1,2,3,4-Tetrahydroisoquinolinyl sulfamic acids as phosphatase PTP1B inhibitors.
High-throughput screening of the P&GP corporate repository against several protein tyrosine phosphatases identified the sulfamic acid moiety as potential phosphotyrosine mimetic. Incorporation of the sulfamic acid onto a 1,2,3,4-tetrahydroisoquinoline scaffold provided a promising starting point for PTP1B inhibitor design.
Klopfenstein
Sean R
SR
Procter & Gamble Pharmaceuticals, Health Care Research Center, 8700 Mason-Montgomery Road, Mason, OH 45040, USA. klopfenstein.sr@pg.com
Evdokimov
Artem G
AG
Colson
Anny-Odile
AO
Fairweather
Neil T
NT
Neuman
Jeffrey J
JJ
Maier
Matthew B
MB
Gray
Jeffrey L
JL
Gerwe
Gina S
GS
Stake
George E
GE
Howard
Brian W
BW
Farmer
Julie A
JA
Pokross
Matthew E
ME
Downs
Thomas R
TR
Kasibhatla
Bhavani
B
Peters
Kevin G
KG
D001665:Binding Sites; D001667:Binding, Competitive; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D018716:Molecular Mimicry; D019000:Phosphotyrosine / Q000378:metabolism; D011485:Protein Binding; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D013451:Sulfonic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D044005:Tetrahydroisoquinolines / Q000737:chemistry*; D018909:src Homology Domains
D004791:Enzyme Inhibitors; D008024:Ligands; D013451:Sulfonic Acids; D044005:Tetrahydroisoquinolines; D019000:Phosphotyrosine; C014843:1,2,3,4-tetrahydroisoquinoline; C005741:sulfamic acid; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases