[EN] METHODS AND COMPOUNDS FOR RESTORING MUTANT p53 FUNCTION<br/>[FR] MÉTHODES ET COMPOSÉS POUR LA RESTAURATION DE LA FONCTION DU P53 MUTANT
申请人:PMV PHARMACEUTICALS INC
公开号:WO2021061643A1
公开(公告)日:2021-04-01
Mutations in oncogenes and tumor suppressors contribute to the development and progression of cancer. The present disclosure describes compounds and methods to recover wild-type function to p53 mutants. The compounds of the present invention can bind to mutant p53 and restore the ability of the p53 mutant to bind DNA and activate downstream effectors involved in tumor suppression. The disclosed compounds can be used to reduce the progression of cancers that contain a p53 mutation.
The development of a novel, efficient and robust method for the general conversion of aliphatic and aromatic carboxylic acids to organic iodides without the use of heavy metals or strong oxidizing agents is reported. Commercially available N‐iodoamides were used for both initiation and halogen donation under irradiative conditions. Isolation of the product is extremely simple and the major co‐product
of bromocyclopropanes with excess dibutylcopperlithium in tetrahydrofuran at −48 °C gives the respective organocopper intermediates which upon quenching with excess alkylhalides afford alkylated cyclo-propanes with retention of the configuration. This process is applied to the synthesis of methyl cascarillate. Bromoarenes are also reduced with dibutylcopperlithium and allylarenes are prepared therefrom
This invention is directed to a process for the preparation of high yield alkyl or aryl iodide from its corresponding carboxylic acid using N-iodo amides.