Abstract
In this paper, we report the synthesis and pharmacological evaluation of pyrazine N-acylhydrazone (NAH) derivatives (2a-s) designed as novel analgesic and anti-inflammatory drug candidates. This series was planned by molecular simplification of prototype 1 (LASSBio-1018), previously described as a non-selective cyclooxygenase inhibitor. Derivatives 2a-s were evaluated in several animal models of pain and inflammation, standing-out compound 2o (2-N'-[(E)-(3,4,5-trimethoxyphenyl) methylidene]-2-pyrazinecarbohydrazide; LASSBio-1181), that was also active in a murine model of chronic inflammation (i.e., adjuvant-induced arthritis test in rats) and can be considered a new analgesic and anti-inflammatory lead for drug development.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Analgesics / chemical synthesis
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Analgesics / chemistry*
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Analgesics / therapeutic use*
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Animals
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Anti-Inflammatory Agents / chemical synthesis
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Anti-Inflammatory Agents / chemistry*
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Anti-Inflammatory Agents / therapeutic use*
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Arthritis / chemically induced
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Arthritis / drug therapy*
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Ear / pathology
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Edema / chemically induced
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Edema / drug therapy
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Female
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Freund's Adjuvant
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Hydrazones / chemical synthesis
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Hydrazones / chemistry*
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Hydrazones / therapeutic use*
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Male
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Mice
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Pain / drug therapy*
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Peritonitis / chemically induced
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Peritonitis / drug therapy
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Pyrazines / chemical synthesis
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Pyrazines / chemistry*
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Pyrazines / therapeutic use*
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Rats
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Rats, Wistar
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Zymosan
Substances
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Analgesics
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Anti-Inflammatory Agents
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Hydrazones
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Pyrazines
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Freund's Adjuvant
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Zymosan