title: Efficient synthesis of 3-O-thia-cPA and preliminary analysis of its biological activity toward autotaxin.
abstract: The efficient synthesis of 3-O-thia-cPAs (4a-d), sulfur analogues of cyclic phosphatidic acid (cPA), has been achieved. The key step of the synthesis is an intramolecular Arbuzov reaction to construct the cyclic thiophosphate moiety. The present synthetic route enables the synthesis of 4a-d in only four steps from the commercially available glycidol. Preliminary biological experiments showed that 4a-d exhibited a similar inhibitory effect on autotaxin (ATX) as original cPA.
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokyo University of Science (RIKADAI), 2641 Yamazaki, Noda-shi, Chiba 278-8510, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Tanaka
authors.forename: Masaru
authors.initials: M
authors.lastname: Kato
authors.forename: Takahiro
authors.initials: T
authors.lastname: Suzuki
authors.forename: Atsuo
authors.initials: A
authors.lastname: Nakazaki
authors.forename: Emi
authors.initials: E
authors.lastname: Nozaki
authors.forename: Mari
authors.initials: M
authors.lastname: Gotoh
authors.forename: Kimiko
authors.initials: K
authors.lastname: Murakami-Murofushi
authors.forename: Susumu
authors.initials: S
authors.lastname: Kobayashi
mesh_terms: D004852:Epoxy Compounds / Q000737:chemistry; D006801:Humans; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009946:Organothiophosphorus Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D010710:Phosphates / Q000737:chemistry; D010712:Phosphatidic Acids / Q000138:chemical synthesis* / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D043264:Phosphodiesterase I / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases; D020005:Propanols / Q000737:chemistry; D011755:Pyrophosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000099189:Lysophospholipase D
chemical_list: D004852:Epoxy Compounds; D009097:Multienzyme Complexes; D009946:Organothiophosphorus Compounds; D010710:Phosphates; D010712:Phosphatidic Acids; D043264:Phosphodiesterase I; D010727:Phosphoric Diester Hydrolases; D020005:Propanols; D011755:Pyrophosphatases; D000099189:Lysophospholipase D; C004312:glycidol; C035638:thiophosphoric acid