Antirheumatic agents. III. Novel methotrexate derivatives bearing an indoline ring and a modified ornithine or glutamic acid.
The synthesis, biological profile and structure-activity relationship of various methotrexate (MTX) derivatives bearing an indoline ring are described. In particular, Nb-(3-carboxyphenyl)-N alpha-[1-[(2,4-diaminopteridin-6-yl)-methyl] indoline-5-ylcarbonyl]-L-glutamine (3d), compared to MTX, exhibited an enhanced anti-proliferative effect on human peripheral blood mononuclear cells obtained from healthy volunteers.
Matsuoka
H
H
Fuji Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan.
Kato
N
N
Ohi
N
N
Miyamoto
K
K
Mihara
M
M
Takeda
Y
Y
D018501:Antirheumatic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D018698:Glutamic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008727:Methotrexate / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009952:Ornithine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D018501:Antirheumatic Agents; D007211:Indoles; D018698:Glutamic Acid; D009952:Ornithine; D008727:Methotrexate