New Analgesics Designed by Molecular Topology

Abstract

Molecular topology has been applied to the design of new analgesic drugs, utilizing linear discriminant analysis and connectivity functions using different topological descriptors. Of a total of 26 compounds selected, 17 showed analgesic activity. The following stood out particularly, showing analgesic values greater than 75% regarding ASA (acetylsalicylic acid), the reference drug: 2-( l-propenyl)phenol, 2'4' dimethylacetophenone, p-chlorobenzohydrazide, I-(p-chlorophenyl) propanol and 4-benzoyl-3-methyl-1 -phenyl-2-pyrazolin-5-one. The usefulness of the design method has been demonstrated in the search of new chemical structures having analgesic effects, some of which could become "lead drugs".

Studies on Some 3(2H)-Pyridazinone Derivatives with Antinociceptive Activity

“…The molecular connectivity method is used to investigate the relationship between the experimental values of physical or biological properties and calculated connectivity indices [25,26] . In recent studies the usefulness of molecular connectivity has been demonstrated in the design of analgesics [27,28] . In this paper, some structural parameters (such as log P, parachor, molar refractivity, and molecular connectivity indices) were studied for possible correlation with antinociceptive activity of some 3(2H)-pyridazinone derivatives (Table 4 and Table 5).…”

Search of Chemical Scaffolds for Novel Antituberculosis Agents

“…Number of graph vertices.4 9 Vk, vertices of degree k, where k is 3 or 4. Number of vertices of degree k.4 9 R, ramification.…”

“…Number of vertices of degree k.4 9 R, ramification. Number of single structural branches.4 9 W, Wiener paths number. Sum of topological distances in the graph.5 3 L, length.…”

“…Sum of topological distances in the graph.5 3 L, length. Maximal topological distance in the graph.4 9 PRk, pairs of ramifications at distance k, where k is between 0 and 3.…”

“…Extramechanistical approaches have been used to design new drugs, model toxicities, and find common structural patterns of the known drugs. [3][4][5][6][7][8] Some of these models are entirely based on the search of common patterns of molecular similarity and have been used for the selection and design of new analgesics, 9 beta-blockers, 10 sedatives, 11 bronchodilators, 12 antihistaminics, 13 antivirals, 14 antibacterials, 15 cytostatics, 16 antimycobacterials, 17 and antifungals, 18,19 many of which can be considered as lead drugs. They have been also successful in the prediction of diverse properties, such as chromatographic, 20 physicochemical, 21,22 soil-sediment sorption coefficients, 23 or drug transfer into breast milk.…”