title: PTP1B inhibitors: synthesis and evaluation of difluoro-methylenephosphonate bioisosteres on a sulfonamide scaffold.
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of triaryl sulfonamide-based PTP1B inhibitors in which a difluoro-methylenephosphonate group of a potent lead has been replaced by potential bioisosteric replacements.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.
authors: Affymax, Inc., 4001 Miranda Avenue, Palo Alto, CA 94304, USA. chris_holmes@affymax.com
authors: Christopher P
authors: CP
authors: Holmes
authors: Xianfeng
authors: X
authors: Li
authors: Yijun
authors: Y
authors: Pan
authors: Caiding
authors: C
authors: Xu
authors: Ashok
authors: A
authors: Bhandari
authors: Claire M
authors: CM
authors: Moody
authors: Joy A
authors: JA
authors: Miguel
authors: Steven W
authors: SW
authors: Ferla
authors: M Nuria
authors: MN
authors: De Francisco
authors: Brian T
authors: BT
authors: Frederick
authors: Siqun
authors: S
authors: Zhou
authors: Natalie
authors: N
authors: Macher
authors: Larry
authors: L
authors: Jang
authors: Jennifer D
authors: JD
authors: Irvine
authors: J Russell
authors: JR
authors: Grove
mesh_terms: D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017611:Fluorine Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D009943:Organophosphorus Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry*
chemical_list: D004791:Enzyme Inhibitors; D017611:Fluorine Compounds; D009943:Organophosphorus Compounds; D013449:Sulfonamides; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1