295341-38-7Relevant articles and documents
Synthesis, biological activities and docking studies of pleuromutilin derivatives with piperazinyl urea linkage
Zhang, Yuanyuan,Xie, Chuan,Liu, Yang,Shang, Feng,Shao, Rushiya,Yu, Jing,Wu, Chunxia,Yao, Xinghui,Liu, Dongfang,Wang, Zhouyu
, p. 764 - 775 (2021/03/29)
Antibiotics resistance is becoming increasingly common, involving almost all antibiotics on the market. Diseases caused by drug resistant bacteria, such as MRSA, have high mortality and negatively affect public health. The development of new drugs would be an effective means of solving this problem. Modifications based on bioactive natural products could greatly shorten drug development time and improve success rate. Pleuromutilin, a natural product from the basidiomycete bacterial species, is a promising antibiotic candidate. In this study, a series of novel pleuromutilin derivatives possessing piperazinyl urea linkage were efficiently synthesised, and their antibacterial activities and bactericidal properties were evaluated via MIC, MBC and Time-kill kinetics assays. The results showed that all compounds exhibited potent activities against tested strains, especially MRSA strains with MIC values as low as 0.125 μg/mL; 8 times lower than that of marketed antibiotic Tiamulin. Docking studies indicate substituted piperazinyl urea derivatives could provide hydrogen bonds and initiate π-π stacking between molecules and surrounding residues.
Design, synthesis, biological evaluation and molecular docking study of arylcarboxamido piperidine and piperazine-based hydroxamates as potential HDAC8 inhibitors with promising anticancer activity
Trivedi, Prakruti,Adhikari, Nilanjan,Amin, Sk. Abdul,Bobde, Yamini,Ganesh, Routholla,Jha, Tarun,Ghosh, Balaram
, (2019/08/20)
HDAC8 has been established as one of the vital targets as far as the cancer is concerned. Different compounds having potential HDAC inhibitory activity have been approved by USFDA. However, none of these compounds are selective towards specific HDAC isoform. In this current study, some new hydroxamate derivatives with alkylpiperidine and alkylpiperazine linker moieties have been designed, synthesized and biologically evaluated. All these compounds are effective HDAC8 inhibitors comprising more or less similar cytotoxic potential against different cancer cell lines. It is observed that the piperazine scaffold containing compound is more active than the compound with piperidine scaffold for exerting HDAC8 inhibitory activity. Moreover, the 4-quinolyl cap group is better than the biphenyl group which is better than the benzyl group for producing higher HDAC8 inhibition as well as cytotoxicity. These compounds displayed selective HDAC8 inhibition over HDAC3. Moreover, these compounds showed an increased caspase3/7 activity suggesting their anticancer potential through modulation of apoptotic pathways. Molecular docking study with three potent compounds was performed with both HDAC3 and HDAC8 enzymes to understand the selectivity profile of these compounds. Compound containing 4-quinolyl cap group with alkyl piperazinyl urea linker moiety has been emerged out as the lead molecule that may be further modified to design more effective and selective HDAC8 inhibitors in future.
Synthesis and Structure–Activity Relationship Studies of Benzo[b][1,4]oxazin-3(4H)-one Analogues as Inhibitors of Mycobacterial Thymidylate Synthase X
Modranka, Jakub,Li, Jiahong,Parchina, Anastasia,Vanmeert, Michiel,Dumbre, Shrinivas,Salman, Mayla,Myllykallio, Hannu,Becker, Hubert F.,Vanhoutte, Roeland,Margamuljana, Lia,Nguyen, Hoai,Abu El-Asrar, Rania,Rozenski, Jef,Herdewijn, Piet,De Jonghe, Steven,Lescrinier, Eveline
, p. 645 - 662 (2019/02/25)
Since the discovery of a flavin-dependent thymidylate synthase (ThyX or FDTS) that is absent in humans but crucial for DNA biosynthesis in a diverse group of pathogens, the enzyme has been pursued for the development of new antibacterial agents against Mycobacterium tuberculosis, the causative agent of the widespread infectious disease tuberculosis (TB). In response to a growing need for more effective anti-TB drugs, we have built upon our previous screening efforts and report herein an optimization campaign of a novel series of inhibitors with a unique inhibition profile. The inhibitors display competitive inhibition toward the methylene tetrahydrofolate cofactor of ThyX, enabling us to generate a model of the compounds bound to their target, thus offering insight into their structure–activity relationships.
Phenylquinoline transient receptor potential vanilloid 1 antagonists for the treatment of pain: Discovery of 1-(2-phenylquinoline-4-carbonyl)-N-(4-(trifluoromethyl)phenyl)pyrrolidine-3-carboxamide
Liao, Chen,Liu, Yan,Liu, Chunxia,Zhou, Jiaqi,Li, Huilan,Wang, Nasi,Li, Jieming,Liu, Taiyu,Ghaleb, Hesham,Huang, Wenlong,Qian, Hai
, p. 845 - 854 (2018/01/10)
Reported herein is the design, synthesis, and pharmacologic characterization of a class of TRPV1 antagonists constructed on a phenylquinoline platform that evolved from Cinchophen lead. This design composes three sections: a phenylquinoline headgroup attached to an aliphatic carboxamides, which is tethered at a phenyl tail group. Optimization of this design led to the identification of 37, comprising a pyrrolidine linker and a trifluoromethyl–phenyl tail. In the TRPV1 functional assay, using cells expressed hTRPV1, 37 antagonized capsaicin-induced Ca2+ influx, with an IC50 value of 10.2 nM. In the complete mice analgesic model, 37 exhibited better antinociceptive activity than the positive control BCTC in diverse pain models. All of these results suggested that 37 could be considered as a lead candidate for the further development of antinociceptive drugs.
