title: 3D Pharmacophore Model-Assisted Discovery of Novel CDC7 Inhibitors.
abstract: A ligand-based 3D pharmacophore model for serine/threonine kinase CDC7 inhibition was created and successfully applied in the discovery of novel 2-(heteroaryl)-6,7-dihydrothieno[3,2-c]pyridin-4(5H)-ones. The pharmacophore model provided a hypothesis for lead generation missed by docking to a homology model. Medicinal chemistry exploration of the series revealed clear structure-activity relationships consistent with the pharmacophore model and pointed to further optimization opportunities.
authors.affiliation: Global Discovery Chemistry/Oncology & Exploratory Chemistry, Novartis Institutes for Biomedical Research , 4560 Horton Street, Emeryville, California 94608, United States.
authors.forename: Mika
authors.initials: M
authors.lastname: Lindvall
authors.affiliation: Global Discovery Chemistry/Oncology & Exploratory Chemistry, Novartis Institutes for Biomedical Research , 4560 Horton Street, Emeryville, California 94608, United States.
authors.forename: Christopher
authors.initials: C
authors.lastname: McBride
authors.affiliation: Global Discovery Chemistry/Oncology & Exploratory Chemistry, Novartis Institutes for Biomedical Research , 4560 Horton Street, Emeryville, California 94608, United States.
authors.forename: Maureen
authors.initials: M
authors.lastname: McKenna
authors.affiliation: Global Discovery Chemistry/Oncology & Exploratory Chemistry, Novartis Institutes for Biomedical Research , 4560 Horton Street, Emeryville, California 94608, United States.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Gesner
authors.affiliation: Global Discovery Chemistry/Oncology & Exploratory Chemistry, Novartis Institutes for Biomedical Research , 4560 Horton Street, Emeryville, California 94608, United States.
authors.forename: Asha
authors.initials: A
authors.lastname: Yabannavar
authors.affiliation: Global Discovery Chemistry/Oncology & Exploratory Chemistry, Novartis Institutes for Biomedical Research , 4560 Horton Street, Emeryville, California 94608, United States.
authors.forename: Kent
authors.initials: K
authors.lastname: Wong
authors.affiliation: Global Discovery Chemistry/Oncology & Exploratory Chemistry, Novartis Institutes for Biomedical Research , 4560 Horton Street, Emeryville, California 94608, United States.
authors.forename: Song
authors.initials: S
authors.lastname: Lin
authors.affiliation: Global Discovery Chemistry/Oncology & Exploratory Chemistry, Novartis Institutes for Biomedical Research , 4560 Horton Street, Emeryville, California 94608, United States.
authors.forename: Annette
authors.initials: A
authors.lastname: Walter
authors.affiliation: Global Discovery Chemistry/Oncology & Exploratory Chemistry, Novartis Institutes for Biomedical Research , 4560 Horton Street, Emeryville, California 94608, United States.
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Shafer
keywords: CDC7; homology model; kinase; lead generation; pharmacophore model; structure−activity relationship