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PTP1B inhibitors: Synthesis and evaluation of difluoro-methylenephosphonate bioisosteres on a sulfonamide scaffold
被引:23
|作者:
Holmes, Christopher P.
[1
]
Li, Xianfeng
[1
]
Pan, Yijun
[1
]
Xu, Caiding
[1
]
Bhandari, Ashok
[1
]
Moody, Claire M.
[1
]
Miguel, Joy A.
[1
]
Ferla, Steven W.
[1
]
De Francisco, M. Nuria
[1
]
Frederick, Brian T.
[1
]
Zhou, Siqun
[1
]
Macher, Natalie
[1
]
Jang, Larry
[1
]
Irvine, Jennifer D.
[1
]
Grove, J. Russell
[1
]
机构:
[1] Affymax Inc, Palo Alto, CA 94304 USA
关键词:
PTP1B;
phosphatase;
bioisostere;
sulfonamide;
D O I:
10.1016/j.bmcl.2008.03.007
中图分类号:
R914 [药物化学];
学科分类号:
100701 ;
摘要:
We have synthesized and evaluated a series of triaryl sulfonamide-based PTP1B inhibitors in which a difluoro-methylenephosphonate group of a potent lead has been replaced by potential bioisosteric replacements. Several mono-or di-charged compounds (8a, 8b, and 15a) were shown exhibit inhibitory activity in the low micromolar range, demonstrating the feasibility of using this approach in identifying non-phosphonate pTyr mimetics in a small molecular scaffold. These results also provide a useful indication of the relative effectiveness of these pTyr mimetics. (C) 2008 Elsevier Ltd. All rights reserved.
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页码:2719 / 2724
页数:6
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