摘要:

A review is presented on: (i) topological indices (TIs) which are numbers derived from constitutional formulas and which have continuously evolved towards higher discriminating power and better correlating ability; (ii) stereochemical descriptors, allowing structures of diastereomers and enantiomers to be encoded in computer language. Uses of these descriptors include: structure encoding and retrieval; quantitative structure-activity relationships (QSAR) and computer-assisted drug design (CADD); creation and exploration of data bases; quantitative assessment of similarity and dissimilarity.

ISSN:1062-936X    

DOI:10.1080/10629369808033259

出版商:Taylor & Francis Group    

年代:1998

数据来源: Taylor

摘要:

An evaluation of the suitability of a number of structural descriptors and clustering methods for use in diversity selection is presented. The methods are compared by their success in simulated biological activity predictions. The results suggest that simple 2D structural descriptors are particularly effective and that hierarchical clustering methods are superior to the non-hierarchical methods traditionally used for diversity related tasks. Results are presented which suggest that the difference in the utility of the descriptors can be accounted for by the different extent to which each encodes information relevant to the forces of ligand-receptor binding.

ISSN:1062-936X    

DOI:10.1080/10629369808033260

出版商:Taylor & Francis Group    

年代:1998

数据来源: Taylor

摘要:

Retrometabolic drug design approaches incorporate metabolic and toxicological considerations into the drug design process and represent a novel, systematic methodology for the design of safe compounds. Two major design concepts aimed to increase the therapeutic index (the activity/toxicity ratio) of drugs were developed.Chemical delivery systems(CDS) are primarily used to allow targeting of the active biological molecules to specific target sites or organs based on predictable enzymatic activation.Soft drugapproaches are used to design new drugs by building in the molecule, in addition to the activity, the most desired way in which the molecule is to be deactivated and detoxified subsequent to exerting its biological effects. Special computer programs were developed that starting from a lead compound generate complete libraries of possible soft analogs and then help ranking these candidates based on isosteric-isoelectronic comparisons, predicted solubility/partition properties, and estimated metabolic rates. The novel field of large peptide-CDSs imposes special challenges, but a new, remarkably simple model was developed to estimate partition properties for a wide range of compounds, including quite large peptide derivatives. A suggested change of about five order of magnitudes in the distribution coefficient can explain the “lock in” mechanism of brain-targeting delivery systems.

ISSN:1062-936X    

DOI:10.1080/10629369808033261

出版商:Taylor & Francis Group    

年代:1998

数据来源: Taylor

摘要:

Automated data classification is an indispensable tool in Drug Design. It allows to select homogeneous training sets or to distinguish compounds with required biological properties. The Kohonen Neural Networks (KNN) suggest new means for classification of biologically interesting compounds. In this paper, first, capabilities of KNN in data dimensionality reduction are presented as compared with the capabilities of Principal Component Analysis (PCA) and Hierarchical Cluster Analysis (HCA). The advantages of KNN become evident with increasing data dimensionality and size of the training set. Then, new methods are suggested to evaluate the quality of KNN models. Finally, a case study on chemical and biological data is presented. The database studied includes more than 2000 organophosphorous potent pesticides. The Kohonen maps were obtained which allow to distinguish compounds with different biological behaviour.

ISSN:1062-936X    

DOI:10.1080/10629369808033262

出版商:Taylor & Francis Group    

年代:1998

数据来源: Taylor

摘要:

Numerous drugs have been identified as presenting adverse effects towards the driving of vehicles. A large set of these drugs was compiled and classified into ten categories. Nonlinear neural mapping (N2M) was used to derive a typology of these molecules and also to link their adverse effects to therapeutic categories and structural information.

ISSN:1062-936X    

DOI:10.1080/10629369808033263

出版商:Taylor & Francis Group    

年代:1998

数据来源: Taylor

ISSN:1062-936X    

DOI:10.1080/10629369808033258

出版商:Taylor & Francis Group    

年代:1998

数据来源: Taylor