ChemInform Abstract: Synthesis and Pharmacological Profile of Two Novel Heterocyclic Chromanols, CP‐80,798 and CP‐85,958, as Potent LTD4 Receptor Antagonists.

Abstract

Synthesis and Pharmacological Profile of Two Novel Heterocyclic Chromanols, 958, as Potent LTD4 Receptor Antagonists.-A straightforward synthesis of the novel chromanols CP-80,798 (-)-( VIIIa), a balanced 5-lipoxygenase inhibitor/leukotriene D4 (LTD4) antagonist, and CP-85,958 (IX), a potent and selective LTD4-antagonist, starting from commercially available chromanone (I) is given. The optically pure chromanols, which are clinical candidates for the treatment of asthma, are obtained by resolution of the corresponding racemate (VIII) with chiral acids followed by hydrolysis of the chiral esters.-(ANDREWS, E. G.; ANTOGNOLI, G. W.; BRESLOW, R.; CARTA, M. P.; CARTY, T. J.; CHAMBERS, R. J.; CHENG, J. B.; COHAN, V. L.; COLLINS, J. L.; DA-MON, D. B.; DELEHUNT, J.; EGGLER, J. F.; ESKRA, J. D.; FREIERT, K. W.; HADA, W. A.; MARFAT, A.; MASAMUNE, H.; MELVIN, L. S.; MULARSKI, C. J.; NACLERIO, B. A.; ET AL.; Bioorg. Med. Chem. Lett. 5