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Substituted benzamides. 1. Potential nondopaminergic antagonists of chemotherapy-induced nausea and emesis.

Abstract
A series of new substituted benzamides has been synthesized and evaluated for dopamine antagonist activity and for antagonism of cisplatin-induced emesis in the dog and in the ferret. It was found that modification of the 2-methoxy substituent of metoclopramide was detrimental to dopaminergic D2 antagonism but not necessarily to antagonism of cisplatin-induced emesis. A number of analogues having a beta-keto, beta-hydroxy, beta-methoxy, beta-imino, or beta-unsaturated alkyloxy substituent instead of methoxy have shown equal or superior protection from emesis to that of metoclopramide. At the same time these compounds were found to be free of dopaminergic D2 antagonism in both in vitro ([3H]spiperone binding) and in vivo tests (rat catalepsy, antagonism of apomorphine-induced stereotypy in the rat, and apomorphine-induced emesis in the dog).
AuthorsI Monković, D Willner, M A Adam, M Brown, R R Crenshaw, C E Fuller, P F Juby, G M Luke, J A Matiskella, T A Montzka
JournalJournal of medicinal chemistry (J Med Chem) Vol. 31 Issue 8 Pg. 1548-58 (Aug 1988) ISSN: 0022-2623 [Print] United States
PMID3397992 (Publication Type: Journal Article)
Chemical References
  • Antiemetics
  • Benzamides
  • Dopamine Antagonists
  • Metoclopramide
  • Cisplatin
Topics
  • Animals
  • Antiemetics (chemical synthesis, therapeutic use)
  • Benzamides (chemical synthesis, therapeutic use)
  • Catalepsy (drug therapy)
  • Chemical Phenomena
  • Chemistry
  • Cisplatin (antagonists & inhibitors)
  • Dogs
  • Dopamine Antagonists
  • Ferrets
  • Metoclopramide (antagonists & inhibitors)
  • Nausea (chemically induced, drug therapy)
  • Rats
  • Structure-Activity Relationship

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