title: Discovery of potent, selective and orally bioavailable imidazo[1,5-a]pyrazine derived ACK1 inhibitors.
abstract: This Letter describes the medicinal chemistry effort towards a series of novel imidazo[1,5-a]pyrazine derived inhibitors of ACK1. Virtual screening led to the discovery of the initial hit, and subsequent exploration of structure-activity relationships and optimization of drug metabolism and pharmacokinetic properties led to the identification of potent, selective and orally bioavailable ACK1 inhibitors.
authors: OSI Pharmaceuticals, LLC, A Wholly-Owned Subsidiary of Astellas US LLC, 1 Bioscience Park Drive, Farmingdale, NY 11735, USA. Meizhong.jin@astellas.com
authors: Meizhong
authors: M
authors: Jin
authors: Jing
authors: J
authors: Wang
authors: Andrew
authors: A
authors: Kleinberg
authors: Mridula
authors: M
authors: Kadalbajoo
authors: Kam W
authors: KW
authors: Siu
authors: Andrew
authors: A
authors: Cooke
authors: Mark A
authors: MA
authors: Bittner
authors: Yan
authors: Y
authors: Yao
authors: April
authors: A
authors: Thelemann
authors: Qunsheng
authors: Q
authors: Ji
authors: Shripad
authors: S
authors: Bhagwat
authors: Kristen M
authors: KM
authors: Mulvihill
authors: Josef A
authors: JA
authors: Rechka
authors: Jonathan A
authors: JA
authors: Pachter
authors: Andrew P
authors: AP
authors: Crew
authors: David
authors: D
authors: Epstein
authors: Mark J
authors: MJ
authors: Mulvihill
mesh_terms: D000284:Administration, Oral; D000818:Animals; D006801:Humans; D007093:Imidazoles / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D051379:Mice; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011719:Pyrazines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D011719:Pyrazines; D011505:Protein-Tyrosine Kinases; C403262:TNK2 protein, human