[EN] 4-OXO-3,4-DIHYDROQUINAZOLINON COMPOUNDS FOR THE TREATMENT OF BRAF-ASSOCIATED DISEASES AND DISORDERS [FR] COMPOSÉS DE 4-OXO-3,4-DIHYDROQUINAZOLINONE POUR LE TRAITEMENT DE MALADIES ET D'AFFECTIONS ASSOCIÉES À BRAF
Regio- and Stereoselective 5-exo Radical Cyclizations on a Chiral Perhydro-1,3-benzoxazine Moiety. An Access to Enantiopure 3-Alkylpyrrolidines
摘要:
Both enantiomers of chiral, nonracemic S-alkyl-substituted pyrolidines are prepared by diastereoselective 5-exo-trig cyclization on (-)-8-aminomenthol-derived perhydro-1,3-benzoxazines used as chiral auxiliaries, followed by elimination of the menthol appendage. The diastereoselective radical cyclization is promoted by tributyltin hydride and occurs on a 3-aza-5-hexenyl-type radical, leading to five-membered rings in high yield. The stereocontrol of the cyclization is strongly influenced by 1,3-allylic strain so that an appropriate substitution pattern on the olefin-acceptor and the presence of a vicinal stereocenter are crucial for achieving good diastereoselectivity. The enantiopure pyrrolidines are obtained in three steps with concomitant recovering of the starting (+)-pulegone auxiliary.
2,3,4,9-TETRAHYDRO-1H-PYRIDO[3,4-B]INDOLE DERIVATIVES AS ESTROGEN RECEPTOR MODULATORS FOR THE TREATMENT OF CANCER
申请人:[en]OLEMA PHARMACEUTICALS, INC.
公开号:WO2024039861A1
公开(公告)日:2024-02-22
The present disclosure provides 2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole derivatives of formula I as estrogen receptor modulators for the treatment of cancer.