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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
https://doi.org/10.1021/jm990211i
Copyright © 1999 American Chemical Society
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    Abstract

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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.

    *

     To whom correspondence should be addressed. Tel:  (604)-532-4652. Fax:  (604)-530-0976. E-mail:  [email protected].

    †

     AnorMED Inc.

    ‡

     Johnson Matthey Pharmaceutical Research.

    §

     Rega Institute for Medical Research.

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    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. https://doi.org/10.1007/s11224-012-9950-0
    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. https://doi.org/10.1016/j.jmgm.2012.06.010
    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. https://doi.org/10.1007/s00894-011-1323-x
    49. Amnon Peled, Ori Wald, Jan Burger. Development of novel CXCR4-based therapeutics. Expert Opinion on Investigational Drugs 2012, 21 (3) , 341-353. https://doi.org/10.1517/13543784.2012.656197
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    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. https://doi.org/10.1002/asia.201100046
    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. https://doi.org/10.1002/ddr.20406
    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. https://doi.org/10.1002/9783527633104.ch1
    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. https://doi.org/10.1007/s10822-010-9393-x
    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. https://doi.org/10.1002/cjoc.201090358
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    58. Erik De Clercq, Piet Herdewijn. Strategies in the Design of Antiviral Drugs. 2010, 1-56. https://doi.org/10.1002/9780470571224.pse026
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    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. https://doi.org/10.1517/13543770802553483
    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. https://doi.org/10.1128/AAC.01226-07
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    68. Dominique Schols. HIV coreceptor CXCR4 antagonists. Current Opinion in HIV and AIDS 2006, 1 (5) , 361-366. https://doi.org/10.1097/01.COH.0000239847.13205.ce
    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. https://doi.org/10.1016/j.cplett.2006.06.034
    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. https://doi.org/10.1016/j.bcp.2005.05.035
    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. https://doi.org/10.1002/jhet.5570420111
    72. L.I. Belen'kii. Alkylnitrogen Compounds: Compounds with NN, NP, NAs, NSb, NBi, NSi, NGe, NB, and NMetal Functional Groups. 2005, 343-381. https://doi.org/10.1016/B0-08-044655-8/00029-5
    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. https://doi.org/10.1128/JVI.78.23.12996-13006.2004
    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. https://doi.org/10.1016/j.virol.2004.06.022
    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. https://doi.org/10.5012/bkcs.2004.25.5.676
    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. https://doi.org/10.1016/S0006-2952(02)01626-X
    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. https://doi.org/10.1016/S0162-0134(03)00008-4
    78. Maria Elena Fuentes, Tara Mirzadegan, Robert S. Wilhelm. Chemokine and Cytokine Modulators. 2003, 119-192. https://doi.org/10.1002/0471266949.bmc062
    79. Jean-Marie Contreras, Jean-Jacques Bourguignon. IDENTICAL AND NON-IDENTICAL TWIN DRUGS. 2003, 251-273. https://doi.org/10.1016/B978-012744481-9/50020-9
    80. Erik De Clercq. New Anti-HIV Agents in Preclinical or Clinical Development. 2003, 1-62. https://doi.org/10.1016/S1075-8593(03)04001-2
    81. Erik De Clercq. New anti‐HIV agents and targets. Medicinal Research Reviews 2002, 22 (6) , 531-565. https://doi.org/10.1002/med.10021
    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. https://doi.org/10.1002/jmv.10191
    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. https://doi.org/10.1016/S0040-4039(02)01756-2
    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. https://doi.org/10.1128/JVI.76.14.6929-6943.2002
    85. Venu Gangur, Neil P. Birmingham, Sirinart Thanesvorakul. Chemokines in health and disease. Veterinary Immunology and Immunopathology 2002, 86 (3-4) , 127-136. https://doi.org/10.1016/S0165-2427(02)00018-1
    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. https://doi.org/10.1016/S0925-4439(02)00089-3
    87. Matthias K. Schwarz, Timothy N. C. Wells. New therapeutics that modulate chemokine networks. Nature Reviews Drug Discovery 2002, 1 (5) , 347-358. https://doi.org/10.1038/nrd795
    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. https://doi.org/10.1016/S1389-0352(01)00070-8
    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. https://doi.org/10.1046/j.1365-2567.2001.01228.x
    90. Lokesh Agrawal, Ghalib Alkhatib. Chemokine receptors: emerging opportunities for new anti-HIV therapies. Expert Opinion on Therapeutic Targets 2001, 5 (3) , 303-326. https://doi.org/10.1517/14728222.5.3.303
    91. Erik De Clercq. New developments in anti-HIV chemotherapy. Il Farmaco 2001, 56 (1-2) , 3-12. https://doi.org/10.1016/S0014-827X(01)01007-2
    92. David H. McDermott, Philip M. Murphy. Chemokines and their receptors in infectious disease. Springer Seminars in Immunopathology 2000, 22 (4) , 393-415. https://doi.org/10.1007/s002810000052
    93. Jim A Turpin, OM Zack Howard. Inhibitors of HIV cellular fusion. Expert Opinion on Therapeutic Patents 2000, 10 (12) , 1899-1909. https://doi.org/10.1517/13543776.10.12.1899
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