2252-63-3Relevant academic research and scientific papers
Synthesis and biological evaluation of novel 3-substituted amino-4-hydroxylcoumarin derivatives as chitin synthase inhibitors and antifungal agents
Ge, Zhiqiang,Ji, Qinggang,Chen, Chunyan,Liao, Qin,Wu, Hualong,Liu, Xiaofei,Huang, Yanrong,Yuan, Lvjiang,Liao, Fei
, p. 219 - 228 (2016)
A series of novel 3-substituted amino-4-hydroxycoumarin derivatives have been designed and synthesized as chitin synthase (CHS) inhibitors. All the synthesized compounds have been screened for their CHS inhibition activity and antimicrobial activity in vitro. The enzymatic assay indicated that most of the compounds have good inhibitory activity against CHS, in which compound 6o with IC50 of 0.10 mmol/L had stronger activity than that of polyoxins B, which acts as control drug with IC50 of 0.18 mmol/L. As far as the antifungal activity is concerned, most of the compounds possessed moderate to excellent activity against some representative pathogenic fungi. Especially, compound 6b was found to be the most potent agent against Cryptococcus neoformans with minimal inhibitory concentration (MIC) of 4 g/mL. Moreover, the results of antibacterial screening showed that these compounds have negligible actions to some tested bacteria. Therefore, these compounds would be promising to develop selective antifungal agents.
Evaluation of substituted n-phenylpiperazine analogs as D3 vs. D2 dopamine receptor subtype selective ligands
Lee, Boeun,Taylor, Michelle,Griffin, Suzy A.,McInnis, Tamara,Sumien, Nathalie,Mach, Robert H.,Luedtke, Robert R.
supporting information, (2021/06/14)
N-phenylpiperazine analogs can bind selectively to the D3 versus the D2 dopamine receptor subtype despite the fact that these two D2-like dopamine receptor subtypes exhibit substantial amino acid sequence homology. The binding for a number of these receptor subtype selective compounds was found to be consistent with their ability to bind at the D3 dopamine receptor subtype in a bitopic manner. In this study, a series of the 3-thiophenephenyl and 4-thiazolylphenyl fluoride substituted N-phenylpiperazine analogs were evaluated. Compound 6a was found to bind at the human D3 receptor with nanomolar affinity with substantial D3 vs. D2 binding selectivity (approximately 500-fold). Compound 6a was also tested for activity in two in-vivo assays: (1) a hallucinogenic-dependent head twitch response inhibition assay using DBA/2J mice and (2) an L-dopa-dependent abnormal involuntary movement (AIM) inhibition assay using unilateral 6-hydroxydopamine lesioned (hemiparkinsonian) rats. Compound 6a was found to be active in both assays. This compound could lead to a better understanding of how a bitopic D3 dopamine receptor selective ligand might lead to the development of pharmacotherapeutics for the treatment of levodopa-induced dyskinesia (LID) in patients with Parkinson’s disease.
7-benzyl-4-(4-phenylpiperazin-1-yl)-7H-pyrrolo[2,3-d]pyrimidine derivatives and Composition for skin whitening and Pharmaceutical composition for use in preventing or treating disorders of Melanin Hyperpigmentation containing the same as an active ingredient
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Paragraph 0200; 0206-0207, (2020/11/06)
The present invention relates to a 7-benzyl-4(4-phenylpiperazin-1-yl)-7H-pyrrolo[2,3-d]pyrimidine derivative, and to a composition for skin whitening, comprising the same as an active ingredient. Since the derivative exhibits the effect of inhibiting the production of melanin even when used in a small amount, it is useful as a pharmaceutical composition for preventing or treating melanin hyperpigmentation diseases, a cosmetic composition for skin whitening, and a health functional food for skin whitening.
