轴手性喹唑啉-4-酮衍生物是强效的非竞争性α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体拮抗剂。
Atropisomeric quinazolin-4-one derivatives are potent noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists.
作者信息
Welch W M, Ewing F E, Huang J, Menniti F S, Pagnozzi M J, Kelly K, Seymour P A, Guanowsky V, Guhan S, Guinn M R, Critchett D, Lazzaro J, Ganong A H, DeVries K M, Staigers T L, Chenard B L
机构信息
Global Research and Development, Groton Laboratories, Pfizer Inc., CT 06340, USA.
出版信息
Bioorg Med Chem Lett. 2001 Jan 22;11(2):177-81. doi: 10.1016/s0960-894x(00)00622-3.
Piriqualone (1) was found to be an antagonist of AMPA receptors. Structure activity optimization was conducted on each of the three rings in 1 to afford a series of potent and selective antagonists. The sterically crowded environment surrounding the N-3 aryl group provided sufficient thermal stability for atropisomers to be isolated. Separation of these atropisomers resulted in the identification of (+)-38 (CP-465,022), a compound that binds to the AMPA receptor with high affinity (IC50 = 36 nM) and displays potent anticonvulsant activity.
匹立喹酮（1）被发现是一种α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体拮抗剂。对1中的三个环分别进行了构效优化，以得到一系列强效且选择性的拮抗剂。N-3芳基周围空间拥挤的环境为分离出阻转异构体提供了足够的热稳定性。这些阻转异构体的分离导致鉴定出（+）-38（CP-465,022），该化合物以高亲和力（IC50 = 36 nM）与AMPA受体结合，并显示出强效的抗惊厥活性。
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