Structure-based optimization of the piperazino-containing 1,3-disubstituted ureas affording sub-nanomolar inhibitors of soluble epoxide hydrolase
文献类型：期刊论文
| 作者 | Huang, Shao-Xu1; Cao, Bin1; Morisseau, Christophe2,3; Tin, Yi4; Hammock, Bruce D.2,3; Long, Ya-Qiu1 |
| 刊名 | MEDCHEMCOMM
 |
| 出版日期 | 2012-03 |
| 卷号 | 3期号:3页码:379-384 |
| ISSN号 | 2040-2503 |
| DOI | 10.1039/c2md00288d |
| 文献子类 | Article |
| 英文摘要 | The inhibition of the soluble epoxide hydrolase (sEH) is a promising new therapy in the treatment of cardiovascular, inflammation and other disorders. A piperazino functionality as the tertiary pharmacophore remarkably improved the drug-like profile of the 1,3-disubstituted urea sEH inhibitors. However, the potency was more dependent on the overall best balance of the hydrophilicity and lipophilicity. Based on the sEH-inhibitor complex structure, further structural optimization on the piperazino-containing 1,3-disubstituted urea scaffold was conducted for an improved potency. The 1-adamantylacetamide and para-phenylcarbonyl group were identified to be an optimal primary pharmacophore and secondary pharmacophore motif, respectively, generating sub-nanomolar sEH inhibitors with favorable water solubility. |
| WOS关键词 | EPOXYEICOSATRIENOIC ACIDS ; TRPV4 ; METABOLISM ; PROTECTS ; CHANNELS ; TARGET ; ROLES |
| 资助项目 | The National Natural Science Foundation of China[81021062] ; The National Natural Science Foundation of China[20872154] ; The National Natural Science Foundation of China[81072527] ; NIEHS[RO1 ES02710] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000301966800017 |
| 出版者 | ROYAL SOC CHEMISTRY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278159]  |
| 专题 | 药物化学研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Long, Ya-Qiu |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA; 3.Univ Calif Davis, Ctr Canc, Davis, CA 95616 USA; 4.Yunnan Univ, Sch Chem Sci & Technol, Kunming 650091, Peoples R China |
| 推荐引用方式 GB/T 7714 | Huang, Shao-Xu,Cao, Bin,Morisseau, Christophe,et al. Structure-based optimization of the piperazino-containing 1,3-disubstituted ureas affording sub-nanomolar inhibitors of soluble epoxide hydrolase[J]. MEDCHEMCOMM,2012,3(3):379-384. |
| APA | Huang, Shao-Xu,Cao, Bin,Morisseau, Christophe,Tin, Yi,Hammock, Bruce D.,&Long, Ya-Qiu.(2012).Structure-based optimization of the piperazino-containing 1,3-disubstituted ureas affording sub-nanomolar inhibitors of soluble epoxide hydrolase.MEDCHEMCOMM,3(3),379-384. |
| MLA | Huang, Shao-Xu,et al."Structure-based optimization of the piperazino-containing 1,3-disubstituted ureas affording sub-nanomolar inhibitors of soluble epoxide hydrolase".MEDCHEMCOMM 3.3(2012):379-384. |
入库方式： OAI收割
来源：上海药物研究所
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