Thiazolothiazepine inhibitors of HIV-1 integrase

Journal of Medicinal Chemistry

Volumn 42, Issue 17, 1999, Pages 3334-3341

  Neamati, Nouri ^a,e   Turpin, Jim A ^b   Winslow, Heather E ^a   Christensen, John L ^a   Williamson, Karen ^b   Orr, Ann ^a   Rice, William G ^c   Pommier, Yves ^a,e   Garofalo, Antonio ^d   Brizzi, Antonella ^d   Campiani, Giuseppe ^d   Fiorini, Isabella ^d   Nacci, Vito ^d  

^a NATIONAL CANCER INSTITUTE   (United States)

^b SOUTHERN RESEARCH INSTITUTE   (United States)

^c Achillion Pharmaceuticals   (United States)

^d UNIVERSITY OF SIENA   (Italy)

^e NCI   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1,13A DIHYDRO 3H,5H,13H NAPHTHO[2,3 F]THIAZOLO[4,3 C][1,4]THIAZEPINE 5,13 DIONE; 2,3 DIHYDRO 5H NAPHTHO[2,3 F]THIAZOLO[2,3 C][1,4]THIAZEPINE 5,13(13AH) DIONE; INTEGRASE INHIBITOR; LEAD; MAGNESIUM ION; MANGANESE; NAPHTHALENE; SULFUR; THIAZEPINE DERIVATIVE; THIAZOLE; UNCLASSIFIED DRUG;

ANTIVIRAL ACTIVITY; ARTICLE; CHEMICAL MODIFICATION; CHEMICAL REACTION; DRUG POTENCY; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME ACTIVE SITE; ENZYME INHIBITION; HUMAN IMMUNODEFICIENCY VIRUS 1; NONHUMAN; STRUCTURE ACTIVITY RELATION; VIRUS REPLICATION;

CELL ADHESION; CELL LINE; HIV INTEGRASE INHIBITORS; HIV PROTEASE INHIBITORS; HIV-1; MAGNESIUM; MANGANESE; NUCLEOCAPSID PROTEINS; REVERSE TRANSCRIPTASE INHIBITORS; STRUCTURE-ACTIVITY RELATIONSHIP; THIAZEPINES; THIAZOLES; THIAZOLIDINEDIONES; VIRUS REPLICATION; ZINC FINGERS;

EID: 13044260233     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm990047z     Document Type: Article

References (42)

