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Details

Stereochemistry ABSOLUTE
Molecular Formula C24H22N4O2
Molecular Weight 398.4571
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of L-365260

SMILES

CN1C2=C(C=CC=C2)C(=N[C@@H](NC(=O)NC3=CC(C)=CC=C3)C1=O)C4=CC=CC=C4

InChI

InChIKey=KDFQABSFVYLGPM-QFIPXVFZSA-N
InChI=1S/C24H22N4O2/c1-16-9-8-12-18(15-16)25-24(30)27-22-23(29)28(2)20-14-7-6-13-19(20)21(26-22)17-10-4-3-5-11-17/h3-15,22H,1-2H3,(H2,25,27,30)/t22-/m0/s1

HIDE SMILES / InChI
Molecular Formula C24H22N4O2
Molecular Weight 398.4571
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
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/10657473 | https://www.ncbi.nlm.nih.gov/pubmed/12566175 | https://www.ncbi.nlm.nih.gov/pubmed/9892884

L-365,260 is an antagonist of gastrin and brain CCK-B receptor. In vivo, oral administration of L-365,260 antagonized gastrin-stimulated acid secretion. L-365,260 is used as a tool compound to investigate gastrin and brain CCK-B and their role in psysiology and disease. In a double-blind placebo-controlled study L-365,260 did not augment the analgesic effect of morphine in subjects with chronic neuropathic pain. Preclinical studies demonstrated modes activity of L-365,260 in models of anxiety and ulcers.

CNS Activity

Originator

Merck
216
Curator's Comment: # Merck

Approval Year

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Antagonist
2778
 2.0 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
Phase II
1132
Unknown

Approved Use

Unknown
Primary
Preclinical
Unknown

Approved Use

Unknown
Primary
Preclinical
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
294.6 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/8728342
25 mg 4 times / day single, oral
dose: 25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
L-365260 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
269.6 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/8728342
25 mg 4 times / day multiple, oral
dose: 25 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
L-365260 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
503.2 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/8728342
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
L-365260 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
846.7 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/8728342
25 mg 4 times / day single, oral
dose: 25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
L-365260 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
2287 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/8728342
25 mg 4 times / day multiple, oral
dose: 25 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
L-365260 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
2807.9 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/8728342
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
L-365260 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
9.9 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/8728342
25 mg 4 times / day multiple, oral
dose: 25 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
L-365260 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
11.13 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/8728342
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
L-365260 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
90 mg 4 times / day multiple, oral (total)
Studied dose
Dose: 90 mg, 4 times / day
Route: oral
Route: multiple
Dose: 90 mg, 4 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/7786960/
unhealthy, ADULT
n = 40
Health Status: unhealthy
Condition: panic disorder
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 40
Sources:
https://pubmed.ncbi.nlm.nih.gov/7786960/
Other AEs: Orthostatic dizziness, Alanine aminotransferase increase...
Other AEs:
Orthostatic dizziness (11%)
Alanine aminotransferase increase (6 patients)
Aspartate aminotransferase increase (6 patients)
Sources:
https://pubmed.ncbi.nlm.nih.gov/7786960/
AEs

AEs

AESignificanceDosePopulation
Orthostatic dizziness 11%
90 mg 4 times / day multiple, oral (total)
Studied dose
Dose: 90 mg, 4 times / day
Route: oral
Route: multiple
Dose: 90 mg, 4 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/7786960/
unhealthy, ADULT
n = 40
Health Status: unhealthy
Condition: panic disorder
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 40
Sources:
https://pubmed.ncbi.nlm.nih.gov/7786960/
Alanine aminotransferase increase 6 patients
90 mg 4 times / day multiple, oral (total)
Studied dose
Dose: 90 mg, 4 times / day
Route: oral
Route: multiple
Dose: 90 mg, 4 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/7786960/
unhealthy, ADULT
n = 40
Health Status: unhealthy
Condition: panic disorder
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 40
Sources:
https://pubmed.ncbi.nlm.nih.gov/7786960/
Aspartate aminotransferase increase 6 patients
90 mg 4 times / day multiple, oral (total)
Studied dose
Dose: 90 mg, 4 times / day
Route: oral
Route: multiple
Dose: 90 mg, 4 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/7786960/
unhealthy, ADULT
n = 40
Health Status: unhealthy
Condition: panic disorder
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 40
Sources:
https://pubmed.ncbi.nlm.nih.gov/7786960/
PubMed

