603-81-6Relevant articles and documents
Identification and development of non-cytotoxic cell death modulators: Impact of sartans and derivatives on PPARγ activation and on growth of imatinib-resistant chronic myelogenous leukemia cells
Gust, Ronald,Obexer, Petra,Salcher, Stefan,Schoepf, Anna M.
supporting information, (2020/04/08)
4’-((2-Propyl-1H-benzo[d]imidazol-1-yl)methyl)-[1,1′-biphenyl]-2-carboxylic acid derived from telmisartan was identified as lead for the design of cell death modulators. In this study, we evaluated the efficacy of telmisartan itself and other sartans in combination with imatinib against K562-resistant cells. The findings were directly used to further optimize the lead structure. Telmisartan and candesartan cilexetil represented the most effective sartans, thus the influence of carboxyl/methyl carboxylate groups at positions 7 (compounds 6, 7) or 4 (compounds 12–14) at the benzimidazole core was studied. Additionally, according to the results of a former structure-activity study, telmisartan was transformed to the related amide (1). Telmisartan amide 1, as well as the esters 6 and 12 markedly sensitized the resistant CML cells to imatinib treatment. Correlation with their potency to activate PPARγ is not given. Candesartan cilexetil, telmisartan and 1 showed the profile of partial agonists at PPARγ with EC50 values of 4.2, 4.3 and 9.1 μM, respectively, while 6 and 12 caused only marginal intrinsic activation at 10 μM (Amax = 22% and 13%). However, the repression of the STAT5 phosphorylation relates with the possibility to sensitize K562-resistant CML cells to imatinib treatment. It is worth mentioning that all compounds were per se non-cytotoxic at relevant concentrations.
Synthesis and Antifungal Activity of Substituted 2-Aryl Benzimidazoles Derivatives
Huang, Daye,Qiu, Fang,Zhang, Zhigang,Shi, Liqiao,Cao, Chunxia,Ke, Shaoyong
supporting information, p. 2494 - 2498 (2019/08/12)
Benzimidazole fungicides were among the early systemic fungicides developed and used for controlling a wide variety of plant diseases. During the course of our screening process for active compounds, two 2-aryl benzimidazoles derivatives bearing sulfoxide group (6b and 6c) have been demonstrated to exhibit good inhibition activity against high-resistant isolate of Botrytis cinerea compared with carbendazim, and the inhibition rates are up to 46.67% and 51.11% at the concentration of 10 μg/mL, which might be considered as the active framework for the discovery of novel fungicide to high-resistant isolate of B. cinerea.
MUSCARINIC M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS
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Page/Page column 50, (2018/03/25)
The present invention relates to compounds of formula (I), or their isotopic forms, stereoisomers, tautomers or pharmaceutically acceptable salt (s) thereof as muscarinic M1 receptor positive allosteric modulators (M1 PAMs). The present invention describes the preparation, pharmaceutical composition and the use of compound formula (I).
Synthesis and pharmacological evaluation of N-benzyl substituted 4-bromo-2,5-dimethoxyphenethylamines as 5-HT2A/2C partial agonists
Hansen, Martin,Jacobsen, Stine Engesgaard,Plunkett, Shane,Liebscher, Gudrun Eckhard,McCorvy, John D.,Br?uner-Osborne, Hans,Kristensen, Jesper Langgaard
supporting information, p. 3933 - 3937 (2015/01/30)
N-Benzyl substitution of phenethylamine 5-HT2A receptor agonists has dramatic effects on binding affinity, receptor selectivity and agonist activity. In this paper we examine how affinity for the 5-HT2A/2C receptors are influenced by N-benzyl substitution of 4-bromo-2,5-dimethoxyphenethylamine derivatives. Special attention is given to the 2′ and 3′-position of the N-benzyl as such compounds are known to be very potent. We found that substitutions in these positions are generally well tolerated. The 2′-position was further examined using a range of substituents to probe the hydrogen bonding requirements for optimal affinity and selectivity, and it was found that small changes in the ligands in this area had a profound effect on their affinities. Furthermore, two ligands that lack a 2′-benzyl substituent were also found to have high affinity contradicting previous held notions. Several high-affinity ligands were identified and assayed for functional activity at the 5-HT2A and 5-HT2C receptor, and they were generally found to be less efficacious agonists than previously reported N-benzyl phenethylamines.
