Jennifer D Irvine

Publications (3)7.85 Total impact

• Article: Designing better coumarin-based fluorogenic substrates for PTP1B.

  Christopher P Holmes, Natalie Macher, J Russell Grove, Larry Jang, Jennifer D Irvine
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  ABSTRACT: As part of a program to develop better PTP1B fluorogenic substrates that more closely mimic the functionality found in the natural substrate, we have prepared and evaluated nine novel analogs of 4-methylumbelliferone phosphate (MUP) with a variety of additional groups occupying the second phosphate binding pocket.
  Bioorganic & medicinal chemistry letters 07/2008; 18(11):3382-5. · 2.65 Impact Factor
• Article: PTP1B inhibitors: synthesis and evaluation of difluoro-methylenephosphonate bioisosteres on a sulfonamide scaffold.

  Christopher P Holmes, Xianfeng Li, Yijun Pan, Caiding Xu, Ashok Bhandari, Claire M Moody, Joy A Miguel, Steven W Ferla, M Nuria De Francisco, Brian T Frederick, Siqun Zhou, Natalie Macher, Larry Jang, Jennifer D Irvine, J Russell Grove
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  ABSTRACT: 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of triaryl sulfonamide-based PTP1B inhibitors in which a difluoro-methylenephosphonate group of a potent lead has been replaced by potential bioisosteric replacements.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.
  Bioorganic & medicinal chemistry letters 05/2008; 18(8):2719-24. · 2.65 Impact Factor
• Article: Discovery and structure-activity relationships of novel sulfonamides as potent PTP1B inhibitors.

  Christopher P Holmes, Xianfeng Li, Yijun Pan, Caiding Xu, Ashok Bhandari, Claire M Moody, Joy A Miguel, Steven W Ferla, M Nuria De Francisco, Brian T Frederick, Siqun Zhou, Natalie Macher, Larry Jang, Jennifer D Irvine, J Russell Grove
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  ABSTRACT: A series of novel sulfonamides containing a single difluoromethylene-phosphonate group were discovered to be potent inhibitors of protein tyrosine phosphatase 1B. Structure-activity relationships around the scaffold were investigated, leading to the identification of compounds with IC50 or Ki values in the low nanomolar range. These sulfonamide-based inhibitors exhibit 100 and 30 times higher inhibitory activity than the corresponding tertiary amines and carboxamides, respectively.
  Bioorganic & Medicinal Chemistry Letters 11/2005; 15(19):4336-41. · 2.55 Impact Factor