- Continuous-Flow Hofmann Rearrangement Using Trichloroisocyanuric Acid for the Preparation of 2-Benzoxazolinone
-
A continuous-flow preparation of 2-benzoxazolinone via the Hofmann rearrangement of salicylamide has been implemented employing trichloroisocyanuric acid as the stable and atom-economic chlorinating agent. The system was optimized to avoid solid accumulation and allow the preparation of hundreds of grams of the pure desired material over a working day. Furthermore, a trichloroisocyanuric acid (TCCA)-based chlorination of 2-benzoxazolone to the corresponding 5-chloro derivative was also carried out under batch conditions.
- Gambacorta, Guido,Baxendale, Ian R.
-
p. 422 - 430
(2022/02/01)
-
- Discovery and structure-activity relationships of modified salicylanilides as cell permeable inhibitors of poly(ADP-ribose) glycohydrolase (PARG)
-
The metabolism of poly(ADP-ribose) (PAR) in response to DNA strand breaks, which involves the concerted activities of poly(ADP-ribose) polymerases (PARPs) and poly(ADP-ribose) glycohydrolase (PARG), modulates cell recovery or cell death depending upon the level of DNA damage. While PARP inhibitors show high promise in clinical trials because of their low toxicity and selectivity for BRCA related cancers, evaluation of the therapeutic potential of PARG is limited by the lack of well-validated cell permeable inhibitors. In this study, target-related affinity profiling (TRAP), an alternative to high-throughput screening, was used to identify a number of druglike compounds from several chemical classes that demonstrated PARG inhibition in the low-micromolar range. A number of analogues of one of the most active chemotypes were synthesized to explore the structure-activity relationship (SAR) for that series. This led to the discovery of a putative pharmacophore for PARG inhibition that contains a modified salicylanilide structure. Interestingly, these compounds also inhibit PARP-1, indicating strong homology in the active sites of PARG and PARP-1 and raising a new challenge for development of PARG specific inhibitors. The cellular activity of a lead inhibitor was demonstrated by the inhibition of both PARP and PARG activity in squamous cell carcinoma cells, although preferential inhibition of PARG relative to PARP was observed. The ability of inhibitors to modulate PAR metabolism via simultaneous effects on PARPs and PARG may represent a new approach for therapeutic development.
- Steffen, Jamin D.,Coyle, Donna L.,Damodaran, Komath,Beroza, Paul,Jacobson, Myron K.
-
p. 5403 - 5413
(2011/10/02)
-
- Certain benzoxazoles and the use thereof as metal extractants
-
Benzoxazoles having the structure STR1 where R is hydrogen or an alkyl group having from 1 to 20 carbon atoms, R' is hydrogen, chlorine or an alkyl group containing from 1 to 20 carbon atoms, X is H or Chlorine and the total number of carbon atoms in R an
- -
-
-