Document Detail

Synthesis and dual antagonistic activity against thromboxane A2 and leukotriene D4 of [4-[1-(benzenesulfonamido)alkyl]phenyl]alkanoic acid derivatives.
MedLine Citation:
PMID:  9178522     Owner:  NLM     Status:  MEDLINE    
In order to find new antiasthmatic agents with dual antagonistic activity against thromboxane A2 (TXA2) and leukotriene D4 (LTD4) receptors, synthesis and pharmacological evaluation of various [4-[1-(benzenesulfonamido)-alkyl]phenyl]alkanoic acid derivatives were undertaken. TXA2 and LTD4 antagonistic activities in vitro were evaluated by measuring the inhibitory effects on L-46619-induced contraction of guinea-pig trachea and LTD4-induced contraction of guinea-pig ileum and trachea. Several compounds showed satisfactory dual antagonistic activities, and their effect (after oral administration) on LTD4-induced bronchoconstriction in guinea-pig in vivo was examined. The results demonstrated that both 4-[4-[1-(4-chlorobenzenesulfonamido)hexyl]phenyl]butyric acid (12e) and 4-[4-[1-(4-chlorobenzenesulfonamido)-5-methylhexyl]phenyl]bu tyric acid (12m) possessed good anti-LTD4 activities. Compounds 12e and 12m were then evaluated for other related pharmacological effects involving the arachidonic acid cascade. These compounds appear to be hybrid eicosanoids antagonists having antagonistic activity against contraction of guinea-pig trachea induced by prostaglandin D2 (PGD2) and PGF2 sigma, as well as TXA2 and LTD4 antagonistic activities.
S Sakurai; N Ogawa; Y Onogi; M Takeshita; H Takahashi; T Ohashi; K Kato; S Yasuda; H Kato
Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  Chemical & pharmaceutical bulletin     Volume:  45     ISSN:  0009-2363     ISO Abbreviation:  Chem. Pharm. Bull.     Publication Date:  1997 May 
Date Detail:
Created Date:  1997-07-21     Completed Date:  1997-07-21     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0377775     Medline TA:  Chem Pharm Bull (Tokyo)     Country:  JAPAN    
Other Details:
Languages:  eng     Pagination:  849-62     Citation Subset:  IM    
Research and Development Division, Hokuriku Seiyaku Co., Ltd., Fukui, Japan.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Anti-Asthmatic Agents / chemical synthesis*,  pharmacology
Bronchodilator Agents / chemical synthesis,  pharmacology
Chromatography, High Pressure Liquid
Guinea Pigs
Ileum / drug effects
Immunoglobulin G / immunology
Leukotriene D4 / antagonists & inhibitors*
Muscle Contraction / drug effects
Muscle, Smooth / drug effects
Receptors, Leukotriene / drug effects,  metabolism
Spectrophotometry, Ultraviolet
Structure-Activity Relationship
Sulfonamides / chemical synthesis*,  pharmacology
Thromboxane A2 / antagonists & inhibitors*
Trachea / drug effects
Reg. No./Substance:
0/Anti-Asthmatic Agents; 0/Bronchodilator Agents; 0/Immunoglobulin G; 0/Receptors, Leukotriene; 0/Sulfonamides; 57576-52-0/Thromboxane A2; 73836-78-9/Leukotriene D4

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Synthesis, affinity at 5-HT2A, 5-HT2B and 5-HT2C serotonin receptors and structure-activity relation...
Next Document:  Medicinal foodstuffs. VI. 1) Histamine release inhibitors from kidney bean, the seeds of Phaseolus v...