A novel class of local antiinflammatory steroids. 1st communication: analogues of methyl 11 beta,17 alpha,21-trihydroxy-3,20-dioxo-pregna-1,4-diene-16 alpha-carboxylate.
A novel class of steroidal 16-esters and amides, 1-8 has been synthesized and evaluated as safer local antiinflammatory agents. These compounds retain the intact ketol side-chain of prednisolone and have an alkanoate ester or carboxamide function at the C-16 of the steroid nucleus. In the cotton pellet granuloma assay a correlation was observed between the size of the C-16 substituent group and the local antiinflammatory activity. The incorporation of a methyl carboxylate group at the C-16 position of prednisolone as in methyl 11 beta,17 alpha,21-trihydroxy-3,20-dioxo-pregna-1,4-diene-16 alpha-carboxylate, 5, resulted in an increase in antiinflammatory activity. The 17-deoxy analogue of 5, 1, retained one-half the activity of prednisolone. These two compounds were further evaluated for their effects on plasma corticosterone, adrenal and thymic weights at their ID50 doses for granuloma formation. Neither 5 nor 1 depressed plasma corticosterone levels or significantly altered adrenal weights. Compound 1 was also devoid of thymolytic activity, whereas 5 produced a 33% thymic involution at its ID50 compared to 47% for prednisolone at its equiactive dose.
Taraporewala
I B
IB
Center for Anti-inflammatory Research, Florida A & M University College of Pharmacy, Tallahassee.
Kim
H P
HP
Heiman
A S
AS
Lee
H J
HJ
D000311:Adrenal Glands / Q000187:drug effects; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D003345:Corticosterone / Q000097:blood; D003368:Gossypium; D006099:Granuloma / Q000139:chemically induced / Q000188:drug therapy; D006801:Humans; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011239:Prednisolone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013950:Thymus Gland / Q000187:drug effects
D000893:Anti-Inflammatory Agents; C059496:methyl 11,17,21-trihydroxy-3,20-dioxopregna-1,4-diene-16-carboxylate; D011239:Prednisolone; D003345:Corticosterone