Kuroita, Takanobu; Sakamori, Masamitsu; Kawakita, Takeshi published the artcile< Design and synthesis of 6-chloro-3,4-dihydro-4-methyl-2H-1,4-benzoxazine-8-carboxamide derivatives as potent serotonin-3 (5-HT3) receptor antagonists>, Safety of (S)-3-Amino-1-azabicyclo[2.2.2]octane, the main research area is benzoxazinecarboxamide preparation serotonin receptor antagonist.
Several 3-substituted 5-chloro-2-methoxybenzamides I (R1 = NMe2, NH2, NMeCOMe) were synthesized and evaluated for serotonin-3 (5-HT3) receptor binding affinity. The 5-HT3 receptor antagonistic activity of zacopride, a representative 5-HT3 receptor antagonist, was unchanged by the replacement of the 4-amino substituent on the aromatic moiety by a 3-dimethylamino substituent. This finding promoted a structural modification of azasetron, another 5-HT3 receptor antagonist. Consequently, a new series of 3,4-dihydro-2H-1,4-benzoxazine-8-carboxamides II (R2 = H, Me, Et, Pr, CH2Ph, COPh, etc., R3 = Cl; R2 = Me, R3 = F, Br, Me, NO2, NH2, H) was obtained and these compounds were found to be more potent than 3,4-dihydro-3-oxo-2H-1,4-benzoxazine-8-carboxamides. In particular, (S)-N-(1-azabicyclo[2.2.2]oct-3-yl)-6-chloro-3,4-dihydro-4-methyl-2H-1,4-benzoxazine-8-carboxamide showed a high affinity for 5-HT3 receptors (K = 0.051 nM) and especially potent antagonistic activity against the von Benzold-Jarisch reflex (ED50 = 0.089 μg/kg i.v.) in rats.
Chemical & Pharmaceutical Bulletin published new progress about 5-HT3 antagonists. 120570-05-0 belongs to class quinuclidine, and the molecular formula is C7H14N2, Safety of (S)-3-Amino-1-azabicyclo[2.2.2]octane.
Referemce:
Quinuclidine – Wikipedia,
Quinuclidine | C7H13N | ChemSpider