Nobuhiro Ohi

IMPROVED SYNTHETIC METHODS OF CP-060S, A NOVEL CARDIOPROTECTIVE DRUG

Abstract Two synthetic methods of CP-060 S , (−)-2-(3,5-di- tert -butyl-4-hydroxyphenyl)-3-[3-[ N -methyl- N -[2-[3,4-(methylenedioxy)phenoxy]ethyl]amino]propyl]-1,3-thiazolidin-4-one (−)- 1 , have been developed. The first method involved preparative HPLC resolution of bromo-intermediate 4 . The second one involved resolution of 1 by crystallization of the corresponding diastereomeric salt.

SEMISYNTHETIC β-LACTAM ANTIBIOTICS

The synthesis and the relationship between in vitro and in vivo activities of 6-[(R)-2-[3-(3,4-dihydroxybenzoyl)-3-R1-1-ureido]-2- phenylacetamido]penicillanic acids having C2 approximately 8 alkyl or substituted alkyl groups as the substituents (R1) are described. In this series, 6-[(R)-2-[3-(3,4-dihydroxybenzoyl)-3-(3-hydroxypropyl)-1-ureido] -2-phenylacetamido]penicillanic acid (1b, AO-1100) showed the most potent protective effect on mice in experimental Pseudomonas aeruginosa infections, although it did not have the strongest in vitro activity among the penicillins we synthesized.