(5-(4-(2-Amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)butyl)-3-fluoropicolinoyl)-L-glutamic Acid

ID: ALA4557278

PubChem CID: 155554671

Max Phase: Preclinical

Molecular Formula: C21H23FN6O6

Molecular Weight: 474.45

Molecule Type: Unknown

Names and Identifiers

Canonical SMILES:  Nc1nc2[nH]c(CCCCc3cnc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)c(F)c3)cc2c(=O)[nH]1

Standard InChI:  InChI=1S/C21H23FN6O6/c22-13-7-10(9-24-16(13)19(32)26-14(20(33)34)5-6-15(29)30)3-1-2-4-11-8-12-17(25-11)27-21(23)28-18(12)31/h7-9,14H,1-6H2,(H,26,32)(H,29,30)(H,33,34)(H4,23,25,27,28,31)/t14-/m0/s1

Standard InChI Key:  STQPVYHCDNSBIJ-AWEZNQCLSA-N

Molfile:  

 
     RDKit          2D

 34 36  0  0  0  0  0  0  0  0999 V2000
    2.7570  -24.5735    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    2.7570  -25.3948    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.4664  -25.7993    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    3.4664  -24.1567    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.1758  -24.5735    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.1803  -25.3958    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.9640  -25.6444    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    5.4413  -24.9757    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.9567  -24.3123    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.0457  -25.8045    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    3.4664  -23.3354    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    6.2626  -24.9711    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.6714  -24.2570    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.4927  -24.2525    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.8974  -23.5384    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.7145  -23.5318    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.1240  -24.2374    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.9404  -24.2312    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   10.3441  -23.5196    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.9255  -22.8129    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.1104  -22.8226    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.1613  -23.5120    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.5765  -24.2158    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   11.5632  -22.8005    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   12.3804  -22.7928    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.7823  -22.0813    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.7956  -23.4966    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.5995  -22.0736    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.0014  -21.3621    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.8186  -21.3545    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   13.5862  -20.6583    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   12.3937  -24.2082    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   13.6128  -23.4890    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   10.3258  -22.1005    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:

   

   ALA4557278

   ---

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: 474.45

Molecular Weight (Monoisotopic): 474.1663

AlogP: 0.98

#Rotatable Bonds: 11

Polar Surface Area: 204.15

Molecular Species: ACID

HBA: 7

HBD: 6

#RO5 Violations: 1

HBA (Lipinski): 12

HBD (Lipinski): 7

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 2.96

CX Basic pKa: 4.80

CX LogP: -0.18

CX LogD: -5.57

Aromatic Rings: 3

Heavy Atoms: 34

QED Weighted: 0.22

Np Likeness Score: -0.18

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