Pyridylmethylthio derivatives as VEGF inhibitors: part 2.
Optimization of compounds 5 and 6 led to the discovery of VEGF inhibitor 10g which reduced CYP inhibition. It was highly active in vitro (VEGF induced HUVEC proliferation assay) and showed efficacies in three disease models in vivo (cancer, RA, and AMD).
Research and Development Center, Santen Pharmaceutical Co. Ltd, 8916-16 Takayama-cho Ikoma-shi, Nara 630-0101, Japan. hisashi.tajima@santen.co.jp
Hisashi
H
Tajima
Takahiro
T
Honda
Kenji
K
Kawashima
Yoshimasa
Y
Sasabuchi
Minoru
M
Yamamoto
Masakazu
M
Ban
Kazuyoshi
K
Okamoto
Kenji
K
Inoue
Takaaki
T
Inaba
Yuriko
Y
Takeno
Takashi
T
Tsuboi
Asaka
A
Tonouchi
Hiroyuki
H
Aono
D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D002478:Cells, Cultured; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D011725:Pyridines / Q000737:chemistry*; D014183:Transplantation, Heterologous; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D011725:Pyridines; D042461:Vascular Endothelial Growth Factor A; D003577:Cytochrome P-450 Enzyme System