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2-{4-[(2,4-Diamino-furo[2,3-d]pyrimidin-5-ylmethyl)-methyl-amino]-benzoylamino}-pentanedioic acid

ID: ALA278515

PubChem CID: 3439

Max Phase: Preclinical

Molecular Formula: C20H22N6O6

Molecular Weight: 442.43

Molecule Type: Small molecule

This compound is available for customization.

Associated Items:

Names and Identifiers

Canonical SMILES:  CN(Cc1coc2nc(N)nc(N)c12)c1ccc(C(=O)NC(CCC(=O)O)C(=O)O)cc1

Standard InChI:  InChI=1S/C20H22N6O6/c1-26(8-11-9-32-18-15(11)16(21)24-20(22)25-18)12-4-2-10(3-5-12)17(29)23-13(19(30)31)6-7-14(27)28/h2-5,9,13H,6-8H2,1H3,(H,23,29)(H,27,28)(H,30,31)(H4,21,22,24,25)

Standard InChI Key:  WXINNGCGSCFUCR-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 32 34  0  0  0  0  0  0  0  0999 V2000
    1.0042   -4.3792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.5750   -4.1917    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.0042   -4.9792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.4792   -5.2875    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0333   -4.3792    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.4792   -4.0792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0333   -4.9875    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.5792   -5.1667    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    3.0667   -1.2042    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.9292   -4.6750    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.6500   -1.0750    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.7542   -3.6167    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.4250   -0.0625    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.3417   -3.4917    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    3.8292   -0.5042    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.8792   -1.7792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.4042   -0.6875    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.5250   -2.9167    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.6542   -0.7625    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.4792   -3.4792    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    2.8417   -0.1917    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    5.5875   -0.1125    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    2.2917   -1.9042    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.2875   -2.2167    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.1167   -2.4792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.1042   -2.7917    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.5583   -5.2875    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    4.4167   -0.3750    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.8167   -0.8167    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.6042    0.5125    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    5.8125   -1.1292    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    2.9292   -3.9917    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  2  1  1  0
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 32 14  1  0
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  7  4  1  0
 23 16  1  0
M  END

Associated Targets(Human)

DHFR Tclin Dihydrofolate reductase (3072 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
TYMS Tclin Thymidylate synthase (1651 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
GART Tclin GAR transformylase (531 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
ATIC Tchem AICAR transformylase (241 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CCRF-CEM (65223 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
ACHN (49357 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
SK-5 (6 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HL-60 (67320 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
K562 (73714 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
NCI-H460 (60772 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HCT-116 (91556 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
SF-268 (49410 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
U-251 (51189 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
LOX IMVI (44321 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
IGROV-1 (47897 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
786-0 (47912 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
PC-3 (62116 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
MDA-MB-435 (38290 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
MDA-N (28205 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
MCF7 (126967 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Homo sapiens (32628 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
R30dm-CCRF-CEM (8 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
FaDu (1726 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Associated Targets(non-human)

Dhfr Dihydrofolate reductase (2343 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
folA Dihydrofolate reductase (640 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Dihydrofolate reductase (1239 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Dihydrofolate reductase (1637 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
thyA Thymidylate synthase (501 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
R1 (16 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
folA Dihydrofolate reductase (350 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Molecule Features

Natural Product: NoOral: NoChemical Probe: NoParenteral: No
Molecule Type: Small moleculeTopical: NoFirst In Class: NoBlack Box: No
Chirality: NoAvailability: NoProdrug: No

Biocomponents

Calculated Properties

Molecular Weight: 442.43Molecular Weight (Monoisotopic): 442.1601AlogP: 1.07#Rotatable Bonds: 9
Polar Surface Area: 197.90Molecular Species: ACIDHBA: 9HBD: 5
#RO5 Violations: HBA (Lipinski): 12HBD (Lipinski): 7#RO5 Violations (Lipinski): 2
CX Acidic pKa: 3.24CX Basic pKa: 5.20CX LogP: -1.06CX LogD: -5.73
Aromatic Rings: 3Heavy Atoms: 32QED Weighted: 0.32Np Likeness Score: -0.49

