Provided are: a five-membered ring compound represented by formula (1) or a pharmaceutically acceptable salt thereof; and a medicine containing the compound or salt. The compound or salt inhibits the infiltration of leukocytes such as eosinophils and lymphocytes, is effective as a therapeutic agent for various kinds of inflammation, and is so safe that the compound or salt can be taken for long.
In formula (1), R
1
is (substituted) phenyl or pyridyl; R
2
is (substituted) pyrazinediyl, pyrimidinediyl, or pyridazinediyl; R
3
to R
5
each is alkyl (provided that —N(R
4
)R
5
may be morpholino); and Y
2
is alkylene.
作者:Elvio Bellasio、Ambrogio Campi、Nunzio Di Mola、Emiliana Baldoli
DOI:10.1021/jm00374a024
日期:1984.8
The hypothesis that the side effects of hydralazine, such as mutagenicity and lupus erythematosus like syndrome, might be due to the NHNH2 group prompted us to incorporate part of this moiety into a pyrrole ring. Therefore, we prepared a series of N-1H-pyrrol-1-yl-3-pyridazinamines and a limited number of N-1H-pyrrol-1-yl-1-phthalazinamines by reaction of 3-hydrazinopyridazines and 1-hydrazinophthalazines with gamma-diketones. Most of these compounds, especially in the pyridazine series, showed moderate to strong antihypertensive activity in spontaneously hypertensive rats. The decrease in blood pressure generally had a slow onset after either oral or intravenous administration. N-(2,5-Dimethyl-1H-pyrrol-1-yl)-6-(4-morpholinyl)-3-pyridazinamine hydrochloride (30) (MDL 899) showed no mutagenic activity in several tests and is now in clinical trials in patients.
EP2272844
申请人:——
公开号:——
公开(公告)日:——
US4016162A
申请人:——
公开号:US4016162A
公开(公告)日:1977-04-05
Bellasio; Ripamonti; Parravicini, Farmaco, Edizione Scientifica, 1972, vol. 27, # 7, p. 591 - 600