(DDATHF) 5,10-Dideazatetrahydrofolic acid2-{4-[2-(2-Amino-4-oxo-3,4,5,6,7,8-hexahydro-pyrido[2,3-d]pyrimidin-6-yl)-ethyl]-benzoylamino}-pentanedioic acid

ID: ALA170101

PubChem CID: 135436405

Max Phase: Preclinical

Molecular Formula: C21H25N5O6

Molecular Weight: 443.46

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  Nc1nc(O)c2c(n1)NCC(CCc1ccc(C(=O)NC(CCC(=O)O)C(=O)O)cc1)C2

Standard InChI:  InChI=1S/C21H25N5O6/c22-21-25-17-14(19(30)26-21)9-12(10-23-17)2-1-11-3-5-13(6-4-11)18(29)24-15(20(31)32)7-8-16(27)28/h3-6,12,15H,1-2,7-10H2,(H,24,29)(H,27,28)(H,31,32)(H4,22,23,25,26,30)

Standard InChI Key:  ZUQBAQVRAURMCL-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 32 34  0  0  0  0  0  0  0  0999 V2000
    3.5042   -4.5042    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.9875   -4.8125    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    3.5042   -3.9042    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.4667   -3.9042    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    2.9875   -3.6042    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.4667   -4.5042    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.0375   -4.8042    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    7.6792   -2.6792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.2042   -2.9792    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    8.7125   -3.8667    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.7042   -3.2667    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.0292   -3.6000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.1542   -2.9792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.9792   -3.0000    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    9.7292   -2.0542    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.6750   -2.0792    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    8.1917   -4.1667    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    1.9417   -4.8125    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    9.7292   -1.4542    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    9.2167   -2.9625    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.1625   -3.5917    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.6292   -2.6875    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.5542   -4.5000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.2167   -2.3625    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.2292   -4.1625    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    4.5542   -3.9000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.1167   -3.5917    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.2542   -2.3500    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    6.6417   -3.8917    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.1125   -2.9917    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.6000   -3.8917    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.0750   -3.5917    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  2  1  2  0
  3  1  1  0
  4  5  1  0
  5  3  2  0
  6  2  1  0
  7  1  1  0
  8 13  1  0
  9  8  1  0
 10 11  1  0
 11  9  1  0
 12  3  1  0
 13 22  1  0
 14  5  1  0
 15 24  1  0
 16  8  2  0
 17 10  2  0
 18  6  1  0
 19 15  2  0
 20 11  1  0
 21 29  1  0
 22 30  2  0
 23  7  1  0
 24 20  1  0
 25 10  1  0
 26 23  1  0
 27 31  1  0
 28 15  1  0
 29 27  2  0
 30 27  1  0
 31 32  1  0
 32 26  1  0
  6  4  2  0
 26 12  1  0
 13 21  2  0
M  END

Alternative Forms

1. Parent:

   

   ALA170101

   ---

Molecule Features

Natural Product: No

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: 443.46

Molecular Weight (Monoisotopic): 443.1805

AlogP: 1.03

#Rotatable Bonds: 9

Polar Surface Area: 187.76

Molecular Species: ACID

HBA: 8

HBD: 6

#RO5 Violations: 1

HBA (Lipinski): 11

HBD (Lipinski): 7

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 3.34

CX Basic pKa: 3.83

CX LogP: 1.40

CX LogD: -4.63

Aromatic Rings: 2

Heavy Atoms: 32

QED Weighted: 0.33

Np Likeness Score: 0.24

References

1. Bigham EC, Hodson SJ, Mallory WR, Wilson D, Duch DS, Smith GK, Ferone R..  (1992)  Synthesis and biological activity of open-chain analogues of 5,6,7,8-tetrahydrofolic acid--potential antitumor agents.,  35  (8): [PMID:1573633] [10.1021/jm00086a008]

2. Borrell JI, Teixidó J, Matallana JL, Martínez-Teipel B, Colominas C, Costa M, Balcells M, Schuler E, Castillo MJ..  (2001)  Synthesis and biological activity of 7-oxo substituted analogues of 5-deaza-5,6,7,8-tetrahydrofolic acid (5-DATHF) and 5,10-dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF).,  44  (14): [PMID:11428931] [10.1021/jm990411u]

3. Taylor EC, Kuhnt D, Shih C, Rinzel SM, Grindey GB, Barredo J, Jannatipour M, Moran RG..  (1992)  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.,  35  (23): [PMID:1447744] [10.1021/jm00101a023]

4. Taylor EC, Dowling JE.  (1997)  Synthesis of a pyrimido[4,5-b]azepine analog of 5,10-dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF),  7  (4): [10.1016/S0960-894X(97)00041-3]

5. Singh SK, Dev IK, Duch DS, Ferone R, Smith GK, Freisheim JH, Hynes JB..  (1991)  Synthesis and biological evaluation of 5-deazaisofolic acid, 5-deaza-5,6,7,8-tetrahydroisofolic acid, and their N9-substituted analogues.,  34  (2): [PMID:1995883] [10.1021/jm00106a021]

6. Gossett LS, Habeck LL, Shackelford KA, Mendelsohn LG, Gates SB, Worzalla JF, Self TD, Theobald KS, Andis SL, Schultz RM, Shih C..  (1999)  The synthesis and biological activity of a series of 2,4-diaminopyrido[2,3-d]pyrimidine based antifolates as antineoplastic and antiarthritic agents.,  9  (1): [PMID:9990460] [10.1016/s0960-894x(98)00683-0]

7. Taylor EC, Harrington PJ, Fletcher SR, Beardsley GP, Moran RG..  (1985)  Synthesis of the antileukemic agents 5,10-dideazaaminopterin and 5,10-dideaza-5,6,7,8-tetrahydroaminopterin.,  28  (7): [PMID:4009615] [10.1021/jm00145a012]

Source

Source(1):

• Scientific Literature