Tuning transthyretin amyloidosis inhibition properties of iododiflunisal by combinatorial engineering of the nonsalicylic ring substitutions
| Autor: | Alfredo Ballesteros, Gregorio Valencia, Maria Rosário Almeida, Maria Vilaró, Gemma Arsequell, Juan Ramón La Parra, Joan Nieto, Antoni Planas |
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| Rok vydání: | 2014 |
| Předmět: |
Amyloid Neuropathies
Familial Amyloid biology Chemistry Stereochemistry nutritional and metabolic diseases Diflunisal Halogenation General Chemistry General Medicine Transthyretin Structure-Activity Relationship Reagent Electrophile medicine biology.protein Combinatorial Chemistry Techniques Humans Turbidimetry Selectivity medicine.drug |
| Zdroj: | ACS combinatorial science. 17(1) |
| ISSN: | 2156-8944 |
| Popis: | Two series of iododiflunisal and diflunisal analogues have been obtained by using a two step sequential reaction solution-phase parallel synthesis. The synthesis combined an aqueous Suzuki-Miyaura cross-coupling and a mild electrophilic aromatic iodination step using a new polymer-supported iodonium version of Barluenga’s reagent. From a selected set of 77 noniodinated and 77 iodinated diflunisal analogues, a subset of good transthyretin amyloid inhibitors has been obtained with improved turbidimetry inhibition constants, high binding affinity to transthyretin, and good selectivity for TTR compared to other thyroxine binding proteins. |
| Databáze: | OpenAIRE |
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