Amino acid derivatives and drugs containing the same as the active ingredient

An amino acid compound of formula (I)

• wherein,
• R1 is a heterocyclic ring, wherein said heterocyclic ring may be substituted with 1-3 of substituent(s) selected from the group consisting of the following (i)-(xi):
• (i) C1-4 alkyl,
• (ii) C1-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) C2-4 alkoxycarbonyl,
• (x) nitro and
• (xi)-NR6R7 (in which R6 and R7 are independently, hydrogen, C1-4 alkyl or C1-4 alkoxycarbonyl, or R6 and R7 taken together with nitrogen atom to which they are attached represents 5-7-membered saturated heterocyclic ring necessarily containing one nitrogen atom and optionally further containing one nitrogen atom or one oxygen atom),
• A is single bond, —CO— or —SO2—,
• R2 is hydrogen or C1-4 alkyl which may be substituted with one phenyl,
• D is C1-4 alkylene or C2-4 alkenylene,
• E is
• 1) —COO—,
• 2) —OCO—,
• 3) —CONR8— (in which R8 is hydrogen or C1-4 alkyl),
• 4) —NR9CO— (in which R9 is hydrogen or C1-4 alkyl),
• 5) —O—,
• 6) —S—,
• 7) —SO—,
• 8) —SO2—,
• 9) —NR10O— (in which R10 is hydrogen or C1-4 alkyl),
• 10) —CO—,
• 11) —SO2NR11— (in which R11 is hydrogen or C1-4 alkyl) or
• 12) —NR12SO2— (in which R12 is hydrogen or C1-4 alkyl),
• R3 is
• 1) carbocyclic ring,
• 2) heterocyclic ring or
• 3) C1-4 alkyl substituted with carbocyclic ring or heterocyclic ring, wherein all the said carbocyclic ring and heterocyclic ring in R3 may be substituted with 1-3 of substituent(s) selected from the group consisting of the following (i)-(xi):
• (i) C1-4 alkyl,
• (ii) C1-4 alkoxy,
• (iii) phenyl,
• (iv) phenoxy,
• (v) benzyloxy,
• (vi) —SR-13 (in which R13 is hydrogen or C1-4 alkyl),
• (vii) C2-5 acyl,
• (viii) halogen,
• (ix) C1-4 alkoxycarbonyl,
• (x) nitro and
• (xi) —NR14R15 (in which R14 and R15 are independently, hydrogen, C1-4 alkyl or C1-4 alkoxycarbonyl, or R14 and R15 taken together with nitrogen atom to which they are attached represents 5-7-membered saturated heterocyclic ring necessarily containing one nitrogen atom and optionally further containing one nitrogen atom or one oxygen atom),
• J is
• 1) —O— or
• 2) —NR16— (in which R16 is hydrogen or C1-4 alkyl),
• R4 is R4−2 or R4−3,
• R4−2 is
• 1) carbocyclic ring,
• 2) heterocyclic ring or
• 3) C1-8 alkyl substituted with 1-3 of substituent(s) selected from the group consisting of the following (i)-(v):
• (i) carbocyclic ring,
• (ii) heterocyclic ring,
• (iii) COOR32 (in which R32 is hydrogen or C1-4 alkyl substituted with one phenyl (in which the said phenyl may be substituted with C1-4 alkoxy),
• (iv) SR33 (in which R33 is hydrogen or C1-4 alkyl) and
• (v) OR34 (in which R34 is hydrogen or C1-4 alkyl),
• provided that when J is —NR16—, R4−2 and R16, taken together with nitrogen atom to which they are attached, may represent heterocyclic ring, wherein at least one ring of all the said carbocyclic ring and heterocyclic ring in R4−2 and the said heterocyclic ring represented by R4−2 and R6, taken together with nitrogen atom to which they are attached, is substituted with one hydroxy or one —O—(C1-4 alkylene)-O—(C1-4 alkyl) and may be substituted with further 1-2 of substituent(s) selected from the group consisting of the following (i)-(xiii):
• (i) C1-4 alkyl,
• (ii) C1-4 alkoxy,
• (iii) phenyl,
• (iv) phenoxy,
• (v) benzyloxy,
• (vi) —SR35 (in which R35 is hydrogen or C1-4 alkyl),
• (vii) C2-5 acyl,
• (viii) halogen,
• (ix) C1-4 alkoxycarbonyl,
• (x) nitro,
• (xi) —NR36R37 (in which R36 and R37 are independently, hydrogen, C1-4 alkyl or C1-4 alkoxycarbonyl, or R36 and R37 taken together with nitrogen atom to which they are attached represents 5-7-membered saturated heterocyclic ring necessarily containing one nitrogen atom and optionally further containing one nitrogen atom or one oxygen atom),
• (xii) hydroxy and
• (xiii) —O—(C1-4 alkylene)-O—(C1-4 alkyl),
• with the proviso that
• when R4−2 is a carbocyclic ring, the carbocyclic ring is substituted with at least one —NR36R37 in which R36 and R37 taken together with the nitrogen atom to which they are attached represents a 5-7 membered saturated heterocyclic ring necessarily containing one nitrogen atom and optionally further containing one nitrogen atom or one oxygen atom, and
• when R4−2 is a C1-8 alkyl substituted with 1-3 substituents, then at least one of the substituents is an optionally-substituted heterocyclic ring, or a carbocyclic ring substituted with at least one —NR36R37 in which R36 and R37 taken together with the nitrogen atom to which they are attached represents a 5-7 membered saturated heterocyclic ring necessarily containing one nitrogen atom and optionally further containing one nitrogen atom or one oxygen atom,
• R4−3 is —L—M,
• —L— is
• 1) -(carbocyclic ring which may be substituted with 1-3 substituent(s))-,
• 2) -(heterocyclic ring which may be substituted with 1-3 substituent(s))- or
• 3) -(C1-4 alkylene)-(carbocyclic ring which may be substituted with 1-3 substituent(s) or heterocyclic ring which may be substituted with 1-3 substituent(s))-,
• provided that when J is —NR16—, L and R16, taken together with nitrogen atom to which they are attached, may represent -(heterocyclic ring which may be substituted with 1-3 of substituent(s))-,
• M is
• 1) carbocyclic ring or heterocyclic ring which may be substituted with 1-3 substituent(s) (with the proviso that when the carbocyclic ring is phenyl, said ring is substituted with at least one substituent(s), and that when the said heterocyclic ring is 5-7-membered saturated heterocyclic ring in which the nitrogen atom in the said heterocyclic ring is bonded to group L shown as
• and which may contain further one nitrogen atom or one oxygen atom, then such a ring is substituted with at least one substituent(s)),
• 2) C1-4 alkyl substituted with 1-2 of substituent(s) selected from the group consisting of the following (i)-(ii):
• (i) carbocyclic ring which may be substituted with 1-3 substituent(s),
• (ii) heterocyclic ring which may be substituted with 1-3 substituent(s),
• 3) —O-(carbocyclic ring or heterocyclic ring which may be substituted with 1-3 of substituent(s)) (with the proviso that when the carbocyclic ring is phenyl, said ring is substituted with at least one substituent(s)),
• 4) —S-(carbocyclic ring or heterocyclic ring which may be substituted with 1-3 of substituent(s)),
• 5) —NR38-(carbocyclic ring or heterocyclic ring which may be substituted with 1-3 of substituent(s)) in which R38 is hydrogen or C1-4 alkyl which may be substituted with one phenyl,
• 6) —O—CH2-(carbocyclic ring which may be substituted with 1-3 of substituent(s)) (with the proviso that when the carbocyclic ring is phenyl, said ring is substituted with at least one substituent(s)),
• 7) —O—(C2-4 alkylene)-(carbocyclic ring which may be substituted with 1-3 of substituent(s)),
• 8) —O—(C1-4 alkylene)-(heterocyclic ring which may be substituted with 1-3 of substituent(s)),
• 9) —S—(C1-4 alkylene)-(carbocyclic ring or heterocyclic ring which may be substituted with 1-3 of substituent(s)),
• 10) —NR39—(C1-4 alkylene)-(carbocyclic ring or heterocyclic ring which may be substituted with 1-3 of substituent(s)) (in which R39 is hydrogen, C1-4 alkyl which may be substituted with one phenyl or C2-5 acyl which may be substituted with 1-3 of halogen) or
• 11) —CO-(carbocyclic ring or heterocyclic ring which may be substituted with 1-3 of substituent(s)),
• wherein the substituent(s) of the said carbocyclic ring and heterocyclic ring in L and M and the said heterocyclic ring represented by each L and R16, L and R17, L and R21, and L and R23 taken together with nitrogen atom to which they are attached is selected from the following (i)-(xiv):
• (i) C1-4 alkyl,
• (ii) C2-4 alkenyl,
• (iii) hydroxy,
• (iv) C1-4 alkoxy,
• (v) —(C1-4 alkylene)-OH,
• (vi) —O—(C14 alkylene)-O—(C1-4 alkyl),
• (vii) halogen,
• (viii) NR40R41 (in which R40 and R41 are independently, hydrogen, C1-4 alkyl or C1-4 alkoxycarbonyl, or R40 and R41 taken together with nitrogen atom to which they are attached represents 5-7-membered saturated heterocyclic ring necessarily containing one nitrogen atom and optionally further containing one nitrogen atom or one oxygen atom),
• (ix) SR42 (in which R42 is hydrogen or C1-4 alkyl),
• (x) nitro,
• (xi) trifluoromethyl,
• (xii) C1-4 alkoxycarbonyl,
• (xiii) oxo and
• (xiv) C2-5 acyl,
• with the proviso that
• at least one optionally substituted heterocyclic ring, or carbocyclic ring substituted with at least one —NR40R41, in which R40 and R41 taken together with the nitrogen atom to which they are attached represents a 5-7 membered saturated heterocyclic ring necessarily containing one nitrogen atom and optionally further containing one nitrogen atom or one oxygen atom, is present in —L—M, or a non-toxic salt thereof or a hydrate thereof.