title: (7-Benzyloxy-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic Acids as S1P1 Functional Antagonists.
abstract: S1P1 is a validated target for treatment of autoimmune disease, and functional antagonists with superior safety and pharmacokinetic properties are being sought as second generation therapeutics. We describe the discovery and optimization of (7-benzyloxy-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic acids as potent, centrally available, direct acting S1P1 functional antagonists, with favorable pharmacokinetic and safety properties.
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Buzard
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Luis
authors.initials: L
authors.lastname: Lopez
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Moody
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Andrew
authors.initials: A
authors.lastname: Kawasaki
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Schrader
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Michelle
authors.initials: M
authors.lastname: Kasem
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Ben
authors.initials: B
authors.lastname: Johnson
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Xiuwen
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Lars
authors.initials: L
authors.lastname: Thoresen
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Tawfik
authors.initials: T
authors.lastname: Gharbaoui
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Dipanjan
authors.initials: D
authors.lastname: Sengupta
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Lorene
authors.initials: L
authors.lastname: Calvano
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Ashwin
authors.initials: A
authors.lastname: Krishnan
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Yinghong
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Graeme
authors.initials: G
authors.lastname: Semple
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Jeff
authors.initials: J
authors.lastname: Edwards
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Barden
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Morgan
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Khawja
authors.initials: K
authors.lastname: Usmani
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Chuan
authors.initials: C
authors.lastname: Chen
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Abu
authors.initials: A
authors.lastname: Sadeque
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Weichao
authors.initials: W
authors.lastname: Chen
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Christopher
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Jayant
authors.initials: J
authors.lastname: Thatte
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Lixia
authors.initials: L
authors.lastname: Fu
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Michelle
authors.initials: M
authors.lastname: Solomon
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Kevin
authors.initials: K
authors.lastname: Whelan
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Hussien
authors.initials: H
authors.lastname: Al-Shamma
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Joel
authors.initials: J
authors.lastname: Gatlin
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Ibragim
authors.initials: I
authors.lastname: Gaidarov
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Todd
authors.initials: T
authors.lastname: Anthony
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Minh
authors.initials: M
authors.lastname: Le
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: David J
authors.initials: DJ
authors.lastname: Unett
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Scott
authors.initials: S
authors.lastname: Stirn
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Anthony
authors.initials: A
authors.lastname: Blackburn
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Dominic P
authors.initials: DP
authors.lastname: Behan
authors.affiliation: Arena Pharmaceuticals, Inc. , 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Jones
keywords: FTY720; Gilenya; S1P1 agonist; Sphingosine-1-phosphate; fingolimod