Biotransformation of terodiline. V. Stereoselectivity in hydroxylation by human liver microsomes.
The stereoselective hydroxylation of N-tert-butyl-4,4-diphenyl-2-butylamine (Terodiline) was studied in human liver microsomes. Formation of the two main metabolites, N-tert-butyl-4(4-hydroxyphenyl)-4-phenyl-2-butylamine (II) and N-(2-hydroxymethyl-2-propyl)-4,4-diphenyl-2-butylamine (VI), was found to be stereoselective. R-Terodiline was preferentially transformed by phenolic hydroxylation to the 2R,4S-II and 2R,4R-II forms with a pronounced selectivity for the former. The formation rate ratio 2R,4S-II/2R,4R-II was about 6, obtained from two liver preparations. S-Terodiline was mainly hydroxylated to the alcohol 2S-VI although phenolic hydroxylation to the 2S,4S-II and 2S,4R-II also occurred, yielding about equal amounts of the two phenols.
Norén
B
B
KabiVitrum AB, R&D, Stockholm, Sweden.
Strömberg
S
S
Ericsson
O
O
Lindeke
B
B
D000328:Adult; D001711:Biotransformation; D002082:Butylamines / Q000378:metabolism* / Q000493:pharmacokinetics; D002121:Calcium Channel Blockers; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006900:Hydroxylation; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D008875:Middle Aged; D015394:Molecular Structure; D010276:Parasympatholytics; D013237:Stereoisomerism
D002082:Butylamines; D002121:Calcium Channel Blockers; D010276:Parasympatholytics; C010637:terodiline