Hudson Sarah, Kiankarimi Mehrak, Eccles Wendy, Dwight Wesley, Mostofi Yalda S, Genicot Marc J, Fleck Beth A, Gogas Kathleen, Aparicio Anna, Wang Hua, Wen Jenny, Wade Warren S
Department of Medicinal Chemistry, Neurocrine Biosciences, Inc., 12790 El Camino Real, San Diego, CA 92130, USA.
Bioorg Med Chem Lett. 2008 Aug 15;18(16):4491-4. doi: 10.1016/j.bmcl.2008.07.049. Epub 2008 Jul 17.
The synthesis and SAR of a series of chiral heterocyclic ring-constrained norepinephrine reuptake inhibitors are described. The best compounds compare favorably with atomoxetine in potency (IC(50)s<10 nM), selectivity against the other monoamine transporters, and inhibition of CYP2D6 (IC(50)s>1 microM). In addition, the compounds are generally more stable than atomoxetine to oxidative metabolism and thus are likely to have lower clearance in humans.
描述了一系列手性杂环环约束去甲肾上腺素再摄取抑制剂的合成及其构效关系。最佳化合物在效力（IC50<10 nM）、对其他单胺转运体的选择性以及对CYP2D6的抑制作用（IC50>1 μM）方面与托莫西汀相当。此外，这些化合物通常比托莫西汀对氧化代谢更稳定，因此在人体内的清除率可能更低。
