Structure-activity relationships of a series of novel topical corticosteroids.
The effect of various heteroaroyl groups in the 17-position of topical corticosteroids has been studied. The corticosteroids esterified at C17 were of 9 alpha,11 beta-dichloro, 9 alpha-chloro 11 beta-hydroxy and 9 alpha-fluoro 11 beta-hydroxy series. Among the 17-acyl groups 2'-furoates were most extensively investigated, although 2'-thenoates, 3'-thenoates and 3'-furoates were also examined. Many of these esters exhibited enhanced topical anti-inflammatory potencies. The most potent compounds investigated were the 21-chloro 17(2'-furoates) either in the 9 alpha,11 beta-dichloro, or in the 9 alpha-chloro 11 beta-hydroxy series. These compounds were at least 6 times as potent as betamethasone 17-valerate. Among 16-substituents studied 16 alpha-methyl compounds had the highest potency. Topical anti-inflammatory potencies were determined by using a 5-day modification of the croton oil ear assay in mice. The more potent compounds were also evaluated in the P. ovale induced chronic psoriaform lesion in the guinea-pig.
Pharmaceutical Research Division, Schering-Plough Corporation, Bloomfield, NJ 07003.
T L
TL
Popper
M J
MJ
Gentles
T T
TT
Kung
J
J
Berkenkopf
B N
BN
Lutsky
A S
AS
Watnick
E L
EL
Shapiro
D000287:Administration, Topical; D000305:Adrenal Cortex Hormones / Q000138:chemical synthesis / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000627:therapeutic use; D055598:Chemical Phenomena; D002621:Chemistry; D003436:Croton Oil; D006168:Guinea Pigs; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy; D051379:Mice; D011565:Psoriasis / Q000188:drug therapy / Q000209:etiology; D013329:Structure-Activity Relationship; D014010:Tinea Versicolor / Q000188:drug therapy
D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D002264:Carboxylic Acids; D003436:Croton Oil