(5-(4-(2-amino-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-6-yl)butyl)thiophene-3-carbonyl)-L-glutamic acid

ID: ALA4783397

PubChem CID: 162666193

Max Phase: Preclinical

Molecular Formula: C20H22N4O6S2

Molecular Weight: 478.55

Molecule Type: Unknown

Names and Identifiers

Canonical SMILES:  Nc1nc2sc(CCCCc3cc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)cs3)cc2c(=O)[nH]1

Standard InChI:  InChI=1S/C20H22N4O6S2/c21-20-23-17(28)13-8-12(32-18(13)24-20)4-2-1-3-11-7-10(9-31-11)16(27)22-14(19(29)30)5-6-15(25)26/h7-9,14H,1-6H2,(H,22,27)(H,25,26)(H,29,30)(H3,21,23,24,28)/t14-/m0/s1

Standard InChI Key:  UEVAKXKCGSGJIG-AWEZNQCLSA-N

Molfile:  

 
     RDKit          2D

 32 34  0  0  0  0  0  0  0  0999 V2000
    1.1666  -13.9706    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.1654  -14.7902    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.7868  -15.2363    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.8717  -13.5618    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.8693  -12.7446    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.4418  -15.1595    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    2.5803  -13.9670    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.5806  -14.7902    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.3635  -15.0444    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
    3.8473  -14.3782    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.3631  -13.7125    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.6644  -14.3779    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.0728  -13.6701    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.8900  -13.6698    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.2983  -12.9620    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.1155  -12.9617    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.5942  -13.6237    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.3713  -13.3709    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.3710  -12.5536    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.5937  -12.3015    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
    9.0326  -13.8510    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.9475  -14.6637    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    9.7790  -13.5184    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   10.4403  -13.9985    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.1868  -13.6658    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.3552  -14.8112    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.6088  -15.1438    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.5236  -15.9566    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.8486  -14.1451    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   11.2724  -12.8523    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    8.7776  -16.2902    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   10.1854  -16.4377    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  2  3  2  0
  3  8  1  0
  7  4  1  0
  4  1  1  0
  4  5  2  0
  2  6  1  0
  7  8  2  0
  8  9  1  0
  9 10  1  0
 10 11  2  0
 11  7  1  0
 10 12  1  0
 12 13  1  0
 13 14  1  0
 14 15  1  0
 15 16  1  0
 16 17  2  0
 17 18  1  0
 18 19  2  0
 19 20  1  0
 20 16  1  0
 18 21  1  0
 21 22  2  0
 21 23  1  0
 24 23  1  6
 24 25  1  0
 24 26  1  0
 26 27  1  0
 27 28  1  0
 25 29  1  0
 25 30  2  0
 28 31  1  0
 28 32  2  0
M  END

Alternative Forms

1. Parent:

   

   ALA4783397

   ---

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Unknown

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 478.55

Molecular Weight (Monoisotopic): 478.0981

AlogP: 2.24

#Rotatable Bonds: 11

Polar Surface Area: 175.47

Molecular Species: ACID

HBA: 8

HBD: 5

#RO5 Violations: ┄

HBA (Lipinski): 10

HBD (Lipinski): 6

#RO5 Violations (Lipinski): 1

CX Acidic pKa: 3.68

CX Basic pKa: 3.37

CX LogP: 1.94

CX LogD: -3.53

Aromatic Rings: 3

Heavy Atoms: 32

QED Weighted: 0.26

Np Likeness Score: -0.74

References

1. Wallace-Povirk A,Tong N,Wong-Roushar J,O'Connor C,Zhou X,Hou Z,Bao X,Garcia GE,Li J,Kim S,Dann CE,Matherly LH,Gangjee A.  (2021)  Discovery of 6-substituted thieno[2,3-d]pyrimidine analogs as dual inhibitors of glycinamide ribonucleotide formyltransferase and 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase in de novo purine nucleotide biosynthesis in folate receptor expressing human tumors.,  37  [PMID:33773393] [10.1016/j.bmc.2021.116093]

2. 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]

3. 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]

4. 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]

5. 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]

6. 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]

7. 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