Abstract:
:Detailed structure-activity relationships of the C3-phenyl moiety that allow for the optimization of antiviral potency of a series of 1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione inhibitors of HIV capsid (CA) assembly are described. Combination of favorable substitutions gave additive SAR and allowed for the identification of the most potent compound in the series, analog 27. Productive SAR also transferred to the benzotriazepine and spirobenzodiazepine scaffolds, providing a solution to the labile stereocenter at the C3 position. The molecular basis of how compound 27 inhibits mature CA assembly is rationalized using high-resolution structural information. Our understanding of how compound 27 may inhibit immature Gag assembly is also discussed.
journal_name
Bioorg Med Chem Lettjournal_title
Bioorganic & medicinal chemistry lettersauthors
Fader LD,Landry S,Goulet S,Morin S,Kawai SH,Bousquet Y,Dion I,Hucke O,Goudreau N,Lemke CT,Rancourt J,Bonneau P,Titolo S,Amad M,Garneau M,Duan J,Mason S,Simoneau Bdoi
10.1016/j.bmcl.2013.03.074subject
Has Abstractpub_date
2013-06-01 00:00:00pages
3401-5issue
11eissn
0960-894Xissn
1464-3405pii
S0960-894X(13)00402-2journal_volume
23pub_type
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