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.
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Authors | Geoffrey D Coxon, Brian L Furman, Alan L Harvey, John McTavish, Mark H Mooney, Mahmoud Arastoo, Alan R Kennedy, Justice M Tettey, Roger D Waigh |
Journal | Journal of medicinal chemistry
(J Med Chem)
Vol. 52
Issue 11
Pg. 3457-63
(Jun 11 2009)
ISSN: 1520-4804 [Electronic] United States |
PMID | 19422230
(Publication Type: Journal Article)
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Chemical References |
- Anti-Obesity Agents
- Benzyl Compounds
- Dietary Fats
- Guanidines
- benzylguanidine
- galegine
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Topics |
- Animals
- Anti-Obesity Agents
(pharmacology)
- Benzyl Compounds
(chemical synthesis, pharmacology)
- Dietary Fats
(administration & dosage)
- Guanidines
(chemical synthesis, metabolism, pharmacology)
- Male
- Mice
- Mice, Inbred BALB C
- Mice, Obese
- Microsomes, Liver
(metabolism)
- Weight Loss
(drug effects)
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