1579976-80-9

Upstream product

• 775344-72-4 (3-(5-chlorofuran-2-yl)-5-methyl-4-phenylisoxazole) 

Downstream Products

• 1579976-83-2 2-[3-(5-chlorofuran-2-yl)-4-phenylisoxazol-5-yl]acetic acid 
• 1613135-53-7 5-(fluoromethyl)-3-(5-chlorofuran-2-yl)-4-phenylisoxazole 

Relevant academic research and scientific papers

Selective COX-1 inhibition as a target of theranostic novel diarylisoxazoles

Cyclooxygenase(COX)-1 role in some diseases is increasingly studied. 3-(5-Chlorofuran-2-yl)-5-methyl-4-phenylisoxazole (P6), a highly selective cyclooxygenase-1 inhibitor, was used as a lead to design new isoxazoles (2a-m), differently selective towards COX-1. Those isoxazoles might be useful as novel theranostic agents and also to better clarify COX-1 role in the human physiology and diseases. 2a-m were prepared in fair to good yields developing suitable synthetic strategies. They were evaluated in vitro for their COX-inhibitory activity and selectivity. Structure-activity relationship studies of the novel set of diarylisoxazoles allowed to identify new key determinants for COX-1 selectivity, and to uncover compounds appropriate for a deep pharmacokinetic and pharmacodynamic investigation. 3-(5-Chlorofuran-2yl)-4- phenylisoxazol-5-amine (2f) was the most active compound of the series, its inhibitory activity was assessed in purified enzyme (COX-1 IC50 = 1.1 μM; COX-2 IC50 > 50 μM) and in the ovarian cancer cell line (OVCAR-3) expressing only COX-1 (IC50 = 0.58 μM). Furthermore, the high inhibitory potency of 2f was rationalized through docking simulations in terms of interactions with a crystallographic model of the COX-1 binding site. We found critical interactions between the inhibitor and constriction residues R120 and Y355 at the base of the active site, as well as with S530 at the top of the side pocket.

PET radiotracer [18F]-P6 selectively targeting COX-1 as a novel biomarker in ovarian cancer: Preliminary investigation

Cyclooxygenase-1 (COX-1), but not COX-2, is expressed at high levels in the early stages of human epithelial ovarian cancer where it seems to play a key role in cancer onset and progression. As a consequence, COX-1 is an ideal biomarker for early ovarian cancer detection. A series of novel fluorinated COX-1-targeted imaging agents derived from P6 was developed by using a highly selective COX-1 inhibitor as a lead compound. Among these new compounds, designed by structural modification of P6, 3-(5-chlorofuran-2-yl)-5- (fluoromethyl)-4-phenylisoxazole ([18/19F]-P6) is the most promising derivative [IC50 = 2.0 μM (purified oCOX-1) and 1.37 μM (hOVCAR-3 cell COX-1)]. Its tosylate precursor was also prepared and, a method for radio[18F]chemistry was developed and optimized. The radiochemistry was carried out using a carrier-free K18F/Kryptofix 2.2.2 complex, that afforded [18F]-P6 in good radiochemical yield (18%) and high purity (>95%). In vivo PET/CT imaging data showed that the radiotracer [18F]-P6 was selectively taken up by COX-1-expressing ovarian carcinoma (OVCAR 3) tumor xenografts as compared with the normal leg muscle. Our results suggest that [18F]-P6 might be an useful radiotracer in preclinical and clinical settings for in vivo PET-CT imaging of tissues that express elevated levels of COX-1.