711007-44-2Relevant academic research and scientific papers
Synthesis and evaluation of 2-(4-[4-acetylpiperazine-1-carbonyl] phenyl)-1H-benzo[d]imidazole-4-carboxamide derivatives as potential PARP-1 inhibitors and preliminary study on structure-activity relationship
Cao, Xuan,Chen, Miaojia,Huang, Honglin,Jiang, Lizhi,Li, Yang,Liu, Yunfan,Peng, Junmei,Tang, Guotao,Wu, Kaiyue
, (2021/06/25)
Although 1H-benzo[d]imidazole-4-carboxamide derivatives have been explored for a long time, the structure–activity relationship of the substituents in the hydrophobic pocket (AD binding sites) has not thoroughly discovered. Here in, a series of 2-(4-[4-acetylpiperazine-1-carbonyl]phenyl)-1H-benzo[d]imidazole-4-carboxamide derivatives have been designed, synthesized, and successful characterization as novel and effective poly ADP-ribose polymerases (PARP)-1 inhibitors to improve the structure–activity relationships about the substituents in the hydrophobic pocket. These derivatives were evaluated for their PARP-1 inhibitory activity and cellular inhibitory against BRCA-1 deficient cells (MDA-MB-436) and wild cells (MCF-7) using PARP kit assay and MTT method. The results indicated that compared with other heterocyclic compounds, furan ring-substituted derivatives 14n-14q showed better PARP-1 inhibitory activity. Among this derivatives, compound 14p displayed the strongest inhibitory effects on PARP-1 enzyme (IC50?=?0.023 μM), which was close to that of Olaparib. 14p (IC50?=?43.56 ± 0.69 μM) and 14q (IC50?=?36.69 ± 0.83 μM) displayed good antiproliferation activity on MDA-MB-436 cells and inactivity on MCF-7 cells, indicating that 14p and 14q have high selectivity and targeting. The molecular docking method was used to explore the binding mode of compound 14p and PARP-1, and implied that the formation of hydrogen bond was essential for PARP-1 inhibition activities. This study also showed that in the hydrophobic pocket (AD binding sites), the introduction of strong electronegative groups (furan ring, e.g.) or halogen atoms in the side chain of benzimidazole might improve its inhibitory activity and this strategy could be applied in further research.
Compound containing benzo five-membered heterocyclic structure and preparation method and application thereof
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Paragraph 0106-0111, (2021/08/14)
The invention relates to the field of medicinal chemistry, and discloses a compound containing a benzo five-membered heterocyclic structure as well as a preparation method and application thereof. The invention also discloses a composition containing the benzo five-membered heterocyclic compound or the pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, and application of the composition in preparation of PARP-1 and ERK inhibitors. The compound can be used for treating diseases such as tumors.
Development of 2-(4-pyridyl)-benzimidazoles as PKN2 chemical tools to probe cancer
Elkins, Jonathan M.,Fala, Angela M.,Massirer, Katlin B.,Pennicott, Lewis E.,Reuillon, Tristan D.,Scott, Fiona,Ward, Simon E.
supporting information, (2020/02/27)
Kinases are signalling proteins which have proven to be successful targets for the treatment of a variety of diseases, predominantly in cancers. However, only a small proportion of kinases (50 of 0.064 μM against PKN2, with ca. 17-fold selectivity over close homologue, PKN1.
PARP inhibitors containing phthalazin-1(2H)-one structure, and preparation method and medical application thereof
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Paragraph 0076; 0078; 0079, (2019/02/04)
The invention relates to the field of medicinal chemistry, specifically to 4-(4-fluoro-3-(1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazinyl-2-carbonyl)benzyl)phthalazin-1(2H)-one derivatives (I). The formula I is as described in the specification, and R in the formula I is as defined in the specification. The invention also discloses a preparation method for the derivatives, and pharmaceutical compositions containing the derivatives. The results of pharmacodynamic tests prove that the derivatives of the invention have PARP inhibitory activity and can be used as a single therapeutic agent fortumors or be used in combination with other antitumor drugs, so the effects of improving the efficacy of conventional antitumor drugs and reducing the dosage and toxicity of conventional antitumor drugs are obtained.
