title: Design and synthesis of new tricyclic indoles as potent modulators of the S1P1 receptor.
abstract: Modulators of S1P1 have proven utility for the treatment of autoimmune disease and efforts to identify new agents with improved safety and pharmacokinetic parameters are ongoing. Several new S1P1 chemotypes were designed and optimized for potency and oral bioavailability. These new agents are characterized by a 'tricyclic fused indole array' and are highly potent agonists of the S1P1 receptor.
authors.affiliation: Arena Pharmaceuticals Inc., 6154 Nancy Ridge Drive, San Diego, CA 92121, United States.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Buzard
authors.affiliation: Arena Pharmaceuticals Inc., 6154 Nancy Ridge Drive, San Diego, CA 92121, United States.
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Schrader
authors.affiliation: Arena Pharmaceuticals Inc., 6154 Nancy Ridge Drive, San Diego, CA 92121, United States.
authors.forename: Xiuwen
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Arena Pharmaceuticals Inc., 6154 Nancy Ridge Drive, San Diego, CA 92121, United States.
authors.forename: Juerg
authors.initials: J
authors.lastname: Lehmann
authors.affiliation: Arena Pharmaceuticals Inc., 6154 Nancy Ridge Drive, San Diego, CA 92121, United States.
authors.forename: Ben
authors.initials: B
authors.lastname: Johnson
authors.affiliation: Arena Pharmaceuticals Inc., 6154 Nancy Ridge Drive, San Diego, CA 92121, United States.
authors.forename: Michelle
authors.initials: M
authors.lastname: Kasem
authors.affiliation: Arena Pharmaceuticals Inc., 6154 Nancy Ridge Drive, San Diego, CA 92121, United States.
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Arena Pharmaceuticals Inc., 6154 Nancy Ridge Drive, San Diego, CA 92121, United States.
authors.forename: Andrew
authors.initials: A
authors.lastname: Kawasaki
authors.affiliation: Arena Pharmaceuticals Inc., 6154 Nancy Ridge Drive, San Diego, CA 92121, United States.
authors.forename: Luis
authors.initials: L
authors.lastname: Lopez
authors.affiliation: Arena Pharmaceuticals Inc., 6154 Nancy Ridge Drive, San Diego, CA 92121, United States.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Moody
authors.affiliation: Arena Pharmaceuticals Inc., 6154 Nancy Ridge Drive, San Diego, CA 92121, United States.
authors.forename: Sangdon
authors.initials: S
authors.lastname: Han
authors.affiliation: Arena Pharmaceuticals Inc., 6154 Nancy Ridge Drive, San Diego, CA 92121, United States.
authors.forename: Yinghong
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Arena Pharmaceuticals Inc., 6154 Nancy Ridge Drive, San Diego, CA 92121, United States.
authors.forename: Jeff
authors.initials: J
authors.lastname: Edwards
authors.affiliation: Arena Pharmaceuticals Inc., 6154 Nancy Ridge Drive, San Diego, CA 92121, United States.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Barden
authors.affiliation: Arena Pharmaceuticals Inc., 6154 Nancy Ridge Drive, San Diego, CA 92121, United States.
authors.forename: Jayant
authors.initials: J
authors.lastname: Thatte
authors.affiliation: Arena Pharmaceuticals Inc., 6154 Nancy Ridge Drive, San Diego, CA 92121, United States.
authors.forename: Joel
authors.initials: J
authors.lastname: Gatlin
authors.affiliation: Arena Pharmaceuticals Inc., 6154 Nancy Ridge Drive, San Diego, CA 92121, United States.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Jones
mesh_terms: D000818:Animals; D004285:Dogs; D015195:Drug Design; D006207:Half-Life; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D051379:Mice; D011485:Protein Binding; D020033:Protein Isoforms / Q000819:agonists / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D049349:Receptors, Lysosphingolipid / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D007211:Indoles; D020033:Protein Isoforms; D049349:Receptors, Lysosphingolipid
keywords: Gilenya®; S1P(1); Sphingosine-1-phosphate