31434-93-2Relevant academic research and scientific papers
Discovery of novel propargylamine-modified 4-aminoalkyl imidazole substituted pyrimidinylthiourea derivatives as multifunctional agents for the treatment of Alzheimer's disease
Xu, Yi-xiang,Wang, Huan,Li, Xiao-kang,Dong, Sheng-nan,Liu, Wen-wen,Gong, Qi,Wang, Tian-duan-yi,Tang, Yun,Zhu, Jin,Li, Jian,Zhang, Hai-yan,Mao, Fei
, p. 33 - 47 (2018)
A series of novel propargylamine-modified pyrimidinylthiourea derivatives (1–3) were designed and synthesized as multifunctional agents for Alzheimer's disease (AD) therapy, and their potential was evaluated through various biological experiments. Among these derivatives, compound 1b displayed good selective inhibitory activity against AChE (vs BuChE, IC50 = 0.324 μM, SI > 123) and MAO-B (vs MAO-A, IC50 = 1.427 μM, SI > 35). Molecular docking study showed that the pyrimidinylthiourea moiety of 1b could bind to the catalytic active site (CAS) of AChE, and the propargylamine moiety interacted directly with the flavin adenine dinucleotide (FAD) of MAO-B. Moreover, 1b demonstrated mild antioxidant ability, good copper chelating property, effective inhibitory activity against Cu2+-induced Aβ1?42 aggregation, moderate neuroprotection, low cytotoxicity, and appropriate blood?brain barrier (BBB) permeability in vitro and was capable of ameliorating scopolamine-induced cognitive impairment in mice. These results indicated that 1b has the potential to be a multifunctional candidate for the treatment of Alzheimer's disease.
Nickel-Catalyzed Reversible Functional Group Metathesis between Aryl Nitriles and Aryl Thioethers
Delcaillau, Tristan,Boehm, Philip,Morandi, Bill
supporting information, p. 3723 - 3728 (2021/04/07)
We describe a new functional group metathesis between aryl nitriles and aryl thioethers. The catalytic system nickel/dcype is essential to achieve this fully reversible transformation in good to excellent yields. Furthermore, the cyanide- and thiol-free reaction shows high functional group tolerance and great efficiency for the late-stage derivatization of commercial molecules. Finally, synthetic applications demonstrate its versatility and utility in multistep synthesis.
1,(3,)5-substituted imidazoles, useful in the treatment of hypertension and methods for their preparation
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Paragraph 0204; 0206; 0210; 0212, (2016/03/04)
The present invention provides novel 1,5 and 1,3,5-substituted imidazole compounds in hydrophilic or lipophilic form, which are useful as angiotensin II ATI receptor antagonists suitable for transdermal delivery. The invention also provides pharmaceutical compositions containing such compounds, processes and intermediates for preparing compounds and their use in methods of treating hypertension and cardiovascular diseases.
NRF2 REGULATORS
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Page/Page column 414; 415, (2015/07/07)
The present invention relates to bis aryl analogs, pharmaceutical compositions containing them and their use as Nrf2 regulators.
Bicyclic Pyrimidine Compounds
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Paragraph 0227; 0228; 0229, (2014/07/23)
The present invention provides compounds of the Formula I: wherein X is a bond or CH2; R is selected from the group consisting of R1 and R2 are each independently selected from the group consisting of CH and N; R3 is H or CH3; R4 is H or CH3; L is selected from the group consisting of —O(CH2)3—, —C(O)NH(CH2)2—, —CH2C(O)NH(CH2)2—, —(CH2)3N(C(O)CH3)CH2—, —(CH2)2N(C(O)CH3)CH2—, —(CH2)3NH—, (CH2)2OCH2—, —(CH2)4—, —(CH2)2NHCH2—, —(CH2)3O—, and —CH2O(CH2)2—; or a pharmaceutically acceptable salt thereof. Compounds of this invention are autotaxin inhibitors.
Facile syntheses of histamine-and imidazole-4-propionic acid-derived room-temperature ionic liquids
Dubey, Ravi Kant,Kumar, Neeraj,Jain, Rahul
experimental part, p. 2207 - 2216 (2012/06/18)
We report synthesis of histamine-and imidazole-4-propionic acid-based ionic liquids containing a variety of alkyl and aryl groups placed at the two different positions of the constituent imidazole ring in convenient steps in good yields.
