SAR, quantitative

QSAR means quantitative SAR. It is a model that relates the chemical structure to an activity. In the so-called SAR the quantitative aspect of the phenomenon is not addressed, and the study refers to categories, such as toxic and non toxic. In a certain way, this is a simplified version of the QSAR model. The expression QSAR sometimes covers both cases. If the modeled feature is a property, the expression QSPR is also used. 

If adequate test data are not available, Structure-activity relationships (SARs) or quantitative SARs (QSARs)... 

GLP Good Laboratory Practice QSAR Quantitative SARs... 

Posner and coworkers have developed versatile methodology for the synthesis of novel 1,2,4-trioxanes that has allowed detailed investigation of their Structure-Activity Relationships (SAR) , while Jefford and coworkers first synthesized fenozan BO-7, so naturally some of their work has centered on its mechanism of action. Avery and coworkers have also contributed significantly to the area by the syntheses and QSAR (Quantitative SAR) studies of many artemisinin analogues. 

Structure-activity relationship (SAR) studies including qualitative and quantitative SAR. 

Even though much is already known about the toxicity of diterpene alkaloids that contribute to the toxicity of Consolida, Delphinium, and Aconitium species, no antiviral study has been so far reported on this type of alkaloids. Therefore, no SAR studies have been encountered by us on the antiviral or antimicrobial activities of these alkaloids. However, a quantitative SAR analysis performed on a number of diterpene alkaloids isolated from an Aconitum sp. indicated that biological activity of these alkaloids may be related to their toxicity rather than to a specific pharmacological action [40]. In a current study on 43 norditerpenoid alkaloids from Consolida, Delphinium, and Aconitum species against several tumor cell lines, lycoctonine and browniine were... 

The x-ray stmcture of complexes of TcAChE with HA and other AChE inhibitors displayed that these noncovalent inhibitors vary greatly in their stmctures and bind to different sites of the enzyme, offering many different starting points for future dmg design. To rationalize the stmcmral requirements of AChE inhibitors, Kaur and Zhang attempted to derive a coherent AChE-inhibitor recognition pattern based on literature data of molecular modeling and quantitative SAR analyses. 

One goal of SAR studies is to put forward a pharmacophore model that can elucidate the activities of synthesized derivatives, as well as predict the activity of novel derivatives. A three-dimensional quantitative SAR study was attempted for ginkgolides and the PAF receptor, using comparative molecular field analysis and 25 ginkgolide analogs, mainly those synthesized by Corey et al. " In agreement with the SAR studies just described, this pharmacophore model predicted that substituents in the lO-OH position of GB would improve activity. 

Potential concerns for a constituent of an additive raised by a qualitative SAR analysis may be addressable by a more in-depth, quantitative SAR (QS AR) analysis. The approach to QSAR used in the food contact notification program is to identify the most appropriate specific structural analogs from the pool of chemicals for which adequate carcinogenicity data are available. If, in the expert judgment of FDA reviewers, the analogs can reasonably be considered to be as toxic or more toxic than the compound of concern, these analogs can be used to develop a quantitative estimate of its upper bound LCR. 

For a constituent of an additive with equivocal (mixed positive and negative) battery of genetic toxicity tests and a EDI of < 150 pg/p/d, SAR analysis for SAs and predictive software such as MDL QSAR (Contrera et al, 2005) and MultiCASE s MC4PC (Rosenkranz and Klopman, 1988 Matthews and Contrera, 1998) may be used as part of the weight of evidence approach in assessing the safety of the compound. If a constituent were of potential concern, a quantitative SAR analysis might be feasible to characterize the expected risk. 

Quantitative SAR (QSAR) analysis in the safety assessment of constituents... 

The qualitative analysis of SARs described above has shed light on the highly complex nature of SARs. In medicinal chemistry, SARs are typically analyzed on a case-by-case basis. Thus far, few if any approaches have been introduced to systematically and quantitatively describe SAR characteristics of different compound classes. In the following, two related approaches are presented that provide a quantitative measure of SAR characteristics only based on 2D structural similarity and binding data. Limiting similarity assessment to 2D molecular representations departs from the 3D similarity-oriented correlation studies described above, but makes it possible to extend quantitative SAR analysis to targets for which no, or only few, relevant X-ray structures are available. 

Table 4.3 Summary of quantitative SAR characteristics of 16 reference classes. ...

The relationship between a chemical s structure and its biological action has been studied extensively for over a century (16). In cases where there is not a complete understanding of the mechanism/mode of action or where the influence of functional groups is not known or obvious, there is a vast body of knowledge on how different structural features within a class of chemicals may correlate with various levels of hazard. Structure-activity relations (SAR) or their mathematical treatment. Quantitative SAR (QSAR) have been developed for myriad endpoints including cancer, developmental and reproductive effects, aquatic toxicity, boiling points, water solubility and many others hazard endpoints. An instructor therefore has many opportunities to incorporate the concept of SAR at several points in the curriculum. 

In recent years, quantitative methods augmented SAR, and earned the name quantitative SAR, or QSAR. The refinements grew in part... 

For the purposes of the present chapter, however, SAR will be used to describe classical compound efficacy unless otherwise stated. Quantitative SAR (QSAR) involves a more mathematical approach involving neural networks and computer assisted design (120-123). 

On the other hand, there is a great deal of experimental data accumulated on different biological activities of chemicals with known molecular constitution and structure. The empirical approach to the problem, which side-steps knowing the biomechanism of activity, is to compare all the active compounds with inactive compounds having related structures and to reveal the similarities and differences between them. Based on this information the main features of the molecules responsible for the activity can be determined. Many such approaches have been investigated during the past two decades, and work in this area is usually published under the title structure-activity relationships (SAR), or quantitative SAR (QSAR). Full development of the QSAR approaches was reached when use of computers became widespread. 

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