title: Discovery of orally bioavailable imidazo[1,2-a]pyrazine-based Aurora kinase inhibitors.
abstract: We report a series of potent imidazo[1,2-a]pyrazine-based Aurora kinase inhibitors. Optimization of the solvent accessible 8-position led to improvements in both oral bioavailability and off-target kinase inhibition. Compound 25 demonstrates anti-tumor activity in an A2780 ovarian tumor xenograft model.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, 320 Bent Street, Cambridge, MA 02141, USA. david.belanger@merck.com
authors.forename: David B
authors.initials: DB
authors.lastname: Belanger
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Williams
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Curran
authors.forename: Amit K
authors.initials: AK
authors.lastname: Mandal
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Meng
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Rainka
authors.forename: Tao
authors.initials: T
authors.lastname: Yu
authors.forename: Neng-Yang
authors.initials: NY
authors.lastname: Shih
authors.forename: M Arshad
authors.initials: MA
authors.lastname: Siddiqui
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.forename: Seema
authors.initials: S
authors.lastname: Tevar
authors.forename: Suining
authors.initials: S
authors.lastname: Lee
authors.forename: Lianzhu
authors.initials: L
authors.lastname: Liang
authors.forename: Kimberly
authors.initials: K
authors.lastname: Gray
authors.forename: Bohdan
authors.initials: B
authors.lastname: Yaremko
authors.forename: Jennifer
authors.initials: J
authors.lastname: Jones
authors.forename: Elizabeth B
authors.initials: EB
authors.lastname: Smith
authors.forename: Dan B
authors.initials: DB
authors.lastname: Prelusky
authors.forename: Andrea D
authors.initials: AD
authors.lastname: Basso
mesh_terms: D000284:Administration, Oral; D000818:Animals; D064127:Aurora Kinases; D001682:Biological Availability; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011719:Pyrazines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D011719:Pyrazines; C556838:imidazo(1,2-a)pyrazine; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases