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Details

Stereochemistry ABSOLUTE
Molecular Formula C26H28F7N5O2.ClH
Molecular Weight 611.983
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of L-760735F HYDROCHLORIDE

SMILES

Cl.C[C@@H](O[C@H]1OCCN(CC2=C(CN(C)C)N=NN2)[C@H]1C3=CC=C(F)C=C3)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F

InChI

InChIKey=VZBKOBSSEVXFNF-QIRDZIKRSA-N
InChI=1S/C26H28F7N5O2.ClH/c1-15(17-10-18(25(28,29)30)12-19(11-17)26(31,32)33)40-24-23(16-4-6-20(27)7-5-16)38(8-9-39-24)14-22-21(13-37(2)3)34-36-35-22;/h4-7,10-12,15,23-24H,8-9,13-14H2,1-3H3,(H,34,35,36);1H/t15-,23+,24-;/m1./s1

HIDE SMILES / InChI
Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE
Molecular Formula C26H28F7N5O2
Molecular Weight 575.5216
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 3 / 3
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/9733503 | https://www.ncbi.nlm.nih.gov/pubmed/11595206 | https://www.ncbi.nlm.nih.gov/pubmed/15875166 | https://www.ncbi.nlm.nih.gov/pubmed/26690860

L-760735 is a non-peptide substance P receptor (Neurokinin 1 (NK1) receptor) antagonist. It exerts anxiolytic, antidepressant and antinociceptive actions in animals. Merck was developing an L- 760735 as a potential antidepressant.

CNS Activity

Originator

Merck
216
Curator's Comment: # Merck & Co

Approval Year

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Antagonist
2778
 0.3 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Preclinical
Unknown

Approved Use

Unknown
Primary
Preclinical
Unknown

Approved Use

Unknown
Primary
Preclinical
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
An NK1 receptor antagonist affects the circadian regulation of locomotor activity in golden hamsters.
1998 Jul 27
Distinct mechanism for antidepressant activity by blockade of central substance P receptors.
1998 Sep 11
Stress-induced C-fos expression in the rat locus coeruleus is dependent on neurokinin 1 receptor activation.
1999
The substance P antagonist L-760,735 inhibits stress-induced NK(1) receptor internalisation in the basolateral amygdala.
1999 Nov 27
Intra-amygdala injection of the substance P [NK(1) receptor] antagonist L-760735 inhibits neonatal vocalisations in guinea-pigs.
2001 Jul
The selective neurokinin 1 receptor antagonist R116301 modulates photic responses of the hamster circadian system.
2001 Mar
Comparison of the phenotype of NK1R-/- mice with pharmacological blockade of the substance P (NK1 ) receptor in assays for antidepressant and anxiolytic drugs.
2001 Nov
Anxiolytic actions of the substance P (NK1) receptor antagonist L-760735 and the 5-HT1A agonist 8-OH-DPAT in the social interaction test in gerbils.
2001 Oct 12
Chronic substance P (NK1) receptor antagonist and conventional antidepressant treatment increases burst firing of monoamine neurones in the locus coeruleus.
2002
Substance P (neurokinin 1) receptor antagonists enhance dorsal raphe neuronal activity.
2002 Sep 1
The substance P (NK1) receptor antagonist L-760735 inhibits fear conditioning in gerbils.
2003 Mar
Chronic psychosocial stress in tree shrews: effect of the substance P (NK1 receptor) antagonist L-760735 and clomipramine on endocrine and behavioral parameters.
2005 Sep
Substance P Receptor Antagonist Suppresses Inflammatory Cytokine Expression in Human Disc Cells.
2015 Aug 15
Role of neurokinin type 1 receptor in nociception at the periphery and the spinal level in the rat.
2016 Mar
Patents

Patents

WO1995018124A1
2

Sample Use Guides

In Vivo Use Guide
Tree shrews were subjected to a 7-day period of psychosocial stress before receiving daily oral administration of L-760735 (10 mg/kg/day)
Route of Administration: Oral
In Vitro Use Guide
Curator's Comment: Treatment of human intervertebral disc cells with L-760735 was able to suppress expression of IL-1β, IL-6, and IL-8 in a dose-dependent manner.
Unknown
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:51:46 GMT 2023
Edited
by admin
on Fri Dec 15 15:51:46 GMT 2023
Record UNII
E4C3XGZ4U7
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
L-760735F HYDROCHLORIDE
Code English
1H-1,2,3-TRIAZOLE-4-METHANAMINE, 5-(((2R,3S)-2-((1R)-1-(3,5-BIS(TRIFLUOROMETHYL)PHENYL)ETHOXY)-3-(4-FLUOROPHENYL)-4-MORPHOLINYL)METHYL)-N,N-DIMETHYL-, HYDROCHLORIDE (1:1)
Systematic Name English
5-((2-(1-(3,5-BIS(TRIFLUOROMETHYL)PHENYL)ETHOXY)-3-(4-FLUOROPHENYL)-4-MORPHOLINYL)METHYL)-N,N-DIMETHYL-1H-1,2,3-TRIAZOLE-4-METHANAMINE HYDROCHLORIDE, 2R-(2AR*,3A)
Common Name English
1H-1,2,3-TRIAZOLE-4-METHANAMINE, 5-(((2R,3S)-2-((1R)-1-(3,5-BIS(TRIFLUOROMETHYL)PHENYL)ETHOXY)-3-(4-FLUOROPHENYL)-4-MORPHOLINYL)METHYL)-N,N-DIMETHYL-, MONOHYDROCHLORIDE
Common Name English
Code System Code Type Description
PUBCHEM
9809076
Created by admin on Fri Dec 15 15:51:46 GMT 2023 , Edited by admin on Fri Dec 15 15:51:46 GMT 2023
PRIMARY
EPA CompTox
DTXSID30430977
Created by admin on Fri Dec 15 15:51:46 GMT 2023 , Edited by admin on Fri Dec 15 15:51:46 GMT 2023
PRIMARY
FDA UNII
E4C3XGZ4U7
Created by admin on Fri Dec 15 15:51:46 GMT 2023 , Edited by admin on Fri Dec 15 15:51:46 GMT 2023
PRIMARY
CAS
188923-01-5
Created by admin on Fri Dec 15 15:51:46 GMT 2023 , Edited by admin on Fri Dec 15 15:51:46 GMT 2023
PRIMARY
Related Record Type Details
Structure of L-760735F
PARENT -> SALT/SOLVATE
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