[0004] The immunohistochemical analysis of each tissue was performed as follows. At first, anti-human type-X sPLA 2 antibody was added to the slides prepared from normal adult cerebral tissues or cerebral tissues prepared from patients of Alzheimer's disease and incubated for several hours. Next, in order to examine the expression of type-X sPLA 2 in the tissues, the expression of type-X sPLA 2 was visualized by using the methods such as the immunohistochemical labeling to detect the type-X sPLA 2 signals. Consequently, the type-X sPLA 2 signals were detected in the slides prepared from cerebral tissues prepared from patients of Alzheimer's disease, suggesting that the expression of type-X sPLA 2 is elevated in cerebral tissues prepared from patients of Alzheimer's disease.

[0005] In addition, the inventors of the present invention performed the experiments for neutralization of type-X sPLA 2 signals. Precisely, before the addition of anti-human type-X sPLA 2 antibody to the slides, the slides were incubated with the purified type-X sPLA 2 protein for several hours. Hereafter, the slides were processed as the same procedures as described above to examine the type-X sPLA 2 signals. Consequently, the type-X sPLA 2 signals were disappeared in the slides prepared from cerebral tissues.

[0006] Thus, the elevated expression of type-X sPLA 2 was confirmed in cerebral tissues prepared from patients of Alzheimer's disease and the inventors of the present invention achieved the following present invention.

[0007] That is to say, the present invention relates to I) a composition for prevention or treatment of Alzheimer's disease which contains a type-X sPLA 2 inhibitor as an active ingredient.

[0008] In more detail, the present invention relates to the following II) to XIII).

[0009] II) A composition for prevention or treatment of Alzheimer's disease which contains as an active ingredient a compound represented by the formula (I): 1 embedded image

[0010] wherein Ring A is represented by the formula (a) to (d): 2 embedded image

[0011] wherein R 1 and R 2 are each independently hydrogen atom, non-interfering substituent, or —(L 1 )-(acidic group) wherein L 1 is an acid linker having an acid linker length of 1 to 5, provided that one of the R 1 and R 2 is —(L 1 )-(acidic group);

[0012] R 3 and R 4 are each independently hydrogen atom, non-interfering substituent, carbocyclic group, carbocyclic group substituted with a non-interfering substituent(s), heterocyclic group, or heterocyclic group substituted by a non-interfering substituent(s); and

[0013] —B— is represented by the formula (e) to (h): 3 embedded image

[0014] wherein R 5 is (j) C1 to C20 alkyl, C2 to C20 alkenyl, C2 to C20 alkynyl, carbocyclic group, or heterocyclic group, (k) the group represented by (j) each substituted independently with at least one group selected from non-interfering substituents, or —(L 2 )—R 8 wherein L 2 is a divalent linking group of 1 to 18 atom(s) selected from hydrogen atom(s), nitrogen atom(s), carbon atom(s), oxygen atom(s), and sulfur atom(s), and

[0015] R 8 is a group selected from the groups (j) and (k);

[0016] R 6 is hydrogen atom, halogen, C1 to C3 alkyl, C3 to C4 cycloalkyl, C3 to C4 cycloalkenyl, C1 to C3 alkyloxy, or C1 to C3 alkylthio;

[0017] R 7 is hydrogen atom or non-interfering substituent;

[0018] R A is represented by the formula: 4 embedded image

[0019] wherein R 9 and R 10 are each independently hydrogen atom, C1 to C3 alkyl, or halogen;

[0020] X and Y are each independently oxygen atom or sulfur atom; and

[0021] Z is —NH 2 or —NHNH 2 ;

[0022] R B is —CONH 2 or —CONHNH 2 ; and,

[0023] Ring D is cyclohexene ring or benzene ring;

[0024] provided that Ring A is (b), (c), or (d) when —B— is (e) or (f), a prodrug thereof, its pharmaceutically acceptable salt, or its solvate.

[0025] III) A composition for prevention or treatment of Alzheimer's disease which contains a compound, a prodrug thereof, its pharmaceutically acceptable salt, or its solvate as described in II) as an active ingredient, wherein R 1 is hydrogen atom or —(L 3 )—R 11 wherein L 3 is —OCH 2 —, —SCH 2 —, —NH—CH 2 —, —CH 2 —CH 2 —, —O—CH(CH 3 )—, or —O—CH(CH 2 CH 2 C 6 H 5 )—; R 11 is —COOH, —CONHSO 2 C 6 H 5 , —SO 3 H, or —P(O)(OH) 2 ; and

[0026] R 2 is hydrogen atom or —(L 4 )—R 12 wherein L 4 is represented by the formula: 5 embedded image

[0027] wherein R 13 and R 14 are each independently hydrogen atom, C1 to C10 alkyl, C1 to C10 aralkyl, carboxy, alkyloxycarbonyl, or halogen; R 12 is —COOH, —SO 3 H, or —P(O)(OH) 2 , provided R 1 and R 2 are not hydrogen atom at the same time.

[0028] IV) A composition for prevention or treatment of Alzheimer's disease which contains a compound, a prodrug thereof, its pharmaceutically acceptable salt, or its solvate as described in II) or III) as an active ingredient, wherein R 3 is hydrogen atom, C1 to C6 alkyl, C3 to C6 cycloalkyl, aryl, or a heterocyclic group and R 4 is hydrogen atom or halogen.

[0029] V) A composition for prevention or treatment of Alzheimer's disease which contains a compound, a prodrug thereof, its pharmaceutically acceptable salt, or its solvate as described in any one of II) to IV) as an active ingredient, wherein R 5 is —(CH 2 ) 1-6 —R 15 wherein R 15 is represented by the formula: 6 embedded image
  

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