10314-98-4Relevant articles and documents
Pyrazolopyrimidines as Potent Stimulators for Transient Receptor Potential Canonical 3/6/7 Channels
Qu, Chunrong,Ding, Mingmin,Zhu, Yingmin,Lu, Yungang,Du, Juan,Miller, Melissa,Tian, Jinbin,Zhu, Jinmei,Xu, Jian,Wen, Meng,Er-Bu,Wang, Jule,Xiao, Yuling,Wu, Meng,McManus, Owen B.,Li, Min,Wu, Jilin,Luo, Huai-Rong,Cao, Zhengyu,Shen, Bing,Wang, Hongbo,Zhu, Michael X.,Hong, Xuechuan
, p. 4680 - 4692 (2017)
Transient receptor potential canonical 3/6/7 (TRPC3/6/7) are highly homologous receptor-operated nonselective cation channels. Despite their physiological significance, very few selective and potent agonists are available for functional examination of these channels. Using a cell-based high throughput screening approach, a lead compound with the pyrazolopyrimidine skeleton was identified as a TRPC6 agonist. Synthetic schemes for the lead and its analogues were established, and structural-activity relationship studies were carried out. A series of potent and direct agonists of TRPC3/6/7 channels were identified, and among them, 4m-4p have a potency order of TRPC3 > C7 > C6, with 4n being the most potent with an EC50 of 20 nM on TRPC3. Importantly, these compounds exhibited no stimulatory activity on related TRP channels. The potent and selective compounds described here should be suitable for evaluation of the roles of TRPC channels in the physiology and pathogenesis of diseases, including glomerulosclerosis and cancer.
Synthesis and biological evaluation of piperidyl benzimidazole carboxamide derivatives as potent PARP-1 inhibitors and antitumor agents
Zhang, Xinwei,Zhang, Cunlong,Tang, Lin,Lu, Kuan,Zhao, Huan,Wu, Weibin,Jiang, Yuyang
, (2019)
We have synthesized a series of compounds based on a piperidyl benzimidazole carboxamide structure, and tested their PARP-1 inhibitory activity, as well as cellular inhibitory activity. Some of them show great potency as PARP-1 inhibitors and antitumor activity, which are valuable for further research. In addition, the predicted ADME properties and proposed binding mode with PARP-1 of the compounds were obtained via computational simulation.
Discovery of the PARP (poly ADP-ribose polymerase) inhibitor 2-(1-(4,4-difluorocyclohexyl)piperidin-4-yl)-1H-benzo[d]imidazole-4-carboxamide for the treatment of cancer
Chen, Dawei,Jiang, Yuyang,Shi, Zhichao,Tang, Lin,Wu, Weibin,Zhai, Xin,Zhang, Cunlong
, (2021)
In this work, two series of cyclic amine-containing benzimidazole carboxamide derivatives were designed and synthesized as potent anticancer agents. PARP1/2 inhibitory activity assays indicated that most of the compounds showed significant activity. The in vitro antiproliferative activity of these compounds was investigated against four human cancer cell lines (MDA-MB-436, MDA-MB-231, MCF-7 and CAPAN-1), and several compounds exhibited strong cytotoxicity to tumor cells. Among them, 2-(1-(4,4-difluorocyclohexyl)piperidin-4-yl)-1H-benzo[d]imidazole-4-carboxamide (17d) was found to be effective PARP1/2 inhibitors (IC50 = 4.30 and 1.58 nM, respectively). In addition, 17d possessed obvious selective antineoplastic activity and noteworthy microsomal metabolic stability. What's more, further studies revealed that 17d was endowed with an excellent ADME profile. These combined results indicated that 17d could be a promising candidate for the treatment of cancer.
Ugi-type reactions of spirocyclic indolenines as a platform for compound library generation
Estévez, Verónica,Kloeters, Laura,Kwietniewska, Natalia,Vicente-García, Esther,Ruijter, Eelco,Orru, Romano V.A.