Design, synthesis and antimycobacterial activity of novel imidazo[1,2-a]pyridine-3-carboxamide derivatives
Lv, Kai,Li, Linhu,Wang, Bo,Liu, Mingliang,Wang, Bin,Shen, Weiyi,Guo, Huiyuan,Lu, Yu
, p. 117 - 125 (2017/06/05)
We report herein the design and synthesis of “novel imidazo [1,2-a]pyridine-3-carboxamides (IPAs)” bearing a variety of different linkers, based on the structure of IMB-1402 discovered in our lab. Results reveal that 2,6-dimethyl-N-[2-(phenylamino)ethyl] IPAs with an electron-donating group on the benzene ring as a potent scaffold. Compounds 26g and 26h have considerable activity (MIC: 0.041–2.64 μM) against drug-sensitive/resistant MTB strains, and they have acceptable safety indices against MTB H37Rv with the SI values of 4395 and 1405, respectively. Moreover, N-[2-(piperazin-1-yl)ethyl] moiety was also identified as a potentially alternative linker (compound 31), opening a new direction for further SAR studies.
Chrysin-piperazine conjugates as antioxidant and anticancer agents
Patel, Rahul V.,Mistry, Bhupendra,Syed, Riyaz,Rathi, Anuj K.,Lee, Yoo-Jung,Sung, Jung-Suk,Shinf, Han-Seung,Keum, Young-Soo
, p. 166 - 177 (2016/05/24)
Synthesis of 7-(4-bromobutoxy)-5-hydroxy-2-phenyl-4H-chromen-4-one intermediate treating chrysin with 1,4-dibromobutane facilitated combination of chrysin with a wide range of piperazine moieties which were equipped via reacting the corresponding amines with bis(2-chloroethyl)amine hydrochloride in diethylene glycol monomethyl ether solvent. Free radical scavenging potential of prepared products was analyzed in vitro adopting DPPH and ABTS bioassay in addition to the evaluation of in vitro anticancer efficacies against cervical cancer cell lines (HeLa and CaSki) and an ovarian cancer cell line SK-OV-3 using SRB assay. Bearable toxicity of 7a-w was examined employing Madin-Darby canine kidney (MDCK) cell line. In addition, cytotoxic nature of the presented compounds was inspected utilizing Human bone marrow derived mesenchymal stem cells (hBM-MSCs). Overall, 7a-w indicated remarkable antioxidant power in scavenging DPPH+ and ABTS++, particularly analogs 7f, 7j, 7k, 7l, 7n, 7q, 7v, 7w have shown promising free radical scavenging activity. Analogs 7j and 7o are identified to be highly active candidates against HeLa and CaSki cell lines, whereas 7h and 7l along with 7j proved to be very sensitive towards ovarian cancer cell line SKOV-3. None of the newly prepared scaffolds showed cytotoxic nature toward hBM-MSCs cells. From the structure-activity point of view, nature and position of the electron withdrawing and electron donating functional groups on the piperazine core may contribute to the anticipated antioxidant and anticancer action. Different spectroscopic techniques (FT-IR, 1H NMR, 13C NMR, Mass) and elemental analysis (CHN) were utilized to confirm the desired structure of final compounds.
Charge-transfer-directed radical substitution enables para-selective C-H functionalization
Boursalian, Gregory B.,Ham, Won Seok,Mazzotti, Anthony R.,Ritter, Tobias
, p. 810 - 815 (2016/07/29)
Efficient C-H functionalization requires selectivity for specific C-H bonds. Progress has been made for directed aromatic substitution reactions to achieve ortho and meta selectivity, but a general strategy for para-selective C-H functionalization has remained elusive. Herein we introduce a previously unappreciated concept that enables nearly complete para selectivity. We propose that radicals with high electron affinity elicit arene-to-radical charge transfer in the transition state of radical addition, which is the factor primarily responsible for high positional selectivity. We demonstrate with a simple theoretical tool that the selectivity is predictable and show the utility of the concept through a direct synthesis of aryl piperazines. Our results contradict the notion, widely held by organic chemists, that radical aromatic substitution reactions are inherently unselective. The concept of radical substitution directed by charge transfer could serve as the basis for the development of new, highly selective C-H functionalization reactions.
