title: 1-Aryl-2-((6-aryl)pyrimidin-4-yl)amino)ethanols as competitive inhibitors of fatty acid amide hydrolase.
abstract: A series of 1-aryl-2-(((6-aryl)pyrimidin-4-yl)amino)ethanols have been found to be competitive inhibitors of fatty acid amide hydrolase (FAAH). One member of this class, JNJ-40413269, was found to have excellent pharmacokinetic properties, demonstrated robust central target engagement, and was efficacious in a rat model of neuropathic pain.
authors: Janssen Pharmaceutical Companies of Johnson & Johnson, 3210 Merryfield Row, San Diego, CA 92121, United States. Electronic address: jkeith@its.jnj.com.
authors: John M
authors: JM
authors: Keith
authors: Janssen Pharmaceutical Companies of Johnson & Johnson, 3210 Merryfield Row, San Diego, CA 92121, United States.
authors: Natalie
authors: N
authors: Hawryluk
authors: Janssen Pharmaceutical Companies of Johnson & Johnson, 3210 Merryfield Row, San Diego, CA 92121, United States.
authors: Richard L
authors: RL
authors: Apodaca
authors: Janssen Pharmaceutical Companies of Johnson & Johnson, 3210 Merryfield Row, San Diego, CA 92121, United States.
authors: Allison
authors: A
authors: Chambers
authors: Janssen Pharmaceutical Companies of Johnson & Johnson, 3210 Merryfield Row, San Diego, CA 92121, United States.
authors: Joan M
authors: JM
authors: Pierce
authors: Janssen Pharmaceutical Companies of Johnson & Johnson, 3210 Merryfield Row, San Diego, CA 92121, United States.
authors: Mark
authors: M
authors: Seierstad
authors: Janssen Pharmaceutical Companies of Johnson & Johnson, 3210 Merryfield Row, San Diego, CA 92121, United States.
authors: James A
authors: JA
authors: Palmer
authors: Janssen Pharmaceutical Companies of Johnson & Johnson, 3210 Merryfield Row, San Diego, CA 92121, United States.
authors: Michael
authors: M
authors: Webb
authors: Janssen Pharmaceutical Companies of Johnson & Johnson, 3210 Merryfield Row, San Diego, CA 92121, United States.
authors: Mark J
authors: MJ
authors: Karbarz
authors: Janssen Pharmaceutical Companies of Johnson & Johnson, 3210 Merryfield Row, San Diego, CA 92121, United States.
authors: Brian P
authors: BP
authors: Scott
authors: Janssen Pharmaceutical Companies of Johnson & Johnson, 3210 Merryfield Row, San Diego, CA 92121, United States.
authors: Sandy J
authors: SJ
authors: Wilson
authors: Janssen Pharmaceutical Companies of Johnson & Johnson, 3210 Merryfield Row, San Diego, CA 92121, United States.
authors: Lin
authors: L
authors: Luo
authors: Janssen Pharmaceutical Companies of Johnson & Johnson, 3210 Merryfield Row, San Diego, CA 92121, United States.
authors: Michelle L
authors: ML
authors: Wennerholm
authors: Janssen Pharmaceutical Companies of Johnson & Johnson, 3210 Merryfield Row, San Diego, CA 92121, United States.
authors: Leon
authors: L
authors: Chang
authors: Janssen Pharmaceutical Companies of Johnson & Johnson, 3210 Merryfield Row, San Diego, CA 92121, United States.
authors: Michele
authors: M
authors: Rizzolio
authors: Janssen Pharmaceutical Companies of Johnson & Johnson, 3210 Merryfield Row, San Diego, CA 92121, United States.
authors: Sandra R
authors: SR
authors: Chaplan
authors: Janssen Pharmaceutical Companies of Johnson & Johnson, 3210 Merryfield Row, San Diego, CA 92121, United States.
authors: J Guy
authors: JG
authors: Breitenbucher
mesh_terms: D000581:Amidohydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000605:Amino Alcohols / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000700:Analgesics / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D020134:Catalytic Domain; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006207:Half-Life; D006801:Humans; D062105:Molecular Docking Simulation; D009437:Neuralgia / Q000188:drug therapy; D011485:Protein Binding; D011743:Pyrimidines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D051381:Rats; D013329:Structure-Activity Relationship; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D000605:Amino Alcohols; D000700:Analgesics; D004791:Enzyme Inhibitors; D011743:Pyrimidines; D000099252:Fatty Acid Amide Hydrolases; C000592502:JNJ-40413269; C030986:pyrimidine
keywords: Analgesia; Crystal structure; Endo-cannabinoids; Enzymes; Fatty acid amide hydrolase (FAAH)