title: Design, synthesis and optimization of novel Alk5 (activin-like kinase 5) inhibitors.
abstract: Using SBDD, a series of 4-amino-7-azaindoles were discovered as a novel class of Alk5 inhibitors that are potent in both Alk5 enzymatic and cellular assays. Subsequently a ring cyclization strategy was utilized to improve ADME properties leading to the discovery of a series of 1H-imidazo[4,5-c]pyridin-2(3H)-one drug like Alk5 inhibitors.
authors.affiliation: Takeda California, 10410 Science Center Drive, San Diego, CA 92121, United States.
authors.forename: Haixia
authors.initials: H
authors.lastname: Wang
authors.affiliation: Takeda California, 10410 Science Center Drive, San Diego, CA 92121, United States.
authors.forename: J David
authors.initials: JD
authors.lastname: Lawson
authors.affiliation: Takeda California, 10410 Science Center Drive, San Diego, CA 92121, United States.
authors.forename: Nick
authors.initials: N
authors.lastname: Scorah
authors.affiliation: Takeda California, 10410 Science Center Drive, San Diego, CA 92121, United States.
authors.forename: Ruhi
authors.initials: R
authors.lastname: Kamran
authors.affiliation: Takeda California, 10410 Science Center Drive, San Diego, CA 92121, United States.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Hixon
authors.affiliation: Takeda California, 10410 Science Center Drive, San Diego, CA 92121, United States.
authors.forename: Joy
authors.initials: J
authors.lastname: Atienza
authors.affiliation: Takeda California, 10410 Science Center Drive, San Diego, CA 92121, United States.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Dougan
authors.affiliation: Takeda California, 10410 Science Center Drive, San Diego, CA 92121, United States.
authors.forename: Mark
authors.initials: M
authors.lastname: Sabat
mesh_terms: D000818:Animals; D003500:Cyclization; D015195:Drug Design; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000737:chemistry; D011758:Pyrroles / Q000737:chemistry; D051381:Rats; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D007211:Indoles; D011743:Pyrimidines; D011758:Pyrroles; D018125:Receptors, Transforming Growth Factor beta; C527741:pyrrolopyrimidine; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human; C000625843:Tgfbr1 protein, rat
keywords: Activin; Alk5; Factor; Growth; Inhibitors; Kinase; SBDD; Transforming