PubMed

TitleDatePubMed
Development of a class of selective cholecystokinin type B receptor antagonists having potent anxiolytic activity.
1990 Sep
The human brain cholecystokinin-B/gastrin receptor. Cloning and characterization.
1993 Apr 15
Gastrin effects on isolated rat enterochromaffin-like cells in primary culture.
1994 Oct
Cholecystokinin and anxiety in normal volunteers: an investigation of the anxiogenic properties of pentagastrin and reversal by the cholecystokinin receptor subtype B antagonist L-365,260.
1995 Mar
The selective cholecystokininB receptor antagonist L-365,260 diminishes the expression of naloxone-induced morphine withdrawal symptoms in normal and neuropathic rats.
1998
Pharmacological analysis of CCK(2) receptor ligands using COS-7 and SK-N-MC cells, expressing the human CCK(2) receptor.
2002 Jan 15
Characterization of gastrin-induced proangiogenic effects in vivo in orthotopic U373 experimental human glioblastomas and in vitro in human umbilical vein endothelial cells.
2004 Dec 15
Role of cholecystokinin in anorexia induction following oral exposure to the 8-ketotrichothecenes deoxynivalenol, 15-acetyldeoxynivalenol, 3-acetyldeoxynivalenol, fusarenon X, and nivalenol.
2014 Apr
Patents

Patents

EP-0517412-A1
1
JPH0525146A
1

Sample Use Guides

In Vivo Use Guide
Curator's Comment: https://www.ncbi.nlm.nih.gov/pubmed/2721567
In study of neuropathic pain L-365260 was administered orally at 30 mg daily dose or 120 mg daily in three divided doses. For in vivo studies of effect of L-365260 on pentagastrin-induced gastric secretion in mice compound was administred at 0.1 mg/kg intraduodenally or orrally. The ED50 value of L-365260 as antagonist of gastrin was 0.029 mg/kg p.o
Route of Administration: Other
In Vitro Use Guide
Binging of L-365260 to CCK from membranes of pancreas and brain membranes was measured using 125I-labeled CCK as a competitive radioligand. L-365260 exhibited nanomolar potency in displacing the specific binding of [125I]gastrin and [125I]CCK to guinea pig gastric glands and brain tissue.
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:30:30 GMT 2023
Edited
by admin
on Fri Dec 15 15:30:30 GMT 2023
Record UNII
370JHF4586
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
L-365260
Common Name English
UREA, N-(2,3-DIHYDRO-1-METHYL-2-OXO-5-PHENYL-1H-1,4-BENZODIAZEPIN-3-YL)-N'-(3-METHYLPHENYL)-, (R)-
Systematic Name English
Code System Code Type Description
EPA CompTox
DTXSID30922600
Created by admin on Fri Dec 15 15:30:30 GMT 2023 , Edited by admin on Fri Dec 15 15:30:30 GMT 2023
PRIMARY
FDA UNII
370JHF4586
Created by admin on Fri Dec 15 15:30:30 GMT 2023 , Edited by admin on Fri Dec 15 15:30:30 GMT 2023
PRIMARY
CAS
118101-09-0
Created by admin on Fri Dec 15 15:30:30 GMT 2023 , Edited by admin on Fri Dec 15 15:30:30 GMT 2023
PRIMARY
PUBCHEM
5311201
Created by admin on Fri Dec 15 15:30:30 GMT 2023 , Edited by admin on Fri Dec 15 15:30:30 GMT 2023
PRIMARY
Related Record Type Details
Structure of L-365260
ACTIVE MOIETY
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