N.C. Cohen

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEstimation of heats of formation of organic compounds by additivity methodsN. Cohen and S. W. BensonCite this: Chem. Rev. 1993, 93, 7, 2419–2438Publication Date (Print):November 1, 1993Publication History Published online1 May 2002Published inissue 1 November 1993https://pubs.acs.org/doi/10.1021/cr00023a005https://doi.org/10.1021/cr00023a005research-articleACS PublicationsRequest reuse permissionsArticle Views4626Altmetric-Citations509LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMolecular modeling software and methods for medicinal chemistryN. Claude Cohen, Jeffrey M. Blaney, Christine Humblet, Peter Gund, and David C. BarryCite this: J. Med. Chem. 1990, 33, 3, 883–894Publication Date (Print):March 1, 1990Publication History Published online1 May 2002Published inissue 1 March 1990https://pubs.acs.org/doi/10.1021/jm00165a001https://doi.org/10.1021/jm00165a001research-articleACS PublicationsRequest reuse permissionsArticle Views1049Altmetric-Citations123LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

Recent observations reveal deficiencies in the accepted theory rationalizing the biological activities of the beta-lactam antibiotics, since a study of strained carbapenem beta-lactams has shown that the observed antibacterial activities do not correlate either with the pyramidal character of the beta-lactam nitrogen atom or with the ease of base hydrolysis of the lactam amide bond. The contradiction can be reconciled by an analysis of the three-dimensional (3-D) features of a set of the representative active and inactive beta-lactam structures, which shows that highly specific 3-D recognition sites may exist in the enzymes in their recognition of the antibiotics. The identification of the geometrical requirements for antibacterial activity also reveals how it could be possible to restore antibiotic activities to inactive structures, up to now considered as devoid of any therapeutic interest.

We have developed a computer program, called NEWLEAD, for the automatic generation of candidate structures conforming to the requirements of a given pharmacophore. The treatment consists in connecting the pharmacophoric pieces with spacers assembled from small chemical entities (atoms, chains, or ring moieties). We have tested the program on several sets of input fragments, each comprising selected functional groups obtained from the bioactive conformations of reference molecules. In addition to the expected solutions, the program can generate new structures that are chemically unrelated to the reference molecules. This provides an unbiased starting point for the design of new generations of lead structures. The concept used in this approach is presented and discussed. The present possibilities of the program are illustrated by some examples. The treatment is very fast, because only a few bonds are created between building blocks already having ideal geometries. The ability to generate rapidly a variety of molecules conforming to a three-dimensional pharmacophoric model makes NEWLEAD a useful tool with wide applicability in rational drug design, including the areas of molecular mimicry and peptidomimetism.