title: An example of designed multiple ligands spanning protein classes: dual MCH-1R antagonists/DPPIV inhibitors.
abstract: A ligand-based approach to identify potential starting points for a dual MCH-1R antagonist/DPPIV inhibitor medicinal chemistry program was undertaken. Potential ligand pairs were identified by analysis of MCH-1R and DPPIV in vitro data. A highly targeted synthetic effort lead to the discovery of pyridone 11, a dual MCH-1R antagonist/DPPIV inhibitor with selectivity over DPP8 and DPP9.
authors.affiliation: Prosidion Ltd, Windrush Court, Watlington Road, Oxford OX4 6LT, United Kingdom. wgattrell@yahoo.co.uk
authors.forename: William T
authors.initials: WT
authors.lastname: Gattrell
authors.forename: Colin P
authors.initials: CP
authors.lastname: Sambrook Smith
authors.forename: Alun J
authors.initials: AJ
authors.lastname: Smith
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D016466:CHO Cells; D006224:Cricetinae; D004150:Dipeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D008024:Ligands; D011728:Pyridones / Q000138:chemical synthesis* / Q000494:pharmacology; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D019440:Anti-Obesity Agents; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D008024:Ligands; C103263:MCHR1 protein, human; D011728:Pyridones; D017481:Receptors, Somatostatin; D004150:Dipeptidases; C471241:DPP9 protein, human; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C042807:DPP4 protein, human; C487997:DPP8 protein, human; D018819:Dipeptidyl Peptidase 4