Lintitript

Identification

Name
Lintitript
Accession Number
DB04867
Type
Small Molecule
Groups
Investigational
Description

Lintitript is a new, highly specific and potent CCK-A receptor antagonist.

Structure
Thumb
Synonyms
Not Available
External IDs
SR 27897
Categories
UNII
3YFV00531K
CAS number
136381-85-6
Weight
Average: 411.861
Monoisotopic: 411.044439726
Chemical Formula
C20H14ClN3O3S
InChI Key
ILNRQFBVVQUOLP-UHFFFAOYSA-N
InChI
InChI=1S/C20H14ClN3O3S/c21-14-7-3-2-6-13(14)15-11-28-20(22-15)23-19(27)17-9-12-5-1-4-8-16(12)24(17)10-18(25)26/h1-9,11H,10H2,(H,25,26)(H,22,23,27)
IUPAC Name
2-(2-{[4-(2-chlorophenyl)-1,3-thiazol-2-yl]carbamoyl}-1H-indol-1-yl)acetic acid
SMILES
OC(=O)CN1C(=CC2=CC=CC=C12)C(=O)NC1=NC(=CS1)C1=CC=CC=C1Cl

Pharmacology

Indication

For the treatment of pancreatic cancer and appetite disorders.

Structured Indications
Not Available
Pharmacodynamics

Lintitript SR 27897 is a selective cholecystokinin type A (CCK-A) receptor antagonist. In February 2000, Sanofi announced that it was halting development of the drug for appetite disorders, and in September 2002, Sanofi announced that it had stopped investigation all together.

Mechanism of action

Cholecystokinin (CCK) modulates feeding and dopamine-induced behavior in the central and peripheral nervous system. Lintitript antagonizes the effect of cholecystokinin by binding to the cholecystokinin type A (CCK-A) receptor. This action presumably alters feeding habits, however the exact mechanism of action is not known.

TargetActionsOrganism
UCholecystokinin receptor type ANot AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Kreiss C, Schwizer W, Borovicka J, Jansen JB, Bouloux C, Pignol R, Bischof Delaloye A, Fried M: Effect of lintitript, a new CCK-A receptor antagonist, on gastric emptying of a solid-liquid meal in humans. Regul Pept. 1998 Jun 30;74(2-3):143-9. [PubMed:9712175]
External Links
PubChem Compound
122077
PubChem Substance
175426876
ChemSpider
108883
BindingDB
82304
ChEBI
92624
ChEMBL
CHEMBL249973

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00854 mg/mLALOGPS
logP4.27ALOGPS
logP4.77ChemAxon
logS-4.7ALOGPS
pKa (Strongest Acidic)4.19ChemAxon
pKa (Strongest Basic)-1.2ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area84.22 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity107.79 m3·mol-1ChemAxon
Polarizability39.75 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.8956
Blood Brain Barrier+0.6572
Caco-2 permeable-0.6096
P-glycoprotein substrateNon-substrate0.5717
P-glycoprotein inhibitor INon-inhibitor0.8211
P-glycoprotein inhibitor IINon-inhibitor0.6439
Renal organic cation transporterNon-inhibitor0.9053
CYP450 2C9 substrateNon-substrate0.7338
CYP450 2D6 substrateNon-substrate0.8452
CYP450 3A4 substrateNon-substrate0.6075
CYP450 1A2 substrateInhibitor0.579
CYP450 2C9 inhibitorInhibitor0.7831
CYP450 2D6 inhibitorNon-inhibitor0.8294
CYP450 2C19 inhibitorInhibitor0.6289
CYP450 3A4 inhibitorNon-inhibitor0.6504
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8393
Ames testNon AMES toxic0.7209
CarcinogenicityNon-carcinogens0.7401
BiodegradationNot ready biodegradable0.9965
Rat acute toxicity2.3523 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.986
hERG inhibition (predictor II)Inhibitor0.5068
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as indolyl carboxylic acids and derivatives. These are compounds containing a carboxylic acid chain (of at least 2 carbon atoms) linked to an indole ring.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Indoles and derivatives
Sub Class
Indolyl carboxylic acids and derivatives
Direct Parent
Indolyl carboxylic acids and derivatives
Alternative Parents
Alpha amino acids and derivatives / N-alkylindoles / Indoles / 2,4-disubstituted thiazoles / Chlorobenzenes / Substituted pyrroles / Aryl chlorides / Heteroaromatic compounds / Propargyl-type 1,3-dipolar organic compounds / Azacyclic compounds
show 9 more
Substituents
Indolyl carboxylic acid derivative / Alpha-amino acid or derivatives / N-alkylindole / Indole / 2,4-disubstituted 1,3-thiazole / Chlorobenzene / Halobenzene / Aryl chloride / Aryl halide / Monocyclic benzene moiety
show 25 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Peptide binding
Specific Function
Receptor for cholecystokinin. Mediates pancreatic growth and enzyme secretion, smooth muscle contraction of the gall bladder and stomach. Has a 1000-fold higher affinity for CCK rather than for gas...
Gene Name
CCKAR
Uniprot ID
P32238
Uniprot Name
Cholecystokinin receptor type A
Molecular Weight
47840.645 Da
References
  1. Kreiss C, Schwizer W, Borovicka J, Jansen JB, Bouloux C, Pignol R, Bischof Delaloye A, Fried M: Effect of lintitript, a new CCK-A receptor antagonist, on gastric emptying of a solid-liquid meal in humans. Regul Pept. 1998 Jun 30;74(2-3):143-9. [PubMed:9712175]

Drug created on October 20, 2007 03:20 / Updated on December 01, 2017 15:33