Syntheses and antifungal activities of novel 3-amido bearing pseudomycin analogues

As a result of our core SAR effort. we discovered a large number of 3-amido pseudomycin B (PSB) analogues (e.g., 4e LY448212 and 5b LY448731) that ret ain good in vitro and in vivo (IP) activities against Candida and Cryptococ cus without inherent tail vein irritation. Several dimethylamino termini be aring 3-amides (e.g., 5b) also exhibited improved potency against Aspergill us in vitro. When evaluated in a two-week rat toxicology study, it was foun d that all animals receiving 4e (up to 75 mg/kg) were found to be normal. O n the basis of these observations, we are convinced that it is possible to broaden the antifungal spectrum and improve the safety profile of pseudomyc in analogues at the same time. (C) 2001 Elsevier Science Ltd. All rights re served.