(S)-2-(7-(2-Amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]-pyrimidin-6-yl)heptanamido)pentanedioic Acid

ID: ALA3086865

PubChem CID: 135567032

Max Phase: Preclinical

Molecular Formula: C18H25N5O6

Molecular Weight: 407.43

Molecule Type: Small molecule

Names and Identifiers

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

Standard InChI:  InChI=1S/C18H25N5O6/c19-18-22-15-11(16(27)23-18)9-10(20-15)5-3-1-2-4-6-13(24)21-12(17(28)29)7-8-14(25)26/h9,12H,1-8H2,(H,21,24)(H,25,26)(H,28,29)(H4,19,20,22,23,27)/t12-/m0/s1

Standard InChI Key:  YFTJOYZLYVUUOD-LBPRGKRZSA-N

Molfile:  

     RDKit          2D

 29 30  0  0  0  0  0  0  0  0999 V2000
   19.2315  -18.1267    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   19.2303  -18.9463    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   19.9384  -19.3553    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   19.9366  -17.7179    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.6452  -18.1232    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.6500  -18.9418    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   21.4300  -19.1902    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   21.9074  -18.5251    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   21.4223  -17.8657    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.5223  -19.3543    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   19.9341  -16.9007    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   22.7246  -18.5203    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   23.1290  -17.8102    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   23.9462  -17.8053    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   24.3506  -17.0952    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   25.1678  -17.0904    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   25.5722  -16.3803    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   26.3893  -16.3755    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   26.7938  -15.6654    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   26.8021  -17.0808    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   27.6109  -15.6606    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   28.0154  -14.9505    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   28.0237  -16.3659    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   28.8325  -14.9457    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   27.6026  -14.2452    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   27.6193  -17.0760    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   28.0320  -17.7813    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   27.6276  -18.4914    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   28.8492  -17.7765    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  2  3  2  0
  3  6  1  0
  5  4  1  0
  4  1  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  1  0
 17 18  1  0
 18 19  1  0
 18 20  2  0
 21 19  1  6
 21 22  1  0
 21 23  1  0
 22 24  1  0
 22 25  2  0
 23 26  1  0
 26 27  1  0
 27 28  1  0
 27 29  2  0
M  END

Alternative Forms

1. Parent:

   

   ALA3086865

   ---

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 407.43

Molecular Weight (Monoisotopic): 407.1805

AlogP: 0.76

#Rotatable Bonds: 12

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: 3.60

CX Basic pKa: 4.97

CX LogP: -0.62

CX LogD: -5.61

Aromatic Rings: 2

Heavy Atoms: 29

QED Weighted: 0.28

Np Likeness Score: 0.29

References

1. Wang Y, Cherian C, Orr S, Mitchell-Ryan S, Hou Z, Raghavan S, Matherly LH, Gangjee A..  (2013)  Tumor-targeting with novel non-benzoyl 6-substituted straight chain pyrrolo[2,3-d]pyrimidine antifolates via cellular uptake by folate receptor α and inhibition of de novo purine nucleotide biosynthesis.,  56  (21): [PMID:24111942] [10.1021/jm401139z]

2. Shih, C C, Habeck, L L LL, Mendelsohn, L G LG, Chen, V J VJ and Schultz, R M RM.  1998  Multiple folate enzyme inhibition: mechanism of a novel pyrrolopyrimidine-based antifolate LY231514 (MTA).  [PMID:9762351]

3. Deng, Yijun and 6 more authors.  2008-08-28  Synthesis and discovery of high affinity folate receptor-specific glycinamide ribonucleotide formyltransferase inhibitors with antitumor activity.  [PMID:18680275]

4. Deng, Yijun Y and 7 more authors.  2009-05-14  Synthesis and biological activity of a novel series of 6-substituted thieno[2,3-d]pyrimidine antifolate inhibitors of purine biosynthesis with selectivity for high affinity folate receptors over the reduced folate carrier and proton-coupled folate transporter for cellular entry.  [PMID:19371039]

5. Wang, Lei and 10 more authors.  2010-02-11  Synthesis and antitumor activity of a novel series of 6-substituted pyrrolo[2,3-d]pyrimidine thienoyl antifolate inhibitors of purine biosynthesis with selectivity for high affinity folate receptors and the proton-coupled folate transporter over the reduced folate carrier for cellular entry.  [PMID:20085328]

6. Wang, Lei and 6 more authors.  2012-02-23  Synthesis and biological activity of 6-substituted pyrrolo[2,3-d]pyrimidine thienoyl regioisomers as inhibitors of de novo purine biosynthesis with selectivity for cellular uptake by high affinity folate receptors and the proton-coupled folate transporter over the reduced folate carrier.  [PMID:22243528]

7. Wang, Yiqiang and 7 more authors.  2013-11-14  Tumor-targeting with novel non-benzoyl 6-substituted straight chain pyrrolo[2,3-d]pyrimidine antifolates via cellular uptake by folate receptor α and inhibition of de novo purine nucleotide biosynthesis.  [PMID:24111942]

8. 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]

9. 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]

10. 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]

11. 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]

12. 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]

13. 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