Unknown

Dataset Information

0

Design of Fluorine-Containing 3,4-Diarylfuran-2(5H)-ones as Selective COX-1 Inhibitors.

ABSTRACT: We report the design and synthesis of fluorine-containing cyclooxygenase-1 (COX-1)-selective inhibitors to serve as prototypes for the development of a COX-1-targeted imaging agent. Deletion of the SO2CH3 group of rofecoxib switches the compound from a COX-2- to a COX-1-selective inhibitor, providing a 3,4-diarylfuran-2(5H)-one scaffold for structure-activity relationship studies of COX-1 inhibition. A wide range of fluorine-containing 3,4-diarylfuran-2(5H)-ones were designed, synthesized, and tested for their ability to selectively inhibit COX-1 in purified protein and human cancer cell assays. Compounds containing a fluoro-substituent on the C-3 phenyl ring and a methoxy-substituent on the C-4 phenyl ring of the 3,4-diarylfuran-2(5H)-one scaffold were the best COX-1-selective agents of those evaluated, exhibiting IC50s in the submicromolar range. These compounds provide the foundation for development of an agent to facilitate radiologic imaging of ovarian cancer expressing elevated levels of COX-1.

SUBMITTER: Uddin MJ 

PROVIDER: S-EPMC4233350 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Design of Fluorine-Containing 3,4-Diarylfuran-2(5H)-ones as Selective COX-1 Inhibitors.

Uddin Md Jashim MJ   Elleman Anna V AV   Ghebreselasie Kebreab K   Daniel Cristina K CK   Crews Brenda C BC   Nance Kellie D KD   Huda Tamanna T   Marnett Lawrence J LJ  

ACS medicinal chemistry letters 20141012 11

We report the design and synthesis of fluorine-containing cyclooxygenase-1 (COX-1)-selective inhibitors to serve as prototypes for the development of a COX-1-targeted imaging agent. Deletion of the SO2CH3 group of rofecoxib switches the compound from a COX-2- to a COX-1-selective inhibitor, providing a 3,4-diarylfuran-2(5H)-one scaffold for structure-activity relationship studies of COX-1 inhibition. A wide range of fluorine-containing 3,4-diarylfuran-2(5H)-ones were designed, synthesized, and t  ...[more]

Similar Datasets

Unknown Design, Synthesis and Comprehensive Investigations of Pyrrolo[3,4-d]pyridazinone-Based 1,3,4-Oxadiazole as New Class of Selective COX-2 Inhibitors.
| S-EPMC7766220 | biostudies-literature
Unknown Design and Synthesis of Imidazopyrazolopyridines as Novel Selective COX-2 Inhibitors.
| S-EPMC6332013 | biostudies-literature
Unknown Aminopyridyl/Pyrazinyl Spiro[indoline-3,4'-piperidine]-2-ones As Highly Selective and Efficacious c-Met/ALK Inhibitors.
| S-EPMC4027565 | biostudies-literature
Unknown Design and Discovery of 2-Arylquinazolin-4-ones as Potent and Selective Inhibitors of Tankyrases.
| S-EPMC4027532 | biostudies-literature
Unknown Design, Synthesis and Biological Evaluation of Novel Peptide-Like Analogues as Selective COX-2 Inhibitors.
| S-EPMC5937080 | biostudies-literature
Unknown Synthesis, Anti-Inflammatory and Anti- Nociceptive Activities and Cytotoxic Effect of Novel Thiazolidin-4-ones Derivatives as Selective Cyclooxygenase (COX-2) Inhibitors.
| S-EPMC3933800 | biostudies-literature
Unknown GLUT1-mediated selective tumor targeting with fluorine containing platinum(II) glycoconjugates.
| S-EPMC5503626 | biostudies-literature
Unknown Design, Synthesis and Biological Evaluation of New Imidazo[2,1-b]Thiazole Derivatives as Selective COX-2 Inhibitors.
| S-EPMC6269562 | biostudies-literature
Unknown Design, synthesis and biological evaluation of tricyclic pyrazolo[1,5-c][1,3]benzoxazin-5(5H)-one scaffolds as selective BuChE inhibitors.
| S-EPMC6179045 | biostudies-literature
Unknown Design, Synthesis, and Antiproliferative Activity of Selective Histone Deacetylases 6 Inhibitors Containing a Tetrahydropyridopyrimidine Scaffold.
| S-EPMC10648541 | biostudies-literature