3V9B

Crystal structure of the catalytic domain of PDE4D2 with (S)-N-(3-{1-[1-(3-Cyclopropylmethoxy-4-difluoromethoxyphenyl)-2-(1-oxypyridin-4-yl)-ethyl]-1H-pyrazl-3-yl}phenyl)acetamide

3V9B の概要

• エントリーDOI: 10.2210/pdb3v9b/pdb
• 分子名称: cAMP-specific 3',5'-cyclic phosphodiesterase 4D, N-(3-{1-[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(1-oxidopyridin-4-yl)ethyl]-1H-pyrazol-3-yl}phenyl)acetamide, ZINC ION, ... (4 entities in total)
• 機能のキーワード: hydrolase, 3', 5'-cyclic-amp phosphodiesterases, cyclic nucleotide, phosphodiesterases, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm (By similarity): Q08499
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 168240.58

構造登録者

Kim, H.T.,Chang, H.J. (登録日: 2011-12-25, 公開日: 2012-01-18, 最終更新日: 2023-11-08)

主引用文献

Park, C.M.,Jeon, D.J.
Stereoselective synthesis of novel pyrazole derivatives using tert-butansulfonamide as a chiral auxiliary
Org.Biomol.Chem., 10:2613-2620, 2012

PubMed Abstract: A novel chiral pyrazole derivative was developed by our research program as a potent PDE4 inhibitor for the treatment of anti-inflammatory diseases, such as asthma and chronic obstructive pulmonary disease. The asymmetric synthesis of the inhibitors carrying the pyrazole moiety, including nitrogen directly bonded to a chiral center, through a novel approach is disclosed. The key steps of the synthetic sequence begin with the preparation of chiral toluenesulfinyl imine by the condensation of (R)- and (S)-tert-butanesulfinamide with an aldehyde. Next, a corresponding chiral amine synthesis by a stereoselective addition reaction of 4-picolyl lithium to the chiral toluenesulfinyl imine is performed, followed by desulfination. The preparation of the cis-type enaminone from the addition of the enaminone to the corresponding chiral amine is then accomplished, with further transformation into the pyrazole derivatives through the amination of the enaminones and subsequent dehydro-cyclization. A total of 8 steps are completed to produce a 5.5% yield (100% ee).

PubMed: 22371117
DOI: 10.1039/c2ob06495b

実験手法

X-RAY DIFFRACTION (2.1 Å)