The
American Chemical Society (ACS) Green Chemistry Institute (GCI)
Pharmaceutical Roundtable conducted a study to elucidate the value
of continuous processing, which had been defined as a key research
area for green engineering. In the course of defining the business
case for continuous processing, individual cases were collected and
evaluated to determine specific drivers to implement continuous processing
and to find key success factors. The magnitude and timing of effects
and the relation to the principles of green chemistry were investigated.
Glutamate is the main excitatory transmitter in the brain, while ATP represents the most important energy currency in any living cell. Yet, these chemicals play an important role in both processes, enabling them with dual-acting functions in metabolic and intercellular signaling pathways. Glutamate can fuel ATP production, while ATP can act as a transmitter in intercellular signaling. We discuss the interface between glutamate and ATP in signaling and metabolism of astrocytes. Not only do glutamate and ATP cross each other's paths in physiology of the brain, but they also do so in its pathology. We present the fabric of this process in (patho)physiology through the discussion of synthesis and metabolism of ATP and glutamate in astrocytes as well as by providing a general description of astroglial receptors for these molecules along with the downstream signaling pathways that may be activated. It is astroglial receptors for these dual-acting molecules that could hold a key for medical intervention in pathological conditions. We focus on two examples disclosing the role of activation of astroglial ATP and glutamate receptors in pathology of two kinds of brain tissue, gray matter and white matter, respectively. Interventions at the interface of metabolism and signaling show promise for translational medicine.
The expression of the leukotoxin (ltx) operon varies significantly among Actinobacillus actinomycetemcomitans strains. The dual promoters driving ltx expression in the highly toxic strain JP2 have been previously characterized (
A robust, green, and sustainable
manufacturing process has been
developed for the synthesis of gefapixant citrate, a P2X3 receptor
antagonist that is under investigation for the treatment of refractory
and unexplained chronic cough. The newly developed commercial process
features low process mass intensity (PMI), short synthetic sequence,
high overall yield, minimal environmental impact, and significantly
reduced API costs. The key innovations are the implementation of a
highly efficient two-step methoxyphenol synthesis, an innovative pyrimidine
synthesis in flow, a simplified sulfonamide synthesis, and a novel
salt metathesis approach to consistently deliver the correct active
pharmaceutical ingredient (API) salt form in high purity.
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