1. Brown, P. O. Integration. In Retroviruses; Coffin, J. M., Hughes, S. H., Varmus, H. E., Eds.; Cold Spring Harbor Press: Cold Spring Harbor, NY, 1998; pp 161-203.
2. Mazumder, A.; Neamati, N.; Sunder, S.; Owen, J.; Pommier, Y. Retroviral Integrase: A Novel Target in Antiviral Development; Basic In Vitro Assays with the Purified Enzyme; The Humana Press: Totowa, NJ, 1999; pp 327-335.
3. Chow, S. A. In vitro assays for activities of retroviral integrase. Methods 1997, 12, 306-17.
4. Chow, S. A.; Vincent, K. A.; Ellison, V.; Brown, P. O. Reversal of integration and DNA splicing mediated by integrase of human immunodeficiency virus. Science 1992, 255, 723-6.
5. Pommier, Y.; Pilon, A.; Bajaj, K.; Mazumder, A.; Neamati, N. HIV-1 integrase as a target for antiviral drugs. Antiviral Chem. Chemother. 1997, 8, 483-503.
6. Neamati, N.; Sunder, S.; Pommier, Y. Design and discovery of HIV-1 integrase inhibitors. Drug Discovery Today 1997, 2, 487-98.
7. Stanwell, C.; Ye, B.; Yuspa, S. H.; Burke, T. R., Jr. Cell protein cross-linking by erbstatin and related compounds. Biochem. Pharmacol. 1996, 52, 475-80.
8. Neamati, N.; Hong, H.; Owen, J. M.; Sunder, S.; Winslow, H. E.; Christensen, J. L.; Zhao, H.; Burke, J. T. R.; Milne, G. W. A.; Pommier, Y. Salicylhydrazine-containing inhibitors of HIV-1 integrase: implication for a selective chelation in the integrase active site. J. Med. Chem. 1998, 41, 3202-9.
9. Neamati, N.; Hong, H.; Mazumder, A.; Wang, S.; Sunder, S.; Nicklaus, M. C.; Milne, G. W.; Proksa, B.; Pommier, Y. Depsides and depsidones as inhibitors of HIV-1 integrase: discovery of novel inhibitors through 3D database searching. J. Med. Chem. 1997, 40, 942-51.
10. Nicklaus, M. C.; Neamati, N.; Hong, H.; Mazumder, A.; Sunder, S.; Chen, J.; Milne, G. W.; Pommier, Y. HIV-1 integrase pharmacophore: discovery of inhibitors through three-dimensional database searching. J. Med. Chem. 1997, 40, 920-9.
11. Lubkowski, J.; Yang, F.; Alexandratos, J.; Wlodawer, A.; Zhao, H.; Burke, T. R., Jr.; Neamati, N.; Pommier, Y.; Merkel, G.; Skalka, A. M. Structure of the catalytic domain of avian sarcoma virus integrase with a bound HIV-1 integrase-targeted inhibitor. Proc. Natl. Acad. Sci. U.S.A. 1998, 95, 4831-6.
12. Neamati, N.; Mazumder, A.; Zhao, H.; Sunder, S.; Burke, T. R., Jr.; Schultz, R. J.; Pommier, Y. Diaryl sulfones, a novel class of human immunodeficiency virus type 1 integrase inhibitors. Antimicrob. Agents Chemother. 1997, 41, 385-93.
13. Neamati, N.; Mazumder, A.; Sunder, S.; Owen, J. M.; Schultz, R. J.; Pommier, Y. 2-Mercaptobenzenesulfonamides as novel class of human immunodeficiency type 1 (HIV-1) integrase and HIV-1 replication. Antiviral Chem. Chemother. 1997, 8, 485-95.
14. Pommier, Y.; Neamati, N. Inhibitors of human immunodeficiency virus integrase. Adv. Virus Res. 1999, 52, 427-458.
15. Garofalo, A.; Balconi, G.; Botta, M.; Corelli, F.; D'Incalci, M.; Fabrizi, G.; Fiorini, I.; Lamba, D.; Nacci, V. Thioanalogues of antitumor antibiotics. II. Synthesis and preliminary in vitro cytotoxicity evaluation of tricyclic [1,4]benzothiazepine derivatives. Eur. J. Med. Chem. 1993, 29, 213-20.
