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Synthesis and Structure−Activity Relationships of Phenylenebis(methylene)- Linked Bis-azamacrocycles That Inhibit HIV-1 and HIV-2 Replication by Antagonism of the Chemokine Receptor CXCR4

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AnorMED Inc., 200-20353 64th Avenue, Langley, British Columbia V2Y 1N5, Canada, Johnson Matthey Pharmaceutical Research, 1401 King Road, West Chester, Pennsylvania 19380, and Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium
Cite this: J. Med. Chem. 1999, 42, 19, 3971–3981
Publication Date (Web):August 26, 1999
Copyright © 1999 American Chemical Society

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    Bis-tetraazamacrocycles such as the bicyclam AMD3100 are a class of potent and selective anti-HIV-1 and HIV-2 agents that inhibit virus replication by binding to the chemokine receptor CXCR4, the co-receptor for entry of X4 viruses. With the aim of optimizing the anti-HIV-1 and HIV-2 activity of bis-azamacrocycles, a series of analogues were synthesized which contain neutral heteroatom (oxygen, sulfur) or heteroaromatic (of lower pKa than a secondary amine) replacements for the amino groups of AMD3100. The introduction of one or more heteroatoms such as oxygen or sulfur into the macrocyclic ring of p-phenylenebis(methylene)-linked dimers (to give N3X or N2X2 bis-macrocycles) gave analogues with substantially reduced anti-HIV-1 (IIIB) and anti-HIV-2 (ROD) potency. In addition, the bis-sulfur analogue was also markedly more cytotoxic to MT-4 cells. However, bis-tetraazamacrocycles featuring a single pyridine group incorporated within the macrocyclic framework exhibited anti-HIV-1 and HIV-2 potency comparable to that of their saturated, aliphatic counterparts. The p-phenylenebis(methylene)-linked dimer of the py[14]aneN4 macrocycle inhibited HIV-1 replication at a 50% effective concentration (EC50) of 0.5 μM while remaining nontoxic to MT-4 cells at concentrations approaching 200 μM. A series of analogues containing macrocyclic heteroaromatic groups of varying pKa were also synthesized, and their ability to inhibit HIV replication was evaluated. Replacing the pyridine moiety of the py[14]aneN4 macrocyclic ring with pyrazine or pyridine groups substituted in the 4-position (with electron-withdrawing or -donating groups) either reduced antiviral potency or increased cytotoxicity to MT-4 cells. Finally, we synthesized a series of analogues in which the ring size of the bis-pyridyl macrocycles was varied between 12 and 16 members per ring including the py[iso-14]aneN4 ring system, an isomer of the py[14]aneN4 macrocycle. The p-phenylenebis(methylene)-linked dimer of the py[iso-14]aneN4 (AMD3329) displayed the highest antiviral activity of the bis-azamacrocyclic analogues reported to date, exhibiting EC50's against the cytopathic effects of HIV-1 and HIV-2 replication of 0.8 and 1.6 nM, respectively, that is, about 3−5-fold lower than the EC50 of AMD3100. AMD3329 also inhibited the binding of a specific CXCR4 mAb and the Ca2+ flux induced by SDF-1α, the natural ligand for CXCR4, more potently than AMD3100. Furthermore, AMD3329 also interfered with virus-induced syncytium formation at an EC50 of 12 nM.


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     AnorMED Inc.

     Johnson Matthey Pharmaceutical Research.


     Rega Institute for Medical Research.

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    14. Zhongli Gao and, William A. Metz. Unraveling the Chemistry of Chemokine Receptor Ligands. Chemical Reviews 2003, 103 (9) , 3733-3752.
    15. Louis S. Hegedus,, Michael J. Sundermann, and, Peter K. Dorhout. Synthesis, Complexation, and Coordination Oligomerization of 1,8-Pyrazine-Capped 5,12-Dioxocyclams. Inorganic Chemistry 2003, 42 (14) , 4346-4354.
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    18. Renato T. Skerlj,, Yuanxi Zhou,, Trevor Wilson, and, Gary J. Bridger. Palladium(0)-Catalyzed Coupling of Organozinc Iodide Reagents with Bromopyridines:  Synthesis of Selectively Protected Pyridine-Containing Azamacrocycles. The Journal of Organic Chemistry 2002, 67 (4) , 1407-1410.
