Compound

Abstract

A compound represented by Formula (I) is provided: wherein Ar 1 represents an imidazolyl group which may be substituted with 1 to 3 substituents; Ar 2 represents a phenyl group which may be substituted with 1 to 3 substituents; X 1 represents (1) —C≡C— or (2) a double bond etc., which may be substituted; R 1 and R 2 represent, for example, a C1-6 alkyl group which may be substituted, or a pharmacologically acceptable salt thereof and to the use thereof as pharmaceutical agents.

1 . A compound represented by Formula (I) or a pharmacologically acceptable salt thereof: 
       
         
           
           
               
               
           
         
         wherein Ar 1  represents an imidazolyl group which may be substituted with 1 to 3 substituents selected from Substituent Group A1 shown below; 
         Ar 2  represents a phenyl group which may be substituted with 1 to 3 substituents selected from Substituent Group A2 shown below; 
         X 1  represents (1) —C≡C— or (2) —CR 3 ═CR 4 —, wherein each of R 3  and R 4  is a substituent selected from Substituent Group A3 shown below; 
         R 1  represents a phenylalkyl or naphthylalkyl; and 
         R 2  represents a hydrogen or an alkyl group; 
       
       Substituent Group A1:
 (1) a hydrogen atom, (2) a halogen atom, and (3) a C1-6 alkyl group (wherein the C1-6 alkyl group may be substituted with 1 to 3 substituents selected from the group consisting of a halogen atom, a hydroxyl group, a cyano group, a C1-6 alkoxy group, a C3-8 cycloalkyl group and a C1-6 alkylcarbonyl group); 
 
       Substituent Group A2:
 (1) a hydrogen atom, (2) a halogen atom, (3) a hydroxyl group, (4) a cyano group, (5) a C1-6 alkoxy group (wherein the C1-6 alkoxy group may be substituted with 1 to 3 substituents selected from the group consisting of a halogen atom, a cyano group, a C1-6 alkoxy group, a C2-6 alkenyl group, a C2-6 alkynyl group and a C3-8 cycloalkyl group), (6) an alkyl group, (7) trifluoromethane, (8) a phenyl, (9) nitro, and (10) an amino; 
 
