（（2S,4R）-4-Hydroxy-N-（2-methylnaphthalen-l-yl）pyrrolidine-2-carboxamide （HMNPC）, an amide derived from 4-hydroxy-L-proline and 2-methyl naphthalen-l-amine, is a powerful ligand for Cu-catalyzed coupling of （he...（（2S,4R）-4-Hydroxy-N-（2-methylnaphthalen-l-yl）pyrrolidine-2-carboxamide （HMNPC）, an amide derived from 4-hydroxy-L-proline and 2-methyl naphthalen-l-amine, is a powerful ligand for Cu-catalyzed coupling of （het- ero）aryl halides with sulfinic acid salts, allowing for first time the metal-catalyzed coupling of （hetero）aryl chlorides and NaSO2Me. A considerable number of （hetero）aryl chlorides worked well, providing the pharmaceutically im- portant （hetero）aryl methylsulfones in good to excellent yields.展开更多
In order to develop novel LpxC inhibitors with good activities and metabolic stability, two series of compounds with hydrophilic terminus have been synthesized and their in vitro antibacterial activities against Esche...In order to develop novel LpxC inhibitors with good activities and metabolic stability, two series of compounds with hydrophilic terminus have been synthesized and their in vitro antibacterial activities against Escherichial coil and Pseudomonas aemginosa were evaluated. Especially, compounds 22b and c exhibited comparable antibacterial activities to CHIR-090 and better metabolic stability than CHIR-090 and LPC-011 in liver microsomes （rat and mouse）, which indicated the terminal methylsulfone may be a preferred structure in the design of LpxC inhibitors and worthy of further investigations.展开更多
基金The authors are grateful to Chinese Academy of Sciences （supported by the Strategic Priority Research Program, grant XDB20020200 ＆ QYZDJ-SSW- SLH029） and the National Natural Science Foundation of China （grant 21621002） for their financial support.
文摘（（2S,4R）-4-Hydroxy-N-（2-methylnaphthalen-l-yl）pyrrolidine-2-carboxamide （HMNPC）, an amide derived from 4-hydroxy-L-proline and 2-methyl naphthalen-l-amine, is a powerful ligand for Cu-catalyzed coupling of （het- ero）aryl halides with sulfinic acid salts, allowing for first time the metal-catalyzed coupling of （hetero）aryl chlorides and NaSO2Me. A considerable number of （hetero）aryl chlorides worked well, providing the pharmaceutically im- portant （hetero）aryl methylsulfones in good to excellent yields.
基金National Science and Technology Major Project for the support of this researchsupported by Key New Drug Creation and Manufacturing Program,China (No.2014ZX09507009-016)
文摘In order to develop novel LpxC inhibitors with good activities and metabolic stability, two series of compounds with hydrophilic terminus have been synthesized and their in vitro antibacterial activities against Escherichial coil and Pseudomonas aemginosa were evaluated. Especially, compounds 22b and c exhibited comparable antibacterial activities to CHIR-090 and better metabolic stability than CHIR-090 and LPC-011 in liver microsomes （rat and mouse）, which indicated the terminal methylsulfone may be a preferred structure in the design of LpxC inhibitors and worthy of further investigations.
