Photodecarboxylation of DX-9065a, a new factor Xa inhibitor, in aqueous solution

Abstract

The photodegradation reaction of (2S)-2-[4-[[(3S)-1-acetimidoyl-3-pyrrolidinyl]oxy]phenyl]-3- (7-amidino-2-naphthyl) propanoic acid hydrochloride pentahydrate (DX-9065a), a new factor Xa inhibitor, was investigated in aqueous solution at various pH values (1.1-8.0) at 25 degrees C. The photodegradation of DX-9065a followed apparent first-order kinetics under artificial sunlight in a fairly good manner. The photodegradation rates of DX-9065a in a neutral solution were higher than those in acidic solution. The log k-pH profile indicated that the photodegradation rate of DX-9065a was related to the dissociation of the carboxyl group and suggested that the main photo-labile species was the carboxylate form. Further kinetic study showed that the carboxylate form of DX-9065a underwent decarboxylation quantitatively to produce D41-1077, the photodecarboxylation product, on irradiation, while the carboxylic acid form of DX-9065a did not perform any photodecarboxylation. Moreover, the photodecarboxylation mechanism was discussed in relation to the kinetics and photodegradation pathway.