16. Nacci, V.; Garofalo, A.; Anzini, M. Thioanalogues of antitumor antibiotics. I. Synthesis of 7,8-disubstituted 5,11-dioxo-1,2,3,-11a-tetrahydro-5H,11H- and 5-oxo-2,3,11,11a-tetrahydro-1H,5H-pyrrolo[2,1-c][1,4]benzothiazepine. Farmaco 1989, 44, 423-33.
17. Nacci, V.; Garofalo, A.; Fiorini, I. Polycondensed heterocycles. II. A new preparative route to 11-oxo-5H,11H-pyrrolo[2,1-c][1,4]-benzothiazepine. J. Heterocycl. Chem. 1986, 23, 769-73.
18. Garofalo, A.; Nacci, V.; Corelli, F.; Campiani, G. Polycondensed heterocycles. V. Synthesis of 5H,11H-pyrrolo[2,1-c][1,4]benzothiazepine. Heterocycles 1990, 31, 1291-1300.
19. Garofalo, A.; Campiani, G.; Ciani, S. M.; Fiorini, I.; Nacci, V. Polycondensed heterocycles. IX. Pyrrolo[2,1-c][1,4]benzothiazepines. Synthesis of 3-(dimethylamino)methyl derivatives. Tetrahedron 1996, 52, 7745-54.
20. Garofalo, A.; Campiani, G.; Nacci, V.; Fiorini, I. Polycondensed heterocycles. VIII. Synthesis of 11-aryl-5H,11H-pyrrolo[2,1-c]-[1,4]benzothiazepines by Pummerer rearrangement-cyclization reaction. Heterocycles 1992, 34, 51-60.
21. Archer, S.; Miller, J. K.; Rej, R.; Periana, C.; Fricker, L. Ring-hydroxylated analogues of lucantone as antitumor agents. J. Med. Chem. 1982, 25, 220-7.
22. Katz, L.; Karger, L. S.; Schroeder, W.; Cohen, M. S. Hydrazine derivatives. I. Benzalthio- and bisbenzaldithio-salicylhydrazides. J. Org. Chem. 1953, 18, 1380-1402.
23. Pendergast, W.; Dickerson, S. H.; Dev, I. K.; Ferone, R.; Duch, D. S.; Smith, G. K. Benzo[f]quinazoline inhibitors of thymidylate synthase: methyleneamino-linked aroylglutamate derivatives. J. Med. Chem. 1994, 37, 838-44.
24. Guise, G. B.; Ollis, W. D.; Peacock, J. E.; Stephanatou, J. S.; Stoddart, J. F. Dithiosalicylides and trithiosalicylides. Their conformational behavior in solution. Tetrahedron Lett. 1980, 21, 4203-6.
25. Vitali, T.; Mossini, F.; Plazzi, P. V. Sintesi ed attivita' antifungine di bis-(3-carbossiamido-2-naftil)disolfuri e di nafto[3,2-d]isotiazolin-3-oni. Farmaco Ed. Sci. 1974, 29, 27-36.
26. Lalezari, I.; Schwartz, E. L. Synthesis and antineoplastic activity of 5-Aryl-2,3-dihydropyrrolo[2,1-b]thiazole-6,7-dimethanol 6,7-bis(isopropylcarbamates). J. Med. Chem. 1988, 31, 1427-9.
27. Falorni, M.; Conti, S.; Giacomelli, G.; Cossu, S.; Optically active 4-oxaproline derivatives: new useful chiral synthons derived from serine and threonine. Tetrahedron: Asymmetry 1995, 6, 287-94.
28. Goldgur, Y.; Dyda, F.; Hickman, A. B.; Jenkins, T. M.; Craigie, R.; Davies, D. R. Three new structures of the core domain of HIV-1 integrase: An active site that binds magnesium. Proc. Natl. Acad. Sci. U.S.A. 1998, 95, 9150-4.
29. Bujacz, G.; Alexandratos, J.; Wlodawer, A.; Merkel, G.; Andrake, M.; Katz, R. A.; Skalka, A. M. Binding of different divalent cations to the active site of avian sarcoma virus integrase and their effects on enzymatic activity. J. Biol. Chem. 1997, 272, 18161-8.
30. Bujacz, G.; Jaskolski, M.; Alexandratos, J.; Wlodawer, A.; Merkel, G.; Katz, R. A.; Skalka, A. M. The catalytic domain of avian sarcoma virus integrase: conformation of the active-site residues in the presence of divalent cations. Structure 1996, 4, 89-96.
31. Fesen, M. R.; Pommier, Y.; Leteurtre, F.; Hiroguchi, S.; Yung, J.; Kohn, K. W. Inhibition of HIV-1 integrase by flavones, caffeic acid phenethyl ester (CAPE) and related compounds. Biochem. Pharmacol. 1994, 48, 595-608.
