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

  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},
  volume={51 6},
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… 

Figures and Tables from this paper

Biological Activities of 2-Mercaptobenzothiazole Derivatives: A Review
This present review article focuses on the pharmacological profile of 2-mercaptobenzothiazoles with their potential activities and examines their antimicrobial and antifungal activities.
First Pharmacophore Model of CCR3 Receptor Antagonists and its Homology Model‐Assisted, Stepwise Virtual Screening
Five hits were identified as potential leads against CCR3 receptor, which exhibited good estimated activities, favorable binding interactions, and high docking scores, and provided useful information on the structurally vital residues of C CR3 receptor involved in the antagonist binding.
Synthesis of 2-N/S/C-substituted benzothiazoles via intramolecular cyclative cleavage of benzotriazole ring.
The synthesis of numerous 2-N/S/C-substituted benzothiazoles was achieved from substituted thiocarbonylbenzotriazoles via free-radical intramolecular cyclative cleavage of the benzotriazole ring in
Selective C-H chalcogenation of thiazoles via thiazol-2-yl-phosphonium salts.
The access to the substituted medicinally relevant C2-thio benzothiazoles enables stereoselectivity improvements in the modified Julia olefinations and features broad scope for both the nucleophiles (electron-rich, electron-poor, sterically hindered thiols) and the various substituted benzoth Diazoles.
Copper-mediated C-H activation/C-S cross-coupling of heterocycles with thiols.
Computational studies suggest a stepwise reaction mechanism based on a hydrogen atom abstraction pathway, which is more energetically feasible than many other possible pathways including β-hydride elimination, single electron transfer, hydrogen atom transfer, oxidative addition/reductive elimination, and σ-bond metathesis.
The discovery of CCR3/H1 dual antagonists with reduced hERG risk.
Synthesis and biological evaluation of some 2-mercaptobenzothiazole derivatives.
Fast and effective relief of pain and inflammation in the human being is continued to be a major challenge for the medicinal chemistry researchers. Non-steroidal anti-inflammatory drugs (NSAIDs)
Chemokine receptor antagonists: part 2
Chemokine receptor antagonists have found mixed success as therapeutics and there have been many failures in the clinic and the idea of promiscuous receptor antagonists as an alternative approach is discussed.
Metal sulfide: An efficient promoter for the synthesis of 2-mercaptobenzothiazoles from 2-haloanilines and carbon disulfide
ABSTRACT A convenient method has been developed for the preparation of a variety of 2-mercaptobenzothiazoles from 2-haloanilines and CS2 mediated by metal sulfide. In this reaction, 2-haloanilines


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.
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.
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.
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.
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.
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
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
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.