title: Discovery and structure-activity relationships of urea derivatives as potent and novel CCR3 antagonists.
abstract: The synthesis and structure-activity relationships of ureas as CCR3 antagonists are described. Optimization starting with lead compound 2 (IC(50)=190 nM) derived from initial screening hit compound 1 (IC(50)=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 (IC(50)=4.9 nM) as a potent CCR3 antagonist.
authors: Pharmaceutical Research Laboratories, Toray Industries, Inc., Kamakura, Kanagawa, Japan. Aiko_Nitta@nts.toray.co.jp
authors: Aiko
authors: A
authors: Nitta
authors: Yosuke
authors: Y
authors: Iura
authors: Hiroki
authors: H
authors: Tomioka
authors: Ippei
authors: I
authors: Sato
authors: Koichiro
authors: K
authors: Morihira
authors: Hirokazu
authors: H
authors: Kubota
authors: Tatsuaki
authors: T
authors: Morokata
authors: Makoto
authors: M
authors: Takeuchi
authors: Mitsuaki
authors: M
authors: Ohta
authors: Shin-ichi
authors: S
authors: Tsukamoto
authors: Takayuki
authors: T
authors: Imaoka
authors: Toshiya
authors: T
authors: Takahashi
mesh_terms: D004353:Drug Evaluation, Preclinical; D006801:Humans; D009281:Naphthalenes / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D011392:Proline / Q000737:chemistry; D011485:Protein Binding; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D054397:Receptors, CCR3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism
chemical_list: C576335:(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; D009281:Naphthalenes; D011759:Pyrrolidines; D054397:Receptors, CCR3; D014508:Urea; D011392:Proline