Phenyl dihydroisoquinolines TRPV1 antagonists and its preparation method and application (by machine translation)
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, (2018/04/03)
The invention relates to the general formula (I) compounds and salts thereof, such compounds have a strong analgesic effect, part of the compound activity is far higher than the cinchophen and BCTC, and almost no hepatotoxins, gastric mucosa injury and body temperature rise side effect, the invention also relates to the preparation method of the compound and pharmaceutical preparations containing them. The invention synthesizes a series of general formula (I) compound and its pharmaceutically acceptable salt. (by machine translation)
1,3,4-OXADIAZOLE DERIVATIVE COMPOUNDS AS HISTONE DEACETYLASE 6 INHIBITOR, AND THE PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
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Paragraph 5444-5446, (2017/02/28)
The present invention relates to novel compounds having histone deacetylase 6 (HDAC6) in-hibitory activity, stereoisomers thereof or pharmaceutically acceptable salts thereof, the use thereof for the preparation of therapeutic medicaments, pharmaceutical compositions containing the same, a method for treating diseases using the composition, and methods for preparing the novel compounds. The novel compounds, stereoisomers thereof or pharmaceutically acceptable salts thereof according to the present invention have histone deacetylase (HDAC) inhibitory activity and are effective for the prevention or treatment of HDAC6-mediated diseases, including infectious diseases; neoplasms; endocrine, nutritional and metabolic diseases; mental and be-havioral disorders; neurological diseases; diseases of the eye and adnexa; cardiovascular diseases; respiratory diseases; digestive diseases; diseases of the skin and subcutaneous tissue; diseases of the musculoskeletal system and connective tissue; or congenital malformations, de? formations and chromosomal abnormalities.
Aryl piperazinyl ureas as inhibitors of fatty acid amide hydrolase (FAAH) in rat, dog, and primate
Keith, John M.,Apodaca, Rich,Tichenor, Mark,Xiao, Wei,Jones, William,Pierce, Joan,Seierstad, Mark,Palmer, James,Webb, Michael,Karbarz, Mark,Scott, Brian,Wilson, Sandy,Luo, Lin,Wennerholm, Michelle,Chang, Leon,Brown, Sean,Rizzolio, Michele,Rynberg, Raymond,Chaplan, Sandra,Breitenbucher, J. Guy
supporting information, p. 823 - 827,5 (2020/09/15)
A series of aryl piperazinyl ureas that act as covalent inhibitors of fatty acid amide hydrolase (FAAH) is described. A potent and selective (does not inhibit FAAH-2) member of this class, JNJ-40355003, was found to elevate the plasma levels of three fatt
The design and synthesis of novel, potent and orally bioavailable N-aryl piperazine-1-carboxamide CCR2 antagonists with very high hERG selectivity
Cumming, John G.,Bower, Justin F.,Waterson, David,Faull, Alan,Poyser, Philip J.,Turner, Paul,McDermott, Benjamin,Campbell, Andrew D.,Hudson, Julian,James, Michael,Winter, Jon,Wood, Christine
scheme or table, p. 3895 - 3899 (2012/07/03)
A novel N-aryl piperazine-1-carboxamide series of human CCR2 chemokine receptor antagonists was discovered. Early analogues were potent at CCR2 but also inhibited the hERG cardiac ion channel. Structural modifications which decreased lipophilicity and basicity resulted in the identification of a sub-series with an improved margin over hERG. The pharmacological and pharmacokinetic properties of the lead compound from this series, N-(3,4-dichlorophenyl)-4-[(2R)-4-isopropylpiperazine-2-carbonyl] piperazine-1-carboxamide, are described.
Benzothiophene piperazine and piperidine urea inhibitors of fatty acid amide hydrolase (FAAH)
Johnson, Douglas S.,Ahn, Kay,Kesten, Suzanne,Lazerwith, Scott E.,Song, Yuntao,Morris, Mark,Fay, Lorraine,Gregory, Tracy,Stiff, Cory,Dunbar Jr., James B.,Liimatta, Marya,Beidler, David,Smith, Sarah,Nomanbhoy, Tyzoon K.,Cravatt, Benjamin F.
scheme or table, p. 2865 - 2869 (2010/02/28)
The synthesis and structure-activity relationships (SAR) of a series of benzothiophene piperazine and piperidine urea FAAH inhibitors is described. These compounds inhibit FAAH by covalently modifying the enzyme's active site serine nucleophile. Activity-based protein profiling (ABPP) revealed that these urea inhibitors were completely selective for FAAH relative to other mammalian serine hydrolases. Several compounds showed in vivo activity in a rat complete Freund's adjuvant (CFA) model of inflammatory pain.
N-heteroarylpiperazinyl ureas as modulators of fatty acid amide hydrolase
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Page/Page column 12, (2008/06/13)
Certain N-heteroarylpiperazinyl urea compounds are described, which are useful as FAAH inhibitors. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by fatty acid
