2-{4-[2-(2,4-Diamino-pteridin-6-yl)-ethyl]-benzoylamino}-pentanedioic acid

ID: ALA296373

Cas Number: 80576-83-6

PubChem CID: 6917908

Max Phase: Phase

Molecular Formula: C22H25N7O5

Molecular Weight: 467.49

Molecule Type: Small molecule

Names and Identifiers

Synonyms: Edatrexate | TCMDC-137768 | CGP 30694 | CGP-30694 | GNF-PF-63 | NSC-626715 | TCMDC-137768 | EDATREXATE|80576-83-6|TCMDC-137768|GNF-Pf-63|CGP 30694|CGP-30694|JT4X6Z1HRR|CHEMBL296373|NSC-626715|L-Glutamic acid, N-(4-(1-((2,4-diamino-6-pteridinyl)methyl)propyl)benzoyl)-|Edatrexato|Edatrexatum|Edatrexate [USAN:INN]|Edatrexatum [INN-Latin]|UNII-JT4X6Z1HRR|Edatrexato [INN-Spanish]|CGP 30694;NSC 626715|EDATREXATE [MI]|EDATREXATE [INN]|Edatrexate (USAN/INN)|EDATREXATE [USAN]|EDATREXATE [MART.]|SCHEMBL46Show More⌵

Canonical SMILES:  CCC(Cc1cnc2nc(N)nc(N)c2n1)c1ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)cc1

Standard InChI:  InChI=1S/C22H25N7O5/c1-2-11(9-14-10-25-19-17(26-14)18(23)28-22(24)29-19)12-3-5-13(6-4-12)20(32)27-15(21(33)34)7-8-16(30)31/h3-6,10-11,15H,2,7-9H2,1H3,(H,27,32)(H,30,31)(H,33,34)(H4,23,24,25,28,29)/t11?,15-/m0/s1

Standard InChI Key:  FSIRXIHZBIXHKT-MHTVFEQDSA-N

Molfile:  

     RDKit          2D

 34 36  0  0  1  0  0  0  0  0999 V2000
    0.9292    1.8000    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.0500    3.3208    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -0.8333    1.8000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.8333    2.8083    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0500    1.2958    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.9292    2.8083    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.7083    1.2958    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.0542   -1.7917    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.7083    3.3208    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.9167   -1.2417    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    2.8542   -2.3750    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.8000   -1.7417    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.8750   -1.2542    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.5875    1.8000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.4250    0.0583    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.5875   -0.2417    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0792   -2.7542    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -3.4708    1.2708    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.4708    0.2583    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.8375   -2.3917    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    3.4250   -0.9417    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.0500    0.2750    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.7375   -1.7917    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.8625   -0.2417    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.8125    3.3208    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -2.5875   -1.2875    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.7375    0.2583    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.5875    2.8083    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.2667   -0.7042    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.1375   -0.7042    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.3625   -3.2417    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    4.2667    0.5708    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -4.3458   -0.2417    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.3458   -1.2875    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  2  6  2  0
  3  5  1  0
  4  2  1  0
  5  1  2  0
  6  1  1  0
  7  3  2  0
  8 13  1  0
  9  4  2  0
 10  8  1  0
 12 11  1  0
 12 10  1  1
 13 24  1  0
 14  7  1  0
 15 30  1  0
 16 19  1  0
 17  8  2  0
 18 14  1  0
 19 18  1  0
 20 11  2  0
 21 15  2  0
 22  5  1  0
 23 26  1  0
 24 27  2  0
 25  6  1  0
 26 16  2  0
 27 16  1  0
 28  9  1  0
 29 12  1  0
 30 29  1  0
 31 11  1  0
 32 15  1  0
 33 19  1  0
 34 33  1  0
  3  4  1  0
 14 28  2  0
 23 13  2  0
M  END

Alternative Forms

1. Parent:

   

   ALA296373

   EDATREXATE

Molecule Features

Natural Product: Yes

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 467.49

Molecular Weight (Monoisotopic): 467.1917

AlogP: 1.37

#Rotatable Bonds: 10

Polar Surface Area: 207.30

Molecular Species: ACID

HBA: 9

HBD: 5

#RO5 Violations: ┄

HBA (Lipinski): 12

HBD (Lipinski): 7

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 3.27

CX Basic pKa: 2.85

CX LogP: 0.98

CX LogD: -5.34

Aromatic Rings: 3

Heavy Atoms: 34

QED Weighted: 0.29

Np Likeness Score: -0.12

References

1. Kotake Y, Iijima A, Yoshimatsu K, Tamai N, Ozawa Y, Koyanagi N, Kitoh K, Nomura H..  (1994)  Synthesis and antitumor activities of novel 6-5 fused ring heterocycle antifolates: N-[4-[omega-(2-amino-4-substituted-6,7-dihydrocyclopenta [d]pyrimidin-5-yl)alkyl]benzoyl]-L-glutamic acids.,  37  (11): [PMID:8201595] [10.1021/jm00037a012]

