ACS Medicinal Chemistry Letters最新文献

Provided herein are novel triazine derivatives as NLRP3 inhibitors, pharmaceutical compositions, use of such compounds in treating asthma or COPD, and processes for preparing such compounds.

The intersection of artificial intelligence (AI), digital therapeutics, and advanced communication frameworks offers transformative opportunities for addressing mental health disorders, neurodegenerative diseases, and communication challenges in modern networks. This Patent Highlight examines three pivotal patents that introduce deuterated empathogens for safer psychiatric treatments, AI-powered digital platforms for cognitive and immune function enhancement, and robust frameworks for AI/ML performance monitoring in wireless systems. Together, these innovations represent a paradigm shift in therapeutic and technological approaches, emphasizing the synergy of molecular and digital advancements in tackling global health and communication challenges.

Provided herein are novel indoline derivatives as serotonergic psychedelic agents, pharmaceutical compositions, use of such compounds in treating psychosis, mental illness and central nervous system (CNS) disorders and processes for preparing such compounds.

The intersection of artificial intelligence (AI), digital therapeutics, and advanced communication frameworks offers transformative opportunities for addressing mental health disorders, neurodegenerative diseases, and communication challenges in modern networks. This Patent Highlight examines three pivotal patents that introduce deuterated empathogens for safer psychiatric treatments, AI-powered digital platforms for cognitive and immune function enhancement, and robust frameworks for AI/ML performance monitoring in wireless systems. Together, these innovations represent a paradigm shift in therapeutic and technological approaches, emphasizing the synergy of molecular and digital advancements in tackling global health and communication challenges.

Provided herein are novel pyrrolopyridine compounds as 5-HT2A agonists, pharmaceutical compositions, use of such compounds in treating mental illnesses, and processes for preparing such compounds.

Provided herein are novel pyrrolopyridine compounds as 5-HT2A agonists, pharmaceutical compositions, use of such compounds in treating mental illnesses, and processes for preparing such compounds.

Lysophosphatidic acid (LPA) is a phospholipid activating different biological functions by binding to G protein-coupled receptors (LPA_1-6). Among these, the role of the LPA₁ receptor in modulating fibrotic processes is well-known, making it a therapeutic target for pulmonary fibrosis and other fibrotic disorders. Herein we report the search for a new class of LPA₁ antagonists for the oral treatment of idiopathic pulmonary fibrosis with a focus on hepatobiliary safety. Compound 7 excelled in in vitro and in vivo efficacy, showing significant efficacy both in PD studies and in a rodent lung fibrosis model, with a promising in vitro hepatic safety profile. However, in a dose range finding (DRF) toxicity study, compound 7 did not ensure safety regarding potential hepatobiliary toxicity, leading to its development being halted.

Provided herein are novel indoline derivatives as serotonergic psychedelic agents, pharmaceutical compositions, use of such compounds in treating psychosis, mental illness and central nervous system (CNS) disorders and processes for preparing such compounds.

Lysophosphatidic acid (LPA) is a phospholipid activating different biological functions by binding to G protein-coupled receptors (LPA_1–6). Among these, the role of the LPA₁ receptor in modulating fibrotic processes is well-known, making it a therapeutic target for pulmonary fibrosis and other fibrotic disorders. Herein we report the search for a new class of LPA₁ antagonists for the oral treatment of idiopathic pulmonary fibrosis with a focus on hepatobiliary safety. Compound 7 excelled in in vitro and in vivo efficacy, showing significant efficacy both in PD studies and in a rodent lung fibrosis model, with a promising in vitro hepatic safety profile. However, in a dose range finding (DRF) toxicity study, compound 7 did not ensure safety regarding potential hepatobiliary toxicity, leading to its development being halted.

Heat shock protein 90 (HSP90) is a promising target for oncology therapeutics. Over the past decades, several small molecule inhibitors have demonstrated significant antitumor activity in clinical trials. However, nearly all HSP90 inhibitors in clinical trials have failed due to toxicity or insufficient efficacy. By leveraging crystal structures and current knowledge, we synthesized and evaluated a series of novel derivatives with potent HSP90 inhibitory activity, optimized from resorcinol-based (2R, 4R)-4-phenylproline. These derivatives underwent SAR analysis, leading to the discovery of compounds 16t and 20m, which exhibit strong HSP90 binding affinity and antiproliferative effects against MCF-7, HCT116, SKBr3, K562, and A549 cell lines. Nevertheless, further optimization of derivatives 16t and 20m was required to enhance their oral bioavailability and isoform selectivity. Our findings provide valuable insights for the ongoing research into selective HSP90α inhibitors and lay a foundation for developing next-generation HSP90α inhibitors and antitumor agents.