Serotoninergic 5-HT3 and 5-HT4 receptor activities of dihydrobenzofuran carboxylic acid derivatives

doi:10.1016/0960-894X(96)00002-9

Bioorganic & Medicinal Chemistry Letters

Volume 6, Issue 3, 6 February 1996, Pages 263-266

https://doi.org/10.1016/0960-894X(96)00002-9 Get rights and content

Abstract

Structure-activity relationships in a series of dihydrobenzofuran derivatives related structurally to the 5-HT₃ antagonist and 5-HT₄ agonist ADR 932 (1) were investigated. Members of this series, such as (18) and (23), were found to be 5-HT₄ agonists or partial agonists endowed with remarkably high affinity and selectivity.

Structure-activity relationships in a series of dihydrobenzofuran-7-carboxylic acids derivatives were investigated. Members of this series, such as 23, were found potent and selective 5-HT₄ agonists or partial agonists.

The 1,3,4-trisubstituted-1,4-benzodiazepin-2-one 2 is a non-peptide mimic of somastatin-14 (SRIF-14). It displaces the radioligand [¹²⁵I-Tyr3]-octreotide with an IC₅₀ of 7 μM.

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However, to our knowledge, the synthetic potential of this reaction for the diastereoselective synthesis of 2,3-disubstituted dihydrobenzofurans has not been explored. As there has been considerable interest in the synthesis of 2,3-disubstituted dihydrobenzofuran systems due to the presence of this moiety in many biologically active natural products such as (±)-obtusafuran,11 (±)-liliflol-B,12 (±)-kadsurinone,13 (±)-denudatin,14 (±)-conocarpan,15 and (+)-lithospermic acid,16 we considered it worthwhile to investigate the scope and utility of this methylene group transfer reaction for the diastereoselective synthesis of such systems. We report herein the reactions of 2-hydroxyaryl-α,β-unsaturated ketones with dimethylsulfonium carbonylmethylides, which lead to the formation of 2,3-disubstituted dihydrobenzofurans in good yields with high diastereoselectivity.
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Serotoninergic 5-HT3 and 5-HT4 receptor activities of dihydrobenzofuran carboxylic acid derivatives

Abstract

Eur. J. Cancer

Trends Pharmacol. Sci

Pharmacol. Res

Biochem. Pharmacol

BioMed. Chem. Lett

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BioMed. Chem. Lett

Med. Chem. Res

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Exp. Opin. Invest. Drugs

Serotoninergic 5-HT₃ and 5-HT₄ receptor activities of dihydrobenzofuran carboxylic acid derivatives