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Discovery of a potent, non-peptide bradykinin B1 receptor antagonist
被引:81
作者
:
Su, DS
论文数:
0
引用数:
0
h-index:
0
机构:
Merck Res Labs, Dept Med Chem, W Point, PA 19486 USA
Merck Res Labs, Dept Med Chem, W Point, PA 19486 USA
Su, DS
[
1
]
Markowitz, MK
论文数:
0
引用数:
0
h-index:
0
机构:
Merck Res Labs, Dept Med Chem, W Point, PA 19486 USA
Markowitz, MK
DiPardo, RM
论文数:
0
引用数:
0
h-index:
0
机构:
Merck Res Labs, Dept Med Chem, W Point, PA 19486 USA
DiPardo, RM
Murphy, KL
论文数:
0
引用数:
0
h-index:
0
机构:
Merck Res Labs, Dept Med Chem, W Point, PA 19486 USA
Murphy, KL
Harrell, CM
论文数:
0
引用数:
0
h-index:
0
机构:
Merck Res Labs, Dept Med Chem, W Point, PA 19486 USA
Harrell, CM
O'Malley, SS
论文数:
0
引用数:
0
h-index:
0
机构:
Merck Res Labs, Dept Med Chem, W Point, PA 19486 USA
O'Malley, SS
Ransom, RW
论文数:
0
引用数:
0
h-index:
0
机构:
Merck Res Labs, Dept Med Chem, W Point, PA 19486 USA
Ransom, RW
Chang, RSL
论文数:
0
引用数:
0
h-index:
0
机构:
Merck Res Labs, Dept Med Chem, W Point, PA 19486 USA
Chang, RSL
Ha, S
论文数:
0
引用数:
0
h-index:
0
机构:
Merck Res Labs, Dept Med Chem, W Point, PA 19486 USA
Ha, S
Hess, FJ
论文数:
0
引用数:
0
h-index:
0
机构:
Merck Res Labs, Dept Med Chem, W Point, PA 19486 USA
Hess, FJ
Pettibone, DJ
论文数:
0
引用数:
0
h-index:
0
机构:
Merck Res Labs, Dept Med Chem, W Point, PA 19486 USA
Pettibone, DJ
Mason, GS
论文数:
0
引用数:
0
h-index:
0
机构:
Merck Res Labs, Dept Med Chem, W Point, PA 19486 USA
Mason, GS
Boyce, S
论文数:
0
引用数:
0
h-index:
0
机构:
Merck Res Labs, Dept Med Chem, W Point, PA 19486 USA
Boyce, S
Freidinger, RM
论文数:
0
引用数:
0
h-index:
0
机构:
Merck Res Labs, Dept Med Chem, W Point, PA 19486 USA
Freidinger, RM
Bock, MG
论文数:
0
引用数:
0
h-index:
0
机构:
Merck Res Labs, Dept Med Chem, W Point, PA 19486 USA
Bock, MG
机构
:
[1]
Merck Res Labs, Dept Med Chem, W Point, PA 19486 USA
[2]
Merck Res Labs, Dept Neurosci, W Point, PA 19486 USA
[3]
Merck Res Labs, Neurosci Res Ctr, Harlow CM20 2QR, Essex, England
来源
:
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
|
2003年
/ 125卷
/ 25期
关键词
:
D O I
:
10.1021/ja0353457
中图分类号
:
O6 [化学];
学科分类号
:
0703 ;
摘要
:
Bradykinin (BK) plays an important role in the pathophysiological processes accompanying pain and inflammation. Selective bradykinin B1 receptor antagonists have been shown to be anti-nociceptive in animal models and could be novel therapeutic agents for the treatment of pain and inflammation. We have explored chemical modifications in a series of dihydroquinoxalinone sulfonamides to evaluate the effects of various structural changes on biological activity. The optimization of a screening lead compound, facilitated by a homology model of the BK B1 receptor, culminated in the discovery of a potent human BK B1 receptor antagonist. Results from site-directed mutagenesis studies and experiments in an animal pain model are presented. Copyright © 2003 American Chemical Society.
引用
收藏
页码:7516 / 7517
页数:2
相关论文
共 12 条
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Identification of a key region of kinin B1 receptor for high affinity binding of peptide antagonists
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Ctr Rech Labs Fournier, F-21121 Daix, France
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Ctr Rech Labs Fournier, F-21121 Daix, France
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;
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论文数:
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引用数:
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h-index:
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机构:
Merck Res Labs, W Point, PA 19486 USA
Merck Res Labs, W Point, PA 19486 USA
Bock, MG
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Univ Montreal, Fac Med, Dept Physiol, Montreal, PQ H3C 3J7, Canada
Univ Montreal, Fac Med, Dept Physiol, Montreal, PQ H3C 3J7, Canada
Couture, R
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Univ Montreal, Fac Med, Dept Physiol, Montreal, PQ H3C 3J7, Canada
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Harrisson, M
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Univ Montreal, Fac Med, Dept Physiol, Montreal, PQ H3C 3J7, Canada
Univ Montreal, Fac Med, Dept Physiol, Montreal, PQ H3C 3J7, Canada
Vianna, RM
;
Cloutier, F
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Univ Montreal, Fac Med, Dept Physiol, Montreal, PQ H3C 3J7, Canada
Univ Montreal, Fac Med, Dept Physiol, Montreal, PQ H3C 3J7, Canada
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A single position in the third transmembrane domains of the human B1 and B2 bradykinin receptors is adjacent to and discriminates between the C-terminal residues of subtype-selective ligands
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Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78284 USA
Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78284 USA
Fathy, DB
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Mathis, SA
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Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78284 USA
Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78284 USA
Mathis, SA
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Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78284 USA
Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78284 USA
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Max Delbruck Ctr Mol Med, Dept Neurosci, Mol Biol Peptide Hormones Grp, D-13092 Berlin, Germany
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Max Delbruck Ctr Mol Med, Dept Neurosci, Mol Biol Peptide Hormones Grp, D-13092 Berlin, Germany
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Max Delbruck Ctr Mol Med, Dept Neurosci, Mol Biol Peptide Hormones Grp, D-13092 Berlin, Germany
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Max Delbruck Ctr Mol Med, Dept Neurosci, Mol Biol Peptide Hormones Grp, D-13092 Berlin, Germany
Max Delbruck Ctr Mol Med, Dept Neurosci, Mol Biol Peptide Hormones Grp, D-13092 Berlin, Germany
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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,
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Identification of a key region of kinin B1 receptor for high affinity binding of peptide antagonists
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Merck Res Labs, W Point, PA 19486 USA
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Couture, R
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Univ Montreal, Fac Med, Dept Physiol, Montreal, PQ H3C 3J7, Canada
Couture, R
;
Harrisson, M
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Univ Montreal, Fac Med, Dept Physiol, Montreal, PQ H3C 3J7, Canada
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Univ Montreal, Fac Med, Dept Physiol, Montreal, PQ H3C 3J7, Canada
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A single position in the third transmembrane domains of the human B1 and B2 bradykinin receptors is adjacent to and discriminates between the C-terminal residues of subtype-selective ligands
[J].
Fathy, DB
论文数:
0
引用数:
0
h-index:
0
机构:
Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78284 USA
Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78284 USA
Fathy, DB
;
Mathis, SA
论文数:
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Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78284 USA
Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78284 USA
Mathis, SA
;
Leeb, T
论文数:
0
引用数:
0
h-index:
0
机构:
Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78284 USA
Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78284 USA
Leeb, T
;
Leeb-Lundberg, LMF
论文数:
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h-index:
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机构:
Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78284 USA
Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78284 USA
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