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    20. Emiko Kikuta,, Shin Aoki, and, Eiichi Kimura. A New Type of Potent Inhibitors of HIV-1 TAR RNA−Tat Peptide Binding by Zinc(II)−Macrocyclic Tetraamine Complexes. Journal of the American Chemical Society 2001, 123 (32) , 7911-7912.
    21. Shin Aoki and, Eiichi Kimura. Highly Selective Recognition of Thymidine Mono- and Diphosphate Nucleotides in Aqueous Solution by Ditopic Receptors Zinc(II)−Bis(cyclen) Complexes (Cyclen = 1,4,7,10-Tetraazacyclododecane). Journal of the American Chemical Society 2000, 122 (19) , 4542-4548.
    22. Liezel A. Lumangtad, Elisa Claeys, Sunil Hamal, Amarawan Intasiri, Courtney Basrai, Expedite Yen-Pon, Davison Beenfeldt, Kurt Vermeire, Thomas W. Bell. Syntheses and anti-HIV and human cluster of differentiation 4 (CD4) down-modulating potencies of pyridine-fused cyclotriazadisulfonamide (CADA) compounds. Bioorganic & Medicinal Chemistry 2020, 28 (24) , 115816.
    23. Yoon Hyeun Oum, Steven A. Kell, Younghyoun Yoon, Zhongxing Liang, Pieter Burger, Hyunsuk Shim. Discovery of novel aminopiperidinyl amide CXCR4 modulators through virtual screening and rational drug design. European Journal of Medicinal Chemistry 2020, 201 , 112479.
    24. Anastasia D. Zubenko, Olga A. Fedorova. Aromatic and heteroaromatic azacrown compounds: advantages and disadvantages of rigid macrocyclic ligands. Russian Chemical Reviews 2020, 89 (7) , 750-786.
    25. Pauline Lejault, Katerina Duskova, Claire Bernhard, Ibai E. Valverde, Anthony Romieu, David Monchaud. The Scope of Application of Macrocyclic Polyamines Beyond Metal Chelation. European Journal of Organic Chemistry 2019, 2019 (36) , 6146-6157.
    26. Lun Kelvin Tsou, Ying‐Huey Huang, Jen‐Shin Song, Yi‐Yu Ke, Jing‐Kai Huang, Kak‐Shan Shia. Harnessing CXCR4 antagonists in stem cell mobilization, HIV infection, ischemic diseases, and oncology. Medicinal Research Reviews 2018, 38 (4) , 1188-1234.
    27. Fatemeh Ghasemi, Khaled Ghasemi, Ali Reza Rezvani, Ardeshir Shokrollahi, Masoud Refahi, Santiago García-Granda, Rafael Mendoza-Meroño. A novel salt of antidiabetic drug metformin resulting from a proton transfer reaction: Synthesis, characterization, crystal structure and solution studies. Journal of Molecular Structure 2017, 1131 , 30-35.
    28. Hatice Vural, İbrahim Uçar. A mixed experimental and theoretical study on chelidamate copper(II) complex with 4-methylpyrimidine. Journal of Coordination Chemistry 2016, 69 (20) , 3010-3020.
    29. Heng Zhang, Dongwei Kang, Boshi Huang, Na Liu, Fabao Zhao, Peng Zhan, Xinyong Liu. Discovery of non-peptide small molecular CXCR4 antagonists as anti-HIV agents: Recent advances and future opportunities. European Journal of Medicinal Chemistry 2016, 114 , 65-78.
    30. Roxana-Maria Amarandi, Gertrud Malene Hjortø, Mette Marie Rosenkilde, Stefanie Karlshøj. Probing Biased Signaling in Chemokine Receptors. 2016, 155-186.
    31. Fatemeh Ghasemi, Khaled Ghasemi, Ali Reza Rezvani, Claudia Graiff. Piperazine as counter ion for insulin-enhancing anions [VO2(dipic-OH)]−: Synthesis, characterization and X-ray crystal structure. Journal of Molecular Structure 2016, 1103 , 20-24.
    32. H. Vural, İ. Uçar, M.S. Soylu. Combined experimental–theoretical characterization of chelidamate nickel complex with 4-methylpyrimidine. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 2016, 152 , 584-590.
    33. İbrahim Uçar, Hatice Vural, Ebru Küçük. Two new chelidamate complexes with the 4-methoxypyridine: A combined theoretical and experimental study. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 2015, 151 , 667-672.
