Benzyl amide-ketoacid inhibitors of HIV-integrase

Bioorganic and Medicinal Chemistry Letters

Volumn 17, Issue 17, 2007, Pages 4886-4890

  Walker, Michael A ^a   Johnson, Timothy ^a   Naidu, B Narasimhulu ^a   Banville, Jacques ^b   Remillard, Roger ^b   Plamondon, Serge ^b   Martel, Alain ^b   Li, Chen ^a   Torri, Albert ^a   Samanta, Himadri ^a   Lin, Zeyu ^a   Dicker, Ira ^a   Krystal, Mark ^a   Meanwell, Nicholas A ^a  

^a BRISTOL MYERS SQUIBB   (United States)

^b Research and Development ^*  (Canada)

Author keywords

AIDS; Amide ketoacid; Antiviral; Diketoacid; HIV; Integrase

Indexed keywords

1 [5 (4 FLUOROBENZYL) 2 FURYL] 3 (1,2,4 TRIAZOL 3 YL) 1,3 PROPANEDIONE; AMIDE; BENZYLAMINE DERIVATIVE; CARBENE; GS 9137; INTEGRASE INHIBITOR; KETONE; MK 0518; N (4 FLUOROBENZYL) 8 HYDROXY 5 (TETRAHYDRO 2H 1,2 THIAZIN 2 YL) 1,6 NAPHTHYRIDINE 7 CARBOXAMIDE S,S DIOXIDE; OXOACID; PHENYL GROUP; UNCLASSIFIED DRUG;

ANTIVIRAL ACTIVITY; ARTICLE; DRUG STRUCTURE; DRUG SYNTHESIS; HUMAN IMMUNODEFICIENCY VIRUS; IC 50; STRUCTURE ACTIVITY RELATION;

AMIDES; ANTI-HIV AGENTS; DRUG DESIGN; ELECTRONS; ENZYME INHIBITORS; HIV INTEGRASE; HIV INTEGRASE INHIBITORS; INHIBITORY CONCENTRATION 50; INTEGRASES; KETO ACIDS; MODELS, CHEMICAL; MOLECULAR STRUCTURE; NITROGEN; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 34547529409     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2007.06.042     Document Type: Article

References (25)

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21. To evaluate in vitro activity against HIV-integrase, 5 pmol of biotin labeled substrate DNA was bound to 100 μg of Streptavidin coated PVT SPA beads (Amersham Pharmacia Biotech). Recombinant integrase (0.26 ng) was incubated with the beads for 90 min at 37 °C. Unbound enzyme was removed by washing the complex followed by addition of inhibitors and 0.1 fmol of P33 labeled target DNA. The reaction was stopped by adding EDTA to a final concentration of 10 mM. Samples were counted in TopCountNXT (Packard) and the CPM was used as a measure of integration. The reaction condition was as described in Engelman, A.; Craigie, R. J. Virol. 1995, 69, 5908-5911. The sequences of substrate and target DNA were described in Nucleic Acid Research 1994 22, 1121-1122.
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25. 50 = 10.5 μM.