The nonselective glucocorticoid receptor (GR) antagonist mifepristone has been approved in the U.S. for the treatment of selected patients with Cushing's syndrome. While this drug is highly effective, lack of selectivity for GR leads to unwanted side effects in some patients. Optimization of the previously described fused azadecalin series of selective GR antagonists led to the identification of CORT125134, which is currently being evaluated in a phase 2 clinical study in patients with Cushing's syndrome.
Bench-scale studies demonstrated the efficacy of hydrothermal oxidation for the treatment of
wastes derived from the alkaline hydrolysis of the high explosive PBX 9404 (94% HMX, 3%
nitrocellulose, and 3% chloroethyl phosphate). Specifically, chemical kinetics studies were used
to deduce major global reaction pathways, and to develop a kinetic model. Although the hydrolysis
liquor is a complicated waste matrix, a three-parameter kinetic model captured major reaction
paths. The kinetic model used total organic carbon (TOC) as a bulk parameter for dissolved
organic materials, while NO
x
- was used to represent the oxidized nitrogen species in solution
(NO2
- and NO3
-). With the use of the kinetic model, an optimal treatment strategy using two
oxidation stages was derived. The first stage involved balancing NO
x
- and O2 redox chemistry
to minimize aqueous nitrogen in the effluent, while the second stage mineralized the remaining
TOC.
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