The �²3 adrenergic receptor is raising as an important drug target for the treatment of\npathologies such as diabetes, obesity, depression, and cardiac diseases among others. Several\nattempts to obtain selective and high affinity ligands have been made. Currently, Mirabegron\nis the only available drug on the market that targets this receptor approved for the treatment of\noveractive bladder. However, the FDA (Food and Drug Administration) in USA and the MHRA\n(Medicines and Healthcare products Regulatory Agency) in UK have made reports of potentially\nlife-threatening side effects associated with the administration of Mirabegron, casting doubts on the\ncontinuity of this compound. Therefore, it is of utmost importance to gather information for the\nrational design and synthesis of new �²3 adrenergic ligands. Herein, we present the first combined\n2D-QSAR (two-dimensional Quantitative Structure-Activity Relationship) and 3D-QSAR/CoMSIA\n(three-dimensional Quantitative Structure-Activity Relationship/Comparative Molecular Similarity\nIndex Analysis) study on a series of potent �²3 adrenergic agonists of indole-alkylamine structure.\nWe found a series of changes that can be made in the steric, hydrogen-bond donor and acceptor,\nlipophilicity and molar refractivity properties of the compounds to generate new promising molecules.\nFinally, based on our analysis, a summary and a regiospecific description of the requirements for\nimproving �²3 adrenergic activity is given.
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