Roles of Fluorine in Drug Design and Drug Action

Author(s): Satya Prakash Gupta*

Journal Name: Letters in Drug Design & Discovery

Volume 16 , Issue 10 , 2019

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Graphical Abstract:


The article discusses the basic properties of fluorine atom that have made it so useful in drug development. It presents several examples of therapeutically useful drugs acting against many life-threatening diseases along with the mechanism as to how fluorine influences the drug activity. It has been pointed out that fluorine, due to its ability to increase the lipophilicity of the molecule, greatly affects the hydrophobic interaction between the drug molecule and the receptor. Because of its small size, it hardly produces any steric effect, rather due to electronic properties enters into electrostatic and hydrogen-bond interactions. Thus, it greatly affects the drug-receptor interaction and leads to increase the activity of the drugs.

Keywords: Fluorine, fluorinated drugs, fluorinated pyrazoles, fluorinated benzazoles, fluorinated quinolones, hydrophobic.

Fluorine in Medicinal Chemistry and Chemical Biology Ojima, I. (Ed.), Blackwell Publishing, Ltd. 2009.
Zhou, Y.; Wang, J.; Gu, Z.; Wang, S.; Zhu, W.; Aceña, J.L.; Soloshonok, V.A.; Izawa, K.; Liu, H. Next generation of fluo-rine-containing pharmaceuticals, compounds currently in phase II−III clinical trials of major pharmaceutical companies: New structural trends and herapeutic areas. Chem. Rev., 2016, 116(2), 422-518.
[] [PMID: 26756377]
Filler, R.; Saha, R. Fluorine in medicinal chemistry: a century of progress and a 60-year retrospective of selected highlights. Future Med. Chem., 2009, 1(5), 777-791.
[] [PMID: 21426080]
Kirk, K.L. Fluorine in medicinal chemistry: Recent therapeu-tic applications of fluorinated small molecules. J. Fluor. Chem., 2006, 127, 1013-1029.
Gakh, A.A.; Burnett, M.N. Extreme modulation properties of aromatic fluorine. J. Fluor. Chem., 2011, 132, 88-93.
Kirk, K.L. Selective fluorination in drug design and development: an overview of biochemical rationales. Curr. Top. Med. Chem., 2006, 6(14), 1447-1456.
[] [PMID: 16918460]
Müller, K.; Faeh, C.; Diederich, F. Fluorine in pharmaceuticals: looking beyond intuition. Science, 2007, 317(5846), 1881-1886.
[] [PMID: 17901324]
Isanbor, C.; O’ Hagan, D. Fluorine in medicinal chemistry: A review of anti- cancer agents. J. Fluor. Chem., 2006, 127, 303-319.
Bégué, J-P.; Bonnet-Delpon, D. Recent advances (1995-2005) in fluorinated pharmaceuticals based on natural products. J. Fluor. Chem., 2006, 127, 992-1012.
Prakesch, P.; Grée, D.; Chandrasekhar, S.; Grée, R. Synthesis of fluoro analogues of unsaturated fatty acids and corre-sponding acyclic metabolites. Eur. J. Org. Chem., 2005, 1221-1232.
Natarajana, R.; Azerada, R.; Badetb, B.; Copin, E. Microbial cleavage of C-F bond. J. Fluor. Chem., 2005, 126, 425-436.
Böhm, H-J.; Banner, D.; Bendels, S.; Kansy, M.; Kuhn, B.; Müller, K.; Obst-Sander, U.; Stahl, M. Fluorine in medicinal chemistry. ChemBioChem, 2004, 5(5), 637-643.
[] [PMID: 15122635]
Jeschke, P. The unique role of fluorine in the design of active ingredients for modern crop protection. ChemBioChem, 2004, 5(5), 571-589.
[] [PMID: 15122630]
Ojima, I. Use of fluorine in the medicinal chemistry and chemical biology of bioactive compounds--a case study on fluorinated taxane anticancer agents. ChemBioChem, 2004, 5(5), 628-635.
[] [PMID: 15122634]
Yoder, N.C.; Kumar, K. Fluorinated amino acids in protein design and engineering. Chem. Soc. Rev., 2002, 31(6), 335-341.
[] [PMID: 12491748]
Smart, B. E Fluorine substituent effects (on bioactivity). J. Fluor. Chem., 2001, 109, 3-11.
Dax, K.; Albert, M.; Ortner, J.; Paul, B.J. Synthesis of deoxyfluoro sugars from carbohydrate precursors. Carbohydr. Res., 2000, 327(1-2), 47-86.
[] [PMID: 10968676]
Schlosser, M. Parametrization of substituents: Effects of fluorine and other heteroatoms on OH, NH, and CH acidities. Angew. Chem. Int. Ed. Engl., 1998, 37(11), 1496-1513.
[<1496:AID-ANIE1496>3.0.CO;2-U] [PMID: 29710919]
O’Hagan, D.; Rzepa, H.S. Some influences of fluorine in bioorganic chemistry. Chem. Commun. (Camb.), 1997, 645-652.
Bush, I.E.; Mahesh, V.B. Metabolism of 11-oxygenated steroids. 3. Some 1-dehydro and 9 α-fluoro steroids. Biochem. J., 1964, 93(2), 236-255.
[] [PMID: 5838655]
Wettstein, A. Chemistry of fluorosteroids and their hormonal properties A Ciba Foundation Symposium:Carbon-Fluorine Compounds, Elsevier Excerpta Medica, Amsterdam, 1972, pp. 281-301.
Hansch, C.; Leo, A.; Hoekman, D.H. Exploring QSAR: Fun-damentals and Applications in Chemistry and Biology; Ameri-can Chemical Society: Washington, D.C., 1995.
Hansch, C.; Leo, A.; Hoekman, D.H. Exploring QSAR: Hy-drophobic, Electronic, and Steric Constants; American Chem-ical Society: Washington, D.C., 1995.
Bock, C.W.; George, P.; Mains, G.J.; Trachtman, M. An ab initio study of the stability of the symmetrical and unsymmet-rical difluoroethylenes relative to ethylene and monofluoroethylene. J. Chem. Soc. Perkin Trans., 1979, 2, 814-821.
Paulini, R.; Müller, K.; Diederich, F. Orthogonal multipolar interactions in structural chemistry and biology. Angew. Chem. Int. Ed. Engl., 2005, 44(12), 1788-1805.
[] [PMID: 15706577]
Black, W.C.; Bayly, C.I.; Davis, D.E.; Desmarais, S.; Falgueyret, J.P.; Léger, S.; Li, C.S.; Massé, F.; McKay, D.J.; Palmer, J.T.; Percival, M.D.; Robichaud, J.; Tsou, N.; Zamboni, R. Trifluoroethylamines as amide isosteres in inhibitors of cathepsin K. Bioorg. Med. Chem. Lett., 2005, 15(21), 4741-4744.
[] [PMID: 16154747]
Sani, M.; Volonterio, A.; Zanda, M. The trifluoroethylamine function as peptide bond replacement. ChemMedChem, 2007, 2(12), 1693-1700.
