Synthesis and preparation method and application of SHP2 and CDK4/6 double-target inhibition compound

• Main Authors: LI WENQIANG, LUO GUANGMEI, SHU CHENGXIA, WU XIAOXING, CHEN XIAOYU, YANG KEXIN
• Format: Patent
• Language: Chinese; English
• Published: 05.05.2023
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

The invention belongs to the field of medicinal chemistry, and particularly relates to synthesis, a preparation method and application of a double-target inhibitor containing SHP2 and CDK4/6. The pharmaceutical composition contains three compounds shown in general formulas I-III and pharmaceutically acceptable salts, enantiomers, diastereoisomers, tautomers, solvates, polymorphic substances or prodrugs thereof. A brand-new SHP2 and CDK4/6 double-target inhibitor is prepared through a pharmacophore fusion and reasonable drug design method, so that the problems that an existing SHP2 inhibitor and an existing CDK4/6 inhibitor are resistant to drugs, poor in drug effect and the like are solved; the important significance of the invention lies in providing the first SHP2 and CDK4/6 double-target inhibitor, and a basis is provided for solving the problem of drug resistance of kinase and phosphatase in the later stage. Meanwhile, the embodiment of the invention proves that the SHP2 inhibitor and the CDK4/6 inhibitor