title: Biaryl analogues of teriflunomide as potent DHODH inhibitors.
abstract: The structure-activity relationships of a novel series of biaryl dihydroorotate dehydrogenase (DHODH) inhibitors related to teriflunomide are disclosed. These biaryl derivatives were the result of structure-based design and proved to be potent DHODH inhibitors which in addition showed good antiproliferative activities on peripheral blood mononuclear cells and good efficacies in vivo in the rat adjuvant-induced-arthritis model.
authors.affiliation: Almirall, R&D Centre, Laureà Miró 408-410, Sant Feliu de Llobregat, 08980 Barcelona, Spain. montse.erra@almirall.com
authors.forename: Montse
authors.initials: M
authors.lastname: Erra
authors.forename: Imma
authors.initials: I
authors.lastname: Moreno
authors.forename: Jordi
authors.initials: J
authors.lastname: Sanahuja
authors.forename: Miriam
authors.initials: M
authors.lastname: Andrés
authors.forename: Raquel F
authors.initials: RF
authors.lastname: Reinoso
authors.forename: Estrella
authors.initials: E
authors.lastname: Lozoya
authors.forename: Pilar
authors.initials: P
authors.lastname: Pizcueta
authors.forename: Núria
authors.initials: N
authors.lastname: Godessart
authors.forename: Julio Cesar
authors.initials: JC
authors.lastname: Castro-Palomino
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy; D001665:Binding Sites; D001713:Biphenyl Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D003198:Computer Simulation; D003437:Crotonates / Q000737:chemistry*; D000090722:Dihydroorotate Dehydrogenase; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D006801:Humans; D006885:Hydroxybutyrates; D009570:Nitriles; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D051381:Rats; D013329:Structure-Activity Relationship; D014052:Toluidines / Q000737:chemistry*
chemical_list: D001713:Biphenyl Compounds; D003437:Crotonates; D000090722:Dihydroorotate Dehydrogenase; D004791:Enzyme Inhibitors; D006885:Hydroxybutyrates; D009570:Nitriles; D014052:Toluidines; C527525:teriflunomide; D044925:Oxidoreductases Acting on CH-CH Group Donors