Himbacine derived thrombin receptor (PAR-1) antagonists: SAR of the pyridine ring.
Himbacine derived thrombin receptor (PAR-1) antagonists: SAR of the pyridine ring.
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辛巴辛衍生的凝血酶受体 (PAR-1) 拮抗剂：吡啶环的 SAR。
DOI：
10.1016/j.bmcl.2007.06.002
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发表时间：
2007
影响因子：
2.7
通讯作者：
M. Chintala
中科院分区：
文献类型：
--
作者：
Yan Xia;S. Chackalamannil;Martin C. Clasby;D. Doller;K. Eagen;W. Greenlee;H. Tsai;Jacqueline Agans;H. Ahn;G. Boykow;Y. Hsieh;C. Lunn;M. Chintala
本文报道了辛巴辛衍生的凝血酶受体（PAR-1）拮抗剂乙烯基吡啶区的构效关系。在5-位被芳基或杂芳基取代的2-乙烯基吡啶基环显示出最好的总体PAR-1亲和力和药代动力学性质。一个新发现的带有5-（3-吡啶基）取代基的类似物显示出优异的PAR-1亲和力（Ki= 22 nM）和口服活性，与早期开发的候选物相比，ClogP降低，脱靶选择性提高。
The structure–activity relationship (SAR) of the vinyl pyridine region of himbacine derived thrombin receptor (PAR-1) antagonists is described. A 2-vinylpyridyl ring substituted with an aryl or a heteroaryl group at the 5-position showed the best overall PAR-1 affinity and pharmacokinetic properties. One of the newly discovered analogs bearing a 5-(3-pyridyl) substituent showed excellent PAR-1 affinity (Ki=22nM) and oral activity with reduced ClogP and improved off-target selectivity compared to an earlier development candidate.