[] [PMID: 17823898]
Maryanoff, B.E.; Costanzo, M.J. Inhibitors of proteases and amide hydrolases that employ an α-ketoheterocycle as a key enabling functionality. Bioorg. Med. Chem., 2008, 16(4), 1562-1595.
[] [PMID: 18053726]
Westerik, J.O.; Wolfenden, R. Aldehydes as inhibitors of papain. J. Biol. Chem., 1972, 247(24), 8195-8197.
[PMID: 4640942]
Thompson, R.C. Use of peptide aldehydes to generate transition-state analogs of elastase. Biochemistry, 1973, 12(1), 47-51.
[] [PMID: 4734224]
Shah, D.O.; Lai, K.; Gorenstein, D.G. Carbon-13 NMR spec-troscopy of “transition-state analog” complexes of N- acetyl-l-phenylalaninal and α-chymotrypsin. J. Am. Chem. Soc., 1984, 106, 4272-4273.
Takahashi, L.H.; Radhakrishnan, R.; Rosenfield, R.E. Jr Crystal - structure of the covalent complex formed by a peptidyl α,α-difluoro-β-ketop amide with porcine pancreatic elastase at 1.78Å resolution. J. Am. Chem. Soc., 1989, 111, 3368-3374.
Brady, K.; Wei, A-Z.; Ringe, D.; Abeles, R.H. Structure of chymotrypsin-trifluoromethyl ketone inhibitor complexes: comparison of slowly and rapidly equilibrating inhibitors. Biochemistry, 1990, 29(33), 7600-7607.
[PMID: 2271520]
Takahashi, L.H.; Radhakrishnan, R.; Rosenfield, R.E., Jr; Meyer, E.F., Jr; Trainor, D.A.; Stein, M. X-ray diffraction analysis of the inhibition of porcine pancreatic elastase by a peptidyl trifluoromethylketone. J. Mol. Biol., 1988, 201(2), 423-428.
[PMID: 3418704]
Veale, C.A.; Bernstein, P.R.; Bryant, C.; Ceccarelli, C.; Damewood, J.R., Jr; Earley, R.; Feeney, S.W.; Gomes, B.; Kosmider, B.J.; Steelman, G.B. Nonpeptidic inhibitors of human leukocyte elastase. 5. Design, synthesis, and X-ray crystallography of a series of orally active 5-aminopyrimidin-6-one-containing trifluoromethyl ketones. J. Med. Chem., 1995, 38(1), 98-108.
[] [PMID: 7837246]
Peet, N.P.; Burkhart, J.P.; Angelastro, M.R.; Giroux, E.L.; Mehdi, S.; Bey, P.; Kolb, M.; Neises, B.; Schirlin, D. Synthesis of peptidyl fluoromethyl ketones and peptidyl α-keto esters as inhibitors of porcine pancreatic elastase, human neutrophil elastase, and rat and human neutrophil cathepsin G. J. Med. Chem., 1990, 33(1), 394-407.
[] [PMID: 2296031]
Angelastro, M.R.; Baugh, L.E.; Bey, P.; Burkhart, J.P.; Chen, T.M.; Durham, S.L.; Hare, C.M.; Huber, E.W.; Janusz, M.J.; Koehl, J.R. Inhibition of human neutrophil elastase with peptidyl electrophilic ketones. 2. Orally active PG-Val-Pro-Val pentafluoroethyl ketones. J. Med. Chem., 1994, 37(26), 4538-4553.
[] [PMID: 7799404]
Ogilvie, W.; Bailey, M.; Poupart, M-A. Abraham, Bhavsar, A.; Bonneau, P.; Bordeleau, J.; Bousquet, Y.; Chabot, C.; Du-ceppe, J-S.; Fazal, G.; Goulet, S.; Chantal, G-M.; Guse, I.; Halmos, T.; Lavallée, P.; Leach. M.; Malenfant, E.; O’Meara, J.; Plante, R.; Plouffe, C.; Poirier, M.; Soucy, F.; Yoakim, C.; Déziel, R. Peptidomimetic inhibitors of the human cytomegal-ovirus protease. J. Med. Chem., 1997, 40, 4113-4135.
[] [PMID: 9406601]
LaPlante, S.R.; Bonneau, P.R.; Aubry, N.; Cameron, D.R.; Déziel, R.; Grand-Maître, C.; Plouffe, C.; Tong, L.; Kawai, S.H. Characterization of the human cytomegalovirus protease as an induced-fit serine protease and the implications to the design of mechanism-based inhibitors. J. Am. Chem. Soc., 1999, 121, 2974-2986.
Warner, P.; Green, R.C.; Gomes, B.; Strimpler, A.M. Non-peptidic inhibitors of human leukocyte elastase. 1. The design and synthesis of pyridone-containing inhibitors. J. Med. Chem., 1994, 37(19), 3090-3099.
[] [PMID: 7932532]
Veale, C.A.; Bernstein, P.R.; Bohnert, C.M.; Brown, F.J.; Bryant, C.; Damewood, J.R., Jr; Earley, R.; Feeney, S.W.; Edwards, P.D.; Gomes, B.; Hulsizer, J.M.; Kosmider, B.J.; Krell, R.D.; Moore, G.; Salcedo, T.W.; Shaw, A.; Silberstein, D.S.; Steelman, G.B.; Stein, M.; Strimpler, A.; Thomas, R.M.; Vacek, E.P.; Williams, J.C.; Wolanin, D.J.; Woolson, S. Orally active trifluoromethyl ketone inhibitors of human leukocyte elastase. J. Med. Chem., 1997, 40(20), 3173-3181.
[PMID: 9379436]
Ding, Y-S.; Fowler, J.S. Fluorine-18 labeled tracers for PET studies in the neurosciences, in Biomedical Frontiers of Fluorine Chemistry, ACS Symposium Series 639 In: American Chemical Society, Washington, D.C. 1996; p. 328 - 343.
Snyder, S.E.; Kilbourn, M.R. Chemistry of fluorine - 18 radiopharmaceuticals.Handbook of Radiopharmaceuticals; Welch, M.J; Redvanly, C.S., Ed.; JohnWiley & Sons, Ltd: Chichester, 2003, pp. 195-227.
Jeschke, P. The unique role of fluorine in the design of active ingredients for modern crop protection. ChemBioChem, 2004, 5(5), 571-589.
[] [PMID: 15122630]
Jeschke, P. The unique role of halogen substituents in the design of modern agrochemicals. Pest Manag. Sci., 2010, 66(1), 10-27.
[] [PMID: 19701961]
Fried, J.; Sabo, E.F. 9α-Fluoro derivatives of cortisone and hydrocortisone. J. Am. Chem. Soc., 1954, 76, 1455-1456.
O’Hagan, D. Fluorine in health care: Organofluorine contain-ing blockbuster drugs. J. Fluor. Chem., 2010, 131, 1071-1081.
McGrath, N.A.; Brichacek, M.; Njardarson, J.T. A Graphical journey of innovative organic architectures that have im-proved our lives. J. Chem. Educ., 2010, 87, 1348-1349.
Top 100 US Prescription and Brand Name Drugs Products. (accessed July 2, 2015).
Ilardi, E.A.; Vitaku, E.; Njardarson, J.T. Data-mining for sulfur and fluorine: an evaluation of pharmaceuticals to reveal opportunities for drug design and discovery. J. Med. Chem., 2014, 57(7), 2832-2842.
[] [PMID: 24102067]
LaRosa, J.C.; Grundy, S.M.; Waters, D.D.; Shear, C.; Barter, P.; Fruchart, J-C.; Gotto, A.M.; Greten, H.; Kastelein, J.J.P.; Shepherd, J.; Wenger, N.K. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N. Engl. J. Med., 2005, 352(14), 1425-1435.
[] [PMID: 15755765]
Ridker, P.M.; Danielson, E.; Fonseca, F.A.H.; Genest, J.; Gotto, A.M., Jr; Kastelein, J.J.P.; Koenig, W.; Libby, P.; Lorenzatti, A.J.; MacFadyen, J.G.; Nordestgaard, B.G.; Shepherd, J.; Willerson, J.T.; Glynn, R.J. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N. Engl. J. Med., 2008, 359(21), 2195-2207.
[] [PMID: 18997196]
Penning, T.D.; Talley, J.J.; Bertenshaw, S.R.; Carter, J.S.; Collins, P.W.; Docter, S.; Graneto, M.J.; Lee, L.F.; Malecha, J.W.; Miyashiro, J.M.; Rogers, R.S.; Rogier, D.J.; Yu, S.S.; Anderson, G.D. Burton, E.G.; Cogburn, J.N.; Gregory, S.A.; Koboldt, C.M.; Perkins, W.E.; Seibert, K.; Veenhuizen, A.W.; Zhang, Y.Y.; Isakson, P.C. Synthesis and biological evaluation of the 1,5-diarylpyrazole class of cyclooxygenase-2 inhibitors: identification of 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benze nesulfonamide (SC-58635, celecoxib). J. Med. Chem., 1997, 40(9), 1347-1365.
[] [PMID: 9135032]
Besset, T.; Poisson, T.; Pannecoucke, X. Recent progress in direct introduction of fluorinated groups on alkenes and alkynes by means of C-H bond functionalization. Chemistry, 2014, 20(51), 16830-16845.
[] [PMID: 25349030]
Wu, J. Review of recent advances in nucleophilic c-f bond- forming reactions at sp3 centers. Tetrahedron Lett., 2014, 55, 4289-4294.
Li, Y.; Wu, Y.; Li, G-S.; Wang, X-S. Palladium-catalyzed c-f bond formation via directed c-h activation. Adv. Synth. Catal., 2014, 356, 1412-1418.
Yang, X.; Wu, T.; Phipps, R.J.; Toste, F.D. Advances in catalytic enantioselective fluorination, mono-, di-, and trifluoromethylation, and trifluoromethylthiolation reactions. Chem. Rev., 2015, 115(2), 826-870.
[] [PMID: 25337896]
Ahrens, T.; Kohlmann, J.; Ahrens, M.; Braun, T. Functionalization of fluorinated molecules by transition-metal-mediated C-F bond activation to access fluorinated building blocks. Chem. Rev., 2015, 115(2), 931-972.
[] [PMID: 25347593]
Alonso, C.; Martínez de Marigorta, E.; Rubiales, G.; Palacios, F. Carbon trifluoromethylation reactions of hydrocarbon derivatives and heteroarenes. Chem. Rev., 2015, 115(4), 1847-1935.
[] [PMID: 25635524]
Zhou, Y.; Wang, J.; Gu, Z.; Wang, S.; Zhu, W.; Aceña, J.L.; Soloshonok, V.A.; Izawa, K.; Liu, H. Next generation of fluo-rine-containing pharmaceuticals, compounds currently in phase II−III clinical trials of major pharmaceutical companies: new structural trends and therapeutic areas. Chem. Rev., 2016, 116(2), 422-518.
[] [PMID: 26756377]
Brown, J.M.; Gouverneur, V. Transition-metal-mediated reactions for C(sp2)-F bond construction: the state of play. Angew. Chem. Int. Ed. Engl., 2009, 48(46), 8610-8614.
[] [PMID: 19827068]
Furuya, T.; Klein, J.E.M.N.; Ritter, T. Carbon-fluorine bond formation for the synthesis of aryl fluorides. Synthesis (Stuttg), 2010, 2010(11), 1804-1821.
[] [PMID: 20953341]
Furuya, T.; Kamlet, A.S.; Ritter, T. Catalysis for fluorination and trifluoromethylation. Nature, 2011, 473(7348), 470-477.
[] [PMID: 21614074]
Liang, T.; Neumann, C.N.; Ritter, T. Introduction of fluorine and fluorine-containing functional groups. Angew. Chem. Int. Ed. Engl., 2013, 52(32), 8214-8264.
[] [PMID: 23873766]
O’Hagan, D. Understanding organofluorine chemistry. An introduction to the C-F bond. Chem. Soc. Rev., 2008, 37(2), 308-319.
[] [PMID: 18197347]
Müller, K.; Faeh, C.; Diederich, F. Fluorine in pharmaceuticals: looking beyond intuition. Science, 2007, 317(5846), 1881-1886.
[] [PMID: 17901324]
Purser, S.; Moore, P.R.; Swallow, S.; Gouverneur, V. Fluorine in medicinal chemistry. Chem. Soc. Rev., 2008, 37(2), 320-330.
[] [PMID: 18197348]
Jeschke, P. The unique role of fluorine in the design of active ingredients for modern crop protection. ChemBioChem, 2004, 5(5), 571-589.
[] [PMID: 15122630]
Hung, M-H.; Farnham, W.B.; Feiring, A.E. Functional Fluo-romonomers and Fluoropolymers. Fluoropolymers: Syn-thesis; Hougham, G.; Cassidy, P.E.; Johns, K; Davidson, T., Ed.; Plenum: New York, 1999, Vol. 1, pp. 51-66.
Ametamey, S.M.; Honer, M.; Schubiger, P.A. Molecular imaging with PET. Chem. Rev., 2008, 108(5), 1501-1516.
[] [PMID: 18426240]
Cametti, M.; Crousse, B.; Metrangolo, P.; Milani, R.; Resnati, G. The fluorous effect in biomolecular applications. Chem. Soc. Rev., 2012, 41(1), 31-42.
[] [PMID: 21691620]
Berger, R.; Resnati, G.; Metrangolo, P.; Weber, E.; Hulliger, J. Organic fluorine compounds: a great opportunity for enhanced materials properties. Chem. Soc. Rev., 2011, 40(7), 3496-3508.
[] [PMID: 21448484]
Campbell, M.G.; Ritter, T. Late-stage fluorination: From fun-damentals to application. Org. Process Res. Dev., 2014, 18(4), 474-480.
