Recent applications of multicomponent reactions in medicinal chemistry

The protein kinase complement of the human genome

Manning, G., Whyte, D. B., Martinez, R., Hunter, T., & Sudarsanam, S. (2002) · Science · doi:10.1126/science.1075762 · Cited by 8,145

In Vivo Activation of the p53 Pathway by Small-Molecule Antagonists of MDM2

Vassilev, L. T., Vu, B. T., Graves, B., Carvajal, D., Podlaski, F., Filipovic, Z., Kong, N., Kammlott, U., Lukacs, C., Klein, C., et al. (2004) · Science · doi:10.1126/science.1092472 · Cited by 4,661

Multicomponent Reactions with Isocyanides

Dömling, A., & Ugi, I. (2000) · Angewandte Chemie · doi:10.1002/1521-3773(20000915)39:18<3168::aid-anie3168>3.0.co;2-u · Cited by 4,077

Targeting multidrug resistance in cancer

Szakács, G., Paterson, J. K., Ludwig, J. A., Booth-Genthe, C., & Gottesman, M. M. (2006) · Nature Reviews Drug Discovery · doi:10.1038/nrd1984 · Cited by 3,609

Natural products as sources of new drugs over the period 1981–2002

Newman, D. J., Cragg, G. M., & Snader, K. M. (2003) · Journal of Natural Products · doi:10.1021/np030096l · Cited by 3,082

Targeting cancer with small molecule kinase inhibitors

Zhang, J., Yang, P. L., & Gray, N. S. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2559 · Cited by 2,576

The evolving role of natural products in drug discovery

Koehn, F. E., & Carter, G. T. (2005) · Nature Reviews Drug Discovery · doi:10.1038/nrd1657 · Cited by 2,572

Chemistry and Biology Of Multicomponent Reactions

Dömling, A., Wang, W., & Wang, K. (2012) · Chemical Reviews · doi:10.1021/cr100233r · Cited by 2,547

Structure of the MDM2 Oncoprotein Bound to the p53 Tumor Suppressor Transactivation Domain

Kussie, P. H., Gorina, S., Marechal, V., Elenbaas, B., Moreau, J., Levine, A. J., & Pavletich, N. P. (1996) · Science · doi:10.1126/science.274.5289.948 · Cited by 2,206

EGFR Antagonists in Cancer Treatment

Ciardiello, F., & Tortora, G. (2008) · New England Journal of Medicine · doi:10.1056/nejmra0707704 · Cited by 2,058

DNA Topoisomerases and Their Poisoning by Anticancer and Antibacterial Drugs

Pommier, Y., Leo, E., Zhang, H., & Marchand, C. (2010) · Chemistry & Biology · doi:10.1016/j.chembiol.2010.04.012 · Cited by 1,829

Protein tyrosine phosphatases: from genes, to function, to disease

Tonks, N. K. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2039 · Cited by 1,677

Translocator protein (18kDa): new nomenclature for the peripheral-type benzodiazepine receptor based on its structure and molecular function

Papadopoulos, V., Baraldi, M., Guilarte, T. R., Knudsen, T. B., Lacapère, J.-J., Lindemann, P., Norenberg, M. D., Nutt, D., Weizman, A., Zhang, M.-R., et al. (2006) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2006.06.005 · Cited by 1,389

Biologically active dihydropyrimidones of the Biginelli-type — a literature survey

Kappe, C. O. (2000) · European Journal of Medicinal Chemistry · doi:10.1016/s0223-5234(00)01189-2 · Cited by 1,352

Bright Ideas for Chemical Biology

Lavis, L. D., & Raines, R. T. (2008) · ACS Chemical Biology · doi:10.1021/cb700248m · Cited by 1,290

Dimethyl sulfoxide to vorinostat: development of this histone deacetylase inhibitor as an anticancer drug

Marks, P. A., & Breslow, R. (2007) · Nature Biotechnology · doi:10.1038/nbt1272 · Cited by 1,196

“Multi-component Reactions : Emerging Chemistry in Drug Discovery” ‘From Xylocain to Crixivan’

Hulme, C., & Gore, V. (2003) · Current Medicinal Chemistry · doi:10.2174/0929867033368600 · Cited by 1,035

