Multicomponent reactions (MCR) in medicinal chemistry: a patent review (2010-2020)

INTRODUCTION Multicomponent reactions (MCR) have been utilized to synthesize a vast range of analogues belonging to diverse classes of heterocyclic compounds offering multidimensional pharmaceutical applications. The unique feature of MCR includes the synthesis of highly functionalized molecules in a single pot to build quick libraries of compounds of biological interest to identify new leads as potential therapeutic agents. AREA COVERED The current review article covers the patents published in last decade in order to highlight the importance of multicomponent reactions for synthesizing complex functionalized molecules of high biological significance. EXPERT OPINION Easily automated one-pot multicomponent reactions (MCRs) have demonstrated successful impact at different stages of the lead discovery, lead optimization, and pre-clinical process development arenas. Application of MCRs is the recent advancement in the field of drug design and discovery which will expectedly lead to the development of medicinally important heterocyclic compounds with a vast range of biological activities.

[1]  V. Hruby,et al.  36 – Antiviral Drugs , 2006 .

[2]  Dinesh Kumar,et al.  Supported protic acid-catalyzed synthesis of 2,3-disubstituted thiazolidin-4-ones: enhancement of the catalytic potential of protic acid by adsorption on solid supports , 2013 .

[3]  S. Shaaban,et al.  Groebke–Blackburn–Bienaymé multicomponent reaction: emerging chemistry for drug discovery , 2015, Molecular Diversity.

[4]  Dinesh Kumar,et al.  Catalytic procedures for multicomponent synthesis of imidazoles: selectivity control during the competitive formation of tri- and tetrasubstituted imidazoles , 2012 .

[5]  Ling Zhang,et al.  Comprehensive Review in Current Developments of Imidazole‐Based Medicinal Chemistry , 2014, Medicinal research reviews.

[6]  A. Chakraborti,et al.  Organocatalytic Applicationof Ionic Liquids: [bmim][MeSO4] asa Recyclable Organocatalyst in the Multicomponent Reaction for thePreparation of Dihydropyrimidinones and -thiones , 2011 .

[7]  A. Riera,et al.  Synthesis of prostaglandin and phytoprostane B1 via regioselective intermolecular Pauson-Khand reactions. , 2009, Organic letters.

[8]  A. Dömling,et al.  Modern Multicomponent Reactions for better Drug Syntheses** , 2014, Organic chemistry frontiers : an international journal of organic chemistry.

[9]  S. Roberts,et al.  A very simple, highly stereoselective and modular synthesis of ferrocene-based P-chiral phosphine ligands. , 2006, Journal of the American Chemical Society.

[10]  B. A. Neto,et al.  What do we know about multicomponent reactions? Mechanisms and trends for the Biginelli, Hantzsch, Mannich, Passerini and Ugi MCRs , 2014 .

[11]  M. Haji Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates , 2016, Beilstein journal of organic chemistry.

[12]  G. Beutner,et al.  A Concise Synthesis of (S)-N-Ethoxycarbonyl-α-methylvaline , 2007 .

[13]  N. Turner,et al.  A highly efficient synthesis of telaprevir by strategic use of biocatalysis and multicomponent reactions. , 2010, Chemical communications.

[14]  K. Gewald,et al.  Heterocyclen aus CH‐aciden Nitrilen, VIII. 2‐Amino‐thiophene aus methylenaktiven Nitrilen, Carbonylverbindungen und Schwefel , 1966 .

[15]  J. Bergman,et al.  The Three‐Component Reaction between Isatin, α‐Amino Acids, and Dipolarophiles , 2004 .

[16]  Tryfon Zarganes Tzitzikas Innovative multicomponent reactions and their use in medicinal chemistry , 2017 .

[17]  A. Basso,et al.  A highly convergent synthesis of tricyclic N-heterocycles coupling an Ugi reaction with a tandem S(N)2'-Heck double cyclization. , 2010, The Journal of organic chemistry.

[18]  J. Sisko A One-Pot Synthesis of 1-(2,2,6,6-tetramethyl-4-piperidinyl)-4- (4-fluorophenyl)-5-(2-amino-4-pyrimidinyl)- imidazole: A Potent Inhibitor of P38 MAP Kinase , 1998 .

