Patent Evaluation: Hydrogenated Rapamycin Derivatives as Antifungal Agents

Summary

Novelty: Hydrogenated derivatives of rapamycin are disclosed as antifungal agents.

Biology: Data are presented which show that both claimed compounds are less active against five strains of Candida albicans than the parent rapamycin. 1,2-Dihydrorapamycin is significantly less active, whereas the 1,2,3,4-tetrahydro derivative was generally only half as effective (MIC = 0.006 μg/ml, compared with 0.003 μg/ml). However, Candida albicans 3669 was more sensitive to the tetrahydroderivative (MIC = 0.0125 μg/ml) than rapamycin (MIC = 0.025 μg/ml). Both new derivatives were relatively inactive in in vitro LAF and in vivo PLN tests and hence lack the immunosuppresive activity associated with rapamycin.

Chemistry: 1,2-Dihydro and 1,2,3,4-tetrahydro rapamycin were prepared by high pressure hydrogenation of rapamycin, which employs tris(triphenylphosphine)rhodium(I)chloride as a catalyst.