title: Discovery and structure-activity relationships of novel sulfonamides as potent PTP1B inhibitors.
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.
authors.affiliation: Affymax, Inc., 4001 Miranda Avenue, Palo Alto, CA 94304, USA. chris_holmes@affymax.com
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Holmes
authors.forename: Xianfeng
authors.initials: X
authors.lastname: Li
authors.forename: Yijun
authors.initials: Y
authors.lastname: Pan
authors.forename: Caiding
authors.initials: C
authors.lastname: Xu
authors.forename: Ashok
authors.initials: A
authors.lastname: Bhandari
authors.forename: Claire M
authors.initials: CM
authors.lastname: Moody
authors.forename: Joy A
authors.initials: JA
authors.lastname: Miguel
authors.forename: Steven W
authors.initials: SW
authors.lastname: Ferla
authors.forename: M Nuria
authors.initials: MN
authors.lastname: De Francisco
authors.forename: Brian T
authors.initials: BT
authors.lastname: Frederick
authors.forename: Siqun
authors.initials: S
authors.lastname: Zhou
authors.forename: Natalie
authors.initials: N
authors.lastname: Macher
authors.forename: Larry
authors.initials: L
authors.lastname: Jang
authors.forename: Jennifer D
authors.initials: JD
authors.lastname: Irvine
authors.forename: J Russell
authors.initials: JR
authors.lastname: Grove
mesh_terms: D000818:Animals; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D063065:Organophosphonates / Q000138:chemical synthesis / Q000494:pharmacology; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D007004:Hypoglycemic Agents; D063065:Organophosphonates; D013449:Sulfonamides; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases