851365-03-2Relevant academic research and scientific papers
Acylurea connected straight chain hydroxamates as novel histone deacetylase inhibitors: Synthesis, SAR, and in vivo antitumor activity
Wang, Haishan,Lim, Ze-Yi,Zhou, Yan,Ng, Melvin,Lu, Ting,Lee, Ken,Sangthongpitag, Kanda,Goh, Kee Chuan,Wang, Xukun,Wu, Xiaofeng,Khng, Hwee Hoon,Goh, Siok Kun,Ong, Wai Chung,Bonday, Zahid,Sun, Eric T.
supporting information; experimental part, p. 3314 - 3321 (2010/08/06)
Thirty-six novel acylurea connected straight chain hydroxamates were designed and synthesized. Structure-activity relationships (SAR) were established for the length of linear chain linker and substitutions on the benzoylurea group. Compounds 5g, 5i, 5n, and 19 showed 10-20-fold enhanced HDAC1 potency compared to SAHA. In general, the cellular potency pIC50 (COLO205) correlates with enzymatic potency pIC50 (HDAC1). Compound 5b (SB207), a structurally simple and close analogue to SAHA, is more potent against HDAC1 and HDAC6 compared to the latter. As a representative example of this series, good in vitro enzymatic and cellular potency plus an excellent pharmacokinetic profile has translated into better efficacy than SAHA in both prostate cancer (PC3) and colon cancer (HCT116) xenograft models.
ACYLUREA CONNECTED AND SULFONYLUREA CONNECTED HYDROXAMATES
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Page/Page column 61-62, (2010/02/11)
The present invention relates to hydroxamate compounds which are inhibitors of histone deacetylase. More particularly, the present invention relates to acylurea/sulfonylurea containing compounds and methods for their preparation. These compounds may be useful as medicaments for the treatment of proliferative disorders as well as other diseases involving, relating to or associated with enzymes having histone deacetylase activities.
