3v9b
From Proteopedia
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
Structural highlights
DiseasePDE4D_HUMAN Note=Genetic variations in PDE4D might be associated with susceptibility to stroke. PubMed:17006457 states that association with stroke has to be considered with caution. Defects in PDE4D are the cause of acrodysostosis type 2, with or without hormone resistance (ACRDYS2) [MIM:614613. ACRDYS2 is a pleiotropic disorder characterized by skeletal, endocrine, and neurological abnormalities. Skeletal features include brachycephaly, midface hypoplasia with a small upturned nose, brachydactyly, and lumbar spinal stenosis. Endocrine abnormalities include hypothyroidism and hypogonadism in males and irregular menses in females. Developmental disability is a common finding but is variable in severity and can be associated with significant behavioral problems.[1] FunctionPDE4D_HUMAN Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.[2] [3] Publication Abstract from PubMedA 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). Stereoselective synthesis of novel pyrazole derivatives using tert-butansulfonamide as a chiral auxiliary.,Park CM, Jeon DJ Org Biomol Chem. 2012 Apr 7;10(13):2613-20. doi: 10.1039/c2ob06495b. Epub 2012, Feb 27. PMID:22371117[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||||
