Structure-activity relationships (SAR) and structure-kinetic relationships (SKR) of pyrrolopiperidinone acetic acids as CRTh2 antagonists
Structure-activity relationships (SAR) and structure-kinetic relationships (SKR) of pyrrolopiperidinone acetic acids as CRTh2 antagonists
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DOI：
10.1016/j.bmcl.2014.08.026
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发表时间：
2014-11-01
影响因子：
2.7
通讯作者：
Roberts, Richard S.
中科院分区：
文献类型：
--
作者：
Andres, Miriam;Buil, Maria Antonia;Roberts, Richard S.
吡咯并哌啶酮乙酸（PPAs）被鉴定为高效CRTh 2受体拮抗剂。此外，这些化合物中的许多显示从受体的缓慢解离动力学。结构-动力学关系（SKR）研究允许优化动力学，以获得具有长达23小时的长受体滞留半衰期的有效类似物。低渗透性是该系列的一般特征，但是通过使用酯前药可以实现口服生物利用度。(C)2014爱思唯尔有限公司版权所有。
Pyrrolopiperidinone acetic acids (PPAs) were identified as highly potent CRTh2 receptor antagonists. In addition, many of these compounds displayed slow-dissociation kinetics from the receptor. Structure-kinetic relationship (SKR) studies allowed optimisation of the kinetics to give potent analogues with long receptor residence half-lives of up to 23 h. Low permeability was a general feature of this series, however oral bioavailability could be achieved through the use of ester prodrugs. (C) 2014 Elsevier Ltd. All rights reserved.