Alpha-ketoamide derivative, and production method and use thereof
The present invention provides a compound represented by the formula (I): (wherein R 1 is a lower alkyl substituted by a lower alkoxy or a heterocyclic group, or a heterocyclic group; R 2 is a lower alkyl optionally substituted by a phenyl; and R 3 is a lower alkyl optionally substituted by a halogen, a lower alkoxy or a phenyl, or a fused polycyclic hydrocarbon group), which is well absorbed orally, exhibits durability of good blood level and has potent calpain inhibitory activity.
1. A compound represented by the formula (I)
wherein R 1 is
(1) a group represented by the formula (IIb) in which n is an integer of 2 to 5,
(2) a straight or branched C 1-6 alkyl substituted by a pyridyl group optionally having a C 1-3 alkyl substituent on the pyridine ring, or
(3) a tetrahydrofuranyl group or a tetrahydropyranyl group;
R 2 is a straight or branched C 1-6 alkyl, optionally substituted by a phenyl; and
R 3 is hydrogen, a straight or branched C 1-6 alkyl or is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.
2. The compound as claimed in claim 1 , wherein R 1 is a group of the formula (IIb)
in which n is an integer of 2 to 5.
3. The compound as claimed in claim 1 , wherein R 3 is cyclopropyl.
4. The compound of claim 1 selected from the group consisting of ((1S)-1-((((1S)-1-benzyl-2,3-dioxo-3-(cyclopropylamino)propyl)amino)carbonyl)-3-methylbutyl)carbamic acid 5-methoxy-3-oxapentyl ester, ((1S)-1-((((1S)-1-benzyl-2,3-dioxo-3-(cyclopropylamino)propyl)amino)carbonyl)-3-methylbutyl)carbamic acid 8-methoxy-3,6-dioxaoctyl ester, ((1S)-1-((((1S)-1-benzyl-2,3-dioxo-3-(cyclopropylamino)propyl)amino)carbonyl)-3-methylbutyl)carbamic acid 11-methoxy-3,6,9-trioxaundecanyl ester, or ((1S)-1-((((1S)-1-benzyl-3-(cyclopropylamino)-2,3-dioxopropyl)amino)carbonyl)-3-methylbutyl)carbamic acid 2-(pyridin-2-yl)ethyl ester.
5. A medicament comprising the compound as claimed in claim 1 .
6. The compound as claimed in claim 1 , which is ((1S)-1-((((1S)-1-benzyl-2,3-dioxo-3-(cyclopropylamino)propyl)amino)carbonyl)-3-methylbutyl)carbamic acid 5-methoxy-3-oxapentyl ester.