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Synthesize a novel series of 5-alkynyl- and 5-aryl-4,6-dithianonanedioic acids and determine their structure-activity relationships as leukotriene receptor antagonists.

August 1, 1986Journal of Medicinal ChemistryOpen Access

Synthesis and structure-activity relationship studies of a series of 5-aryl-4,6-dithianonanedioic acids and related compounds: a novel class of leukotriene antagonists

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Synthesize a novel series of 5-alkynyl- and 5-aryl-4,6-dithianonanedioic acids and determine their structure-activity relationships as leukotriene receptor antagonists.
Synthesized alkynyl analogues via thioacetal exchange and prepared aryl derivatives from substituted benzaldehydes using Meyers' oxazoline method, palladium coupling, or hydroxybenzaldehyde alkylation.
Tested compounds in vitro for competitive inhibition of [3H]LTD4 binding to guinea pig lung membranes and functional antagonism of LTD4-induced tracheal smooth muscle contractions, followed by in vivo bronchoconstriction assays.
Active antagonists required an optimal lipid tail length of 10–12 atoms and two methylene units in the polar head, whereas conformational rigidification eliminated activity.
Ortho- and meta-substituted aromatic derivatives exhibited potent antagonist activity, with terminal phenyl and acetylene analogues displaying superior potency, while para-substituted variants were inactive.

Authors

CPCarl D. PerchonockUpsher-Smith Laboratories (United Kingdom)IUIrene N. UzinskasSouth College MMMary E. McCarthyLumentum (United States)

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Implication

Preclinical evaluation reveals potent LTD4 receptor antagonism by 5-aryl-4,6-dithianonanedioic acids in guinea pig airway models, highlighting their therapeutic potential for asthma.

Cite This Study

Perchonock et al. (1986) studied this question.

synapsesocial.com/papers/6a84501d002ab1506fb2ac8a https://doi.org/10.1021/jm00158a021

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Implication

Preclinical evaluation reveals potent LTD4 receptor antagonism by 5-aryl-4,6-dithianonanedioic acids in guinea pig airway models, highlighting their therapeutic potential for asthma.

Synthesis and structure-activity relationship studies of a series of 5-aryl-4,6-dithianonanedioic acids and related compounds: a novel class of leukotriene antagonists

Key Points

Discussion

Implication

Cite This Study

Synthesis and structure-activity relationship studies of a series of 5-aryl-4,6-dithianonanedioic acids and related compounds: a novel class of leukotriene antagonists

Key Points

Discussion

Implication

Cite This Study

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