Patent Evaluation: Novel Rapamycin Derivatives

Summary

Novelty: Novel amide ester and carbamate derivatives of rapamycin, possessing immuno-suppressive activity, are disclosed. The compounds are potentially useful for the treatment of transplantation rejection, host vs graft disease, autoimmune disease, inflammation and as antitumour and antifungal agents.

Biology: The immunosuppressive effects of the representative compounds were evaluated by the comitogen-induced thymocyte proliferation procedure (LAF). An in vivo popliteal lymph node (PLN) test procedure was used for testing host vs graft disease. Another in vivo procedure designed to determine the survival time of pinch skin graft from male DBB/2 donors transplanted to male BALB/C recipients is also described.

Chemistry: Rapamycin 42-ester with 4-(dimethylamino)-4-oxobutanoic acid is one of four specifically claimed compounds in US5118677; rapamycin 42-ester with (4-fluorophenyl) carbamic acid is one of fourteen specifically claimed compounds in US5118678.