Macrocycle and composition comprising thereof
A macrocycle represented by formula (I) and a pharmaceutical composition comprising the macrocycle, or a crystalline form, pharmaceutically acceptable salt, hydrate or solvent compound, stereoisomer, prodrug, or isotopic variant of the macrocycle. The macrocycle and the composition thereof inhibit a protein kinase.
1. A deuterium-enriched substituted macrocyclic compound, which is a macrocyclic compound represented by formula (I), or a crystal form, a pharmaceutically acceptable salt, a prodrug, a stereoisomer, a hydrate or a solvate thereof,
wherein R 1 , R 2 , R 3 , R 4 , R 8 , R 9 , R 10 , R 13 , R 14 , and R 15 are each independently hydrogen, deuterium, or halogen;
R 5 , R 6 , R 7 , R 11 , R 12 , R 16 , and R 17 are each hydrogen;
provided that at least one of R 1 , R 2 , R 3 , R 4 , R 8 , R 9 , R 10 , R 13 , R 14 , and R 15 is deuterium.
2. The macrocyclic compound according to claim 1 , wherein R 13 , R 14 , and R 15 are deuterium.
3. The macrocyclic compound according to claim 1 , wherein R 8 , R 9 , and R 10 are deuterium.
4. The macrocyclic compound according to claim 2 , wherein R 8 , R 9 , and R 10 are deuterium.
5. The macrocyclic compound according to claim 1 , wherein R 1 , R 2 , R 3 , and R 4 are deuterium.
6. The macrocyclic compound according to claim 2 , wherein R 1 , R 2 , R 3 , and R 4 are deuterium.
7. The macrocyclic compound according to claim 3 , wherein R 1 , R 2 , R 3 , and R 4 are deuterium.
8. The macrocyclic compound according to claim 4 , wherein R 1 , R 2 , R 3 , and R 4 are deuterium.
9. The macrocyclic compound according to claim 1 , wherein the compound is selected from the group consisting of the following compounds or pharmaceutically acceptable salts thereof:
10. The macrocyclic compound according to claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
11. The macrocyclic compound according to claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
12. The macrocyclic compound according to claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
13. The macrocyclic compound according to claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
14. A pharmaceutical composition, comprising:
a pharmaceutically acceptable carrier, and
the macrocyclic compound according to claim 1 , or a crystal form, a pharmaceutically acceptable salt, a hydrate or a solvate, a stereoisomer, a prodrug or an isotopic variant thereof.
15. The pharmaceutical composition according to claim 14 , further comprising other therapeutic drugs which are drugs for cancer, cardiovascular disease, inflammation, infection, immune disease, cell proliferative disease, viral disease, metabolic disease, or organ transplant.
16. A method of inhibiting anaplastic lymphoma kinase, comprising administering the macrocyclic compound according to claim 1 , or a crystal form, a pharmaceutically acceptable salt, a hydrate or a solvate, a stereoisomer, a prodrug or an isotopic variant thereof.