Recent developments in asymmetric multicomponent reactions

de Graaff, C., Ruijter, E., & Orru, R. V. A. (2012) · Chemical Society Reviews · doi:10.1039/c2cs15361k · Cited by 876

The future challenges facing the development of new antimicrobial drugs

Coates, A., Hu, Y., Bax, R., & Page, C. (2002) · Nature Reviews Drug Discovery · doi:10.1038/nrd940 · Cited by 704

Protein-tyrosine phosphatases and cancer

Östman, A., Hellberg, C., & Böhmer, F. D. (2006) · Nature Reviews Cancer · doi:10.1038/nrc1837 · Cited by 657

New antibiotics from bacterial natural products

Clardy, J., Fischbach, M. A., & Walsh, C. T. (2006) · Nature Biotechnology · doi:10.1038/nbt1266 · Cited by 615

Zur Kenntniss der Ketene. Diphenylketen

Staudinger, H. (1907) · Justus Liebigs Annalen der Chemie · doi:10.1002/jlac.19073560106 · Cited by 549

The Application of Multi-Component Reactions in Drug Discovery

Weber, L. (2002) · Current Medicinal Chemistry · doi:10.2174/0929867023368719 · Cited by 534

Biology‐Oriented Synthesis

Wetzel, S., Bon, R. S., Kumar, K., & Waldmann, H. (2011) · Angewandte Chemie International Edition · doi:10.1002/anie.201007004 · Cited by 505

Condensationsprodukte aus Aldehydammoniak und ketonartigen Verbindungen

Hantzsch, A. (1881) · Berichte der deutschen chemischen Gesellschaft · doi:10.1002/cber.18810140214 · Cited by 496

Antibiotics at the crossroads

Nathan, C. (2004) · Nature · doi:10.1038/431899a · Cited by 410

Impact of Epidermal Growth Factor Receptor and KRAS Mutations on Clinical Outcomes in Previously Untreated Non–Small Cell Lung Cancer Patients: Results of an Online Tumor Registry of Clinical Trials

Jackman, D. M., Miller, V. A., Cioffredi, L.-A., Yeap, B. Y., Jänne, P. A., Riely, G. J., Ruiz, M. G., Giaccone, G., Sequist, L. V., & Johnson, B. E. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-0888 · Cited by 379

Association between genital schistosomiasis and HIV in rural Zimbabwean women

Kjetland, E. F., Ndhlovu, P. D., Gomo, E., Mduluza, T., Midzi, N., Gwanzura, L., Mason, P. R., Sandvik, L., Friis, H., & Gundersen, S. G. (2006) · AIDS · doi:10.1097/01.aids.0000210614.45212.0a · Cited by 370

Antivirals and antiviral strategies

Clercq, E. D. (2004) · Nature Reviews Microbiology · doi:10.1038/nrmicro975 · Cited by 370

Histone Deacetylase Inhibitors: From Bench to Clinic

Paris, M., Porcelloni, M., Binaschi, M., & Fattori, D. (2008) · Journal of Medicinal Chemistry · doi:10.1021/jm7011408 · Cited by 367

PTP1B inhibitors as potential therapeutics in the treatment of Type 2 diabetes and obesity

Zhang, Z.-Y., & Lee, S.-Y. (2003) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.12.2.223 · Cited by 271

Tubulysins, New Cytostatic Peptides from Myxobacteria Acting on Microtubuli. Production, Isolation, Physico-chemical and Biological Properties.

SASSE, F., SIEINMETZ, H., HEIL, J., HÖFLE, G., & REICHENBACH, H. (2000) · The Journal of Antibiotics · doi:10.7164/antibiotics.53.879 · Cited by 257

Hit discovery and hit-to-lead approaches

Keserű, G. M., & Makara, G. M. (2006) · Drug Discovery Today · doi:10.1016/j.drudis.2006.06.016 · Cited by 256

A shot in the arm

Leeb, M. (2004) · Nature · doi:10.1038/431892a · Cited by 225

A highly efficient synthesis of telaprevir by strategic use of biocatalysis and multicomponent reactions

Znabet, A., Polak, M. M., Janssen, E., de Kanter, F. J. J., Turner, N. J., Orru, R. V. A., & Ruijter, E. (2010) · Chemical Communications · doi:10.1039/c0cc02823a · Cited by 205

A regio- and stereoselective 1,3-dipolar cycloaddition for the synthesis of novel spiro-pyrrolothiazolyloxindoles and their antitubercular evaluation

