(S)-2-(4-(2-(3-(2,4-Diamino-6-oxo-1,6-dihydropyrimidin-5-yl)propyl)-1,3-dithian-2-yl)benzamido)pentanedioic Acid

ID: ALA452837

PubChem CID: 135924170

Max Phase: Preclinical

Molecular Formula: C23H29N5O6S2

Molecular Weight: 535.65

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  Nc1nc(N)c(CCCC2(c3ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)cc3)SCCCS2)c(=O)[nH]1

Standard InChI:  InChI=1S/C23H29N5O6S2/c24-18-15(20(32)28-22(25)27-18)3-1-10-23(35-11-2-12-36-23)14-6-4-13(5-7-14)19(31)26-16(21(33)34)8-9-17(29)30/h4-7,16H,1-3,8-12H2,(H,26,31)(H,29,30)(H,33,34)(H5,24,25,27,28,32)/t16-/m0/s1

Standard InChI Key:  QWVPZTYSIMAXEN-INIZCTEOSA-N

Molfile:  

     RDKit          2D

 36 38  0  0  0  0  0  0  0  0999 V2000
   12.6542  -18.4167    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.9375  -18.0042    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
   11.2259  -18.4163    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.2247  -19.2426    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.9414  -19.6551    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.6592  -19.2413    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
   13.3708  -18.8292    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.3708  -19.6542    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.0829  -20.0625    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.7949  -19.6542    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.7949  -18.8292    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.0829  -18.4125    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.6527  -17.5938    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.3660  -17.1792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.0817  -17.5896    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.7949  -17.1750    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.5087  -17.5907    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.2198  -17.1796    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   16.2217  -16.3543    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.5061  -15.9417    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   14.7888  -16.3544    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.5073  -18.4157    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   16.9365  -15.9424    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   14.0731  -15.9441    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   15.5087  -20.0677    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.5075  -20.8927    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   16.2238  -19.6562    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   16.9377  -20.0698    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.6528  -19.6583    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.3666  -20.0719    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   17.6539  -18.8333    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   16.9365  -20.8948    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.6504  -21.3083    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.6492  -22.1333    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.3630  -22.5468    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   16.9341  -22.5448    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
  2  3  1  0
  3  4  1  0
  4  5  1  0
  7 12  1  0
 16 21  2  0
 17 18  1  0
 18 19  1  0
 19 20  2  0
 20 21  1  0
  8  9  1  0
 17 22  2  0
  9 10  2  0
 19 23  1  0
 10 11  1  0
 21 24  1  0
 11 12  2  0
 10 25  1  0
  7  1  1  0
 25 26  2  0
  5  6  1  0
 25 27  1  0
  1 13  1  0
 27 28  1  0
  7  8  2  0
 28 29  1  0
 13 14  1  0
 29 30  1  0
 29 31  2  0
 14 15  1  0
 28 32  1  6
  1  2  1  0
 32 33  1  0
 15 16  1  0
 33 34  1  0
 16 17  1  0
 34 35  1  0
  1  6  1  0
 34 36  2  0
M  END

Alternative Forms

1. Parent:

   

   ALA452837

   ---

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: 535.65

Molecular Weight (Monoisotopic): 535.1559

AlogP: 2.03

#Rotatable Bonds: 11

Polar Surface Area: 201.49

Molecular Species: ACID

HBA: 9

HBD: 6

#RO5 Violations: 2

HBA (Lipinski): 11

HBD (Lipinski): 8

#RO5 Violations (Lipinski): 3

CX Acidic pKa: 3.16

CX Basic pKa: ┄

CX LogP: 1.68

CX LogD: -5.03

Aromatic Rings: 2

Heavy Atoms: 36

QED Weighted: 0.25

Np Likeness Score: 0.10

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