Design, Synthesis, and Biological Evaluation of Indoline and Indole Derivatives as Potent and Selective alpha(1A)-Adrenoceptor Antagonists
文献类型：期刊论文
| 作者 | Zhao, Fei2; Li, Jing1 ; Chen, Ying1; Tian, Yanxin1; Wu, Chenglin1; Xie, Yanan1; Zhou, Yu1; Wang, Jiang1; Xie, Xin1; Lie, Hong1
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| 刊名 | JOURNAL OF MEDICINAL CHEMISTRY
 |
| 出版日期 | 2016-04-28 |
| 卷号 | 59期号:8页码:3826-3839 |
| ISSN号 | 0022-2623 |
| DOI | 10.1021/acs.jmedchem.5b02023 |
| 文献子类 | Article |
| 英文摘要 | A series of indoline and indole derivatives were designed, synthesized, and evaluated as selective a1A-adrenergic receptor (a1A-AR) antagonists for the treatment of benign prostatic hyperplasia (BPH). In this study, two highly selective and potent a1A-AR antagonists, compounds (R)-14r (IC50 = 2.7 nM, a1B/a1A = 640.1, a1D/a1A = 408.2) and (R)-23l (IC50 = 1.9 nM, a1B/a1A = 1506, a1D/a1A = 249.6), which exhibited similar activities and better selectivities in cell-based calcium assays as compared with the marketed drug silodosin (IC50 = 1.9 nM, a1B/a1A = 285.9, a1D/a1A = 14.4), were identified. In the functional assays with isolated rat tissues, compounds (R)-14r and (R)-23l also showed high potency and uroselectivity. Most importantly, (R)-14r and (R)-23l can significantly decrease the micturition frequency and increase the mean voided volume of the BPH rats in a dose-dependent manner, making them worthy of further investigation for the development of anti-BPH agents |
| WOS关键词 | BENIGN PROSTATIC HYPERPLASIA ; URINARY-TRACT SYMPTOMS ; QUALITY-OF-LIFE ; ALPHA(1)-ADRENOCEPTOR SUBTYPES ; PHARMACOLOGICAL CHARACTERIZATION ; MEN ; TAMSULOSIN ; SILODOSIN ; RECEPTORS ; EFFICACY |
| 资助项目 | National Natural Science Foundation of China[21021063] ; National Natural Science Foundation of China[91229204] ; National Natural Science Foundation of China[81025017] ; National Natural Science Foundation of China[21372235] ; National Natural Science Foundation of China[81425024] ; National S&T Major Projects[2012ZX09103101-072] ; National S&T Major Projects[2012ZX09301001-005] ; National S&T Major Projects[2013ZX09507-001] ; National S&T Major Projects[2014ZX09507002-001] ; Shanghai Institute of Materia Medica[CASIMM0120151007] ; Chengdu University[2081915037] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000375519900016 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276065]  |
| 专题 | 药物化学研究室 国家新药筛选中心 |
| 通讯作者 | Xie, Xin; Lie, Hong |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, 555 Chong Zhi Rd, Shanghai 201203, Peoples R China 2.Chengdu Univ, Sichuan Ind Inst Antibiot, Antibiot Res & Reevaluat Key Lab Sichuan Prov, 168 Hua Guan Rd, Chengdu 610052, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Zhao, Fei,Li, Jing,Chen, Ying,et al. Design, Synthesis, and Biological Evaluation of Indoline and Indole Derivatives as Potent and Selective alpha(1A)-Adrenoceptor Antagonists[J]. JOURNAL OF MEDICINAL CHEMISTRY,2016,59(8):3826-3839. |
| APA | Zhao, Fei.,Li, Jing.,Chen, Ying.,Tian, Yanxin.,Wu, Chenglin.,...&Lie, Hong.(2016).Design, Synthesis, and Biological Evaluation of Indoline and Indole Derivatives as Potent and Selective alpha(1A)-Adrenoceptor Antagonists.JOURNAL OF MEDICINAL CHEMISTRY,59(8),3826-3839. |
| MLA | Zhao, Fei,et al."Design, Synthesis, and Biological Evaluation of Indoline and Indole Derivatives as Potent and Selective alpha(1A)-Adrenoceptor Antagonists".JOURNAL OF MEDICINAL CHEMISTRY 59.8(2016):3826-3839. |
入库方式： OAI收割
来源：上海药物研究所
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