(6,7-Diaryldihydropyrrolizin-5-yl)acetic acids, a novel class of potent dual inhibitors of both cyclooxygenase and 5-lipoxygenase.

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Laufer SA, Augustin J, Dannhardt G, Kiefer W

(6,7-Diaryldihydropyrrolizin-5-yl)acetic acids, a novel class of potent dual inhibitors of both cyclooxygenase and 5-lipoxygenase.

J Med Chem. 1994 Jun 10;37(12):1894-7.

PubMed ID

8021931 [ View in PubMed

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Abstract

A novel class of nonantioxidant dual inhibitors of both CO and 5-LO is described. The balance between the activity against CO and 5-LO can be shifted by modifying the substitution pattern of the phenyl moiety at the 6-position of the pyrrolizine ring. Structure-activity relationships are discussed. Compound 3e with a 4-Cl substituent (IC50 = 0.21 microM (CO); 0.18 microM (5-LO)) and 3n with a 4-OCH3 substituent (IC50 = 0.1 microM (CO); 0.24 microM (5-LO)) are the most potent and well-balanced dual inhibitors of both enzymes. The inhibition of CO was determined in a bovine thrombocyte intact cell assay and that of 5-LO using intact bovine PMNL. Compound 3e was also investigated in human cells.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Licofelone	Arachidonate 5-lipoxygenase	IC 50 (nM)	230	N/A	N/A	Details