title: The design, synthesis and structure-activity relationships of novel isoindoline-based histone deacetylase inhibitors.
abstract: The design, synthesis and biological evaluation of a novel series of isoindoline-based hydroxamates is described. Several analogs were shown to inhibit HDAC1 with IC(50) values in the low nanomolar range and inhibit cellular proliferation of HCT116 human colon cancer cells in the sub-micromolar range. The cellular potency of compound 17e was found to have greater in vitro anti-proliferative activity than several compounds in late stage clinical trials for the treatment of cancer. The in vitro safety profiles of selected compounds were assessed and shown to be suitable for further lead optimization.
authors: Novartis Institutes for Biomedical Research, Inc., 250 Massachusetts Avenue, Cambridge, MA 02139, USA. michael.shultz@novartis.com
authors: Michael
authors: M
authors: Shultz
authors: Jianmei
authors: J
authors: Fan
authors: Christine
authors: C
authors: Chen
authors: Young Shin
authors: YS
authors: Cho
authors: Nicole
authors: N
authors: Davis
authors: Sheri
authors: S
authors: Bickford
authors: Kristen
authors: K
authors: Buteau
authors: Xueying
authors: X
authors: Cao
authors: Mats
authors: M
authors: Holmqvist
authors: Meier
authors: M
authors: Hsu
authors: Lei
authors: L
authors: Jiang
authors: Gang
authors: G
authors: Liu
authors: Qiang
authors: Q
authors: Lu
authors: Chetan
authors: C
authors: Patel
authors: Joghee Raju
authors: JR
authors: Suresh
authors: Mannangatti
authors: M
authors: Selvaraj
authors: Laszlo
authors: L
authors: Urban
authors: Ping
authors: P
authors: Wang
authors: Yan
authors: Y
authors: Yan-Neale
authors: Lewis
authors: L
authors: Whitehead
authors: Haiyan
authors: H
authors: Zhang
authors: Liping
authors: L
authors: Zhou
authors: Peter
authors: P
authors: Atadja
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D056284:Histone Deacetylase 1 / Q000037:antagonists & inhibitors*; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D054833:Isoindoles / Q000737:chemistry*; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D054833:Isoindoles; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1