A non-peptide NK1 receptor agonist showing subpicomolar affinity

被引：16

作者：

Cappelli, A

Giuliani, G

Mohr, GLP

Gallelli, A

Anzini, M

Vomero, S

Cupello, A

Scarrone, S

Matarrese, M

Moresco, RM

Fazio, F

Finetti, F

Morbidelli, L

Ziche, M

机构：

[1] Univ Siena, Dipartimento Farmaco Chim Tecnol, I-53100 Siena, Italy

[2] Univ Siena, European Res Ctr Drug Discovery & Dev, I-53100 Siena, Italy

[3] CNR, Sez Genova, Inst Bioimmagini & Fisiol Mol, I-16132 Genoa, Italy

[4] Univ Milano Bicocca, Ist Bioimmagini & Fisiol Mol, CNR, Ist HS Raffaele, I-20132 Milan, Italy

[5] Univ Siena, Sez Farmacol, Dipartimento Biol Mol, I-53100 Siena, Italy

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2004年 / 47卷 / 06期

关键词：

D O I：

10.1021/jm034219a

中图分类号：

R914 [药物化学];

学科分类号：

100701 [药物化学];

摘要：

3-Quinolinecarboxamides have been synthesized and evaluated for their binding to the human NK1 receptor. Several secondary amide derivatives show NK1 receptor affinity in the picomolar range. The most active compound, hydroxymethylcarboxamide 3h showing an IC50 value in the subpicomolar range, behaved as an agonist of NK1 receptor in endothelial cell proliferation, inositol phosphate turnover, and NO-mediated cyclic GMP accumulation, thus proving it to be the first non-peptide NK, receptor agonist showing very high potency.

引用

页码：1315 / 1318

页数：4

共 16 条

[1]

Mapping and fitting the peripheral benzodiazepine receptor binding site by carboxamide derivatives. Comparison of different approaches to quantitative ligand-receptor interaction modeling [J].