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Details

Stereochemistry ABSOLUTE
Molecular Formula C31H35F7N4O2
Molecular Weight 628.624
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ORVEPITANT

SMILES

[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=XWNBGDJPEXZSQM-VZOBGQTKSA-N
InChI=1S/C31H35F7N4O2/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/h4,6,12-15,19,24-25,27H,5,7-11,16-17H2,1-3H3/t19-,24+,25+,27-/m1/s1

HIDE SMILES / InChI
Molecular Formula C31H35F7N4O2
Molecular Weight 628.624
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 4 / 4
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: description was created based on several sources, including: https://www.ncbi.nlm.nih.gov/pubmed/23539641 | https://en.wikipedia.org/wiki/Orvepitant | http://adisinsight.springer.com/drugs/800020168 | https://www.ncbi.nlm.nih.gov/pubmed/24075145

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

GlaxoSmithKline
198
Curator's Comment: https://www.google.com/patents/EP2297152A1

Approval Year

Unknown
127998
Targets

Targets

Primary TargetPharmacologyConditionPotency
Antagonist
2737
 10.2 null [pKi]
Modulator
817
 2.27 µM [Ki]
Modulator
817
 0.94 µM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase II
1133
Unknown

Approved Use

Unknown
Primary
Phase II
1133
Unknown

Approved Use

Unknown
Primary
Phase II
1133
Unknown

Approved Use

Unknown
Primary
Phase II
1133
Unknown

Approved Use

Unknown
Doses

Doses

DosePopulationAdverse events​
30 mg 1 times / day multiple, oral (unknown)
Highest studied dose,Studied dose
Dose: 30 mg, 1 times / day
Route: oral
Route: multiple
Dose: 30 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/32034016
unhealthy
n = 16
Health Status: unhealthy
Condition: cancer
Sex: M+F
Food Status: UNKNOWN
Population Size: 16
Sources:
https://pubmed.ncbi.nlm.nih.gov/32034016
Other AEs: Hyperhidrosis, Asthenia...
Other AEs:
Hyperhidrosis (moderate, 6.3%)
Asthenia (mild, 6.3%)
Dry mouth (mild, 6.3%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/32034016
AEs

AEs

AESignificanceDosePopulation
Asthenia mild, 6.3%
30 mg 1 times / day multiple, oral (unknown)
Highest studied dose,Studied dose
Dose: 30 mg, 1 times / day
Route: oral
Route: multiple
Dose: 30 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/32034016
unhealthy
n = 16
Health Status: unhealthy
Condition: cancer
Sex: M+F
Food Status: UNKNOWN
Population Size: 16
Sources:
https://pubmed.ncbi.nlm.nih.gov/32034016
Dry mouth mild, 6.3%
30 mg 1 times / day multiple, oral (unknown)
Highest studied dose,Studied dose
Dose: 30 mg, 1 times / day
Route: oral
Route: multiple
Dose: 30 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/32034016
unhealthy
n = 16
Health Status: unhealthy
Condition: cancer
Sex: M+F
Food Status: UNKNOWN
Population Size: 16
Sources:
https://pubmed.ncbi.nlm.nih.gov/32034016
Hyperhidrosis moderate, 6.3%
30 mg 1 times / day multiple, oral (unknown)
Highest studied dose,Studied dose
Dose: 30 mg, 1 times / day
Route: oral
Route: multiple
Dose: 30 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/32034016
unhealthy
n = 16
Health Status: unhealthy
Condition: cancer
Sex: M+F
Food Status: UNKNOWN
Population Size: 16
Sources:
https://pubmed.ncbi.nlm.nih.gov/32034016
Sourcing

Sourcing

Vendor/AggregatorIDURL
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
Matrix Scientific
148038
http://www.matrixscientific.com/148038.html
MolPort
MolPort-042-665-725
https://www.molport.com/shop/molecule-link/MolPort-042-665-725
eMolecules
300580143
https://orderbb.emolecules.com/search/#?query=300580143
eMolecules
44848352
https://orderbb.emolecules.com/search/#?query=44848352
eMolecules
50415089
https://orderbb.emolecules.com/search/#?query=50415089
PubMed

