136199-02-5Relevant articles and documents
Convenient one-pot synthesis of 8-substituted xanthines from 6-amino-5- nitrosouracils
Moore,Schow,Lum,Nelson,Melville
, p. 1123 - 1126 (2007/10/03)
C-8 substituted 1,3-dipropylxanthines are typically prepared by reduction of the aminonitrosouracil 2 to the corresponding diamine, which is acylated and then treated with strongly basic or dehydrating reagents to afford the xanthine 1. Working to discover a milder, more efficient, reaction sequence it was found that the C-6 amino group of 2 can be acylated, and that treatment of the resulting compounds with Sn(OAc)2 gave 8-substituted xanthines. Overall, a one-pot conversion of the aminonitrosouracil 2 to dipropylxanthines 1a-i was achieved involving in situ acylation, reduction, and cyclodehydration. These conditions can be used to generate the imidazole substructure in the presence of acid and base sensitive groups on the C-8 position that may be problematic the conventional three-step xanthine syntheses.
8-Polycycloalkyl-1,3-dipropylxanthines as potent and selective antagonists for A1-adenosine receptors
Shimada,Suzuki,Nonaka,Ishii
, p. 924 - 930 (2007/10/02)
With the aim of characterizing the hydrophobic interactions between xanthines and the A1 receptor site, 1,3-dipropyl-8-substituted xanthines were synthesized. Introduction of a quaternary carbon and the conformationally restricted cyclopentyl moiety into the 8-position of xanthines enhanced the adenosine A1 antagonism. 1,3-Dipropyl-8-(3- noradamantyl)xanthine (42) was identified to be a selective and the most potent A1 receptor antagonist reported to date. Under our structure-activity relationship, the 8-substituent of xanthine antagonists and the N6- substituent of adenosine agonists appears to bind to the same region of the A1 receptor.
