Synthesis and biological evaluation of optically active Ki16425

Takanao Sato; Kenji Sugimoto; Asuka Inoue; Shinichi Okudaira; Junken Aoki; Hidetoshi Tokuyama

doi:10.1016/j.bmcl.2012.05.012

Synthesis and biological evaluation of optically active Ki16425

Takanao Sato, Kenji Sugimoto, Asuka Inoue, Shinichi Okudaira, Junken Aoki^*, Hidetoshi Tokuyama

^*Corresponding author for this work

Synthetic and Medicinal Chemistry

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

An enantionselective synthesis of both enantiomers of Ki16425, which possesses selective LPA antagonistic activity, was achieved. The isoxazole core was constructed by a 1,3-dipolar cycloaddition of nitrile oxide with alkyne and condensation with the optically active α-phenethyl alcohol segment, which was prepared by an enantioselective reduction of arylmethylketone. Biological evaluation of both enantiomers of Ki16425 revealed that the (R)-isomer showed much higher antagonistic activity for LPA ₁ and LPA ₃ receptors.

Original language	English
Pages (from-to)	4323-4326
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	22
Issue number	13
DOIs	https://doi.org/10.1016/j.bmcl.2012.05.012
State	Published - 2012/07/01

Keywords

Cell migration assay
Enantioselective synthesis
Ki16425
LPA antagonistic activity
LPA inhibitory assay

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2012.05.012

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title = "Synthesis and biological evaluation of optically active Ki16425",

abstract = "An enantionselective synthesis of both enantiomers of Ki16425, which possesses selective LPA antagonistic activity, was achieved. The isoxazole core was constructed by a 1,3-dipolar cycloaddition of nitrile oxide with alkyne and condensation with the optically active α-phenethyl alcohol segment, which was prepared by an enantioselective reduction of arylmethylketone. Biological evaluation of both enantiomers of Ki16425 revealed that the (R)-isomer showed much higher antagonistic activity for LPA 1 and LPA 3 receptors.",

keywords = "Cell migration assay, Enantioselective synthesis, Ki16425, LPA antagonistic activity, LPA inhibitory assay",

author = "Takanao Sato and Kenji Sugimoto and Asuka Inoue and Shinichi Okudaira and Junken Aoki and Hidetoshi Tokuyama",

note = "Funding Information: This work was supported by the Targeted Proteins Research Program and the Funding Program for Next Generation World-Leading Researchers (LS008), the Cabinet Office, Government of Japan. ",

year = "2012",

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doi = "10.1016/j.bmcl.2012.05.012",

language = "英語",

volume = "22",

pages = "4323--4326",

journal = "Bioorganic and Medicinal Chemistry Letters",

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TY - JOUR

T1 - Synthesis and biological evaluation of optically active Ki16425

AU - Sato, Takanao

AU - Sugimoto, Kenji

AU - Inoue, Asuka

AU - Okudaira, Shinichi

AU - Aoki, Junken

AU - Tokuyama, Hidetoshi

N1 - Funding Information: This work was supported by the Targeted Proteins Research Program and the Funding Program for Next Generation World-Leading Researchers (LS008), the Cabinet Office, Government of Japan.

PY - 2012/7/1

Y1 - 2012/7/1

N2 - An enantionselective synthesis of both enantiomers of Ki16425, which possesses selective LPA antagonistic activity, was achieved. The isoxazole core was constructed by a 1,3-dipolar cycloaddition of nitrile oxide with alkyne and condensation with the optically active α-phenethyl alcohol segment, which was prepared by an enantioselective reduction of arylmethylketone. Biological evaluation of both enantiomers of Ki16425 revealed that the (R)-isomer showed much higher antagonistic activity for LPA 1 and LPA 3 receptors.

AB - An enantionselective synthesis of both enantiomers of Ki16425, which possesses selective LPA antagonistic activity, was achieved. The isoxazole core was constructed by a 1,3-dipolar cycloaddition of nitrile oxide with alkyne and condensation with the optically active α-phenethyl alcohol segment, which was prepared by an enantioselective reduction of arylmethylketone. Biological evaluation of both enantiomers of Ki16425 revealed that the (R)-isomer showed much higher antagonistic activity for LPA 1 and LPA 3 receptors.

KW - Cell migration assay

KW - Enantioselective synthesis

KW - Ki16425

KW - LPA antagonistic activity

KW - LPA inhibitory assay

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U2 - 10.1016/j.bmcl.2012.05.012

DO - 10.1016/j.bmcl.2012.05.012

M3 - 学術論文

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AN - SCOPUS:84862214832

SN - 0960-894X

VL - 22

SP - 4323

EP - 4326

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 13

ER -

Synthesis and biological evaluation of optically active Ki16425

Abstract

Keywords

ASJC Scopus subject areas

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