摘要:

AbstractIn a previous study, we derived a 9 point model of the binding site ofS. faeciumdihydrofolate reductase, given only the binding data for a set of 68 quinazoline inhibitors. We have now used this model to search for novel chemical classes of inhibitors with comparable predicted activity. The computer algorithm consults a library of ring systems and other molecular fragments of known structure and fits the most likely of these into the site, making chemical modifications where appropriate. The search has located diaminopteridines with calculated activity comparable to that of the best quinazolines for which the site was constructed. In addition, the search algorithm's unfettered imagination proposes much more bizarre candidates, such as a benzoxazoline‐2‐one dimer. Our present purpose is not to claim we have performed an exhaustive search for all possible antifolates, but rather to outline how the calculations are done and to demonstrate that these preliminary results are reasona

ISSN:0931-8771    

DOI:10.1002/qsar.19830020302

出版商:WILEY‐VCH Verlag    

年代:1983

数据来源: WILEY

摘要:

AbstractAzine π‐values are discussed in terms of Δπ, which is the difference in π‐value from that expected for benzene. It is shown that Δπ is close to zero for alkyl and most halogen groups, but for polar substituents capable of hydrogen bonding may be as high asca.1.6. Except forperi‐positions, these Δπ‐values may be correlated by a set of equations specific for different types of substituent position and containing terms which separately parameterise proton donor and acceptor ability. The rationale behind this treatment is justified in terms of the nature of the octanol‐water partitioning process and the manner in which electronic effects are expected to operate, in this context and that of the individual molecule. These equations will correlate those compounds for which they are expected to be applicable to Δ logP ± 0.12. Other topics discussed include: reasons for deviations among “irregular” substituents; the special problems ofperi‐positions; multi‐substitution; and some consequences of this analysis

ISSN:0931-8771    

DOI:10.1002/qsar.19830020303

出版商:WILEY‐VCH Verlag    

年代:1983

数据来源: WILEY

摘要:

AbstractA method for the rational selection of test series with low collinearities of molecular descriptors and high data variance is presented (RVS method). This method selects analogs on the basis of a selection criterium which combines multiple correlation coefficients R, relative parameter variances V and the synthetic feasibility S of test series. Special flexibility of the method is provided by weighting factors which are adapted until a satisfactory series is obtained. Examples of the application of the RVS method are given, and the results are compared with results from other selection techniques.

ISSN:0931-8771    

DOI:10.1002/qsar.19830020304

出版商:WILEY‐VCH Verlag    

年代:1983

数据来源: WILEY

摘要:

AbstractComputer programs called PREHAC1 and PREHAC2, which aid in the impartial selection of substituents for the synthesis of highly bioactive compounds among congeners based on the Hansch‐Fujita analysis, were developed. The PREHAC1 and 2 programs are for aliphatic and aromatic monosubstituted derivatives and for aromatic disubstituted derivatives, respectively. Thirteen sets of physicochemical parameter values of 408 useful substituents were previously input into a data file as Master Data. PREHAC programs are activated by the input of the coefficients and intercept of the QSAR equation with the corresponding parameter codes, the information on the number of the substituents to be printed out, etc., and then Master Data is searched. Calculated activity values are ranked in descending order and the high‐ranking substituents are printed out according to the specified number. An example is presented to illustrate the progr

ISSN:0931-8771    

DOI:10.1002/qsar.19830020305

出版商:WILEY‐VCH Verlag    

年代:1983

数据来源: WILEY

摘要:

AbstractCorrelation analysis was applied to pKavalues of a series of 91 aliphatic carboxylic acids in order to obtain substantial evidence for a σI= 0.00 parametrization of alkyl groups. A very good correlation with r = 0.998 could be established. The results confirm our findings with aliphatic amines as discussed in a previous paper in this series. Some apparent anomalies in the pKavalues of amino‐substituted carboxylic acids, diamines and dicarboxylic acids will be treat

ISSN:0931-8771    

DOI:10.1002/qsar.19830020306

出版商:WILEY‐VCH Verlag    

年代:1983

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19830020307

出版商:WILEY‐VCH Verlag    

年代:1983

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19830020301

出版商:WILEY‐VCH Verlag    

年代:1983

数据来源: WILEY