Combiphore (structure and ligand based pharmacophore) – approach for the design of GPR40 modulators in the management of diabetes was written by Gajjar, Krishna A.;Gajjar, Anuradha K.. And the article was included in Current Drug Discovery Technologies in 2020.Name: 2-(3-(Hydroxy(phenyl)methyl)phenyl)propanoic acid This article mentions the following:
Pharmacophore mapping and mol. docking can be synergistically integrated to improve the drug design and discovery process. A rational strategy, combiphore approach, derived from the combined study of Structure and Ligand based pharmacophore has been described to identify novel GPR40 modulators. DISCOtech module from Discovery studio was used for the generation of the Structure and Ligand based pharmacophore models which gave hydrophobic aromatic, ring aromatic and neg. ionizable as essential pharmacophoric features. The generated models were validated by screening active and inactive datasets, GH scoring and ROC curve anal. The best model was exposed as a 3D query to screen the hits from databases like GLASS (GPCR-Ligand Association), GPCR SARfari and Mini-Maybridge. Various filters were applied to retrieve the hit mols. having good drug-like properties. A known protein structure of hGPR40 (pdb: 4PHU) having TAK-875 as ligand complex was used to perform the mol. docking studies; using SYBYL-X 1.2 software. Clustering both the models gave RMSD of 0.89. Therefore, the present approach explored the maximum features by combining both ligand and structure based pharmacophore models. A common structural motif as identified in combiphore for GPR40 modulation consists of the para-substituted Ph propionic acid scaffold. Therefore, the combiphore approach, whereby maximum structural information (from both ligand and biol. protein) is explored, gives maximum insights into the plausible protein-ligand interactions and provides potential lead candidates as exemplified in this study. In the experiment, the researchers used many compounds, for example, 2-(3-(Hydroxy(phenyl)methyl)phenyl)propanoic acid (cas: 59960-32-6Name: 2-(3-(Hydroxy(phenyl)methyl)phenyl)propanoic acid).
2-(3-(Hydroxy(phenyl)methyl)phenyl)propanoic acid (cas: 59960-32-6) belongs to alcohols. The oxygen atom of the strongly polarized O―H bond of an alcohol pulls electron density away from the hydrogen atom. This polarized hydrogen, which bears a partial positive charge, can form a hydrogen bond with a pair of nonbonding electrons on another oxygen atom. Alcohols may be oxidized to give ketones, aldehydes, and carboxylic acids. These functional groups are useful for further reactions. Oxidation of organic compounds generally increases the number of bonds from carbon to oxygen (or another electronegative element, such as a halogen), and it may decrease the number of bonds to hydrogen.Name: 2-(3-(Hydroxy(phenyl)methyl)phenyl)propanoic acid
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