Benzo five-membered nitrogen heterocyclic piperidine or piperazine derivatives and preparation methods and pharmaceutical compositions thereof

1. A compound of the following formula (I) or pharmaceutically acceptable salt thereof:

wherein:

R 1 represents an aromatic group which is mono- or polysubstituted with R 3 , wherein the aromatic group is phenyl or benzisothiazolyl;

R 3 is H, Cl, CF 3 , or CH 3 ; when R 3 are groups for polysubstitution, each R 3 is independently selected from the group consisting of the above-mentioned groups;

A, B and X each represents N;

R 2 is H; and

Y represents butylene group.

2. The compound of claim 1 , wherein the pharmaceutically acceptable salt is hydrochloride salt, hydrobromide salt, sulfate salt, trifluoroacetate salt, methanesulfonate salt, tartrate salt, malate salt, succinate salt, maleate salt, citrate salt, phosphate salt, lactate salt, pyruvate salt, acetate salt, fumarate salt, oxaloacetate salt, ethanesulfonate salt, oxalate salt, besylate salt or isethionate salt.

3. The compound of claim 1 , wherein the aromatic group is phenyl.

4. The compound of claim 1 , wherein R 3 is CF 3 .

5. The compound of claim 1 , selected from:

I-63 1-(4-(4-(3-chlorophenyl)piperazin-1-yl)butyl)-1H-benzotriazole,

I-65 1-(4-(4-(3-trifluoromethylphenyl)piperazin-1-yl)butyl)-1H-benzotriazole,

I-68 3-(4-(4-(1H-benzotriazol-1-yl)butyl)piperazin-1-yl)benzisothiazole, and

I-81 1-(4-(4-(3-(6-fluorobenzisothiazolyl))piperazin-1-yl)butyl)-1H-benzotriazole.

6. A method for preparing the compound of claim 1 , comprising:

scheme (I)

wherein a compound

are reacted in a solvent in the presence of an inorganic base and a phase transfer catalyst, in a first reaction step, to yield a compound

and then under reflux, the resulting compound is reacted with

in a solvent in the presence of an organic base, in a second reaction step, to yield a compound

wherein A, B, X, R 1 , and R 2 are as defined in claim 1 , and wherein n is 3.

7. A pharmaceutical composition comprising the compound or pharmaceutically acceptable salt thereof according to claim 1 , optionally together with one or more pharmaceutically acceptable excipients or other active substances having effect of relaxing vascular smooth muscle spasm.

8. The compound of claim 5 , selected from:

I-63 1-(4-(4-(3-chlorophenyl)piperazin-1-yl)butyl)-1H-benzotriazole,

I-65 1-(4-(4-(3-trifluoromethylphenyl)piperazin-1-yl)butyl)-1H-benzotriazole, and

I-68 3-(4-(4-(1H-benzotriazol-1-yl)butyl)piperazin-1-yl)benzisothiazole.

9. The method of claim 6 , wherein in scheme (I), in the first reaction step:

the inorganic base is sodium hydride, sodium hydroxide, sodium methoxide, sodium ethoxide, sodium carbonate, sodium hydrogencarbonate, potassium hydride, potassium hydroxide, potassium methoxide, potassium ethoxide, potassium carbonate or potassium bicarbonate;

the phase transfer catalyst is tetrabutylammonium bromide, tetrabutylammonium chloride, tetrabutyl ammonium hydrogen sulfate or 1,4,7,10,13,16-hexaoxacyclooctadecane;

the solvent is water except when sodium hydride is used, N-methylpyrrolidone (NMP), N,N-dimethylformamide (DMF), or a mixture of two or more thereof;

reaction temperature is 10-150° C.; and

reaction time is 0.5-20 hours.

10. The method of claim 6 , wherein in scheme (I), in the second reaction step:

potassium iodide is present;

the organic base is diisopropylethylamine, diethylamine, triethylamine, pyridine, t-butylamine, cyclopropylamine, di-n-butylamine, diisopropylamine, or 1,2-dimethylpropylamine;

the solvent is acetonitrile, DMF, dimethylsulfoxide (DMSO) or methyl ethyl ketone, or a mixture of two or more thereof; and

reaction time is 1-30 hours.