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

• Published in: Bioorganic & medicinal chemistry letters Vol. 22; no. 15; pp. 5031 - 5034
• Main Authors: Hansen, Finn K., Khankischpur, Mehdi, Tolaymat, Ibrahim, Mesaros, Renata, Dannhardt, Gerd, Geffken, Detlef
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.08.2012; Elsevier
• Subjects: 5-LOX; Arachidonate 5-Lipoxygenase - chemistry; Arachidonate 5-Lipoxygenase - metabolism; Benzothiophene; Biological and medical sciences; carboxylic acids; Carboxylic Acids - chemical synthesis; Carboxylic Acids - chemistry; Carboxylic Acids - metabolism; chemical derivatives; Chemistry; Chemistry, Medicinal; Chemistry, Organic; COX-1/2; Cyclooxygenase 1 - chemistry; Cyclooxygenase 1 - metabolism; Cyclooxygenase Inhibitors - chemical synthesis; Cyclooxygenase Inhibitors - chemistry; Cyclooxygenase Inhibitors - metabolism; Dual inhibitors; enzyme inhibition; enzyme inhibitors; in vitro studies; inhibitory concentration 50; Licofelone; Life Sciences & Biomedicine; Lipoxygenase Inhibitors - chemical synthesis; Lipoxygenase Inhibitors - chemistry; Lipoxygenase Inhibitors - metabolism; Medical sciences; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Physical Sciences; prostaglandin synthase; Protein Binding; Science & Technology; Structure-Activity Relationship; structure-activity relationships; Thiophenes - chemical synthesis; Thiophenes - chemistry; Thiophenes - metabolism; Benzothiophene; Licofelone; 5-LOX; Dual inhibitors; COX-1/2; LIPOXYGENASE-CYCLOOXYGENASE INHIBITOR; DUAL INHIBITION; COX-2; DISEASE; 5-LIPOXYGENASE; Prostaglandin-endoperoxide synthase; Enzyme; Cyclooxygenase 2; Antiinflammatory agent; Cyclooxygenase 1; Biological activity; Benzothiophene derivatives; Thiophene derivatives; Carboxylic acid; Arachidonate 5-lipoxygenase; Inhibitor; Oxidoreductases; Chemical synthesis
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2012.06.012

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 IC50 values for inhibition of 5-LOX and COX-1, respectively.