       Substituent Group A3: (1) a hydrogen atom, (2) a halogen atom, (3) a cyano group, and (4) a C1-6 alkyl group (wherein the C1-6 alkyl group may be substituted with 1 to 3 substituents selected from the group consisting of a formyl group, a halogen atom, a hydroxyl group, a hydroxyl group having a protecting group, a cyano group, a C2-6 alkenyl group, a C2-6 alkynyl group, a C3-8 cycloalkyl group, a C1-6 alkoxy group, a C1-6 alkylthio group, a C1-6 alkylsulfinyl group, a C1-6 alkylsulfonyl group, a C1-6 alkylcarbonyl group, an amino group (wherein the amino group may be substituted with a C1-6 alkyl group optionally having 1 to 5 halogen atoms), a 6- to 14-membered aromatic hydrocarbon ring group which may be substituted with 1 to 3 substituents selected from Substituent Group A4, a 5- to 14-membered aromatic heterocyclic group which may be substituted with 1 to 3 substituents selected from Substituent Group A4, a 3- to 14-membered non-aromatic hydrocarbon ring group which may be substituted with 1 to 3 substituents selected from Substituent Group A4, a 5- to 14-membered non-aromatic heterocyclic group which may be substituted with 1 to 3 substituents selected from Substituent Group A4 and —X-A (wherein X represents an imino group, —O— or —S— and A represents a 6- to 14-membered aromatic hydrocarbon ring group or 5- to 14-membered aromatic heterocyclic group which may be substituted with 1 to 3 substituents selected from Substituent Group A4)); 
       Substituent Group A4:
 (1) a hydrogen atom, 
 (2) a halogen atom, 
 (3) a hydroxyl group, 
 (4) a cyano group, 
 (5) a nitro group, 
 (6) a C3-8 cycloalkyl group, 
 (7) a C2-6 alkenyl group, 
 (8) a C2-6 alkynyl group, 
 (9) a C3-8 cycloalkoxy group, 
 (10) a C3-8 cycloalkylthio group, 
 (11) a formyl group, 
 (12) a C1-6 alkylcarbonyl group, 
 (13) a C1-6 alkylthio group, 
 (14) a C1-6 alkylsulfinyl group, 
 (15) a C1-6 alkylsulfonyl group, 
 (16) a hydroxyimino group, 
 (17) a C1-6 alkoxyimino group, 
 (18) a C1-6 alkyl group (wherein the C1-6 alkyl group may have 1 to 3 substituents selected from the following substituent group:
 (a) a halogen atom, 
 (b) a hydroxyl group, 
 (c) a cyano group, 
 (d) a C3-8 cycloalkyl group, 
 (e) a C1-6 alkylthio group, 
 (f) a C1-6 alkylsulfinyl group, 
 (g) a C1-6 alkylsulfonyl group, 
 (h) a C1-6 alkylcarbonyl group, 
 (i) a hydroxyimino group, 
 (j) a C1-6 alkoxyimino group, 
 (k) a C1-6 alkoxy group (wherein the C1-6 alkoxy group may be substituted with a hydroxyl group), 
 (l) a carbamoyl group (wherein the carbamoyl group may be substituted with 1 to 2 substituents selected from the group consisting of a C1-6 alkyl group, a C2-6 alkenyl group and a C2-6 alkynyl group), 
 (m) a 6- to 14-membered aromatic hydrocarbon ring group (wherein the 6- to 14-membered aromatic hydrocarbon ring group may be substituted with 1 to 3 substituents selected from Substituent Group A4-1 shown below), 
 (n) a 3- to 14-membered non-aromatic hydrocarbon ring group (wherein the 3- to 14-membered non-aromatic hydrocarbon ring group may be substituted with 1 to 3 substituents selected from Substituent Group A4-1 shown below), 
 (o) a 5- to 14-membered aromatic heterocyclic group (wherein the 5- to 14-membered aromatic heterocyclic group may be substituted with 1 to 3 substituents selected from Substituent Group A4-1 shown below), 
 (p) a 5- to 14-membered non-aromatic heterocyclic group (wherein the 5- to 14-membered non-aromatic heterocyclic group may be substituted with 1 to 3 substituents selected from Substituent Group A4-1 shown below) and 
 (q) —X-A (wherein X represents an imino group, —O— or —S— and A represents a 6- to 14-membered aromatic hydrocarbon ring group or 5- to 14-membered aromatic heterocyclic group which may be substituted with 1 to 3 substituents selected from Substituent Group A4-1 shown below)), 
 
 (19) a C1-6 alkoxy group, 
 (20) an amino group (wherein the amino group may be substituted with 1 to 2 substituents selected from the group consisting of a C1-6 alkyl group which may be substituted with a 6- to 14-membered aromatic hydrocarbon ring group, a C2-6 alkenyl group and a C2-6 alkynyl group), 
 (21) a carbamoyl group (wherein the carbamoyl group may be substituted with 1 to 2 substituents selected from the group consisting of a C1-6 alkyl group, a C2-6 alkenyl group and a C2-6 alkynyl group), 
 (22) a 6- to 14-membered aromatic hydrocarbon ring group (wherein the 6- to 14-membered aromatic hydrocarbon ring group may be substituted with 1 to 3 substituents selected from Substituent Group A4-1 shown below), 
 (23) a 5- to 14-membered aromatic heterocyclic group (wherein the 5- to 14-membered aromatic heterocyclic group may be substituted with 1 to 3 substituents selected from Substituent Group A4-1 shown below), 
 (24) a 3- to 14-membered non-aromatic hydrocarbon ring group (wherein the 3- to 14-membered non-aromatic hydrocarbon ring group may be substituted with 1 to 3 substituents selected from Substituent Group A4-1 shown below), 
 (25) a 5- to 14-membered non-aromatic heterocyclic group (wherein the 5- to 14-membered non-aromatic heterocyclic group may be substituted with 1 to 3 substituents selected from Substituent Group A4-1 shown below), 
 (26) a C2-6 alkenyloxy group, 
 (27) a C2-6 alkynyloxy group, 
 (28) a C3-8 cycloalkylsulfinyl group, 
 (29) a C3-8 cycloalkylsulfonyl group, 
 (30) —X-A (wherein X represents an imino group, —O— or —S— and A represents a 6- to 14-membered aromatic hydrocarbon ring group or 5- to 14-membered aromatic heterocyclic group which may be substituted with 1 to 3 substituents selected from Substituent Group A4-1 shown below), 
 (31) —CO-A (wherein A is the same as defined above) and 
 (32) ═CH-A (wherein A is the same as defined above); 
 
