2-{4-[(2-Amino-4-oxo-3,4-dihydro-pyrido[2,3-d]pyrimidin-6-ylamino)-methyl]-benzoylamino}-pentanedioic acid

ID: ALA157857

PubChem CID: 135887126

Max Phase: Preclinical

Molecular Formula: C20H20N6O6

Molecular Weight: 440.42

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  Nc1nc(O)c2cc(NCc3ccc(C(=O)NC(CCC(=O)O)C(=O)O)cc3)cnc2n1

Standard InChI:  InChI=1S/C20H20N6O6/c21-20-25-16-13(18(30)26-20)7-12(9-23-16)22-8-10-1-3-11(4-2-10)17(29)24-14(19(31)32)5-6-15(27)28/h1-4,7,9,14,22H,5-6,8H2,(H,24,29)(H,27,28)(H,31,32)(H3,21,23,25,26,30)

Standard InChI Key:  AYDSBKMPDDZABS-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 32 34  0  0  0  0  0  0  0  0999 V2000
    1.6917   -3.0667    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.1875   -2.1417    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    2.2250   -2.7667    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.7167   -1.8542    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.2375   -2.1667    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.1750   -2.7417    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.4375   -1.0417    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.7417   -3.0875    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    6.9542   -1.3500    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    7.4917   -0.4542    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.4792   -1.0542    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.7667   -1.8792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.9042   -1.3292    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.0500   -1.3875    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.7250   -1.2542    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    6.4417   -0.4292    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    6.9750   -0.1417    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.6500   -3.0417    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    3.8042   -1.9000    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    9.0417   -1.9917    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    8.0042   -1.3667    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.2792   -2.1875    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.3875   -1.0167    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.8917   -1.9375    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.2667   -2.7917    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.5292   -1.0792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.0250   -0.1542    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    4.3292   -2.2042    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.8542   -1.9167    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.5750   -1.0917    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    5.3667   -2.2292    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.8625   -1.3167    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  2  6  2  0
  3  1  2  0
  4  2  1  0
  5  3  1  0
  6  1  1  0
  7 13  1  0
  8  3  1  0
  9  7  1  0
 10 11  1  0
 11  9  1  0
 12  5  1  0
 13 23  1  0
 14 26  1  0
 15  4  1  0
 16  7  2  0
 17 10  2  0
 18  6  1  0
 19 22  1  0
 20 14  2  0
 21 11  1  0
 22 25  1  0
 23 32  2  0
 24 31  1  0
 25  8  2  0
 26 21  1  0
 27 10  1  0
 28 19  1  0
 29 28  1  0
 30 14  1  0
 31 29  2  0
 32 29  1  0
  4  5  2  0
 12 22  2  0
 13 24  2  0
M  END

Alternative Forms

1. Parent:

   

   ALA157857

   ---

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: 440.42

Molecular Weight (Monoisotopic): 440.1444

AlogP: 0.97

#Rotatable Bonds: 9

Polar Surface Area: 200.65

Molecular Species: ACID

HBA: 9

HBD: 6

#RO5 Violations: 1

HBA (Lipinski): 12

HBD (Lipinski): 7

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 3.29

CX Basic pKa: 0.17

CX LogP: 0.64

CX LogD: -5.94

Aromatic Rings: 3

Heavy Atoms: 32

QED Weighted: 0.28

Np Likeness Score: -0.69

References

1. 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]

2. Shih, C C, Habeck, L L LL, Mendelsohn, L G LG, Chen, V J VJ and Schultz, R M RM.  1998  Multiple folate enzyme inhibition: mechanism of a novel pyrrolopyrimidine-based antifolate LY231514 (MTA).  [PMID:9762351]

3. Deng, Yijun and 6 more authors.  2008-08-28  Synthesis and discovery of high affinity folate receptor-specific glycinamide ribonucleotide formyltransferase inhibitors with antitumor activity.  [PMID:18680275]

4. Deng, Yijun Y and 7 more authors.  2009-05-14  Synthesis and biological activity of a novel series of 6-substituted thieno[2,3-d]pyrimidine antifolate inhibitors of purine biosynthesis with selectivity for high affinity folate receptors over the reduced folate carrier and proton-coupled folate transporter for cellular entry.  [PMID:19371039]

5. Wang, Lei and 10 more authors.  2010-02-11  Synthesis and antitumor activity of a novel series of 6-substituted pyrrolo[2,3-d]pyrimidine thienoyl antifolate inhibitors of purine biosynthesis with selectivity for high affinity folate receptors and the proton-coupled folate transporter over the reduced folate carrier for cellular entry.  [PMID:20085328]

6. Wang, Lei and 6 more authors.  2012-02-23  Synthesis and biological activity of 6-substituted pyrrolo[2,3-d]pyrimidine thienoyl regioisomers as inhibitors of de novo purine biosynthesis with selectivity for cellular uptake by high affinity folate receptors and the proton-coupled folate transporter over the reduced folate carrier.  [PMID:22243528]

7. Wang, Yiqiang and 7 more authors.  2013-11-14  Tumor-targeting with novel non-benzoyl 6-substituted straight chain pyrrolo[2,3-d]pyrimidine antifolates via cellular uptake by folate receptor α and inhibition of de novo purine nucleotide biosynthesis.  [PMID:24111942]

8. Golani, Lalit K and 9 more authors.  2014-10-09  Structure-activity profiles of novel 6-substituted pyrrolo[2,3-d]pyrimidine thienoyl antifolates with modified amino acids for cellular uptake by folate receptors α and β and the proton-coupled folate transporter.  [PMID:25234128]

9. Wang, Yiqiang and 7 more authors.  2015-02-12  Novel 5-substituted pyrrolo[2,3-d]pyrimidines as dual inhibitors of glycinamide ribonucleotide formyltransferase and 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase and as potential antitumor agents.  [PMID:25602637]

10. Wang, Lei and 16 more authors.  2015-09-10  6-Substituted Pyrrolo[2,3-d]pyrimidine Thienoyl Regioisomers as Targeted Antifolates for Folate Receptor α and the Proton-Coupled Folate Transporter in Human Tumors.  [PMID:26317331]

11. Golani, Lalit K and 19 more authors.  2016-09-08  Tumor Targeting with Novel 6-Substituted Pyrrolo [2,3-d] Pyrimidine Antifolates with Heteroatom Bridge Substitutions via Cellular Uptake by Folate Receptor α and the Proton-Coupled Folate Transporter and Inhibition of de Novo Purine Nucleotide Biosynthesis.  [PMID:27458733]

12. Ravindra, Manasa and 11 more authors.  2018-03-08  Tumor Targeting with Novel Pyridyl 6-Substituted Pyrrolo[2,3- d]Pyrimidine Antifolates via Cellular Uptake by Folate Receptor α and the Proton-Coupled Folate Transporter and Inhibition of De Novo Purine Nucleotide Biosynthesis.  [PMID:29425443]

13. Ravindra, Manasa and 11 more authors.  2018-05-10  Fluorine-Substituted Pyrrolo[2,3- d]Pyrimidine Analogues with Tumor Targeting via Cellular Uptake by Folate Receptor α and the Proton-Coupled Folate Transporter and Inhibition of de Novo Purine Nucleotide Biosynthesis.  [PMID:29701475]

Source

Source(1):

• Scientific Literature