Pd-Catalyzed Synthesis of Piperazine Scaffolds under Aerobic and Solvent-Free Conditions
Reilly, Sean W.,Mach, Robert H.
supporting information, p. 5272 - 5275 (2016/10/31)
A facile Pd-catalyzed methodology providing an efficient synthetic route to biologically relevant arylpiperazines under aerobic conditions is reported. Electron donating and sterically hindered aryl chlorides were aminated to afford yields up to 97%, with examples using piperazine as solvent, illustrating an ecofriendly, cost-effective synthesis of these privileged structures.
4-Aryl piperazine and piperidine amides as novel mGluR5 positive allosteric modulators
Xiong, Hui,Brugel, Todd A.,Balestra, Michael,Brown, Dean G.,Brush, Kelly A.,Hightower, Caprice,Hinkley, Lindsay,Hoesch, Valerie,Kang, James,Koether, Gerard M.,McCauley Jr., John P.,McLaren, Francis M.,Panko, Laura M.,Simpson, Thomas R.,Smith, Reed W.,Woods, James M.,Brockel, Becky,Chhajlani, Vijay,Gadient, Reto A.,Spear, Nathan,Sygowski, Linda A.,Zhang, Minli,Arora, Jalaj,Breysse, Nathalie,Wilson, Julie M.,Isaac, Methvin,Slassi, Abdelmalik,King, Megan M.
scheme or table, p. 7381 - 7384 (2011/02/26)
Positive allosteric modulation of metabotropic glutamate receptor 5 (mGluR5) is regarded as a potential novel treatment for schizophrenic patients. Herein we report the synthesis and SAR of 4-aryl piperazine and piperidine amides as potent mGluR5 positive allosteric modulators (PAMs). Several analogs have excellent activity and desired drug-like properties. Compound 2b was further characterized as a PAM using several in vitro experiments, and produced robust activity in several preclinical animal models.
Discovery and Initial SAR of Arylsulfonylpiperazine Inhibitors of 11β-Hydroxysteroid Dehydrogenase Type 1 (11β-HSD1)
Sun, Daqing,Wang, Zhulun,Di, Yongmei,Jaen, Juan C.,Labelle, Marc,Ma, Ji,Miao, Shichang,Sudom, Athena,Tang, Liang,Tomooka, Craig S.,Tu, Hua,Ursu, Stefania,Walker, Nigel,Yan, Xuelei,Ye, Qiuping,Powers, Jay P.
scheme or table, p. 3513 - 3516 (2009/04/11)
High-throughput screening of a small-molecule compound library resulted in the identification of a series of arylsulfonylpiperazines that are potent and selective inhibitors of human 11β-Hydroxysteroid Dehydrogenase Type 1 (11β-HSD1). Optimization of the initial lead resulted in the discovery of compound (R)-45 (11β-HSD1 IC50 = 3 nM).
Potent, selective, and orally active adenosine A2A receptor antagonists: Arylpiperazine derivatives of pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines
Neustadt, Bernard R.,Hao, Jinsong,Lindo, Neil,Greenlee, William J.,Stamford, Andrew W.,Tulshian, Deen,Ongini, Ennio,Hunter, John,Monopoli, Angela,Bertorelli, Rosalia,Foster, Carolyn,Arik, Leyla,Lachowicz, Jean,Ng, Kwokei,Feng, Kung-I
, p. 1376 - 1380 (2008/02/05)
Antagonism of the adenosine A2A receptor offers great promise in the treatment of Parkinson's disease. Employing the known pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine A2A antagonist SCH 58261 as a starting point, we identified the potent and selective (vs. A1) antagonist 11 h, orally active in the rat haloperidol-induced catalepsy model. We further optimized this lead to the methoxyethoxyethyl ether 12a (SCH 420814), which shows broad selectivity, good pharmacokinetic properties, and excellent in vivo activity.
