(S)-2-(4-(4-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)butyl)-3-fluorothiophene-2-carboxamido)pentanedioic acid

ID: ALA4465095

PubChem CID: 155530762

Max Phase: Preclinical

Molecular Formula: C20H22FN5O6S

Molecular Weight: 479.49

Molecule Type: Unknown

Names and Identifiers

Canonical SMILES:  Nc1nc2[nH]c(CCCCc3csc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)c3F)cc2c(=O)[nH]1

Standard InChI:  InChI=1S/C20H22FN5O6S/c21-14-9(8-33-15(14)18(30)24-12(19(31)32)5-6-13(27)28)3-1-2-4-10-7-11-16(23-10)25-20(22)26-17(11)29/h7-8,12H,1-6H2,(H,24,30)(H,27,28)(H,31,32)(H4,22,23,25,26,29)/t12-/m0/s1

Standard InChI Key:  JWZBILLJZHUAOY-LBPRGKRZSA-N

Molfile:  

 
     RDKit          2D

 33 35  0  0  0  0  0  0  0  0999 V2000
   15.9299  -25.2258    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   15.9299  -26.0535    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.6448  -26.4611    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   16.6448  -24.8057    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.3597  -25.2258    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.3643  -26.0544    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.1540  -26.3050    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   18.6350  -25.6311    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.1467  -24.9626    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.2131  -26.4663    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   16.6448  -23.9781    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   19.4627  -25.6265    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   19.8747  -24.9068    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.7024  -24.9023    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   21.1102  -24.1826    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   21.9336  -24.1760    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   22.4240  -24.8350    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   23.2051  -24.5742    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
   23.1985  -23.7506    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   22.4132  -23.5026    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   23.9073  -23.3334    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   24.6239  -23.7391    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   23.9004  -22.5099    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   24.6101  -22.0921    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   24.6032  -21.2686    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   25.3267  -22.4979    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   25.3128  -20.8509    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   25.3060  -20.0274    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   26.0156  -19.6095    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   24.5893  -19.6216    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   25.3337  -23.3213    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   26.0364  -22.0801    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   22.1518  -22.7216    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  1  0
 19 20  2  0
 20 16  1  0
 19 21  1  0
 21 22  2  0
 21 23  1  0
 23 24  1  0
 24 25  1  0
 24 26  1  1
 25 27  1  0
 27 28  1  0
 28 29  2  0
 28 30  1  0
 26 31  2  0
 26 32  1  0
 20 33  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA4465095

   ---

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: 479.49

Molecular Weight (Monoisotopic): 479.1275

AlogP: 1.65

#Rotatable Bonds: 11

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: 3.59

CX Basic pKa: 4.90

CX LogP: 0.66

CX LogD: -4.40

Aromatic Rings: 3

Heavy Atoms: 33

QED Weighted: 0.22

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