    34. Sophie Poty, Pauline Désogère, Christine Goze, Frédéric Boschetti, Thomas D‘huys, Dominique Schols, Christopher Cawthorne, Stephen J. Archibald, Helmut R. Maëcke, Franck Denat. New AMD3100 derivatives for CXCR4 chemokine receptor targeted molecular imaging studies: synthesis, anti-HIV-1 evaluation and binding affinities. Dalton Transactions 2015, 44 (11) , 5004-5016.
    35. Anne Steen, Olav Larsen, Stefanie Thiele, Mette M. Rosenkilde. Biased and G Protein-Independent Signaling of Chemokine Receptors. Frontiers in Immunology 2014, 5
    36. Fangfang Deng, Meihong Xie, Xiaoyun Zhang, Peizhen Li, Yueli Tian, Honglin Zhai, Yang Li. Combined molecular docking, molecular dynamics simulation and quantitative structure–activity relationship study of pyrimido[1,2-c][1,3]benzothiazin-6-imine derivatives as potent anti-HIV drugs. Journal of Molecular Structure 2014, 1067 , 1-13.
    37. Zahra Kalantari Khoramdareh, Seyed Abolfazl Hosseini-Yazdi, Bernhard Spingler, Ali Akbar Khandar. Copper(II) and zinc(II) complexes of mono- and tri-linked azacrown macrocycles: Synthesis, characterization, X-ray structure, phosphodiester hydrolysis and DNA cleavage. Inorganica Chimica Acta 2014, 415 , 7-13.
    38. Hatice Vural, İbrahim Uçar, M. Serkan Soylu. An experimental and theoretical approach of spectroscopic and structural properties of a new chelidamate copper (II) complex. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 2014, 122 , 758-766.
    39. Paul Ghattas, Joseph W. Carlin, Steven L. Murkli, Danielle L. Jacobs. Solvent-Free Microwave-Assisted Preparation of N -(2-(Pyridin-2-yl)-ethyl)sulfonamides. Synthetic Communications 2014, 44 (4) , 520-529.
    40. Hossein Eshtiagh-Hosseini, Masoud Mirzaei, Sara Zarghami, Antonio Bauzá, Antonio Frontera, Joel T. Mague, Morteza Habibi, Mojtaba Shamsipur. Crystal engineering with coordination compounds of 2,6-dicarboxy-4-hydroxypyridine and 9-aminoacridine fragments driven by different nature of the face-to-face π⋯π stacking. CrystEngComm 2014, 16 (7) , 1359-1377.
    41. Simon P Fricker, Markus Metz. Chemokine receptor modeling: an interdisciplinary approach to drug design. Future Medicinal Chemistry 2014, 6 (1) , 91-114.
    42. Carla Cruz, Elisa Cairrão, Olga Lourenço, Paulo Almeida, Ignacio Verde, João A. Queiroz. Polyazamacrocycles as Potential Antitumor Agents for Human Prostate Cancer Cells. Chemical Biology & Drug Design 2013, 81 (4) , 517-526.
    43. Nicholas A. Meanwell, Stanley V. D'Andrea, Christopher W. Cianci, Ira B. Dicker, Kap‐Sun Yeung, Makonen Belema, Mark Krystal. Antiviral Drug Discovery. 2013, 439-515.
    44. Simon P. Fricker. Physiology and Pharmacology of Plerixafor. Transfusion Medicine and Hemotherapy 2013, 40 (4) , 237-245.
    45. Tia L. Walker, Wilhelm Malasi, Swaranjali Bhide, Thomas Parker, Dan Zhang, Abegel Freedman, Jody M. Modarelli, James T. Engle, Christopher J. Ziegler, Paul Custer, Wiley J. Youngs, Michael J. Taschner. Synthesis and characterization of 1,8-dithia-4,11-diazacyclotetradecane. Tetrahedron Letters 2012, 53 (48) , 6548-6551.
    46. Francisco C. A. Lima, Rommel B. Viana, José W. M. Carneiro, Moacyr Comar, Albérico B. F. da Silva. Metal binding selectivity of oxa-aza macrocyclic ligand: a DFT study of first- and second-row transition metal for four coordination systems. Structural Chemistry 2012, 23 (5) , 1539-1545.
