5-Hydroxytryptamine (5-HT3) receptor antagonists. 2. 1-Indolinecarboxamides.
Indazole 1 has previously been shown to be a potent and selective 5-HT3 receptor antagonist. A novel series of potent 5-HT3 receptor antagonists, 1-indolinecarboxamides 2a-q and 1-indolecarboxamides 3b,i,j,k, is described. The activity of the indolines suggests that aromaticity of the 5-membered ring is not an essential requirement for potency provided that an "in plane" orientation of the carbonyl group is favored. Upon the basis of this hypothesis indene 9 was prepared in which the "in plane" orientation of the carbonyl group is maintained by conjugation with the aromatic ring through the sp2 hybridized carbon. It was also found to be a potent 5-HT3 receptor antagonist.
Bermudez
J
J
Beecham Pharmaceuticals Research Division, Harlow, Essex, England.
Dabbs
S
S
Joiner
K A
KA
King
F D
FD
D000818:Animals; D006339:Heart Rate / Q000187:drug effects; D007202:Indicators and Reagents; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D015394:Molecular Structure; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D012018:Reflex / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000138:chemical synthesis*; D013329:Structure-Activity Relationship
D007202:Indicators and Reagents; D007211:Indoles; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin