US 7,166,590 B2 · Amino acid derivatives

Abstract

A compound of the formula (I): [wherein R1 is (substituted) alkyl, alkoxy, phenyl, hetero ring etc.; A is bond, CO, SO2; R2 is H, (substituted) alkyl etc.; D is alkylene etc.; E is COO, OCO, O, S, SO, SO2 etc.; R3 is (substituted) alkyl, carbocyclic ring, hetero ring; J is O, NR16 (R16 is H, substituted alkyl); R4 is (substituted) alkyl, carbocyclic ring, hetero ring.] or non-toxic salt thereof, and an N-type calcium channel blocker comprising it as an active ingredient. The compounds of the formula (I) possess an inhibitory action on N-type calcium channel, so they are useful as agent for the prevention and/or treatment of cerebral infarct, transient ischemic attack, encephalomyelopathy after cardiac operation, spinal angiopathy, hypertension with stress, neurosis or epilepsy etc. or agent for the treatment of pain.

An amino acid compound of the formula (I):

wherein R1 is
a 5-15 membered saturated, partially saturated or unsaturated mono-cyclic or bi-cyclic hetero ring containing 1-2 nitrogen atoms, 1-2 oxygen atoms and/or one sulfur atom, (with the proviso that, all 5-15 membered saturated, partially saturated or unsaturated mono-cyclic or bi-cyclic hetero rings containing 1-2 nitrogen atoms, 1-2 oxygen atoms and/or one sulfur atom in the R1 group may be substituted by 1˜3 substituents selected from the following (i)˜(xi);
(i) C1-4 alkyl,
(ii) C1-4 alkoxy,
(iii) phenyl,
(iv) phenoxy,
(v) benzyloxy,
(vi) —SR5 (in which R5 is hydrogen or C1-4 alkyl),
(vii) C2-5 acyl,
(viii) halogen,
(ix) C1-4 alkoxycarbonyl,
(x) nitro,
(xi) —NR6R7 (in which R6 and R7 each independently, is hydrogen,
C1-4 alkyl or C1-4 alkoxycarbonyl, or R6 and R7 taken together with the nitrogen atom to which they are attached may represent a 5˜7 membered saturated hetero ring optionally containing another one nitrogen atom or one oxygen atom));
A is bond, —CO— or —SO2—,
R2 is hydrogen or C1-4 alkyl optionally substituted by one phenyl;
D is C1-4 alkylene or C2-4 alkenylene;
E is
1) —OCO—,
2) —CONR8— (in which R8 is hydrogen or C1-4 alkyl),
3) —NR9CO— (in which R9 is hydrogen or C1-4 alkyl),
4) —O——,
5) —S—,
6) —SO—,
7) —SO2—,
8) —NR10— (in which R10 is hydrogen or C1-4 alkyl),
9) —CO—,
10) —SO2NR11— (in which R11 is hydrogen or C1-4 alkyl), or
11) —NR12SO2— (in which R12 is hydrogen or C1-4 alkyl);
R3 is
C1-4 alkyl substituted by C3-10 mono-, bi- and bridged carbocyclic ring (with the proviso that, all C3-10 mono-, bi- and bridged carbocyclic rings in R3, may be substituted by 1˜3 substituents selected from the following (i)˜(xi);
(i) C1-4 alkyl,
(ii) C1-4 alkoxy,
(iii) phenyl,
(iv) phenoxy,
(v) benzyloxy,
(vi) —SR13 (in which R13 is hydrogen or C1-4 alkyl),
(vii) C2-5 acyl,
(viii) halogen,
(ix) C1-4 alkoxycarbonyl,
(x) nitro,
(xi) —NR14R15 (in which R14 and R15 each independently, is hydrogen,
C1-4 alkyl or C1-4 alkoxycarbonyl, or R14 and R15 taken together with the nitrogen atom to which they are attached may represent a 5˜7 membered saturated hetero ring optionally containing another one nitrogen atom or one oxygen atom));
J is —O— or —NR16— (in which R16 is hydrogen or C1-4 alkyl);
R4 is
a C1-8 alkyl substituted by C3-10 mono-, bi- and bridged carbocyclic ring (with the proviso that, all C3-10 mono-, bi- and bridged carbocyclic rings in R4, may be substituted by 1˜3 of substituents selected from the following (i)˜(xi);
(i) C1-4 alkyl,
(ii) C1-4 alkoxy,
(iii) phenyl,
(iv) phenoxy,
(v) benzyloxy,
(vi) —SR20 (in which R20 is hydrogen or C1-4 alkyl),
(vii) C2-5 acyl,
(viii) halogen,
(ix) C1-4 alkoxycarbonyl,
(x) nitro,
(xi) —NR21R22 (in which R21 and R22 each independently, is hydrogen,
C1-4 alkyl or C1-4 alkoxycarbonyl, or R21 and R22 taken together with the nitrogen atom to which they are attached may represent a 5˜7 membered saturated hetero ring optionally containing another one nitrogen atom or one oxygen atom))
a non-toxic salt thereof, or a hydrate thereof.

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Amino acid derivatives

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Amino acid derivatives

Life of this patent

Abstract

Claims8