    47. Jesús M. Planesas, Violeta I. Pérez-Nueno, José I. Borrell, Jordi Teixidó. Impact of the CXCR4 structure on docking-based virtual screening of HIV entry inhibitors. Journal of Molecular Graphics and Modelling 2012, 38 , 123-136.
    48. Francisco C. A. Lima, Rommel B. Viana, Thais T. da Silva, Solange M. S. V. Wardell, Armando P. Nascimento do Filho, José Walkimar M. Carneiro, Moacyr Comar, Albérico B. F. da Silva. First- and second-row transition metal oxa-aza macrocyclic complexes: a DFT study of an octahedral conformation. Journal of Molecular Modeling 2012, 18 (7) , 3243-3253.
    49. Amnon Peled, Ori Wald, Jan Burger. Development of novel CXCR4-based therapeutics. Expert Opinion on Investigational Drugs 2012, 21 (3) , 341-353.
    50. Ido D. Weiss, Orit Jacobson, Dale O. Kiesewetter, John P. Jacobus, Lawrence P. Szajek, Xiaoyuan Chen, Joshua M. Farber. Positron Emission Tomography Imaging of Tumors Expressing the Human Chemokine Receptor CXCR4 in Mice with the Use of 64Cu-AMD3100. Molecular Imaging and Biology 2012, 14 (1) , 106-114.
    51. Thangavel Sathiya Kamatchi, Nataraj Chitrapriya, Hyosun Lee, Chris F. Fronczek, Frank R. Fronczek, Karuppannan Natarajan. Ruthenium(II)/(III) complexes of 4-hydroxy-pyridine-2,6-dicarboxylic acid with PPh3/AsPh3 as co-ligand: Impact of oxidation state and co-ligands on anticancer activity in vitro. Dalton Trans. 2012, 41 (7) , 2066-2077.
    52. Jacky Pouessel, Carla Bazzicalupi, Andrea Bencini, Hélène Bernard, Claudia Giorgi, Henri Handel, Irene Matera, Nathalie Le Bris, Raphaël Tripier, Barbara Valtancoli. Exploring New Molecular Architectures for Anion Recognition: Synthesis and ATP Binding Properties of New Cyclam‐Based Ditopic Polyammonium Receptors.. Chemistry – An Asian Journal 2011, 6 (6) , 1582-1594.
    53. Violeta I. Pérez‐Nueno, David W. Ritchie. Applying in silico tools to the discovery of novel CXCR4 inhibitors. Drug Development Research 2011, 72 (1) , 95-111.
    54. Nicola J. Farrer, Peter J. Sadler. Medicinal Inorganic Chemistry: State of the Art, New Trends, and a Vision of the Future. 2011, 1-47.
    55. Marco A. C. Neves, Sérgio Simões, M. Luisa Sá e Melo. Ligand-guided optimization of CXCR4 homology models for virtual screening using a multiple chemotype approach. Journal of Computer-Aided Molecular Design 2010, 24 (12) , 1023-1033.
    56. Zohreh Derikvand, Gholam Reza Talei, Hossein Aghabozorg, Marilyn M. Olmstead, Azadeh Azadbakht, Andya Nemati, Jafar Attar Gharamaleki. Synthesis, Crystal Structure, Spectroscopic, Electrochemical and Antimicrobial Properties of Cu(II) Complex with the Mixed Ligands of 2,9‐Dimethyl‐1,10‐phenanthroline and 4‐Hydroxypyridine‐2,6‐dicarboxylic Acid. Chinese Journal of Chemistry 2010, 28 (11) , 2167-2173.
    57. Jonathan Toma, Jeannette M Whitcomb, Christos J Petropoulos, Wei Huang. Dual-tropic HIV type 1 isolates vary dramatically in their utilization of CCR5 and CXCR4 coreceptors. AIDS 2010, 24 (14) , 2181-2186.
    58. Erik De Clercq, Piet Herdewijn. Strategies in the Design of Antiviral Drugs. 2010, 1-56.
    59. Orit Jacobson, Ido D. Weiss, Lawrence Szajek, Joshua M. Farber, Dale O. Kiesewetter. 64Cu-AMD3100—A novel imaging agent for targeting chemokine receptor CXCR4. Bioorganic & Medicinal Chemistry 2009, 17 (4) , 1486-1493.
