Structure-activity relationships of 2-(benzothiazolylthio)acetamide class of CCR3 selective antagonist.
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 selective compounds (1b, r, s) exhibiting nano-molar binding affinity (IC(50)s: 1.5-3.0 nM) and greater than 800-fold selectivity for the CCR3 receptor over the CCR1 receptor.
Naya
Akira
A
Banyu Tsukuba Research Institute, Ibaraki, Japan. nayaak@banyu.co.jp
Kobayashi
Kensuke
K
Ishikawa
Makoto
M
Ohwaki
Kenji
K
Saeki
Toshihiko
T
Noguchi
Kazuhito
K
Ohtake
Norikazu
N
D000081:Acetamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D052160:Benzothiazoles; D001667:Binding, Competitive; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D006224:Cricetinae; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D054389:Receptors, CCR1; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014162:Transfection
C480246:2-(benzothiazolylthio)acetamide; D000081:Acetamides; D052160:Benzothiazoles; C515300:CCR1 protein, human; C515350:CCR3 protein, human; C480245:N-(1-(3,4-dichlorobenzyl)piperidin-4-yl)-(6-amino-2-benzothiazolylthio)acetamide; D054389:Receptors, CCR1; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D013844:Thiazoles; D002118:Calcium