Development and Application of New Steric Substituent Parameters in Drug Design

Verloop, A.; Hoogenstraaten, W.; Tipker, J.

doi:10.1016/b978-0-12-060307-7.50010-9

Cited by 379 publications

(243 citation statements)

References 24 publications

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“…Rank order correlations were investigated between the biological variables for ATP antagonist activity (DR) and smooth muscle relaxant activity (MR) and a wide variety of physicochemical parameters. These were: lipophilicity, 7 (Martin, 1978) and f (Rekker, 1977); steric effects, Es (Martin, 1978) and Verloop constants (Verloop, Hoogenstraaten & Tipker, 1976); molar refractivity, (Martin, 1978); electronic effects, (Foster, Hooper, Spedding, Sweetman & Weetman, 1978). ap, am, a+, a- (Martin, 1978).…”

Section: Analysis Of Resultsmentioning

confidence: 99%

Increased inhibitory action against adenosine 5′‐triphosphate in the isolated taenia of the guinea‐pig caecum by substitution in the A‐ring of 2‐phenylisatogen

Foster¹,

Hooper²,

Imam³

et al. 1983

British J Pharmacology

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1 The ability of a series of 17 isatogen derivatives to relax smooth muscle, inhibit adenosine 5'-diphosphate (ADP)-stimulated respiration in isolated mitochondria and to antagonize the inhibitory effects of adenosine 5'-triphosphate (ATP) on smooth muscle was measured. 2 Substitution in the 4-and 7-positions of the A-ring gave compounds that were strong inhibitors of mitochondrial ATP synthesis and potent, non-specific smooth muscle relaxants. The compounds also possessed ATP-receptor blocking activity. 3 Substitution in the 5-and 6-positions of the A-ring decreased both the relaxant effect on smooth muscle and inhibition of ATP synthesis, whilst enhancing ATP-receptor antagonism. 4 In a series of 6-substituted 2-phenylisatogens, 6-methoxy-2-phenylisatogen was the most effective ATP-receptor antagonist. This compound also showed the greatest separation of the desired, pharmacological activity (ATP-receptor blockade) from the other two activities (smooth muscle relaxation and inhibition of mitochondrial ATP synthesis).

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Section: Analysis Of Resultsmentioning

confidence: 99%

Increased inhibitory action against adenosine 5′‐triphosphate in the isolated taenia of the guinea‐pig caecum by substitution in the A‐ring of 2‐phenylisatogen

Foster¹,

Hooper²,

Imam³

et al. 1983

British J Pharmacology

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show abstract

“…The logP values reflect the overall lipophilicity of a molecule, a property of major importance in Biochemical applications, and these values were also generated using the same software by fragmentation method using the command 'best estimate'. The values of Hammett's sigma parameters, the Verloop's constants and molar refractivity were obtained from the standard tables [19,20].…”

Section: Qsar Calculationsmentioning

confidence: 99%

Antibacterial Activity of Some 3-(Arylideneamino)-2-phenylquinazoline-4(3H)-ones: Synthesis and Preliminary QSAR Studies

2007

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Synthesis of ten 3-(arylideneamino)-2-phenylquinazoline-4(3H)-ones is reported. All the compounds contained a common phenyl group at the 2-position, while the substituents on the arylideneamino group were varied. The compounds were investigated for their antimicrobial activity against both Gram-positive (Staphylococcus aureus 6571 and Bacillus subtilis) and Gram-negative bacteria (Escherichia coli K12 and Shigella dysenteriae 6) using a turbidometric assay method. It was found that the incorporation of the 3-arylideneamino substituent enhanced the anti-bacterial activity of the quinazolone system. The preliminary QSAR studies were done using some computer derived property descriptors, calculated values of partition coefficients as well as usual Hammett's sigma constants and the substituent's molar refractivity.

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“…The sterimol parameter L is defined as the length of a substituent along the axis of the bond between the first atom of the substituent and the parent molecule [22][23]. Therefore, a positive L in the QSAR equation (5) suggests that there are long substituents in a specific direction.…”

Section: Qsar Analysismentioning

confidence: 99%

Triazoloquinazolines as Human A3 Adenosine Receptor Antagonists: A QSAR Study

Kim

Hong

Lee

2006

IJMS

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Abstract:Multiple linear regression analysis was performed on the quantitative structureactivity relationships (QSAR) of the triazoloquinazoline adenosine antagonists for human A 3 receptors. The data set used for the QSAR analysis encompassed the activities of 33 triazoloquinazoline derivatives and 72 physicochemical descriptors. A template molecule was derived using the known molecular structure for one of the compounds when bound to the human A 2B receptor, in which the amide bond was in a cis-conformation. All the test compounds were aligned to the template molecule. In order to identify a reasonable QSAR equation to describe the data set, we developed a multiple linear regression program that examined every possible combination of descriptors. The QSAR equation derived from this analysis indicates that the spatial and electronic effects is greater than that of hydrophobic effects in binding of the antagonists to the human A 3 receptor. It also predicts that a large sterimol length parameter is advantageous to activity, whereas large sterimol width parameters and fractional positive partial surface areas are nonadvatageous.

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Development and Application of New Steric Substituent Parameters in Drug Design

Cited by 379 publications

References 24 publications

Increased inhibitory action against adenosine 5′‐triphosphate in the isolated taenia of the guinea‐pig caecum by substitution in the A‐ring of 2‐phenylisatogen

Increased inhibitory action against adenosine 5′‐triphosphate in the isolated taenia of the guinea‐pig caecum by substitution in the A‐ring of 2‐phenylisatogen

Antibacterial Activity of Some 3-(Arylideneamino)-2-phenylquinazoline-4(3H)-ones: Synthesis and Preliminary QSAR Studies

Triazoloquinazolines as Human A3 Adenosine Receptor Antagonists: A QSAR Study

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