Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1994-05-12
1996-07-23
Shah, Mukund J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
514 19, 544 62, 544143, 544373, 546168, 546201, 546256, 546 14, 5462774, 5462781, 548455, 548496, 530331, 540481, 540597, 540598, 540583, A61K 3702, C07K 508
Patent
active
055389503
DESCRIPTION:
BRIEF SUMMARY
This application is the national phase, filed under 37 C.F.R. 1.371 of PCT/JP92/01405, filed Oct. 30, 1992.
The present invention relates to new compound and a pharmaceutically acceptable salt thereof.
More particularly, it relates to new peptide compound and a pharmaceutically acceptable salt thereof which have pharmacological activities such as endotheline antagonistic activity and the like, to processes for its preparation, to a pharmaceutical composition comprising the same, and to a method of using the same therapeutically in the treatment and the prevention of endothelin mediated diseases such as hypertension, and the like.
One object of the present invention is to provide new and useful peptide compound and a pharmaceutically acceptable salt thereof which have pharmacological activities such as endothelin antagonistic activity and the like.
Another object of the present invention is to provide processes for the preparation of said peptide compound and a salt thereof.
A further object of the present invention is to provide a pharmaceutical composition comprising, as an active ingredient, said peptide compound or a pharmaceutically acceptable salt thereof.
Still further object of the present invention is to provide a method of using the same for the treatment and the prevention of endothelin mediated diseases such as hypertension, and the like.
DISCLOSURE OF INVENTION
The object compound of the present invention can be represented by the following general formula (I). ##STR2## in which R.sup.3 is hydrogen or lower alkyl,
R.sup.4 is pyridyl(lower)alkyl; and
R.sup.1 is C.sub.3 -C.sub.8 alkyleneamino, N,N-di(lower)alkylamino, N-lower alkyl-N-arylamino, N-lower alkyl-N-C.sub.3 -C.sub.8 cycloalkylamino, or C.sub.5 -C.sub.10 bicyclic alkyleneamino,
R.sup.2 is lower alkyl,
R.sup.5 is C.sub.3 -C.sub.8 alkyleneamino, N,N-di(lower)alkylamino, morpholino, thiomorpholino, N',N'-di(lower)alkylhydrazino, morpholinoamino, lower alkylpiperazinylamino, lower alkoxy(lower)alkylamino, morpholino(lower)alkylamino, C.sub.3 -C.sub.8 alkyleneamino(lower)alkylamino which may be substituted by oxo, or pyridyl(lower)alkylamino, and
A is lower alkylene; or
R.sup.1 is piperidin-1-yl, lower alkylpiperidin-1-yl, octahydroazocin-1-yl, indolin-1-yl, 1,2,3,4-tetrahydroquinolin-1-yl, N,N-di(lower)alkylamino, N-lower alkyl-N-arylamino, N-lower alkyl-N-C.sub.3 -C.sub.8 cycloalkylamino, or C.sub.5 -C.sub.10 bicyclic alkyleneamino,
R.sup.2 is lower alkyl,
R.sup.5 is amino or lower alkylamino, and
A is lower alkylene; or
R.sup.1 is piperidin-1-yl, octahydroazocin-1-yl, N,N-di(lower)alkylamino, or C.sub.5 -C.sub.10 bicyclic alkyleneamino,
R.sup.2 is lower alkyl,
R.sup.5 is amino, lower alkylamino, N,N-di(lower)alkylamino, C.sub.3 -C.sub.8 alkyleneamino, or morpholino, and
A is --NH--; or
R.sup.1 is hexahydro-1H-azepin-1-yl,
R.sup.2 is isobutyl,
R.sup.5 is ethylamino, and
A is methylene; or
R.sup.1 is N-[1-(dimethylcarbamoyl)-2,2-dimethylpropyl]amino,
R.sup.2 is isobutyl,
R.sup.5 is amino, and
A is --NH--; or
R.sup.1 is N,N-di(lower)alkylamino, 1,2,3,4-tetrahydroquinolin-1-yl, N-lower alkyl-N-arylamino, or N-lower alkyl-N-C.sub.3 -C.sub.8 cycloalkylamino,
R.sup.2 is lower alkyl,
R.sup.5 is hydroxy or CO--R.sup.5 is protected carboxy, and
A is lower alkylene; or
R.sup.1 is C.sub.5 -C.sub.10 bicyclic alkyleneamino,
R.sup.2 is lower alkyl,
R.sup.5 is hydroxy or CO--R.sup.5 is protected carboxy, and
A is lower alkylene or --NH--; or
R.sup.1 is N-ethyl-N-(1-ethylpropyl)amino, N-ethyl-N-isopropylamino, N-ethyl-N-neopentylamino, or N-(1-ethylpropyl)-N-propylamino,
R.sup.2 is isobutyl,
R.sup.5 is hydroxy or CO--R.sup.5 is protected carboxy, and
A is --NH--; or
R.sup.1 is piperidin-1-yl,
R.sup.2 is isobutyl,
R.sup.5 is hydroxy or CO--R.sup.5 is protected carboxy, and
A is methylene; or
R.sup.1 is hexahydro-1H-azepin-1-yl,
R.sup.2 is propyl,
R.sup.5 is hydroxy or CO--R.sup.5 is protected carboxy, and
A is --NH--;
Particularly, the compound represented by the following formula (I') is more useful as an endothelin antagonist and the like. ##STR3## in
REFERENCES:
patent: 5284828 (1994-02-01), Hemmi et al.
patent: 5321032 (1994-06-01), Matsuo et al.
Fukami Naoki
Hashimoto Masashi
Hemmi Keiji
Kayakiri Natsuko
Neya Masahiro
Fujisawa Pharmaceutical Co. Ltd.
Grumbling Matthew V.
Shah Mukund J.
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