LINETASTINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C35H40N2O6
Molecular Weight	584.7019
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	2
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCOC(=O)OC1=CC=C(\C=C\C=C\C(=O)NCCN2CCC(CC2)OC(C3=CC=CC=C3)C4=CC=CC=C4)C=C1OC

InChI

InChIKey=LUOUCHOLMUUZBO-SVSXJNCISA-N

InChI=1S/C35H40N2O6/c1-3-41-35(39)43-31-19-18-27(26-32(31)40-2)12-10-11-17-33(38)36-22-25-37-23-20-30(21-24-37)42-34(28-13-6-4-7-14-28)29-15-8-5-9-16-29/h4-19,26,30,34H,3,20-25H2,1-2H3,(H,36,38)/b12-10+,17-11+

HIDE SMILES / InChI

Description
Sources: https://adisinsight.springer.com/drugs/800002311 | https://www.ncbi.nlm.nih.gov/pubmed/8902877 | https://www.ncbi.nlm.nih.gov/pubmed/10940813

Linetastine has anti-inflammatory and anticarcinogenic effects. It is a potent inhibitor of 5-lipoxygenase. It also inhibits histamine release and epidermal cyclooxygenase activity. It also markedly inhibited TPA-stimulated leukotriene B4 formation, but inhibited formation of prostaglandin E2, a cyclooxygenase product, only slightly. This suggested that neither cyclooxygenase inhibition nor antihistaminic activity were essential to the anti-inflammatory action of linetastine. The anti-inflammatory effect of oral linetastine is probably due to 5-lipoxygenase inhibition. Oral administration of linetastine almost completely suppressed Cyp1a1 mRNA levels in mouse epidermis induced by a topical application of 3-methylcholanthrene or benzo[a]pyrene to mouse skin. Oral administration of linetastine inhibited DMBA-caused skin tumor initiation at least in part by inhibiting Cyp1a1 mRNA induction and epidermal aryl hydrocarbon hydroxylase activity. Linetastine had been in phase II clinical trial for the treatment of allergic rhinitis. However, this study was discontinued.

Originator

Approval Year

PubMed

Title	Date	PubMed
[Changes in arachidonic acid-induced respiratory distress in streptozotocin-diabetic mice].	1992 Feb	1532787
Inhibition of two-stage skin carcinogenesis as well as complete skin carcinogenesis by oral administration of TMK688, a potent lipoxygenase inhibitor.	1994 May	8200079
Anti-inflammatory action of orally active 5-lipoxygenase inhibitor TMK688.	1994 May	8016188
Inhibitory effect of TMK688 on skin tumor initiation caused by 7,12-dimethylbenz[a]anthracene in relation to inhibition of aryl hydrocarbon hydroxylase activity and Cyp1a1 mRNA induction.	1996 Aug	8902877
5-Lipoxygenase inhibitory and antihistamine activities of linetastine.	1996 Nov	8955867
Effects of TMK688, a novel anti-allergic drug, on allergic nasal obstruction and exudative responses in sensitized guinea pigs.	1997 Dec	9453468
The inhibitory effect of TMK688, a novel anti-allergic drug having both 5-lipoxygenase inhibitory activity and anti-histamine activity, against bronchoconstriction, leukotriene production and inflammatory cell infiltration in sensitized guinea pigs.	1997 Jan	9117875
Mechanisms of non-drowsiness after oral administration of TMK688, a novel antiallergic drug.	1998 Oct	9825114
Nitric oxide, superoxide radicals and mast cells in pathogenesis of indomethacin-induced small intestinal lesions in rats.	1999 Mar	10210152
Inhibitory effect of TMK-688 on late asthmatic responses as well as T-cell and eosinophilic infiltration in guinea pigs with asthmatic reactions.	2000 Feb	10684996
Preview of potential therapeutic applications of leukotriene B4 inhibitors in dermatology.	2000 Sep-Oct	10940813
Pathogenic importance of cysteinyl leukotrienes in development of gastric lesions induced by ischemia/reperfusion in mice.	2010 Apr	20042530

Patents

Sample Use Guides

In Vivo Use Guide

30 mg/kg at 6 h and 30 min prior to and at 30 min after a single topical application of 7,12-dimethylbenz[a]anthracene (DMBA)

Route of Administration: Oral

Name

Type

Language

LINETASTINE

Official Name

English

linetastine [INN]

Common Name

English

(2E,4E)-N-(2-(4-(DIPHENYLMETHOXY)PIPERIDINO)ETHYL)-5-(4-HYDROXY-3-METHOXYPHENYL)-2,4-PENTADIENAMIDE ETHYL CARBONATE (ESTER)

Common Name

English

LINAZOLAST [JAN]

Common Name

English

LINAZOLAST

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29578