       Substituent Group A4-1:
 (1) a halogen atom, 
 (2) a hydroxyl group, 
 (3) a cyano group, 
 (4) a nitro group, 
 (5) a C1-6 alkylcarbonyl group, 
 (6) a C1-6 alkylthio group, 
 (7) a C1-6 alkylsulfinyl group, 
 (8) a C1-6 alkylsulfonyl group, 
 (9) a C1-6 alkoxy group (wherein the C1-6 alkoxy group may be substituted with 1 to 3 substituents selected from the group consisting of a hydroxyl group and a halogen atom), 
 (10) a C2-6 alkenyloxy group, 
 (11) a C2-6 alkynyloxy group, 
 (12) a C1-6 alkyl group (wherein the C1-6 alkyl group may have 1 to 3 substituents selected from the following substituent group:
 (i) a halogen atom, 
 (ii) a hydroxyl group, 
 (iii) a C1-6 alkoxy group (wherein the C1-6 alkoxy group may be substituted with a C3-8 cycloalkyl group), 
 (iv) a C2-6 alkenyloxy group, 
 (v) a C2-6 alkynyloxy group, 
 (vi) a C1-6 alkylthio group, 
 (vii) a C1-6 alkylsulfinyl group, 
 (viii) a C1-6 alkylsulfonyl group, 
 (ix) a 6- to 14-membered aromatic hydrocarbon ring group (wherein the 6- to 14-membered aromatic hydrocarbon ring group may have 1 to 3 substituents selected from the group consisting of a halogen atom, a C1-6 alkyl group which may be substituted with 1 to 3 halogen atoms, a C2-6 alkenyl group, a C2-6 alkynyl group, a C1-6 alkoxy group which may be substituted with 1 to 3 halogen atoms, a C2-6 alkenyloxy group, a C2-6 alkynyloxy group, a C1-6 alkylthio group, a C1-6 alkylsulfinyl group and a C1-6 alkylsulfonyl group), 
 (x) a 3- to 14-membered non-aromatic hydrocarbon ring group (wherein the 3- to 14-membered non-aromatic hydrocarbon ring group may have 1 to 3 substituents selected from the group consisting of a halogen atom, a C1-6 alkyl group which may be substituted with 1 to 3 halogen atoms, a C2-6 alkenyl group, a C2-6 alkynyl group, a C1-6 alkoxy group which may be substituted with 1 to 3 halogen atoms, a C2-6 alkenyloxy group, a C2-6 alkynyloxy group, a C1-6 alkylthio group, a C1-6 alkylsulfinyl group and a C1-6 alkylsulfonyl group), 
 (xi) a 5- to 14-membered aromatic heterocyclic group (wherein the 5- to 14-membered aromatic heterocyclic group may have 1 to 3 substituents selected from the group consisting of a halogen atom, a C1-6 alkyl group which may be substituted with 1 to 3 halogen atoms, a C2-6 alkenyl group, a C2-6 alkynyl group, a C1-6 alkoxy group which may be substituted with 1 to 3 halogen atoms, a C2-6 alkenyloxy group, a C2-6 alkynyloxy group, a C1-6 alkylthio group, a C1-6 alkylsulfinyl group and a C1-6 alkylsulfonyl group) and 
 (xii) a 5- to 14-membered non-aromatic heterocyclic group (wherein the 5- to 14-membered non-aromatic heterocyclic group may have 1 to 3 substituents selected from the group consisting of a halogen atom, a C1-6 alkyl group which may be substituted with 1 to 3 halogen atoms, a C2-6 alkenyl group, a C2-6 alkynyl group, a C1-6 alkoxy group which may be substituted with 1 to 3 halogen atoms, a C2-6 alkenyloxy group, a C2-6 alkynyloxy group, a C1-6 alkylthio group, a C1-6 alkylsulfinyl group and a C1-6 alkylsulfonyl group), 
 
