Structure-based design, synthesis, and biological evaluation of novel pyrrolyl aryl sulfones: HIV-1 non-nucleoside reverse transcriptase inhibitors active at nanomolar concentrations

Journal of Medicinal Chemistry

Volumn 43, Issue 9, 2000, Pages 1886-1891

  Artico, Marino ^a   Silvestri, Romano ^a   Pagnozzi, Eugenia ^a   Bruno, Biancamaria ^a   Novellino, Ettore ^b   Greco, Giovanni ^b   Massa, Silvio ^c   Ettorre, Alessandro ^d   Loi, Anna Giulia ^e   Scintu, Franca ^e   La Colla, Paolo ^e  

^a SAPIENZA UNIVERSITY OF ROME   (Italy)

^b UNIVERSITY OF NAPLES FEDERICO II   (Italy)

^c UNIVERSITY OF SIENA   (Italy)

^d Menarini Ricerche SpA   (Italy)

^e UNIVERSITY OF CAGLIARI   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ARYLSULFONIC ACID DERIVATIVE; ETHYL 1 [(2 AMINO 5 CHLOROPHENYL)SULFONYL] 1H PYRROLE 2 CARBOXYLATE; PYRROLE DERIVATIVE; RNA DIRECTED DNA POLYMERASE INHIBITOR; UNCLASSIFIED DRUG;

ARTICLE; CRYSTAL STRUCTURE; DRUG DESIGN; DRUG STRUCTURE; DRUG SYNTHESIS; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION;

CELL SURVIVAL; CHEMISTRY, PHYSICAL; CRYSTALLOGRAPHY, X-RAY; CYTOPATHOGENIC EFFECT, VIRAL; DRUG DESIGN; HIV-1; HIV-1 REVERSE TRANSCRIPTASE; HUMANS; MODELS, MOLECULAR; MOLECULAR CONFORMATION; PYRROLES; REVERSE TRANSCRIPTASE INHIBITORS; STRUCTURE-ACTIVITY RELATIONSHIP; TRITERPENES;

EID: 0034075488     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm9901125     Document Type: Article

References (17)

