TETOMILAST

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H18N2O4S
Molecular Weight	370.422
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCOC1=CC=C(C=C1OCC)C2=NC(=CS2)C3=NC(=CC=C3)C(O)=O

InChI

InChIKey=XDBHURGONHZNJF-UHFFFAOYSA-N

InChI=1S/C19H18N2O4S/c1-3-24-16-9-8-12(10-17(16)25-4-2)18-21-15(11-26-18)13-6-5-7-14(20-13)19(22)23/h5-11H,3-4H2,1-2H3,(H,22,23)

HIDE SMILES / InChI

Molecular Formula	C19H18N2O4S
Molecular Weight	370.422
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23043390 | https://www.ncbi.nlm.nih.gov/pubmed/17241861 | https://www.ncbi.nlm.nih.gov/pubmed/15906198

Otsuka Pharmaceutical Co developed tetomilast, a thiazole derivative for the treatment of inflammatory bowel disease and chronic obstructive pulmonary disease. Tetomilast acts as a selective inhibitor of phosphodiesterase-4 results in increased intracellular levels of cyclic adenosine monophosphate (cAMP), and subsequent anti-inflammatory effects. Specifically, the release of pro-inflammatory mediators including TNF-a and IL-12 is suppressed, and there is stimulation of the release of anti-inflammatory mediators including IL-10 and prostaglandin E2. Unfortunately, tetomilast clinical trials in patients with ulcerative colitis failed to demonstrate superior efficacy compared to mesalamine and further development of tetomilast was discontinued.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Phosphodiesterase 4 52 Target ID: CHEMBL2093863 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23043390	Inhibitor 8146

PubMed

Title	Date	PubMed
OPC-6535, a superoxide anion production inhibitor, attenuates acute lung injury.	1997 Sep	9344716
OPC-compounds prevent oxidant-induced carbonylation and depolymerization of the F-actin cytoskeleton and intestinal barrier hyperpermeability.	2001 Feb 1	11165875
A practical synthesis of 3,4-diethoxybenzthioamide based on Friedel-Crafts reaction with potassium thiocyanate in methanesulfonic acid.	2002 Sep 2	12161124
Effects of OPC-6535 on lipopolysaccharide-induced acute liver injury in the rat: involvement of superoxide and tumor necrosis factor-alpha from hepatic macrophages.	2003 Nov	14639361
Gateways to clinical trials.	2004 Dec	15672123
Medical therapy for ulcerative colitis: the state of the art and beyond.	2004 Dec	15527679
Digestive Disease Week 2004. Bowel inflammation.	2004 Jun	15197649
Tetomilast.	2005 Jun	15906198
A randomized, placebo-controlled, phase II study of tetomilast in active ulcerative colitis.	2007 Jan	17241861
Gateways to clinical trials.	2007 Sep	17982511
Tetomilast suppressed production of proinflammatory cytokines from human monocytes and ameliorated chronic colitis in IL-10-deficient mice.	2008 Nov	18618633
Can the anti-inflammatory potential of PDE4 inhibitors be realized: guarded optimism or wishful thinking?	2008 Oct	18660832
Phosphodiesterase 4 inhibitors in inflammatory bowel disease: a comprehensive review.	2010	21128899
Tetomilast: new promise for phosphodiesterase-4 inhibitors?	2012 Dec	23043390

Patents

Sample Use Guides

In Vivo Use Guide

50 mg/day for 8 weeks

Route of Administration: Oral

Substance Class	Chemical Created by `admin` on `Fri Dec 16 21:10:13 UTC 2022` Edited by `admin` on `Fri Dec 16 21:10:13 UTC 2022`
Record UNII	S6RXB5KF56
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

TETOMILAST

Official Name

English

tetomilast [INN]

Common Name

English

6-(2-(3,4-DIETHOXYPHENYL)-1,3-THIAZOL-4-YL)PYRIDINE-2-CARBOXYLIC ACID

Systematic Name

English

OPC-6535

Code

English

2-PYRIDINECARBOXYLIC ACID, 6-(2-(3,4-DIETHOXYPHENYL)-4-THIAZOLYL)-

Common Name

English

Tetomilast [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C744