Journal ArticleDOI
"Multi-component reactions : emerging chemistry in drug discovery" 'from xylocain to crixivan'.
Reads0
Chats0
TLDR
This review details developments of new, highly atom-economic MCR derived chemical methods, which enable the fast and efficient production of chemical libraries comprised of a variety of biologically relevant templates, and focuses on applications of isocyanide based MCR (IMCR) reactions.Abstract:
With the recent emergence of combinatorial chemistry and high-speed parallel synthesis for drug discovery applications, the multi-component reaction (MCR) has seen a resurgence of interest. Easily automated one-pot reactions, such as the Ugi and Passerini reactions, are powerful tools for producing diverse arrays of compounds, often in one step and high yield. Despite this synthetic potential, the Ugi reaction is limited by producing products that are flexible and peptide-like, often being classified as 'non drug-like'. This review details developments of new, highly atom-economic MCR derived chemical methods, which enable the fast and efficient production of chemical libraries comprised of a variety of biologically relevant templates. Representative examples will also be given demonstrating the successful impact of MCR combinatorial methods at different stages of the lead discovery, lead optimization and pre-clinical process development arenas. This will include applications spanning biological tools, natural products and natural product-like diversity, traditional small molecule and 'biotech' therapeutics respectively. In particular, this review will focus on applications of isocyanide based MCR (IMCR) reactions.read more
Citations
More filters
Journal ArticleDOI
Ionic liquid-promoted multi-component reaction: novel and efficient preparation of pyrazolo[3,4-b]pyridinone, pyrazolo[3,4-b]-quinolinone and their hybrids with pyrimidine nucleoside.
TL;DR: The utilization of an ionic liquid, [bmim][BF4] as both reaction medium and promoter for a multi-component reaction of aldehyde and 5-amino-3-methyl-1-phenylpyrazole with Meldrum acid or dimedone is studied and showed such advantages as environmentally benign nature, enhanced efficiency, simple operation process, and mild reaction conditions.
Journal ArticleDOI
TMSCl-promoted isocyanide-based MCR of ethylenediamines: an efficient assembling of 2-aminopyrazine core
Volodymyr M. Kysil,Sergey Tkachenko,Alexander Viktorovich Khvat,Caroline Williams,Sergey Tsirulnikov,Marina Churakova,Alexandre V. Ivachtchenko +6 more
TL;DR: In this article, a trimethylchlorosilane (TMSCl) promoted multicomponent reaction (MCR) was proposed for the synthesis of a variety of highly substituted 3,4,5,6-tetrahydropyrazin-2-amines including corresponding spirocyclic compounds.
Journal ArticleDOI
Efficient construction of C–N and C–S bonds in 2-iminothiazoles via cascade reaction of enaminones with potassium thiocyanate
TL;DR: A novel and highly efficient protocol has been developed for the regioselective synthesis of 2-iminothiazole derivatives with potential biochemical interest by the reaction of enaminones, potassium thiocyanate (KSCN), and N-bromo succinimide (NBS) under mild conditions.
Journal ArticleDOI
Synthesis of a terphenyl substituted 4-aza-2,3-didehydropodophyllotoxin analogues as inhibitors of tubulin polymerization and apoptosis inducers.
Ahmed Kamal,Jaki R. Tamboli,V. Lakshma Nayak,Syed Farooq Adil,M.V.P.S. Vishnuvardhan,Sistla Ramakrishna +5 more
TL;DR: Overall, the current study demonstrated that the synthesis of terphenyl based 4-aza-2,3-didehydropodophyllotoxin conjugates as promising anticancer agents with G2/M cell cycle arrest and apoptotic-inducing activities via targeting tubulin.
Journal ArticleDOI
A 1,3-dipolar cycloaddition-annulation protocol for the expedient regio-, stereo- and product-selective construction of novel hybrid heterocycles comprising seven rings and seven contiguous stereocentres
Natarajan Arumugam,Abdulrahman I. Almansour,Raju Suresh Kumar,Subbu Perumal,Hazem A. Ghabbour,Hoong-Kun Fun +5 more
TL;DR: An expedient regio-, stereo- and product-selective synthesis of novel hybrid heterocyclic systems comprising [1,2-c]oxazolidine, pyrrolidine and piperidine units, in good to excellent yields, has been developed via three-component 1,3-dipolar cycloaddition/annulation domino reactions.