32231-07-5Relevant academic research and scientific papers
Design, synthesis and SAR of antitubercular benzylpiperazine ureas
Satish, Sohal,Chitral, Rohan,Kori, Amitkumar,Sharma, Basantkumar,Puttur, Jayashree,Khan, Afreen A.,Desle, Deepali,Raikuvar, Kavita,Korkegian, Aaron,Martis, Elvis A. F.,Iyer, Krishna R.,Coutinho, Evans C.,Parish, Tanya,Nandan, Santosh
, p. 73 - 96 (2021/01/04)
Abstract: N-furfuryl piperazine ureas disclosed by scientists at GSK Tres Cantos were chosen as antimycobacterial hits from a phenotypic whole-cell screen. Bioisosteric replacement of the furan ring in the GSK Tres Cantos molecules with a phenyl ring led to molecule (I) with an MIC of 1?μM against Mtb H37Rv, low cellular toxicity (HepG2 IC50 ~ 80?μM), good DMPK properties and specificity for Mtb. With the aim of delineating the SAR associated with (I), fifty-five analogs were synthesized and screened against Mtb. The SAR suggests that the piperazine ring, benzyl urea and piperonyl moieties are essential signatures of this series. Active compounds in this series are metabolically stable, have low cellular toxicity and are valuable leads for optimization. Molecular docking suggests these molecules occupy the Q0 site of QcrB like Q203. Graphic Abstract: Bioisosteric replacement of N-furfuryl piperazine-1-carboxamides yielded molecule (I) a novel lead with satisfactory PD, metabolism, and toxicity profiles.[Figure not available: see fulltext.]
Synthesis and antimalarial activity of hydroxyethylpiperazine derivatives
Cunico, Wilson,Gomes, Claudia R.B.,Moreth, Marcele,Manhanini, Diogo P.,Figueiredo, Isabela H.,Penido, Carmen,Henriques, Maria G.M.O.,Varotti, Fernando P.,Krettli, Antoniana U.
body text, p. 1363 - 1368 (2009/09/27)
The antimalarial activity of hydroxyethylpiperazine derivatives, synthesized from the reaction of (2S,3S)Boc-phenylalanine epoxide with benzylpiperazines in good yields (76-96%), has been evaluated in vitro against the Plasmodium falciparum W2 clone (chlo
Flavonoid-related modulators of multidrug resistance: Synthesis, pharmacological activity, and structure-activity relationships
Ferté, Jacques,Kühnel, Jean-Marc,Chapuis, Geneviève,Rolland, Yves,Lewin, Guy,Schwaller, Marc A.
, p. 478 - 489 (2007/10/03)
A series of 28 flavonoid derivatives containing a N-benzylpiperazine chain have been synthesized and tested for their ability to modulate multidrug resistance (MDR) in vitro. At 5 μM, most compounds potentiated doxorubicin cytotoxicity on resistant K562/DOX cells. They were also able to increase the intracellular accumulation of JC-1, a fluorescent molecule recently described as a probe of P-glycoprotein-mediated MDR. This suggests that these compounds act, at least in part, by inhibiting P-glycoprotein activity. As in other studies, lipophilicity was shown to influence MDR- modulating activity but was not the only determinant. Diverse di- and trimethoxy substitutions on N-benzyl were examined and found to affect the activity differently. The most active compounds had a 2,3,4- trimethoxybenzylpiperazine chain attached to either a flavone or a flavanone moiety (13, 19, 33, and 37) and were found to be more potent than verapamil.
Use of polymer supported reagents for clean multi-step organic synthesis: Preparation of amines and amine derivatives from alcohols for use in compound library generation
Ley, Steven V.,Bolli, Martin H.,Hinzen, Berthold,Gervois, Anne-Geraldine,Hall, Beverley J.
, p. 2239 - 2241 (2007/10/03)
The automated sequential application of polymer supported perruthenate (PSP) and polymer supported cyanoborohydride (PSCBH) in an oxidation-reductive amination procedure allowed the efficient transformation of simple alcohols into more complex amines which can be further derivatised by the use of polymer bound amino sulfonylpyridinium chlorides.