    60. Jian-Ping Zou, Guo-Wei Zhou, Xing Zhang, Ming-Sheng Wang, Ying-Bing Lu, Wei-Wei Zhou, Zhang-Jing Zhang, Guo-Cong Guo, Jin-Shun Huang. A novel heterometal–organic coordination polymer with chelidamic acid: nonlinear optical and magnetic properties,. CrystEngComm 2009, 11 (6) , 972.
    61. Cara A Mosley, Lawrence J Wilson, John M Wiseman, Jason W Skudlarek, Dennis C Liotta. Recent patents regarding the discovery of small molecule CXCR 4 antagonists. Expert Opinion on Therapeutic Patents 2009, 19 (1) , 23-38.
    62. Signe Fransen, Gary Bridger, Jeannette M. Whitcomb, Jonathan Toma, Eric Stawiski, Neil Parkin, Christos J. Petropoulos, Wei Huang. Suppression of Dualtropic Human Immunodeficiency Virus Type 1 by the CXCR4 Antagonist AMD3100 Is Associated with Efficiency of CXCR4 Use and Baseline Virus Composition. Antimicrobial Agents and Chemotherapy 2008, 52 (7) , 2608-2615.
    63. Sean P. Troth, Alan D. Dean, Edward A. Hoover. In vivo CXCR4 expression, lymphoid cell phenotype, and feline immunodeficiency virus infection. Veterinary Immunology and Immunopathology 2008, 123 (1-2) , 97-105.
    64. P. Hermann, J. Kotek. Ten-membered Rings or Larger with One or More Nitrogen Atoms. 2008, 613-666.
    65. Mette M. Rosenkilde, Lars-Ole Gerlach, Sigrid Hatse, Renato T. Skerlj, Dominique Schols, Gary J. Bridger, Thue W. Schwartz. Molecular Mechanism of Action of Monocyclam Versus Bicyclam Non-peptide Antagonists in the CXCR4 Chemokine Receptor. Journal of Biological Chemistry 2007, 282 (37) , 27354-27365.
    66. Lihua Yang, Erin Jackson, B. Mark Woerner, Arie Perry, David Piwnica-Worms, Joshua B. Rubin. Blocking CXCR4-Mediated Cyclic AMP Suppression Inhibits Brain Tumor Growth In vivo. Cancer Research 2007, 67 (2) , 651-658.
    67. Dominique Schols. HIV co-receptor inhibitors as novel class of anti-HIV drugs. Antiviral Research 2006, 71 (2-3) , 216-226.
    68. Dominique Schols. HIV coreceptor CXCR4 antagonists. Current Opinion in HIV and AIDS 2006, 1 (5) , 361-366.
    69. Guo-Wei Zhou, You-Zhao Lan, Fa-Kun Zheng, Xin Zhang, Meng-Hai Lin, Guo-Cong Guo, Jin-Shun Huang. [Zn(C7H3O5N)]n·nH2O: A third-order NLO Zn coordination polymer with spiroconjugated structure. Chemical Physics Letters 2006, 426 (4-6) , 341-344.
    70. Sigrid Hatse, Katrien Princen, Erik De Clercq, Mette M. Rosenkilde, Thue W. Schwartz, Pedro E. Hernandez-Abad, Renato T. Skerlj, Gary J. Bridger, Dominique Schols. AMD3465, a monomacrocyclic CXCR4 antagonist and potent HIV entry inhibitor. Biochemical Pharmacology 2005, 70 (5) , 752-761.
    71. Martalena Rami, Ying Dong, Leonard F. Lindoy, Suzanne V. Smith, J.Gerald Wilson. Synthesis of one-, two- and three-ring macrocyclic, bifunctional compounds for use in radiolabelling monoclonal antibodies. Journal of Heterocyclic Chemistry 2005, 42 (1) , 77-83.
    72. L.I. Belen'kii. Alkylnitrogen Compounds: Compounds with NN, NP, NAs, NSb, NBi, NSi, NGe, NB, and NMetal Functional Groups. 2005, 343-381.
    73. Katrien Princen, Sigrid Hatse, Kurt Vermeire, Stefano Aquaro, Erik De Clercq, Lars-Ole Gerlach, Mette Rosenkilde, Thue W. Schwartz, Renato Skerlj, Gary Bridger, Dominique Schols. Inhibition of Human Immunodeficiency Virus Replication by a Dual CCR5/CXCR4 Antagonist. Journal of Virology 2004, 78 (23) , 12996-13006.
