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PDBsum entry 4y2b
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Hydrolase/hydrolase inhibitor
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PDB id
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4y2b
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PDB id:
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| Name: |
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Hydrolase/hydrolase inhibitor
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Title:
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Co-crystal structure of 3-ethyl-2-(isopropylamino)-7-(pyridin-3-yl) thieno[3,2-d]pyrimidin-4(3h)-one bound to pde7a
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Structure:
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High affinity camp-specific 3',5'-cyclic phosphodiesterase 7a. Chain: a. Fragment: unp residues 130-482. Synonym: hcp1,tm22. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: pde7a. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
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Resolution:
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2.20Å
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R-factor:
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0.160
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R-free:
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0.196
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Authors:
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Y.Endo,K.Kawai,T.Asano,S.Amano,Y.Asanuma,K.Sawada,Y.Onodera,N.Ueo, N.Takahashi,Y.Sonoda,N.Kamei,T.Irie
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Key ref:
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Y.Endo
et al.
(2015).
2-(Isopropylamino)thieno[3,2-d]pyrimidin-4(3H)-one derivatives as selective phosphodiesterase 7 inhibitors with potent in vivo efficacy.
Bioorg Med Chem Lett,
25,
1910-1914.
PubMed id:
DOI:
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Date:
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09-Feb-15
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Release date:
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08-Apr-15
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PROCHECK
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Headers
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References
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Q13946
(PDE7A_HUMAN) -
High affinity cAMP-specific 3',5'-cyclic phosphodiesterase 7A from Homo sapiens
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Seq:
Struc:
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482 a.a.
318 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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Enzyme class:
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E.C.3.1.4.53
- 3',5'-cyclic-AMP phosphodiesterase.
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Reaction:
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3',5'-cyclic AMP + H2O = AMP + H+
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3',5'-cyclic AMP
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+
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H2O
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=
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AMP
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+
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H(+)
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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DOI no:
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Bioorg Med Chem Lett
25:1910-1914
(2015)
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PubMed id:
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2-(Isopropylamino)thieno[3,2-d]pyrimidin-4(3H)-one derivatives as selective phosphodiesterase 7 inhibitors with potent in vivo efficacy.
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Y.Endo,
K.Kawai,
T.Asano,
S.Amano,
Y.Asanuma,
K.Sawada,
Y.Onodera,
N.Ueo,
N.Takahashi,
Y.Sonoda,
N.Kamei,
T.Irie.
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ABSTRACT
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A new series of thienopyrimidinones is synthesized and evaluated as selective
phosphodiesterase 7 (PDE7) inhibitors for the treatment of inflammatory
diseases. The modification of the substituents on thienopyrimidinone revealed
that an isopropylamino group at the 2-position was favorable for aqueous
solubility. The introduction of 3-pyrrolidines at the 7-position resulted in
good solubility, highly potent activity, and good PDE7 selectivity. Among the
synthesized compounds, compound 46 exhibited the greatest inhibition of ear
edema in a phorbol ester-induced mouse model.
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Links