, p. 376 - 380 (2017)
A simple and efficient method for the synthesis of highly substituted spiroindoline derivatives is presented. A Fischer indolization is combined with Ugi-type reactions to explore the chemical space concerning this privileged structure. Moreover, spiropip
Structure-Activity Relationship of Anti-Mycobacterium abscessus Piperidine-4-carboxamides, a New Class of NBTI DNA Gyrase Inhibitors
Alvarez, Nadine,Beuchel, Andreas,Dick, Thomas,Hoenke, Sophie,Imming, Peter,Madani, Abdeldjalil,Mann, Lea,Negatu, Dereje A.,Richter, Adrian,Robaa, Dina,Zimmerman, Matthew D.,Csuk, René
supporting information, p. 417 - 427 (2022/03/16)
Mycobacterium abscessus causes difficult-to-cure pulmonary infections. The bacterium is resistant to most anti-infective agents, including first line antituberculosis (anti-TB) drugs. MMV688844 (844) is a piperidine-4-carboxamide (P4C) with bactericidal properties against M. abscessus. We recently identified DNA gyrase as the molecular target of 844. Here, we present in silico docking and genetic evidence suggesting that P4Cs display a similar binding mode to DNA gyrase as gepotidacin. Gepotidacin is a member of the Novel Bacterial Topoisomerase Inhibitors (NBTIs), a new class of nonfluoroquinolone DNA gyrase poisons. Thus, our work suggests that P4Cs present a novel structural subclass of NBTI. We describe structure-activity relationship studies of 844 leading to analogues showing increased antibacterial activity. Selected derivatives were tested for their inhibitory activity against recombinant M. abscessus DNA gyrase. Further optimization of the lead structures led to improved stability in mouse plasma and increased oral bioavailability.
CASPASE INHIBITOR AND PHARMACEUTICAL COMPOSITION, USE AND THERAPEUTIC METHOD THEREOF
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, (2019/04/05)
Disclosed are a class of compounds as a caspase inhibitor, and in particular the compound as shown in formula (I) or a pharmaceutically acceptable salt thereof, and the use of the compound in treating caspase-related diseases.
Caspase inhibitor and pharmaceutical composition, application and treatment method thereof
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, (2019/05/28)
The invention provides a compound serving as a caspase inhibitor and particularly relates to a novel compound with caspase inhibition activity or a pharmaceutically acceptable salt of the novel compound, a preparation method of the novel compound and a ph
Silver-Promoted Synthesis of 5-[(Pentafluorosulfanyl)methyl]-2-oxazolines
Gilbert, Audrey,Bertrand, Xavier,Paquin, Jean-Fran?ois
supporting information, p. 7257 - 7260 (2018/11/23)
The synthesis of 5-[(pentafluorosulfanyl)methyl]-2-oxazolines is reported. The use of a silver promoter allows the intramolecular cyclization of N-[2-chloro-3-(pentafluorosulfanyl)propyl]amide to occur without elimination of the chlorine atom, a reaction
Benzonaphthyrindines compounds and pharmaceutical compositions thereof and its application in pharmacy
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Paragraph 0059; 0060, (2019/01/28)
The invention provides a pyrazolopyrimidine compound shown as a structural formula (I), a pharmaceutical composition taking the pyrazolopyrimidine compound as an active component, a preparation method of the pyrazolopyrimidine compound and the pharmaceutical composition as well as an application of the pyrazolopyrimidine compound and the pharmaceutical composition in preparation of a TRPC6 (Transient Receptor Potential Channel 6) adjustor probe medicine and related medicines for preventing and treating glomerulopathy and myocardial hypertrophy. The pyrazolopyrimidine compound and derivatives provided by the invention can be used to prepare medical preparations in various forms which comprise oral liquids, injections, pulmonary inhalation preparations and transdermal preparations, specifically injections, oral liquids, troches, capsules, granules, aerosols, dry powder inhalation, patches and the like.
TYROSINE KINASE INHIBITORS
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Page/Page column 112, (2012/12/13)
The present disclosure provides compounds and pharmaceutically acceptable salts that are tyrosine kinase inhibitors, in particular BLK, BMX, EGFR, HER2, HER4, ITK, JAK3, TEC, BTK, and TXK and are therefore useful for the treatment of diseases treatable by