[] [PMID: 25838756]
Campbell, M.G.; Ritter, T. Modern carbon-fluorine bond forming reactions for aryl fluoride synthesis. Chem. Rev., 2015, 115(2), 612-633.
[] [PMID: 25474722]
Shannon, R.D. Revised effective ionic radii and systematic studies of interatomic distances in halides and chalcogenides. Acta Crystallogr. A, 1976, 32, 751-767.
Emsley, J. Very strong hydrogen bonding. Chem. Soc. Rev., 1980, 9, 91-124.
Adams, D.J.; Clark, J.H. Nucleophilic routes to selectively fluorinated aromatics. Chem. Soc. Rev., 1999, 28, 225-231.
Kirsch, P. Modern Fluoroorganic Chemistry: Synthesis, Reac-tivity, Applications; Wiley: Weinheim, Germany, 2004.
Balz, G.; Schiemann, G. Über aromatische fluorverbindungen, I.: Ein neues verfahren zu ihrer darstellung. Chem. Ber., 1927, 60, 1186-1190.
Gribble, G.W. Balz-Schiemann Reaction.Name Reactions for Functional Group Transformations; Li, J.J., Ed.; Wiley: Hoboken, NJ, 2007, pp. 552-563.
Rutherford, K.G.; Redmond, W.; Rigamonti, J. The use of hexafluorophosphoric acid in the Schiemann reaction. J. Org. Chem., 1961, 26, 5149-5152.
Sellers, C.; Suschitzky, H. The use of arenediazonium hex-afluoro-antimonates and -arsenates in the preparation of aryl fluorides. J. Chem. Soc. C, 1968, 2317-2319.
Gottlieb, H.B. The replacement of chlorine by fluorine in organic compounds. J. Am. Chem. Soc., 1936, 58, 532-533.
Grushin, V.V.; Marshall, W. Fluorination of nonactivated haloarenes via arynes under mild conditions, resulting from further studies toward Ar−F reductive elimination from palla-dium (II). J. Organometallics, 2008, 27, 4825-4828.
Sheppard, T.D. Metal-catalysed halogen exchange reactions of aryl halides. Org. Biomol. Chem., 2009, 7(6), 1043-1052.
[] [PMID: 19262919]
Luo, Y-R. Handbook of Bond Dissociation Energies in Or-ganic Compounds; CRC Press: Boca Raton, FL, 2002.
Wu, X-F.; Anbarasan, P.; Neumann, H.; Beller, M. From noble metal to Nobel Prize: palladium-catalyzed coupling reactions as key methods in organic synthesis. Angew. Chem. Int. Ed. Engl., 2010, 49(48), 9047-9050.
[] [PMID: 21031398]
Hartwig, J.F. Carbon-heteroatom bond formation catalysed by organometallic complexes. Nature, 2008, 455(7211), 314-322.
[] [PMID: 18800130]
Hartwig, J.F. Carbon−heteroatom bond-forming reductive eliminations of amines, ethers, and sulfides. Acc. Chem. Res., 1998, 31, 852-860.
Muci, A.R.; Buchwald, S.L. Practical palladium catalysts for C-N and C-O bond Formation. Top. Curr. Chem., 2002, 219, 131-209.
Grushin, V.V. The organometallic fluorine chemistry of palladium and rhodium: studies toward aromatic fluorination. Acc. Chem. Res., 2010, 43(1), 160-171.
[] [PMID: 19788304]
Mu, X.; Liu, G. Copper-mediated/-catalyzed fluorination reac-tions: new routes to aryl fluorides. Org. Chem. Front., 2014, 1, 430-433.
Minkovsky, N.; Berezov, A. BIBW-2992, a dual receptor tyrosine kinase inhibitor for the treatment of solid tumors. Curr. Opin. Investig. Drugs, 2008, 9(12), 1336-1346.
[PMID: 19037840]
Miller, V.A.; Hirsh, V.; Cadranel, J.; Chen, Y-M.; Park, K.; Kim, S-W.; Zhou, C.; Su, W-C.; Wang, M.; Sun, Y.; Heo, D.S.; Crino, L.; Tan, E.H.; Chao, T.Y.; Shahidi, M.; Cong, X.J.; Lorence, R.M.; Yang, J.C. Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1): a phase 2b/3 randomised trial. Lancet Oncol., 2012, 13(5), 528-538.
[] [PMID: 22452896]
Fong, P.C.; Boss, D.S.; Yap, T.A.; Tutt, A.; Wu, P.; Mergui-Roelvink, M.; Mortimer, P.; Swaisland, H.; Lau, A.; O’Connor, M.J.; Ashworth, A.; Carmichael, J.; Kaye, S.B.; Schellens, J.H.; de Bono, J.S.; Schellens, J.H.; de Bono, J.S. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N. Engl. J. Med., 2009, 361(2), 123-134.
[] [PMID: 19553641]
Gunderson, C.C.; Moore, K.N. Olaparib: an oral PARP-1 and PARP-2 inhibitor with promising activity in ovarian cancer. Future Oncol., 2015, 11(5), 747-757.
[] [PMID: 25757679]
Morrow, D.A.; Scirica, B.M.; Fox, K.A.A.; Berman, G.; Strony, J.; Veltri, E.; Bonaca, M.P.; Fish, P.; McCabe, C.H.; Braunwald, E. Evaluation of a novel antiplatelet agent for secondary prevention in patients with a history of atherosclerotic disease: design and rationale for the Thrombin-Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2 ° P)-TIMI 50 trial. Am. Heart J., 2009, 158(3), 335-341.e3.
[] [PMID: 19699854]
Frampton, J.E. Vorapaxar: a review of its use in the long-term secondary prevention of atherothrombotic events. Drugs, 2015, 75(7), 797-808.
[] [PMID: 25895464]
Im, W.B.; Choi, S.H.; Park, J-Y.; Choi, S.H.; Finn, J.; Yoon, S-H. Discovery of torezolid as a novel 5-hydroxymethyl-oxazolidinone antibacterial agent. Eur. J. Med. Chem., 2011, 46(4), 1027-1039.
[] [PMID: 21292356]
Bhatia, H.K.; Singh, H.; Grewal, N.; Natt, N.K. Sofosbuvir: A novel treatment option for chronic hepatitis C infection. J. Pharmacol. Pharmacother., 2014, 5(4), 278-284.
[] [PMID: 25422576]
Keating, G.M.; Vaidya, A. Sofosbuvir: first global approval. Drugs, 2014, 74(2), 273-282.
[] [PMID: 24442794]
Gu, W-G. Newly approved integrase inhibitors for clinical treatment of AIDS. Biomed. Pharmacother., 2014, 68(8), 917-921.
[] [PMID: 25451165]
Serrao, E.; Odde, S.; Ramkumar, K.; Neamati, N. Raltegravir, elvitegravir, and metoogravir: the birth of “me-too” HIV-1 integrase inhibitors. Retrovirology, 2009, 6, 25.
