- Design, Synthesis and Evaluation of Oxazaborine Inhibitors of the NLRP3 Inflammasome
-
The NLRP3 inflammasome is an important regulator of the sterile inflammatory response, and its activation by host-derived sterile molecules leads to the intracellular activation of caspase-1, processing of the pro-inflammatory cytokines interleukin-1β (IL-1β)/IL-18, and pyroptotic cell death. Inappropriate activation of NLRP3 drives a chronic inflammatory response and is implicated in several non-communicable diseases, including gout, atherosclerosis, type II diabetes and Alzheimer's disease. In this study, we report the design, synthesis and biological evaluation of novel boron compounds (NBCs) as NLRP3 inflammasome inhibitors. Structure–activity relationships (SAR) show that 4-fluoro substituents on the phenyl rings retain NLRP3 inhibitory activity, whereas more steric and lipophilic substituents diminish activity. Loss of inhibitory activity is also observed if the CCl3 group on the oxazaborine ring is replaced by a CF3 group. These findings provide additional understanding of the NBC series and will aid in the development of these NLRP3 inhibitors as tool compounds or therapeutic candidates for sterile inflammatory diseases.
- Baldwin, Alex G.,Tapia, Victor S.,Swanton, Tessa,White, Claire S.,Beswick, James A.,Brough, David,Freeman, Sally
-
p. 312 - 320
(2018/02/09)
-
- PROCESS FOR MANUFACTURING PICOLINATE BORINIC ESTERS
-
The present invention relates to the field of boron-containing compounds, particularly boron compounds and pharmaceutical compositions thereof that exhibit with antibacterial and/or anti-inflammatory activities, and uses thereof. Methods for preparing and
- -
-
Page/Page column 14-15
(2008/06/13)
-
- Topical formulations of borinic acid antibiotics and their methods of use
-
Disclosed are topical formulations, for example, creams, gels, or lotions, of borinic acid antibiotic compounds active against acne vulgaris or secondarily infected skin conditions.
- -
-
Page/Page column 11
(2008/06/13)
-
- Identification of a novel boron-containing antibacterial agent (AN0128) with anti-inflammatory activity, for the potential treatment of cutaneous diseases
-
A series of borinic acid picolinate esters were synthesized and screened for their minimum inhibitory concentration (MIC) against Gram-positive and -negative bacteria. Our lead compounds were then screened for anti-inflammatory activity. From these studie
- Baker, Stephen J.,Akama, Tsutomu,Zhang, Yong-Kang,Sauro, Vittorio,Pandit, Chetan,Singh, Rajeshwar,Kully, Maureen,Khan, Jehangir,Plattner, Jacob J.,Benkovic, Stephen J.,Lee, Ving,Maples, Kirk R.
-
p. 5963 - 5967
(2007/10/03)
-
- Anti-viral uses of borinic acid complexes
-
Compositions and methods of use of borinic acid complexes, especially hydroxyquinoline, imidazole and picolinic acid derivatives, as anti-viral agents as well as therapeutic agents for the treatment of diseases caused by viruses are described.
- -
-
Page/Page column 17-18
(2008/06/13)
-
- ANTI-PARASITIC USES OF BORINIC ACID COMPLEXES
-
Compositions and methods of use of borinic acid complexes, especially hydroxyquinoline, imidazole and picolinic acid derivatives as anti-parasitic agents as well as therapeutic agents for the treatment of diseases caused by parasite are described.
- -
-
Page/Page column 64
(2010/02/15)
-
- BORON-CONTAINING COMPOUNDS AND METHODS OF USE
-
Methods of treating and/or preventing surface infections, such as acne, in an animal, such as a human being, using antibiotics incorporating borinic acid complexes, especially picolinic acid derivatives, are disclosed, along with compositions of these ant
- -
-
Page/Page column 40-41
(2010/02/15)
-
