Synthesis of a potent transition-state inhibitor of 5'-deoxy-5'-methylthioadenosine phosphorylase.
Human 5'-deoxy-5'-methylthioadenosine phosphorylase (MTAP) participates in the purine salvage pathway to generate adenine and methylthioribose-1-phosphate, which in turn is converted into adenine nucleotides and methionine. Hence, inhibition of MTA phosphorylase may be an effective target in the design of potential antiproliferative agents. Presented herein is the synthesis of 2-(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)-5-methylsulfanylmethylpyrrolidin-3,4-diol (1), a potent inhibitor of MTAP.
BioCryst Pharmaceuticals Inc., 2190 Parkway Lake Drive, Birmingham, Alabama 35244.
Vivekanand P
VP
Kamath
Sandya
S
Ananth
Shanta
S
Bantia
Philip E
PE
Morris
D000241:Adenosine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D011683:Purine-Nucleoside Phosphorylase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
C483889:2-(4-amino-5H-pyrrolo-(3,2-d)pyrimidin-7-yl)-5-methylsulfanylmethylpyrrolidin-3,4-diol; D000970:Antineoplastic Agents; D011759:Pyrrolidines; D011683:Purine-Nucleoside Phosphorylase; C021784:5'-methylthioadenosine phosphorylase; D000241:Adenosine