10-Formyl-5,8,10-trideazafolic acid (10-formyl-TDAF): A potent inhibitor of glycinamide ribonucleotide transformylase

Dale L. Boger; Nancy Ellen Haynes; Paul A. Kitos; Mark S. Warren; Joseph Ramcharan; Ariane E. Marolewski; Stephen J. Benkovic

doi:10.1016/S0968-0896(97)00120-X

10-Formyl-5,8,10-trideazafolic acid (10-formyl-TDAF): A potent inhibitor of glycinamide ribonucleotide transformylase

Dale L. Boger, Nancy Ellen Haynes, Paul A. Kitos, Mark S. Warren, Joseph Ramcharan, Ariane E. Marolewski, Stephen J. Benkovic

Chemistry

Research output: Contribution to journal › Article › peer-review

44 Scopus citations

Abstract

The synthesis of 10-formyl-5,8,10-trideazafolic acid (3) as a potential inhibitor of glycinamide ribonucleotide transformylase (GAR Tfase) is reported. The target compound was prepared by a convergent synthesis utilizing the alkylation of hydrazone 5 with benzylic bromide 6 to construct the core heterocycle 7. The aldehyde 3 and related agents were evaluated as inhibitors of purN GAR Tfase and avian AICAR Tfase. Compound 3 exhibited potent inhibition of GAR Tfase with a K(i) of 0.26 ± 0.05 μM. In contrast, 3 exhibited more moderate inhibition of aminoimidazole carboxamide ribonucleotide transformylase (AICAR Tfase), with K(i) of 7.6 ± 1.5 μM.

Original language	English (US)
Pages (from-to)	1817-1830
Number of pages	14
Journal	Bioorganic and Medicinal Chemistry
Volume	5
Issue number	9
DOIs	https://doi.org/10.1016/S0968-0896(97)00120-X
State	Published - Sep 1997

All Science Journal Classification (ASJC) codes

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

Access to Document

10.1016/S0968-0896(97)00120-X

Cite this

@article{55d17553091946aaad2f19d5882d09ad,

title = "10-Formyl-5,8,10-trideazafolic acid (10-formyl-TDAF): A potent inhibitor of glycinamide ribonucleotide transformylase",

abstract = "The synthesis of 10-formyl-5,8,10-trideazafolic acid (3) as a potential inhibitor of glycinamide ribonucleotide transformylase (GAR Tfase) is reported. The target compound was prepared by a convergent synthesis utilizing the alkylation of hydrazone 5 with benzylic bromide 6 to construct the core heterocycle 7. The aldehyde 3 and related agents were evaluated as inhibitors of purN GAR Tfase and avian AICAR Tfase. Compound 3 exhibited potent inhibition of GAR Tfase with a K(i) of 0.26 ± 0.05 μM. In contrast, 3 exhibited more moderate inhibition of aminoimidazole carboxamide ribonucleotide transformylase (AICAR Tfase), with K(i) of 7.6 ± 1.5 μM.",

author = "Boger, {Dale L.} and Haynes, {Nancy Ellen} and Kitos, {Paul A.} and Warren, {Mark S.} and Joseph Ramcharan and Marolewski, {Ariane E.} and Benkovic, {Stephen J.}",

year = "1997",

month = sep,

doi = "10.1016/S0968-0896(97)00120-X",

language = "English (US)",

volume = "5",

pages = "1817--1830",

journal = "Bioorganic and Medicinal Chemistry",

issn = "0968-0896",

publisher = "Elsevier Limited",

number = "9",

}

TY - JOUR

T1 - 10-Formyl-5,8,10-trideazafolic acid (10-formyl-TDAF)

T2 - A potent inhibitor of glycinamide ribonucleotide transformylase

AU - Boger, Dale L.

AU - Haynes, Nancy Ellen

AU - Kitos, Paul A.

AU - Warren, Mark S.

AU - Ramcharan, Joseph

AU - Marolewski, Ariane E.

AU - Benkovic, Stephen J.

PY - 1997/9

Y1 - 1997/9

N2 - The synthesis of 10-formyl-5,8,10-trideazafolic acid (3) as a potential inhibitor of glycinamide ribonucleotide transformylase (GAR Tfase) is reported. The target compound was prepared by a convergent synthesis utilizing the alkylation of hydrazone 5 with benzylic bromide 6 to construct the core heterocycle 7. The aldehyde 3 and related agents were evaluated as inhibitors of purN GAR Tfase and avian AICAR Tfase. Compound 3 exhibited potent inhibition of GAR Tfase with a K(i) of 0.26 ± 0.05 μM. In contrast, 3 exhibited more moderate inhibition of aminoimidazole carboxamide ribonucleotide transformylase (AICAR Tfase), with K(i) of 7.6 ± 1.5 μM.

AB - The synthesis of 10-formyl-5,8,10-trideazafolic acid (3) as a potential inhibitor of glycinamide ribonucleotide transformylase (GAR Tfase) is reported. The target compound was prepared by a convergent synthesis utilizing the alkylation of hydrazone 5 with benzylic bromide 6 to construct the core heterocycle 7. The aldehyde 3 and related agents were evaluated as inhibitors of purN GAR Tfase and avian AICAR Tfase. Compound 3 exhibited potent inhibition of GAR Tfase with a K(i) of 0.26 ± 0.05 μM. In contrast, 3 exhibited more moderate inhibition of aminoimidazole carboxamide ribonucleotide transformylase (AICAR Tfase), with K(i) of 7.6 ± 1.5 μM.

UR - http://www.scopus.com/inward/record.url?scp=0030852355&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030852355&partnerID=8YFLogxK

U2 - 10.1016/S0968-0896(97)00120-X

DO - 10.1016/S0968-0896(97)00120-X

M3 - Article

C2 - 9354237

AN - SCOPUS:0030852355

SN - 0968-0896

VL - 5

SP - 1817

EP - 1830

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 9

ER -

10-Formyl-5,8,10-trideazafolic acid (10-formyl-TDAF): A potent inhibitor of glycinamide ribonucleotide transformylase

Abstract

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this