A dideazatetrahydrofolate analogue lacking a chiral center at C-6, N-[4-[2-(2-amino-3,4-dihydro-4-oxo-7H-pyrrolo[2,3-d]pyrimidin-5- yl)ethyl]benzoyl]-L-glutamic acid, is an inhibitor of thymidylate synthase.
N-[4-[2-(2-Amino-3,4-dihydro-4-oxo-7H-pyrrolo[2,3-d]pyrimidin-5- yl)ethyl]benzoyl]-L-glutamic acid (15), prepared in five steps from 2-pivaloyl-7-deazaguanine, has been found to be an antitumor agent with its primary site of action at thymidylate synthase rather than purine synthesis. This compound appears to be a promising candidate for clinical evaluation.
Taylor
E C
EC
Department of Chemistry, Princeton University, New Jersey 08544.
Kuhnt
D
D
Shih
C
C
Rinzel
S M
SM
Grindey
G B
GB
Barredo
J
J
Jannatipour
M
M
Moran
R G
RG
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D005971:Glutamates / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D006147:Guanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000627:therapeutic use; D006801:Humans; D007939:Leukemia L1210 / Q000188:drug therapy; D007945:Leukemia, Lymphoid / Q000188:drug therapy; D051379:Mice; D000068437:Pemetrexed; D013329:Structure-Activity Relationship; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D013940:Thymidylate Synthase