Benzimidazole Derivatives and Preparation Process and Pharmaceutical Uses Thereof

摘要

The invention belongs to the technical field of pharmaceutical chemistry, and particularly pertains to benzimidazole derivatives, and preparation process and pharmaceutical uses thereof. Benzimidazole derivatives include Ligustrazine and NO donor derivatives. The kind of the compounds can rapidly release Ligustrazine or No in vivo, so that they can produce effective synergetic effects with Azilsartan, to enhance the anti-hypertension effect, and reduce adverse effects, and the released Ligustrazine can produce ideal protection to patients' livers and kidneys, thereby filling blanks in the prior art

主权项

1. A compound as represented by the general formula I, or pharmaceutically acceptable salts, solvates or polymorphs thereof,
characterized in that: R in the formula I representswherein a=0, 1, 2, 3, 4, 5 or 6;
R1 represents C2-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl,(CH2)nO(CH2)m,phenyl, substituted phenyl, aromatic heterocycle or substituted aromatic heterocycle, where inb, c=0, 1, 2, 3, 4, 5 or 6; in (CH2)nO(CH2)m, n, m=1, 2, 3, 4, 5 or 6;
R2 represents hydrogen, halogens, trifluoromethyl, C1-C8 alkoxy, C1-C8 alkyl, nitro, sulfonamido, amino or cyano; R3 represents C1-C8 alkylidene, C1-C8 alkoxy, C2-C8 alkenyloxy, C2-C8 alkynyloxy, (C1-C6)O(C1-C6),phenyl, substituted phenyl, aromatic heterocycle or substituted aromatic heterocycle, where inb, c=0, 1, 2, 3, 4, 5 or 6;
R4 represents a phenyl, substituted phenyl, benzene sulphonyl, 5- to 6-membered aromatic heterocycle, substituted 5- to 6-membered aromatic heterocycle, cyano, trifluoromethyl, C1-C8 alkyoxy, C1-C8 nitrate ester group or C1-C8 alkyl; R5 represents phenyl, substituted phenyl, 5- to 6-membered aromatic heterocycle, substituted 5- to 6-membered aromatic heterocycle, cyano, trifluoromethyl, C1-C8 alkoxy, C1-C8 nitrate ester group, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alknyl,or (CH2)nO(CH2)m, wherein R3, R4, a, n, m have the meanings as previously described;
R6 and R7 represent hydrogen, C1-C8 alkoxy or C1-C8 alkyl; R8 and R9 represent hydrogen, C1-C8 alkoxy, C1-C8 nitrate ester group or C1-C8 alkyl; wherein the “substituted phenyl” means a phenyl which is substituted with one or more selected from the group consisting of hydroxyl, C1-C6 alkyl, C1-C6 alkoxy, halogens, nitro, amino, cyano, trifluoromethyl, —CH═CHCO2R11, each of which may be the same or different from each other, wherein R11 represents hydrogen or C1-C6 alkyl; the “aromatic heterocycle” means a 5 to 7-membered aromatic cycle containing 1 to 4 heteroatoms, the heteroatoms, independently from each other, being selected from the group of O, S, or N; the “substituted aromatic heterocycle” means optionally being substituted with one or more group selected from the group consisting of C1-C6 alkyl, C1-C6 alkoxy, halogen substituted, each of which may be the same or different.