(S)-2-(4-((S)-4-(2,4-Diamino-6-oxo-1,6-dihydropyrimidin-5-yl)-1-hydroxybutyl)benzamido)pentanedioic Acid

ID: ALA453348

PubChem CID: 135924167

Max Phase: Preclinical

Molecular Formula: C20H25N5O7

Molecular Weight: 447.45

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  Nc1nc(N)c(CCC[C@H](O)c2ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)cc2)c(=O)[nH]1

Standard InChI:  InChI=1S/C20H25N5O7/c21-16-12(18(30)25-20(22)24-16)2-1-3-14(26)10-4-6-11(7-5-10)17(29)23-13(19(31)32)8-9-15(27)28/h4-7,13-14,26H,1-3,8-9H2,(H,23,29)(H,27,28)(H,31,32)(H5,21,22,24,25,30)/t13-,14-/m0/s1

Standard InChI Key:  OGTRQJJZWHQCBC-KBPBESRZSA-N

Molfile:  

     RDKit          2D

 32 33  0  0  0  0  0  0  0  0999 V2000
   -2.7500  -10.1458    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.7500  -10.9708    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.0380  -11.3792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.3260  -10.9708    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.3260  -10.1458    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.0380   -9.7292    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.4657   -9.7354    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.4681   -8.9104    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.7548   -8.4958    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.0392   -8.9062    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.3259   -8.4917    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.6122   -8.9074    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0990   -8.4963    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.1008   -7.6709    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.6147   -7.2583    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.3321   -7.6711    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.6135   -9.7324    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.8156   -7.2590    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -2.0478   -7.2607    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -0.6121  -11.3844    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.6133  -12.2094    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.1030  -10.9729    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.8168  -11.3864    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.5319  -10.9750    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.2458  -11.3885    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    1.5331  -10.1500    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.8157  -12.2114    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.5295  -12.6250    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.5283  -13.4500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.2422  -13.8635    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.8133  -13.8614    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -4.1789  -10.1500    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
 14 15  2  0
 15 16  1  0
  7  8  1  0
 12 17  2  0
  1  6  1  0
 14 18  1  0
  8  9  1  0
 16 19  1  0
  2  3  1  0
  4 20  1  0
  9 10  1  0
 20 21  2  0
  3  4  2  0
 20 22  1  0
 10 11  1  0
 22 23  1  0
 11 12  1  0
 23 24  1  0
  4  5  1  0
 24 25  1  0
  5  6  2  0
 24 26  2  0
 23 27  1  6
  1  7  1  0
 27 28  1  0
  1  2  2  0
 28 29  1  0
 11 16  2  0
 29 30  1  0
 12 13  1  0
 29 31  2  0
 13 14  1  0
  7 32  1  1
M  END

Alternative Forms

1. Parent:

   

   ALA453348

   ---

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: 447.45

Molecular Weight (Monoisotopic): 447.1754

AlogP: 0.04

#Rotatable Bonds: 11

Polar Surface Area: 221.72

Molecular Species: ACID

HBA: 8

HBD: 7

#RO5 Violations: 1

HBA (Lipinski): 12

HBD (Lipinski): 9

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 3.16

CX Basic pKa: ┄

CX LogP: -0.44

CX LogD: -7.16

Aromatic Rings: 2

Heavy Atoms: 32

QED Weighted: 0.24

Np Likeness Score: 0.11

References

1. DeMartino JK, Hwang I, Connelly S, Wilson IA, Boger DL..  (2008)  Asymmetric synthesis of inhibitors of glycinamide ribonucleotide transformylase.,  51  (17): [PMID:18686942] [10.1021/jm800555h]

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