Antirheumatic Agents. I. Novel Methotrexate Derivatives Bearing an Indoline Moiety
| Autor: | Noriaki Maruyama, Keiichi Yano, Hiroshi Suzuki, Nobuaki Kato, Hiroharu Matsuoka, Keiichiro Tsuji, Masahiko Mihara, Yasuhisa Takeda |
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| Rok vydání: | 1996 |
| Předmět: |
Male
Pharmacology Peripheral blood mononuclear cell chemistry.chemical_compound In vivo Drug Discovery medicine Animals Humans Moiety Cells Cultured Chemistry Synovial Membrane General Chemistry General Medicine medicine.disease Arthritis Experimental In vitro Rats Antirheumatic Agents Methotrexate Biochemistry Rheumatoid arthritis Indoline Leukocytes Mononuclear Cell Division medicine.drug |
| Zdroj: | Chemical and Pharmaceutical Bulletin. 44:1332-1337 |
| ISSN: | 1347-5223 0009-2363 |
| Popis: | Various novel methotrexate (MTX) derivatives bearing an indoline moiety were synthesized and tested for biological activities using human peripheral blood mononuclear cell (hPBMC) and human synovial cells (hSC) derived from patients with rheumatoid arthritis (RA). Compounds having potent activity in vitro were further evaluated using an adjuvant arthritis model in vivo. N-[1-(2,4-Diamino-6-pteridinylmethyl)indoline-5-carbonyl]-L-glutam ic acid 2f showed more potent activities than MTX in vitro and in vivo, and N-[1-(2,4-diamino-6-pteridinylmethyl)-indoline-5-carbonyl]-L-2-ami noadipic acid 2d exhibited fairly good activities in vitro and considerable activity in vivo. Compound 2d was, as expected, not sensitive to folyl-polyglutamate synthetase (FPGS) and did not undergo polyglutamation, a process which may be responsible for a side-effect during MTX therapy. |
| Databáze: | OpenAIRE |
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