Substituted tetrahydrocarbazoles with potent activity against human papillomaviruses

Bioorganic and Medicinal Chemistry Letters

Volumn 19, Issue 13, 2009, Pages 3489-3492

  Gudmundsson, Kristjan S ^a   Sebahar, Paul R ^a   Richardson, Leah D'Aurora ^a   Catalano, John G ^a   Boggs, Sharon D ^a   Spaltenstein, Andrew ^a   Sethna, Phiroze B ^a   Brown, Kevin W ^a   Harvey, Robert ^a   Romines, Karen R ^a  

^a GLAXOSMITHKLINE   (United States)

Author keywords

Antiviral; Human papillomavirus; Tetrahydrocarbazole

Indexed keywords

1,2,3,4 TETRAHYDROCARBAZOLE DERIVATIVE; 6 BROMO N (1 PHENYLETHYL) 2,3,4,9 TETRAHYDRO 1H CARBAZOL 1 AMINE; UNCLASSIFIED DRUG; VIRUS DNA;

ANTIVIRAL ACTIVITY; ARTICLE; CHIRALITY; CONTROLLED STUDY; DRUG CYTOTOXICITY; DRUG SYNTHESIS; EPISOME; HUMAN; HUMAN CELL; HUMAN PAPILLOMAVIRUS TYPE 16; IC 50; MALE; NONHUMAN; SKIN FIBROBLAST; STRUCTURE ACTIVITY RELATION; WART VIRUS;

ANIMALS; ANTIVIRAL AGENTS; CARBAZOLES; CELL LINE; DNA, VIRAL; FEMALE; HUMANS; PAPILLOMAVIRIDAE; RATS; STRUCTURE-ACTIVITY RELATIONSHIP;

HUMAN PAPILLOMAVIRUS; PAPILLOMAVIRIDAE;

EID: 66349130961     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2009.05.003     Document Type: Article

References (27)

1. Howley P.M. In: Howley P.M. (Ed). Fundamental Virology (1996), Lippincott-Raven, Philadelphia, PA 947
2. Kroutsky L. Am. J. Med. 102 (1997) 3
3. Wilson F.X. Expert Opin. Emerging Drugs 6 (2001) 199
4. Department of Health and Human Services Center for Disease Control and Prevention. Genital HPV infection-CDC factsheet. www.cdc.gov/std/HPV/STDFact-HPV.htm#common.
5. Dunne E.F., Unger E.R., Sternberg M., McQuillan G., Swan D.C., Patel S.S., and Markowitz L.E. J. Am. Med. Assoc. 297 (2007) 813
6. Syrjanen K., Mantyjarvi R., Saarikoski S., Vayrynen M., Syrjanen S., Parkkinen S., Yliskoski M., Saastamoinen J., and Castren O. Br. J. Obstet. Gynaeccol. 95 (1988) 1096
7. Wilson V.G., and Rosas-Acosta G. Curr. Drug Targets-Infect. Disord. 3 (2003) 221
8. Severson J., Evans T.Y., Lee P., Chan T.-S., Arany I., and Tyring S.K. J. Cutan. Med. Surg. 5 (2001) 43
9. Bosch F.X., Lorincz A., Munoz N., Meijer C.J.L.M., and Shah K.V. J. Clin. Pathol. 55 (2002) 244
10. zur Hausen H. Nat. Rev. 2 (2002) 342
11. Schmiedeskamp M.R., and Kockler D.R. Ann. Pharmacother. 40 (2006) 1344
12. Haug C.J. N. Engl. J. Med. 359 (2008) 861
13. For a description of the W12 cell line see:. Stanley M.A., Browne H.M., Appleby M., and Minson A.C. Int. J. Cancer 43 (1989) 672
14. For assay see: Boggs, S.; Catalano, J.; Gudmundsson, K. S.; Richardson, L. D.; Sebahar, P. R. WO 2005/023245.
15. For previous syntheses of the tetrahydrocarbazole core see:. Chakraborty D.P., Islam A., and Bhattacharya P. J. Org. Chem. 38 (1973) 2728
16. Chakraborty D.P., and Chowdhury B.K. J. Org. Chem. 32 (1968) 1265
17. Shoeb A., Anwer F., Kapil R.S., and Popli S.P. J. Med. Chem. 16 (1973) 425
18. Mahboobi S., Kuhr S., and Meindl W. Arch. Pharm. 327 (1994) 611
19. Balamurali R., and Rajendra Prasad K.J. Il Farmaco 56 (2001) 229
20. Tautomer of 2-formylcyclohexanone prepared as described by:. Tishler M., Gal G., and Stein G.A. Org. Synth. 39 (1959) 27
21. Borsche W., Witte A., and Bothe W. Justus Liebigs Ann. Chem. 359 (1908) 49
22. Borsche W., and Kienitz G.A. Chem. Ber. 43 (1910) 2335
23. Gataullin R.R., Minnigulov F.F., Fatykhov A.A., Spirikhin L.V., and Abdrakhmanov I.B. Russ. J. Org. Chem. 37 (2001) 1289
24. Due to the poor activity of C-7 (and C-8) substituted compounds, C-5 and other alternative substitution patterns were not pursued.
25. -1. The gaussian 98 Suite of computational programs was used to calculate model VCD spectra. Stereochemical assignments made by comparing calculated and measured spectra. For reference:. Chesseman J.R., Frisch M.J., Devlin F.J., and Stephens P.J. Chem. Phys. Lett. 252 (1996) 211
26. Stephens P.J., and Devlin F.J. Chirality 12 (2000) 172
27. While compound 33 shows similar potency and selectivity as 31 it is only obtained as a minor isomer from the reductive amination of 6-bromotetrahydrocarbazolone and (S)-α-methylbenzylamine.