Synthesis of N-(1-ethyl-4-methylhexahydro-1,4-diazepin-6-yl)nicotinamides and their affinities for 5-HT3 and dopamine D2 receptors.
A series of N-(1-ethyl-4-methylhexahydro-1,4-diazepin-6-yl)nicotinamide derivatives were prepared and evaluated for their binding to 5-HT3 and dopamine D2 receptors. Among them, the 5-bromo-2-methoxy-6-methylaminonicotinamide 16 and its (R)-isomer were found to have potent affinities for both receptors. The affinities of (R)-16 for 5-HT3 and dopamine D2 receptors are approximately 3-fold higher than those of the corresponding benzamide (R)-1 (IC50: 1.1 and 12 nM vs. 2.9 and 35 nM, respectively).
Hirokawa
Y
Y
Discovery Research Laboratory I, Dainippon Pharmaceutical Co., Ltd., Osaka, Japan.
Yoshida
N
N
Kato
S
S
D000818:Animals; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D044406:Receptors, Serotonin, 5-HT3; D013329:Structure-Activity Relationship
D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D009536:Niacinamide