References

1. Gangjee A, Devraj R, McGuire JJ, Kisliuk RL, Queener SF, Barrows LR..  (1994)  Classical and nonclassical furo[2,3-d]pyrimidines as novel antifolates: synthesis and biological activities.,  37  (8): [PMID:8164259] [10.1021/jm00034a015]
2. Gangjee A, Elzein E, Queener SF, McGuire JJ..  (1998)  Synthesis and biological activities of tricyclic conformationally restricted tetrahydropyrido annulated furo[2,3-d]pyrimidines as inhibitors of dihydrofolate reductases.,  41  (9): [PMID:9554874] [10.1021/jm9705420]
3. Gangjee, A A and 5 more authors.  1994-04-15  Classical and nonclassical furo[2,3-d]pyrimidines as novel antifolates: synthesis and biological activities.  [PMID:8164259]
4. Tarnchompoo, Bongkoch B and 8 more authors.  2002-03-14  Development of 2,4-diaminopyrimidines as antimalarials based on inhibition of the S108N and C59R+S108N mutants of dihydrofolate reductase from pyrimethamine-resistant Plasmodium falciparum.  [PMID:11881993]
5. Santos, M Amélia MA and 5 more authors.  2007-02-01  Methotrexate gamma-hydroxamate derivatives as potential dual target antitumor drugs.  [PMID:17127067]
6. Thurmond, John J and 17 more authors.  2008-02-14  Synthesis and biological evaluation of novel 2,4-diaminoquinazoline derivatives as SMN2 promoter activators for the potential treatment of spinal muscular atrophy.  [PMID:18205293]
7. Gangjee, Aleem; Jain, Hiteshkumar D; Queener, Sherry F and Kisliuk, Roy L.  2008-08-14  The effect of 5-alkyl modification on the biological activity of pyrrolo[2,3-d]pyrimidine containing classical and nonclassical antifolates as inhibitors of dihydrofolate reductase and as antitumor and/or antiopportunistic infection agents.  [PMID:18605720]
8. Gangjee, Aleem; Qiu, Yibin; Li, Wei and Kisliuk, Roy L.  2008-09-25  Potent dual thymidylate synthase and dihydrofolate reductase inhibitors: classical and nonclassical 2-amino-4-oxo-5-arylthio-substituted-6-methylthieno[2,3-d]pyrimidine antifolates.  [PMID:18800768]
9. Izbicka, E and 6 more authors.  2009-10  Distinct mechanistic activity profile of pralatrexate in comparison to other antifolates in in vitro and in vivo models of human cancers.  [PMID:19221750]
10. Gangjee, Aleem and 6 more authors.  2009-08-13  Design, synthesis, and X-ray crystal structure of classical and nonclassical 2-amino-4-oxo-5-substituted-6-ethylthieno[2,3-d]pyrimidines as dual thymidylate synthase and dihydrofolate reductase inhibitors and as potential antitumor agents.  [PMID:19719239]
11. Gangjee, Aleem and 9 more authors.  2009-10-15  Design, synthesis, and X-ray crystal structures of 2,4-diaminofuro[2,3-d]pyrimidines as multireceptor tyrosine kinase and dihydrofolate reductase inhibitors.  [PMID:19748785]
12. Gangjee, Aleem and 5 more authors.  2010-01-15  2,4-Diamino-5-methyl-6-substituted arylthio-furo[2,3-d]pyrimidines as novel classical and nonclassical antifolates as potential dual thymidylate synthase and dihydrofolate reductase inhibitors.  [PMID:20056546]
13. Gangjee, Aleem and 5 more authors.  2010-02-25  Single agents with designed combination chemotherapy potential: synthesis and evaluation of substituted pyrimido[4,5-b]indoles as receptor tyrosine kinase and thymidylate synthase inhibitors and as antitumor agents.  [PMID:20092323]
