Benzoxazole and benzothiazole amides as novel pharmacokinetic enhancers of HIV protease inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 22, Issue 15, 2012, Pages 4998-5002

  Jonckers, Tim H M ^a   Rouan, Marie Claude ^a   Haché, Geerwin ^a   Schepens, Wim ^a   Hallenberger, Sabine ^a   Baumeister, Judith ^a,b   Sasaki, Jennifer C ^a,c  

^a JANSSEN RESEARCH FOUNDATION   (Belgium)

^b ABLYNX NV   (Belgium)

^c ALKERMES INC   (United States)

Author keywords

Amides; Benzothiazoles; Benzoxazoles; Boosting; CYP3A4 inhibition

Indexed keywords

AMIDE; BENZOTHIAZOLE DERIVATIVE; BENZOXAZOLE DERIVATIVE; CYTOCHROME P450 3A4; DARUNAVIR; PROTEINASE INHIBITOR; RITONAVIR; THIAZOL 5 YLMETHYL 4 (2 (ETHYL(METHYL)AMINO) N ISOBUTYLBENZOL[D]OXAZOLE 6 CARBOXAMIDO) 3 HYDROXY 1 PHENYLBUTAN 2 YLCARBAMATE; TMC 558445; UNCLASSIFIED DRUG;

ANTIVIRAL ACTIVITY; AREA UNDER THE CURVE; ARTICLE; DOG; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DESIGN; DRUG METABOLISM; DRUG PENETRATION; DRUG POTENCY; ENZYME INHIBITION; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; NONHUMAN; RAT; SINGLE DRUG DOSE; STRUCTURE ACTIVITY RELATION;

AMIDES; ANIMALS; BENZOTHIAZOLES; BENZOXAZOLES; CACO-2 CELLS; CYTOCHROME P-450 CYP3A; DOGS; HALF-LIFE; HIV PROTEASE INHIBITORS; HIV-1; HUMANS; RATS; STRUCTURE-ACTIVITY RELATIONSHIP;

CANIS FAMILIARIS;

EID: 84863982334     PISSN: 0960894X     EISSN: 14643405     Source Type: Journal    
DOI: 10.1016/j.bmcl.2012.06.022     Document Type: Article

References (20)

1. J.A. Bartlett, R. DeMasi, J. Quinn, C. Moxham, and F. Rousseau Aids 15 2001 1369
2. R.D. MacArthur, R.M. Novak, G. Peng, L. Chen, Y. Xiang, K.H. Hullsiek, M.J. Kozal, M. van den Berg-Wolf, C. Henely, B. Schmetter, and M. Dehlinger Lancet 368 2006 2125
3. P.A. Cane J. Antimicrob. Chemother. 64 2009 i37
4. E.D. Deeks, and C.M. Perry Drugs 70 2010 2315
5. L. Xu, and M.C. Desai Curr. Opin. Investig. Drugs 10 2009 775
6. G.N. Kumar, J. Dykstra, E.M. Roberts, V.K. Jayanti, D. Hickman, J. Uchic, Y. Yao, B. Surber, S. Thomas, and G.R. Granneman Drug Metab. Dispos. 27 1999 902
7. M. Youle J. Antimicrob. Chemother. 60 2007 1195
8. Pfizer reported on pyrazole derivatives as Cyp450 inhibitors. See: WO2008022345, WO2007034312, and WO2008004100.
9. Abbott Laboratories: C.A. Flentge, J.T. Randolph, P.P. Huang, L.L. Klein, K.C. Marsh, J.E. Harlan, and D.J. Kempf Bioorg. Med. Chem. Lett. 19 2009 5444
10. L. Xu, H. Liu, B.P. Murray, C. Callebaut, M.S. Lee, A. Hong, R.G. Strickley, L.K. Tsai, K.M. Stray, Y. Wang, G.R. Rhodes, and M.C. Desai ACS Med. Chem. Lett. 1 2010 209
11. http://www.gilead.com/pipeline.
12. tenofovir DF means tenofovir disoproxil fumarate.
13. L. Schueller, L. Baert, S. Lachau-Durand, H. Borghys, E. Clessens, G. Van Den Mooter, E. Vangyseghem, T.H.M. Jonckers, P. Van Remoortere, P. Wigerinck, and J. Rosier Int. J. Pharm. 355 2008 45
14. D.J. Kempf, K.C. Marsh, G.N. Kumar, A.D. Rodrigues, J.F. Denissen, E. McDonald, M.J. Kukulka, A. Hsu, G.R. Granneman, P.A. Baroldi, E. Sun, D. Pizzuti, J.J. Plattner, D.W. Norbeck, and J.W. Leonard Antimicrob. Agents Chemother. 41 1997 654
15. For a general overview of Cytochrome P450 inhibition see: J.H. Lin, and A.Y.H. Lu Clin. Pharmacokinet. 35 1998 361
16. N.M. King, M. Prabu-Jeyabalan, E.A. Nalivaika, P. Wigerinck, M.P. De Bethune, and C.A. Schiffer J. Virol. 78 2004 12012
17. For an example of the direct sulfonamide interaction with I50 & I50' see: M.N.L. Nalam, A. Peeters, T.H.M. Jonckers, I. Dierynck, and C.A. Schiffer J. Virol. 81 2007 9512
18. J.H. Rigby, and J.Z. Wilson Tetrahedron Lett. 25 1984 1429
19. D.L.N.G. Surleraux, A. Tahri, W.G. Verschueren, G.M.E. Pille, H.A. de Kock, T.H.M. Jonckers, A. Peeters, S. De Meyer, H. Azijn, R. Pauwels, M. de Bethune, N.M. King, M. Prabu-Jeyabalan, C.A. Schiffer, and P.B.T.P. Wigerinck J. Med. Chem. 48 2005 1813
20. C. McCoy Clin. Ther. 29 2007 1559