[] [PMID: 19265512]
Biftu, T.; Sinha-Roy, R.; Chen, P.; Qian, X.; Feng, D.; Kuethe, J.T.; Scapin, G.; Gao, Y.D.; Yan, Y.; Krueger, D.; Bak, A.; Eiermann, G.; He, J.; Cox, J.; Hicks, J.; Lyons, K.; He, H.; Salituro, G.; Tong, S.; Patel, S.; Doss, G.; Petrov, A.; Wu, J.; Xu, S.S.; Sewall, C.; Zhang, X.; Zhang, B.; Thornberry, N.A.; Weber, A.E. Omarigliptin (MK-3102): a novel long-acting DPP-4 inhibitor for once-weekly treatment of type 2 diabetes. J. Med. Chem., 2014, 57(8), 3205-3212.
[] [PMID: 24660890]
Burness, C.B. Omarigliptin: first global approval. Drugs, 2015, 75(16), 1947-1952.
[] [PMID: 26507988]
Guinea, J.; Peláez, T.; Recio, S.; Torres-Narbona, M.; Bouza, E. In vitro antifungal activities of isavuconazole (BAL4815), voriconazole, and fluconazole against 1,007 isolates of zygomycete, Candida, Aspergillus, Fusarium, and Scedosporium species. Antimicrob. Agents Chemother., 2008, 52(4), 1396-1400.
[] [PMID: 18212101]
Lepak, A.J.; Marchillo, K.; Vanhecker, J.; Andes, D.R. Isavuconazole (BAL4815) pharmacodynamic target determination in an in vivo murine model of invasive pulmonary aspergillosis against wild-type and cyp51 mutant isolates of Aspergillus fumigatus. Antimicrob. Agents Chemother., 2013, 57(12), 6284-6289.
[] [PMID: 24100500]
Guinea, J.; Bouza, E. Isavuconazole: a new and promising antifungal triazole for the treatment of invasive fungal infections. Future Microbiol., 2008, 3(6), 603-615.
[] [PMID: 19072177]
Blanco, J-L.; Varghese, V.; Rhee, S-Y.; Gatell, J.M.; Shafer, R.W. HIV-1 integrase inhibitor resistance and its clinical implications. J. Infect. Dis., 2011, 203(9), 1204-1214.
[] [PMID: 21459813]
Link, J.O.; Taylor, J.G.; Xu, L.; Mitchell, M.; Guo, H.; Liu, H.; Kato, D.; Kirschberg, T.; Sun, J.; Squires, N.; Parrish, J.; Kellar, T.; Yang, Z.Y.; Yang, C.; Matles, M.; Wang, Y.; Wang, K.; Cheng, G.; Tian, Y.; Mogalian, E.; Mondou, E.; Cornpropst, M.; Perry, J.; Desai, M.C. Discovery of ledipasvir (GS-5885): a potent, once-daily oral NS5A inhibitor for the treatment of hepatitis C virus infection. J. Med. Chem., 2014, 57(5), 2033-2046.
[] [PMID: 24320933]
Rheault, T.R.; Stellwagen, J.C.; Adjabeng, G.M.; Hornberger, K.R.; Petrov, K.G.; Waterson, A.G.; Dickerson, S.H.; Mook, R.A., Jr; Laquerre, S.G.; King, A.J.; Rossanese, O.W.; Arnone, M.R.; Smitheman, K.N.; Kane-Carson, L.S.; Han, C.; Moorthy, G.S.; Moss, K.G.; Uehling, D.E. Discovery of dabrafenib: A selective inhibitor of raf kinases with antitumor activity against BRaf- driven tumors. ACS Med. Chem. Lett., 2013, 4(3), 358-362.
[] [PMID: 24900673]
Wong, H.; Vernillet, L.; Peterson, A.; Ware, J.A.; Lee, L.; Martini, J-F.; Yu, P.; Li, C.; Del Rosario, G.; Choo, E.F.; Hoeflich, K.P.; Shi, Y.; Aftab, B.T.; Aoyama, R.; Lam, S.T.; Belvin, M.; Prescott, J. Bridging the gap between preclinical and clinical studies using pharmacokinetic-pharmacodynamic modeling: an analysis of GDC-0973, a MEK inhibitor. Clin. Cancer Res., 2012, 18(11), 3090-3099.
[] [PMID: 22496205]
Sithanandam, G.; Kolch, W.; Duh, F.M.; Rapp, U.R. Complete coding sequence of a human B-raf cDNA and detection of B-raf protein kinase with isozyme specific antibodies. Oncogene, 1990, 5, 1775-1780.
Sithanandam, G.; Druck, T.; Cannizzaro, L.A.; Leuzzi, G.; Huebner, K.; Rapp, U.R. B-raf and a B-raf pseudogene are lo-cated on 7q in man. Oncogene, 1992, 7, 795-799.
[PMID: 1565476]
Cantley, L.C. The phosphoinositide 3-kinase pathway. Science, 2002, 296(5573), 1655-1657.
[] [PMID: 12040186]
Azab, F.; Muz, B.; de la Puente, P.; Salama, N.; Azab, A.K. Buparlisib (NVP-BKM-120). Drugs Future, 2013, 38, 73-80.
Maira, S-M.; Pecchi, S.; Huang, A.; Burger, M.; Knapp, M.; Sterker, D.; Schnell, C.; Guthy, D.; Nagel, T.; Wiesmann, M.; Brachmann, S.; Fritsch, C.; Dorsch, M.; Chène, P.; Shoemaker, K.; De Pover, A.; Menezes, D.; Martiny-Baron, G.; Fabbro, D.; Wilson, C.J.; Schlegel, R.; Hofmann, F.; García-Echeverría, C.; Sellers, W.R.; Voliva, C.F. Identification and characterization of NVP-BKM120, an orally available pan-class I PI3-kinase inhibitor. Mol. Cancer Ther., 2012, 11(2), 317-328.
[] [PMID: 22188813]
Pecchi, S.; Renhowe, P.A.; Taylor, C.; Kaufman, S.; Merritt, H.; Wiesmann, M.; Shoemaker, K.R.; Knapp, M.S.; Ornelas, E.; Hendrickson, T.F.; Fantl, W.; Voliva, C.F. Identification and structure-activity relationship of 2-morpholino 6-(3-hydroxyphenyl) pyrimidines, a class of potent and selective PI3 kinase inhibitors. Bioorg. Med. Chem. Lett., 2010, 20(23), 6895-6898.
[] [PMID: 21035331]
Hafner, A.; Bräse, S. Trifluoromethylation of 1-aryl-3,3-diisopropyltriazenes. Adv. Synth. Catal., 2013, 355, 996-1000.
Warnke, C.; Meyer zu Hörste, G.; Hartung, H-P.; Stüve, O.; Kieseier, B.C. Review of teriflunomide and its potential in the treatment of multiple sclerosis. Neuropsychiatr. Dis. Treat., 2009, 5, 333-340.
[PMID: 19557143]
Saliu, O.Y.; Crismale, C.; Schwander, S.K.; Wallis, R.S. Bactericidal activity of OPC-67683 against drug-tolerant Mycobacterium tuberculosis. J. Antimicrob. Chemother., 2007, 60(5), 994-998.
