63823-75-6Relevant academic research and scientific papers
Benzoheterocyclic Oxime Carbamates Active against Mycobacterium tuberculosis: Synthesis, Structure-Activity Relationship, Metabolism, and Biology Triaging
Van Der Westhuyzen, Renier,Mabhula, Amanda,Njaria, Paul M.,Müller, Rudolf,Ngumbu Muhunga, Denis,Taylor, Dale,Lawrence, Nina,Njoroge, Mathew,Brunschwig, Christel,Moosa, Atica,Singh, Vinayak,Rao, Srinivasa P.S.,Manjunatha, Ujjini H.,Smith, Paul W.,Warner, Digby F.,Street, Leslie J.,Chibale, Kelly
supporting information, p. 9444 - 9457 (2021/07/19)
Screening of a library of small polar molecules against Mycobacterium tuberculosis (Mtb) led to the identification of a potent benzoheterocyclic oxime carbamate hit series. This series was subjected to medicinal chemistry progression underpinned by structure-activity relationship studies toward identifying a compound for proof-of-concept studies and defining a lead optimization strategy. Carbamate and free oxime frontrunner compounds with good stability in liver microsomes and no hERG channel inhibition liability were identified and evaluated in vivo for pharmacokinetic properties. Mtb-mediated permeation and metabolism studies revealed that the carbamates were acting as prodrugs. Toward mechanism of action elucidation, selected compounds were tested in biology triage assays to assess their activity against known promiscuous targets. Taken together, these data suggest a novel yet unknown mode of action for these antitubercular hits.
Compound with benzimidazole structure and preparation method and application thereof
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Paragraph 0021; 0032-0034, (2021/06/09)
The invention discloses a compound with a benzimidazole structure and a preparation method and application thereof. The invention discloses a compound shown in a formula (I), and further discloses application of the compound in preparation of a medicine for preventing or treating Alzheimer's disease. The inventor uses butyrylcholine esterase inhibitory activity, selective screening and Morris water maze experiments as carriers to evaluate the compound shown in the formula (I) for treating the Alzheimer's disease (especially moderate and severe Alzheimer's disease), and finds that the compound has good in-vitro and in-vivo activity and extremely high selectivity, and can be used for preparing the compound for treating the Alzheimer's disease. The compound can be used as a precursor substance for further developing the effect of treating the Alzheimer's disease by selectively inhibiting butyrylcholine esterase.
Highly Potent and Selective Butyrylcholinesterase Inhibitors for Cognitive Improvement and Neuroprotection
Li, Qi,Chen, Ying,Xing, Shuaishuai,Liao, Qinghong,Xiong, Baichen,Wang, Yuanyuan,Lu, Weixuan,He, Siyu,Feng, Feng,Liu, Wenyuan,Chen, Yao,Sun, Haopeng
, p. 6856 - 6876 (2021/05/29)
Butyrylcholinesterase (BChE) has been considered as a potential therapeutic target for Alzheimer's disease (AD) because of its compensation capacity to hydrolyze acetylcholine (ACh) and its close association with Aβ deposit. Here, we identified S06-1011 (hBChE IC50 = 16 nM) and S06-1031 (hBChE IC50 = 25 nM) as highly effective and selective BChE inhibitors, which were proved to be safe and long-acting. Candidate compounds exhibited neuroprotective effects and the ability to improve cognition in scopolamine- and Aβ1-42 peptide-induced cognitive deficit models. The best candidate S06-1011 increased the level of ghrelin, a substrate of BChE, which can function as improving the mental mood appetite. The weight gain of the S06-1011-treated group remarkably increased. Hence, BChE inhibition not only plays a protective role against dementia but also exerts a great effect on treating and nursing care.
Discovery and Biological Evaluation of a Novel Highly Potent Selective Butyrylcholinsterase Inhibitor
Li, Qi,Xing, Shuaishuai,Chen, Ying,Liao, Qinghong,Xiong, Baichen,He, Siyu,Lu, Weixuan,Liu, Yang,Yang, Hongyu,Li, Qihang,Feng, Feng,Liu, Wenyuan,Chen, Yao,Sun, Haopeng
, p. 10030 - 10044 (2020/10/18)
To discover novel BChE inhibitors, a hierarchical virtual screening protocol followed by biochemical evaluation was applied. The most potent compound 8012-9656 (eqBChE IC50 = 0.18 ± 0.03 μM, hBChE IC50 = 0.32 ± 0.07 μM) was purchased and synthesized. It inhibited BChE in a noncompetitive manner and could occupy the binding pocket forming diverse interactions with the target. 8012-9656 was proven to be safe in vivo and in vitro and showed comparable performance in ameliorating the scopolamine-induced cognition impairment to tacrine. Additionally, treatment with 8012-9656 could almost entirely recover the Aβ1-42 (icv)-impaired cognitive function to the normal level and showed better behavioral performance than donepezil. The evaluation of the Aβ1-42 total amount confirmed its anti-amyloidogenic profile. Moreover, 8012-9656 possessed blood-brain barrier (BBB) penetrating ability, a long T1/2, and low intrinsic clearance. Hence, the novel potential BChE inhibitor 8012-9656 can be considered as a promising lead compound for further investigation of anti-AD agents.
