180000-91-3Relevant academic research and scientific papers
Metal-free oxidative decarbonylative halogenation of fused imidazoles
Kumar, Gulshan,Shankar, Ravi,Singh, Davinder,Tali, Javeed Ahmad
, p. 20551 - 20555 (2021/11/23)
An efficient strategy has been developed for the deformylative halogenation of carbaldehyde imidazo-fused heterocycles in the presence of TBHP controlled by temperature. A convenient and sequential functionalization (C8 to C3) portrays the synthetic utility of the current method.N-Heterocycle benzamide products were also observedviathe ring opening of imidazopyridines through the cleavage of C-C bond at high temperatures. Features of this method include temperature-controlled excellent regioselectivity, mild conditions and functional group tolerance.
Discovery of benzimidazole derivatives as potent and selective aldehyde dehydrogenase 1A1 (ALDH1A1) inhibitors with glucose consumption improving activity
Feng, Yu,Jiang, Cheng,Jiang, Ling,Li, Bingyan,Liang, Dailin,Liu, Li,Ma, Zonghui
, (2021/08/17)
Aldehyde dehydrogenase 1A1 (ALDH1A1) plays vital physiological and toxicological functions in many areas, such as CNS, inflammation, metabolic disorders, and cancers. Overexpression of ALDH1A1 has been disclosed to play an important role in obesity, diabetes and other diseases, indicating the potential need for the identification and development of small molecule ALDH1A1 inhibitors. Herein, a series of benzimidazole derivatives was designed, synthesized and evaluated. Among them, compounds 21, 27, 29, 61 and 65 exhibited excellent inhibitory activity against ALDH1A1 with IC50 values in the low micromolar range and high selectivity over ALDH1A2, ALDH1A3, ALDH2 and ALDH3A1. Moreover, an in vitro study demonstrated that all five compounds effectively improved glucose consumption in HepG2 cells, of which, 61 and 65 at 10 μM produced nearly equal glucose consumption with positive control Metformin (Met) at 1 mM. Furthermore, 61 and 65 showed desirable metabolic stability in human liver microsomes. All these results suggest that 61 and 65 are suitable for further studies.
Design, synthesis and biological evaluation of benzimidazole-rhodanine conjugates as potent topoisomerase II inhibitors
Li, Penghui,Zhang, Wenjin,Jiang, Hong,Li, Yongliang,Dong, Changzhi,Chen, Huixiong,Zhang, Kun,Du, Zhiyun
supporting information, p. 1194 - 1205 (2018/08/01)
In this study, a series of benzimidazole-rhodanine conjugates were designed, synthesized and investigated for their topoisomerase II (Topo II) inhibitory and cytotoxic activities. The results from Topo II-mediated pBR322 DNA relaxation and cleavage assays showed that the synthesized compounds might act as Topo II catalytic inhibitors. Certain compounds displayed potent Topo II inhibition at 10 μM. The cytotoxic activities of these compounds against HeLa, A549, Raji, PC-3, MDA-MB-201, and HL-60 cancer cell lines were evaluated. The results indicated that these compounds exhibited strong antiproliferative activity. A good relationship was observed between the Topo II inhibitory potency and the cytotoxicity of these compounds. The structure-activity relationship revealed that the electronic effects, the phenyl group, and the rhodanine moiety were particularly important for the Topo II inhibitory potency and cytotoxicity.
Magnesiation of N-Heterocycles Using i-PrMgCl · LiCl and catalytic diisopropylamine
Nxumalo,Dinsmore
supporting information, p. 2478 - 2484 (2015/11/10)
The direct magnesiation of various N-heterocyclic compounds with i-PrMgCl · LiCl and catalytic diisopropylamine allows for preparation of 2-substituted pyrroles, imidazole, indoles, and benzimidazoles, in moderate to good yields. The magnesiated substrates canreadily undergo a Kumada-type coupling with iodo-aryls in the presence of catalytic Pd(PPh3)4.
