Structure based design of novel 6,5 heterobicyclic mitogen-activated protein kinase kinase (MEK) inhibitors leading to the discovery of imidazo[1,5-a] pyrazine G-479

Bioorganic and Medicinal Chemistry Letters

Volumn 24, Issue 19, 2014, Pages 4714-4723

  Robarge, Kirk D ^a   Lee, Wendy ^a   Eigenbrot, Charles ^a   Ultsch, Mark ^a   Wiesmann, Christian ^a   Heald, Robert ^b   Price, Steve ^b   Hewitt, Joanne ^b   Jackson, Philip ^b   Savy, Pascal ^b   Burton, Brenda ^b   Choo, Edna F ^a   Pang, Jodie ^a   Boggs, Jason ^a   Yang, April ^a   Yang, Xioaye ^a   Baumgardner, Matthew ^a  

^a GENENTECH INC   (United States)

^b Argenta Discovery Ltd   (United Kingdom)

Author keywords

Imidazo 1,5 a pyrazine Imidazo 1,5 a pyridine Structure based drug design (SBDD) Oncology; inhibitors; MEK inhibitors; Mitogen activated protein kinase kinase; RAS signaling pathway

Indexed keywords

CYTOCHROME P450 INHIBITOR; HETEROCYCLIC COMPOUND; HYDROXAMIC ACID; IMIDAZO[1,5 ALPHA] PYRIDINE DERIVATIVE; MITOGEN ACTIVATED PROTEIN KINASE INHIBITOR; NITROGEN; PYRIDINE DERIVATIVE; UNCLASSIFIED DRUG; G-479 COMPOUND; IMIDAZO(1,5-A)PYRAZINE; IMIDAZOLE DERIVATIVE; MITOGEN ACTIVATED PROTEIN KINASE KINASE; PROTEIN KINASE INHIBITOR; PYRAZINE DERIVATIVE;

ANIMAL CELL; AREA UNDER THE CURVE; ARTICLE; CELL PROLIFERATION; CONTROLLED STUDY; CRYSTAL STRUCTURE; CRYSTALLOGRAPHY; DRUG CLEARANCE; DRUG DESIGN; DRUG DISTRIBUTION; DRUG HALF LIFE; DRUG POTENCY; DRUG STRUCTURE; HUMAN; HUMAN CELL; HYDROGEN BOND; LIVER MICROSOME; NONHUMAN; PATCH CLAMP TECHNIQUE; PLASMA PROTEIN BINDING; ANTAGONISTS AND INHIBITORS; CHEMICAL STRUCTURE; CHEMISTRY; DOSE RESPONSE; DRUG DEVELOPMENT; DRUG EFFECTS; HCT116 CELL LINE; METABOLISM; STRUCTURE ACTIVITY RELATION; SYNTHESIS; TUMOR CELL LINE;

CELL LINE, TUMOR; CELL PROLIFERATION; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG DISCOVERY; HCT116 CELLS; HETEROCYCLIC COMPOUNDS; HUMANS; IMIDAZOLES; MITOGEN-ACTIVATED PROTEIN KINASE KINASES; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PROTEIN KINASE INHIBITORS; PYRAZINES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84907200841     PISSN: 0960894X     EISSN: 14643405     Source Type: Journal    
DOI: 10.1016/j.bmcl.2014.08.008     Document Type: Article

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