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of triaryl sulfonamide-based PTP1B inhibitors in which a difluoro-methylenephosphonate group of a potent lead has been replaced by potential bioisosteric replacements.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.
引用
收藏
页码:2719 / 2724
页数:6
相关论文
共 50 条
  • [21] Synthesis and biological evaluation of novel thiadiazole amides as potent Cdc25B and PTP1B inhibitors
    Li, Yingjun
    Yu, Yang
    Jin, Kun
    Gao, Lixin
    Luo, Tongchuan
    Sheng, Li
    Shao, Xin
    Li, Jia
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2014, 24 (17) : 4125 - 4128
  • [22] Identification of novel PTP1B inhibitors by pharmacophore based virtual screening, scaffold hopping and docking
    Balaramnavar, Vishal M.
    Srivastava, Rohit
    Rahuja, Neha
    Gupta, Swati
    Rawat, Arun K.
    Varshney, Salil
    Chandasana, Hardik
    Chhonker, Yashpal S.
    Doharey, Pawan Kumar
    Kumar, Santosh
    Gautam, Sudeep
    Srivastava, Swayam Prakash
    Bhatta, Rabi Sankar
    Saxena, Jitendra Kumar
    Gaikwad, Anil Nilkanth
    Srivastava, Arvind K.
    Saxena, Anil K.
    EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2014, 87 : 578 - 594
  • [23] Design, synthesis and insulin-sensitising effects of novel PTP1B inhibitors
    Tang, Yan-Bo
    Lu, Dianyun
    Chen, Zheng
    Hu, Chun
    Yang, Ying
    Tian, Jin-Ying
    Ye, Fei
    Wu, Li
    Zhang, Zhong-Yin
    Xiao, Zhiyan
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2013, 23 (08) : 2313 - 2318
  • [24] Synthesis and biological evaluation of novel N-(alkoxyphenyl)-aminocarbonylbenzoic acid derivatives as PTP1B inhibitors
    Tong, Yuan Feng
    Zhang, Pei
    Chen, Feng
    Hao, Ling Hua
    Ye, Fei
    Tian, Jin Ying
    Wu, Song
    CHINESE CHEMICAL LETTERS, 2010, 21 (12) : 1415 - 1418
  • [26] Dithiocarbamates as potential PTP1B inhibitors for diabetes management
    Deshpande, Tanvi A.
    Martinez-Malaga, Jimena
    Priefer, Ronny
    RESULTS IN CHEMISTRY, 2022, 4
  • [27] Peptidomimetics as Potent and Selective PTP1B Inhibitors#
    Patel, Dipam
    Jain, Mukul
    Shah, Shailesh R.
    Bahekar, Rajesh
    Jadav, Pradip
    Shah, Kiran
    Joharapurkar, Amit
    Shaikh, Mubeen
    Sairam, Kalapatapu V. V. M.
    MEDICINAL CHEMISTRY, 2013, 9 (05) : 660 - 671
  • [28] Inhibitors of protein tyrosine phosphatase 1B (PTP1B)
    Taylor, SD
    CURRENT TOPICS IN MEDICINAL CHEMISTRY, 2003, 3 (07) : 759 - 782
  • [29] Recent advance on PTP1B inhibitors and their biomedical applications
    Sharma, Bigyan
    Xie, Liuxing
    Yang, Fen
    Wang, Wei
    Zhou, Quanming
    Xiang, Menghua
    Zhou, Shizhe
    Lv, Wanting
    Jia, Yan
    Pokhrel, Laxman
    Shen, Jun
    Xiao, Qicai
    Gao, Liqian
    Deng, Wenbin
    EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2020, 199
  • [30] Natural PTP1B inhibitors from Broussonetia papyrifera
    Chen, RM
    Hu, LH
    An, TY
    Li, J
    Shen, Q
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2002, 12 (23) : 3387 - 3390