[19]  T. Lampe,et al.  Medicinal Chemistry Optimization of Acyldepsipeptides of the Enopeptin Class Antibiotics , 2006, ChemMedChem.

[20]  J. Wildeman,et al.  Chemistry of sulfonylmethyl isocyanides. 12. Base-induced cycloaddition of sulfonylmethyl isocyanides to carbon,nitrogen double bonds. Synthesis of 1,5-disubstituted and 1,4,5-trisubstituted imidazoles from aldimines and imidoyl chlorides , 1977 .

[21]  A. Dömling,et al.  Efficient multicomponent reaction synthesis of the schistosomiasis drug praziquantel. , 2010, Chemistry.

[22]  R. Orru,et al.  Multicomponent reactions - opportunities for the pharmaceutical industry. , 2013, Drug discovery today. Technologies.

[23]  W. Wuest,et al.  Natural Products as Platforms To Overcome Antibiotic Resistance. , 2017, Chemical reviews.

[24]  A. De Mesmaeker,et al.  Multicomponent reactions in fungicide research: the discovery of mandipropamid. , 2008, Bioorganic & medicinal chemistry.

[25]  J. W. Campbell,et al.  Bacterial fatty acid biosynthesis: targets for antibacterial drug discovery. , 2001, Annual review of microbiology.

[26]  Eelco Ruijter,et al.  Multicomponent reaction design in the quest for molecular complexity and diversity. , 2011, Angewandte Chemie.

[27]  D. Shi,et al.  Efficient synthesis of functionalized dihydro-1H-indol-4(5H)-ones via one-pot three-component reaction under catalyst-free conditions. , 2013, ACS combinatorial science.

[28]  A. T. Khan,et al.  Iodine catalyzed one-pot five-component reactions for direct synthesis of densely functionalized piperidines , 2010 .

[29]  A. Dömling,et al.  The Groebke-Blackburn-Bienaymé Reaction. , 2019, European journal of chemistry.

[30]  Wei Wang,et al.  Chemistry and biology of multicomponent reactions. , 2012, Chemical reviews.

[31]  A. Basso,et al.  Ugi and Passerini reactions of biocatalytically derived chiral aldehydes: application to the synthesis of bicyclic pyrrolidines and of antiviral agent telaprevir. , 2015, The Journal of organic chemistry.

[32]  J. Clader,et al.  Discovery of 1-(4-fluorophenyl)-(3R)-[3-(4-fluorophenyl)-(3S)-hydroxypropyl]-(4S)-(4 -hydroxyphenyl)-2-azetidinone (SCH 58235): a designed, potent, orally active inhibitor of cholesterol absorption. , 1998, Journal of medicinal chemistry.

[33]  Eelco Ruijter,et al.  Multicomponent reactions: advanced tools for sustainable organic synthesis , 2014 .

[34]  J. Menéndez,et al.  Multicomponent reactions for the synthesis of pyrroles. , 2010, Chemical Society reviews.

[35]  J. S. Roberts,et al.  An efficient and highly stereoselective synthesis of new P-chiral 1,5-diphosphanylferrocene ligands and their use in enantioselective hydrogenation. , 2006, Chemical communications.

[36]  Dinesh Kumar,et al.  Convenient synthesis of 2,3-disubstituted quinazolin-4(3H)-ones and 2-styryl-3-substituted quinazolin-4(3H)-ones: applications towards the synthesis of drugs , 2015 .

[37]  Andrea Basso,et al.  Photoinduced Multicomponent Reactions. , 2016, Angewandte Chemie.

[38]  R. Šebesta,et al.  Synthesis of epimer of Taniaphos ligand , 2016 .

[39]  Victor J. Hruby,et al.  Synthesis of Essential Drugs , 2006 .

[40]  J. Aizpurua,et al.  Asymmetric Synthesis of β‐Lactams by Staudinger Ketene‐Imine Cycloaddition Reaction , 1999 .

[41]  P. Van der Veken,et al.  ClpP Protease, a Promising Antimicrobial Target , 2019, International journal of molecular sciences.

[42]  Kan Wang,et al.  Cyanoacetamide MCR (III): three-component Gewald reactions revisited. , 2010, Journal of combinatorial chemistry.