50487-61-1

Upstream product

• 38204-36-3 p-chlorothiobenzoylthioacetic acid 
• 3335-29-3 (4-chlorophenyl)(piperidin-1-yl)methanethione 
• 536-40-3 4-chlorobenzoic acid hydrazide 

Downstream Products

• 106746-18-3 2-(4-chlorophenyl)-5-(pyrid-3-yl)-4,5-dihydro-1,3,4-thiadiazole 
• 84352-95-4 5-(4-chlorophenyl)-1,3,4-thiadiazol-2(3H)-one 
• 117342-61-7 2-(4-chlorophenyl)-1,3,4-thiadiazole 
• 55210-95-2 2-(4-chlorophenyl)-5-methyl-1,3,4-thiadiazole 
• 74397-03-8 5-(4-Chloro-phenyl)-2-methoxycarbonylmethyl-2,3-dihydro-[1,3,4]thiadiazole-2-carboxylic acid methyl ester 
• 74397-06-1 [5-(4-Chloro-phenyl)-2,3-dihydro-[1,3,4]thiadiazol-2-yl]-acetic acid methyl ester 

Relevant academic research and scientific papers

5-Phenyl-1,3,4-oxadiazol-2(3 H)-ones Are Potent Inhibitors of Notum Carboxylesterase Activity Identified by the Optimization of a Crystallographic Fragment Screening Hit

Carboxylesterase Notum is a negative regulator of the Wnt signaling pathway. There is an emerging understanding of the role Notum plays in disease, supporting the need to discover new small-molecule inhibitors. A crystallographic X-ray fragment screen was performed, which identified fragment hit 1,2,3-Triazole 7 as an attractive starting point for a structure-based drug design hit-To-lead program. Optimization of 7 identified oxadiazol-2-one 23dd as a preferred example with properties consistent with drug-like chemical space. Screening 23dd in a cell-based TCF/LEF reporter gene assay restored the activation of Wnt signaling in the presence of Notum. Mouse pharmacokinetic studies with oral administration of 23dd demonstrated good plasma exposure and partial blood-brain barrier penetration. Significant progress was made in developing fragment hit 7 into lead 23dd (>600-fold increase in activity), making it suitable as a new chemical tool for exploring the role of Notum-mediated regulation of Wnt signaling.

Compounds and compositions as lxr modulators

The invention provides compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with the activity of liver X receptors (LXRs).

ANTIFUNGAL AGENTS

Compounds of formula (I), and pharmaceutically acceptable salts thereof, may be used in therapy, for example as antifungal agents, wherein: R1, R2 and R3 are as defined herein. Certain compounds of formula (I) are also provided. Compounds of formula (I), and agriculturally acceptable salts thereof, may also be used as agricultural fungicides.