title: Design and campaign synthesis of pyridine-based histone deacetylase inhibitors.
abstract: A lead benzamide, bearing a cyanopyridyl moiety (3), was identified as a potent and low molecular weight histone deacetylase (HDAC) inhibitor. Various replacements of the cyano group were explored at the C3-position, along with the exploration of solubility-enhancing groups at the C5-position. It was determined that cyano substitution at the C3-position of the pyridyl core, along with a methylazetidinyl substituent at the C5-position yielded optimal HDAC1 inhibition and anti-proliferative activity in HCT-116 cells.
authors: Cancer and Infection Research, AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK. david.andrews@astrazeneca.com
authors: David M
authors: DM
authors: Andrews
authors: Keith M
authors: KM
authors: Gibson
authors: Mark A
authors: MA
authors: Graham
authors: Zbigniew S
authors: ZS
authors: Matusiak
authors: Craig A
authors: CA
authors: Roberts
authors: Elaine S E
authors: ES
authors: Stokes
authors: Madeleine C
authors: MC
authors: Brady
authors: Christine M
authors: CM
authors: Chresta
mesh_terms: D000818:Animals; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D015394:Molecular Structure; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D011725:Pyridines; D006655:Histone Deacetylases; C023666:pyridine