Synthesis of a magnosalin derivative, 4-(3,4,5-trimethoxyphenyl)-6-(2,4,5-trimethoxyphenyl)-2-diethylaminopyrimidine, and the anti-angiogenic and anti-rheumatic effect on mice by oral administration.
We describe here the synthesis and the anti-angiogenic and anti-rheumatic activities of 4-(3,4,5-trimethoxyphenyl)-6-(2,4,5-trimethoxyphenyl)-2-diethylaminopyrimidine (TAS-202), a derivative of magnosalin, which is a natural product isolated from Flos magnoliae. TAS-202 inhibited the proliferation of vascular endothelial cells more potently than magnosalin, and when given orally it inhibited basic fibroblast growth factor (bFGF)-induced angiogenesis and collagen-induced arthritis in mice. This magnosalin derivative with anti-angiogenic effects is a candidate for the treatment of rheumatoid arthritis.
Tanaka
Katsunao
K
Pharmacobioregulation Research Laboratory, Taiho Pharmaceutical Co., Ltd., 1-27Misugidai, Hanno-City, 357-8527, Saitama, Japan. katsunaot@taiho.co.jp
Konno
Yasuo
Y
Kuraishi
Yasushi
Y
Kimura
Ikuko
I
Suzuki
Takashi
T
Kiniwa
Mamoru
M
D000284:Administration, Oral; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D001168:Arthritis / Q000139:chemically induced / Q000188:drug therapy; D002455:Cell Division / Q000187:drug effects; D003503:Cyclobutanes / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006454:Hemoglobins / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D023421:Models, Animal; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011743:Pyrimidines / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
C475781:4-(3,4,5-trimethoxyphenyl)-6-(2,4,5-trimethoxyphenyl)-2-diethylaminopyrimidine; D020533:Angiogenesis Inhibitors; D018501:Antirheumatic Agents; D003503:Cyclobutanes; D006454:Hemoglobins; D011743:Pyrimidines; D016222:Fibroblast Growth Factor 2; C069674:magnosalin