22219-23-4Relevant academic research and scientific papers
SUBSTITUTED BENZIMIDAZOLE CARBOXAMIDES AND THEIR USE IN THE TREATMENT OF MEDICAL DISORDERS
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Paragraph 00296; 00302; 00404, (2021/04/01)
The invention provides substituted benzimidazole carboxamides and related compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat a medical disorder, e.g., cancer, lysosomal storage disorder, neurodegenerative disorder, inflammatory disorder, in a patient.
Development of novel benzimidazole-derived neddylation inhibitors for suppressing tumor growth in vitro and in vivo
Chen, Xin,Yang, Xi,Mao, Fei,Wei, Jinlian,Xu, Yixiang,Li, Baoli,Zhu, Jin,Ni, Shuaishuai,Jia, Lijun,Li, Jian
, (2020/11/02)
Ubiquitin-like protein neddylation is overactivated in various human cancers and correlates with disease progression, and targeting this pathway represents a valuable therapeutic strategy. Our previous work disclosed an antihypertensive agent, candesartan cilexetic (CDC), serves as a novel neddylation inhibitor for suppressing tumor growth by targeting Nedd8-activating enzyme (NAE). In this study, 42 benzimidazole derivatives were designed and synthesized based on lead compound CDC to improve the neddylation inhibition and anticancer efficacy. Optimal benzimidazole-derived 35 displayed superior neddylation inhibition in enzyme assay compared to CDC (IC50 = 5.51 μM vs 16.43 μM), along with promising target inhibitory activity and killing selectivity in cancer cell. The results of cellular mechanism research combined with tumor growth suppression in human lung cancer cell A549 in vivo, accompanied with docking model, revealed that 35 has the potential to be developed as a promising neddylation inhibitor for anticancer therapy.
Benzimidazole compound and medical application thereof
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Paragraph 0030-0032, (2021/05/05)
The invention relates to the field of medicinal chemistry and pharmacotherapeutics, and particularly discloses a benzimidazole compound which has a structure as shown in a formula I. In the formula I, R1 is H, hydroxyl and C1-C3 alkoxy; R2 is H or a C4-C6-membered heterocyclic ring; R3 is H, C1-C6 straight-chain or branched-chain alkyl, C1-C6 straight-chain or branched-chain hetero-alkyl, C3-C6 alicyclic ring, C3-C6 heterocyclic ring, substituted or unsubstituted aromatic ring, substituted or unsubstituted aromatic heterocyclic ring, substituent groups are fluorine, chlorine, bromine, methyl, ester group or methoxy group, and the number of the substituent groups is an integer from 0 to 2. The invention also discloses an application of the benzimidazole compound in preparation of a medicine for treating diseases participated in or mediated by a Neddylation pathway, and the compound can be used for treating tumor diseases by inhibiting the Neddylation pathway.
A new method for synthesizing flibanserin (by machine translation)
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Paragraph 0052-0057; 0070-0073; 0081-0084; 0092-0095, (2019/02/04)
The invention relates to a new method for synthesizing of flibanserin, which belongs to the technical field of organic synthesis. The invention respectively in order to triethanolamine and between amino benzotrifluoride as the starting material, to prepare the piperazine intermediate; then to the O-phenylene diamine and the original four carbonate as raw material, the preparation of the ethoxy and imidazole intermediate; the obtained piperazine intermediate and benzimidazole intermediate undergo the substitution reaction, and hydrochloric acid deprotection to obtain the target product of flibanserin. The invention has few synthetic steps, few by-products, intermediate products and the target product yield is relatively high, intermediate product 2 - ethoxy and imidazole yield up 94.2%, the target product yield can reach 56.2%, it can be seen, the invention overcomes the substance in the prior art synthesis step is tedious, and more byproducts, target low yield of product defect. In addition, the present invention has a simple structure, high purity of product, the economic and environmental protection industrial line, has a very wide range of use and potential economic benefits. (by machine translation)
A Facile Route of Synthesis for Making Flibanserin
Yang, Feipu,Wu, Chunhui,Li, Zhiqiang,Tian, Guanghui,Wu, Jianzhong,Zhu, Fuqiang,Zhang, Jian,He, Yang,Shen, Jingshan
, p. 1576 - 1580 (2016/09/23)
A novel and efficient route of synthesis for making flibanserin via 2-ethoxy-1H-benzo[d]imidazole (12) was described with excellent yield. This protocol provided a more facile approach to flibanserin.
