title: An efficient synthetic method and theoretical calculations of olmesartan methyl ether: study of biological function of AT1 antagonism.
abstract: The dissolution of the antihypertensive AT1 antagonist olmesartan in methanol generates in situ a new highly bioactive methyl ether analogue via SN1 mechanism involving an intramolecular proton transfer from carboxyl to hydroxyl group. Theoretical calculations confirmed the thermodynamic control preference of methyl ether versus the antagonistic product methyl ester. Α facile synthetic method for olmesartan methyl ether from olmesartan or olmesartan medoxomil is also described. Interestingly, the introduction of the methyl group to olmesartan did not alter its pharmacological properties. This observation opens new avenues in the synthesis of novel drugs, since hydroxyl and carboxylate groups have an orthogonal relationship in many drugs.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Ntountaniotis
authors.forename: George
authors.initials: G
authors.lastname: Agelis
authors.forename: Amalia
authors.initials: A
authors.lastname: Resvani
authors.forename: Maria
authors.initials: M
authors.lastname: Halabalaki
authors.forename: George
authors.initials: G
authors.lastname: Liapakis
authors.forename: Katerina
authors.initials: K
authors.lastname: Spyridaki
authors.forename: Simona Golic
authors.initials: SG
authors.lastname: Grdadolnik
authors.forename: Franci
authors.initials: F
authors.lastname: Merzel
authors.forename: Sarantos
authors.initials: S
authors.lastname: Kostidis
authors.forename: Constantinos
authors.initials: C
authors.lastname: Potamitis
authors.forename: Theodore
authors.initials: T
authors.lastname: Tselios
authors.forename: John
authors.initials: J
authors.lastname: Matsoukas
authors.forename: Leandros Alexios
authors.initials: LA
authors.lastname: Skaltsounis
authors.affiliation: (Dimitrios Ntountaniotis) Department of Chemistry, Laboratory of Organic Chemistry, University of Athens, Zografou 15771, Athens, Greece. djjesusc6@yahoo.gr.
authors.forename: Thomas
authors.initials: T
authors.lastname: Mavromoustakos
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000138:chemical synthesis / Q000737:chemistry*; D000959:Antihypertensive Agents / Q000138:chemical synthesis / Q000737:chemistry; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry*; D008962:Models, Theoretical; D015394:Molecular Structure; D013777:Tetrazoles / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D007093:Imidazoles; D013777:Tetrazoles; C437965:olmesartan