ChemInform Abstract: Structure of the Antimalarial (.+-.)-Mefloquine Hydrochloride.

Abstract

R*, 12S*)-( __. )-a-2-Piperidinyl-2,8-bis- (trifluoromethyl)-4-quinolinemethanol monohydro- chloride, C)7H)vF6N2 O+ .Cl-.05CH3OH, Mr = 430.8, tetragonal, P42/n (origin at center of symme- try), a = b = 24.595 (4), c = 6.398 (2) .~,, V = 38700A 3, Z =8, Dx = 1.48gcm -3, CuKce, A= 1.54178 A, /x = 24.28 cm-l, F(000) = 1768, room temperature, final R = 7.5% for 2067 reflections with !Fo > 3o-(F). Mefloquine hydrochloride crystallized as a secondary amine salt with channels of dis- ordered methanol solvent. The trifluoromethyl group on the C adjacent to the quinoline N atom exhibited rotational disorder. Each chloride ion accepts three hydrogen bonds, one each from the hydroxyl group and the two H atoms of the amine group of meflo- quine from three separate molecules. The angle between the average plane of the quinoline ring and the average plane of the piperidine ring is 110.5 °. Introduction. (___)-Mefloquine hydrochloride was developed by the Walter Reed Army Institute of Research and Roche Laboratories (Nutley, N J) as an alternative treatment for multi-drug-resistant malaria. ( __+ )-Mefloquine hydrochloride was approved for treating malaria in 1989 by the Food and Drug Administration and is marketed under the trade name Lariam. Not only is malaria a disease of worldwide epidemic proportions with estimated yearly cases in the 100 millions and an estimated yearly death rate in the millions, chloroquine- resistant malaria, first confirmed in South America and Southeast Asia in the 1960's, now resides in malaria endemic areas around the globe (Wyler, 1983; Payne, 1987). Mefloquine is a quinoline-containing amino alco- hol antimalarial whose structure is derived from the