title: Synthesis and optimization of furano[3,2-d]pyrimidines as selective spleen tyrosine kinase (Syk) inhibitors.
abstract: A series of furano[3,2-d]pyrimidine Syk inhibitors were synthesized and optimized for their enzyme potency and selectivity versus other kinases. In addition, ADME properties were assessed and compounds were prepared with optimized profiles for in vivo experiments. Compound 23 was identified as having acceptable pharmacokinetic properties and demonstrated efficacy in a rat collagen induced arthritis model.
authors: AbbVie Bioresearch Center, 100 Research Dr., Worcester, MA 01545, United States.
authors: Michael
authors: M
authors: Hoemann
authors: AbbVie, 1 North Waukegan Rd., North Chicago, IL 60064, United States.
authors: Noel
authors: N
authors: Wilson
authors: AbbVie Bioresearch Center, 100 Research Dr., Worcester, MA 01545, United States.
authors: Maria
authors: M
authors: Argiriadi
authors: AbbVie Bioresearch Center, 100 Research Dr., Worcester, MA 01545, United States.
authors: David
authors: D
authors: Banach
authors: AbbVie Bioresearch Center, 100 Research Dr., Worcester, MA 01545, United States.
authors: Andrew
authors: A
authors: Burchat
authors: AbbVie Bioresearch Center, 100 Research Dr., Worcester, MA 01545, United States.
authors: David
authors: D
authors: Calderwood
authors: Reset Therapeutics, One Corporate Drive, South San Francisco, CA 94080, United States(†).
authors: Bruce
authors: B
authors: Clapham
authors: AbbVie, 1 North Waukegan Rd., North Chicago, IL 60064, United States.
authors: Phil
authors: P
authors: Cox
authors: AbbVie Bioresearch Center, 100 Research Dr., Worcester, MA 01545, United States.
authors: David B
authors: DB
authors: Duignan
authors: AbbVie Bioresearch Center, 100 Research Dr., Worcester, MA 01545, United States.
authors: Don
authors: D
authors: Konopacki
authors: AbbVie Bioresearch Center, 100 Research Dr., Worcester, MA 01545, United States.
authors: Gagandeep
authors: G
authors: Somal
authors: AbbVie, 1 North Waukegan Rd., North Chicago, IL 60064, United States.
authors: Anil
authors: A
authors: Vasudevan
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000201:enzymology; D004285:Dogs; D005663:Furans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D062105:Molecular Docking Simulation; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D000072377:Syk Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D005663:Furans; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000072377:Syk Kinase
keywords: Furano[3,2-d]pyrimidine; Kinase inhibitor; Rheumatoid arthritis; Spleen tyrosine kinase; Syk