Pellicciari R, Natalini B, Marinozzi M, Sadeghpour B M, Cordi A A, Lanthorn T H, Hood W F, Monahan J B
Istituto di Chimica Farmaceutica e Tecnica Farmaceutica, Università Degli Studi, Perugia, Italy.
Farmaco. 1991 Nov;46(11):1243-64.
The four D-2-amino-4,5-methano-adipates 26, 27, 32, 33 were synthesized and their biological activity at the N-methyl-D-aspartate (NMDA) receptor was assessed. The synthesis involved as a key step a rhodium acetate dimer catalyzed addition of ethyl diazoacetate to the protected D-allylglycine (17). In vitro receptor binding using L-[3H]glutamate as the radioligand provided affinity data, while modulation of [3H]TCP binding was used as a functional assay. The analogues were also evaluated in [3H]kainate and [3H]AMPA binding to assess selectivity over non-NMDA glutamate receptors. Three of the four diastereoisomer, D-CAA B (27), C (32) and D (33) were shown to have agonist properties at the NMDA-site, while the fourth, (2R,4R,5R) D-CAA A (26) was characterized as an NMDA-site atypic antagonist.
合成了四种D-2-氨基-4,5-亚甲基己二酸酯26、27、32、33，并评估了它们在N-甲基-D-天冬氨酸（NMDA）受体上的生物活性。合成过程中的关键步骤是乙酸铑二聚体催化重氮乙酸乙酯加成到受保护的D-烯丙基甘氨酸（17）上。使用L-[3H]谷氨酸作为放射性配体的体外受体结合实验提供了亲和力数据，而[3H]TCP结合的调节则用作功能测定。还对这些类似物进行了[3H]海人藻酸和[3H]α-氨基-3-羟基-5-甲基-4-异恶唑丙酸结合实验，以评估其对非NMDA谷氨酸受体的选择性。四种非对映异构体中的三种，即D-CAA B（27）、C（32）和D（33）在NMDA位点表现出激动剂特性，而第四种（2R,4R,5R）D-CAA A（26）则被表征为NMDA位点的非典型拮抗剂。
