130205-25-3Relevant academic research and scientific papers
Novel potassium channel activators: Synthesis and structure-activity relationship studies of 3,4-dihydro-2H-1,4-benzoxazine derivatives
Matsumoto, Yuzo,Tsuzuki, Ryuji,Matsuhisa, Akira,Takayama, Kazuhisa,Yoden, Toru,Uchida, Wataru,Asano, Masaharu,Fujita, Shigeo,Yanagisawa, Isao,Fujikura, Takashi
, p. 103 - 114 (2007/10/03)
Strong potassium channel-activating effects were found among a series of novel 4-substituted 3,4-dihydro-2H-1,4-benzoxazine derivatives. The key step in preparation was the nucleophilic substitution of 3,4-dihydro-2H-1,4- benzoxazine (3) with activated halogenopyridines, such as halogenopyridine N- oxides (15a-c) and the borane adduct (15d) of 4-bromopyridine. Structure- activity relationship studies identified 2-(3,4-dihydro-2,2-dimethyl-6- nitro-2H-1,4-benzoxazin-4-yl)pyridine-1-oxide (16a: YM934) as the optimal compound. This compound (16a) showed a more potent oral antihypertensive effect than cromakalim in conscious spontaneously hypertensive rats.
Dual-Acting Thromboxane Receptor Antagonist/Synthase Inhibitors: Synthesis and Biological Properties of alkenoic Acids
Faull, Alan W.,Brewster, Andrew G.,Brown, George R.,Smithers, Michael J.,Jackson, Ruth
, p. 686 - 694 (2007/10/02)
The design, synthesis, and pharmacology of a new class of compounds possessing bith thromboxane receptor antagonist and thromboxane synthase inhibitory properties are described.Replacement of the phenol group of the known thromboxane antagonist series 4(Z)-6-hex-4-enoic acid by a 3-pyridyl group led to a series of compounds, 5, which were potent thromboxane synthase inhibitors and weak thromboxane antagonists.Further modifications at the dioxane C2 position led to compounds, 7, which were potent dual-acting agents.In the case of compound 7w, the dual activity was shown to reside almost exclusively in the (-)-enantiomer, 7x.Following oral dosing to rats and dogs, 7x (3 mg/kg) displayed significant dual activity over a period of at least 8 h.
