Drug design and discovery最新文献_第3页

Interactions of the dimeric triad of HIV-1 aspartyl protease with inhibitors. HIV-1天冬氨酸蛋白酶二聚体与抑制剂的相互作用。

Drug design and discovery Pub Date : 2003-01-01

Peter P Mager, Erik De Clercq, Matheus Froeyen, Robert Reinhardt

引用次数: 0

QSAR modeling of anti-HIV activities of alkenyldiarylmethanes using topological and physicochemical descriptors. 使用拓扑和物理化学描述符的烯基二芳基甲烷抗hiv活性的QSAR建模。

Drug design and discovery Pub Date : 2003-01-01 DOI: 10.3109/10559610390484221

J. Leonard, K. Roy

引用次数: 12

Predicting acyl-coenzyme A: cholesterol O-acyltransferase inhibitory activity: computational approach using topological descriptors. 预测酰基辅酶A:胆固醇o -酰基转移酶抑制活性:使用拓扑描述符的计算方法。

Drug design and discovery Pub Date : 2003-01-01 DOI: 10.3109/10559610390464124

Viney Lather, A. Madan

{"title":"Predicting acyl-coenzyme A: cholesterol O-acyltransferase inhibitory activity: computational approach using topological descriptors.","authors":"Viney Lather, A. Madan","doi":"10.3109/10559610390464124","DOIUrl":"https://doi.org/10.3109/10559610390464124","url":null,"abstract":"Relationship between the topological indices and acyl-coenzyme A:cholesterol O-acyltransferase (ACAT) inhibitory activity of (aminosulfonyl)ureas has been investigated. Three topological indices, Wiener's index--a distance-based topological descriptor, molecular connectivity index--an adjacency-based topological index, and eccentric connectivity index--an adjacency-cum-distance-based topological descriptor, were used for the present investigations. A data set comprising 41 analogues of substituted (aminosulfonyl)ureas was selected for the present studies. The values of wiener's index, eccentric connectivity index, and molecular connectivity index for each of the 41 compounds comprising the data set were computed using an in-house computer program. Resultant data were analyzed and suitable models were developed after identification of active ranges. Subsequently, a biological activity was assigned to each compound using these models, which was then compared with the reported in vitro ACAT inhibitory activity. Accuracy of prediction using these models was found to vary from a minimum of approximately 83% to a maximum of approximately 91%.","PeriodicalId":11297,"journal":{"name":"Drug design and discovery","volume":"154 1","pages":"117-22"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86056881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

QSAR with electrotopological state atom index: human factor Xa inhibitor N2-aroylanthranilamides. 具有电拓扑状态原子指数的QSAR:人因子Xa抑制剂n2 -芳酰氰胺。

Drug design and discovery Pub Date : 2002-01-01 DOI: 10.3109/10559610213502

K. Roy, A. De, C. Sengupta

{"title":"QSAR with electrotopological state atom index: human factor Xa inhibitor N2-aroylanthranilamides.","authors":"K. Roy, A. De, C. Sengupta","doi":"10.3109/10559610213502","DOIUrl":"https://doi.org/10.3109/10559610213502","url":null,"abstract":"Recently, N2-aroylanthranilamides have been reported as novel series of possible anticoagulant drug candidates and the two aryl rings (A and B) have been suggested to interact with S1 and S4 regions, respectively, of human factor Xa (hfXa). In the present effort, quantitative structure-activity relationship (QSAR) of the hfXa binding affinity of 32 N2-aroylanthranilamides have been attempted, in continuation of our previous report on the QSAR analysis of the data set using linear free energy related (LFER) model, with electrotopological state atom (ETSA) index (Kier and Hall, 1991, Adv. Drug Design., 22, 1-38), to explore the atoms/regions of the compounds that modulate the activity comparatively to the greater extent. The univariate and bivariate relations involving the ETSA values of different common atoms of the compounds show importance of the atom nos. 12, 3 and 17 (arbitrary numbering): B ring carbon bearing meta R2 substituents, C ring carbon bearing R4 substituent, and carbonyl oxygen of A ring amide linkage. The importance of atom 12 is suggested to be due to detrimental effects of meta R2 substituents (B ring) on the hfXa binding affinity, which may be owing to interference in the attainment of the proper orientation of the phenyl ring in the S4 site. Atom 3 signifies the impact of R4 substituents (central C ring) on the binding affinity. Again, atom 17 (carbonyl oxygen of A ring amide linkage) has been suggested to form hydrogen bonding with the NH group of the other amide linkage, producing a pseudo ring and thus stabilizing the structure. The relations were improved further using indicator and physicochemical variables and the present results are in good agreement with the previous findings of the Hansch analysis.","PeriodicalId":11297,"journal":{"name":"Drug design and discovery","volume":"1 1","pages":"33-43"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73355792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 17

QSAR of human factor Xa inhibitor N2-aroylanthranilamides using principal component factor analysis. 主成分因子分析法对人Xa因子抑制剂n2 -芳酰氰胺类药物的QSAR研究。

Drug design and discovery Pub Date : 2002-01-01

Kunal Roy, A U De, Chandana Sengupta

引用次数: 0

Oxazole- and imidazole-based Ser-Leu dipeptide mimetics in potent inhibitors of antigen presentation by MHC class II DR molecules. 基于恶唑和咪唑的Ser-Leu二肽模拟物对MHC II类DR分子抗原呈递的有效抑制作用。

Drug design and discovery Pub Date : 2002-01-01 DOI: 10.3109/10559610213501

R. Sarabu, D. Bolin, R. Campbell, J. R. Cooper, D. Cox, D. Gaizband, R. Makofske, Z. Nagy, G. Olson

{"title":"Oxazole- and imidazole-based Ser-Leu dipeptide mimetics in potent inhibitors of antigen presentation by MHC class II DR molecules.","authors":"R. Sarabu, D. Bolin, R. Campbell, J. R. Cooper, D. Cox, D. Gaizband, R. Makofske, Z. Nagy, G. Olson","doi":"10.3109/10559610213501","DOIUrl":"https://doi.org/10.3109/10559610213501","url":null,"abstract":"Imidazole and oxazole derivatives 1 to 4 were designed and prepared as dipeptide mimetics to replace the Ser-Leu dipeptide sequence of Ro-25-9980 (Ac-(Cha)-RAMA-S-L-NH2), a peptidic inhibitor of antigen binding to major histocompatibility complex (MHC) class II DR molecules linked to rheumatoid arthritis (RA). The most potent analog in binding assays (IC50 = 30 nM in DRB1*0401 binding; 1.6 times as potent as Ro 25-9980) was 16, Ac-(Cha)RAMA-(S)S-psi(oxazole)-L-NH2. The SAR of peptide hybrids 10 to 24, prepared by incorporating the dipeptide mimetics 1 to 4 is discussed. Of these hybrids, 23 and 24, analogs that incorporated the imidazole and oxazole mimetics as well as optimized variants at positions 3 to 5, were found to have 70 to 80 nM binding affinity comparable to the parent peptide in DRB 1*0401 binding and were also active in DRB1*0101 binding, while being resistant to proteolysis by cathepsin B. Both of these compounds showed inhibitory activity in an antigen-stimulated T-cell proliferation assay, indicating their potential to suppress autoimmune responses and as leads for therapeutic agents to treat RA.","PeriodicalId":11297,"journal":{"name":"Drug design and discovery","volume":"105 1","pages":"3-7"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80635115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Oxazole- and imidazole-based Ser-Leu dipeptide mimetics in potent inhibitors of antigen presentation by MHC class II DR molecules. 基于恶唑和咪唑的Ser-Leu二肽模拟物对MHC II类DR分子抗原呈递的有效抑制作用。

Drug design and discovery Pub Date : 2002-01-01

Ramakanth Sarabu, David R Bolin, Robert Campbell, Joel R Cooper, Donald Cox, Diana Gaizband, Raymond Makofske, Zoltan Nagy, Gary L Olson

{"title":"Oxazole- and imidazole-based Ser-Leu dipeptide mimetics in potent inhibitors of antigen presentation by MHC class II DR molecules.","authors":"Ramakanth Sarabu, David R Bolin, Robert Campbell, Joel R Cooper, Donald Cox, Diana Gaizband, Raymond Makofske, Zoltan Nagy, Gary L Olson","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Imidazole and oxazole derivatives 1 to 4 were designed and prepared as dipeptide mimetics to replace the Ser-Leu dipeptide sequence of Ro-25-9980 (Ac-(Cha)-RAMA-S-L-NH2), a peptidic inhibitor of antigen binding to major histocompatibility complex (MHC) class II DR molecules linked to rheumatoid arthritis (RA). The most potent analog in binding assays (IC50 = 30 nM in DRB1*0401 binding; 1.6 times as potent as Ro 25-9980) was 16, Ac-(Cha)RAMA-(S)S-psi(oxazole)-L-NH2. The SAR of peptide hybrids 10 to 24, prepared by incorporating the dipeptide mimetics 1 to 4 is discussed. Of these hybrids, 23 and 24, analogs that incorporated the imidazole and oxazole mimetics as well as optimized variants at positions 3 to 5, were found to have 70 to 80 nM binding affinity comparable to the parent peptide in DRB 1*0401 binding and were also active in DRB1*0101 binding, while being resistant to proteolysis by cathepsin B. Both of these compounds showed inhibitory activity in an antigen-stimulated T-cell proliferation assay, indicating their potential to suppress autoimmune responses and as leads for therapeutic agents to treat RA.</p>","PeriodicalId":11297,"journal":{"name":"Drug design and discovery","volume":"18 1","pages":"3-7"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22061136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

QSAR of human factor Xa inhibitor N2-aroylanthranilamides using principal component factor analysis. 主成分因子分析法对人Xa因子抑制剂n2 -芳酰氰胺类药物的QSAR研究。

Drug design and discovery Pub Date : 2002-01-01 DOI: 10.3109/10559610213503

K. Roy, A. De, C. Sengupta

引用次数: 9

Combinatorial solid phase synthesis of multiply substituted 1,4-benzodiazepines and affinity studies on the CCK2 receptor (part 1). 多取代1,4-苯二氮卓类药物的组合固相合成及其对CCK2受体的亲和力研究(第一部分)。

Drug design and discovery Pub Date : 2002-01-01

Eric Lattmann, David C Billington, David R Poyner, Pornthip Arayarat, Stephen B Howitt, Spencer Lawrence, Michael Offel

引用次数: 0

Combinatorial solid phase synthesis of multiply substituted 1,4-benzodiazepines and affinity studies on the CCK2 receptor (part 1). 多取代1,4-苯二氮卓类药物的组合固相合成及其对CCK2受体的亲和力研究(第一部分)。

Drug design and discovery Pub Date : 2002-01-01 DOI: 10.1080/10559610213504

E. Lattmann, D. Billington, D. Poyner, Pornthip Arayarat, S. B. Howitt, Spencer Lawrence, M. Offel

引用次数: 15