Day: November 9, 2022

Du, Zhi; Yu, Dongqin; Du, Xiubo; Scott, Peter; Ren, Jinsong; Qu, Xiaogang published an article in 2019, the title of the article was Self-triggered click reaction in an Alzheimer’s disease model: in situ bifunctional drug synthesis catalyzed by neurotoxic copper accumulated in amyloid-beta plaques.COA of Formula: C14H12N2S And the article contains the following content:

Cu is one of the essential elements for life. Its dyshomeostasis has been demonstrated to be closely related to neurodegenerative disorders, such as Alzheimer’s disease (AD), which is characterized by amyloid-beta (Abeta) aggregation and Cu accumulation. It is a great challenge as to how to take advantage of neurotoxic Cu to fight disease and make it helpful. Herein, we report that the accumulated Cu in Abeta plaques can effectively catalyze an azide-alkyne bioorthogonal cycloaddition reaction for fluorophore activation and drug synthesis in living cells, a transgenic AD model of Caenorhabditis elegans CL2006, and brain slices of triple transgenic AD mice. More importantly, the in situ synthesized bifunctional drug 6 can disassemble Abeta-Cu aggregates by extracting Cu and photo-oxygenating Abeta synergistically, suppressing Abeta-mediated paralysis and diminishing the locomotion defects of the AD model CL2006 strain. Our results demonstrate that taking the accumulated Cu ions in the Abeta plaque for an in situ click reaction can achieve both a self-triggered and self-regulated drug synthesis for AD therapy. To the best of our knowledge, a click reaction catalyzed by local Cu in a physiol. environment has not been reported. This work may open up a new avenue for in situ multifunctional drug synthesis by using endogenous neurotoxic metal ions for the treatment of neurodegenerative diseases. The experimental process involved the reaction of 2-(4-Aminophenyl)-6-methylbenzothiazole(cas: 92-36-4).COA of Formula: C14H12N2S

The Article related to alzheimer disease copper amyloid beta, Biochemical Methods: Biological and other aspects.COA of Formula: C14H12N2S

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

On May 21, 2008, Brak, Katrien; Doyle, Patricia S.; McKerrow, James H.; Ellman, Jonathan A. published an article.COA of Formula: C8H7NOS The title of the article was Identification of a New Class of Nonpeptidic Inhibitors of Cruzain. And the article contained the following:

Cruzain is the major cysteine protease of Trypanosoma cruzi, which is the causative agent of Chagas disease and is a promising target for the development of new chemotherapy. With the goal of developing potent nonpeptidic inhibitors of cruzain, the substrate activity screening (SAS) method was used to screen a library of protease substrates initially designed to target the homologous human protease cathepsin S. Structure-based design was next used to further improve substrate cleavage efficiency by introducing addnl. binding interactions in the S3 pocket of cruzain. The optimized substrates were then converted to inhibitors by the introduction of cysteine protease mechanism-based pharmacophores. Inhibitor 38 was determined to be reversible even though it incorporated the vinyl sulfone pharmacophore that is well documented to give irreversible cruzain inhibition for peptidic inhibitors. The previously unexplored β-chloro vinyl sulfone pharmacophore provided mechanistic insight that led to the development of potent irreversible acyl- and aryl-oxymethyl ketone cruzain inhibitors. For these inhibitors, potency did not solely depend on leaving group pKa, with 2,3,5,6-tetrafluorophenoxymethyl ketone 54 identified as one of the most potent inhibitors with a second-order inactivation constant of 147,000 s-1 M-1. This inhibitor completely eradicated the T. cruzi parasite from mammalian cell cultures and consequently has the potential to lead to new chemotherapeutics for Chagas disease. The experimental process involved the reaction of Benzo[d]thiazol-6-ylmethanol(cas: 19989-66-3).COA of Formula: C8H7NOS

The Article related to nonpeptidic inhibitor cruzain structure chagas disease, Pharmacology: Structure-Activity and other aspects.COA of Formula: C8H7NOS

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

On September 1, 2019, Sami, Yuichi; Morita, Masataka; Kubota, Hirokazu; Hirabayashi, Ryoji; Seo, Ryushi; Nakagawa, Nobuaki published an article.Synthetic Route of 2010-06-2 The title of the article was Discovery of a novel orally active TRPV4 inhibitor: Part 1. Optimization from an HTS hit. And the article contained the following:

Novel oral TRPV4 inhibitors were prepared and their potential for pain management in osteoarthritis discussed. The experimental process involved the reaction of 4-Phenylthiazol-2-amine(cas: 2010-06-2).Synthetic Route of 2010-06-2

The Article related to oral trpv4 inhibitor preparation analgesic osteoarthritis, Pharmacology: Structure-Activity and other aspects.Synthetic Route of 2010-06-2

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica