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

ID: ALA452324

PubChem CID: 135924169

Max Phase: Preclinical

Molecular Formula: C21H27N5O7

Molecular Weight: 461.48

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  CO[C@H](CCCc1c(N)nc(N)[nH]c1=O)c1ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)cc1

Standard InChI:  InChI=1S/C21H27N5O7/c1-33-15(4-2-3-13-17(22)25-21(23)26-19(13)30)11-5-7-12(8-6-11)18(29)24-14(20(31)32)9-10-16(27)28/h5-8,14-15H,2-4,9-10H2,1H3,(H,24,29)(H,27,28)(H,31,32)(H5,22,23,25,26,30)/t14-,15+/m0/s1

Standard InChI Key:  RUSXEZDHZQNDSF-LSDHHAIUSA-N

Molfile:  

     RDKit          2D

 33 34  0  0  0  0  0  0  0  0999 V2000
    5.1833  -18.5458    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.1833  -19.3708    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.8954  -19.7792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.6074  -19.3708    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.6074  -18.5458    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.8954  -18.1292    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.4677  -18.1354    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.4652  -17.3104    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.1785  -16.8958    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.8942  -17.3062    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.6074  -16.8917    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.3212  -17.3074    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.0323  -16.8963    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    8.0342  -16.0709    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.3186  -15.6583    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    6.6013  -16.0711    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.3198  -18.1324    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    8.7490  -15.6590    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    5.8856  -15.6607    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    7.3212  -19.7844    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.3200  -20.6094    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    8.0363  -19.3729    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    8.7502  -19.7864    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.4653  -19.3750    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.1791  -19.7885    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    9.4664  -18.5500    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    8.7490  -20.6114    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.4629  -21.0250    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.4617  -21.8500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.1755  -22.2635    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    8.7466  -22.2614    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    3.7544  -18.5500    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    3.0387  -18.1396    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  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  6
 14 15  2  0
 32 33  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA452324

   ---

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: 461.48

Molecular Weight (Monoisotopic): 461.1910

AlogP: 0.69

#Rotatable Bonds: 12

Polar Surface Area: 210.72

Molecular Species: ACID

HBA: 8

HBD: 6

#RO5 Violations: 1

HBA (Lipinski): 12

HBD (Lipinski): 8

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 3.16

CX Basic pKa: ┄

CX LogP: 0.20

CX LogD: -6.52

Aromatic Rings: 2

Heavy Atoms: 33

QED Weighted: 0.26

Np Likeness Score: 0.19

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