Optimization of biaryl piperidine and 4-amino-2-biarylurea MCH1 receptor antagonists using QSAR modeling, classification techniques and virtual screening

Melagraki, G; Afantitis, A; Sarimveis, H; Koutentis, PA; Markopoulos, J; Igglessi-Markopoulou, O

dc.contributor.author	Melagraki, G	en
dc.contributor.author	Afantitis, A	en
dc.contributor.author	Sarimveis, H	en
dc.contributor.author	Koutentis, PA	en
dc.contributor.author	Markopoulos, J	en
dc.contributor.author	Igglessi-Markopoulou, O	en
dc.date.accessioned	2014-03-01T01:26:50Z
dc.date.available	2014-03-01T01:26:50Z
dc.date.issued	2007	en
dc.identifier.issn	0920-654X	en
dc.identifier.uri	https://dspace.lib.ntua.gr/xmlui/handle/123456789/18244
dc.subject	Classification	en
dc.subject	MCH1R	en
dc.subject	QSAR	en
dc.subject	SVM	en
dc.subject	Virtual screening	en
dc.subject.classification	Biochemistry & Molecular Biology	en
dc.subject.classification	Biophysics	en
dc.subject.classification	Computer Science, Interdisciplinary Applications	en
dc.subject.other	4 amino 2 biarylurea	en
dc.subject.other	biaryl piperidine	en
dc.subject.other	hormone receptor blocking agent	en
dc.subject.other	melanin concentrating hormone receptor blocking agent	en
dc.subject.other	piperidine derivative	en
dc.subject.other	tetrahydroisoquinoline	en
dc.subject.other	unclassified drug	en
dc.subject.other	urea derivative	en
dc.subject.other	article	en
dc.subject.other	binding affinity	en
dc.subject.other	controlled study	en
dc.subject.other	drug classification	en
dc.subject.other	drug potency	en
dc.subject.other	drug screening	en
dc.subject.other	drug structure	en
dc.subject.other	external validity	en
dc.subject.other	mathematical analysis	en
dc.subject.other	multiple linear regression analysis	en
dc.subject.other	prediction	en
dc.subject.other	priority journal	en
dc.subject.other	process optimization	en
dc.subject.other	quantitative structure activity relation	en
dc.subject.other	support vector machine	en
dc.subject.other	Drug Design	en
dc.subject.other	Models, Molecular	en
dc.subject.other	Piperidines	en
dc.subject.other	Quantitative Structure-Activity Relationship	en
dc.subject.other	Receptors, Somatostatin	en
dc.subject.other	Urea	en
dc.title	Optimization of biaryl piperidine and 4-amino-2-biarylurea MCH1 receptor antagonists using QSAR modeling, classification techniques and virtual screening	en
heal.type	journalArticle	en
heal.identifier.primary	10.1007/s10822-007-9112-4	en
heal.identifier.secondary	http://dx.doi.org/10.1007/s10822-007-9112-4	en
heal.language	English	en
heal.publicationDate	2007	en
heal.abstract	This paper presents the results of an optimization study on biaryl piperidine and 4-amino-2-biarylurea MCH1 receptor antagonists, which was accomplished by using quantitative-structure activity relationships (QSARs), classification and virtual screening techniques. First, a linear QSAR model was developed using Multiple Linear Regression (MLR) Analysis, while the Elimination Selection-Stepwise Regression (ES-SWR) method was adopted for selecting the most suitable input variables. The predictive activity of the model was evaluated using an external validation set and the Y-randomization technique. Based on the selected descriptors, the Support Vector Machines (SVM) classification technique was utilized to classify data into two categories: ""actives"" or ""non-actives"". Several attempts were made to optimize the scaffold of most potent compounds by inducing various structural modifications. Potential derivatives with improved activities were identified, as they were classified ""actives"" by the SVM classifier. Their activities were estimated using the produced MLR model. A detailed analysis on the model applicability domain defined the compounds, whose estimations can be accepted with confidence. © Springer Science+Business Media, LLC 2007.	en
heal.publisher	SPRINGER	en
heal.journalName	Journal of Computer-Aided Molecular Design	en
dc.identifier.doi	10.1007/s10822-007-9112-4	en
dc.identifier.isi	ISI:000245886800003	en
dc.identifier.volume	21	en
dc.identifier.issue	5	en
dc.identifier.spage	251	en
dc.identifier.epage	267	en