Synthesis of novel IP agonists via N-aminoethyl cyclic amines prepared by decarboxylative ring-opening reactions

Yasuhiro Morita; Takeshi Ishigaki; Kuniaki Kawamura; Ryoji Hayashi; Masafumi Isogaya; Mika Kitsukawa; Mitsuko Miyamoto; Masashi Uchida; Katsuhiko Iseki

doi:10.3390/molecules17021233

Synthesis of novel IP agonists via N-aminoethyl cyclic amines prepared by decarboxylative ring-opening reactions

Molecules. 2012 Jan 31;17(2):1233-46. doi: 10.3390/molecules17021233.

Authors

Yasuhiro Morita¹, Takeshi Ishigaki, Kuniaki Kawamura, Ryoji Hayashi, Masafumi Isogaya, Mika Kitsukawa, Mitsuko Miyamoto, Masashi Uchida, Katsuhiko Iseki

Affiliation

¹ Pharmaceutical Research Laboratories, Toray Industries Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan.

Abstract

An efficient synthesis of a highly potent and selective IP (PGI(2) receptor) agonist that is not structurally analogous to PGI(2) is described. This synthesis is accomplished through the following key steps: Nucleophilic ring-opening of 3-(4-chlorophenyl)-oxazolidin-2-one prepared by a one-pot procedure with 4-piperidinol and selective O-alkylation of 1-(2-(4-chlorophenylamino)ethyl)piperidin-4-ol. The obtained compound is a potent and selective IP agonist displaying a long duration of action.

MeSH terms

Alkylation
Amines / chemistry*
Cyclization
Magnetic Resonance Spectroscopy
Receptors, Epoprostenol / agonists*
Spectrometry, Mass, Fast Atom Bombardment

Substances

Amines
Receptors, Epoprostenol