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

ID: ALA4538151

PubChem CID: 155548982

Max Phase: Preclinical

Molecular Formula: C21H22FN5O6

Molecular Weight: 459.43

Molecule Type: Unknown

Names and Identifiers

Canonical SMILES:  Nc1nc2[nH]c(CCCc3ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)c(F)c3)cc2c(=O)[nH]1

Standard InChI:  InChI=1S/C21H22FN5O6/c22-14-8-10(2-1-3-11-9-13-17(24-11)26-21(23)27-19(13)31)4-5-12(14)18(30)25-15(20(32)33)6-7-16(28)29/h4-5,8-9,15H,1-3,6-7H2,(H,25,30)(H,28,29)(H,32,33)(H4,23,24,26,27,31)/t15-/m0/s1

Standard InChI Key:  VEKHZPVGFDPVJG-HNNXBMFYSA-N

Molfile:  

 
     RDKit          2D

 33 35  0  0  0  0  0  0  0  0999 V2000
   36.0885  -15.8527    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   36.0885  -16.6740    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   36.7979  -17.0785    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   36.7979  -15.4358    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   37.5073  -15.8527    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   37.5118  -16.6750    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   38.2955  -16.9236    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   38.7728  -16.2548    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   38.2882  -15.5915    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   35.3772  -17.0836    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   36.7979  -14.6145    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   39.5941  -16.2503    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   40.0029  -15.5362    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   40.8242  -15.5316    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   41.2289  -14.8217    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   42.0463  -14.8219    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   42.4509  -14.1128    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   42.0384  -13.4064    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   41.2170  -13.4135    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   40.8161  -14.1232    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   42.4421  -12.6959    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   43.2593  -12.6903    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   42.0287  -11.9910    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   43.6630  -11.9798    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   44.4802  -11.9742    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   43.2496  -11.2749    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   43.6533  -10.5644    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   43.2399   -9.8595    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   43.6436   -9.1490    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   42.4227   -9.8651    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   44.8936  -12.6791    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   44.8839  -11.2637    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   40.8020  -12.7096    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  2  0
 16 17  1  0
 17 18  2  0
 18 19  1  0
 19 20  2  0
 20 15  1  0
 18 21  1  0
 21 22  1  0
 21 23  2  0
 22 24  1  0
 24 25  1  1
 24 26  1  0
 26 27  1  0
 27 28  1  0
 28 29  2  0
 28 30  1  0
 25 31  2  0
 25 32  1  0
 19 33  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA4538151

   ---

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: 459.43

Molecular Weight (Monoisotopic): 459.1554

AlogP: 1.20

#Rotatable Bonds: 10

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: 4.80

CX LogP: 0.17

CX LogD: -5.06

Aromatic Rings: 3

Heavy Atoms: 33

QED Weighted: 0.26

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