Synthesis and anti-HIV activity of new metabolically stable alkenyldiarylmethane non-nucleoside reverse transcriptase inhibitors incorporating N-methoxy imidoyl halide and 1,2,4-oxadiazole systems

Journal of Medicinal Chemistry

Volumn 50, Issue 14, 2007, Pages 3314-3321

  Sakamoto, Takeshi ^a   Cullen, Matthew D ^a   Hartman, Tracy L ^b   Watson, Karen M ^b   Buckheit, Robert W ^b   Pannecouque, Christophe ^c   De Clercq, Erik ^c   Cushman, Mark ^a  

^a PURDUE UNIVERSITY   (United States)

^b ImQuest Biosciences   (United States)

^c REGA INSTITUTE FOR MEDICAL RESEARCH   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

1,2,4 OXADIAZOLE DERIVATIVE; [1 (3,7 DIMETHYL 2 OXO 2,3 DIHYDROBENZ[D]OXAZOL 5 YL) 5 (3 METHYL 1,2,4 OXADIAZOL 5 YL)PENT 1 ENYL] N,2 DIMETHOXY 3 METHYLBENZIMIDOYL FLUORIDE; ALKENYLDIARYLMETHANE; ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; FLUORIDE; HALIDE; RNA DIRECTED DNA POLYMERASE; RNA DIRECTED DNA POLYMERASE INHIBITOR; UNCLASSIFIED DRUG;

ANTIVIRAL ACTIVITY; ARTICLE; CARBON NUCLEAR MAGNETIC RESONANCE; CYTOPATHOGENIC EFFECT; DRUG CYTOTOXICITY; DRUG HALF LIFE; DRUG STABILITY; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME INHIBITION; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; IN VITRO STUDY; NONHUMAN; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PLASMA; PROTON NUCLEAR MAGNETIC RESONANCE; RAT;

ALLOSTERIC REGULATION; ANTI-HIV AGENTS; CELL LINE; ELECTROSTATICS; HALOGENS; HUMANS; IMIDES; MAGNETIC RESONANCE SPECTROSCOPY; OXADIAZOLES; REVERSE TRANSCRIPTASE INHIBITORS; SPECTROMETRY, MASS, ELECTROSPRAY IONIZATION;

EID: 34447514125     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm070236e     Document Type: Article

References (33)

