title: 2-Amino-7-substituted benzoxazole analogs as potent RSK2 inhibitors.
abstract: 2-Amino-7-substituted benzoxazole analogs were identified by HTS as inhibitors of RSK2. Molecular modeling and medicinal chemistry techniques were employed to explore the SAR for this series with a focus of improving in vitro and target modulation potency and physicochemical properties.
authors.affiliation: Global Discovery Chemistry/Oncology & Exploratory Chemistry, Novartis Institutes for Biomedical Research, 4560 Horton Street, Emeryville, CA 94608, USA.
authors.forename: Abran
authors.initials: A
authors.lastname: Costales
authors.affiliation: Global Discovery Chemistry/Oncology & Exploratory Chemistry, Novartis Institutes for Biomedical Research, 4560 Horton Street, Emeryville, CA 94608, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Mathur
authors.affiliation: Global Discovery Chemistry/Oncology & Exploratory Chemistry, Novartis Institutes for Biomedical Research, 4560 Horton Street, Emeryville, CA 94608, USA.
authors.forename: Savithri
authors.initials: S
authors.lastname: Ramurthy
authors.affiliation: Global Discovery Chemistry/Oncology & Exploratory Chemistry, Novartis Institutes for Biomedical Research, 4560 Horton Street, Emeryville, CA 94608, USA.
authors.forename: Jiong
authors.initials: J
authors.lastname: Lan
authors.affiliation: Global Discovery Chemistry/Oncology & Exploratory Chemistry, Novartis Institutes for Biomedical Research, 4560 Horton Street, Emeryville, CA 94608, USA.
authors.forename: Sharadha
authors.initials: S
authors.lastname: Subramanian
authors.affiliation: Global Discovery Chemistry/Oncology & Exploratory Chemistry, Novartis Institutes for Biomedical Research, 4560 Horton Street, Emeryville, CA 94608, USA.
authors.forename: Rama
authors.initials: R
authors.lastname: Jain
authors.affiliation: Global Discovery Chemistry/Oncology & Exploratory Chemistry, Novartis Institutes for Biomedical Research, 4560 Horton Street, Emeryville, CA 94608, USA.
authors.forename: Gordana
authors.initials: G
authors.lastname: Atallah
authors.affiliation: Global Discovery Chemistry/Oncology & Exploratory Chemistry, Novartis Institutes for Biomedical Research, 4560 Horton Street, Emeryville, CA 94608, USA.
authors.forename: Lina
authors.initials: L
authors.lastname: Setti
authors.affiliation: Global Discovery Chemistry/Oncology & Exploratory Chemistry, Novartis Institutes for Biomedical Research, 4560 Horton Street, Emeryville, CA 94608, USA.
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, CA 94608, USA.
authors.forename: Brent A
authors.initials: BA
authors.lastname: Appleton
authors.affiliation: Global Discovery Chemistry/Oncology & Exploratory Chemistry, Novartis Institutes for Biomedical Research, 4560 Horton Street, Emeryville, CA 94608, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Ornelas
authors.affiliation: Global Discovery Chemistry/Oncology & Exploratory Chemistry, Novartis Institutes for Biomedical Research, 4560 Horton Street, Emeryville, CA 94608, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Feucht
authors.affiliation: Global Discovery Chemistry/Oncology & Exploratory Chemistry, Novartis Institutes for Biomedical Research, 4560 Horton Street, Emeryville, CA 94608, USA.
authors.forename: Bob
authors.initials: B
authors.lastname: Warne
authors.affiliation: Global Discovery Chemistry/Oncology & Exploratory Chemistry, Novartis Institutes for Biomedical Research, 4560 Horton Street, Emeryville, CA 94608, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Doyle
authors.affiliation: Global Discovery Chemistry/Oncology & Exploratory Chemistry, Novartis Institutes for Biomedical Research, 4560 Horton Street, Emeryville, CA 94608, USA.
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Basham
authors.affiliation: Global Discovery Chemistry/Oncology & Exploratory Chemistry, Novartis Institutes for Biomedical Research, 4560 Horton Street, Emeryville, CA 94608, USA.
authors.forename: Ida
authors.initials: I
authors.lastname: Aronchik
authors.affiliation: Global Discovery Chemistry/Oncology & Exploratory Chemistry, Novartis Institutes for Biomedical Research, 4560 Horton Street, Emeryville, CA 94608, USA.
authors.forename: Anne B
authors.initials: AB
authors.lastname: Jefferson
authors.affiliation: Global Discovery Chemistry/Oncology & Exploratory Chemistry, Novartis Institutes for Biomedical Research, 4560 Horton Street, Emeryville, CA 94608, USA. Electronic address: cynthia.shafer@novartis.com.
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Shafer
mesh_terms: D001583:Benzoxazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006801:Humans; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D001583:Benzoxazoles; D047428:Protein Kinase Inhibitors; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C069330:ribosomal protein S6 kinase, 90kDa, polypeptide 3
keywords: Benzoxazole; HTS; Heterocycle; Kinase; RSK