442-52-4
442-52-4 結(jié)構(gòu)式
基本信息
吡咯咪唑鹽酸鹽
1-[(4-氯苯基)甲基]-2-(吡咯烷-1-基甲基)苯并咪唑
1-(4-CHLOROBENZYL)-2-(PYRROLIDIN-1-YLMETHYL)-1H-BENZO[D]IMIDAZOLE HYDROCHLORIDE
Depocural
Histakool
NSC 46261
Lergopenin
1-p-Chlorobenzyl-2-pyrrolidino-methylbenzimidazole
1-(p-Chlorobenzyl)-2-pyrrolidylmethylenebenzimidazole
1-p-Chlorobenzyl-2-[1-pyrrolidinylmethyl] benzimidazole
1-(4-Chlorobenzyl)-2-(pyrrolizinomethyl)-1H-benzimidazole
1-(4-chlorobenzyl)-2-(pyrrolidin-1-ylmethyl)benzimidazole
物理化學(xué)性質(zhì)
常見問題列表
622-95-7
2948-92-7
442-52-4
在氮?dú)獗Ｗo(hù)下，將化合物10（0.24 mmol，49 mg）溶解于新蒸餾的四氫呋喃（THF，0.75 mL）中，隨后冷卻至0℃。向該溶液中緩慢加入60%氫化鈉（NaH）的油分散液（0.36 mmol，14.4 mg），并在0℃下攪拌反應(yīng)混合物5分鐘。接著，加入4-氯芐基溴（0.26 mmol，54 mg）和四丁基碘化銨（TBAI，0.024 mmol，9 mg）。將反應(yīng)混合物在室溫下攪拌過夜。反應(yīng)完成后，用水（2 mL）和乙酸乙酯（EtOAc，5 mL）稀釋反應(yīng)混合物。分離水相，并用乙酸乙酯（每次5 mL）萃取兩次。合并有機(jī)相，用無水硫酸鎂（MgSO4）干燥，過濾后減壓濃縮。通過硅膠柱色譜法（洗脫劑：乙酸乙酯）純化粗產(chǎn)物，得到目標(biāo)化合物11，為無色固體，產(chǎn)率65%（51 mg），熔點(diǎn)101-102℃。1H NMR（300 MHz，CDCl3）δ 7.83-7.77（m，1H），7.32-7.22（m，5H），7.06（d，J = 8.7 Hz，2H），5.58（s，2H），3.90（s，2H），2.58（m，4H），1.76（m，4H）；13C NMR（75 MHz，CDCl3）δ 152.3，142.5，135.9，135.3，133.6，129.1（2C），128.1（2C），122.9，122.7，120.0，109.7，54.8（2C），53.2，46.8，23.7（2C）；HRMS（ESI）：計(jì)算值C19H21N3Cl [M + H]+：326.1424，實(shí)測(cè)值326.1427；FTIR（neat，cm-1）2958，2927，2875，2810，1488，1463，1403，1294，1088，1034，1014，742，487。
參考文獻(xiàn)：
[1] Tetrahedron, 2015, vol. 71, # 4, p. 700 - 708
[2] Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 21, p. 6788 - 6795
| Target | Value |
|
H1 receptor
() | |
|
TRPC5
() |
Clemizole hydrochloride is found to inhibit HCV RNA replication in cell culture that is mediated by its suppression of NS4B’s RNA binding, with little toxicity for the host cell. The EC 50 of Clemizole on the W55R mutant J6/JFH RNA is ~18 μM (2.25 times the EC 50 of the wild-type RNA). Clemizole is a novel inhibitor of TRPC5 channels. Clemizole efficiently blocks TRPC5 currents and Ca 2+ entry in the low micromolar range (IC 50 =1.0-1.3 μM). Clemizole exhibits a six-fold selectivity for TRPC5 over TRPC4β (IC 50 =6.4 μM), the closest structural relative of TRPC5, and an almost 10-fold selectivity over TRPC3 (IC 50 =9.1 μM) and TRPC6 (IC 50 =11.3 μM). Clemizole hydrochloride as a novel blocker of TRPC5 with a half-maximal inhibitory concentration of 1.1 μM. The concentration-response curves confirmed a concentration-dependent block of TRPC5 by Clemizole and revealed an apparent IC 50 of 1.1±0.04 μM.
Clemizole hydrochloride has an unexpectedly short plasma half-life (measured at 0.15 hours); it is very rapidly biotransformed into a glucuronide (M14) and a dealkylated metabolite (M12) and into a variety of lesser metabolites in C57BL/6J mice.