التفاصيل البيبلوغرافية
| العنوان: |
Accelerated Development of a Scalable Synthesis of CY6463, a CNS-Penetrant sGC Stimulator for the Treatment of Neurodegenerative Diseases |
| المؤلفون: |
Debra J. Wallace (1789080), Thomas Storz (2145397), Anna Balanov (11428238), William S. Kissel (2717260) |
| سنة النشر: |
2021 |
| المجموعة: |
Smithsonian Institution: Digital Repository |
| مصطلحات موضوعية: |
Biochemistry, Medicine, Cell Biology, Genetics, Neuroscience, Immunology, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, Physical Sciences not elsewhere classified, triazole formation reaction, thereby accelerating advancement, pot negishi coupling, novel triazole formation, noncentral nervous system, enter clinical trials, early clinical studies, penetrant sgc stimulator, increase nitric oxide, synthesis features, studied clinically, small molecules, scalable synthesis, safety considerations, rapid generation, protected amidrazone, positively impact, neurodegenerative diseases, mechanistic study, larger quantities, cyanation sequence |
| الوصف: |
Soluble guanylate cyclase (sGC) stimulators are small molecules that increase nitric oxide (NO) signaling by binding to sGC, leading to an increase in cyclic guanosine monophosphate production. Such compounds have previously been studied clinically for noncentral nervous system (CNS) disorders. CY6463 is the first CNS-penetrant sGC stimulator to enter clinical trials and has the potential to positively impact a range of neurodegenerative diseases. In this paper, we present the development of an efficient, robust, and scalable synthesis of this compound that allowed for rapid generation of larger quantities of material, thereby accelerating advancement into early clinical studies, while minimizing the use of resources. The synthesis features a palladium-catalyzed one-pot Negishi coupling/cyanation sequence and a novel triazole formation from a Boc-protected amidrazone. Optimization of the reactions, safety considerations, and control of impurities, as well as a mechanistic study of the triazole formation reaction, are discussed. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
unknown |
| العلاقة: |
https://figshare.com/articles/journal_contribution/Accelerated_Development_of_a_Scalable_Synthesis_of_CY6463_a_CNS-Penetrant_sGC_Stimulator_for_the_Treatment_of_Neurodegenerative_Diseases/16614005Test |
| DOI: |
10.1021/acs.oprd.1c00204.s001 |
| الإتاحة: |
https://doi.org/10.1021/acs.oprd.1c00204.s001Test |
| حقوق: |
CC BY-NC 4.0 |
| رقم الانضمام: |
edsbas.DBF11E09 |
| قاعدة البيانات: |
BASE |
