2D-QSAR and 3D-QSAR/CoMSIA studies on a series of (R)-2-((2-(1H-Indol-2-yl)ethyl)amino)-1-phenylethan-1-ol with human β3-adrenergic activity

Gastón Apablaza, Luisa Montoya, Cesar Morales-Verdejo, MARCO ANDRÉS MELLADO GARCÍA, Mauricio Cuellar, Carlos F. Lagos, Jorge Soto-Delgado, Hery Chung, Carlos David Pessoa-Mahana, Jaime Mella

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

The β3 adrenergic receptor is raising as an important drug target for the treatment of pathologies such as diabetes, obesity, depression, and cardiac diseases among others. Several attempts to obtain selective and high affinity ligands have been made. Currently, Mirabegron is the only available drug on the market that targets this receptor approved for the treatment of overactive bladder. However, the FDA (Food and Drug Administration) in USA and the MHRA (Medicines and Healthcare products Regulatory Agency) in UK have made reports of potentially life-threatening side effects associated with the administration of Mirabegron, casting doubts on the continuity of this compound. Therefore, it is of utmost importance to gather information for the rational design and synthesis of new β3 adrenergic ligands. Herein, we present the first combined 2D-QSAR (two-dimensional Quantitative Structure-Activity Relationship) and 3D-QSAR/CoMSIA (three-dimensional Quantitative Structure-Activity Relationship/Comparative Molecular Similarity Index Analysis) study on a series of potent β3 adrenergic agonists of indole-alkylamine structure. We found a series of changes that can be made in the steric, hydrogen-bond donor and acceptor, lipophilicity and molar refractivity properties of the compounds to generate new promising molecules. Finally, based on our analysis, a summary and a regiospecific description of the requirements for improving β3 adrenergic activity is given.

Original languageEnglish
Article number404
JournalMolecules
Volume22
Issue number3
DOIs
StatePublished - 1 Mar 2017

Keywords

  • Beta-3 adrenergic receptor
  • CoMSIA
  • Diabetes
  • Indole
  • Mirabegron
  • Obesity
  • QSAR
  • Vibegron

Fingerprint Dive into the research topics of '2D-QSAR and 3D-QSAR/CoMSIA studies on a series of (R)-2-((2-(1H-Indol-2-yl)ethyl)amino)-1-phenylethan-1-ol with human β<sub>3</sub>-adrenergic activity'. Together they form a unique fingerprint.

Cite this