Interaction model for the antiinflammatory action of benzoic and salicylic acids and phenols

Mehler, Ernest L.; Gerhards, J.

doi:10.1002/qua.560350113

Cited by 15 publications

(20 citation statements)

References 15 publications

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“…These results are in agreement with the re-charge transference model proposed by Mehler and Gerhards for benzoic and salicylic acids [13].…”

Section: Quantitative Structure--activity Relationshipssupporting

confidence: 82%

“…In this model the phenyl ring of NSAIDs occupies the ~-system of carbons 13-15 in the arachidonic acid. Mehler and Gerhards [13] found an interesting correlation between the antiinflammatory activity of phenols, salicylic acids and benzoic acids with molecular orbital parameters such as the energies and charges in the frontier orbital HOMO (highest occupied ~-orbital) and LUMO (lowest unoccupied ~-orbital). This correlation suggests a charge transfer process from the receptor to the acidic function of the drug and from the aromatic ring of the drug to the receptor.…”

Section: Introductionmentioning

confidence: 99%

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QSAR and conformational analysis of the antiinflammatory agent amfenac and analogues

Ruiz

Lopez

Milà

et al. 1993

J Computer-Aided Mol Des

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The new nonsteroidal antiinflammatory drug (NSAID) arylacetic amfenac (2-amino-3-benzoylphenylacetic acid) and 19 substituted derivatives were studied in order to correlate the biological activities with the structure-related parameters. The geometry of amfenac in neutral and anionic form was totally optimized, starting from standard geometries and crystallographic data, using semiempirical AM1 and MNDO quantum-mechanical methods. Conformational analysis shows the existence of a rigid structure for rotations of the acetic acid chain (alpha degrees) and the central carbonyl group (gamma degrees) around the bonds with the phenylamine ring, whereas the carboxyl group (beta degrees) and the phenyl ring of the benzoyl group (delta degrees) can rotate almost freely. Electrostatic potential maps were analyzed and showed that the electrostatic orientation effect seems to make an important contribution to the binding of the active compounds to prostaglandin synthase. An electrostatic orientation model of the binding site is proposed. The frontier orbital charge distribution was also described for each compound. On the other hand, steric, electronic and hydrophobic (log P) parameters were calculated and QSAR analysis showed that the most significant parameter for the antiinflammatory activity was the pi-electron density of the HOMO orbital in the second aromatic ring. These results suggest a possible electronic charge transfer between the aromatic fragments and the receptor.

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“…These results are in agreement with the re-charge transference model proposed by Mehler and Gerhards for benzoic and salicylic acids [13].…”

Section: Quantitative Structure--activity Relationshipssupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

QSAR and conformational analysis of the antiinflammatory agent amfenac and analogues

Ruiz

Lopez

Milà

et al. 1993

J Computer-Aided Mol Des

View full text Add to dashboard Cite

show abstract

“…Five pairs of compounds in the present data set allow a test of this hypothesis. These are the 3,4,5 compounds 3 and 38 (potency ratio = 2.0), and 14 and 50 (ratio = 2.7), and the three 2,4,5 pairs 17, 56 (ratio = 4.0), 16, 57 (ratio = 5.6), and 5, 39 (compound 5 is inactive, ratio is at least 20). Deleting the last pair and applying the unpaired t test (from any elementary statistics text) one obtains a significance (a) value of 0.107-that is the difference between the means is not significant, even at 90% confidence.…”

Section: Analysis Of Regression Resultsmentioning

confidence: 99%

“…This results in low activity for this compound. In DOM (56), hydrophobicity and volume both contribute strongly to activity. As the alkyl chain lengthens, the hydrophobicity becomes more favorable, but the volume becomes even more strongly unfavorable, the activity passing through a maximum in DOET (57) and declining rapidly, until in DOAM (61) it is only 1/10 of its maximum value.…”

Section: Analysis Of Regression Resultsmentioning

confidence: 99%

Structure-activity correlations for psychotomimetics. 1. Phenylalkylamines: electronic, volume, and hydrophobicity parameters

Clare¹

1990

J. Med. Chem.

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CNDO/2 calculations have been performed on a series of alkyl, alkoxy, and alkylthio derivatives of phenethylamine and phenylisopropylamine. The results of these, of van der Waals volume calculations, and of Hansch type hydrophobicity calculations were correlated with psychotomimetic activity by chemometric methods. Eight parameters, involving seven chemical descriptors, were found to be highly significant. Directional hydrophobicity and volume effects were found, which suggests that steric and hydrophobic interactions in the neighborhood of the receptor site are important. A puzzling but strong interaction effect between meta and para substituents was noted. Electronic terms may be explicable in terms of formation of charge-transfer complexes by accepting, rather than by donating, charge, as has been believed in the past. A charge effect indicates that a charge or dipole is influential at the binding site, or alternatively, a specific reactivity at the meta position is involved.

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“…In the present work, we focus on crystal structures, thermal analysis, and aqueous solubility of the Arbidol salts with benzoic (BA) and salicylic (SA) acids and two solvates of Arbidol salicylate with acetonitrile (ACN) and chloroform (CHCl 3 ). It is important to note that benzoic and salicylic acids are well-known for their analgesic and anti-inflammatory properties. , Inflammation usually accompanies viral illnesses, such as coronavirus infection and flu diseases, for the treatment of which Arb is used. Thus, this research is an attempt to design a drug–drug cocrystal with double functional action.…”

Section: Introductionmentioning

confidence: 99%

New Solid Forms of the Antiviral Drug Arbidol: Crystal Structures, Thermodynamic Stability, and Solubility

et al. 2015

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Salts of the antiviral drug Arbidol (umifenovir) with pharmaceutically relevant benzoate and salicylate anions were obtained, and their crystal structures were described. For Arbidol salicylate, an unstable solvate with acetonitrile was also found and characterized. Analysis of the conformational preferences of the Arbidol molecule in the crystal structures showed that it adopts two types of conformations, namely "open" and "closed", both of which correspond to local conformational energy minima of the isolated molecule. Thermal stability of the Arbidol salicylate solvates with chloroform and acetonitrile was analyzed by means of differential scanning calorimetry and thermogravimetric analysis. The standard thermodynamic functions of the salt formation were determined. The Gibbs energy change of the process was found to be negative, indicating that the formation of the salts from individual components is a spontaneous process. The dissolution study of the Arbidol salts performed in aqueous buffer solutions with pH 1.2 and 6.8 showed that both salts dissolve incongruently to form an Arbidol hydrochloride monohydrate at pH 1.2 and an Arbidol base at pH 6.8, respectively.

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Interaction model for the antiinflammatory action of benzoic and salicylic acids and phenols

Cited by 15 publications

References 15 publications

QSAR and conformational analysis of the antiinflammatory agent amfenac and analogues

QSAR and conformational analysis of the antiinflammatory agent amfenac and analogues

Structure-activity correlations for psychotomimetics. 1. Phenylalkylamines: electronic, volume, and hydrophobicity parameters

New Solid Forms of the Antiviral Drug Arbidol: Crystal Structures, Thermodynamic Stability, and Solubility

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