Hydrazide hydrazone HIF-2alpha inhibitor and application thereof

• Main Authors: SHENG RONG, CHEN SIYUAN, GUAN MENGYING, HU YUNZHEN, YAN HUIHUI
• Format: Patent
• Language: Chinese; English
• Published: 23.06.2023
• Subjects: ACYCLIC OR CARBOCYCLIC COMPOUNDS; CHEMISTRY; 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 relates to the technical field of medical biology, and discloses a hydrazide hydrazone HIF-2alpha inhibitor and application thereof. The hydrazide hydrazone HIF-2 alpha inhibitor provided by the invention can be used for blocking the dimerization of HIF-2 alpha/ARNT, so that the effect of transcriptional inhibition of HIF-2 is exerted. The HIF-2 alpha inhibitor compound has the activity of antagonizing HIF-2 transcription, and shows VEGF (vascular endothelial growth factor) protein inhibitory activity in a human renal clear cell carcinoma cell strain 786-O. Therefore, the compound has the prospect of being applied to preparation of drugs for treating VHL deficiency or HIF-2 alpha abnormal expression diseases including cancers, inflammations, autoimmune diseases and iron overload related diseases. 本发明涉及医药生物技术领域，公开了一种酰肼腙类HIF-2α抑制剂及其应用。本发明提供的酰肼腙类HIF-2α抑制剂，能够阻断HIF-2α/ARNT二聚化，进而发挥HIF-2转录抑制的作用。该HIF-2α抑制剂化合物具有拮抗HIF-2转录的活性，在人肾透明细胞癌细胞株786-O中，显示出VEGF蛋白抑制活性。因此，该化合物具有应用于制备治疗VHL缺失或HIF-2α异常表达疾病包括癌症、炎症、自身免疫性疾病