Prasanna, P., Balamurugan, K., Perumal, S., Yogeeswari, P., & Sriram, D. (2010) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2010.09.019 · Cited by 163

Novel Inhibitor of p38 MAP Kinase as an Anti-TNF-α Drug: Discovery of N -[4-[2-Ethyl-4-(3-methylphenyl)-1,3-thiazol-5-yl]-2-pyridyl]benzamide (TAK-715) as a Potent and Orally Active Anti-Rheumatoid Arthritis Agent

Miwatashi, S., Arikawa, Y., Kotani, E., Miyamoto, M., Naruo, K., Kimura, H., Tanaka, T., Asahi, S., & Ohkawa, S. (2005) · Journal of Medicinal Chemistry · doi:10.1021/jm050165o · Cited by 148

Discovery and Investigation of Antiproliferative and Apoptosis-Inducing Properties of New Heterocyclic Podophyllotoxin Analogues Accessible by a One-Step Multicomponent Synthesis

Magedov, I. V., Manpadi, M., slambrouck, S. V., Steelant, W. F. A., Николаевна, Р. Е., Пржевальский, Н. М., Rogelj, S., & Kornienko, A. (2007) · Journal of Medicinal Chemistry · doi:10.1021/jm070528f · Cited by 145

Discovery of 7-Hydroxy-6-methoxy-2-methyl-3-(3,4,5-trimethoxybenzoyl)benzo[b]furan (BNC105), a Tubulin Polymerization Inhibitor with Potent Antiproliferative and Tumor Vascular Disrupting Properties

Flynn, B. L., Gill, G. S., Grobelny, D. W., et al. (2011) · Journal of Medicinal Chemistry · doi:10.1021/jm200454y · Cited by 143

Robust Generation of Lead Compounds for Protein–Protein Interactions by Computational and MCR Chemistry: p53/Hdm2 Antagonists

Czarna, A., Beck, B., Srivastava, S., Popowicz, G. M., Wolf, S., Huang, Y., Biśta, M., Holak, T. A., & Dömling, A. S. S. (2010) · Angewandte Chemie International Edition · doi:10.1002/anie.201001343 · Cited by 137

A facile 1,3-dipolar cycloaddition of azomethine ylides to 2-arylidene-1,3-indanediones: Synthesis of dispiro-oxindolylpyrrolothiazoles and their antimycobacterial evaluation

Maheswari, S. U., Balamurugan, K., Perumal, S., Yogeeswari, P., & Sriram, D. (2010) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2010.10.080 · Cited by 135

A new anti-tubulin agent containing the benzo[b]thiophene ring system

Pinney, K. G., Bounds, A. D., Dingeman, K. M., Mocharla, V. P., Pettit, G. R., Bai, R., & Hamel, E. (1999) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/s0960-894x(99)00143-2 · Cited by 120

Natural Product Inspired Diversity Oriented Synthesis of Tetrahydroquinoline Scaffolds as Antitubercular Agent

Kumar, A., Srivastava, S., Gupta, G., Chaturvedi, V., Sinha, S. K., & Srivastava, A. K. (2010) · ACS Combinatorial Science · doi:10.1021/co100022h · Cited by 119

Overexpression of Cdc25B, an androgen receptor coactivator, in prostate cancer

Ngan, E., Hashimoto, Y., Ma, Z.-Q., Tsai, M., & Tsai, S. Y. (2003) · Oncogene · doi:10.1038/sj.onc.1206121 · Cited by 118

Natural product–inspired cascade synthesis yields modulators of centrosome integrity

Dückert, H., Pries, V., Khedkar, V., Menninger, S., Bruss, H., Bird, A. W., Maliga, Z., Brockmeyer, A., Janning, P., Hyman, A. A., et al. (2011) · Nature Chemical Biology · doi:10.1038/nchembio.758 · Cited by 115

First Total Synthesis of Tubulysin B

Pando, O., Dörner, S., Preusentanz, R., Denkert, A., Porzel, A., Richter, W., & Wessjohann, L. A. (2009) · Organic Letters · doi:10.1021/ol902320w · Cited by 111

Suppression of Androgen Receptor-mediated Transactivation and Cell Growth by the Glycogen Synthase Kinase 3β in Prostate Cells