1. McMahon, J. B.; Gulakowsky, R. J.; Weislow, O. S.; Schoktz, R. J.; Narayanan, V. L.; Clanton, D. J.; Pedemonte, R.; Wassmundt, F. W.; Buckheit, R. W., Jr.; Decker, W. D.; White, E. L.; Bader, J, P.; Boyd, M. R. Diaryl sulfones, a New Chemical Class of Non-Nucleoside Antiviral Inhibitors of Human Immunodeficiency Virus Type 1 Reverse Transcriptase. Antimicrob. Agents Chemother. 1993, 37, 754-760.
2. Williams, T. M.; Ciccarone, T. M.; MacTough, S. C.; Rooney, C. S.; Balani, S. K.; Condra, J. H.; Emini, E. A.; Goldman, M. E.; Greenlee, W. J.; Kauffman, L. R.; O'Brien, J. A.; Sardana, V. V.; Schleif, W. A.; Theoharides, A. D.; Anderson, P. S. 5-Chloro-3-(phenylsulfonyl)indole-2-carboxamide: A Novel, Non-Nucleoside Inhibitor of HIV-1 Reverse Transcriptase. J. Med. Chem. 1993, 36, 1291-1294.
3. Artico, M.; Silvestri, R.; Stefancich, G.; Massa, S.; Pagnozzi, E.; Musiu, D.; Scintu, F.; Pinna, E.; Tinti, E.; La Colla, P. Synthesis of Pyrryl Aryl Sulfones Targeted at the HIV-1 Reverse Tran-scriptase. Arch. Pharm. (Weinheim) 1995, ,328, 223-229.
4. Artico, M.; Silvestri, R.; Massa, S.; Loi, A. G.; Corrias, S.; Piras, G.; La Colla, P. 2-Sulfonyl-4-chloroanilino Moiety: A Potent Pharmacophore for the Anti-Human Immunodeficiency Virus Type 1 Activity of Pyrrolyl Aryl Sulfones. J. Med. Chem. 1996, 39, 522-530.
5. Clark, M.; Cramer, R. D., III; Van Opdenbosch, N. Validation of the General Purpose Tripos 5.2 Force Field. J. Comput. Chem. 1989, 10, 982-1012.
6. SYBYL Molecular Modeling System (version 6.2); Tripos Inc., St. Louis, MO.
7. Ren, J.; Esnouf, R.; Garman, E.; Somers, D.; Ross, C.; Kirby, I.; Keeling, J.; Darby, G.; Jones, Y.; Stuart, D.; Stammers, D. High-Resolution Structures of HIV-1 RT from four RT-Inhibitor Complexes. Nat. Struct. Biol. 1995, 2, 293-302.
8. Hopkins, A. L.; Ren, J.; Esnouf, R. M.; Willcox, B. E.; Jones, E. Y.; Ross, C.; Miyasaka, T.; Walker, R. T.; Tanaka, H.; Stammers, D. K; Stuart, D. I. Complexes of HIV-1 Reverse Transcriptase with Inhibitors of the HEPT Series Reveal Conformational Changes Relevant to the Design of Potent Non-Nucleoside Inhibitors. J. Med. Chem. 1996, 39, 1589-1600.
9. Ding, J.; Das, K.; Moereels, H.; Koymans, L.; Andries, K.; Janssen, P. A. J.; Hughes, S. H., Arnold, E. Structure of HIV-1 RT/TIBO R 86183 Complex Reveals Similarity in the Binding of Diverse Nonnucleoside Inhibitors. Nat. Struct. Biol. 1995, 2, 407-415.
10. Ren, J.; Esnouf, R.; Hopkins, A.; Ross, C.; Jones, Y.; Stammers, D.; Stuart, D. The structure of HIV-1 Reverse Transcriptase Complexed with 9-Chloro-TIBO: Lessons for Inhibitor Design. Structure 1995, 3, 915-926.
11. Bernstein, F. C.; Koetzle, T. F.; Williams, G. J. B.; Meyer Jr., E. F.; Brice, M. D.; Rodgers, J. R.; Kennard, O.; Shimanouchi, T.; Tasumi, T. The Protein Data Bank: A Computer Based Archival File for Macromolecular Structures. J. Mol. Biol. 1977, 112, 535-542.
12. TEXAN-TEXRAY Single-Crystal Structure Analysis Software (version 5.0, 1989); Molecular Structure Corp., The Woodlands, TX 77381.
13. Gasteiger, J.; Marsili, M. Iterative Partial Equalization of Orbital Electronegativity. Tetrahedron 1980, 36, 3219-3228.
14. Purcel, V. P.; Singer, J. A. A Brief Review and Table of Semiepirical Parameters Used in the Hückel Molecular Orbital Method. J. Chem. Eng. Data 1967, 12, 235-246.
15. Head, J.; Zerner, M. C. A Broyden-Fletcher-Goldfarb-Shanno Optimization Procedure for Molecular Geometries. Chem. Phys. Lett. 1985, 122, 264-274.
16. Allen, F. H.; Bellard, S. Brice, M. D.; Cartwright, B. A.; Doubleday: A.; Higgs, H.; Hummelink, T.; Hummelink-Peterd, B. G.; Kennard, O.; Motherwell, W. D. S.; Rodgers, J. R.; Watson, D. G. The Cambridge Crystallographic Data Centre: Computer-Based Search, Retrival, Analysis and Display of Information. Acta Crystallogr. 1979, B35, 2331-2339.
17. Krystek, Jr., S. R.; Hunt, J. T.; Stein, P. D.; Stouch, T. R. Three-Dimensional Quantitative Structure-Activity Relationships of Sulfonamide Endothelin Inhibitors. J. Med. Chem. 1995, 38, 659-668.