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
Summary for 3V9B
| Entry DOI | 10.2210/pdb3v9b/pdb |
| Descriptor | 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) |
| Functional Keywords | hydrolase, 3', 5'-cyclic-amp phosphodiesterases, cyclic nucleotide, phosphodiesterases, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | Homo sapiens (human) |
| Cellular location | Cytoplasm (By similarity): Q08499 |
| Total number of polymer chains | 4 |
| Total formula weight | 168240.58 |
| Authors | Kim, H.T.,Chang, H.J. (deposition date: 2011-12-25, release date: 2012-01-18, Last modification date: 2023-11-08) |
| Primary citation | 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 Cited by 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: 22371117DOI: 10.1039/c2ob06495b PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
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