 (13) an amino group (wherein the amino group may be substituted with 1 to 2 substituents selected from the group consisting of a C1-6 alkyl group, a C2-6 alkenyl group and a C2-6 alkynyl group), 
 (14) a 6- to 14-membered aromatic hydrocarbon ring group (wherein the 6- to 14-membered aromatic hydrocarbon ring group may be substituted with 1 to 3 substituents selected from the group consisting of a halogen atom, a C1-6 alkyl group, a C2-6 alkenyl group, a C2-6 alkynyl group, a C1-6 alkoxy group, a C2-6 alkenyloxy group, a C2-6 alkynyloxy group, a C1-6 alkylthio group, a C1-6 alkylsulfinyl group and a C1-6 alkylsulfonyl group), 
 (15) a 3- to 14-membered non-aromatic hydrocarbon ring group (wherein the 3- to 14-membered non-aromatic hydrocarbon ring group may be substituted with 1 to 3 substituents selected from the group consisting of a halogen atom, a C1-6 alkyl group, a C2-6 alkenyl group, a C2-6 alkynyl group, a C1-6 alkoxy group, a C2-6 alkenyloxy group, a C2-6 alkynyloxy group, a C1-6 alkylthio group, a C1-6 alkylsulfinyl group and a C1-6 alkylsulfonyl group), 
 (16) a 5- to 14-membered aromatic heterocyclic group (wherein the 5- to 14-membered aromatic heterocyclic group may be substituted with 1 to 3 substituents selected from the group consisting of a halogen atom, a hydroxyl group, a C1-6 alkyl group which may be substituted with 1 to 3 hydroxyl groups, a C2-6 alkenyl group, a C2-6 alkynyl group, a C1-6 alkoxy group which may be substituted with 1 to 3 halogen atoms, a C2-6 alkenyloxy group, a C2-6 alkynyloxy group, a C1-6 alkylthio group, a C1-6 alkylsulfinyl group and a C1-6 alkylsulfonyl group), 
 (17) a 5- to 14-membered non-aromatic heterocyclic group (wherein the 5- to 14-membered non-aromatic heterocyclic group may be substituted with 1 to 3 substituents selected from the group consisting of a halogen atom, a C1-6 alkyl group, a C2-6 alkenyl group, a C2-6 alkynyl group, a C1-6 alkoxy group, a C2-6 alkenyloxy group, a C2-6 alkynyloxy group, a C1-6 alkylthio group, a C1-6 alkylsulfinyl group and a C1-6 alkylsulfonyl group), 
 (18) —X-A (wherein X represents an imino group, —O— or —S— and A represents a 6- to 14-membered aromatic hydrocarbon ring group or 5- to 14-membered aromatic heterocyclic group which may be substituted with 1 to 3 halogen atoms) and 
 (19) —CO-A (wherein A represents a 6- to 14-membered aromatic hydrocarbon ring group or 5- to 14-membered aromatic heterocyclic group which may be substituted with 1 to 3 halogen atoms). 
 
     
     
         2 . The compound or pharmacologically acceptable salt thereof according to  claim 1 , wherein Ar 1  is the imidazolyl group which is substituted with 1 to 2 substituents selected from the group consisting of (1) a hydrogen atom, (2) a halogen atom, and (3) a C1-6 alkyl group wherein the C1-6 alkyl group may be substituted with 1 to 3 halogen atoms. 
     
     
         3 . The compound or pharmacologically acceptable salt thereof according to  claim 1 , wherein Ar 2  is the phenyl group which is substituted with 1 to 3 substituents selected from the group consisting of (1) a hydrogen atom, (2) a halogen atom, (3) a hydroxyl group, and (4) a cyano group. 
     
     
         4 . The compound or pharmacologically acceptable salt thereof according to  claim 2 , wherein Ar 1  is the imidazolyl group which is substituted with 1 to 2 substituents selected from the group consisting of (1) a hydrogen atom, (2) a halogen atom, and (3) a C1-6 alkyl group. 
     
     
         5 . The compound or pharmacologically acceptable salt thereof according to  claim 1 , wherein Ar 2  is the phenyl group which may be substituted with 1 to 3 substituents selected from the group consisting of (1) a hydrogen atom, (2) a halogen atom, (4) a cyano group and (5) a C1-6 alkoxy group. 
     
