71759-92-7Relevant academic research and scientific papers
Synthesis, Structure and Antitumoural Activity of Triazole-Functionalised NHC–Metal Complexes
Monticelli, Marco,Bellemin-Laponnaz, Stéphane,Tubaro, Cristina,Rancan, Marzio
, p. 2488 - 2495 (2017)
Silver(I), gold(I), copper(I) and ruthenium(II) N-heterocyclic carbene (NHC) complexes have been synthesised and their cytotoxic activities towards various cancer cell lines have been evaluated. The N-heterocyclic carbene ligand has been functionalised with a 1,2,3-triazole moiety tethered in the backbone of the ligand. The molecular structure of the silver(I) and gold(I) complexes has been solved by X-ray diffraction analysis. The AgI, AuI and RuII complexes display good stability in aqueous conditions and show cytotoxic activities comparable or slightly superior to those of similar unfunctionalised complexes.
Rapid discovery of a novel series of Abl kinase inhibitors by application of an integrated microfluidic synthesis and screening platform
Desai, Bimbisar,Dixon, Karen,Farrant, Elizabeth,Feng, Qixing,Gibson, Karl R.,Van Hoorn, Willem P.,Mills, James,Morgan, Trevor,Parry, David M.,Ramjee, Manoj K.,Selway, Christopher N.,Tarver, Gary J.,Whitlock, Gavin,Wright, Adrian G.
supporting information, p. 3033 - 3047 (2013/05/22)
Drug discovery faces economic and scientific imperatives to deliver lead molecules rapidly and efficiently. Using traditional paradigms the molecular design, synthesis, and screening loops enforce a significant time delay leading to inefficient use of data in the iterative molecular design process. Here, we report the application of a flow technology platform integrating the key elements of structure-activity relationship (SAR) generation to the discovery of novel Abl kinase inhibitors. The platform utilizes flow chemistry for rapid in-line synthesis, automated purification, and analysis coupled with bioassay. The combination of activity prediction using Random-Forest regression with chemical space sampling algorithms allows the construction of an activity model that refines itself after every iteration of synthesis and biological result. Within just 21 compounds, the automated process identified a novel template and hinge binding motif with pIC50 > 8 against Abl kinase - both wild type and clinically relevant mutants. Integrated microfluidic synthesis and screening coupled with machine learning design have the potential to greatly reduce the time and cost of drug discovery within the hit-to-lead and lead optimization phases.
Discovery of 5-(arenethynyl) hetero-monocyclic derivatives as potent inhibitors of BCR-ABL including the T315I gatekeeper mutant
Thomas, Mathew,Huang, Wei-Sheng,Wen, David,Zhu, Xiaotian,Wang, Yihan,Metcalf, Chester A.,Liu, Shuangying,Chen, Ingrid,Romero, Jan,Zou, Dong,Sundaramoorthi, Raji,Li, Feng,Qi, Jiwei,Cai, Lisi,Zhou, Tianjun,Commodore, Lois,Xu, Qihong,Keats, Jeff,Wang, Frank,Wardwell, Scott,Ning, Yaoyu,Snodgrass, Joseph T.,Broudy, Marc I.,Russian, Karin,Iuliucci, John,Rivera, Victor M.,Sawyer, Tomi K.,Dalgarno, David C.,Clackson, Tim,Shakespeare, William C.
scheme or table, p. 3743 - 3748 (2011/08/06)
Ponatinib (AP24534) was previously identified as a pan-BCR-ABL inhibitor that potently inhibits the T315I gatekeeper mutant, and has advanced into clinical development for the treatment of refractory or resistant CML. In this study, we explored a novel series of five and six membered monocycles as alternate hinge-binding templates to replace the 6,5-fused imidazopyridazine core of ponatinib. Like ponatinib, these monocycles are tethered to pendant toluanilides via an ethynyl linker. Several compounds in this series displayed excellent in vitro potency against both native BCR-ABL and the T315I mutant. Notably, a subset of inhibitors exhibited desirable PK and were orally active in a mouse model of T315I-driven CML.
Discovery and optimization of substituted piperidines as potent, selective, CNS-penetrant α4β2 nicotinic acetylcholine receptor potentiators
Albrecht, Brian K.,Berry, Virginia,Boezio, Alessandro A.,Cao, Lei,Clarkin, Kristie,Guo, Wenhong,Harmange, Jean-Christophe,Hierl, Markus,Huang, Liyue,Janosky, Brett,Knop, Johannes,Malmberg, Annika,McDermott, Jeff S.,Nguyen, Hung Q.,Springer, Stephanie K.,Waldon, Daniel,Woodin, Katrina,McDonough, Stefan I.
scheme or table, p. 5209 - 5212 (2009/05/07)
The discovery of a series of small molecule α4β2 nAChR potentiators is reported. The structure-activity relationship leads to potent compounds selective against nAChRs including α3β2 and α3β4 and optimized for CNS penetrance. Compounds increased currents through recombinant α4β2 nAChRs, yet did not compete for binding with the orthosteric ligand cytisine. High potency and efficacy on the rat channel combined with good PK properties will allow testing of the α4β2 potentiator mechanism in animal models of disease.
Terminal alkynes from aldehydes via dehydrohalogenation of (Z)-1-iodo-1-alkenes with TBAF
Beshai, Mira,Dhudshia, Bhartesh,Mills, Ryan,Thadani, Avinash N.
supporting information; experimental part, p. 6794 - 6796 (2009/04/07)
Terminal alkynes were prepared in near quantitative yields via dehydrohalogenation of (Z)-1-iodo-1-alkenes with tetrabutylammonium fluoride (TBAF) under mild conditions. The methodology was expanded to include a one-pot, direct synthesis of terminal alkynes from aldehydes without the necessity of isolating and purifying the intermediate iodoalkene.
Palladium-Catalyzed Reactions of Terminal Acetylenes and Olefins with Halo-1,3-azoles
Sakamoto, Takao,Nagata, Hideo,Kondo, Yoshinori,Shiraiwa, Masafumi,Yamanaka, Hiroshi
, p. 823 - 828 (2007/10/02)
The palladium-catalyzed reactions of 4-bromo- and 5-bromothiazoles, as well as 4-bromo and 5-bromooxazoles with terminal acetylenes gave ethynyl derivatives in 43-89percent yields, whereas the reactions of 2-bromothiazoles and iodo-N-methylimidazoles affo