[] [PMID: 17761500]
Xavier, A.S.; Lakshmanan, M. Delamanid: A new armor in combating drug-resistant tuberculosis. J. Pharmacol. Pharmacother., 2014, 5(3), 222-224.
[] [PMID: 25210407]
Gler, M.T.; Skripconoka, V.; Sanchez-Garavito, E.; Xiao, H.; Cabrera-Rivero, J.L.; Vargas-Vasquez, D.E.; Gao, M.; Awad, M.; Park, S.K.; Shim, T.S.; Suh, G.Y.; Danilovits, M.; Ogata, H.; Kurve, A.; Chang, J.; Suzuki, K.; Tupasi, T.; Koh, W.J.; Seaworth, B.; Geiter, L.J.; Wells, C.D. Delamanid for multidrug-resistant pulmonary tuberculosis. N. Engl. J. Med., 2012, 366(23), 2151-2160.
[] [PMID: 22670901]
Duffy, R.A.; Morgan, C.; Naylor, R.; Higgins, G.A.; Varty, G.B.; Lachowicz, J.E.; Parker, E.M. Rolapitant (SCH 619734): a potent, selective and orally active neurokinin NK1 receptor antagonist with centrally-mediated antiemetic effects in ferrets. Pharmacol. Biochem. Behav., 2012, 102(1), 95-100.
[] [PMID: 22497992]
Jordan, K.; Jahn, F.; Aapro, M. Recent developments in the prevention of chemotherapy-induced nausea and vomiting (CINV): a comprehensive review. Ann. Oncol., 2015, 26(6), 1081-1090.
[] [PMID: 25755107]
Cao, G.; Beyer, T.P.; Zhang, Y.; Schmidt, R.J.; Chen, Y.Q.; Cockerham, S.L.; Zimmerman, K.M.; Karathanasis, S.K.; Cannady, E.A.; Fields, T.; Mantlo, N.B. Evacetrapib is a novel, potent, and selective inhibitor of cholesteryl ester transfer protein that elevates HDL cholesterol without inducing aldosterone or increasing blood pressure. J. Lipid Res., 2011, 52(12), 2169-2176.
[] [PMID: 21957197]
Nicholls, S.J.; Brewer, H.B.; Kastelein, J.J.; Krueger, K.A.; Wang, M.D.; Shao, M.; Hu, B.; McErlean, E.; Nissen, S.E. Effects of the CETP inhibitor evacetrapib administered as monotherapy or in combination with statins on HDL and LDL cholesterol: a randomized controlled trial. JAMA, 2011, 306(19), 2099-2109.
[] [PMID: 22089718]
Miura, K.; Satoh, M.; Kinouchi, M.; Yamamoto, K.; Hasegawa, Y.; Philchenkov, A.; Kakugawa, Y.; Fujiya, T. The preclinical development of regorafenib for the treatment of colorectal cancer. Expert Opin. Drug Discov., 2014, 9(9), 1087-1101.
[] [PMID: 24896071]
Wilhelm, S.M.; Dumas, J.; Adnane, L.; Lynch, M.; Carter, C.A.; Schütz, G.; Thierauch, K-H.; Zopf, D. Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity. Int. J. Cancer, 2011, 129(1), 245-255.
[] [PMID: 21170960]
Smith, R.A.; Barbosa, J.; Blum, C.L.; Bobko, M.A.; Caringal, Y.V.; Dally, R.; Johnson, J.S.; Katz, M.E.; Kennure, N. Kingery- Wood, J.; Lee, W.; Lowinger, T.B.; Lyons, J.; Marsh, V.; Rogers, D.H.; Swartz, S.; Walling, T.; Wild, H. Discovery of heterocyclic ureas as a new class of Raf kinase inhibitors: Identification of a second generation lead by a om-binatorial chemistry approach. Bioorg. Med. Chem. Lett., 2001, 11, 2775-2778.
[] [PMID: 11591521]
Pinard, E.; Alanine, A.; Alberati, D.; Bender, M.; Borroni, E.; Bourdeaux, P.; Brom, V.; Burner, S.; Fischer, H.; Hainzl, D.; Halm, R.; Hauser, N.; Jolidon, S.; Lengyel, J.; Marty, H.P.; Meyer, T.; Moreau, J.L.; Mory, R.; Narquizian, R.; Nettekoven, M.; Norcross, R.D.; Puellmann, B.; Schmid, P.; Schmitt, S.; Stalder, H.; Wermuth, R.; Wettstein, J.G.; Zimmerli, D. Selective GlyT1 inhibitors: discovery of [4-(3-fluoro-5-trifluoromethylpyridin-2-yl)piperazin-1-yl][5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methylethoxy)phenyl]methanone (RG1678), a promising novel medicine to treat schizophrenia. J. Med. Chem., 2010, 53(12), 4603-4614.
[] [PMID: 20491477]
Lindsley, C.W.; Wolkenberg, S.E.; Kinney, G.G. Progress in the preparation and testing of glycine transporter type-1 (GlyT1) inhibitors. Curr. Top. Med. Chem., 2006, 6(17), 1883-1896.
[] [PMID: 17017963]
Chen, C.; Wu, D.; Guo, Z.; Xie, Q.; Reinhart, G.J.; Madan, A.; Wen, J.; Chen, T.; Huang, C.Q.; Chen, M.; Chen, M.; Chen, Y.; Tucci, F.C.; Rowbottom, M.; Pontillo, J.; Zhu, Y.F.; Wade, W.; Saunders, J.; Bozigian, H.; Struthers, R.S. Discovery of sodium R-(+)-4-2-[5-(2-Fluoro-3-methoxyphenyl)-3-(2-fluoro-6-[trifluoromethyl]-benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]- 1-phenylethylaminobutyrate (Elagolix), a potent and orally available nonpeptide antagonist of the human gonadotropin-releasing hormone receptor. J. Med. Chem., 2008, 51, 7478-7485.
[] [PMID: 19006286]
Betz, S.F.; Zhu, Y-F.; Chen, C.; Struthers, R.S. Non-peptide gonadotropin-releasing hormone receptor antagonists. J. Med. Chem., 2008, 51(12), 3331-3348.
[] [PMID: 18419112]
Lipunova, G.N.; Nosova, E.V.; Charushin, V.N.; Chupakhin, O.N. Fluorine-containing pyrazoles and their condensed de-rivatives: Synthesis and biological activity. J. Fluor. Chem., 2015, 175, 84-109.
Genin, M.J.; Biles, C.; Keiser, B.J.; Poppe, S.M.; Swaney, S.M.; Tarpley, W.G.; Yagi, Y.; Romero, D.L. Novel 1,5-diphenylpyrazole nonnucleoside HIV-1 reverse transcriptase inhibitors with enhanced activity versus the delavirdine-resistant P236L mutant: lead identification and SAR of 3- and 4-substituted derivatives. J. Med. Chem., 2000, 43(5), 1034-1040.
