Halogen-substituted phenylate compound and applications thereof
A compound of formula (I) or an optical isomer thereof, and pharmaceutically acceptable salts, prodrugs, aquo-complexes or non-aqueous-solvent complexes thereof are provided. Experiments prove that, compared with a control compound MGL-3196, the compound of formula (I), which is obtained through specific substitution sites and specific substitution types, is higher in agonist activity to THR-beta and significantly improved in selectivity on THR-beta/THR-alpha. The compound can be used in preparing THR-beta agonist and drugs for treating adaption diseases (including dyslipidemia, hypercholesteremia, non-alcoholic steatohepatitis and non-alcoholic fatty liver disease) applicable to the THR-beta agonist.
1. The compound represented by formula (I), or an optical isomer thereof, or a salt thereof:
wherein, each of R 1 -R 7 , R 9 , and R 10 is independently selected from H and D; A is selected from the group consisting of CH and CD; B is N; X and Y are each independently selected from the group consisting of Cl and Br; X and Y are not Cl at the same time.
2. The compound according to claim 1 or an optical isomer, a salt thereof, characterized in that said compound has the structure of formula (II):
wherein, each of R 1 -R 7 , R 9 , and R 10 is independently selected from H and D; A is selected from the group consisting of CH and CD; B is N.
3. The compound according to claim 2 , or an optical isomer thereof, or a salt thereof, characterized in that said compound has the structure of formula (IV):
wherein, R 7 , R 9 , and R 10 are each independently selected from H; each of R 1 -R 6 is independently selected from H and D; A is selected from CH and CD.
4. The compound according to claim 1 , or an optical isomer thereof, or a salt thereof, characterized in that said compound has the structure of formula (III):
wherein, each of R 1 -R 7 , R 9 , and R 10 is independently selected from H and D; A is selected from the group consisting of CH and CD; B is N.
5. The compound according to claim 4 , or an optical isomer thereof, or a salt thereof, characterized in that said compound has the structure of formula (V):
wherein, R 7 , R 9 , and R 10 are each independently selected from H; each of R 1 -R 6 is independently selected from H and D; A is selected from CH and CD.
6. The compound according to claim 1 , or an optical isomer thereof, or a salt thereof, characterized in that said compound is selected from the group consisting of the following compounds:
7. A medicament for lowering cholesterol and treating dyslipidemia and nonalcoholic fatty liver disease, characterized by which it is a formulated drug product containing an active ingredient that is the compound according to claim 1 , or an optical isomer, or a salt thereof, and pharmaceutically acceptable auxiliary materials and excipients.
8. A method of activating THR-β receptors, comprising administering an effective amount of a composition that contains the compound according to claim 1 , or an optical isomer, or a salt thereof to a subject in need thereof.
9. A method of treating diffuse toxic goiter, comprising administering an effective amount of a THR-α agonist to a subject in need thereof, wherein the THR-α agonist is the compound according to claim 1 , or an optical isomer thereof, or a salt thereof.
10. The method of claim 8 , wherein the composition is a drug for lowering cholesterol, and treating dyslipidemia and nonalcoholic fatty liver disease.
11. The method of claim 8 , wherein the composition is a drug for the treatment of familial hypercholesterolemia and non-alcoholic steatohepatitis.