Madsen, Christian published the artcile5-Substituted Imidazole-4-acetic Acid Analogues: Synthesis, Modeling, and Pharmacological Characterization of a Series of Novel γ-Aminobutyric AcidC Receptor Agonists, Synthetic Route of 45533-87-7, the publication is Journal of Medicinal Chemistry (2007), 50(17), 4147-4161, database is CAplus and MEDLINE.
A series of ring-substituted analogs of imidazole-4-acetic acid (IAA), a partial agonist at both GABAA and GABAC receptors (GABA = γ-aminobutyric acid), have been synthesized. The synthesized compounds, e.g. I·HCl, have been evaluated as ligands for the α1β2γ2S GABAA receptors and the ρ1 GABAC receptors using the FLIPR membrane potential (FMP) assay and by electrophysiol. techniques. None of the tested compounds displayed activity at the GABAA receptors at concentrations up to 1000 μM. However, the 5-Me, 5-Ph, 5-p-Me-Ph, and 5-p-F-Ph IAA analogs, displayed full agonist activities at the ρ1 receptors in the FMP assay (EC50 in the range 22-420 μM). Ligand-protein docking identified the Thr129 in the α1 subunit and the corresponding Ser168 residue in ρ1 as determinants of the selectivity displayed by the 5-substituted IAA analogs. The fact that GABA, IAA, and I·HCl displayed decreased agonist potencies at a ρ1Ser168Thr mutant compared to the WT ρ1 receptor strongly supported this hypothesis. However, in contrast to GABA and IAA, which exhibited increased agonist potencies at a α1(Thr129Ser)β2γ2 mutant compared to WT GABAA receptor, the data obtained for I·HCl at the WT and mutant receptors were nonconclusive.
Journal of Medicinal Chemistry published new progress about 45533-87-7. 45533-87-7 belongs to imidazoles-derivatives, auxiliary class Imidazole,Alcohol,Imidazole, name is (2-Methyl-1H-imidazol-4-yl)methanol, and the molecular formula is C5H8N2O, Synthetic Route of 45533-87-7.
Referemce:
https://en.wikipedia.org/wiki/Imidazole,
Imidazole | C3H4N2 – PubChem