Synthesis and biological evaluation of 3-(4-substituted-phenyl)-N-hydroxy-2-propenamides, a new class of histone deacetylase inhibitors.
Inhibitors of histone deacetylases (HDACs) have been shown to induce differentiation and/or apoptosis of human tumor cells. Novel 3-(4-substituted-phenyl)-N-hydroxy-2-propenamides have been prepared as a new class of HDAC inhibitors and evaluated for their antiproliferative activity and HDAC inhibitory activity. Incorporation of a 1,4-phenylene carboxamide linker, shown by 5, and a 4-(dimethylamino)phenyl or 4-(pyrrolidin-1-yl)phenyl group as a cap substructure generated highly potent hydroxamic acid-based HDAC inhibitors 5a and 5b.
Kim
Dae-Kee
DK
In2Gen Co. Ltd., 28 Yongon-dong, Chongno-gu, Seoul 110-799, Korea. dkkim@ewha.ac.kr
Lee
Ju Young
JY
Kim
Jae-Sun
JS
Ryu
Je-Ho
JH
Choi
Jin-Young
JY
Lee
Jun Won
JW
Im
Guang-Jin
GJ
Kim
Tae-Kon
TK
Seo
Jung Woo
JW
Park
Hyun-Ju
HJ
Yoo
Jakyung
J
Park
Jung-Hyun
JH
Kim
Tae-You
TY
Bang
Yung-Jue
YJ
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001549:Benzamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D011485:Protein Binding; D013329:Structure-Activity Relationship
C480612:4-dimethylamino-N-(4-(2-hydroxycarbamoylvinyl)benzyl)benzamide; D000970:Antineoplastic Agents; D001549:Benzamides; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C480613:N-(4-(2-hydroxycarbamoylvinyl)benzyl)-4-pyrrolidin-1-ylbenzamide