Structure-activity relationships of 2-(benzothiazolylthio)acetamide class of CCR3 selective antagonist.

@article{Naya2003StructureactivityRO,
  title={Structure-activity relationships of 2-(benzothiazolylthio)acetamide class of CCR3 selective antagonist.},
  author={Akira Naya and Kensuke Kobayashi and Makoto. Ishikawa and Kenji Ohwaki and Toshihiko Saeki and Kazuhito Noguchi and Norikazu Ohtake},
  journal={Chemical \& pharmaceutical bulletin},
  year={2003},
  volume={51 6},
  pages={
          697-701
        }
}
The structure activity relationships of novel selective CCR3 receptor antagonists, 2-(benzothiazolylthio)acetamimde derivatives were described. A lead structure (1a) was discovered from the screening of the focused library that was based on the structure of our dual antagonists for the human CCR1 and CCR3 receptors. Derivatization of 1a including incorporation of substituent(s) into each benzene ring of the benzothiazole and piperidine side chain resulted in the identification of potent and… 

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References

SHOWING 1-10 OF 17 REFERENCES
Discovery of a novel CCR3 selective antagonist.
1-(3-Cyanobenzylpiperidin-4-yl)-5-methyl-4-phenyl-1, 3-dihydroimidazol-2-one: a selective high-affinity antagonist for the human dopamine D(4) receptor with excellent selectivity over ion channels.
TLDR
A novel and regioselective "four-step/one-pot" procedure was developed which proved to be applicable to rapid investigation of the SAR of the 1, 3-dihydroimidazol-2-one ring and was ultimately achieved by meta substitution of the benzyl group of 8 with various substituents.
Design, synthesis, and discovery of a novel CCR1 antagonist.
TLDR
This work has identified xanthene-9-carboxamide 1a, the first murine CCR1 receptor antagonist, which may be a useful tool for clarifying the role of C CR1 receptors in murine models of disease.
18F-labeled benzamides for studying the dopamine D2 receptor with positron emission tomography.
TLDR
Results of these studies indicated compounds 23, 26b, and 34 have the selectivity needed for in vivo studies of the D2 (and possibly D3) receptors and are suitable candidates for further evaluation in positron emission tomography imaging studies.
The synthesis of substituted [[3(S)-(acylamino)-2-oxo-1-azetidinyl]thio]acetic acids
Synthese des composes du titre par sulfenylation d'acylamino-3 azetidinones-2 par le phtalimidosulfenylacetate de t-butyle suivie de desesterification par l'acide trifluoroacetique
International union of pharmacology. XXII. Nomenclature for chemokine receptors.
TLDR
A widely accepted receptor nomenclature system is described, ratified by the International Union of Pharmacology, that is facilitating clear communication in this area and updating current concepts of the biology and pharmacology of the chemokine system.
Chemokine receptor usage by human eosinophils. The importance of CCR3 demonstrated using an antagonistic monoclonal antibody.
TLDR
A mAb, 7B11, is described that is selective for CCR3 and has the properties of a true receptor antagonist and the feasibility of completely antagonizing this receptor is demonstrated.
Eotaxin: a potent eosinophil chemoattractant cytokine detected in a guinea pig model of allergic airways inflammation
TLDR
Evidence was obtained that eotaxin shares a binding site with RANTES on guinea pig eosinophils, which suggests the possibility that similar molecules may be important in the human asthmatic lung.
Targeted Disruption of the Chemokine Eotaxin Partially Reduces Antigen-induced Tissue Eosinophilia
TLDR
A contributory role for eotaxin is indicated in the generation of peripheral blood and antigen-induced tissue eosinophilia in the peripheral circulation, suggesting an important role in vivo of this C–C chemokine.
...
...