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

ID: ALA4445651

PubChem CID: 155518053

Max Phase: Preclinical

Molecular Formula: C19H20FN5O6S

Molecular Weight: 465.46

Molecule Type: Unknown

Names and Identifiers

Canonical SMILES:  Nc1nc2[nH]c(CCCc3csc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)c3F)cc2c(=O)[nH]1

Standard InChI:  InChI=1S/C19H20FN5O6S/c20-13-8(2-1-3-9-6-10-15(22-9)24-19(21)25-16(10)28)7-32-14(13)17(29)23-11(18(30)31)4-5-12(26)27/h6-7,11H,1-5H2,(H,23,29)(H,26,27)(H,30,31)(H4,21,22,24,25,28)/t11-/m0/s1

Standard InChI Key:  WMTFSFGBNBUALY-NSHDSACASA-N

Molfile:  

 
     RDKit          2D

 32 34  0  0  0  0  0  0  0  0999 V2000
   28.7338  -24.3548    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   28.7338  -25.1761    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   29.4432  -25.5806    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   29.4432  -23.9379    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   30.1526  -24.3548    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   30.1571  -25.1771    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   30.9408  -25.4257    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   31.4181  -24.7569    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   30.9335  -24.0936    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   28.0225  -25.5857    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   29.4432  -23.1166    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   32.2394  -24.7524    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   32.6482  -24.0383    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   33.4695  -24.0337    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   33.8742  -23.3238    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   34.2716  -22.0654    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   34.2643  -21.2470    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   34.9683  -20.8320    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   33.5529  -20.8448    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   33.5456  -20.0276    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   32.8342  -19.6254    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   34.2496  -19.6127    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   32.8269  -18.8082    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   32.1155  -18.4060    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   32.1082  -17.5888    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   31.4115  -18.8209    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   34.9609  -20.0149    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   34.2422  -18.7955    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   33.6175  -22.5514    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   34.6959  -23.3201    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   34.9417  -22.5395    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
   32.8382  -22.3056    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
 16 17  1  0
 17 18  2  0
 17 19  1  0
 19 20  1  0
 20 21  1  0
 20 22  1  1
 21 23  1  0
 23 24  1  0
 24 25  2  0
 24 26  1  0
 22 27  2  0
 22 28  1  0
 16 29  2  0
 29 15  1  0
 15 30  2  0
 30 31  1  0
 31 16  1  0
 29 32  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA4445651

   ---

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: 465.46

Molecular Weight (Monoisotopic): 465.1118

AlogP: 1.26

#Rotatable Bonds: 10

Polar Surface Area: 191.26

Molecular Species: ACID

HBA: 7

HBD: 6

#RO5 Violations: 1

HBA (Lipinski): 11

HBD (Lipinski): 7

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 3.57

CX Basic pKa: 4.74

CX LogP: 0.27

CX LogD: -4.93

Aromatic Rings: 3

Heavy Atoms: 32

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