Synthesis and biological evaluation of both enantiomers of L-761,000 as inhibitors of cyclooxygenase 1 and 2

Bioorganic & Medicinal Chemistry Letters
1996.0

Abstract

Both enantiomers of L-761,000 were prepared and evaluated for their cyclooxygenase activities.In the preceding paper l we have demonstrated that it is possible to develop a selective cyclooxygenase-2 (COX-2) inhibitor from a non-selective class of cyclooxygenase inhibitors. The structural modifications of indomethacin have led to the discovery of L-761,000, a potent and selective COX-2 inhibitor.It is well established that enantiomers can possess different intrinsic activities against enzymes and receptors. 2 In addition, the pharmacokinetics ofenantiomers might differ considerably. 3 For these reasons, the synthesis of both antipodes of L-761,000 was undertaken in order to compare their in vitro and in vivo activities.

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