Synthesis and evaluation of antiinflammatory activities of a series of corticosteroid 17α-esters containing a functional group

Article abstract of DOI:10.1021/jm00112a023

A series of 21-desoxy-21-chlorocorticosteroids that contain a functionalized ester group at 17α has been prepared and examined to separate their systemic activity from topical antiinflammatory activity. Introduction of the functionalized ester group at 17α was carried out by an acid-catalyzed formation of cyclic ortho esters with 17α,21-hydroxyl groups of corticosteroids and subsequent acid-catalyzed hydrolysis. As for the functional group, chloro, methoxy, acetoxy, cyano, cyclopropyl, or alkoxycarbonyl group was introduced at the terminal carbon atom of the 17α-alkanoate group. The topical antiinflammatory activity and systemic activity of these compounds were examined and found to be signficantly dependent on the functionalities in the 17α-esters. Among these derivatives, a series of 17α-(alkoxycarbonyl)alkanoates (17α-OCO(CH₂)(n)COOR) showed an excellent separation of the systemic activity from topical activity. The effects of the number of methylene groups (n) and of the alkyl groups of the ester (R) on either topical or systemic activity of the corticosteroid derivatives were also investigated.