32. Hazuda, D. J.; Felock, P. J.; Hastings, J. C.; Pramanik, B.; Wolfe, A. L. Differential divalent cation requirements uncouple the assembly and catalytic reactions of human immunodeficiency virus type 1 integrase. J. Virol. 1997, 71, 7005-11.
33. Farnet, C. M.; Wang, B.; Lipford, J. R.; Bushman, F. D. Differential inhibition of HIV-1 preintegration complexes and purified integrase protein by small molecules. Proc. Natl. Acad. Sci. U.S.A. 1996, 93, 9742-7.
34. Clanton, D. J.; Buckheit, R. W., Jr.; Terpening, S. J.; Kiser, R.; Mongelli, N.; Borgia, A. L.; Schultz, R.; Narayanan, V.; Bader, J. P.; Rice, W. G. Novel sulfonated and phosphonated analogues of distamycin which inhibit the replication of HIV. Antiviral Res. 1985, 27, 335-54.
35. Bader, J. P.; McMahon, J. B.; Schultz, R. J.; Narayanan, V. L.; Pierce, J. B.; Harrison, W. A.; Weislow, O. S.; Midelfort, C. F.; Stinson, S. F.; Boyd, M. R. Oxathiin carboxanilide, a potent inhibitor of human immunodeficiency virus reproduction. Proc. Natl. Acad. Sci. U.S.A. 1991, 88, 6740-4.
36. Kageyama, S.; Mimoto, T.; Murakawa, Y.; Nomizu, M.; Ford, H., Jr.; Shirasaka, T.; Gulnik, S.; Erickson, J.; Takada, K.; Hayashi, H.; et al. In vitro anti-human immunodeficiency virus (HIV) activities of transition state mimetic HIV protease inhibitors containing allophenylnorstatine. Antimicrob. Agents Chemother. 1993, 37, 810-7.
37. Buckheit, R. W., Jr.; Roberson, J. L.; Lackman-Smith, C.; Wyatt, J. R.; Vickers, T. A.; Ecker, D. J. Potent and specific inhibition of HIV envelope-mediated cell fusion and virus binding by G quartet-forming oligonucleotide (ISIS 5320). AIDS Res. Hum. Retroviruses 1994, 10, 1497-506.
38. Rice, W. G.; Supko, J. G.; Malspeis, L.; Buckheit, R. W., Jr.; Clanton, D.; Bu, M.; Graham, L.; Schaeffer, C. A.; Turpin, J. A.; Domagala, J.; et al. Inhibitors of HIV nucleocapsid protein zinc fingers as candidates for the treatment of AIDS. Science 1995, 270, 1194-7.
39. Engelman, A.; Craigie, R. Efficient magnesium-dependent human immunodeficiency virus type 1 integrase activity. J. Virol. 1995, 69, 5908-11.
40. Turpin, J. A.; Terpening, S. J.; Schaeffer, C. A.; Yu, G.; Glover, C. J.; Felsted, R. L.; Sausville, E. A.; Rice, W. G. Inhibitors of human immunodeficiency virus type 1 zinc fingers prevent normal processing of gag precursors and result in the release of noninfectious virus particles. J. Virol. 1996, 70, 6180-9.
41. Rice, W. G.; Baker, D. C.; Schaeffer, C. A.; Graham, L.; Bu, M.; Terpening, S.; Clanton, D.; Schultz, R.; Bader, J. P.; Buckheit, R. W., Jr.; Field, L.; Singh, P. K.; Turpin, J. A. Inhibition of multiple phases of human immunodeficiency virus type 1 replication by a dithiane compound that attacks the conserved zinc fingers of retroviral nucleocapsid proteins. Antimicrob. Agents Chemother. 1997, 41, 419-26.
42. Weislow, O. W.; Kiser, R.; Fine, D.; Bader, J.; Shoemaker, R. H.; Boyd, M. R. New soluble-formazan assay for HIV-1 cytopathic effects: application to high-flux screening of synthetic and natural products for AIDS antiviral activity. J. Natl. Cancer Inst. 1989, 81, 577-86.