Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P46098 (5-HT3 receptor)
 2,290 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A series of pyrido[1,2-alpha]indol-6(7-H)-ones was prepared and evaluated for 5-HT3 receptor antagonist activity. The structural requirements for the 5-HT3 receptor antagonist have been defined as an aromatic moiety, a basic nitrogen, and a linking acyl group. The (5-methylimidazol-4-yl)methyl group as a basic nitrogen moiety was an important element for high potency. The highest potency was observed for compounds which have 7- and 10-methyl substituents on the pyrido[1,2-alpha]indol-6(7H)-one ring. From this series, (+)-11b (FK 1052) was selected for further evaluation. FK 1052 was a potent 5-HT3 receptor antagonist in the Bezold-Jarisch reflex test in rats (ED50 0.9 microgram/kg, i.v.) and a very effective antiemetic agent against cisplatin-induced emesis in dogs (ED50 1.2 x 2 micrograms/kg, i.v. and 2.7 x 2 micrograms/kg, p.o.).
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PMID:New 5-HT3 (serotonin-3) receptor antagonists. I. Synthesis and structure-activity relationships of pyrido[1,2-a]indoles. 769 71

A series of pyrimido[1,6-alpha]indol-1(2H)-ones was prepared and evaluated for 5-HT3 receptor antagonist activity. The compounds in this series were regarded as bioisosters of the pyrido[1,2-alpha]indol-6(7H)-ones previously reported. High potency was found for compounds having 5-methyl substituents on both the pyrimido[1,6-alpha]indole ring and the imidazole ring. Optimized members of this series, 8b and (+)-26a, were potent 5-HT3 receptor antagonists as determined by measuring inhibition of the Bezold-Jarisch reflex in anesthetized rats (ED50 0.6 and 0.8 microgram/kg i.v., respectively), being equipotent to or more potent than FK 1052 (1) in the previous paper and 20- to 30-fold more potent than ondansetron (2).
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PMID:New 5-HT3 (serotonin-3) receptor antagonists, II. Synthesis and structure-activity relationships of pyrimido[1,6-a]indoles. 769 72