摘要:

AbstractThe hydrolysis of a set of 31 phenyl substituted hippurates by the enzyme subtilisin (Carlsberg, EC 3.4.21.3) was studied. The following quantitative structure‐activity relationship was formulated: log 1/Km= 0.41 σ + 0.20 MR4+ 0.19 π′3+ 3.81. In this expression, Kmis the Michaelis constant, σ is the Hammett constant, MR4is the molar refractivity of para substituents and π′3is the hydrophobic parameter for meta substituents. π′3applies only to the more hydrophobic of the two possible meta

ISSN:0931-8771    

DOI:10.1002/qsar.19850040402

出版商:WILEY‐VCH Verlag    

年代:1985

数据来源: WILEY

摘要:

AbstractThe partition coefficients of 45 neutral aliphatic amines and the ion‐pair formation‐partition equilibrium constants with picrate of 66 aliphatic ammonium ions, determined using a 1‐octanol/water system, were analyzed by means of free‐energy‐related substituent constants and the multiple regression technique. The hydrophobic, electronic, steric, and hydrogen bonding effects of N‐substituents governing the partitioning behaviors were quantitatively separated by means of an equation: log K = a∑π + ρI∑σI∑δiE s′C(Ri) + bnH+ c, where K is the equilibrium constant, and ρI, δi, b, and c are susceptibility constants and the intercept. ∑π and ∑σI, are, respectively, the sum of the hydrophobic π values and the inductive electronic σIvalues of three or four N‐substituents. E s′C(Ri) is a modified steric constant derived from the Dubois E′svalue considering the branching effect of N‐substituents, Rj, in which i = 1 ∼ 3 for amines and i = 1 ∼ 4 for ammonium ions. Riis classified according to the relative magnitude of E s′Cvalues so that E s′C(R1) ≤ E s′C(R2) ≤ E s′C(R3) ≤ E s′C(R4). nHis the number of NH hydrogens of the (conjugate) ammonium ion. It was shown that the definitely intermolecular type of steric effect in the ion‐pa

ISSN:0931-8771    

DOI:10.1002/qsar.19850040403

出版商:WILEY‐VCH Verlag    

年代:1985

数据来源: WILEY

摘要:

AbstractA series of 6‐(p‐X‐phenyl)pteridine‐4‐ones (X=H (4a), F(4b), Cl (4c), Br (4d), I (4e), methyl (4f), ethyl (4g), n‐propyl (4h), i‐propyl (4i), t‐butyl (4j), methoxy (4k), n‐butyl (4l), and OH (4m)) was synthesized, and these compounds were then tested as inhibitors of xanthine oxidase. The compounds were synthesized by condensation of the 4,5‐diaminopyrimidine‐6‐one with the appropriate arylglyoxal in ethanol at ph 2.7; the resulting mixture of 6‐ and 7‐arylisomers of the pteridine‐4‐one was then separated by crystallization from dimethyl sulfoxide. Based on their Ki values when xanthine was used as a substrate, compounds 4a and 41 inhibited xanthine oxidase about 40 times more effectively than allopurinol, a well‐known inhibitor; when 7‐phenylpteridine‐4‐one was used as a substrate, 4a inhibited xanthine oxidase about 60 times more effectively than allopurinol. A quantitative structure‐activity relationship (QSAR) analysis of the compounds using the sterical parameters B1and MR is presented. This analysis shows that, in contrast to spherical substituents, rod‐shaped substituents like n‐butyl

ISSN:0931-8771    

DOI:10.1002/qsar.19850040404

出版商:WILEY‐VCH Verlag    

年代:1985

数据来源: WILEY

摘要:

AbstractA model previously developed for describing PCB binding to cytosol receptors is tested with binding data from a set of PCBs [Bandieraet al., Biochem. Pharmacol. 32: 3803–3813 (1983)] which exhibit a broad range of intermolecular forces. The binding of molecules which would be expected to be dominated by dispersive interactions is correlated well with binding constants determined by polarizability and stacking distance parameters. The binding data for molecules which have substituents capable of exerting other electronic effects on binding correlate less well as expected. The stacking model was shown to be consistent with the minimum separation distances found by molecular mechanics. This simple model based on molecular parameters is a more universally applicable model for Ah receptor‐aromatic hydrocarbon binding since it can explain the exceptions found for the previous rectangular (3 × 10Å) box

ISSN:0931-8771    

DOI:10.1002/qsar.19850040405

出版商:WILEY‐VCH Verlag    

年代:1985

数据来源: WILEY

摘要:

AbstractQuantitative structure‐activity relationships were derived for acetyl‐ and butyrylcholinesterase inhibition by various organophosphorus esters. Bimolecular inhibition rate constants correlate well with hydrophobic substituent constants, and with the presence or absence of cationic groups on the inhibitor, but not with steric substituent constants. CNDO/2 calculations were performed on a separate set of organophosphorus esters, RR′P(O)X, where R and R′ are alkyl and/or alkoxy groups and X is fluorine, chlorine or a phenoxy group. For each subset with the same X, the CNDO‐derived net atomic charge at the central phosphorus atom in the ester correlates well with the alkaline hydrolysis rate constant. For the whole set of esters with different X, two equations were derived that relate either charge and leaving group steric bulk, or orbital energy and bond order to the hydrolysis rate

ISSN:0931-8771    

DOI:10.1002/qsar.19850040406

出版商:WILEY‐VCH Verlag    

年代:1985

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19850040408

出版商:WILEY‐VCH Verlag    

年代:1985

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19850040409

出版商:WILEY‐VCH Verlag    

年代:1985

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19850040410

出版商:WILEY‐VCH Verlag    

年代:1985

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19850040401

出版商:WILEY‐VCH Verlag    

年代:1985

数据来源: WILEY