Benzo[4,5]imidazole[1,2-a]pyrazine ketone derivatives as well as preparation method and application thereof
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Paragraph 0090; 0092-0093, (2019/05/28)
The invention provides benzo[4,5]imidazole[1,2-a]pyrazine ketone derivatives and pharmaceutically acceptable salt, wherein the structure is as shown in a general formula I. The invention also discloses a preparation method of the benzo[4,5]imidazole[1,2-a]pyrazine ketone derivatives as well as the application of the benzo[4,5]imidazole[1,2-a]pyrazine ketone derivatives to the preparation of anti-tumor medicines and the preparation of PARP inhibitor medicines.
Medicine compounds for curing metastatic tumors
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Paragraph 0022; 0023; 0024, (2018/04/01)
The invention discloses medicine compounds for curing metastatic tumors. The medicine compounds are represented by a formula I, wherein R is H, alkyl with 1-3 carbon atoms or a halogen. The medicine compounds are researched based on a veliparib structure and is a novel medicine for curing the metastatic tumors, the medicine compounds can effectively inhibit PARP (poly ADP-ribose polymerase) activity, and has remarkable treatment effects on metastatic breast cancer, colon cancer, metastatic melanoma and brain tumor aspects.
Design, synthesis and biological evaluation of 4-amidobenzimidazole acridine derivatives as dual PARP and Topo inhibitors for cancer therapy
Yuan, Zigao,Chen, Shaopeng,Chen, Changjun,Chen, Jiwei,Chen, Chengken,Dai, Qiuzi,Gao, Chunmei,Jiang, Yuyang
, p. 1135 - 1146 (2017/08/02)
PARP-1 could repair the DNA damages induced by Topo inhibitors, therefore inhibiting Topo and PARP-1 simultaneously might be able to overcome resistance and improve outcomes. In this study a series of 4-amidobenzimidazole acridines were designed and synthesized as dual Topo and PARP-1 inhibitors. Compound 11l displayed good inhibitory activities against Topo and PARP-1, as well as significantly inhibited cancer cells proliferation. Further mechanistic evaluations indicated that 11l treatment in MCF-7 cells induced accumulated DNA double-strand breaks, prompted remarkable apoptosis, and caused prominent G0/G1 cell cycle arrest. Moreover, 11l greatly suppressed tumor growth in mice, and displayed favorable metabolic properties in liver microsomes. Our study suggested that single agents inhibiting Topo and PARP concurrently might be an alternative for cancer therapy and 11l represented a potential lead compound for development of antitumor agents.
Compound for treating metastatic tumors and application thereof
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Paragraph 0015, (2016/11/28)
The invention discloses a compound for treating metastatic tumors and application thereof. The compound is shown in the formula I, wherein R1-R8 are independently selected from alkyl groups or part of deuterated alkyl groups of H, D and C1-C3 respectively. The compound is a new drug for treating metastatic tumors and is developed on the basis of a veliparib structure, and the activity of PARP can be effectively restrained. The compound can serve as a drug for treating uterine cancers or lung cancers or gastric cancers or melanoma or breast cancers or prostatic cancers or colorectal cancers or intracranial tumors. The formula I is shown in the description.
Fluoroalkyl-substituted 2-amidobenzimidazoles and their effect on plant growth
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Paragraph 0051, (2013/03/26)
Use of fluoroalkyl-substituted 2-amidobenzimidazoles of the formula (I), or agriculturally acceptable salts thereof, for the treatment of plants for inducing growth regulating responses on plants, on seeds from which they grow or on the locus in which they grow in their normal habitat and in the absence of extraordinary environmental conditions and which result in superior growth of these treated plants, certain parts of these plants or, more generally, crop yield.
Fluoroalkyl-substituted 2-amidobenzimidazoles
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Page/Page column 11, (2011/10/02)
Use of fluoroalkyl-substituted 2-amidobenzimidazoles of the formula (I), or salts thereof, for enhancing stress tolerance in plants to abiotic stress, especially for strengthening plant growth and/or for increasing plant yield, and selected processes for preparing such fluoroalkyl-substituted 2-amidobenzimidazoles of the formula (I).
