287729-03-7Relevant articles and documents
WEE1 Protein degradation agent
-
, (2021/09/21)
WEE1 Protein degradation agents are provided. , The invention provides a compound as shown V, or a pharmaceutically acceptable salt thereof, or a stereoisomer, Y-L-M thereof. WEE1 (V) Wherein M. WEE1 A WEE1 binding moiety capable of binding to WEE1 protein kinase is provided. Y Is E3 ubiquitin ligase ligand moiety, and L Is a linking group.
METHODS OF MAKING WEE1 INHIBITOR COMPOUNDS
-
, (2021/12/31)
The invention relates to a method of producing a WEE1 inhibitor of formula (1A) useful in the treatment of pathological conditions characterized by excessive cell proliferation, such as cancer. In some embodiments, the invention relates to methods for producing intermediate compounds of formulas (3), (5) and (6) as defined in the description.
Development of Potent Pyrazolopyrimidinone-Based WEE1 Inhibitors with Limited Single-Agent Cytotoxicity for Cancer Therapy
Matheson, Christopher J.,Casalvieri, Kimberly A.,Backos, Donald S.,Reigan, Philip
, p. 1681 - 1694 (2018/08/01)
WEE1 kinase regulates the G2/M cell-cycle checkpoint, a critical mechanism for DNA repair in cancer cells that can confer resistance to DNA-damaging agents. We previously reported a series of pyrazolopyrimidinones based on AZD1775, a known WEE1 inhibitor, as an initial investigation into the structural requirements for WEE1 inhibition. Our lead inhibitor demonstrated WEE1 inhibition in the same nanomolar range as AZD1775, and potentiated the effects of cisplatin in medulloblastoma cells, but had reduced single-agent cytotoxicity. These results prompted the development of a more comprehensive series of WEE1 inhibitors. Herein we report a series of pyrazolopyrimidinones and identify a more potent WEE1 inhibitor than AZD1775 and additional compounds that demonstrate that WEE1 inhibition can be achieved with reduced single-agent cytotoxicity. These studies support that WEE1 inhibition can be uncoupled from the potent cytotoxic effects observed with AZD1775, and this may have important ramifications in the clinical setting where WEE1 inhibitors are used as chemosensitizers for DNA-targeted chemotherapy.
WEE 1 KINASE INHIBITORS AND METHODS OF MAKING AND USING THE SAME
-
, (2017/05/17)
A compound, or a pharmaceutically acceptable salt thereof, having a chemical structure of formula (I) or formula (II), and methods of using these compounds to treat cancer in an individual.
New Synthesis of 1,1-Substituted Hydrazines by Alkylation of N-Acyl- or N-alkyloxycarbonylaminophthalimide Using the Mitsunobu Protocol
Brosse, Nicolas,Pinto, Maria-Fatima,Jamart-Gregoire, Brigitte
, p. 4370 - 4374 (2007/10/03)
N-acyl- and N-alkoxycarbonylaminophthalimides are prepared using a convenient reaction and are efficiently used as acid partners in Mitsunobu reaction. This reaction allows them to be alkylated by primary, secondary or benzyl groups. Comparison of the reactivities and pKa values of these N-substituted aminophthalimides suggest that the success of the Mitsunobu reaction in this case seems to be governed more by steric than by electronic effects. A final dephthaloylation step results in an efficient method for the preparation of 1,1-substituted hydrazines.
