2-(4-甲磺酰氨基苯基)丙酰胺 TRPV1 拮抗剂：B 区和 C 区的结构-活性关系。
2-(4-Methylsulfonylaminophenyl) propanamide TRPV1 antagonists: Structure-activity relationships in the B and C-regions.
机构信息
Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China.
出版信息
Bioorg Med Chem. 2012 Feb 1;20(3):1310-8. doi: 10.1016/j.bmc.2011.12.014. Epub 2011 Dec 23.
Abstract
On the basis of the previous lead N-4-t-butylbenzyl 2-(3-fluoro-4-methylsulfonylaminophenyl) propanamide (3) as a potent TRPV1 antagonist, structure-activity relationships for the B (propanamide part) and C-region (4-t-butylbenzyl part) have been investigated for rTRPV1 in CHO cells. The B-region was modified with dimethyl, cyclopropyl and reverse amides and then the C-region was replaced with 4-substituted phenyl, aryl alkyl and diaryl alkyl derivatives. Among them, compound 50 showed high binding affinity with K(i)=21.5nM, which was twofold more potent than 3 and compound 54 exhibited potent antagonism with K(i(ant))=8.0nM comparable to 3.
摘要
在前驱物 N-4-叔丁基苯甲酰基 2-(3-氟-4-甲磺酰氨基苯基)丙酰胺（3）作为一种有效的 TRPV1 拮抗剂的基础上，对 CHO 细胞中的 rTRPV1 的 B（丙酰胺部分）和 C 区（4-叔丁基苄基部分）进行了构效关系研究。B 区用二甲基、环丙基和反向酰胺进行修饰，然后 C 区用 4-取代苯基、芳基烷基和二芳基烷基衍生物取代。其中，化合物 50 表现出与 K(i)=21.5nM 的高结合亲和力，比 3 高两倍，化合物 54 表现出与 K(i(ant))=8.0nM 的有效拮抗作用，与 3 相当。
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