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.
Ahn
Jin Hee
JH
Medicinal Science Division, Korea Research Institute of Chemical Technology, Taejon 305-600, Republic of Korea.
Cho
Sung Yun
SY
Ha
Jae Du
JD
Chu
So Young
SY
Jung
Sun Ho
SH
Jung
Yoon Sung
YS
Baek
Ji Yoen
JY
Choi
In Kyung
IK
Shin
Eun Young
EY
Kang
Seung Kyu
SK
Kim
Sung Soo
SS
Cheon
Hyae Gyeong
HG
Yang
Sung-Don
SD
Choi
Joong-Kwon
JK
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