QSAR and pharmacophore analysis of a series of piperidinyl urea derivatives as hERG blockers and H3 antagonists

Current Drug Discovery Technologies

Volumn 10, Issue 1, 2013, Pages 47-58

  Moorthy, N S Hari Narayana ^a   Ramos, Maria J ^a   Fernandes, Pedro A ^a  

^a UNIVERSITY OF PORTO   (Portugal)

Author keywords

H3 antagonistic; HERG; Pharmacophore; Piperidinyl urea; QSAR

Indexed keywords

HISTAMINE H3 RECEPTOR ANTAGONIST; PIPERIDINYL UREA; UNCLASSIFIED DRUG;

AROMATIZATION; ARTICLE; HYDROPHOBICITY; PHARMACOPHORE; PRIORITY JOURNAL; QUANTITATIVE STRUCTURE ACTIVITY RELATION;

EID: 84875452236     PISSN: 15701638     EISSN: 18756220     Source Type: Journal    
DOI: 10.2174/1570163811310010007     Document Type: Article

References (39)

1. Moorthy NSHN, Karthikeyan C, Trivedi P. Synthesis, cytotoxic evaluation and in silico pharmacokinetic prediction of some benzo[a]phenazine-5-sulfonic acid derivatives. Med Chem 2009; 5(6): 549-57.
2. Bugrim A, Nikolskaya T, Nikolsky Y. Early prediction of drug metabolism and toxicity: systems biology approach and modeling. Drug Discov Today 2004; 9(3): 127-35.
3. Aronov AM. Predictive in silico modeling for hERG channel blockers. Drug Discov Today: Biosilico 2005; 10: 149-55.
4. Clark DE. In silico prediction of bloodbrain barrier permeation. Drug Discov Today 2003; 8: 927-33.
5. Mitcheson JS, Perry MD. Molecular determinants of high-affinity drug binding to hERG channels. Curr Opin Drug Discov Develop 2003; 6: 667-74.
6. Moorthy NSHN, Sousa SF, Ramos MJ, Fernandes PA. In silico based structural analysis of arylthiophene derivatives for FTase inhibitory activity, hERG and other toxic effects. J Biomol Screen 2011; 16: 1037-46.
7. Zhu BY, Jia ZJ, Zhang P, et al. Inhibitory effect of carboxilic acid group on hERG binding. Bioorg Med Chem Lett 2006; 16: 5507-12.
8. Jamieson C, Moir EM, Rankovic Z, Wishart G. Medicinal chemistry of hERG optimization: Highlights and Hang-ups. J Med Chem 2006; 49: 5029-49.
9. Brown AM. Drugs, hERG and sudden death. Cell Calcium 2004; 35: 543-7.
10. Moorthy NSHN, Karthikeyan C, Trivedi P. QSAR studies on cytotoxic acridine 5,7 diones: A comparative study using P-VSA descriptors and topological descriptors. Indian J Chem B 2007; 46B: 177-84.
11. Patel A, Karthikeyan C, Moorthy NSHN, Trivedi P. QSAR study on N-(aryl)-4-(azolylethyl) thiazole-5-carboxamides: Novel potent inhibitors of VEGF receptors I and II. Med Chem 2009; 5: 455-61.
12. Moorthy NSHN, Ramos MJ, Fernandes PA. Prediction of the relationship between the structural features of andrographolide derivatives and -glucosidase inhibitory activity: A quantitative structure activity relationship (QSAR) study. J Enz Inhibit Med Chem 2011; 26: 78-87.
13. Moorthy NSHN, Ramos MJ, Fernandes PA. Analysis of van der Waals surface area properties for human ether-a-go-go-related gene blocking activity: Computational study on structurally diverse compounds. SAR QSAR Environ Res 2012; 23: 521-36.
14. Moorthy NSHN, Ramos MJ, Fernandes PA. Structural analysis of 2-piperidin-4-yl-actamide derivatives for hERG blocking and MCH R1 antagonistic activities. Curr Drug Discov Tech 2012; 9(1): 25-38.
15. Moorthy NSHN, Ramos MJ, Fernandes PA. hERG binding feature analysis of structurally diverse compounds by QSAR and fragmental analysis. RSC Adv 2011; 1: 1126-36. DOI: 10.1039/c1ra00131k.
16. Berlin M, Lee YJ, Boyce CW, et al. Reduction of hERG inhibitory activity in the 4-piperidinyl urea series of H3 antagonists. Bioorg Med Chem Lett 2010; 20: 2359-64.
17. Du L, Li M, You Q, Xia L. A novel structure-based virtual screening model for the hERG channel blockers. Biochem Biophy Res Comm 2007; 355: 889-94.
18. Du LP, Tsai KC, Li MY, You QD, Xia L. The pharmacophore hypotheses of I(Kr) potassium channel blockers: Novel class III antiarrhythmic agents. Bioorg Med Chem Lett 2004; 14: 4771-7.
19. Cianchetta G, Li Y, Kang J, Rampe D, Fravolini A, Cruciani G, Vaz RJ. Predictive models for hERG potassium channel blockers. Bioorg Med Chem Lett 2005; 15: 3637-42.
20. Yoshida K, Niwa T. Quantitative structure-activity relationship studies on inhibition of hERG potassium channels. J Chem Inf Model 2006; 46: 1371-8.
21. Beshore DC, Liverton NJ, McIntyre CJ, et al. Discovery of triarylethanolamine inhibitors of the Kv1.5 potassium channel. Bioorg Med Chem Lett 2010; 20: 2493-6.
22. Seierstad M, Agrafiotis DK. A QSAR model of hERG binding using a large, diverse, and internally consistent training set. Chem Biol Drug Des 2006; 67: 284-96.
23. Lin A. QuaSAR-descriptors. Chemical Computing Group Inc. Montreal, H3A 2R7 Canada, 2002.
24. Moorthy NSHN, Ramos MJ, Fernandes PA. QSAR analysis of isosteviol derivatives as -glucosidase inhibitors with element count and other descriptors. Lett Drug Des Dis 2011; 8: 14-25.
25. Moorthy NSHN, Cerqueira NMFS, Ramos MJ, Fernandes PA. QSAR and pharmacophore analysis of thiosemicarbazone derivatives as ribonucleotide reductase inhibitors. Med Chem Res 2012; 21: 739-746; DOI: 10.1007/s00044-011- 9580-x.
26. Roy PP, Roy K. On some aspects of variable selected for partial least squares regression models. QSAR Comb Sci 2008; 27: 302-13.
27. Golbraikh A, Tropsha A. Beware of Q2. J Mol Graphs Model 2002; 20: 269-76.
28. Moorthy NSHN, Ramos MJ, Fernandes PA. Analysis of - glucosidase inhibitory activity of chromenone derivatives by its molecular features: A computational study. Med Chem 2011; 7(6): 526-33.
29. Bilodeau MT, Balitza AE, Koester TJ, et al. Potent N-(1,3-Thiazol- 2-yl)pyridine-2-amine vascular endothelial growth factor receptor tyrosine kinase inhibitors with excellent pharmacokinetics and low affinity for hERG ion channel. J Med Chem 2004; 47: 6363-72.
30. Gramatica P. Principle of QSAR model validation: Internal and external. QSAR Comb Sci 2007; 26: 694-701.
31. Kiralj R, Ferreira MMC. Basic validation procedures for regression models in QSAR and QSPR studies: Theory and applications. J Braz Chem Soc 2009; 20: 770-87.
32. Moorthy NSHN, Sousa SF, Ramos MJ, Fernandes PA. Structural feature study of benzofuran derivatives as farnesyltransferase inhibitors. J Enz Inhibit Med Chem 2011; 26(6): 777-91.
33. Moorthy NSHN, Cerqueira NS, Ramos MJ, Fernandes PA. QSAR analysis of 2-benzoxazolyl hydrazone derivatives for anticancer activity and its possible target prediction. Med Chem Res 2012; 21(2): 133-44. DOI 10.1007/s00044-010- 9510-3.
34. Moorthy NSHN, Ramos MJ, Fernandes PA. Topological, hydrophobicity and other descriptors on -glucosidase inhibition: A QSAR study on xanthone derivatives. J Enz Inhibit Med Chem 2012; 26(6): 755-66.
35. Durbin J, Watson GS. Testing for serial correlation in least squares regression. 1. Biometrika 1950; 37: 409-28.
36. Cruciani C, Crivori P, Carrupt PA, Testa B. Molecular fields in quantitative structure-permeation relationships: The VolSurf approach. J Mol Struct (Theochem) 2000; 503: 17-30.
37. Gasteiger J, Marsili M. Iterative partial equalization of orbital electronegativity - A rapid access to atomic charges. Tetrahedron 1980; 36: 3219-228.
38. Wildman SA, Crippen GM. Prediction of physicochemical parameters by atomic contributions. J Chem Inf Comput Sci 1999; 39: 868-73.
39. Choe H, Nah KH, Lee SN, et al. A novel hypothesis for the binding mode of hERG channel blockers. Biochem Biophy Res Comm 2006; 344: 72-8.