title: The discovery of novel cyclohexylamide CCR2 antagonists.
abstract: As a result of further SAR studies on a piperidinyl piperidine scaffold, we report the discovery of compound 44, a potent, orally bioavailable CCR2 antagonist. While having some in vitro hERG activity, this molecule was clean in an in vivo model of QT prolongation. In addition, it showed excellent efficacy when dosed orally in a transgenic murine model of acute inflammation.
authors: Johnson & Johnson Pharmaceutical Research and Development, Welsh & McKean Roads, Spring House, PA 19002, USA. jlanter@its.jnj.com
authors: James C
authors: JC
authors: Lanter
authors: Thomas P
authors: TP
authors: Markotan
authors: Xuqing
authors: X
authors: Zhang
authors: Nalin
authors: N
authors: Subasinghe
authors: Fu-An
authors: FA
authors: Kang
authors: Cuifen
authors: C
authors: Hou
authors: Monica
authors: M
authors: Singer
authors: Evan
authors: E
authors: Opas
authors: Sandra
authors: S
authors: McKenney
authors: Carl
authors: C
authors: Crysler
authors: Dana
authors: D
authors: Johnson
authors: Christopher J
authors: CJ
authors: Molloy
authors: Zhihua
authors: Z
authors: Sui
mesh_terms: D000208:Acute Disease; D000284:Administration, Oral; D000577:Amides / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D051379:Mice; D008822:Mice, Transgenic; D051381:Rats; D054390:Receptors, CCR2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D000893:Anti-Inflammatory Agents; D054390:Receptors, CCR2