Functional dihydro-1H-imidazole derivatives for MALDI signal enhancement of a lysine-specific chemical modification
Ho, Ming-Yi,Shieh, Yu-Tse,Liao, Chung-Lin,Chen, Yau-Hung,Cheng, Chien-Chung
scheme or table, p. 987 - 994 (2010/08/13)
The enhancement of signal sensitivity and quantification of low-abundance proteins is of great importance in proteomic analysis. The preparation of 2-methoxy-4,5-dihydro-1H-imidazole (MeO-DHIM) derivatives was accomplished by one-step synthesis of O-methyl-isourea. The signal enhancement induced by these attached moieties increases in an order of compound 1 ≈ 4 2 5 ≈ 6 3 in MALDI mass spectrometry. Peptide-compound 3 adduct was approximately 20 times signal enhancement of the unmodified peptide and of 9 times of the peptide-compound 1 adduct. This result demonstrates that the rational designed organic molecules are capable of providing a sensitive tool in the detection of low-abundance proteins in proteomics.
A facile one-pot synthesis of benzimidazoles from 2-nitroanilines by reductive cyclization
Liu, Zheng,Li, Haihong,Zhao, Qingjie,Shen, Jingshan
scheme or table, p. 1907 - 1911 (2009/04/06)
A facile one-pot process to prepare benzimidazole derivatives is described. Reductive cyclization of a serial of 2-nitroanilines with orthoesters in the presence of Pd/C in methanol at room temperature, which is promoted by a catalytic amount of acetic acid, affords the corresponding benzimidazole derivatives in high yields.
Orthoamides, XXXVIII. - Contributions to the Chemistry of Orthocarbonic Acid Esters and α,α,α-Trialkoxyacetonitriles
Kantlehner, Willi,Maier, Thomas,Loeffler, Wolfgang,Kapassakalidis, Joanis J.
, p. 507 - 529 (2007/10/02)
The reactivity of the orthocarbonates 4 and the nitriles 1 has been investigated.Carboxylic acids are esterified by 4b. Orthocarbonates 4c-f and 9b are prepared by transesterification of 4b.Mixed substituted orthocarbonates 8c-f are obtained from the nitriles 1a,b.The nitriles 2a and 3a react with alkali alcoholate in alcohol to yield the orthocarbamic acid esters 13a,b. Spirocyclic orthocarbonates 17a-d are prepared from 4b and 1,2 or 1,3-dioles, respectively. The reaction of phenol with 1b affords the mixed substituted orthocarbonate 18a. Catechol is converted by 1a into the orthocarbonate 20a.Reactions of 4b with amines and ami ne derivatives are studied. In the course of these investigations guanidines 21, imidocarbonic acid esters 22a-c, 30, carbamic acid esters 25, ureas 26, the isourea derivative 29, as well as the 1,3,4-oxadiazole 31 are prepared. The mechanism of these reactions is discussed. Imidocarbonic acid esters 22d-f, 38, N-cyanocarbamates 39, and isoureas 37 can be prepared from 1b and amines or amine derivatives. 2a as well as 13b react with cyanamide to give the N-cyanoisourea 40. Ureas 26 are formed in the reaction of 1a,b with secondary amines at elevated temperatures.The guanidinium cyanide 41a can be obtained by reaction of pyrrolidine with 1b in ether, whereas under similiar conditions from 1a and pyrrolidine the amidine 42 is produced. o-Aminophenol, o-phenylenediamine and anthranilic acid are cyclized by 4b or 1b to afford the heterocyclic compounds 43-45. α- and β-amino acids are transformed by 4b or 1b into the N-(ethoxycarbonyl)amino acid esters 46 and 47, respectively.
