- Reactions of methyl 4-aminofurazan-3-carboximidate with nitrogen-containing nucleophiles
-
Methyl 4-aminofurazan-3-carboximidate reacts with aromatic amines and hydrazines to give the corresponding amidines and amidrazones. The reaction of the title compound with o-phenylenediamine yields 3-amino-4-(2-benzimidazolyl)furazan, and with acylhydraz
- Sergievskii,Pirogov,Mel'nikova,Tselinskii
-
-
Read Online
- Discovery and Biological Evaluation of a Novel Highly Potent Selective Butyrylcholinsterase Inhibitor
-
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.
- 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
-
-
Read Online
- Compound with benzimidazole structure and preparation method and application thereof
-
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
-
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.
- 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)
-
- Benzimidazole bifurazan series compounds and synthesis method thereof
-
The invention provides benzimidazole bifurazan series compounds and a synthesis method thereof. The molecular structure of the compounds is represented by a formula I, wherein R1 is selected from hydrogen, halogen, trifluoromethyl, nitryl, amino, sulfo, methyl, tert-butyl, methoxyl, carboxyl, ethoxyformyl or benzoyl; R2 is selected from hydrogen or fluorine. On the basis, the invention discloses an efficient method for preparing the series of compounds. The preparation method comprises the steps: synthesizing an intermediate 4-amino-1,2,5-oxadiazole-3-methoxyamidine by taking malononitrile asa starting raw material, carrying out a reaction on the intermediate with o-phenylenediamine or a substitute thereof under a heating reflux condition by taking acetic acid as a solvent, cooling, adding water, stirring to separate out a solid after the reaction is finished, and carrying out suction filtration, washing, drying and the like to obtain a final product. According to the method, a pure product can be obtained without recrystallization, column chromatography separation and other steps, the method is simple, rapid and practical, and the yield can generally reach 80% or above.
- -
-
Paragraph 0046-0053
(2020/07/28)
-
- Butyrylcholine esterase selective inhibitor and preparation method and application thereof
-
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.
- -
-
-
- A facile synthesis and microtubule-destabilizing properties of 4-(1H-benzo[d]imidazol-2-yl)-furazan-3-amines
-
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.
- 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.
-
p. 237 - 251
(2015/03/30)
-
- FURAZANOBENZIMIDAZOLES AS PRODRUGS TO TREAT NEOPLASTIC OR AUTOIMMUNE DISEASES
-
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.
- -
-
Page/Page column 29; 31
(2011/02/24)
-