    74. Qian Zhao, Yuxian He, Gabriel Alespeiti, Asim Kumar Debnath. A novel assay to identify entry inhibitors that block binding of HIV-1 gp120 to CCR5. Virology 2004, 326 (2) , 299-309.
    75. . 3-D Hydrogen-Bonded Frameworks of Two Metal Complexes with Chelidamic Acid: Syntheses, Structures and Magnetism. Bulletin of the Korean Chemical Society 2004, 676-680.
    76. David J. Grainger, Jill Reckless. Broad-spectrum chemokine inhibitors (BSCIs) and their anti-inflammatory effects in vivo. Biochemical Pharmacology 2003, 65 (7) , 1027-1034.
    77. Jian Gao, Joseph H Reibenspies, Arthur E Martell. Synthesis and DNA binding properties of a cationic 2,2′:6′,2″-terpyridine cobalt(II) complex containing an oligopeptide. Journal of Inorganic Biochemistry 2003, 94 (3) , 272-278.
    78. Maria Elena Fuentes, Tara Mirzadegan, Robert S. Wilhelm. Chemokine and Cytokine Modulators. 2003, 119-192.
    79. Jean-Marie Contreras, Jean-Jacques Bourguignon. IDENTICAL AND NON-IDENTICAL TWIN DRUGS. 2003, 251-273.
    80. Erik De Clercq. New Anti-HIV Agents in Preclinical or Clinical Development. 2003, 1-62.
    81. Erik De Clercq. New anti‐HIV agents and targets. Medicinal Research Reviews 2002, 22 (6) , 531-565.
    82. Sherry M. Owen, Donna Rudolph, Dominique Schols, Nobutaka Fujii, Naoki Yamamoto, Renu B. Lal. Susceptibility of diverse primary HIV isolates with varying co‐receptor specificity's to CXCR4 antagonistic compounds. Journal of Medical Virology 2002, 68 (2) , 147-155.
    83. Renato T. Skerlj, Siqiao Nan, Yuanxi Zhou, Gary J. Bridger. Facile synthesis of a selectively protected triazamacrocycle. Tetrahedron Letters 2002, 43 (42) , 7569-7571.
    84. Livia Pedroza-Martins, W. John Boscardin, Deborah J. Anisman-Posner, Dominique Schols, Yvonne J. Bryson, Christel H. Uittenbogaart. Impact of Cytokines on Replication in the Thymus of Primary Human Immunodeficiency Virus Type 1 Isolates from Infants. Journal of Virology 2002, 76 (14) , 6929-6943.
    85. Venu Gangur, Neil P. Birmingham, Sirinart Thanesvorakul. Chemokines in health and disease. Veterinary Immunology and Immunopathology 2002, 86 (3-4) , 127-136.
    86. Erik De Clercq. New developments in anti-HIV chemotherapy. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 2002, 1587 (2-3) , 258-275.
    87. Matthias K. Schwarz, Timothy N. C. Wells. New therapeutics that modulate chemokine networks. Nature Reviews Drug Discovery 2002, 1 (5) , 347-358.
    88. Shin Aoki, Eiichi Kimura. Recent progress in artificial receptors for phosphate anions in aqueous solution. Reviews in Molecular Biotechnology 2002, 90 (2) , 129-155.
    89. Jill Reckless, Lauren M. Tatalick, David J. Grainger. The pan‐chemokine inhibitor NR58‐3.14.3 abolishes tumour necrosis factor‐α accumulation and leucocyte recruitment induced by lipopolysaccharide in vivo. Immunology 2001, 103 (2) , 244-254.
    90. Lokesh Agrawal, Ghalib Alkhatib. Chemokine receptors: emerging opportunities for new anti-HIV therapies. Expert Opinion on Therapeutic Targets 2001, 5 (3) , 303-326.
    91. Erik De Clercq. New developments in anti-HIV chemotherapy. Il Farmaco 2001, 56 (1-2) , 3-12.
    92. David H. McDermott, Philip M. Murphy. Chemokines and their receptors in infectious disease. Springer Seminars in Immunopathology 2000, 22 (4) , 393-415.
    93. Jim A Turpin, OM Zack Howard. Inhibitors of HIV cellular fusion. Expert Opinion on Therapeutic Patents 2000, 10 (12) , 1899-1909.

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