Synthesis and alpha 2-adrenoceptor antagonist activity of some disulfonamidobenzoquinolizines.
A series of disulfonamidobenzo[a]quinolizines were synthesized and evaluated for their alpha 2- and alpha 1-adrenoceptor antagonist activity on the rat vas deferens and anococcygeus muscle, respectively. N-((2 beta,11b alpha)-1,3,4,6,7,11b-Hexahydro-2H-benzo[a]quinolizin-2-yl)-N- [2-[(methylsulfonyl)amino]ethyl]methanesulfonamide (4) and its N-[2-[(methylsulfonyl)amino]ethyl]ethanesulfonamide (22), N-[2-[(ethylsulfonyl)amino]ethyl]ethanesulfonamide (27), and N-[2-[(methylsulfonyl)amino]ethyl]-4-methylbenzenesulfonamide (30) analogues showed 400-fold or greater selectivity in favor of alpha 2- over alpha 1-adrenoceptor blockade.
Ward
T J
TJ
Department of Chemistry, Wyeth Research, UK, Taplow, Maidenhead, England.
Warrellow
G J
GJ
Stirrup
J A
JA
Lattimer
N
N
Rhodes
K F
KF
D000317:Adrenergic alpha-Antagonists / Q000138:chemical synthesis*; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D008297:Male; D011807:Quinolizines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D011807:Quinolizines; D013449:Sulfonamides