32150-91-7Relevant articles and documents
Chemoselective Amide-Forming Ligation Between Acylsilanes and Hydroxylamines Under Aqueous Conditions
Deng, Xingwang,Zhou, Guan,Tian, Jing,Srinivasan, Rajavel
supporting information, p. 7024 - 7029 (2020/12/29)
We report the facile amide-forming ligation of acylsilanes with hydroxylamines (ASHA ligation) under aqueous conditions. The ligation is fast, chemoselective, mild, high-yielding and displays excellent functional-group tolerance. Late-stage modifications of an array of marketed drugs, peptides, natural products, and biologically active compounds showcase the robustness and functional-group tolerance of the reaction. The key to the success of the reaction could be the possible formation of the strong Si?O bond via a Brook-type rearrangement. Given its simplicity and efficiency, this ligation has the potential to unfold new applications in the areas of medicinal chemistry and chemical biology.
AMINO ACID DERIVATIVES FOR THE TREATMENT OF INFLAMMATORY DISEASES
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Page/Page column 50; 67, (2020/08/13)
The present disclosure provides certain amino acid derivatives that inhibit NF-kB activation and are therefore useful for the treatment of inflammatory diseases. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.
Flupirtine and retigabine as templates for ligand-based drug design of KV7.2/3 activators
Surur, Abdrrahman S.,Bock, Christian,Beirow, Kristin,Wurm, Konrad,Schulig, Lukas,Kindermann, Markus K.,Siegmund, Werner,Bednarski, Patrick J.,Link, Andreas
supporting information, p. 4512 - 4522 (2019/05/17)
Drug induced liver injury (DILI) and tissue discoloration led to the recent discontinuation of the therapeutic use of the closely related drugs flupirtine and retigabine, respectively. Experience gained with these drugs strongly suggests that heterotetramer, voltage-gated potassium channels 2 and 3 (KV7.2/3) are valid targets for effective treatment of pain and epilepsy. Because the adverse effects are not related to the mechanism of action, it appears promising to investigate chemical modifications of these clinically validated, drug-like leads. In the present retro-metabolic drug design study, a series of 43 compounds were synthesized and characterized with regard to KV7.2/3 opening activity and efficacy. The most active compound 22d displays excellent potency (EC50 = 4 nM) and efficacy (154%) as a KV7.2/3 opener. Limited aqueous solubility hampered toxicity testing at concentrations higher than 63 μM, but this concentration was nontoxic to two hepatocellular cell lines (HEP-G2 and TAMH) in culture. The slightly less active but more soluble compound 25b (EC50 = 11 nM, efficacy 111%) showed an improved toxicity/activity ratio compared to flupirtine by three orders of magnitude and represents an attractive lead structure for the development of safer analgesics and antiepileptics.