111205-03-9

Seven luminescent copper(I) complexes bearing four-coordinate N-heterocyclic carbene (NHC) ligands with varying electron-withdrawing substituents including –CF3, –CN, –COCH3, and –CHO groups at the pyridine ring part of the carbene are reported in this study. P1-P4 without the methyl group show better light absorption in low-energy region compared with P5-P7 with the methyl group at the α-position of the pyridine ring. The emitting state of all the complexes is regarded as the 3MLCT/3LLCT character. P1-P4 exhibit the emission maximum in the range of 537–547 nm with the photoluminescence quantum yields (PLQY) of 12.7–21.9% in PMMA films and excited state lifetimes (τ) of 14.7–22.6 μs. The emission wavelengths of P5-P7 are blue-shifted to 505–513 nm compared with those of P1-P4, showing the higher PLQY of 38.0–57.3% and longer τ of 36.2–84.8 μs. Theoretical calculations were used to rationalize the photophysical properties.

Protein-protein modulation has emerged as a proven approach to drug discovery. While significant progress has been gained in developing protein-protein interaction (PPI) inhibitors, the orthogonal approach of PPI stabilization lacks established methodologies for drug design. Here, we report the systematic ″bottom-up″ development of a reversible covalent PPI stabilizer. An imine bond was employed to anchor the stabilizer at the interface of the 14-3-3/p65 complex, leading to a molecular glue that elicited an 81-fold increase in complex stabilization. Utilizing protein crystallography and biophysical assays, we deconvoluted how chemical properties of a stabilizer translate to structural changes in the ternary 14-3-3/p65/molecular glue complex. Furthermore, we explore how this leads to high cooperativity and increased stability of the complex.

The present invention provides a compound which has a cholinergic muscarinic M1 receptor positive allosteric modulator activity and may be useful as a medicament such as an agent for the prophylaxis or treatment of Alzheimer's disease, schizophrenia, pain, sleep disorder, Parkinson's disease dementia, Lewy body dementia and the like. The present invention relates to a compound represented by the formula (I) or a salt thereof. In the formula (I), each symbol is as described in the attached specification.

This invention relates to pyridone-pyridyl-imidazolyl and triazolyl compounds, including methods for increasing cardiac contractility, pharmaceutical compositions including the same and methods for the preparation thereof.

Compounds of the formula STR1 wherein: Het is imidazol-1-yl or 1,2,4-triazol-1-yl; py is 2-, 3-, or 4-pyridyl; R and R2 are H or alkyl; R1 is H, alkyl or vicinal R1 groups from a C--C double bond; and x is 0 or 1; or a pharmaceutically acceptable salt thereof, and pharmaceutical compositions including the same for cardiotonic uses and methods of treating congestive heart failure.