118778-41-9Relevant academic research and scientific papers
Potent tetracyclic guanine inhibitors of PDE1 and PDE5 cyclic guanosine monophosphate phosphodiesterases with oral antihypertensive activity
Ahn, Ho-Sam,Bercovici, Ana,Boykow, George,Bronnenkant, Alan,Chackalamannil, Samuel,Chow, Jason,Cleven, Renee,Cook, John,Czarniecki, Michael,Domalski, Carol,Fawzi, Ahmad,Green, Michael,Gündes, Asli,Ho, Ginny,Laudicina, Malvina,Lindo, Neil,Ma, Ke,Manna, Mahua,McKittrick, Brian,Mirzai, Bita,Nechuta, Terry,Neustadt, Bernard,Puchalski, Chester,Pula, Kathryn,Silverman, Lisa,Smith, Elizabeth,Stamford, Andrew,Tedesco, Richard P.,Tsai, Hsingan,Tulshian, Deen,Vaccaro, Henry,Watkins, Robert W.,Weng, Xiaoyu,Witkowski, Joseph T.,Xia, Yan,Zhang, Hongtao
, p. 2196 - 2210 (2007/10/03)
Tetracyclic guanines have been shown to be potent and selective inhibitors of the cGMP-hydrolyzing enzymes PDE1 and PDE5. In general, these compounds are inactive or only weakly active as inhibitors of PDE3, which is a major isozyme involved in cAMP hydrolysis. Structureactivity relationships are developed at N-l, C-2, N-3, and N-5 on the core nucleus. Compound 31, with an IC50 of 70 pM, is the most potent inhibitor of PDE1, while 50, with an IC50 of 4 nM, is the most potent inhibitor of PDE5. Compounds 20, 22, 30, and 50 are potent dual inhibitors with IC50 values below 30 nM for both PDE1 and PDE5. Compounds 12, 20, and 28 reduced blood pressure by more than 45 mmHg when administered orally at 10 mg/kg to the spontaneously hypertensive rat (SHR).
Purines, Pyrimidines, and Imidazoles. Part 64. Alkylation and Acylation of Some Aminoimidazoles Related to Intermediates in Purine Nucleotide de novo and Thiamine Biosynthesis
Mackenzie, Grahame,Wilson, Hilary A.,Shaw, Gordon,Ewing, David
, p. 2541 - 2546 (2007/10/02)
Treatment of ethyl-5-amino-1-benzylimidazole-4-carboxylate with butyl-lithium and methyl iodide gave the 5-N-methylamino derivative (4b) and the 3-methiodide (5) whereas ethyl-5-amino-1-(2,3-O-isopropylidene-β-D-ribofuranosyl)imidazole-4-carboxylate gave both the 5-N-methylamino (6b) and 2-methyl (6d) derivatives.Ethyl 5-amino-1-benzylimidazole-4-carboxylate with acetic anhydride or acetyl chloride gave various products, according to the conditions, including the 5-N-mono- and -N,N-di-acetylamino derivatives (4d) and (4c), respectively, and N,N'-dibenzyloxamide (9).The oxamide also arose from treatment of the imidazole (4a) with formaldehyde. 3-Cyanopropanimidate with ethyl α-amino-α-cyano acetate followed by benzylamine or 2,3-O-isopropylidene-D-ribosylamine afforded ethyl 5-amino-1-benzyl-2-(2-cyanoethyl)imidazole-4-carboxylate and ethyl 5-amino-1-(2,3-O-isopropylidene-α- and β-D-ribofuranosyl)imidazole-4-carboxylates, respectively.Ethyl 5-amino-(2,3-O-isopropylidene-β-D-ribofuranosyl)-2-ethoxycarbonylethylimidazole-4-carboxylate and the corresponding 2-ethoxyethyl nucleoside (6i) were similarly prepared.Oxidation of ethyl 5-amino-2-methylimidazole-4-carboxylate with N-chlorosuccinimide and potassium hydroxide led to ethyl 5-amino-1-benzyl-2-formylimidazole-4-carboxylate and oxidation of the protected 2-ethoxycarbonylethyl nucleoside (6j) with selenium dioxide produced the urea derivative (6l).
