Structure-based design, synthesis, and antimicrobial activity of purine derived SAH/MTA nucleosidase inhibitors.
The structure-based design, synthesis, and biological activity of novel inhibitors of S-adenosyl homocysteine/methylthioadenosine (SAH/MTA) nucleosidase are described. Using 6-substituted purine and deaza purines as the core scaffolds, a systematic and structure guided series of modifications provided low nM inhibitors with broad-spectrum antimicrobial activity.
Tedder
Martina E
ME
Department of Medicinal Chemistry, Quorex Pharmaceuticals, Carlsbad, CA 92008, USA.
Nie
Zhe
Z
Margosiak
Stephen
S
Chu
Shaosong
S
Feher
Victoria A
VA
Almassy
Robert
R
Appelt
Krzysztof
K
Yager
Kraig M
KM
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006710:Homocysteine / Q000037:antagonists & inhibitors / Q000378:metabolism; D009699:N-Glycosyl Hydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011683:Purine-Nucleoside Phosphorylase / Q000037:antagonists & inhibitors / Q000378:metabolism; D011687:Purines / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D011687:Purines; D006710:Homocysteine; D011683:Purine-Nucleoside Phosphorylase; C021784:5'-methylthioadenosine phosphorylase; D009699:N-Glycosyl Hydrolases