Synthesis and PTP1B inhibition of 1,2-naphthoquinone derivatives as potent anti-diabetic agents.
A new series of 1,2-naphthoquinone derivatives was synthesized by various synthetic methods and evaluated for their ability to inhibit protein tyrosine phosphatase 1B (PTP1B). 1,2-Naphthoquinone derivatives with substituent at R(4) position showed submicromolar inhibitory activity, and compound 24 demonstrated 10- to 60-fold selectivity against the tested phosphatases. Also, several 4-aryl-1,2-naphthoquinone derivatives with substituents at R(3), R(6), R(7), or/and R(8) showed submicromolar inhibitory activity and good plasma stability.
Medicinal Science Division, Korea Research Institute of Chemical Technology, Taejon 305-600, Republic of Korea.
Jin Hee
JH
Ahn
Sung Yun
SY
Cho
Jae Du
JD
Ha
So Young
SY
Chu
Sun Ho
SH
Jung
Yoon Sung
YS
Jung
Ji Yoen
JY
Baek
In Kyung
IK
Choi
Eun Young
EY
Shin
Seung Kyu
SK
Kang
Sung Soo
SS
Kim
Hyae Gyeong
HG
Cheon
Sung-Don
SD
Yang
Joong-Kwon
JK
Choi
D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D009285:Naphthoquinones / Q000737:chemistry* / Q000494:pharmacology*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D009285:Naphthoquinones; C040756:1,2-naphthoquinone; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases