Design, synthesis and biological activity of novel non-amidine factor Xa inhibitors. Part 1: P1 structure–activity relationships of the substituted 1-(2-Naphthyl)-1H-pyrazole-5-carboxylamides
摘要:
Based on DuPont Pharmaceuticals' monobenzamidine lead structure SN429, we have designed the biphenyl 1-(2-naphthyl)-1H-pyrazole-5-carboxylamides as a novel series of non-basic factor Xa inhibitors. We have discovered that the displacement of the benzamidine moiety with substituted 2-naphthyl structures not only results in highly potent factor Xa inhibitors, but also significantly increases their enzyme specificity and oral bioavailability. (C) 2002 Elsevier Science Ltd. All rights reserved.
Design, synthesis and biological activity of novel non-amidine factor Xa inhibitors. Part 1: P1 structure–activity relationships of the substituted 1-(2-Naphthyl)-1H-pyrazole-5-carboxylamides
摘要:
Based on DuPont Pharmaceuticals' monobenzamidine lead structure SN429, we have designed the biphenyl 1-(2-naphthyl)-1H-pyrazole-5-carboxylamides as a novel series of non-basic factor Xa inhibitors. We have discovered that the displacement of the benzamidine moiety with substituted 2-naphthyl structures not only results in highly potent factor Xa inhibitors, but also significantly increases their enzyme specificity and oral bioavailability. (C) 2002 Elsevier Science Ltd. All rights reserved.
Asymmetric synthesis of atropisomeric pyrazole <i>via</i> an enantioselective reaction of azonaphthalene with pyrazolone
作者:Huijun Yuan、Yao Li、Hanhui Zhao、Zhihong Yang、Xin Li、Wenjun Li
DOI:10.1039/c9cc06360a
日期:——
The first catalytic asymmetricreaction of azonaphthalene with pyrazolone has been established. A wide range of axially chiral pyrazole derivatives have been achieved in good yields (68–99%) with excellent enantioselectivities (83–98% ee) by utilizing chiral phosphoric acid as a catalyst. This strategy provides an efficient and facile approach for the construction of axially chiral pyrazole derivatives
asymmetric cycloaddition, a nitrogen-nitrogen double bond has never been investigated in chiral phosphine catalysis. In this paper, we present phosphine-catalyzed asymmetric [3+2] cycloaddition of diazenes with Morita-Baylis-Hillman (MBH) carbonates to give chiral dihydropyrazoles in high yields with excellent enantioselectivities. Various MBH carbonates and diazenes worked well under the mild reaction conditions