14. Zhang, Xin X and 5 more authors.  2011-06-01  Design, synthesis, biological evaluation and X-ray crystal structure of novel classical 6,5,6-tricyclic benzo[4,5]thieno[2,3-d]pyrimidines as dual thymidylate synthase and dihydrofolate reductase inhibitors.  [PMID:21550809]
15. Gangjee, Aleem A and 5 more authors.  2012-07-15  Novel tricyclic indeno[2,1-d]pyrimidines with dual antiangiogenic and cytotoxic activities as potent antitumor agents.  [PMID:22739090]
16. Gangjee, Aleem and 5 more authors.  2013-06-13  Design, synthesis, and molecular modeling of novel pyrido[2,3-d]pyrimidine analogues as antifolates; application of Buchwald-Hartwig aminations of heterocycles.  [PMID:23627352]
17. Cao, Sheng-Li SL and 10 more authors.  2013-06  Synthesis and antiproliferative activity of 4-substituted-piperazine-1-carbodithioate derivatives of 2,4-diaminoquinazoline.  [PMID:23665106]
18. Piras, Sandra S and 7 more authors.  2014-03-21  2-[N-Alkyl(R-phenyl)-aminomethyl]-3-phenyl-7-trifluoromethylquinoxalines as anticancer agents inhibitors of folate enzymes.  [PMID:24531230]
19. G-Dayanandan, Narendran and 11 more authors.  2014-03-27  Propargyl-linked antifolates are dual inhibitors of Candida albicans and Candida glabrata.  [PMID:24568657]
20. Chao, Bo; Li, Bingbing X and Xiao, Xiangshu.  2015-04-01  The chemistry and pharmacology of privileged pyrroloquinazolines.  [PMID:25937878]
21. Welsch, Matthew E ME and 9 more authors.  2016-12-08  Discovery of Potent and Selective Leads against Toxoplasma gondii Dihydrofolate Reductase via Structure-Based Design.  [PMID:27994750]
22. Gopalsamy, Ariamala A and 18 more authors.  2017-04-13  Design of Potent mRNA Decapping Scavenger Enzyme (DcpS) Inhibitors with Improved Physicochemical Properties To Investigate the Mechanism of Therapeutic Benefit in Spinal Muscular Atrophy (SMA).  [PMID:28257199]
23. Zaware, Nilesh N, Kisliuk, Roy R, Bastian, Anja A, Ihnat, Michael A MA and Gangjee, Aleem A.  2017-04-01  Synthesis and evaluation of 5-(arylthio)-9H-pyrimido[4,5-b]indole-2,4-diamines as receptor tyrosine kinase and thymidylate synthase inhibitors and as antitumor agents.  [PMID:28258797]
24. Tonelli, Michele M and 8 more authors.  2017-07-28  Host dihydrofolate reductase (DHFR)-directed cycloguanil analogues endowed with activity against influenza virus and respiratory syncytial virus.  [PMID:28477572]
25. Shah, Khushbu and 5 more authors.  2018-05-15  Targeting species specific amino acid residues: Design, synthesis and biological evaluation of 6-substituted pyrrolo[2,3-d]pyrimidines as dihydrofolate reductase inhibitors and potential anti-opportunistic infection agents.  [PMID:29691153]
26. Francesconi, Valeria V and 7 more authors.  2018-07-15  Synthesis, biological evaluation and molecular modeling of novel azaspiro dihydrotriazines as influenza virus inhibitors targeting the host factor dihydrofolate reductase (DHFR).  [PMID:29886325]
27. Hopper, Allen T and 8 more authors.  2019-02-14  Discovery of Selective Toxoplasma gondii Dihydrofolate Reductase Inhibitors for the Treatment of Toxoplasmosis.  [PMID:30624926]
28. Sharma, Kalicharan K and 8 more authors.  2019-04-01  Expansion of a novel lead targeting M. tuberculosis DHFR as antitubercular agents.  [PMID:30827867]

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