9 research outputs found
CoMFA Study of Novel Phenyl Ring-Substituted 3α-(Diphenylmethoxy)tropane Analogues at the Dopamine Transporter
No full textDesign and Synthesis of [(2,3-Dichlorophenyl)piperazin-1-yl]alkylfluorenylcarboxamides as Novel Ligands Selective for the Dopamine D 3
No full textDesign and Synthesis of [(2,3-Dichlorophenyl)piperazin-1-yl]alkylfluorenylcarboxamides as Novel Ligands Selective for the Dopamine D 3
No full textHighly Selective Chiral N-Substituted 3α-[Bis(4‘-fluorophenyl)methoxy]tropane Analogues for the Dopamine Transporter: Synthesis and Comparative Molecular Field Analysis
No full textStructure−Activity Relationships at Monoamine Transporters and Muscarinic Receptors for N
No full text
Discovery of (<i>S</i>)‑1-(1-(4-Chloro-3-fluorophenyl)-2-hydroxyethyl)-4-(2-((1-methyl‑1<i>H</i>‑pyrazol-5-yl)amino)pyrimidin-4-yl)pyridin-2(1<i>H</i>)‑one (GDC-0994), an Extracellular Signal-Regulated Kinase 1/2 (ERK1/2) Inhibitor in Early Clinical Development
No full textThe extracellular
signal-regulated kinases ERK1/2 represent an
essential node within the RAS/RAF/MEK/ERK signaling cascade that is
commonly activated by oncogenic mutations in BRAF or RAS or by upstream
oncogenic signaling. While targeting upstream nodes with RAF and MEK
inhibitors has proven effective clinically, resistance frequently
develops through reactivation of the pathway. Simultaneous targeting
of multiple nodes in the pathway, such as MEK and ERK, offers the
prospect of enhanced efficacy as well as reduced potential for acquired
resistance. Described herein is the discovery and characterization
of GDC-0994 (<b>22</b>), an orally bioavailable small molecule
inhibitor selective for ERK kinase activity
