On October 3, 2013, Saito, Noriko; Egi, Jun; Nagai, Hiroshi; Ueno, Megumi; Shintani, Yusuke; Inaba, Yusuke; Adachi, Michiaki; Hirai, Yuichi; Kawazu, Takeshi; Yasutake, Koichi; Takahashi, Daiki published a patent.Synthetic Route of 386704-04-7 The title of the patent was Preparation of triazinone compounds as T-type calcium channel inhibitors. And the patent contained the following:
The title compounds [I; R1 = H, halo, each (un)substituted C1-6 alkyl, C1-6 alkoxy, C1-6 alkylthio, mono- or di(C1-6 alkyl)amino, or C3-11 cycloalkyl; L1, L2 = a single bond, (un)substituted NH or C1-6 alkylene, O, S(O), SO2; B = each (un)substituted C3-11 cycloalkylene, C3-11 cycloalkenylene, 3-11 membered heterocyclylene, C6-14 arylene, 5-10 membered heteroarylene, C1-6 alkylene, C2-6 alkenylene, or C2-6 alkynylene; A = each (un)substituted C1-6 alkyl, C2-6 alkenyl, C3-11 cycloalkyl, C3-11 cycloalkenyl, 3-11 membered heterocyclyl, C6-14 aryl, or 5-10 membered heteroaryl; L3 = (un)substituted C1-6 alkylene optionally having one of the methylene groups replaced by C(O) or C(S); D = each (un)substituted C3-11 cycloalkyl, C3-11 cycloalkenyl, 3-11 membered heterocyclyl, C6-14 aryl, or 5-10 membered heteroaryl], tautomers or pharmaceutically acceptable salts of the compounds, or solvates of the compounds, the tautomers or the pharmaceutically acceptable salts are prepared These compounds have an inhibitory activity on a T-type voltage-dependent calcium channel and are useful for the prevention, treatment, and/or improvement of diseases for which the T-type calcium channel-inhibitory activity are effective, in particular pain, more specifically neuropathic pain. Thus, amination of 1,3,5-trichlorotriazine with 1-(4-fluorophenyl)piperazine dihydrochloride in the presence of Na2CO3 in THF at room temperature for 3 days quant. gave 2,4-dichloro-6-[4-(4-fluorophenyl)piperazin-1-yl]-1,3,5-triazine which underwent hydrolysis with aqueous NaOH solution at room temperature for 2 days and 2 h to give 79% 6-chloro-4-[4-(4-fluorophenyl)piperazin-1-yl]-1,3,5-triazin-2(1H)-one (II; X = Cl). Hydrogenation of II (X = Cl) in the presence of Pd(OH)2/activated charcoal in aqueous acetic acid solution under hydrogen atm. at room temperature for 3 days gave 99% 4-[4-(4-fluorophenyl)piperazin-1-yl]-1,3,5-triazin-2(1H)-one II (X = H) which underwent benzylation by 4-chlorobenzyl bromide in the presence of K2CO3 in N,N-dimethylformamide at 70° for 5 h to give 53% 1-(4-Chlorobenzyl)-4-[4-(4-fluorophenyl)piperazin-1-yl]-1,3,5-triazin-2(1H)-one (III). III and (R)-4-[4-(4-fluorophenyl)-5-hydroxy-5,6-dihydropyridin-1(2H)-yl]-1-[[5-(trifluoromethyl)thiophen-2-yl]methyl]-1,3,5-triazin-2(1H)-one (IV) showed IC50 of 0.17 and 0.00046 μM, resp., for inhibiting the cellular calcium influx in KSE293 cells expressing human type T calcium channel (Cav3.2). The experimental process involved the reaction of (6-(Trifluoromethyl)pyridin-3-yl)methanol(cas: 386704-04-7).Synthetic Route of 386704-04-7
The Article related to triazinone preparation t type calcium channel inhibitor, benzylphenylpiperazinyltriazinone phenylpyridinylthiophenylmethyltriazinone preparation t type calcium channel inhibitor, pain neuropathic pain treatment prevention improvement triazinone preparation and other aspects.Synthetic Route of 386704-04-7
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