Aromatic substituent constants (lipophilic x, electronic am and ,,, and steric MR, molar refractivitv) have been collected for 236 substituents including 128 jr values and 191 values for which both and ,, were found. Swain and Lupton's 5 and (R values could then be calculated for these 191 substituents by a corrected procedure. The mutual correlation of am and " is high, r = 0.903, while T and are essentially orthogonal.

Systematic reviews and systematic maps represent powerful tools to identify, collect, evaluate and summarise primary research pertinent to a specific research question or topic in a highly standardised and reproducible manner. Even though they are seen as the "gold standard" when synthesising primary research, systematic reviews and maps are typically resource-intensive and complex activities. Thus, managing the conduct and reporting of such reviews can become a time consuming and challenging task. This paper introduces the open access online tool CADIMA, which was developed through a collaboration between the Julius Kühn-Institut and the Collaboration for Environmental Evidence, in order to increase the efficiency of the evidence synthesis process and facilitate reporting of all activities to maximise methodological rigour. Furthermore, we analyse how CADIMA compares with other available tools by providing a comprehensive summary of existing software designed for the purposes of systematic review management. We show that CADIMA is the only available open access tool that is designed to: (1) assist throughout the systematic review/map process; (2) be suited to reviews broader than medical sciences; (3) allow for offline data extraction; and, (4) support working as a review team.

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The large number of possible substituents that might be selected for an initial set of derivatives presents a formidable problem in decision making. By factoring such a set into more or less homogeneous subgroups with respect to various physicochemical parameters of importance, one can then focus upon such special considerations as Hbonding effects, metabolic behavior, or ease of synthesis. If the clusters are formed by an objective procedure such as minimum Euclidian distance between the points in a parameter space, selecting one derivative from each cluster will tend to give a maximum range in parameter type and help to establish a viable structure-activity relationship more rapidly. Thus, by the use of hierarchical clustering, 90 substituents have been successively clustered into 5, 10, 20, and 60 clusters with respect to various combinations of the lipophilic (and tt2) constant, electronic Swain and Lupton-type ÍF and (R constants, and the approximate steric MR (molar refractivity) and MW (molecular weight) constants. Clusters at the 60 level approach bioisosteric combinations, while clusters at the low cluster level (5-20) reflect increasing loss of information. Noncollinearity and variance of the substituents selected can be tested by a separate procedure.

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Five criteria are presented for selecting a "best equation" to correlate biological activity: selection of independent variables, statistical justification of the choice of independent variables in the "best equation," principle of parsimony, ratio of data to variables, and, most importantly, agreement between qualitative and quantitative models; that is, the equation must be in accord with the known physical-organic and biomedicinal chemistry of the process under study. These criteria are applied to a reexamination of the blocking action of /3-halo-j3-phenylalkylamines at various levels of factorization of the variables. An equation involving a , , and rvp (van der Waals' radii from the para position) is selected. The electronic nature of the process is confirmed by a new set of substituent constants (Swain-Unger) S and P which are both optimized and orthonormalized. Agreement with the qualitative model of Chapman, et al., is briefly

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