Identification of novel non-peptide CXCR4 antagonists by ligand-based design approach

Satoshi Ueda; Manabu Kato; Shinsuke Inuki; Hiroaki Ohno; Barry Evans; Zi xuan Wang; Stephen C. Peiper; Kazuki Izumi; Eiichi Kodama; Masao Matsuoka; Hideko Nagasawa; Shinya Oishi; Nobutaka Fujii

doi:10.1016/j.bmcl.2008.05.092

Identification of novel non-peptide CXCR4 antagonists by ligand-based design approach

Satoshi Ueda, Manabu Kato, Shinsuke Inuki, Hiroaki Ohno, Barry Evans, Zi xuan Wang, Stephen C. Peiper, Kazuki Izumi, Eiichi Kodama, Masao Matsuoka, Hideko Nagasawa, Shinya Oishi, Nobutaka Fujii

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

29 Citations (Scopus)

Abstract

The design and synthesis of novel non-peptide CXCR4 antagonists is described. The peptide backbone of highly potent cyclic peptide-based CXCR4 antagonists was entirely replaced by an indole framework, which was expected to reproduce the disposition of the key pharmacophores consistent with those of potential bioactive conformations of the original peptides. A structure-activity relationship study on a series of modified indoles identified novel small-molecule antagonists having three pharmacophore functional groups through the appropriate linkers.

Original language	English
Pages (from-to)	4124-4129
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	18
Issue number	14
DOIs	https://doi.org/10.1016/j.bmcl.2008.05.092
Publication status	Published - 2008 Jul 15
Externally published	Yes

Keywords

Anti-HIV
CXCR4
Chemokine
Indole
SDF-1

ASJC Scopus subject areas

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bmcl.2008.05.092

Cite this

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title = "Identification of novel non-peptide CXCR4 antagonists by ligand-based design approach",

abstract = "The design and synthesis of novel non-peptide CXCR4 antagonists is described. The peptide backbone of highly potent cyclic peptide-based CXCR4 antagonists was entirely replaced by an indole framework, which was expected to reproduce the disposition of the key pharmacophores consistent with those of potential bioactive conformations of the original peptides. A structure-activity relationship study on a series of modified indoles identified novel small-molecule antagonists having three pharmacophore functional groups through the appropriate linkers.",

keywords = "Anti-HIV, CXCR4, Chemokine, Indole, SDF-1",

author = "Satoshi Ueda and Manabu Kato and Shinsuke Inuki and Hiroaki Ohno and Barry Evans and Wang, {Zi xuan} and Peiper, {Stephen C.} and Kazuki Izumi and Eiichi Kodama and Masao Matsuoka and Hideko Nagasawa and Shinya Oishi and Nobutaka Fujii",

note = "Funding Information: This work was supported by Grant-in-Aid for Scientific Research and Targeted Proteins Research Program from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, and Health and Labour Sciences Research Grants (Research on HIV/AIDS). Computation time was provided by the Supercomputer Laboratory, Institute for Chemical Research, Kyoto University. S.U. and S.I. are grateful to the JSPS Research Fellowships for Young Scientists.",

year = "2008",

month = jul,

day = "15",

doi = "10.1016/j.bmcl.2008.05.092",

language = "English",

volume = "18",

pages = "4124--4129",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

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number = "14",

}

TY - JOUR

T1 - Identification of novel non-peptide CXCR4 antagonists by ligand-based design approach

AU - Ueda, Satoshi

AU - Kato, Manabu

AU - Inuki, Shinsuke

AU - Ohno, Hiroaki

AU - Evans, Barry

AU - Wang, Zi xuan

AU - Peiper, Stephen C.

AU - Izumi, Kazuki

AU - Kodama, Eiichi

AU - Matsuoka, Masao

AU - Nagasawa, Hideko

AU - Oishi, Shinya

AU - Fujii, Nobutaka

N1 - Funding Information: This work was supported by Grant-in-Aid for Scientific Research and Targeted Proteins Research Program from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, and Health and Labour Sciences Research Grants (Research on HIV/AIDS). Computation time was provided by the Supercomputer Laboratory, Institute for Chemical Research, Kyoto University. S.U. and S.I. are grateful to the JSPS Research Fellowships for Young Scientists.

PY - 2008/7/15

Y1 - 2008/7/15

N2 - The design and synthesis of novel non-peptide CXCR4 antagonists is described. The peptide backbone of highly potent cyclic peptide-based CXCR4 antagonists was entirely replaced by an indole framework, which was expected to reproduce the disposition of the key pharmacophores consistent with those of potential bioactive conformations of the original peptides. A structure-activity relationship study on a series of modified indoles identified novel small-molecule antagonists having three pharmacophore functional groups through the appropriate linkers.

AB - The design and synthesis of novel non-peptide CXCR4 antagonists is described. The peptide backbone of highly potent cyclic peptide-based CXCR4 antagonists was entirely replaced by an indole framework, which was expected to reproduce the disposition of the key pharmacophores consistent with those of potential bioactive conformations of the original peptides. A structure-activity relationship study on a series of modified indoles identified novel small-molecule antagonists having three pharmacophore functional groups through the appropriate linkers.

KW - Anti-HIV

KW - CXCR4

KW - Chemokine

KW - Indole

KW - SDF-1

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DO - 10.1016/j.bmcl.2008.05.092

M3 - Article

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AN - SCOPUS:47149090722

SN - 0960-894X

VL - 18

SP - 4124

EP - 4129

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 14

ER -

Identification of novel non-peptide CXCR4 antagonists by ligand-based design approach

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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