1373944-75-2

Upstream product

• 184475-71-6 4-(3-chloro-4-fluorophenylamino)-6-hydroxy-7-methoxyquinazoline 
• 1012057-13-4 thyl 2-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)acetate 
• 184475-35-2 gefitinib 

Downstream Products

• 1373944-84-3 C₂₈H₂₄ClFN₆O₂ 
• 1373944-81-0 C₂₈H₂₂ClFN₆O₃ 

Relevant academic research and scientific papers

Rational Design and Synthesis of Novel Dual PROTACs for Simultaneous Degradation of EGFR and PARP

Inspired by the success of dual-targeting drugs, especially bispecific antibodies, we propose to combine the concept of proteolysis targeting chimera (PROTAC) and dual targeting to design and synthesize dual PROTAC molecules with the function of degrading two completely different types of targets simultaneously. A library of novel dual-targeting PROTAC molecules has been rationally designed and prepared. A convergent synthetic strategy has been utilized to achieve high synthetic efficiency. These dual PROTAC structures are characterized using trifunctional natural amino acids as star-type core linkers to connect two independent inhibitors and E3 ligands together. In this study, gefitinib, olaparib, and CRBN or VHL E3 ligands were used as substrates to synthesize novel dual PROTACs. They successfully degraded both the epidermal growth factor receptor (EGFR) and poly(ADP-ribose) polymerase (PARP) simultaneously in cancer cells. Being the first successful example of dual PROTACs, this technique will greatly widen the range of application of the PROTAC method and open up a new field for drug discovery.

Compound for simultaneously inducing EGFR and PARP protein degradation as well as preparation method and application thereof

The invention discloses a compound capable of simultaneously inducing EGFR and PARP protein degradation as well as a preparation method and an application thereof, and belongs to the field of medicinal chemistry. The invention provides an application of a series of novel dual-targeting degradation compounds with two independent inhibitor units and an E3 ligase ligand or pharmaceutically acceptable salts, hydrates, stereoisomers or prodrugs thereof in preparation of drugs for treating or preventing tumors. The compound provided by the invention can effectively induce E3 ligase dependent degradation of EGFR and PARP in pancreatic cancer cell lines and 1299 cells at the same time, and can effectively inhibit the growth of cancer cells. The target diversity of advanced cancers with tumor heterogeneity and reverse chemotherapy drug resistance can be solved. The method provided by the invention provides a new treatment mode for treatment of EGFR and PARP mediated tumors and/or other diseases.

QUINAZOLINE DERIVATIVES AND QUINAZOLINE COMPLEX PROTEIN KINASE INHIBITOR FOR INHIBITING MULTIPLICAITON OF TUMOR CELLS AND PREPARATION METHOD THEREOF

Quinazoline derivatives represented by general formula (1) and quinazoline complexes as protein kinase inhibitors, and their preparation methods are provided. Wherein, in general formula (1), at least one of R and R′ is a group containing an atom capable