Armour Duncan R, de Groot Marcel J, Price David A, Stammen Blanda L C, Wood Anthony, Perros Manos, Burt Catherine
Chem Biol Drug Des. 2006 Apr;67(4):305-8. doi: 10.1111/j.1747-0285.2006.00376.x.
The development of compound 1, a piperidine-based CCR5 receptor antagonist with Type I CYP2D6 inhibition, into the tropane-derived analogue 5, is described. This compound, which is devoid of CYP2D6 liabilities, is a highly potent ligand for the CCR5 receptor and has broad-spectrum activity against a range of clinically relevant HIV isolates. The identification of human ether a-go-go-related gene channel inhibition within this series is described and the potential for QTc interval prolongation discussed. Furthermore, structure activity relationship (SAR) around the piperidine moiety is also described.
描述了将化合物1（一种具有I型CYP2D6抑制作用的基于哌啶的CCR5受体拮抗剂）开发为托烷衍生类似物5的过程。该化合物没有CYP2D6相关问题，是CCR5受体的高效配体，对一系列临床相关的HIV分离株具有广谱活性。描述了该系列中人类醚 - 去极化相关基因通道抑制的鉴定，并讨论了QTc间期延长的可能性。此外，还描述了哌啶部分周围的构效关系（SAR）。