Wang, L., Lin, H.-K., Hu, Y., Xie, S., Yang, L., & Chang, C. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m313963200 · Cited by 96

Medicinal Chemistry Optimization of Acyldepsipeptides of the Enopeptin Class Antibiotics

Hinzen, B., Raddatz, S., Paulsen, H., Lampe, T. F. J., Schumacher, A., Häbich, D., Hellwig, V., Benet‐Buchholz, J., Endermann, R., Labischinski, H., et al. (2006) · ChemMedChem · doi:10.1002/cmdc.200600055 · Cited by 93

Total Synthesis of (−)-Muraymycin D2 and Its Epimer

Tanino, T., Ichikawa, S., Shiro, M., & Matsuda, A. (2010) · The Journal of Organic Chemistry · doi:10.1021/jo9027193 · Cited by 93

Bicalutamide (Casodex®) in the treatment of prostate cancer

Fradet, Y. (2004) · Expert Review of Anticancer Therapy · doi:10.1586/14737140.4.1.37 · Cited by 92

Synthesis, antibacterial activity evaluation and QSAR studies of novel dispiropyrrolidines

Karthikeyan, K., Sivakumar, P. M., Doble, M., & Perumal, P. T. (2010) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2010.04.035 · Cited by 90

Application of multicomponent reactions to antimalarial drug discovery. Part 2: New antiplasmodial and antitrypanosomal 4-aminoquinoline γ- and δ-lactams via a ‘catch and release’ protocol

Musonda, C. C., Gut, J., Rosenthal, P. J., Yardley, V., de Souza, R. C. C., & Chibale, K. (2006) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2006.04.035 · Cited by 82

Structural Simplification of Bioactive Natural Products with Multicomponent Synthesis. 3. Fused Uracil-Containing Heterocycles as Novel Topoisomerase-Targeting Agents

Evdokimov, N. M., slambrouck, S. V., Heffeter, P., Tu, L., Calvé, B. L., Lamoral‐Theys, D., Hooten, C., Uglinskii, P. Y., Rogelj, S., Robert Kiss, A., et al. (2011) · Journal of Medicinal Chemistry · doi:10.1021/jm1009428 · Cited by 78

An atom economic synthesis and antitubercular evaluation of novel spiro-cyclohexanones

Kumar, R. R., Perumal, S., Manju, S. C., Bhatt, P., Yogeeswari, P., & Sriram, D. (2009) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2009.05.018 · Cited by 77

Application of multi-component reactions to antimalarial drug discovery. Part 1: Parallel synthesis and antiplasmodial activity of new 4-aminoquinoline Ugi adducts

Musonda, C. C., Taylor, D., Lehman, J., Gut, J., Rosenthal, P. J., & Chibale, K. (2004) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2004.05.063 · Cited by 76

A highly atom economic, chemo-, regio- and stereoselective synthesis, and discovery of spiro-pyrido-pyrrolizines and pyrrolidines as antimycobacterial agents

Kumar, R. R., Perumal, S., Senthilkumar, P., Yogeeswari, P., & Sriram, D. (2008) · Tetrahedron · doi:10.1016/j.tet.2008.01.072 · Cited by 75

Praziquantel and Schistosomiasis

Dömling, A. S. S., & Khoury, K. (2010) · ChemMedChem · doi:10.1002/cmdc.201000202 · Cited by 70

Diversity-oriented synthesis of cyclic acyldepsipeptides leads to the discovery of a potent antibacterial agent

Socha, A. M., Tan, N. Y., LaPlante, K. L., & Sello, J. K. (2010) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2010.08.032 · Cited by 70

Synthesis and Biological Evaluation of Muraymycin Analogues Active against Anti-Drug-Resistant Bacteria

Tanino, T., Ichikawa, S., Al-Dabbagh, B., Bouhss, A., Ōyama, H., & Matsuda, A. (2010) · ACS Medicinal Chemistry Letters · doi:10.1021/ml100057z · Cited by 66

1,4‐Thienodiazepine‐2,5‐diones via MCR (I): Synthesis, Virtual Space and p53‐Mdm2 Activity

Huang, Y., Wolf, S., Biśta, M., Meireles, L., Camacho, C. J., Holak, T. A., & Dömling, A. S. S. (2010) · Chemical Biology & Drug Design · doi:10.1111/j.1747-0285.2010.00989.x · Cited by 65