Inhibitory properties of 2-substituent-1H-benzimidazole-4-carboxamide derivatives against enteroviruses
Xue, Fei,Luo, Xianjin,Ye, Chenghao,Ye, Weidong,Wang, Yue
body text, p. 2641 - 2649 (2011/06/11)
A series of novel benzimidazole derivatives were designed, synthesized, and evaluated for their activities against four kinds of enteroviruses, that is, Coxsackie virus A16, B3, B6 and Enterovirus 71 in VERO cells. Strong activities against enterovirus replication and low cytotoxicities were observed in these benzimidazoles generally. The most promising compound was (l)-2-(pyridin-2-yl)- N-(2-(4-nitrophenyl)pentan-3-yl)-1H-benzimidazole-4-carboxamide (16), with a high antiviral potency (IC50 = 1.76 μg/mL) and a remarkable selectivity index (328). These compounds were selected for further evaluation as novel enterovirus inhibitors.
Benzimidazole-4-Carboxamide Derivatives, Their Preparation Methods, Pharmaceutical Compositions And Their Uses
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, (2011/11/12)
The present invention relates to the benzimidazole-4-carboxamide derivatives, their preparation methods, pharmaceutical compositions and their uses; wherein X represents monosubstituted or bissubstituted or polysubstitued C1-C14 alkoxy, monosubstituted or bisubstituted or polysubstitued C1-C14 alkyl, monosubstituted or bisubstituted or polysubstitued C2-C14 alkenyl, monosubstituted or bisubstituted or polysubstitued C6-C14 aryl, or monosubstituted or bisubstituted or polysubstitued 5 to 6 membered heterocyclic group, or monosubstituted or bisubstituted or polysubstitued fused ring group containing nitrogen heteroatom; Y represents hydrogen, monosubstituted or bisubstituted or polysubstitued C1-C16 alkyl, monosubstituted or bisubstituted or polysubstitued C6-C12 aryl, or monosubstituted or bisubstituted or polysubstitued 5 to 6 membered heterocyclic group, or monosubstituted or bisubstituted or polysubstitued fused ring group containing nitrogen heteroatom. The derivatives of the present invention have the functions of antiviral medicine.
Synthesis and antiviral activity against Coxsackie virus B3 of some novel benzimidazole derivatives
Cheng, Jun,Xie, Jiangtao,Luo, Xianjin
, p. 267 - 269 (2007/10/03)
Some benzimidazole derivatives were synthesized and the antiviral evaluation against Coxsackie virus B3 is reported. These compounds are proved to be excellent inhibitors of CVB3. Some benzimidazole derivatives were synthesized and evaluated for their antiviral properties. Compounds 20 and 21 showed potent selective activity against Coxsackie virus B3 in VERO cells. Some structure-activity relationships were discussed.
On benzo[b][1,4]diazepinium-olates, -thiolates and -carboxylates as anti-Hueckel mesomeric betaines
Schmidt, Andreas,Gholipour Shilabin, Abbas,Nieger, Martin
, p. 4342 - 4350 (2007/10/03)
2,3-Diaminophenol 4, 3,4-diaminophenol 5, 4-methoxy-1,2-diaminobenzene 6, 3,4-diaminobenzenthiol 7, 2,3-diaminobenzoic acid 8, and 3,4-diaminobenzoic acid 9 were reacted with 2,4-pentanedione to yield the corresponding benzo[b][1,4]diazepinium salts, respectively. The hydroxy-benzo[b][1,4]diazepinium salts 17 and 18 do not form mesomeric betaines (MB) on deprotonation. Instead, they are converted into the diimines 24 and 25. By contrast, the 7-mercaptobenzo[b][1,4]diazepinium salt 20 yields the corresponding thiolate on increasing the pH of the solution. This MB, which possesses 4n π-electrons, does not fit into the classification system of heterocyclic mesomeric betaines accepted today. Deprotonation of the betaine results in the formation of an instable anionic thiolate 31 which oxidizes immediately to the disulfide 32. The carboxy derivatives 21 and 22 readily form cross-conjugated mesomeric betaines. Whereas the diimine 34 proved to be instable, the sodium salt of the diimine 36 was unambiguously characterized. An X-ray single crystal analysis of 22 as its picrate is presented in order to gain additional insights into these 4n π-electron systems.
Substituted benzimidazoles
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, (2008/06/13)
Compounds of formula I are suitable for the production of pharmaceuticals for the prophylaxis and therapy of disorders in whose course an increased activity of NFκB is involved.
3-thienyl and 3-furanyl pyrrolidine modulators of chemokine receptor activity
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, (2008/06/13)
The present invention is directed to pyrrolidine compounds of the formula I: (wherein R1, R2, R3, R4c, R4d, and R4fare defined herein) which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptors CCR-3 and/or CCR-5.
