RESUMO
Using an electrochemical C(sp3)-H fluorination reaction, a series of α-fluorinated tropane compounds were synthesized and their druglikeness parameters were assessed to compare with the parent compounds. Improvements were observed in membrane permeability, P-gp liability, and inhibitory effects on hERG and Nav1.5 channels, accompanied with a trend of decreased aqueous solubility and microsomal stability. It was also revealed that α-fluorination reduced the basicity of tropane nitrogen atom for about 1000-fold.
Assuntos
Halogenação , Solubilidade , Tropanos , Humanos , Tropanos/química , Tropanos/síntese química , Tropanos/farmacologia , Relação Estrutura-Atividade , Canais de Potássio Éter-A-Go-Go/metabolismo , Canais de Potássio Éter-A-Go-Go/antagonistas & inibidores , Permeabilidade da Membrana Celular/efeitos dos fármacos , Animais , Estrutura Molecular , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidoresRESUMO
A grand opening: N-Boc-N-alkylsulfamides are effective substrates for the title transformation. Oxidative cyclization is highly chemoselective as well as being both stereospecific and diastereoselective. With the advent of new protocols that facilitate ring opening of the six-membered-ring heterocyclic products, access to differentially protected 1,3-diamines has been made possible (see scheme).
Assuntos
Diaminas/síntese química , Ródio/química , Carbono/química , Catálise , Diaminas/química , Hidrogênio/química , EstereoisomerismoRESUMO
The total synthesis of (+)-duocarmycin A and SA through a common indoline intermediate is described. The key reactions include selective lithiation of a 2,6-dibromoiodobenzene derivative and diastereoselective addition to a chiral nitroalkene, copper-mediated aryl amination, and addition of aryllithium to azlactones.
