912962-95-9Relevant articles and documents
Novel BuChE-IDO1 inhibitors from sertaconazole: Virtual screening, chemical optimization and molecular modeling studies
Zhou, You,Lu, Xin,Du, Chenxi,Liu, Yijun,Wang, Yifan,Hong, Kwon Ho,Chen, Yao,Sun, Haopeng
, (2021)
In our effort towards the identification of novel BuChE-IDO1 dual-targeted inhibitor for the treatment of Alzheimer's disease (AD), sertaconazole was identified through a combination of structure-based virtual screening followed by MM-GBSA rescoring. Preliminary chemical optimization was performed to develop more potent and selective sertaconazole analogues. In consideration of the selectivity and the inhibitory activity against target proteins, compounds 5c and 5d were selected for the next study. Further modification of compound 5c led to the generation of compound 10g with notably improved selectivity towards BuChE versus AChE. The present study provided us with a good starting point to further design potent and selective BuChE-IDO1 inhibitors, which may benefit the treatment of late stage AD.
BuChE-IDO1 inhibitor as well as preparation method and application thereof
-
, (2021/04/26)
The invention relates to the field of medicines, and particularly discloses a BuChE-IDO1 inhibitor as well as a preparation method and application thereof. The 7-chlorine-3-substituted benzothiophene part of sertaconazole is chemically modified, the influence of the 7-chlorine-3-substituted benzothiophene part of sertaconazole on the in-vitro inhibitory activity of AChE, BuChE and IDO1 is explored, the target compound is further optimized, and the technical problems that an existing BuChE-IDO1 inhibitor is poor in pertinence and safety are solved. What is explored is that an appropriate substituent group introduced to a 2-benzothiazole ring can form additional interaction with surrounding amino acids and heme iron, so that the binding affinity of the analogue with BuChE and IDO1 is increased, and a new idea is broadened for more efficient and targeted treatment of advanced AD diseases.
Diaryl-containing imidazole compound and preparation method and medical application thereof
-
, (2019/02/21)
The invention discloses a diaryl-containing imidazole compound. The invention further discloses application of the diaryl-containing imidazole compound to preparation of drugs for preventing or treating Alzheimer's disease. The inventor screens butyrylcholine esterase and IDO1 as carriers for inhibiting the activity to evaluate the effect of the diaryl imidazole compound to treat Alzheimer's disease, and finds that the diaryl imidazole compound has good in vitro activity, and can be further developed as a precursor substance for performing the Alzheimer's disease resistant effect by inhibitingthe activity of cholinesterase. (The formula is shown in the description).
Potholing of the hydrophobic heme oxygenase-1 western region for the search of potent and selective imidazole-based inhibitors
Salerno, Loredana,Amata, Emanuele,Romeo, Giuseppe,Marrazzo, Agostino,Prezzavento, Orazio,Floresta, Giuseppe,Sorrenti, Valeria,Barbagallo, Ignazio,Rescifina, Antonio,Pittalà, Valeria
, p. 54 - 62 (2018/02/19)
Here we report the design, synthesis, and molecular modeling of new potent and selective imidazole-based HO-1 inhibitors in which the imidazole nucleus and the hydrophobic groups are linked by a phenylethanolic spacer. Most of the tested compounds showed
From the first selective non-peptide AT2 receptor agonist to structurally related antagonists
Murugaiah,Wu, Xiongyu,Wallinder, Charlotta,Mahalingam,Wan, Yiqian,Sk?ld, Christian,Botros, Milad,Guimond, Marie-Odile,Joshi, Advait,Nyberg, Fred,Gallo-Payet, Nicole,Hallberg, Anders,Alterman, Mathias
, p. 2265 - 2278 (2012/05/04)
A para substitution pattern of the phenyl ring is a characteristic feature of the first reported selective AT2 receptor agonist M024/C21 (1) and all the nonpeptidic AT2 receptor agonists described so far. Two series of compounds structurally related to 1 but with a meta substitution pattern have now been synthesized and biologically evaluated for their affinity to the AT1 and AT2 receptors. A high AT 2/AT1 receptor selectivity was obtained with all 41 compounds synthesized, and the majority exhibited Ki ranging from 2 to 100 nM. Five compounds were evaluated for their functional activity at the AT2 receptor, applying a neurite outgrowth assay in NG108-15 cells. Notably, four of the five compounds, with representatives from both series, acted as potent AT2 receptor antagonists. These compounds were found to be considerably more effective than PD 123,319, the standard AT2 receptor antagonist used in most laboratories. No AT2 receptor antagonists were previously reported among the derivatives with a para substitution pattern. Hence, by a minor modification of the agonist 1 it could be transformed into the antagonist, compound 38. These compounds should serve as valuable tools in the assessment of the role of the AT2 receptor in more complex physiological models.
NEW TRICYCLIC ANGIOTENSIN II AGONISTS
-
, (2008/06/13)
There is provided compounds of Formula (I), wherein A, X1, X2, X3, X4, Y1, Y2, Y3, Y4, Z1, Z2, R4 and R5 have meanings given in the description, and pharmaceuticalfy-acceptable salts thereof, which compounds are useful as selective agonists of the AT2 receptor, and thus, in particular, in the treatment of inter alia gastrointestinal conditions, such as dyspepsia, IBS and MOF, and cardiovascular disorders.
