Crystalstructures,absoluteconfigurationsandmoleculardockingstudiesofnaftopidilenantiomersasα1D-adrenoceptorantagonists

摘要： Chiraldrugnaftopidil(NAF),aspecificα1D-adrenoceptor(AR)antagonistforthetreatmentofbenignprostatichyperplasia,wasusedinracemicformforseveraldecades.OurrecentworkdeclaredthatNAFenantiomersshowedthesameantagonisticeffectsontheα1D-AR,butthebindingmechanismofthesetwostereochemicalNAFisomerstotheα1Dreceptorremainedunclear.Herein,wereportedthecrystallographicstructuresofopticallypureNAFstereoisomersforthefirsttimeandunambiguouslydeterminedtheirabsoluteconfigurations.ThecrystaldataofRandSenantiomersmatchedsatisfactorilythepharmacophoremodelforα1D-selectiveantagonists.Basedontheconstructedα1Dhomologymodel,moleculardockingstudiesshedlightonthemolecularmechanismofNAFenantiomersbindingtoα1D-AR.TheresultsindicatedthatNAFenantiomersexhibitedtheverysimilarbindingposesandoccupiedthesamebindingpocket. ... （共6頁）