PubMed

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

Patents

08309553
3
20050176715
3
20110166150
3
EP2297152 A1
3

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
Created
by admin
on Fri Dec 16 21:19:41 UTC 2022
Edited
by admin
on Fri Dec 16 21:19:41 UTC 2022
Record UNII
IIU6V0W3JD
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ORVEPITANT
INN   USAN  
INN   USAN  
Official Name English
orvepitant [INN]
Common Name English
ORVEPITANT [USAN]
Common Name English
GW-823296
Common Name English
(2R,4S)-N-{(1R)-1-[3,5-Bis(trifluoromethyl)phenyl]ethyl}-2-(4-fluoro-2-methylphenyl)-N-methyl-4-[(8aS)-6-oxohexahydro-1H-pyrrolo[1,2-a]pyrazin-2-yl]piperidine-1-carboxamide
Common 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)-
Common Name English
GW823296X
Code English
GW-823296X
Code English
Classification Tree Code System Code
NCI_THESAURUS C28197
Created by admin on Fri Dec 16 21:19:41 UTC 2022 , Edited by admin on Fri Dec 16 21:19:41 UTC 2022
NCI_THESAURUS C265
Created by admin on Fri Dec 16 21:19:41 UTC 2022 , Edited by admin on Fri Dec 16 21:19:41 UTC 2022
Code System Code Type Description
DRUG BANK
DB12427
Created by admin on Fri Dec 16 21:19:41 UTC 2022 , Edited by admin on Fri Dec 16 21:19:41 UTC 2022
PRIMARY
USAN
WW-127
Created by admin on Fri Dec 16 21:19:41 UTC 2022 , Edited by admin on Fri Dec 16 21:19:41 UTC 2022
PRIMARY
NCI_THESAURUS
C90613
Created by admin on Fri Dec 16 21:19:41 UTC 2022 , Edited by admin on Fri Dec 16 21:19:41 UTC 2022
PRIMARY
PUBCHEM
9852175
Created by admin on Fri Dec 16 21:19:41 UTC 2022 , Edited by admin on Fri Dec 16 21:19:41 UTC 2022
PRIMARY
INN
8684
Created by admin on Fri Dec 16 21:19:41 UTC 2022 , Edited by admin on Fri Dec 16 21:19:41 UTC 2022
PRIMARY
FDA UNII
IIU6V0W3JD
Created by admin on Fri Dec 16 21:19:41 UTC 2022 , Edited by admin on Fri Dec 16 21:19:41 UTC 2022
PRIMARY
CAS
579475-18-6
Created by admin on Fri Dec 16 21:19:41 UTC 2022 , Edited by admin on Fri Dec 16 21:19:41 UTC 2022
PRIMARY
WIKIPEDIA
Orvepitant
Created by admin on Fri Dec 16 21:19:41 UTC 2022 , Edited by admin on Fri Dec 16 21:19:41 UTC 2022
PRIMARY
EPA CompTox
DTXSID40973522
Created by admin on Fri Dec 16 21:19:41 UTC 2022 , Edited by admin on Fri Dec 16 21:19:41 UTC 2022
PRIMARY
ChEMBL
CHEMBL2105667
Created by admin on Fri Dec 16 21:19:41 UTC 2022 , Edited by admin on Fri Dec 16 21:19:41 UTC 2022
PRIMARY
Related Record Type Details
SUBSTANCE-P RECEPTOR
TARGET -> INHIBITOR
Structure of ORVEPITANT MALEATE
SALT/SOLVATE -> PARENT
Structure of ORVEPITANT HYDROCHLORIDE
SALT/SOLVATE -> PARENT
Related Record Type Details
Structure of ORVEPITANT
ACTIVE MOIETY
NIH
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