Naloxone hydrazone derivatives

Hydrazone derivatives 258 of oxymorphone, naloxone, and naltrexone have been made by reaction with anhydrous hydrazine and designated oxymor-phazone (170), naloxazone (171), and naltrexazone (172). All three hydrazones exhibited a high binding affinity for in vitro rat brain receptor sites. 

Hydrazone derivatives of naloxone and naltrexone produce a remarkably long blockade of opioid receptors as judged by binding and antinociceptive tests 52 (oxymorphuzonc, the /V-mclhyl analog, produced prolonged analgesia... 

Studies related to other derivatives of the morphine alkaloids include the receptor-binding480 and narcotic effects481 of naloxone 6-hydrazone the effects of... 

The Myers two-step, single-flask procedure differs from the Cram procedure in that the requisite hydrazones are more reliably made and do not require isolation. The reduction of simple aliphatic hydrazones generally takes place at ambient temperature, whereas sterically hindered hydrazones required some heating (100 °C) for the reaction to proceed at a reasonable rate. Complex structures such as the steroid hecogenin (12, eq 5), and other tertiary hydrazones, are efficiently reduced in high yield. The morphine derivative naloxone (14, eq 6) underwent the expected Kishner-Leonard elimination under the standard conditions. ... 

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