Abstract
Peptides containing N2-acyl piperazic or 1,6-dehydropiperazic acids can be formed efficiently via a novel multicomponent reaction of 1,4,5,6-tetrahydropyridazines, isocyanides, and carboxylic acids. Remarkably, the reaction's induced intramolecularity can enable the regiospecific formation of products with N2-acyl piperazic acid, which counters the intrinsic and troublesome propensity for piperazic acids to react at N1 in acylations. The utility of the methodology is demonstrated in the synthesis of the bicyclic core of the interleukin-1β converting enzyme inhibitor, Pralnacasan.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Acylation
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Azepines / chemical synthesis*
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Azepines / chemistry
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Azepines / pharmacology
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Biological Products / chemical synthesis
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Biological Products / chemistry
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Carboxylic Acids / chemistry
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Caspase 1 / drug effects
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Caspase Inhibitors / chemical synthesis*
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Caspase Inhibitors / chemistry
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Caspase Inhibitors / pharmacology
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Combinatorial Chemistry Techniques
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Isoquinolines / chemical synthesis*
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Isoquinolines / chemistry
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Isoquinolines / pharmacology
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Molecular Structure
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Nitriles / chemistry
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Peptides / chemical synthesis*
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Peptides / chemistry
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Pyridazines / chemical synthesis*
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Pyridazines / chemistry*
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Pyridazines / pharmacology
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Stereoisomerism
Substances
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Azepines
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Biological Products
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Carboxylic Acids
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Caspase Inhibitors
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Isoquinolines
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Nitriles
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Peptides
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Pyridazines
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piperazic acid
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Caspase 1
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pralnacasan