2. Rosowsky A, Wright JE, Vaidya CM, Forsch RA, Bader H..  (2000)  Analogues of the potent nonpolyglutamatable antifolate N(alpha)-(4-amino-4-deoxypteroyl)-N(delta)-hemiphthaloyl-L-ornithine (PT523) with modifications in the side chain, p-aminobenzoyl moiety, or 9,10-bridge: synthesis and in vitro antitumor activity.,  43  (8): [PMID:10780919] [10.1021/jm990630f]

3. Nair MG, Nanavati NT, Kumar P, Gaumont Y, Kisliuk RL..  (1988)  Synthesis and biological evaluation of poly-gamma-glutamyl metabolites of 10-deazaaminopterin and 10-ethyl-10-deazaaminopterin.,  31  (1): [PMID:2447278] [10.1021/jm00396a029]

4. DeGraw JI, Christie PH, Kisliuk RL, Gaumont Y, Sirotnak FM..  (1990)  Synthesis and antifolate properties of 9-alkyl-10-deazaminopterins.,  33  (1): [PMID:2296020] [10.1021/jm00163a035]

5. Rosowsky A, Bader H, Wright JE, Keyomarsi K, Matherly LH..  (1994)  Synthesis and biological activity of N omega-hemiphthaloyl-alpha,omega- diaminoalkanoic acid analogues of aminopterin and 3',5-dichloroaminopterin.,  37  (14): [PMID:8035423] [10.1021/jm00040a008]

6. DeGraw JI, Colwell WT, Piper JR, Sirotnak FM..  (1993)  Synthesis and antitumor activity of 10-propargyl-10-deazaaminopterin.,  36  (15): [PMID:8340923] [10.1021/jm00067a020]

7. Abraham A, McGuire JJ, Galivan J, Nimec Z, Kisliuk RL, Gaumont Y, Nair MG..  (1991)  Folate analogues. 34. Synthesis and antitumor activity of non-polyglutamylatable inhibitors of dihydrofolate reductase.,  34  (1): [PMID:1992121] [10.1021/jm00105a035]

8. DeGraw JI, Colwell WT, Crase J, Smith RL, Piper JR, Waud WR, Sirotnak FM..  (1997)  Analogues of methotrexate in rheumatoid arthritis. 1. Effects of 10-deazaaminopterin analogues on type II collagen-induced arthritis in mice.,  40  (3): [PMID:9022804] [10.1021/jm9505526]

9. Gossett LS, Habeck LL, Gates SB, Andis SL, Worzalla JF, Schultz RM, Mendelsonn LG, Kohler W, Ratnam M, Grindey GB, Shih C.  (1996)  Synthesis and biological evaluation of a new series of dihydrofolate reductase inhibitors based on the 4-(2,6-diamino-5-pyrimidinyl)alkyl-L-glutamic acid structure,  6  (4): [10.1016/0960-894X(96)00053-4]

10. Gamo FJ, Sanz LM, Vidal J, de Cozar C, Alvarez E, Lavandera JL, Vanderwall DE, Green DV, Kumar V, Hasan S, Brown JR, Peishoff CE, Cardon LR, Garcia-Bustos JF..  (2010)  Thousands of chemical starting points for antimalarial lead identification.,  465  (7296): [PMID:20485427] [10.1038/nature09107]

11. Plouffe D, Brinker A, McNamara C, Henson K, Kato N, Kuhen K, Nagle A, Adrián F, Matzen JT, Anderson P, Nam TG, Gray NS, Chatterjee A, Janes J, Yan SF, Trager R, Caldwell JS, Schultz PG, Zhou Y, Winzeler EA..  (2008)  In silico activity profiling reveals the mechanism of action of antimalarials discovered in a high-throughput screen.,  105  (26): [PMID:18579783] [10.1073/pnas.0802982105]

12. USP Dictionary of USAN and International Names (2010 edition) and USAN registrations 2007-date, 

13. Biour M, Ben Salem C, Chazouillères O, Grangé JD, Serfaty L, Poupon R..  (2004)  [Drug-induced liver injury; fourteenth updated edition of the bibliographic database of liver injuries and related drugs].,  28  (8-9): [PMID:15646539] [10.1016/s0399-8320(04)95062-2]

14. St. Jude Leishmania screening dataset.,  [10.6019/CHEMBL3433997]

Source

Source(5):

• Scientific Literature
• GSK Malaria Screening
• Novartis Malaria Screening
• USP Dictionary of USAN and International Drug Names
• St Jude Leishmania Screening