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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

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
The selective cholecystokininB receptor antagonist L-365,260 diminishes the expression of naloxone-induced morphine withdrawal symptoms in normal and neuropathic rats.
1998
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
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.
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
ACTIVE MOIETY
Structure of L-365260
NIH
NCATS
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ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
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