Benzylguanidines and other galegine analogues inducing weight loss in mice

Geoffrey D. Coxon, Brian L. Furman, Alan L. Harvey, John McTavish, Mark H. Mooney, Mahmoud Arastoo, A.R. Kennedy, J.N.A. Tettey, R.D. Waigh

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Dimethylallylguanidine, also known as galegine, isolated from Galega officinalis, has been shown to have weight reducing properties in vivo. Substitution of the guanidine group with an N-cyano group and replacement of guanidine with amidine, pyrimidine, pyridine, or the imidazole moieties removed the weight reducing properties when evaluated in BALB/c mice. However, retention of the guanidine and replacement of the dimethylallyl group by a series of functionalized benzyl substituents was shown to exhibit, and in some cases significantly improve, the weight reducing properties of these molecules in BALB/c, ob/ob, and diet induced obesity (DIO) mice models. The lead compound identified, across all models, was 1-(4-chlorobenzyl)guanidine hemisulfate, which gave an average daily weight difference (% from time-matched controls; +/- SEM) of -19.7 +/- 1.0, -11.0 +/- 0.7, and -7.3 +/- 0.8 in BALB/c, ob/ob, and DIO models, respectively.
LanguageEnglish
Pages3457-3463
Number of pages7
JournalJournal of Medicinal Chemistry
Volume52
Issue number11
DOIs
Publication statusPublished - 7 May 2009

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Guanidine
Weight Loss
Weights and Measures
Galega
Obesity
Amidines
Diet
benzylguanidine
galegine

Keywords

  • benzylguanidine
  • galegine analogues
  • weight loss
  • mice
  • pharmacology
  • biomedical sciences

Cite this

Coxon, Geoffrey D. ; Furman, Brian L. ; Harvey, Alan L. ; McTavish, John ; Mooney, Mark H. ; Arastoo, Mahmoud ; Kennedy, A.R. ; Tettey, J.N.A. ; Waigh, R.D. / Benzylguanidines and other galegine analogues inducing weight loss in mice. In: Journal of Medicinal Chemistry. 2009 ; Vol. 52, No. 11. pp. 3457-3463.
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Benzylguanidines and other galegine analogues inducing weight loss in mice. / Coxon, Geoffrey D.; Furman, Brian L.; Harvey, Alan L.; McTavish, John; Mooney, Mark H.; Arastoo, Mahmoud; Kennedy, A.R.; Tettey, J.N.A.; Waigh, R.D.

In: Journal of Medicinal Chemistry, Vol. 52, No. 11, 07.05.2009, p. 3457-3463.

Research output: Contribution to journalArticle

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AU - Coxon, Geoffrey D.

AU - Furman, Brian L.

AU - Harvey, Alan L.

AU - McTavish, John

AU - Mooney, Mark H.

AU - Arastoo, Mahmoud

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