Novel 8-substituted dipyridodiazepinone inhibitors with a broad-spectrum of activity against HIV-1 strains resistant to non-nucleoside reverse transcriptase inhibitors

Journal of Medicinal Chemistry

Volumn 48, Issue 17, 2005, Pages 5580-5588

  O'Meara, Jeff A ^a   Yoakim, Christiane ^a   Bonneau, Pierre R ^a   Bös, Michael ^a   Cordingley, Michael G ^a,b   Déziel, Robert ^a   Doyon, Louise ^a   Duan, Jianmin ^a   Garneau, Michel ^a   Guse, Ingrid ^a   Landry, Serge ^a   Malenfant, Eric ^a   Naud, Julie ^a   Ogilvie, William W ^a,c   Thavonekham, Bounkham ^a   Simoneau, Bruno ^a  

^a BOEHRINGER INGELHEIM CANADA LTD   (Canada)

^b METHYLGENE INC   (Canada)

^c UNIVERSITY OF OTTAWA   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

4 [2 (11 ETHYL 5 METHYL 6 OXO 6,11 DIHYDRO 5H DIPYRIDO[2,3 E:3',2' B][1,4]DIAZEPIN 8 YL)ETHOXY] 3 METHYLBENZOIC ACID; ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; BENZOIC ACID DERIVATIVE; DIAZEPINE DERIVATIVE; DIPYRIDODIAZEPINONE INHIBITOR; RNA DIRECTED DNA POLYMERASE INHIBITOR; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIVIRAL ACTIVITY; ARTICLE; CONTROLLED STUDY; DOG; DRUG POTENCY; DRUG SYNTHESIS; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; MALE; MOUSE; NONHUMAN; RHESUS MONKEY; VIRUS INFECTION; VIRUS MUTANT; VIRUS REPLICATION; VIRUS RESISTANCE; VIRUS STRAIN;

ANIMALS; ANTI-HIV AGENTS; AZEPINES; CACO-2 CELLS; DOGS; DRUG RESISTANCE, VIRAL; HIV-1; HUMANS; MACACA MULATTA; MALE; MICROSOMES, LIVER; MUTATION; PERMEABILITY; PYRIDINES; RATS; RATS, SPRAGUE-DAWLEY; REVERSE TRANSCRIPTASE INHIBITORS; STRUCTURE-ACTIVITY RELATIONSHIP; VIRUS REPLICATION;

EID: 23944520311     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm050255t     Document Type: Article

References (24)

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19. Each value represents the mean of at least three determinations. The reproducibility of the assay was gauged using an internal standard.
20. Data not shown and will be published elsewhere.
21. For oral gavage, the aqueous vehicle contains 0.5% methocel and 0.3% Tween-80. For intravenous bolus injection, the compound was dissolved in a vehicle containing N,N-dimethylacetamide and 0.9% aqueous NaCl (30:70).
22. d = 7.3 ± 0.1 L/kg).
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24. 1/2 values for phase I oxidative metabolic stability were determined using male human or rat liver microsomes at a starting concentration of 10 μM for the compounds.