1. UNAIDS/World Health Organization 2006 AIDS Epidemic Update, December 2006, UNAIDS/World Health Organization: Geneva, 2006.
2. De Clercq, E. Highlights in the Development of New Antiviral Agents. Mini-Rev. Med. Chem. 2002, 2, 163-175.
3. Cushman, M.; Golebiewski, M.; Buckheit, R. W., Jr.; Graham, L.; Rice, W. G. Synthesis and Biological Evaluation of an Alkenyl-diarylmethane (ADAM) Which Acts as a Novel Non-nucleoside HIV-1 Reverse Transcriptase Inhibitor. Bioorg. Med. Chem. Lett. 1995, 5, 2713-2716.
4. Cushman, M.; Golebiewski, W. M.; Graham, L.; Turpin, J. A.; Rice, W. G.; Fliakas-Boltz, V.; Buckheit, R. W., Jr. Synthesis and Biological Evaluation of Certain Alkenyldiarylmethanes as Anti-HIV-1 Agents Which Act as Non-Nucleoside Reverse Transcriptase Inhibitors. J. Med. Chem. 1996, 39, 3217-3227.
5. Cushman, M.; Casimiro Garcia, A.; Hejchman, E.; Ruell, J. A.; Huang, M.; Schaeffer, C. A.; Williamson, K.; Rice, W. G.; Buckheit, R. W., Jr. New Alkenyldiarylmethanes with Enhanced Potencies as Anti-HIV Agents Which Act as Non-Nucleoside Reverse Transcriptase Inhibitors. J. Med. Chem. 1998, 41, 2076-2089.
6. Cushman, M.; Casimiro Garcia, A.; Williamson, K.; Rice, W. G. Synthesis of a Non-Nucleoside Reverse Transcriptase Inhibitor in the Alkenyldiarylmethane (ADAM) Series with Optimized Potency and Therapeutic Index. Bioorg. Med. Chem. Lett. 1998, 8, 195-198.
7. Casimiro Garcia, A.; Micklatcher, M.; Turpin, J. A.; Stup, T. L.; Watson, K.; Buckheit, R. W.; Cushman, M. Novel Modifications in the Alkenyldiarylmethane (ADAM) Series of Non-Nucleoside Reverse Transcriptase Inhibitors. J. Med. Chem. 1999, 42, 4861-4874.
8. Xu, G.; Micklatcher, M.; Silvestri, M.; Hartman, T. L.; Burrier, J.; Osterling, M. C.; Wargo, H.; Turpin, J. A.; Buckheit, R. W., Jr.; Cushman, M. The Biological Effects of Structural Variation at the Meta Position of the Aromatic Rings and at the End of the Alkenyl Chain in the Alkenyldiarylmethane Series of Non-Nucleoside Reverse Transcriptase Inhibitors. J. Med. Chem. 2001, 44, 4092-4113.
9. Xu, G.; Loftus, T. L.; Wargo, H.; Turpin, J. A.; Buckheit, R. W., Jr.; Cushman, M. Solid-Phase Synthesis of Non-Nucleoside Reverse Transcriptase Inhibitors. J. Org. Chem. 2001, 66, 5958-5964.
10. Xu, G.; Hartman, T. L.; Wargo, H.; Turpin, J. A.; Buckheit, R. W., Jr.; Cushman, M. Synthesis of Alkenyldiarylmethane (ADAM) Non-Nucleoside Reverse Transcriptase Inhibitors with Non-Identical Aromatic Rings. Bioorg. Med. Chem. Lett. 2002, 10, 283-290.
11. Silvestri, M. A.; Nagarajan, M.; De Clercq, E.; Pannecouque, C.; Cushman, M. Design, Synthesis, Anti-HIV Activities, and Metabolic Stabilities of Alkenyldiarylmethane (ADAM) Non-nucleoside Reverse Transcriptase Inhibitors. J. Med. Chem. 2004, 47, 3149-3162.
12. Deng, B.-L.; Hartman, T. L.; Buckheit, R. W., Jr.; Pannecouque, C.; De Clercq, E.; Fanwick, P. E.; Cushman, M. Synthesis, Anti-HIV Activity, and Metabolic Stability of New Alkenyldiarylmethane HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors. J. Med. Chem. 2005, 48, 6140-6155.
13. Deng, B.-L.; Cullen, M. D.; Zhou, Z.; Hartman, T. L.; Buckheit, R. W., Jr.; Pannecouque, C.; De Clercq, E.; Fanwick, P. E.; Cushman, M. Synthesis and Anti-HIV Activity of New Alkenyldiarylmethane (ADAM) Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) Incorporating Benzoxazolone and Benzisoxazole Rings. Bioorg. Med. Chem. 2006, 14, 2366-2374.
14. Deng, B.-L.; Hartman, T. L.; Buckheit, R. W., Jr.; Pannecouque, C.; De Clercq, E.; Fanwick, P. E.; Cushman, M. Replacement of the Metabolically Labile Methyl Esters in the Alkenyldiarylmethane Series of Non-Nucleoside Reverse Transcriptase Inhibitors with Isoxazolone, Isoxazole, Oxazolone, or Cyano Substituents. J. Med. Chem. 2006, 49, 5319-5323.
15. Orlek, B. S.; Blaney, F. E.; Brown, F.; Clark, M. S. G.; Hadley, M. S.; Hatcher, J.; Riley, G. J.; Rosenberg, H. E.; Wadsworth, H. J.; Wyman, P. Comparison of Azabicyclic Esters and Oxadiazoles as Ligands for the Muscarinic Receptor. J. Med. Chem. 1991, 34, 2726-2735.
