title: Exploration of the HDAC2 foot pocket: Synthesis and SAR of substituted N-(2-aminophenyl)benzamides.
abstract: A series of N-(2-amino-5-substituted phenyl)benzamides (3-21) were designed, synthesized and evaluated for their inhibition of HDAC2 and their cytotoxicity in HCT116 cancer cells. Multiple compounds from this series demonstrated time-dependent binding kinetics that is rationalized using a co-complex crystal structure of HDAC2 and N-(4-aminobiphenyl-3-yl)benzamide (6).
authors.affiliation: Takeda San Diego, San Diego, CA 92121, USA.
authors.forename: Jerome C
authors.initials: JC
authors.lastname: Bressi
authors.forename: Andy J
authors.initials: AJ
authors.lastname: Jennings
authors.forename: Robert
authors.initials: R
authors.lastname: Skene
authors.forename: Yiqin
authors.initials: Y
authors.lastname: Wu
authors.forename: Robert
authors.initials: R
authors.lastname: Melkus
authors.forename: Ron
authors.initials: R
authors.lastname: De Jong
authors.forename: Shawn
authors.initials: S
authors.lastname: O'Connell
authors.forename: Charles E
authors.initials: CE
authors.lastname: Grimshaw
authors.forename: Marc
authors.initials: M
authors.lastname: Navre
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Gangloff
mesh_terms: D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D001665:Binding Sites; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D045325:HCT116 Cells; D056464:Histone Deacetylase 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D006801:Humans; D007700:Kinetics; D013329:Structure-Activity Relationship
chemical_list: D001549:Benzamides; D056572:Histone Deacetylase Inhibitors; D056464:Histone Deacetylase 2