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An Efficient Synthetic Method and Theoretical Calculations of Olmesartan Methyl Ether: Study of Biological Function of AT1 Antagonism

[ Vol. 17 , Issue. 8 ]


Dimitrios Ntountaniotis, George Agelis, Amalia Resvani, Maria Halabalaki, George Liapakis, Katerina Spyridaki, Simona Golic Grdadolnik, Franci Merzel, Sarantos Kostidis, Constantinos Potamitis, Theodore Tselios, John Matsoukas, Leandros Alexios Skaltsounis and Thomas Mavromoustakos   Pages 652 - 662 ( 11 )


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.


Angiotensin II AT1 receptor blocker, drug discovery, ethers, NMR, olmesartan, synthetic method, theoretical calculations.


(Dimitrios Ntountaniotis) Department of Chemistry, Laboratory of Organic Chemistry, University of Athens, Zografou 15771, Athens, Greece.

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