TULOPAFANT

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C25H19N3O2S
Molecular Weight	425.502
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O=C(NC1=CC=CC(=C1)C(=O)C2=CC=CC=C2)C3=C4CS[C@@H](N4C=C3)C5=CN=CC=C5

InChI

InChIKey=PQQFNXGONTVQLM-RUZDIDTESA-N

InChI=1S/C25H19N3O2S/c29-23(17-6-2-1-3-7-17)18-8-4-10-20(14-18)27-24(30)21-11-13-28-22(21)16-31-25(28)19-9-5-12-26-15-19/h1-15,25H,16H2,(H,27,30)/t25-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C25H19N3O2S
Molecular Weight	425.502
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://adisinsight.springer.com/drugs/800001254 | https://www.ncbi.nlm.nih.gov/pubmed/3967244 | https://www.ncbi.nlm.nih.gov/pubmed/7812682

Tulopafant [RP 59227] is a platelet-activating factor (PAF) antagonist which was being developed by Rhône-Poulenc Rorer as an antiasthmatic agent. Double-blind, placebo-controlled clinicacl trial showed that RP 59227 attenuated the release of NCA and ECA after antigen challenge, and reduced the effect of exogenously added PAF in inducing eosinophil chemotaxis but did not protect against the antigen-induced early or late phase response in asthmatics. RP 59227 has also been shown to effectively reduce myocardial infarct size and the incidence of ischemia and reperfusion-induced arrhythmias in barbital-anesthetized dogs. Development of Tulopafant for asthma treatment has been discontinued.

Originator

Approval Year

PubMed

Title	Date	PubMed
[PAF-acether antagonistic pyrrolo[1,2-c]thiazoles: from RP 48740 to RP 59227].	1990 May-Jun	2205718
The platelet activating factor receptor antagonist, RP 59227, blocks platelet activating factor receptors mediating liberation of reactive oxygen species in guinea pig macrophages and human polymorphonuclear leukocytes.	1991 Aug	1650834
Tulopafant, a PAF receptor antagonist, increases capillary patency and prolongs survival in discordant cardiac xenotransplants.	1993 May	8395256

Patents

Sample Use Guides

In Vivo Use Guide

Safety and efficacy of a 240 mg oral dose of Tulopafant [RP 59227] in attenuating the early and late phase antigen challenge in eight asthmatics, using a double-blind, placebo-controlled, crossover design was studied.

Route of Administration: Oral

In Vitro Use Guide

PAF produced a dose-related increase in superoxide generation from elicited guinea pig peritoneal macrophages (IC50 41 +/- 16 nM, n = 9). After a 5 min preincubation time Tulopafant [RP 59227] (0.1, 1.0 and 10 uM) produced a dose-related rightward displacement of the PAF dose-response curve, the Schild plot gave a pA2 of 7.39 +/- 0.07 (n = 5) with a slope of 1.17 +/- 0.11, indicating competitive antagonism. Increasing the preincubation time to 30 min increased the affinity of RP 59227 (apparent pA2 8.76 +/- 0.28, n = 5).

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:31:23 GMT 2023` Edited by `admin` on `Fri Dec 15 15:31:23 GMT 2023`
Record UNII	IQ3Q8N1287
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TULOPAFANT

Official Name

English

tulopafant [INN]

Common Name

English

(+)-3'-BENZOYL-3-(3-PYRIDYL)-1H,3H-PYRROLO(1,2-C)THIAZOLE-7-CARBOXANILIDE

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1327