title: Pyrrolidinyl phenylurea derivatives as novel CCR3 antagonists.
abstract: Optimization starting with our lead compound 1 (IC(50)=4.9 nM) led to the identification of pyrrolidinyl phenylurea derivatives. Further modification toward improvement of the bioavailability provided (R)-1-(1-((6-fluoronaphthalen-2-yl)methyl)pyrrolidin-3-yl)-3-(2-(2-hydroxyethoxy)phenyl)urea 32 (IC(50)=1.7 nM), a potent and orally active CCR3 antagonist.
authors.affiliation: Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan. Aiko_Nitta@nts.toray.co.jp.
authors.forename: Aiko
authors.initials: A
authors.lastname: Nitta
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Iura
authors.forename: Hideki
authors.initials: H
authors.lastname: Inoue
authors.forename: Ippei
authors.initials: I
authors.lastname: Sato
authors.forename: Koichiro
authors.initials: K
authors.lastname: Morihira
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kubota
authors.forename: Tatsuaki
authors.initials: T
authors.lastname: Morokata
authors.forename: Makoto
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Ohta
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Tsukamoto
authors.forename: Takayuki
authors.initials: T
authors.lastname: Imaoka
authors.forename: Toshiya
authors.initials: T
authors.lastname: Takahashi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D006207:Half-Life; D008252:Macaca fascicularis; D010671:Phenylurea Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D054397:Receptors, CCR3 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: C578847:1-(1-((6-fluoronaphthalen-2-yl)methyl)pyrrolidin-3-yl)-3-(2-(2-hydroxyethoxy)phenyl)urea; D010671:Phenylurea Compounds; D011759:Pyrrolidines; D054397:Receptors, CCR3; C032519:pyrrolidine