[] [PMID: 10715167]
Nenajdenko, V., Ed.; Fluorine in Heterocyclic Chemistry; Springer, 2014, Vol. 1 and 2, .
Petrov, V.A. Fluorinated Heterocyclic Compounds: Synthesis, Chemistry and Applications; Wiley: New York, 2009.
Gakh, A.; Kirk, K.L., Eds.; Fluorinated Heterocycles; ACS, 2009.
Nosova, E.V.; Lipunova, G.N.; Charushin, V.N.; Chupakhin, O.N.; Fluorinated Azines, O.N. Chupakhin; O.N. Fluorinated Azines and Benzazines, UrO RAN: Ekaterinburg, 2011.
Storer, R.; Ashton, C.J.; Baxter, A.D.; Hann, M.M.; Marr, C.L.P.; Mason, A.M.; Mo, C.L.; Myers, P.L.; Noble, S.A.; Penn, C.R.; Weir, N.G.; Woods, J.M.; Coe, P.L. The synthesis and antiviral activity of 4-fluoro-1-beta-D-ribofuranosyl-1H-pyrazole-3-carboxamide. Nucleosides Nucleotides, 1999, 18(2), 203-216.
[] [PMID: 10067273]
Jones, P.; Pryde, D.C.; Tran, T.D. Patent WO 2007093901, 2007 August;
Oslob, J.D.; McDowell, R.S.; Johnson, R.; Yang, H.; Evanchik, M.; Zaharia, C.A.; Cai, H.; Hu, L.W. Patent WO 2014008197, 2014 January;
England, K.; Mason, H.; Osborne, R.; Roberts, L. An im-proved synthesis of a novel α1A partial agonist including a new two-step synthesis of 4-fluoropyrazole. Tetrahedron Lett., 2010, 51, 2849-2851.
Roberts, L.R.; Bryans, J.; Conlon, K.; McMurray, G.; Stobie, A.; Whitlock, G.A. Novel 2-imidazoles as potent, selective and CNS penetrant α1A adrenoceptor partial agonists. Bioorg. Med. Chem. Lett., 2008, 18(24), 6437-6440.
[] [PMID: 18980842]
Dressen, D.; Garofalo, A.W.; Hawkinson, J.; Hom, D.; Jagodzinski, J.; Marugg, J.L.; Neitzel, M.L.; Pleiss, M.A.; Szoke, B.; Tung, J.S.; Wone, D.W.; Wu, J.; Zhang, H. Preparation and optimization of a series of 3-carboxamido-5-phenacylaminopyrazole bradykinin B1 receptor antagonists. J. Med. Chem., 2007, 50(21), 5161-5167.
[] [PMID: 17880055]
Tung, J.S.; Garofalo, A.W.; Pleiss, M.A.; Wu, J.; Wone, D.W.G.; Guinn, A.C.; Dressen, D.; Neitz, R.J.; Marugg, J.L.; Neitzel, M.L. Patent WO 2004098589, 2004 November 18;
Gibson, C.; Tradler, T.; Schnatbaum, K.; Pfeifer, J.; Locardi, E.; Scharn, D.; Paschke, M.; Reimer, U.; Richter, U.; Hummel, G.; Reineke, U. Patent WO 2008116620, 2008 October 2;
Gibson, C.; Schnatbaum, K.; Tradler, T.; Pfeifer, J.; Scharn, D.; Reimer, U.; Richter, U.; Hummel, G.; Reineke, U.; Locar-di, E.; Paschke, M. Patent WO 2010031589, 2010 March 25;
Zhou, C.; Zou, W.; Hua, Y.; Dang, Q. Patent WO 2013040790, 2013 March 28;
Dang, Q.; Zhou, C.; Zou, W.; Hua, Y. Patent WO 2013043624, 2013 March 28;
Letavic, M.; Rudolph, D.A.; Savall, B.M.; Shireman, B.T.; Swanson, D. Patent WO 2012145581, 2012 October 26;
Lipunova, G.N.; Nosova, E.V.; Charush, V.N. Fluorinated quinolines: synthesis, properties and applications. Fluorine in Heterocyclic Chemistry, 2013, 2, 59-108.
Bigot, A.; Ahmad, J.; Malleron, J.; Martin, J.; Mignani, S.; Pantel, G.; Ronan, B.; Tabart, M. 4-Substituted quinoline derivatives, the preparation thereof and compositions containing same, useful as antimicrobials. FR Patent 2852954, 2004.
Bacque, E.; Bigot, A.; El Ahmad, Y.; Malleron, J.; Mignani, S.; Ronan, B.; Tabatr, M.; Viviani, F. New 4-(3-(quinolin-4-yl)-3- oxopropyl)-piperidine derivatives, useful as potent, low toxicity antibacterial agents effective against Gram positive and Gram positive bacteria. FR Patent 2844270, 2004 Mar 12;
Freeman, G.A.; Andrews Iii, C.W., III; Hopkins, A.L.; Lowell, G.S.; Schaller, L.T.; Cowan, J.R.; Gonzales, S.S.; Koszalka, G.W.; Hazen, R.J.; Boone, L.R.; Ferris, R.G.; Creech, K.L.; Roberts, G.B.; Short, S.A.; Weaver, K.; Reynolds, D.J.; Milton, J.; Ren, J.; Stuart, D.I.; Stammers, D.K.; Chan, J.H. Design of non-nucleoside inhibitors of HIV-1 reverse transcriptase with improved drug resistance properties. 2. J. Med. Chem., 2004, 47(24), 5923-5936.
[] [PMID: 15537347]
Schuurman, H. Use of brequinar and derivatives in chronic rejection of allografts and xenotransplantation. WO Patent 42953, 1997.
Oshima, E.; Yanase, M.; Sone, H. Preparation of 7-(2-fl uorophenyl)- 1-benzosuberone by coupling of 7-halo-1-benzosuberone with halofl uorobenzene. JP Patent 07607, 2000.
Oshima, E.; Yanase, M.; Sone, H. Method for preparation of 7-(2-fl uorophenyl)-1- benzosuberone derivatives. JP Patent 07606, 2000.
Liang, C. Preparation of quinolinone derivatives as protein Kinase inhibitors. WO Patent 54183, 2005.
Stadlwieser, J.; Barbler, P.; Taylor, S. 8-Fluoro-6-(methoxymethoxy)-quinoline: synthesis and regioselective functionalization via reaction with organolithium compounds. Helv. Chim. Acta, 1998, 81, 1088-1094.
Chan, W.; Smith, P.; Wyman, P. Preparation of quinoline-4- carboxamide derivatives as neurokinin 3 receptor antagonists. WO Patent 14575, 2005.
Cai, S.; Chou, J.; Harwood, E.; Heise, C.; Machajewski, T.; Ryckman, D.; Shang, X.; Wiesmann, M.; Zhu, S. Preparation of benzimidazole quinolinones for inhibiting FGFR3 and treatingmultiple myeloma. WO Patent 47244, 2005.
