Benzylguanidines and Other Galegine Analogues Inducing Weight Loss in Mice

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.

Natural products in anti-obesity therapy

“…113 Chemical modification of galegine to 1-(4-chlorobenzyl)-guanidine-hemisulfate resulted in significant improvement of weight reducing properties. 114 It is evident that this group of scientists is taking great strides towards the development of a chemically synthesized antiobesity preparation from the blueprint provided by galegine isolated from G. officinalis. No toxicity was revealed in a 28-day study on galegine, 113 Garcinia cambogia Desr.…”

Novel atom-economic reaction: comprehensive utilization of S-alkylisothiouronium salt in the synthesis of thioethers and guanidinium salts

“…Compounds 1a-f, 5 2a-c, 19 3a-c, 10,17 4a-r, [19][20][21][22][23][24][25][26] 5a-e, [15][16][17][18]…”

Guanylated Diamines, Triamines, and Polyamines: Chemistry and Biological Properties

“…Arcaine is also a well-known inhibitor of NO synthase and a NMDA antagonist acting as a competitive inhibitor at the polyamine site . Its properties are strictly related to its analogy with agmatine . Arcaine also has been isolated in Lathyrus sativus , and mediation of its synthesis in vitro from agmatine by the transamidinase has been demonstrated .…”