Abstract |
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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Authors | Yusuke Endo, Kentaro Kawai, Takeshi Asano, Seiji Amano, Yoshihito Asanuma, Keisuke Sawada, Yuuta Onodera, Noriko Ueo, Nobuaki Takahashi, Yo Sonoda, Noriyuki Kamei, Tetsumi Irie |
Journal | Bioorganic & medicinal chemistry letters
(Bioorg Med Chem Lett)
Vol. 25
Issue 9
Pg. 1910-4
(May 01 2015)
ISSN: 1464-3405 [Electronic] England |
PMID | 25866242
(Publication Type: Journal Article)
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Copyright | Copyright © 2015 Elsevier Ltd. All rights reserved. |
Chemical References |
- 2-(isopropylamino)thieno(3,2-d)pyrimidin-4(3H)-one
- Phorbol Esters
- Pyrimidinones
- Cyclic Nucleotide Phosphodiesterases, Type 7
- Pde7a protein, mouse
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Topics |
- Animals
- Cyclic Nucleotide Phosphodiesterases, Type 7
(antagonists & inhibitors, metabolism)
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Edema
(chemically induced, drug therapy)
- Male
- Mice
- Mice, Inbred ICR
- Models, Molecular
- Molecular Structure
- Phorbol Esters
- Pyrimidinones
(chemical synthesis, chemistry, pharmacology)
- Solubility
- Structure-Activity Relationship
- Substrate Specificity
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