(4-(4-(2-Amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)butyl)-2-fluorobenzoyl)-L-glutamic Acid

ID: ALA4540298

PubChem CID: 155549935

Max Phase: Preclinical

Molecular Formula: C22H24FN5O6

Molecular Weight: 473.46

Molecule Type: Unknown

Names and Identifiers

Canonical SMILES:  Nc1nc2[nH]c(CCCCc3ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)c(F)c3)cc2c(=O)[nH]1

Standard InChI:  InChI=1S/C22H24FN5O6/c23-15-9-11(5-6-13(15)19(31)26-16(21(33)34)7-8-17(29)30)3-1-2-4-12-10-14-18(25-12)27-22(24)28-20(14)32/h5-6,9-10,16H,1-4,7-8H2,(H,26,31)(H,29,30)(H,33,34)(H4,24,25,27,28,32)/t16-/m0/s1

Standard InChI Key:  BDXBDXZHMOFNOY-INIZCTEOSA-N

Molfile:  

 
     RDKit          2D

 34 36  0  0  0  0  0  0  0  0999 V2000
   23.2569  -15.1098    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   23.2569  -15.9311    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   23.9663  -16.3356    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   23.9663  -14.6929    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   24.6757  -15.1098    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   24.6803  -15.9321    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   25.4639  -16.1807    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   25.9413  -15.5119    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   25.4566  -14.8486    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   22.5457  -16.3407    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   23.9663  -13.8716    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   26.7626  -15.5074    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   27.1713  -14.7933    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   27.9926  -14.7887    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   28.3973  -14.0747    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   29.2145  -14.0681    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   29.6240  -14.7736    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   30.4404  -14.7674    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   30.8441  -14.0559    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   30.4254  -13.3492    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   29.6104  -13.3589    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   31.6612  -14.0482    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   32.0765  -14.7521    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   32.0632  -13.3367    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   32.8803  -13.3291    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   33.2823  -12.6176    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   33.2956  -14.0329    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   34.0994  -12.6099    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   34.5014  -11.8984    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   35.3185  -11.8907    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   34.0862  -11.1945    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   32.8936  -14.7444    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   34.1127  -14.0253    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   30.8258  -12.6368    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  1  4  1  0
  2  3  2  0
  3  6  1  0
  5  4  1  0
  5  6  2  0
  6  7  1  0
  7  8  1  0
  8  9  2  0
  9  5  1  0
  2 10  1  0
  4 11  2  0
  8 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 21  2  0
 21 16  1  0
 19 22  1  0
 22 23  2  0
 22 24  1  0
 24 25  1  0
 25 26  1  0
 25 27  1  1
 26 28  1  0
 28 29  1  0
 29 30  2  0
 29 31  1  0
 27 32  2  0
 27 33  1  0
 20 34  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA4540298

   ---

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: 473.46

Molecular Weight (Monoisotopic): 473.1711

AlogP: 1.59

#Rotatable Bonds: 11

Polar Surface Area: 191.26

Molecular Species: ACID

HBA: 6

HBD: 6

#RO5 Violations: 1

HBA (Lipinski): 11

HBD (Lipinski): 7

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 3.20

CX Basic pKa: 4.85

CX LogP: 0.56

CX LogD: -4.59

Aromatic Rings: 3

Heavy Atoms: 34

QED Weighted: 0.23

Np Likeness Score: -0.26

References

1. Ravindra M, Wilson MR, Tong N, O'Connor C, Karim M, Polin L, Wallace-Povirk A, White K, Kushner J, Hou Z, Matherly LH, Gangjee A..  (2018)  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.,  61  (9): [PMID:29701475] [10.1021/acs.jmedchem.8b00408]

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