Efficient synthesis and 5-LOX/COX-inhibitory activity of some 3-hydroxybenzo[b]thiophene-2-carboxylic acid derivatives

Finn K Hansen; Mehdi Khankischpur; Ibrahim Tolaymat; Renata Mesaros; Gerd Dannhardt; Detlef Geffken

doi:10.1016/j.bmcl.2012.06.012

Efficient synthesis and 5-LOX/COX-inhibitory activity of some 3-hydroxybenzo[b]thiophene-2-carboxylic acid derivatives

Bioorg Med Chem Lett. 2012 Aug 1;22(15):5031-4. doi: 10.1016/j.bmcl.2012.06.012. Epub 2012 Jun 13.

Authors

Finn K Hansen¹, Mehdi Khankischpur, Ibrahim Tolaymat, Renata Mesaros, Gerd Dannhardt, Detlef Geffken

Affiliation

¹ Pharmaceutical Chemistry Division, Institute of Pharmacy, University of Hamburg, Hamburg, Germany. finn.hansen@hhu.de

PMID: 22749420
DOI: 10.1016/j.bmcl.2012.06.012

Abstract

A series of 3-hydroxybenzo[b]thiophene-2-carboxylic acid derivatives has been prepared and subsequently evaluated with regards to the inhibition of 5-LOX/COX. Structure optimization furnished derivatives with promising in vitro activity as dual 5-LOX/COX inhibitors with submicromolar IC(50) values for inhibition of 5-LOX and COX-1, respectively.

MeSH terms

Arachidonate 5-Lipoxygenase / chemistry*
Arachidonate 5-Lipoxygenase / metabolism
Carboxylic Acids / chemical synthesis
Carboxylic Acids / chemistry
Carboxylic Acids / metabolism
Cyclooxygenase 1 / chemistry*
Cyclooxygenase 1 / metabolism
Cyclooxygenase Inhibitors / chemical synthesis*
Cyclooxygenase Inhibitors / chemistry
Cyclooxygenase Inhibitors / metabolism
Lipoxygenase Inhibitors / chemical synthesis*
Lipoxygenase Inhibitors / chemistry
Lipoxygenase Inhibitors / metabolism
Protein Binding
Structure-Activity Relationship
Thiophenes / chemical synthesis
Thiophenes / chemistry*
Thiophenes / metabolism

Substances

6-chloro-3-hydroxybenzo(b)thiophene-2-carboxylic acid
Carboxylic Acids
Cyclooxygenase Inhibitors
Lipoxygenase Inhibitors
Thiophenes
benzothiophene
2-thiophene carboxylic acid
Arachidonate 5-Lipoxygenase
Cyclooxygenase 1