PMID- 15848772
OWN - NLM
STAT- MEDLINE
DCOM- 20050908
LR  - 20131121
IS  - 0968-0896 (Print)
IS  - 0968-0896 (Linking)
VI  - 13
IP  - 10
DP  - 2005 May 16
TI  - Synthesis and biological evaluation of 
      N-[4-[5-(2,4-diamino-6-oxo-1,6-dihydropyrimidin-5-yl)-2-(2,2,2-trifluoroacetyl)pentyl]benzoyl]-L-glutamic 
      acid as a potential inhibitor of GAR Tfase and the de novo purine biosynthetic 
      pathway.
PG  - 3593-9
AB  - The synthesis and evaluation of 
      N-[4-[5-(2,4-diamino-6-oxo-1,6-dihydropyrimidin-5-yl)-2-(2,2,2-trifluoroacetyl)pentyl]benzoyl]-L-glutamic 
      acid (2) as an inhibitor of glycinamide ribonucleotide transformylase (GAR Tfase) 
      and aminoimidazole carboxamide ribonucleotide transformylase (AICAR Tfase) are 
      reported. The inhibitor 2 was prepared in a convergent synthesis involving 
      C-alkylation of methyl 4-(4,4,4-trifluoro-3-dimethylhydrazonobutyl)benzoate with 
      1-chloro-3-iodopropane followed by construction of the pyrimidinone ring. 
      Compound 2 was found to be an effective inhibitor of recombinant human GAR Tfase 
      (K(i) = 0.50 microM), whereas it was inactive (K(i) > 100 microM) against E. coli 
      GAR Tfase as well as recombinant human AICAR Tfase. Compound 2 exhibited modest, 
      purine-sensitive growth inhibitory activity against the CCRF-CEM cell line (IC50 
      = 6.0 microM).
FAU - Cheng, Heng
AU  - Cheng H
AD  - Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines 
      Road, La Jolla, CA 92037, USA.
FAU - Hwang, Inkyu
AU  - Hwang I
FAU - Chong, Youhoon
AU  - Chong Y
FAU - Tavassoli, Ali
AU  - Tavassoli A
FAU - Webb, Michael E
AU  - Webb ME
FAU - Zhang, Yan
AU  - Zhang Y
FAU - Wilson, Ian A
AU  - Wilson IA
FAU - Benkovic, Stephen J
AU  - Benkovic SJ
FAU - Boger, Dale L
AU  - Boger DL
LA  - eng
GR  - CA 63536/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Bioorg Med Chem
JT  - Bioorganic & medicinal chemistry
JID - 9413298
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 
      (N-(4-(5-(2,4-diamino-6-oxo-1,6-dihydropyrimidin-5-yl)-2-(2,2,2-trifluoroacetyl)pentyl)benzoyl)-L-glutamic 
      acid)
RN  - 0 (Purines)
RN  - 0 (Pyrimidines)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - EC 2.1.2.- (Hydroxymethyl and Formyl Transferases)
RN  - EC 2.1.2.2 (Phosphoribosylglycinamide Formyltransferase)
RN  - EC 2.1.2.3 (Phosphoribosylaminoimidazolecarboxamide Formyltransferase)
SB  - IM
MH  - *Antineoplastic Agents/chemical synthesis/pharmacology
MH  - *Enzyme Inhibitors/chemical synthesis/pharmacology
MH  - Glutamic Acid/*analogs & derivatives/chemical synthesis/pharmacology
MH  - Humans
MH  - Hydroxymethyl and Formyl Transferases/*antagonists & inhibitors
MH  - Molecular Structure
MH  - Phosphoribosylaminoimidazolecarboxamide Formyltransferase
MH  - Phosphoribosylglycinamide Formyltransferase
MH  - Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism/pathology
MH  - Purines/antagonists & inhibitors/*biosynthesis
MH  - Pyrimidines/*chemical synthesis/*pharmacology
MH  - Structure-Activity Relationship
MH  - Tumor Cells, Cultured
EDAT- 2005/04/26 09:00
MHDA- 2005/09/09 09:00
CRDT- 2005/04/26 09:00
PHST- 2004/08/27 00:00 [received]
PHST- 2004/11/24 00:00 [revised]
PHST- 2004/11/24 00:00 [accepted]
PHST- 2005/04/26 09:00 [pubmed]
PHST- 2005/09/09 09:00 [medline]
PHST- 2005/04/26 09:00 [entrez]
AID - S0968-0896(04)00949-6 [pii]
AID - 10.1016/j.bmc.2004.11.049 [doi]
PST - ppublish
SO  - Bioorg Med Chem. 2005 May 16;13(10):3593-9. doi: 10.1016/j.bmc.2004.11.049.