ki]
Sigma opioid receptor 63	Modulator 828	0.94 µM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Major depressive disorder 173	Primary	Phase II 1,132	Unknown
Post-traumatic stress disorder 20	Primary	Phase II 1,132	Unknown
Pruritus 29	Primary	Phase II 1,132	Unknown
Chronic refractory cough 3	Primary	Phase II 1,132	Unknown

Doses

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Dose	Population	Adverse events
30 mg 1 times / day multiple, oral (unknown) Highest studied dose,Studied dose	unhealthy n = 16	Other AEs: Hyperhidrosis, Asthenia...

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AEs

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AE	Significance	Dose	Population
Asthenia	mild, 6.3%	30 mg 1 times / day multiple, oral (unknown) Highest studied dose,Studied dose	unhealthy n = 16
Dry mouth	mild, 6.3%	30 mg 1 times / day multiple, oral (unknown) Highest studied dose,Studied dose	unhealthy n = 16
Hyperhidrosis	moderate, 6.3%	30 mg 1 times / day multiple, oral (unknown) Highest studied dose,Studied dose	unhealthy n = 16

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Sourcing

Sourcing

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Vendor/Aggregator	ID	URL
Angene	AGN-PC-0SOQO4	http://www.angenechemical.com/productshow/AGN-PC-0SOQO4.html
Axon MedChem	1618	https://www.axonmedchem.com/product/1618
BOC Sciences	579475-18-6	http://www.bocsci.com/description.asp?cas=579475-18-6
Compound Cloud	44225656
Compound Cloud	9852175

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PubMed

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Title	Date	PubMed
Full central neurokinin-1 receptor blockade is required for efficacy in depression: evidence from orvepitant clinical studies.	2013 May	23539641
Identification, biological characterization and pharmacophoric analysis of a new potent and selective NK1 receptor antagonist clinical candidate.	2013 Nov 1	24075145
Neurokinin-1 receptor antagonist orvepitant is an effective inhibitor of itch-associated response in a Mongolian gerbil model of scratching behaviour.	2014 Nov	25078633

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Patents

Sample Use Guides

In Vivo Use Guide

10 mg/day, 20 mg/day and 30 mg/day

Route of Administration: Oral

In Vitro Use Guide

Orvepitant (0.3–10 nM) pre-incubated for 1 h at 37 C before adding the agonist substance P produced a non-surmountable antagonism of agonist CRC with apparent pKB values of 10.30 ± 0.30 (n = 4).

Substance Class	Chemical
Record UNII	HAX0H28B6W
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ORVEPITANT MALEATE

Official Name

English

1-PIPERIDINECARBOXAMIDE, N-((1R)-1-(3,5-BIS(TRIFLUOROMETHYL)PHENYL)ETHYL)-2-(4-FLUORO-2-METHYLPHENYL)-4-((8AS)-HEXAHYDRO-6-OXOPYRROLO(1,2-A)PYRAZIN-2(1H)-YL)-N-METHYL-, (2R,4S)-, (2Z)-2-BUTENEDIOATE (1:1)

Common Name

English

GW823296B

Code

English

GW-823296B

Code

English

(2R,4S)-N-{(1R)-1-[3,5-Bis(trifluoromethyl)phenyl]ethyl}-2-(4-fluoro-2-methylphenyl)-N-methyl-4-[(8aS)-6-oxohexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl]piperidine-1-carboxamide hydrogen mono[(2Z)-but-2-enedioate]

Common Name

English

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