Mechanochemical and conformational study of N-heterocyclic carbonyl-oxime transformations
Primoi, Ines,Hrenar, Tomica,Baumann, Kreimir,Krito, Lucija,Krii, Ivana,Tomi, Srdlanka
, p. 153 - 160 (2015/02/19)
New mechanochemical pathways for the transformation of six N-heterocyclic carbonyl compounds into oximes using hydroxylamine hydrochloride were explored. Reactions were performed first without any base since the heterocyclic moieties (imidazole, benzimidazole, pyridine and quinuclidine) have an intrinsic basic nitrogen atom. This green, solvent free method was suitable for all compounds (up to quantitative yields) except for N-benzyl substituted imidazole and benzimidazole-2-carbaldehyde. For the slower reacting aldehydes, reactions with liquid assisted grinding and addition of sodium hydroxide were performed as well. Conformational analysis and quantum-chemical calculations revealed steric and electronic reasons for the lower reactivity of N-benzyl substituted derivatives.
Design, synthesis and anticancer activity of 4-morpholinothieno[3,2-d]- pyrimidine derivatives bearing arylmethylene hydrazine moiety
Zhu, Wufu,Zhai, Xin,Fu, Qiangqiang,Guo, Fei,Bai, Mei,Wang, Jianqiang,Wang, Haiyan,Gong, Ping
experimental part, p. 1037 - 1045 (2012/10/08)
Three series of 4-morpholinothieno[3,2-d]pyrimidine derivatives containing arylmethylene hydrazine moiety (11a-f, 13a-k and 15a-h) were synthesized and their chemical structures as well as the relative stereochemistry were confirmed. The synthesized compounds were evaluated for their cytotoxicity against three cancer cell lines (H460, HT-29, MDA-MB-231). Most of them exhibited moderate to significant cytotoxicity and high-selectivity against one or more cell lines, especially compounds 11c, 13b, 15f and 15g possessing dramatically increased cytotoxicity as compared with the positive controls, which were further evaluated for six other cancer cell lines and one normal cell line. The most promising compound 11c, bearing 3,4-methylenedioxy phenyl group, showed remarkable cytotoxicity against H460, HT-29 and MDA-MB-231 cell lines with IC50 values of 0.003 μM, 0.42 μM and 0.74 μM, which was 1.6- to 290-fold more potent than GDC-0941.
Design, synthesis and 3D-QSAR analysis of novel 2-hydrazinyl-4- morpholinothieno[3,2-d]pyrimidine derivatives as potential antitumor agents
Zhu, Wufu,Liu, Yajing,Zhai, Xin,Wang, Xiao,Zhu, Yan,Wu, Di,Zhou, Hongyu,Gong, Ping,Zhao, Yanfang
, p. 162 - 175 (2013/01/15)
A series of 2-hydrazinyl-4-morpholinothieno[3,2-d]pyrimidine derivatives were synthesized and evaluated for their cytotoxic activities against five cancer cell lines. Most of them exhibited moderate to significant cytotoxic activities and high-selectivity against one or more cell lines, and nearly all of them had higher potency than positive controls against MDA-MB-231 cell line. The most promising compound 15f showed strong cytotoxic activities against H460, HT-29 and MDA-MB-231 cell lines, which were 1.7- to 66.5-folds more active than 2-(1H-Indazol-4-yl)-6-((4-(methylsulfonyl)-1-piperazinyl)methyl)-4-(4- morpholinyl)thieno[3,2-d]pyrimidine(GDC-0941). To investigate the SARs of thieno[3,2-d]pyrimidine derivatives in more details, CoMFA (q2 = 0.436, r2 = 0.937) and CoMSIA (q2 = 0.706, r2 = 0.947) models on H460 cell line were established. The generated 3D-QSAR models can be used for further rational design of novel thienopyrimidines as highly potent and selective cytotoxic agents.
5,10,15,20-Tetrakis(N-protected-imidazol-2-yl)porphyrins
Milgrom, Lionel R.,Dempsey, Philip J.F.,Yahioglu, Gokhan
, p. 9877 - 9890 (2007/10/03)
It is shown that examples of title porphyrins can be prepared from suitably N-protected imidazole-2-carboxaldehydes and pyrrole in refluxing propionic acid: subsequent deprotection, affords a synthetic route to 5,10,15,20-tetrakis(substituted-imadizol-2-y) porphyrins (TIPs).
