Synthesis and structure-activity relationships of 2-sulfonamido-1,3,4,6,7,11b alpha-hexahydro-2H-benzo[a]quinolizines as alpha 2-adrenoceptor antagonists.
A series of 2-sulfonamido-1,3,4,6,7,11b alpha-hexahydro-2H-benzo[a]quinolizines were synthesized and examined for alpha 2- and alpha 1-adrenoceptor antagonist activity on the rat vas deferens and anococcygeus muscle, respectively. A number of compounds in this series were shown to be potent and selective alpha 2-adrenoceptor antagonists. Studies on the resolved enantiomers of compounds 6, 10, and 16 showed that alpha 2-adrenoceptor antagonist activity resided primarily in the 2R,11bS isomers, related to the absolute configuration of the alpha 2-antagonist yohimbine, such that the benzene ring and sulfonamide groups in this series were superimposable on the pyrrole and ester groups of yohimbine.
Ward
T J
TJ
Department of Chemistry, Wyeth Research (U.K.), Taplow, Maidenhead, Berkshire, England.
White
J F
JF
Lattimer
N
N
Rhodes
K F
KF
Sharma
S
S
Waterfall
J F
JF
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D003000:Clonidine / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D019329:Idazoxan; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D008968:Molecular Conformation; D009119:Muscle Contraction / Q000187:drug effects; D009132:Muscles / Q000502:physiology; D011807:Quinolizines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000502:physiology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology; D014649:Vas Deferens / Q000502:physiology; D015016:Yohimbine / Q000494:pharmacology
D004146:Dioxanes; D011807:Quinolizines; D011942:Receptors, Adrenergic, alpha; D013449:Sulfonamides; D015016:Yohimbine; D008729:Methoxamine; D003000:Clonidine; D019329:Idazoxan