Cai, S.; Chou, J.; Haewood, E.; Heise, C.; Machajewski, T.; Ryckman, D.; Shang, X.; Wiesmann, M.; Zhu, S. Preparation of benzimidazole quinolinones for inhibiting FGFR3 and treating multiple myeloma. US Patent 261307, 2005.
Carling, W.R.; Moore, K.W. Preparation of quinoline derivatives which enhance cognition via the GABA-A receptor. WO Patent 43930, 2004.
Hackler, R.; Jourdan, G.; Johnson, P.; Thoreen, B. Samari-toni, J.N. N-(4-pyridyl or 4- quinolinyl) arylacetamide and 4-(araloxy or aralkylamino) pyridine pesticides US Patent 5399564, 1995.
Nishizuko, T.; Kurihara, H.; Yamamoto, K. Process for producing 2,3,6-trialkyl-8-fl uoro- 4- quinoline derivatives. WO Patent 007460, 2004.
Kotovskaya, S.K.; Baskakova, Z.M.; Charushin, V.N.; Chupakhin, O.N.; Belanov, E.F. ormotov, N. I.; Balakhnin, S. M.; Serova, O. A. Synthesis and antiviral activity of fluori-nated pyrido[1,2-a]benzimidazoles. Russ. Chem. Pharm. J., 2005, 39, 574-578.
Protein-Ligand interactons(Eds.: H.J. Bohm, G.Schneider), Wiley- VCH, Weinheim, 2003.
Gupta, S.P.; Maheswaran, B.; Pande, V.; Kumar, D. A com-parative quantitative structure- activity relationship study on carbonic anhydrase and matrix metalloproteinase inhibition by sulfonylated amino acid hydroxamates. J. Enzyme Inhib. Med. Chem., 2003, 18, 7-13.
[] [PMID: 12751815]
Scozzafava, A.; Supuran, C.T. Carbonic anhydrase and matrix metalloproteinase inhibitors: sulfonylated amino acid hydroxamates with MMP inhibitory properties act as efficient inhibitors of CA isozymes I, II, and IV, and N-hydroxysulfonamides inhibit both these zinc enzymes. J. Med. Chem., 2000, 43(20), 3677-3687.
[] [PMID: 11020282]
Supuran, C.T.; Scozzafaca, A. Matrix metalloproteinases.Proteinase and Peptidase Inhibition; Recent Potential Targets for Drug Development; Smith, H.J; Simons, C., Ed.; Taylor and Francis: London, New York, 2002, pp. 35-61.
Gupta, S.P.; Kumaran, S. A quantitative structure-activity relationship study on Clostridium histolyticum collagenase inhibitors: roles of electrotopological state indices. Bioorg. Med. Chem., 2003, 11(14), 3065-3071.
[] [PMID: 12818668]
Gupta, S.P. Quantitative structure-activity relationship studies on zinc-containing metalloproteinase inhibitors. Chem. Rev., 2007, 107(7), 3042-3087.
[] [PMID: 17622180]
Paulini, R.; Müller, K.; Diederich, F. Orthogonal multipolar interactions in structural chemistry and biology. Angew. Chem. Int. Ed. Engl., 2005, 44(12), 1788-1805.
[] [PMID: 15706577]
Kim, C.Y.; Chandra, P.P.; Jain, A.; Christianson, D.W. Fluoroaromatic-fluoroaromatic interactions between inhibitors bound in the crystal lattice of human carbonic anhydrase II. J. Am. Chem. Soc., 2001, 123(39), 9620-9627.
[] [PMID: 11572683]
Zhou, P.; Zou, J.; Tian, F.; Shang, Z. Fluorine bonding--how does it work in protein-ligand interactions? J. Chem. Inf. Model., 2009, 49(10), 2344-2355.
[] [PMID: 19788294]
Olsen, J.A.; Banner, D.W.; Seiler, P.; Wagner, B.; Tschopp, T.; Obst-Sander, U.; Kansy, M.; Müller, K.; Diederich, F. Fluorine interactions at the thrombin active site: protein backbone fragments H-C(α)-C=O comprise a favorable C-F environment and interactions of C-F with electrophiles. ChemBioChem, 2004, 5(5), 666-675.
[] [PMID: 15122639]
Peterson, S.A.; Klabunde, T.; Lashuel, H.A.; Purkey, H.; Sacchettini, J.C.; Kelly, J.W. Inhibiting transthyretin conformational changes that lead to amyloid fibril formation. Proc. Natl. Acad. Sci. USA, 1998, 95(22), 12956-12960.
[] [PMID: 9789022]
Singh, N.; Shaik, B.; Agrawal, N.; Anita, K.; Agrawal, V.K.; Gupta, S.P. QSAR and molecular modeling studies on a series of potent indole-based pyridone analogues acting as hepatitis c virus (HCV) ns5b polymerase inhibitors. Lett. Drug Des. Discov., 2016, 13, 757-770.
Shaik, B.; Gupta, S.P. QSAR and molecular docking studies on a series of oxazolidinones as HIV-1 protease inhibitors. J. Appl. Biopharm. Pharmaco., 2017, 5, 30-36.
Sheik, B.; Agrawal, V.K.; Gupta, S.P.; Menon, U. Quantitative structure-activity relationsip and docking studies on a series of oxadiazole and triazole substituted naphthyridines as HIV-1 integrase inhibitors. Lett. Drug Des. Discov., 2017, 14, 10-27.
Shaik, B.; Deeb, O.; Agrawal, V.K.; Gupta, S.P. QSAR and molecular docking studies on series of cinnamic acid ana-logues as epidermal growth factor receptor (EGFR) inhibitors. Lett. Drug Des. Discov., 2017, 14, 83-95.
Shaik, B.; Gupta, S.P.; Zafar, T.; Anita, K. QSAR and molecu-lar docking studies on a series of 1-amino-5H-pyrido [4, 3-b] indol-4-carboxamide as janus kinase 2 (JAK2) inhibitors. Lett. Drug Des. Discov., 2018, 15, 169-180.
Chen, K.X.; Vibulbhan, B.; Yang, W.; Sannigrahi, M.; Ve-lazquez, F. Chan Tin-Yan; Venkatraman, S.; Anilkumar, G. N.; Zeng Q.; Bennet F.; Jiang Y.; Lesburg C.A.; Duca J.; Pinto P.; Gavalas S.; Huang Y.; Wu W.; Selyutin O.; Agrawal S.; Feld B.; Huang H.C.; Li C.; Cheng K.C.; Shih N.Y.; Kozlowski A.J.; Rosenblum B.S.; Njoroge G.F. Structure- activity rela-tionship (SAR) development and discovery of potent indole-based inhibitors of the hepatitis C virus (HCV) NS5B poly-merase. J. Med. Chem., 2012, 55, 754-765.
[] [PMID: 22148957]
Vulpetti, A. Protein interactions with fluorine and other halo-gens; Mol. Interact. Drug Discov, 2013, pp. 1-27.

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Year: 2019
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DOI: 10.2174/1570180816666190130154726
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