203258-18-8Relevant academic research and scientific papers
Enhancing the intestinal absorption of molecules containing the polar guanidino functionality: A double-targeted prodrug approach
Sun, Jing,Dahan, Arik,Amidon, Gordon L.
experimental part, p. 624 - 632 (2010/06/19)
A prodrug strategy was applied to guanidino-containing analogues to increase oral absorption via hPEPT1 and hVACVase. L-Valine, L-isoleucine, and L-phenylalanine esters of [3-(hydroxymethyl)-phenyl]guanidine (3-HPG) were synthesized and evaluated for transport and activation. In HeLa/ hPEPT1 cells, Val-3-HPG and Ile-3-HPG exhibited high affinity to hPEPT1 (IC50: 0.65 and 0.63 mM, respectively), and all three L-amino acid esters showed higher uptake (2.6- to 9-fold) than the parent compound 3-HPG. Val-3-HPG and Ile-3-HPG demonstrated remarkable Caco-2 permeability enhancement, and Val-3-HPG exhibited comparable permeability to valacyclovir. In rat perfusion studies, Val-3-HPG and Ile-3-HPG permeabilities were significantly higher than 3-HPG and exceeded/matched the high-permeability standard metoprolol, respectively. All the L-amino acid 3-HPG esters were effectively activated in HeLa and Caco-2 cell homogenates and were found to be good substrates of hVACVase (k cat/Km in mM-1 · s-1: Val-3-HPG, 3370; Ile-3-HPG, 1580; Phe-3-HPG, 1660). In conclusion, a prodrug strategy is effective at increasing the intestinal permeability of polar guanidino analogues via targeting hPEPT1 for transport and hVACVase for activation.
A convenient and versatile method for the synthesis of protected guanidines
Guo, Zhao-Xia,Cammidge, Andrew N.,Horwell, David C.
, p. 2933 - 2943 (2007/10/03)
Aromatic, aliphatic and sterically hindered amines react smoothly with commercially available N, N'-bis-BOC-S-methylisothiourea 2 in the presence of mercury chloride to give the protected guanidine in good yield. It is particularly noteworthy that 2 can a
Solution phase combinatorial chemistry. Discovery of 13- and 15-membered polyazapyridinocyclophane libraries with antibacterial activity
An, Haoyun,Wang, Tingmin,Mohan, Venkatraman,Griffey, Richard H.,Dan Cook
, p. 3999 - 4012 (2007/10/03)
A solution phase simultaneous addition of functionalities (SPSAF) combinatorial approach was utilized to synthesize 40 polyazacyclophane libraries (total complexity of 4275). Eighteen different functionality sets, utilizing 42 functionalities, were design
