Optimization of activity, selectivity, and liability profiles in 5-oxopyrrolopyridine DPP4 inhibitors leading to clinical candidate (Sa)-2-(3-(aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-5-oxo-5H-pyrrolo[3,4-b]pyridin-6(7H)-yl)-N,N-dimethylacetamide (BMS-767778). | LitMetric
Metabolic Diseases Chemistry, ‡Metabolic Diseases Biology, §Pharmaceutical Candidate Optimization, ∥Protein Science and Structure, ⊥Computer-Assisted Drug Design, Bristol-Myers Squibb Research and Development , Princeton, New Jersey 08543-5400, United States.
Published: September 2013
AI Article Synopsis
Article Abstract
Optimization of a 5-oxopyrrolopyridine series based upon structure-activity relationships (SARs) developed from our previous efforts on a number of related bicyclic series yielded compound 2s (BMS-767778) with an overall activity, selectivity, efficacy, PK, and developability profile suitable for progression into the clinic. SAR in the series and characterization of 2s are described.
Osteoarthritis (OA) is a degenerative joint disease that primarily affects the elderly worldwide. It is characterized by local inflammation, which can be targeted therapeutically using natural anti-inflammatory compounds such as curcumin. This scoping review explores the therapeutic effects and mechanisms of curcumin in OA management.
Northeast Normal University, Key Laboratory of Polyoxometalate and Reticular Material Chemistry of Ministry of Education, Institute of Functional Material Chemistry, Local United Engineering Lab for Power Battery, CHINA.
Construction of metal-organic cages (MOCs) with internal modifications is a promising avenue to build enzyme-like cavities and unlocking the mystery of highly catalytic activity and selectivity of enzymes. However, current interests are mainly focused on single-metal-node cages, little achievement has been expended to metalloclusters-based architectures, and the in situ endogenous generation of metal clusters. Herein, based on the hard-soft-acids-bases (HSAB), the metalloclusters-based heterometallic MOC (Cu3VMOP) constructed of [Cu3OPz3]+ and [V6O6(OCH3)9(SO4)(CO2)3]2- clusters was obtained by one-pot method.
The reverse water gas shift (RWGS) reaction provides a convenient approach to convert CO2 to CO, which facilitates to achieve the goals of carbon peaking and carbon neutrality. Herein, the Cu/CeO2 catalyst prepared by a co-precipitation method using a mixture of Na2CO3 and NaOH at pH of 10 (sample Cu/CeO2-10) achieved an intrinsic reaction rate of 428.4 mmol•gcat-1•h-1 with 100% CO selectivity at 400 °C and CO2/H2 ratio of 1:4, which is much higher than Cu/CeO2 prepared by impregnation and other methods.
Laboratório Associado para a Química Verde (LAQV), Rede de Química e Tecnologia (REQUIMTE), Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal.
The photoswitching of supramolecular host-guest complexes is the basis of numerous molecularly controlled macroscopic functions, such as sol-gel transition, photopharmacology, the active transport of ions or molecules, light-powered molecular machines, and much more. The most commonly used systems employ photoactive azobenzene guests and synthetic host molecules, which bind as the stable isomers and dissociate as the forms after exposure to UV light. We present a new, extraordinarily efficient cucurbit[7]uril (CB7)/diazocine host/guest complex with inverted stability that self-assembles under UV irradiation and dissociates in the dark.
Copper-based sulfides are attractive candidates for NIR I and II responsive photothermal therapy but often suffer from high hydrophobicity, suboptimal photothermal conversion, and poor biostability and biocompatibility. In the present work, a rapid, one-pot synthesis method was developed to obtain Au-doped CuS (ACSH NDs) dual plasmonic nanodots. ACSH NDs exhibit excellent peroxidase-like catalytic activity for pH-responsive OH radical generation along with efficient glutathione depletion under tumor microenvironment mimicking conditions.
