Steroidal Indoxyls: Evaluation of Pk, values and anti-inflammatory activity

Abstract

Three steroidal indoxyls, 3-oxo-16,17-seco-16;.nor-l,4-androstadien-15-(7'-methoxy-2-indoxyliden)17-oic acid, 1-(2'-indoxyliden)-2-nor-l,2-secocholestan-3~ oic acid and 1-(5'- chloro-2-indoxyliden)-2-nor-l,2-secocholestan-3-oic acid were synthesized and screened for anti-inflammatory activity. Their pK. values were also determined using a solubility method. The first compound, 3-oxo-16,17- seco-16-nor-l ,4-androstadien-15-(7' -methoxy-2-indoxyliden) 17 -oic acid, had an EDso value of 15.3 mg/kg and a pK. of 7.09. The cholestane derivative, 1-(2'-indoxyliden)-2-nor-l,2-secocholestan-3-oic acid, and its chloro analogue 1-(5'-chloro-2-indoxyliden)-2-nor-l,2-secocholestan-3-oic acid had EDso values of 16.2 and 22.8 mg/kg, while their pK. values were 6.56 and 7.07, respectively, suggesting that these compounds are relatively weak acids.