Quantitative Structure-Activity Relationships & Combinatorial Science最新文献

Refinement and 3D-QSAR Studies of Inhibitors of Cyclophilin A Containing Amide Linker. 含酰胺连接剂的亲环蛋白A抑制剂的提纯及3D-QSAR研究。

Quantitative Structure-Activity Relationships & Combinatorial Science Pub Date : 2009-02-01 Epub Date: 2008-11-28 DOI: 10.1002/qsar.200860076

Feng Fan, Jin Zhu, Shuaishuai Ni, Jiagao Cheng, Yun Tang, Congmin Kang, Jian Li, Hualiang Jiang

{"title":"Refinement and 3D-QSAR Studies of Inhibitors of Cyclophilin A Containing Amide Linker.","authors":"Feng Fan, Jin Zhu, Shuaishuai Ni, Jiagao Cheng, Yun Tang, Congmin Kang, Jian Li, Hualiang Jiang","doi":"10.1002/qsar.200860076","DOIUrl":"10.1002/qsar.200860076","url":null,"abstract":"Cyclophilin A (CypA) is a ubiquitous cellular enzyme playing essential role in many biological processes, and the discovery of CypA inhibitor is now of special interest in the treatment of immunological disorders. In this work, molecular modeling studies were performed to develop a predictive Common Pharmacophore Hypothesis (CPH) and use it for alignment in 3D-QSAR studies using CoMFA and CoMSIA. A total of 30 compounds containing an amide fragment as the key linker, consisting of 17 of our previously discovered CypA inhibitors and 13 other inhibitors reported in the literature, were selected for pharmacophore refinement and 3D-QSAR studies. The best pharmacophore hypothesis AADR, which had two hydrogen bond acceptors, a hydrogen bond donor, and an aromatic ring, was obtained and used for the alignment of molecules in CoMFA and CoMSIA model development. The models showed a good r 2 value of 0.992 and 0.949 for CoMFA and CoMSIA, respectively. The contour maps of the models were analyzed to give structural insight for activity improvement of future novel CypA inhibitors. The CPH can also provide a powerful template for virtual screening and design of new CypA inhibitors.","PeriodicalId":49134,"journal":{"name":"Quantitative Structure-Activity Relationships & Combinatorial Science","volume":"28 2","pages":"183-193"},"PeriodicalIF":0.0,"publicationDate":"2009-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/qsar.200860076","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37866694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Literature Highlights in Combinatorial Science: Solid-phase Synthesis. 组合科学的文献亮点:固相合成。

Quantitative Structure-Activity Relationships & Combinatorial Science Pub Date : 2006-11-01 Epub Date: 2006-11-08 DOI: 10.1002/qsar.200660012

引用次数: 0

Fluorous 2,4-Dichloro-1,3,5-triazines (F-DCTs) as Nucleophile Scavengers. 作为核亲和剂清除剂的多氟 2,4-二氯-1,3,5-三嗪（F-DCTs）。

Quantitative Structure-Activity Relationships & Combinatorial Science Pub Date : 2006-07-11 DOI: 10.1002/qsar.200640042

Yimin Lu, Wei Zhang

引用次数: 0

Fluorous 2,4-Dichloro-1,3,5-triazine (F-DCT) as Amide Coupling Agent. 作为酰胺偶联剂的多氟 2,4-二氯-1,3,5-三嗪 (F-DCT)。

Quantitative Structure-Activity Relationships & Combinatorial Science Pub Date : 2006-07-11 DOI: 10.1002/qsar.200640041

Wei Zhang, Yimin Lu

引用次数: 0

Literature Highlights in Combinatorial Science: QSAR Comb. Sci. 9/2005. 组合科学的文献亮点:QSAR梳。Sci。9/2005。

Quantitative Structure-Activity Relationships & Combinatorial Science Pub Date : 2005-11-01 Epub Date: 2005-11-22 DOI: 10.1002/qsar.200590050

引用次数: 0

CoMFA/CoMSIA/HQSAR and Docking Study of the Binding Mode of Selective Cyclooxygenase (COX-2) Inhibitors. 选择性环氧化酶 (COX-2) 抑制剂结合模式的 CoMFA/CoMSIA/HQSAR 和对接研究。

Quantitative Structure-Activity Relationships & Combinatorial Science Pub Date : 2004-02-01 Epub Date: 2004-02-18 DOI: 10.1002/qsar.200330844

Haifeng Chen, Qiang Li, Xiaojun Yao, BoTao Fan, Shengang Yuan, A Panaye, J P Doucet

{"title":"CoMFA/CoMSIA/HQSAR and Docking Study of the Binding Mode of Selective Cyclooxygenase (COX-2) Inhibitors.","authors":"Haifeng Chen, Qiang Li, Xiaojun Yao, BoTao Fan, Shengang Yuan, A Panaye, J P Doucet","doi":"10.1002/qsar.200330844","DOIUrl":"10.1002/qsar.200330844","url":null,"abstract":"The intermolecular interaction between four types of anti-inflammatory inhibitors (oxazoles, pyrazoles, pyrroles and imidazoles) and COX-2 receptor was studied. The results of docking suggest that they have similar interaction mechanism. The most active compounds of these four types of inhibitors could both form several hydrogen bonds with residues His90, Arg513, Leu352 and Arg120, and develop hydrophobic interaction with residues Phe518, Leu352 and Leu359. This is consistent with the investigation reported by R. G. Kurumbail et al. (Nature. 1996, 384, 644-648). A common 3D-QSAR model could be constructed with these four categories of COX-2 inhibitors using the method of docking- guided conformer selection. The cross-validated q2 values are found as 0.741 and 0.632 for CoMFA and CoMSIA respectively. And the non-cross-validated r2 values are 0.887 and 0.885. 54 inhibitors constitute the test set used to validate the model. The results show that this model possesses good predictive ability for diverse COX-2 inhibitors. Furthermore, a HQSAR model was used to evaluate the influence of substituents on anti-inflammatory activity. Compared with the results of previous works, our model possesses significantly better prediction ability. It could help us to well understand the interaction mechanism between inhibitors and COX-2 receptor, and to make quantitative prediction of their inhibitory activities.","PeriodicalId":49134,"journal":{"name":"Quantitative Structure-Activity Relationships & Combinatorial Science","volume":"23 1","pages":"36-55"},"PeriodicalIF":0.0,"publicationDate":"2004-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168538/pdf/QSAR-23-36.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37866748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Microwave-assisted synthesis of a 3-aminoimidazo[1,2-a]-pyridine/pyrazine library by fluorous multicomponent reactions and subsequent cross-coupling reactions. 含氟多组分反应及其交叉偶联反应微波辅助合成3-氨基咪唑[1,2-a]-吡啶/吡嗪文库

Quantitative Structure-Activity Relationships & Combinatorial Science Pub Date : 2004-01-01

Yimin Lu, Wei Zhang

引用次数: 0