16. Wadsworth, H. J.; Jenkins, S. M.; Orlek, B. S.; Cassidy, F.; Clark, M. S. G.; Brown, F.; Riley, G. J.; Graves, D.; Hawkins, J.; Naylor, C. B. Synthesis and Muscarinic Activities of Quinuclidin-3-yltriazole and -tetrazole Dervatives. J. Med. Chem. 1992, 35, 1280-1290.
17. Bromidge, S. M.; Brown, F.; Cassidy, F.; Clark, M. S. G.; Dabbs, S.; Hadley, M. S.; Hawkins, J.; Loudon, J. M.; Naylor, C. B.; Orlek, B. S.; Riley, G. J. Design of [R-(Z)]-(+)-α-(Methoxyimino)-1-azabicyclo[2.2.2] octane-3-acetonitrile (SB 202026), a Functionally Selective Azabicyclic Muscarinic M1 Agonist Incorporating the N-Methoxy Imidoyl Nitrile Group as a Novel Ester Bioisostere. J. Med. Chem. 1997, 40, 4265-4280.
18. Singh, R. P.; Shreeve, J. M. Recent Advances in Nucleophilic Fluorination Reaction of Organic Compounds Using Deoxofluor and DAST. Synthesis 2002, 2561-2578.
19. Lai, G. S.; Pez, G. P.; Peasaresim, R, J.; Prozonic, F. M.; Cheng, H. Bis(2-methoxyethyl)aminosulfur Trifluoride: A New Broad-Spectrum Deoxofluorinating Agent with Enhanced Thermal Stability. J. Org. Chem. 1999, 64, 7048-7054.
20. (a) Clark, J. H.; Hyde, A. J.; Smith, D. K. Calcium Fluoride-Supported Alkali Metal Fluorides. New Reagents for Nucleophilic Fluorine Transfer Reactions. J. Chem. Soc., Chem. Commun. 1986, 791-793.
21. (b) Ichihara, J.; Matsuo, T.; Hanafusa, T.; Ando, T. The Combination of Potassium Fluoride and Calcium Fluoride: A Useful Heterogeneous Fluorinating Reagent. J. Chem. Soc., Chem. Commun. 1986, 793-794.
22. Chang, S.; Lee, M.; Kim, S. N-Alkoxyimidoyl Bromides as a New and Efficient Coupling Partner in Pd-Catalyzed Stille Reaction. Synlett 2001, 1557-1558.
23. 2 (vane's PGX). Tetrahedron Lett. 1997, 40, 3529-3532.
24. Mee, S. P. H.; Lee, V.; Baldwin, J. E. Stille Coupling Made Easier - Synergic Effect of Copper(I) Salts and the Fluoride Ion. Angew. Chem., Int. Ed. 2004, 43, 1132-1136.
25. Trost, B. M.; Dong, G. New Class of Nucleophiles for Palladium-Catalyzed Asymmetric Allylic Alkylation. Total Synthesis of Agelastatin A. J. Am. Chem. Soc. 2006, 128, 6054-6055.
26. Trzexciak, A.; Bannworth, W. Selective Cleavage of tert-Butyl Esters in the Presence of tert-Butyl Ethers. Application to the Synthesis of tert-Butoxy Amino Acids. Synthesis 1996, 1433-1434.
27. Poulain, R. F.; Tartar, A. L.; Deprez, B. P. Parallel Synthesis of 1,2,4-Oxadiazoles from Carboxylic Acids Using an Improved, Uronium-Based, Activation. Tetrahedron Lett. 2001, 42, 1495-1498.
28. Johnson, J. E.; Nalley, E. A.; Kunz, Y. K.; Springfield, J. R. The Geometric Isomers of O-Alkylbenzohydroximoyl Chlorides. Synthesis, Identification, and Acid-Catalyzed Isomerization. J. Org. Chem. 1976, 41, 252-259.
29. Johnson, J. E.; Cornell, S. C. Mechanism and Solvolysis Reactions of O-Methylbenzohydroximoyl Halides. Stereoelectronic Control in Formation of and Nucleophilic Addition to Nitrilum Ions. J. Org. Chem. 1980, 45, 4144-4148.
30. Takeda, K.; Akiyama, A.; Nakamura, H.; Takizawa, S.; Mizuno, Y.; Takayanagi, H.; Harigaya, Y. Dicarbonates: Convenient 4-Dimethylaminopyridine Catalyzed Esterification Reagents. Synthesis 1994, 1063-1066.
31. Buckheit, R. W. J.; Fliakas-Boltz, V.; Decker, W. D.; Robertson, J. L.; Stup, T. L.; Pyle, C. A.; White, E. L.; McMahon, J. B.; Currens, M. J.; Boyd, M. R.; Bader, J. P. Comparative Anti-HIV Evaluation of Diverse HIV-1-Specific Reverse Transcriptase Inhibitor-Resistant Virus Isolates Demonstrates the Existence of Distinct Phenotypic Subgroups. Antiviral Res. 1995, 26, 117-132.
32. Rice, W. G.; Bader, J. P. Discovery and in Vitro Development of AIDS Antiviral Drags as Biopharmaceuticals. Adv. Pharmacol. 1995, 6, 389-438.
33. Pauwels, R.; Balzarini, J.; Baba, M.; Snoeck, R.; Schols, D.; Herdewijn, P.; Desmyter, J.; De Clercq, E. Rapid and Automated Terazolium-Based Colorimetric Assay for Detection of Anti-HIV Compounds. J. Virol. Methods 1988, 20, 309-321.