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

ID: ALA4759798

PubChem CID: 162658194

Max Phase: Preclinical

Molecular Formula: C19H20N4O6S2

Molecular Weight: 464.53

Molecule Type: Unknown

Names and Identifiers

Canonical SMILES:  Nc1nc2sc(CCCc3csc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)c3)cc2c(=O)[nH]1

Standard InChI:  InChI=1S/C19H20N4O6S2/c20-19-22-15(26)11-7-10(31-17(11)23-19)3-1-2-9-6-13(30-8-9)16(27)21-12(18(28)29)4-5-14(24)25/h6-8,12H,1-5H2,(H,21,27)(H,24,25)(H,28,29)(H3,20,22,23,26)/t12-/m0/s1

Standard InChI Key:  QXWUFUZJYLBZQF-LBPRGKRZSA-N

Molfile:  

 
     RDKit          2D

 31 33  0  0  0  0  0  0  0  0999 V2000
   12.9581  -10.1612    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   12.9569  -10.9807    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.5783  -11.4268    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   13.6632   -9.7523    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.6608   -8.9351    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   12.2333  -11.3501    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   14.3718  -10.1576    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.3721  -10.9808    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.1550  -11.2350    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
   15.6388  -10.5688    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.1546   -9.9031    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.4559  -10.5685    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.8643   -9.8607    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.6815   -9.8604    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.0898   -9.1525    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.9020   -9.0642    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   19.0716   -8.2648    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.3637   -7.8564    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
   17.7567   -8.4035    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   19.8180   -7.9321    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   19.9032   -7.1194    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   20.4793   -8.4122    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   20.6496   -6.7867    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.7347   -5.9740    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   21.3109   -7.2668    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   21.2257   -8.0796    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   21.8870   -8.5597    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   21.4803   -5.6389    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   20.0726   -5.4914    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   21.8057   -9.3741    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   22.6373   -8.2287    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  1  0
 19 15  2  0
 17 20  1  0
 20 21  1  0
 20 22  2  0
 23 21  1  6
 23 24  1  0
 23 25  1  0
 25 26  1  0
 26 27  1  0
 24 28  1  0
 24 29  2  0
 27 30  1  0
 27 31  2  0
M  END

Alternative Forms

1. Parent:

   

   ALA4759798

   ---

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: 464.53

Molecular Weight (Monoisotopic): 464.0824

AlogP: 1.85

#Rotatable Bonds: 10

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: 3.67

CX Basic pKa: 3.34

CX LogP: 1.52

CX LogD: -3.98

Aromatic Rings: 3

Heavy Atoms: 31

QED Weighted: 0.30

Np Likeness Score: -0.75

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