Cobalt-Catalyzed Selective Synthesis of Isoquinolines Using Picolinamide as a Traceless Directing Group

Picolinamide has first been employed as a traceless directing group for the cobalt-catalyzed oxidative annulation of benzylamides with alkynes to synthesize isoquinolines through C–H/N–H bonds activation. Oxygen is used as a terminal oxidant. This protocol exhibits good functional group tolerance and excellent regioselectivity. Both terminal and internal alkynes can be efficiently applied to this catalytic system as substrates

Cobalt-Catalyzed Selective Synthesis of Isoquinolines Using Picolinamide as a Traceless Directing Group

Picolinamide has first been employed as a traceless directing group for the cobalt-catalyzed oxidative annulation of benzylamides with alkynes to synthesize isoquinolines through C–H/N–H bonds activation. Oxygen is used as a terminal oxidant. This protocol exhibits good functional group tolerance and excellent regioselectivity. Both terminal and internal alkynes can be efficiently applied to this catalytic system as substrates

Cobalt-Catalyzed Selective Synthesis of Isoquinolines Using Picolinamide as a Traceless Directing Group

Picolinamide has first been employed as a traceless directing group for the cobalt-catalyzed oxidative annulation of benzylamides with alkynes to synthesize isoquinolines through C–H/N–H bonds activation. Oxygen is used as a terminal oxidant. This protocol exhibits good functional group tolerance and excellent regioselectivity. Both terminal and internal alkynes can be efficiently applied to this catalytic system as substrates

One-Pot Regiospecific Synthesis of Quinoxalines via a CH₂‑Extrusion Reaction

A convenient “one-pot” regiospecific synthesis of substituted quinoxalines from <i>o</i>-phenylenediamines and ynones under metal-free conditions has been developed. An intermolecular Michael addition reaction, a dehydration condensation, and a base-promoted C-α-CH₂-extrusion were involved in this procedure, which features high regioselectivity, efficiency, and environmental friendliness. Various quinoxalines were provided in up to 95% yield for 33 examples

Drug Effect Prediction by Polypharmacology-Based Interaction Profiling

Most drugs exert their effects via multitarget interactions, as hypothesized by polypharmacology. While these multitarget interactions are responsible for the clinical effect profiles of drugs, current methods have failed to uncover the complex relationships between them. Here, we introduce an approach which is able to relate complex drug–protein interaction profiles with effect profiles. Structural data and registered effect profiles of all small-molecule drugs were collected, and interactions to a series of nontarget protein binding sites of each drug were calculated. Statistical analyses confirmed a close relationship between the studied 177 major effect categories and interaction profiles of ca. 1200 FDA-approved small-molecule drugs. On the basis of this relationship, the effect profiles of drugs were revealed in their entirety, and hitherto uncovered effects could be predicted in a systematic manner. Our results show that the prediction power is independent of the composition of the protein set used for interaction profile generation