(S)-2-(4-((R)-4-(2,4-Diamino-6-oxo-1,6-dihydropyrimidin-5-yl)-1-(methylthio)butyl)benzamido)pentanedioic AcidF

ID: ALA453090

PubChem CID: 135566722

Max Phase: Preclinical

Molecular Formula: C21H27N5O6S

Molecular Weight: 477.54

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  CS[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/C21H27N5O6S/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:  GEZLAVXTPLTVRU-LSDHHAIUSA-N

Molfile:  

     RDKit          2D

 33 34  0  0  0  0  0  0  0  0999 V2000
   -3.3125   -0.8708    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.3125   -1.6958    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.6005   -2.1042    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.8885   -1.6958    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.8885   -0.8708    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.6005   -0.4542    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.0282   -0.4604    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.0306    0.3646    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.7414   -0.8750    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
   -5.4571   -0.4646    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.3173    0.7792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.6017    0.3688    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.8884    0.7833    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1747    0.3676    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4635    0.7787    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4617    1.6041    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1772    2.0167    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.8946    1.6039    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1760   -0.4574    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.2531    2.0160    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -2.6103    2.0143    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1746   -2.1094    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1758   -2.9344    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4595   -1.6979    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.2543   -2.1114    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.9694   -1.7000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.6833   -2.1135    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.9706   -0.8750    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.2532   -2.9364    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.9670   -3.3500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.9658   -4.1750    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.6797   -4.5885    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.2508   -4.5864    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
 13 18  2  0
 14 15  1  0
 15 16  1  0
 16 17  2  0
 17 18  1  0
  7  9  1  6
 14 19  2  0
  2  3  1  0
 16 20  1  0
  9 10  1  0
 18 21  1  0
  3  4  2  0
  4 22  1  0
  8 11  1  0
 22 23  2  0
  4  5  1  0
 22 24  1  0
 11 12  1  0
 24 25  1  0
  5  6  2  0
 25 26  1  0
 12 13  1  0
 26 27  1  0
 13 14  1  0
 26 28  2  0
 25 29  1  6
  1  7  1  0
 29 30  1  0
  1  2  2  0
 30 31  1  0
  7  8  1  0
 31 32  1  0
  1  6  1  0
 31 33  2  0
M  END

Alternative Forms

1. Parent:

   

   ALA453090

   ---

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: 477.54

Molecular Weight (Monoisotopic): 477.1682

AlogP: 1.41

#Rotatable Bonds: 12

Polar Surface Area: 201.49

Molecular Species: ACID

HBA: 8

HBD: 6

#RO5 Violations: 1

HBA (Lipinski): 11

HBD (Lipinski): 8

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 3.23

CX Basic pKa: ┄

CX LogP: 1.09

CX LogD: -5.59

Aromatic Rings: 2

Heavy Atoms: 33

QED Weighted: 0.26

Np Likeness Score: -0.06

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