     
         6 . The compound or pharmacologically acceptable salt thereof according to  claim 1 , wherein X 1  is —C≡C—. 
     
     
         7 . The compound or pharmacologically acceptable salt thereof according to  claim 1 , wherein X 1  represents —CR 3 ═CR 4 —, and R 3  and R 4  are as defined above. 
     
     
         8 . The compound or pharmacologically acceptable salt thereof according to  claim 7 , wherein X 1  is —CR 31 ═CR 41 — (wherein R 31  is a group selected from the group consisting of (1) a hydrogen atom, (2) a halogen atom, and (3) a C1-6 alkyl group; and R 41  represents a group selected from the group consisting of (1) a hydrogen atom, (2) a halogen atom, and (3) a C1-6 alkyl group (wherein the C1-6 alkyl group may be substituted with 1 to 3 substituents selected from the group consisting of a halogen atom, a hydroxyl group, a cyano group, a C3-8 cycloalkyl group, a C1-6 alkyl group, a C1-6 alkoxy group, an amino group (wherein the amino group may be substituted with a C1-6 alkyl group optionally having 1 to 5 halogen atoms), a 6- to 14-membered aromatic hydrocarbon ring group which may be substituted with 1 to 3 substituents selected from Substituent Group A5, a 5- to 14-membered aromatic heterocyclic group which may be substituted with 1 to 3 substituents selected from Substituent Group A5, a 5- to 14-membered non-aromatic heterocyclic group which may be substituted with 1 to 3 substituents selected from Substituent Group A5 and —O-A 1  (wherein A 1  represents a 6- to 14-membered aromatic hydrocarbon ring group which may be substituted with 1 to 3 substituents selected from Substituent Group A5 or a 5- to 14-membered aromatic heterocyclic group which may be substituted with 1 to 3 substituents selected from Substituent Group A5))); 
       Substituent Group A5:
 (1) a hydrogen atom, (2) a halogen atom, (3) a hydroxyl group, (4) a cyano group, (5) a C3-8 cycloalkyl group, (6) a C3-8 cycloalkoxy group, (7) a C1-6 alkyl group (wherein the C1-6 alkyl group may be substituted with 1 to 5 halogen atoms), (8) a C1-6 alkoxy group (wherein the C1-6 alkoxy group may be substituted with 1 to 5 halogen atoms) and (9) an amino group (wherein the amino group may be substituted with a C1-6 alkyl group optionally having 1 to 5 halogen atoms). 
 
     
     
         9 . The compound or pharmacologically acceptable salt thereof according to  claim 8 , wherein X 1  is —CR 32 ═CR 42 — (wherein R 32  represents a hydrogen atom or a halogen atom; and R 42  represents a substituent selected from the group consisting of a hydrogen atom, a halogen atom, and a C1-6 alkyl group (wherein the C1-6 alkyl group may be substituted with a C3-8 cycloalkyl group or a phenyl group) and a phenyl group). 
     
     
         10 . The compound or pharmacologically acceptable salt thereof according to  claim 1 , wherein R 1  is phenylalkyl. 
     
     
         11 . The compound or pharmacologically acceptable salt thereof according to  claim 1 , wherein R 1  is naphthylalkyl. 
     
     
         12 . The compound or pharmacologically acceptable salt thereof according to  claim 1 , wherein R 2  is hydrogen. 
     
     
         13 . The compound or pharmacologically acceptable salt thereof according to  claim 1 , wherein R 2  is the alkyl group. 
     
     
         14 . A pharmaceutical composition comprising:
 the compound or pharmacologically acceptable salt thereof according to  claim 1  as an active ingredient; and   a pharmacologically acceptable carrier.   
     
     
         15 . The pharmaceutical composition according to  claim 14 , wherein the compound or pharmacologically acceptable salt thereof is in an effective amount to treat a disease resulting from amyloid betas. 
     
     
         16 . The pharmaceutical composition according to  claim 14 , wherein the disease resulting from amyloid betas is Alzheimer's disease, senile dementia, Down syndrome or amyloidosis. 
     
     
         17 . The pharmaceutical composition according to  claim 14 , wherein the active ingredient is present in an amount effective to treat the disease resulting from amyloid betas, said disease being Alzheimer's disease, senile dementia, Down syndrome or amyloidosis.