Rational design synthesis and evaluation of a novel near-infrared fluorescent probe for selective imaging of amyloid-β aggregates in Alzheimer's disease.

Alzheimer's disease (AD) is a degenerative neurological disorder that remains incurable to date, seriously affecting the quality of life and health of those affected. One of the key neuropathological hallmarks of AD is the formation of amyloid-β (Aβ) plaques. Near-infrared (NIR) probes that possess a large Stokes shift show great potential for imaging of Aβ plaques in vivo and in vitro.

Design, synthesis and biological evaluation of small molecule fluorescent probes targeting EGFR for tumor detection and treatment.

The epidermal growth factor receptor (EGFR) is a tyrosine kinase receptor that plays a crucial role in cell differentiation and tumor progression, and its overexpression is closely associated with the development and metastasis of multiple cancers. The development of a fluorescent probe capable of targeting EGFR while simultaneously integrating diagnostic and therapeutic functions could have a profound impact on the treatment of related cancers. In this study, we developed a series of EGFR-targeting probes that consisted of an environment-sensitive 1,8-naphthalimide fluorophore, a linker unit and a targeting unit (gefitinib), using a coupling strategy.

Novel dual-target μ‑opioid and TRPV1 ligands as potential pharmacotherapeutics for pain management.

Currently, the development of effective analgesic drugs with few side effects remains a great challenge. Studies have suggested that multi-target drug treatments show high efficacy and reduced side effects compared to single-target drug therapies. In this work, we designed and synthesized two series of novel MOR/TRPV1 dual active ligands in which the phenylpiperidine group or the N-phenyl-N-(piperidin-4-yl) propionamide group as the MOR pharmacophore was fused to the benzylpiperazinyl urea-based TRPV1 pharmacophore.

Discovery of (S)-N-(3-isopropylphenyl)-2-(5-phenylthiazol-2-yl)pyrrolidine-1-carboxamide as potent and brain-penetrant TRPV1 antagonist.

Transient receptor potential vanilloid 1 (TRPV1) antagonists can inhibit the transmission of nociceptive signals from the peripheral to the central nervous system (CNS), providing a new strategy for pain relief. In this work, in order to develop potent, CNS-penetrant, and orally available TRPV1 antagonists, three series of novel molecules based on the key pharmacophore structures of classic TRPV1 ligands SB-705498 and MDR-652 were designed and synthesized. Through systematic in vitro and in vivo bioassays, (S)-N-(3-isopropylphenyl)-2-(5-phenylthiazol-2-yl)pyrrolidine-1-carboxamide (7q) was finally identified, which had enhanced TRPV1 antagonistic activity (IC (capsaicin) = 2.