Novel tetracyclic benzo[b]carbazolones as highly potent and orally bioavailable ALK inhibitors: Design, synthesis, and structure-activity relationship study
文献类型：期刊论文
| 作者 | Jiang, Xiaolong1,3; Zhou, Ji2; Ai, Jing2 ; Song, Zilan1; Peng, Xia2; Xing, Li1; Xi, Yong2; Guo, Junfeng1; Yao, Qizheng3; Ding, Jian2
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| 刊名 | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
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| 出版日期 | 2015-11-13 |
| 卷号 | 105页码:39-56 |
| 关键词 | Benzo[b]carbazolones ALK inhibitors Anti-cancer Anti-resistance Non-small-cell lung cancer |
| ISSN号 | 0223-5234 |
| DOI | 10.1016/j.ejmech.2015.10.005 |
| 文献子类 | Article |
| 英文摘要 | Four series of tetracyclic benzo[b]carbazolone compounds possessing more rotatable bonds and higher molecular flexibility were designed by either inserting a linker within the C8-side chain or by opening the middle ketone ring on the basis of compound 5 (Alectinib, CH5424802). Compound 15b was identified showing nearly identical high potency against both wild-type and the gatekeeper mutant ALK kinase (3.4 vs 3.9 nM). This compound has favorable PK profile with an oral bioavailability of 67.1% in rats. Moreover, compound 15b showed significant growth inhibition against ALK driven cancer cells and KARPAS-299 xenograft model. (C) 2015 Elsevier Masson SAS. All rights reserved. |
| WOS关键词 | ANAPLASTIC LYMPHOMA KINASE ; CELL LUNG-CANCER ; CLINICALLY-ACQUIRED-RESISTANCE ; TYROSINE KINASE ; PHARMACOLOGICAL EVALUATION ; BIOLOGICAL EVALUATION ; CRIZOTINIB ; DISCOVERY ; CH5424802 ; EML4-ALK |
| 资助项目 | Chinese NSF[81430080] ; Chinese NSF[81125021] ; Chinese NSF[81373277] ; Chinese NSF[81473243] ; Chinese NSF[81321092] ; Major State Basic Research Development Program[2015CB910603] ; SIMM[CASIMM0120154002/2002] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000364891400002 |
| 出版者 | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276323]  |
| 专题 | 药理学第一研究室 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 药物化学研究室 |
| 通讯作者 | Zhang, Ao |
| 作者单位 | 1.Chinese Acad Sci, CAS Key Lab Receptor Res, Synthet Organ & Med Chem Lab, SIMM, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Div Antitumor Pharmacol, State Key Lab Drug Res, SIMM, Shanghai 201203, Peoples R China; 3.China Pharmaceut Univ, Dept Med Chem, Nanjing 210009, Peoples R China |
| 推荐引用方式 GB/T 7714 | Jiang, Xiaolong,Zhou, Ji,Ai, Jing,et al. Novel tetracyclic benzo[b]carbazolones as highly potent and orally bioavailable ALK inhibitors: Design, synthesis, and structure-activity relationship study[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2015,105:39-56. |
| APA | Jiang, Xiaolong.,Zhou, Ji.,Ai, Jing.,Song, Zilan.,Peng, Xia.,...&Zhang, Ao.(2015).Novel tetracyclic benzo[b]carbazolones as highly potent and orally bioavailable ALK inhibitors: Design, synthesis, and structure-activity relationship study.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,105,39-56. |
| MLA | Jiang, Xiaolong,et al."Novel tetracyclic benzo[b]carbazolones as highly potent and orally bioavailable ALK inhibitors: Design, synthesis, and structure-activity relationship study".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 105(2015):39-56. |
入库方式： OAI收割
来源：上海药物研究所
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