Butyrylcholine esterase selective inhibitor and preparation method and application thereof
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Paragraph 0032; 0033; 0034, (2019/02/19)
The invention discloses a butyrylcholine esterase selective inhibitor and a preparation method and application thereof. The invention discloses a compound shown in a formula (I), and also discloses application of the compound in preparation of medicines for preventing or treating Alzheimer's disease. An inventor uses the inhibiting activity of butyrylcholine esterase, selective screening and Morris water maze experiment as carriers to evaluate the function of the compound in the formula (I) for treating the Alzheimer's disease (especially medium and severe Alzheimer's disease), the good in-vitro and in-vivo activities and higher selectivity are found, and the compound can be further developed into a precursor substance which can selectively inhibit the butyrylcholine esterase to reach thefunction of treating the Alzheimer's disease. The formula (I) is shown in the specification.
Synthesis and antifungal activity of novel α-alkoxyimino-(1H-benzoimidazol-2-yl)acetonitriles containing piperazine moiety
Jin, Qingdong,Li, Fubo,Li, Ying,Jin, Fei,Jiang, Lin
, p. 7695 - 7702 (2015/02/19)
A series of α-alkoxyimino-[1-(4-methylpiperazino-1-yl)carbonylmethyl-1H-benzimidazol-2-yl] acetonitriles were synthesized from o-phenylenediamine, ethyl cyanoacetate, chloroacetyl piperazine, and haloalkane/benzyl chloride by multi-step reactions. The structures of the target compounds were elucidated by IR, 1H NMR, MS, and elemental analysis. All the target compounds were tested for in vitro antifungal activities against Sclerotinia sclerotiorum and Botrytis cinerea by the mycelium growth rate method, and the results indicated that some compounds displayed higher antifungal activity as compared to carbendazim.
A facile synthesis and microtubule-destabilizing properties of 4-(1H-benzo[d]imidazol-2-yl)-furazan-3-amines
Stepanov, Andrei I.,Astrat'ev, Alexander A.,Sheremetev, Aleksei B.,Lagutina, Nataliya K.,Palysaeva, Nadezhda V.,Tyurin, Aleksei Yu.,Aleksandrova, Nataliya S.,Sadchikova, Nataliya P.,Suponitsky, Kyrill Yu.,Atamanenko, Olga P.,Konyushkin, Leonid D.,Semenov, Roman V.,Firgang, Sergei I.,Kiselyov, Alex S.,Semenova, Marina N.,Semenov, Victor V.
supporting information, p. 237 - 251 (2015/03/30)
A series of 4-(1H-benzo[d]imidazol-2-yl)-furazan-3-amines (BIFAs) were prepared in good yields (60-90% for each reaction step) via a novel procedure from aminofurazanyl hydroximoyl chlorides and o-diaminobenzenes. The synthetic sequence was run under mild reaction conditions, it was robust and did not require extensive purification of intermediates or final products. Furthermore, there was no need for protection of reactive moieties allowing for the parallel synthesis of diverse BIFA derivatives. Subsequent biological evaluation of the resulting compounds revealed their anti-proliferative effects in the sea urchin embryo model and in cultured human cancer cell lines. The most active compounds showed 0.2-2 μM activities in both assay systems. The unsubstituted benzene ring of the benzoimidazole template as well as the unsubstituted amino group in the furazan ring were essential prerequisites for the antimitotic activity of BIFAs. Compound 57 bearing the 2-chlorophenyl acetamide substituent at the nitrogen atom of the imidazole ring was the most active molecule in the examined set.
FURAZANOBENZIMIDAZOLES AS PRODRUGS TO TREAT NEOPLASTIC OR AUTOIMMUNE DISEASES
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Page/Page column 29; 30; 31, (2011/02/24)
A compound of formula (II) wherein (a) represents a divalent benzene residue which is unsubstituted or substituted by one or two additional substituents independently selected from lower alkyl, halo-lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, acyloxy-lower alkyl, phenyl, hydroxy, lower alkoxy, hydroxy-lower alkoxy, lower alkoxy-lower alkoxy, phenyl-lower alkoxy, lower alkylcarbonyloxy, amino, mono(lower alkyl)amino, di(lower alkyl)amino, mono(lower alkenyl)amino, di(lower alkenyl)amino, lower alkoxycarbonylamino, lower alkylcarbonylamino, substituted amino wherein the two substituents on nitrogen form together with the nitrogen heterocyclyl, lower alkylcarbonyl, carboxy, lower 15 alkoxycarbonyl, cyano, halogen, and nitro; or wherein two adjacent substituents can be methylenedioxy; or a divalent pyridine residue (Z = N) which is unsubstituted or substituted additionally by lower alkyl, lower alkoxy, lower alkoxy-lower alkoxy,amino, optionally substituted by one or two substituents selected from lower alkyl, lower alkenyl and alkylcarbonyl, halo-20 lower alkyl, lower alkoxy-lower alkyl, or halogen; R1 represents hydrogen, lower alkylcarbonyl, hydroxy-lower alkylor cyano-loweralkyl; and R2 represents a group selected from: (b), (c) and (d); or pharmaceutically acceptable salts thereof.
