Discovery and structure–activity relationships of urea derivatives as potent and novel CCR3 antagonists
| Autor: | Shin-ichi Tsukamoto, Makoto Takeuchi, Toshiya Takahashi, Yosuke Iura, Mitsuaki Ohta, Koichiro Morihira, Ippei Sato, Takayuki Imaoka, Aiko Nitta, Tatsuaki Morokata, Hirokazu Kubota, Hiroki Tomioka |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Pyrrolidines
Proline Stereochemistry Chemistry Receptors CCR3 Organic Chemistry Clinical Biochemistry Drug Evaluation Preclinical Antagonist Pharmaceutical Science Naphthalenes Biochemistry Structure-Activity Relationship chemistry.chemical_compound Drug Discovery Humans Urea Molecular Medicine Urea derivatives Molecular Biology Lead compound Protein Binding |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 22:4951-4954 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2012.06.042 |
| Popis: | The synthesis and structure–activity relationships of ureas as CCR3 antagonists are described. Optimization starting with lead compound 2 (IC50 = 190 nM) derived from initial screening hit compound 1 (IC50 = 600 nM) led to the identification of (S)-N-((1R,3S,5S)-8-((6-fluoronaphthalen-2-yl)methyl)-8-azabicyclo[3.2.1]octan-3-yl)-N-(2-nitrophenyl)pyrrolidine-1,2-dicarboxamide 27 (IC50 = 4.9 nM) as a potent CCR3 antagonist. |
| Databáze: | OpenAIRE |
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