Optical isomerization of R(−)-clidanac to the biologically active S(+)-isomer in guinea-pigs

Abstract

Optical isomerization of clidanac (RS-6-chloro-5-cyclohexyl-1-indancarboxylic acid, I), an anti-inflammatory drug having a chiral centre in its molecule, was evaluated in guinea-pigs. After oral administration of R(−)-I, the biologically active S(+)-isomer was detectable in the plasma, in the early stages. At 3 h after dosing R(−)-I, the plasma contained above 90% of the S(+)-isomer. Little conversion of S(+)-I to R(−)-I was observed. This may account for the equivalent in vivo activities of R(−)- and S(+)-I in this species. Determination of the enantiomeric composition required derivatization of the enantiomers to their diastereomeric amides after which thin layer chromatography (t.l.c.) was used for the separation. The quantitative determination of the compounds so-separated was accomplished by in situ measurements of the u.v.-reflectance. The t.l.c.-u.v.-densitometric procedure was also used to determine the plasma concentration of I.