Molecular Modeling Studies on Carbazole Carboxamide Based BTK Inhibitors Using Docking and Structure-Based 3D-QSAR
文献类型：期刊论文
| 作者 | Li, Rui2; Du, Yongli2; Gao, Zhipei2; Shen, Jingkang1 |
| 刊名 | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
 |
| 出版日期 | 2018-04 |
| 卷号 | 19期号:4 |
| 关键词 | rheumatoid arthritis (RA) Broton's tyrosine kinase (BTK) carbazole carboxamide derivatives 3D-QSAR comparative molecular field analysis (CoMFA) comparative molecular similarity indices analysis (CoMSIA) |
| ISSN号 | 1422-0067 |
| DOI | 10.3390/ijms19041244 |
| 文献子类 | Article |
| 英文摘要 | Rheumatoid arthritis (RA) is the second common rheumatic immune disease with chronic, invasive inflammatory characteristics. Non-steroidal anti-inflammatory drugs (NSAIDs), slow-acting anti-rheumatic drugs (SAARDs), or glucocorticoid drugs can improve RA patients' symptoms, but fail to cure. Broton's tyrosine kinase (BTK) inhibitors have been proven to be an efficacious target against autoimmune indications and B-cell malignancies. Among the current 11 clinical drugs, only BMS-986142, classified as a carbazole derivative, is used for treating RA. To design novel and highly potent carbazole inhibitors, molecular docking and three dimensional quantitative structure-activity relationship (3D-QSAR) were applied to explore a dataset of 132 new carbazole carboxamide derivatives. The established comparative molecular field analysis (CoMFA) (q(2) = 0.761, r(2) = 0.933) and comparative molecular similarity indices analysis (CoMSIA) (q(2) = 0.891, r(2) = 0.988) models obtained high predictive and satisfactory values. CoMFA/CoMSIA contour maps demonstrated that bulky substitutions and hydrogen-bond donors were preferred at R1 and 1-position, respectively, and introducing hydrophilic substitutions at R-1 and R-4 was important for improving BTK inhibitory activities. These results will contribute to the design of novel and highly potent BTK inhibitors. |
| WOS关键词 | BRUTONS TYROSINE KINASE ; RHEUMATOID-ARTHRITIS ; IRREVERSIBLE INHIBITORS ; LUNG-DISEASE ; ACTIVATION ; DISCOVERY ; COMFA ; FIELD |
| 资助项目 | National Natural Science Foundation of China[81202389] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000434978700323 |
| 出版者 | MDPI |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279814]  |
| 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 | Du, Yongli |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China 2.Qilu Univ Technol, Sch Chem & Pharmaceut Engn, Shandong Acad Sci, 3501 Daxue Rd, Jinan 250353, Shandong, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Li, Rui,Du, Yongli,Gao, Zhipei,et al. Molecular Modeling Studies on Carbazole Carboxamide Based BTK Inhibitors Using Docking and Structure-Based 3D-QSAR[J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,2018,19(4). |
| APA | Li, Rui,Du, Yongli,Gao, Zhipei,&Shen, Jingkang.(2018).Molecular Modeling Studies on Carbazole Carboxamide Based BTK Inhibitors Using Docking and Structure-Based 3D-QSAR.INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,19(4). |
| MLA | Li, Rui,et al."Molecular Modeling Studies on Carbazole Carboxamide Based BTK Inhibitors Using Docking and Structure-Based 3D-QSAR".INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 19.4(2018). |
入库方式： OAI收割
来源：上海药物研究所
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