Anticancer Properties of an Important Drug Lead Podophyllotoxin Can Be Efficiently Mimicked by Diverse Heterocyclic Scaffolds Accessible via One-Step Synthesis

Magedov, I. V., Frolova, L. V., Manpadi, M., Bhoga, U. D., Tang, H., Evdokimov, N. M., George, O., Georgiou, K. H., Renner, S., Getlik, M., et al. (2011) · Journal of Medicinal Chemistry · doi:10.1021/jm200410r · Cited by 65

Discovery of a novel bicycloproline P2 bearing peptidyl α-ketoamide LY514962 as HCV protease inhibitor

Yip, Y. Y., Victor, F., Lamar, J., et al. (2003) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2003.09.074 · Cited by 64

Isoquinolin‐1‐one Inhibitors of the MDM2–p53 Interaction

Rothweiler, U., Czarna, A., Krajewski, M., Ciombor, J., Kalinski, C., Khazak, V., Roß, G., Skobeleva, N., Weber, L., & Holak, T. A. (2008) · ChemMedChem · doi:10.1002/cmdc.200800025 · Cited by 55

CLOPIDOGREL: THE FUTURE CHOICE FOR PREVENTING PLATELET ACTIVATION DURING CORONARY STENTING?

Gurbel, P. A., O’Connor, C. M., Cummings, C. C., et al. (1999) · Pharmacological Research · doi:10.1006/phrs.1999.0478 · Cited by 49

Synthesis of 2-Hydrazolyl-4-Thiazolidinones Based on Multicomponent Reactions and Biological Evaluation Against Trypanosoma Cruzi

Pizzo, C., Saiz, C., Talevi, A., Gavernet, L., Palestro, P. H., Bellera, C. L., Bruno‐Blanch, L. E., Benítez, D., Cazzulo, J. J., Chidichimo, A. M., et al. (2010) · Chemical Biology & Drug Design · doi:10.1111/j.1747-0285.2010.01071.x · Cited by 42

Convergent 18 F radiosynthesis: A new dimension for radiolabelling

Li, L., Hopkinson, M. N., Yona, R. L., Béjot, R., Gee, A. D., & Gouverneur, V. (2010) · Chemical Science · doi:10.1039/c0sc00362j · Cited by 38

Synthesis, Biological Evaluation, and Molecular Docking of Ugi Products Containing a Zinc-Chelating Moiety as Novel Inhibitors of Histone Deacetylases

Grolla, A. A., Podestà, V., Chini, M. G., Micco, S. D., Vallario, A., Genazzani, A. A., Canonico, P. L., Bifulco, G., Tron, G. C., Sorba, G., et al. (2009) · Journal of Medicinal Chemistry · doi:10.1021/jm801529c · Cited by 38

Discovery and Preclinical Evaluation of a Novel Class of Cytotoxic Propynoic Acid Carbamoyl Methyl Amides (PACMAs)

Yamada, R., Cao, X., Butkevich, A. N., Millard, M., Odde, S., Mordwinkin, N., Gundla, R., Zandi, E., Louie, S. G., Petasis, N. A., et al. (2011) · Journal of Medicinal Chemistry · doi:10.1021/jm101655d · Cited by 36

Synthesis, molecular docking and biological evaluation as HDAC inhibitors of cyclopeptide mimetics by a tandem three-component reaction and intramolecular [3+2] cycloaddition

Pirali, T., Faccio, V., Mossetti, R., Grolla, A. A., Micco, S. D., Bifulco, G., Genazzani, A. A., & Tron, G. C. (2009) · Molecular Diversity · doi:10.1007/s11030-009-9153-9 · Cited by 27

Regioselective addition reactions at C-2 of 3,4-dihydropyrimidinones. Synthesis and evaluation of multifunctionalized tetrahydropyrimidines

Singh, K., Arora, D., & Balzarini, J. M. (2010) · Tetrahedron · doi:10.1016/j.tet.2010.08.034 · Cited by 15

What do we know about multicomponent reactions? Mechanisms and trends for the Biginelli, Hantzsch, Mannich, Passerini and Ugi MCRs

Alvim, H. G. O., da Silva Júnior, E. N., & Neto, B. A. D. (2014) · RSC Adv. · doi:10.1039/c4ra10651b · Cited by 261