Preparation of seven-membered rings by the reaction of cyclopropylcarbene-tungsten and molybdenum complexes with alkynes

The reaction between alkynes and cyclopropylcarbene-tungsten and molybdenum complexes has been examined. Depending upon the conditions of the reaction, either cycloheptadienones or furanones are obtained. The scope, limitation, and mechanistic rationale for observed selectivities are discussed

The anxiolytic-like effects of the novel, orally active nociceptin NOP receptor agonist, 8-[bis(2-methylphenyl)methyl]-3-phenyl-8- azabicyclo[3.2.1]octan-3-ol (SCH 221510) JPET #136937 2 Running Title: Anxiolytic-like effects of the NOP agonist, SCH 22151

Abstract Orphanin FQ/nociceptin (OFQ/N) is the endogenously occurring peptide ligand for the nociceptin opioid receptor (NOP) that produces anxiolytic-like effects in mice and rats

Discovery and Structure Enabled Synthesis of 2,6-Diaminopyrimidin-4-one IRAK4 Inhibitors

We report the identification and synthesis of a series of aminopyrimidin-4-one IRAK4 inhibitors. Through high throughput screening, an aminopyrimidine hit was identified and modified via structure enabled design to generate a new, potent, and kinase selective pyrimidin-4-one chemotype. This chemotype is exemplified by compound <b>16</b>, which has potent IRAK4 inhibition activity (IC₅₀ = 27 nM) and excellent kinase selectivity (>100-fold against 99% of 111 tested kinases), and compound <b>31</b>, which displays potent IRAK4 activity (IC₅₀ = 93 nM) and good rat bioavailability (<i>F</i> = 42%)