Computer‐Assisted Prediction of Bioactive Compounds Based on the Hansch‐Fujita Analysis

Abstract

Computer 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 programs.

Hydrophobicity of Di‐ and Tripeptides Having Unionizable Side Chains and Correlation with Substituent and Structural Parameters

“…By the correction, they tried to eliminate a component attributable to possible hyperconjugation effects on such reference reactions as acid-catalyzed hydrolysis of esters, to define the E, value. As indicated previously [23], however, the "corrected" Elc value is not the parameter corrected for the hyperconjugation effect attributable to the a-hydrogen atoms of substituents, but the parameter representing not only the steric bulk but also the effect of a-branching. The coefficient of the correction term is fixed as -0.306 in Eq.…”

“…2, but values between -0.25 and -0.35 were shown to work as well. The relevance of the use of E," for the steric effect of aliphatic substituents was discussed in detail in our previous analyses of the log P value of aliphatic amines and the ion-pair formation-partition constant of aliphatic ammonium ions [23].…”

Quantitative Analyses of Hydrophobicity of Di- to Pentapeptides Having Un-ionizable Side Chains with Substituent and Structural Parameters

“…The slope of the Z,(N) term (-0.81) was of the same order of magnitude as that previously observed (-0.52) for the effect of the decrease in the number of N+-H bonds on the ion-pair formation-partition equilibrium for various aliphatic ammonium ions and picrate in a 1-octanol: water system. 19 At positions other than the N-terminus, one of the amide NH sites, working as the hydrogen donor, is reduced by…”

Cyclische Phenyl‐carbamate des Miotin‐Typs und ihre Wirkung auf die Acetylcholinesterase

“…fur C,,Hl,N20 (234, 299): C 66, 6,H 7,7,N 12,0,0 13,7;gef. : C 66,3,H 7,8,N 12,0,0 13, N,N,a-trimethyl-4-(2-nitroethenyl) 4-(a'-Aminoethyl)-3-methoxy-N,N,a-trimethylbenzylamin (12a). In eine Suspension von 2,85 g (75,11 mmol) LiAIH, in 100 ml THF tropfte man bei 25-35' eine Lsg.…”