Synthesis, structure-activity relationships, and biological profiles of a dihydrobenzoxathiin class of histamine H(3) receptor inverse agonists.
Synthesis, structure-activity relationships, and biological profiles of a dihydrobenzoxathiin class of histamine H(3) receptor inverse agonists.
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DOI：
10.1016/j.bmcl.2009.05.101
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发表时间：
2009-08
影响因子：
2.7
通讯作者：
Takahide Sasaki;Toshiyuki Takahashi;T. Nagase;Takashi Mizutani;Sayaka Ito;Yuko Mitobe;Y. Miyamoto;Maki Kanesaka;R. Yoshimoto;Takeshi Tanaka;N. Takenaga;S. Tokita;N. Sato
中科院分区：
文献类型：
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作者：
Takahide Sasaki;Toshiyuki Takahashi;T. Nagase;Takashi Mizutani;Sayaka Ito;Yuko Mitobe;Y. Miyamoto;Maki Kanesaka;R. Yoshimoto;Takeshi Tanaka;N. Takenaga;S. Tokita;N. Sato
A series of novel dihydrobenzoxathiin derivatives was synthesized and evaluated as potent human histamine H3receptor inverse agonists. After systematic modification of lead 1a, the potent and selective histamine H3inverse agonist 1-(3-{4-[(2S,3S)-8-methoxy-3-methyl-4,4-dioxido-2,3-dihydro-1,4-benzoxathiin-2-yl]phenoxy}propyl)pyrrolidine (5k) was identified. Compound 5k showed good pharmacokinetic profiles and brain penetrability in laboratory animals. After 3mg/kg oral administration of 5k, significant elevation of brain histamine levels was observed in rats where the brain H3receptor was fully occupied.