Towards non-peptide ANG II AT1 receptor antagonists based on urocanic acid: Rational design, synthesis and biological evaluation
Agelis, George,Resvani, Amalia,Matsoukas, Minos-Timotheos,Tselios, Theodore,Kelaidonis, Konstantinos,Kalavrizioti, Dimitra,Vlahakos, Demetrios,Matsoukas, John
, p. 411 - 420 (2011/10/04)
A series of o-, m- and p-benzyl tetrazole derivatives 11a-c has been designed, synthesized and evaluated as potential Angiotensin II AT1 receptor antagonists, based on urocanic acid. Compound 11b with tetrazole moiety at the m-position showed moderate, however, higher activity compared to the o- and p-counterpart analogues. Molecular modelling techniques were performed in order to extract their putative bioactive conformations and explore their binding modes.
Structure based design of novel inhibitors for histidinol dehydrogenase from Geotrichum candidum
Pahwa, Sonia,Kaur, Simranjeet,Jain, Rahul,Roy, Nilanjan
supporting information; experimental part, p. 3972 - 3976 (2010/09/03)
Histidinol dehydrogenase, the product of the HisD gene, mediates the final step in the histidine biosynthetic pathway. This enzyme has captured attention for drug discovery studies in past few years. Recently, our group cloned and expressed Geotrichum candidum histidinol dehydrogenase and successful screening of substrate analog inhibitors of histidinol dehydrogenase led to some antifungal compounds with IC50 values in micromolar range. In this study, we have done docking analysis of these antifungal agents in G. candidum. Two new compounds were designed based on the docking results and these compounds turned out to be potent inhibitors of G. candidum histidinol dehydrogenase, showing IC50 values as low as 3.17 μM.
N-benzyl imidazole derivatives and their use as aldosterone synthase inhibitors
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Page/Page column 6-7, (2009/09/26)
The invention relates to the use of a N-benzyl 5-substituted imidazole derivative having the general formula I wherein R is (C1-3)alkyl, (C1-3)alkyloxy, halogen, nitro or cyano; R1 is (C1-6)alkyl, optionally substituted with OH, (C1-3)alkyloxy, (C1-3)alkylcarbonyloxy, (C1-3)alkyloxycarbonyl or halogen, or (C1-3)alkyloxycarbonyl; or R1 is phenyl, optionally substituted with 1-3 substituents independently selected from (C1-3)alkyl, (C1-3)alkyloxy, hydroxylmethyl and halogen; or a pharmaceutically acceptable salt thereof, for the preparation of a medicament for the treatment of a disorder or disease in a subject mediated by aldosterone synthase or responsive to inhibition of aldosterone synthase.
Acylguanidines as bioisosteres of guanidines: NG-acylated imidazolylpropylguanidines, a new class of histamine h2 receptor agonists
Ghorai, Prasanta,Kraus, Anja,Keller, Max,G?tte, Carsten,Igel, Patrick,Schneider, Erich,Schnell, David,Bernhardt, Günther,Dove, Stefan,Zabel, Manfred,Elz, Sigurd,Seifert, Roland,Buschauer, Armin
scheme or table, p. 7193 - 7204 (2009/10/02)
N1-Aryl(heteroaryl)alkyl-N2-[3-(1H-imidazol-4-yl) propyl]guanidines are potent histamine H2-receptor (H2R) agonists, but their applicability is compromised by the lack of oral bioavailability and CNS penetration. To improve pharmacokinetics, we introduced carbonyl instead of methylene adjacent to the guanidine moiety, decreasing the basicity of the novel H2R agonists by 4-5 orders of magnitude. Some acylguanidines with one phenyl ring were even more potent than their diaryl analogues. As demonstrated by HPLC-MS, the acylguanidines (bioisosteres of the alkylguanidines) were absorbed from the gut of mice and detected in brain. In GTPase assays using recombinant receptors, acylguanidines were more potent at the guinea pig than at the human H2R. At the hH1R and hH3R, the compounds were weak to moderate antagonists or partial agonists. Moreover, potent partial hH4R agonists were identified. Receptor subtype selectivity depends on the imidazolylpropylguanidine moiety (privileged structure), opening an avenue to distinct pharmacological tools including potent H4R agonists.
