Conformationally constrained bicyclic derivatives of the potent and selective κ-opioid receptor agonist 2-(3,4-dichlorophenyl)-N-methyl-N- [(1S)-1-phenyl-2- (1-pyrrolidinyl)-ethyl] acetam^ide (3, ICI-199, 441) were...Conformationally constrained bicyclic derivatives of the potent and selective κ-opioid receptor agonist 2-(3,4-dichlorophenyl)-N-methyl-N- [(1S)-1-phenyl-2- (1-pyrrolidinyl)-ethyl] acetam^ide (3, ICI-199, 441) were designed to explore the effect of the conformational restriction and stereochemistry of the pharmacophoric ethylenediamine incorporated into the pyrrolidine on the affinity and κ-selectivity. A facile enantiospecific synthetic route was established to afford all four stereoisomers starting from readily available amino acids through mild cyclization and amide formation.展开更多
A novel and simple procedure for the enantiospecific synthesis of penehyclidine hydrochloride （8018） isomers and the R configuration derivatives was described. The intramolecular asymmetric cyclization of the monosu...A novel and simple procedure for the enantiospecific synthesis of penehyclidine hydrochloride （8018） isomers and the R configuration derivatives was described. The intramolecular asymmetric cyclization of the monosulfonate of compound 1,2-diol was applied to the execution of the synthesis of the key chiral building block for the first time. The aimed products were obtained with moderate yield in〉99% ee.展开更多
文摘Conformationally constrained bicyclic derivatives of the potent and selective κ-opioid receptor agonist 2-(3,4-dichlorophenyl)-N-methyl-N- [(1S)-1-phenyl-2- (1-pyrrolidinyl)-ethyl] acetam^ide (3, ICI-199, 441) were designed to explore the effect of the conformational restriction and stereochemistry of the pharmacophoric ethylenediamine incorporated into the pyrrolidine on the affinity and κ-selectivity. A facile enantiospecific synthetic route was established to afford all four stereoisomers starting from readily available amino acids through mild cyclization and amide formation.
基金Project supported by the National Natural Science Foundation of China （No. 203900508）.
文摘A novel and simple procedure for the enantiospecific synthesis of penehyclidine hydrochloride （8018） isomers and the R configuration derivatives was described. The intramolecular asymmetric cyclization of the monosulfonate of compound 1,2-diol was applied to the execution of the synthesis of the key chiral building block for the first time. The aimed products were obtained with moderate yield in〉99% ee.
