N-((1H-tetrazol-5-yl)methyl)-4-(6-(2,4-diamino-6-oxo-1,6-dihydropyrimidin-5-yl)-1,1,1-trifluoro-2-oxohexan-3-yl)benzamide

ID: ALA381706

PubChem CID: 135491785

Max Phase: Preclinical

Molecular Formula: C19H20F3N9O3

Molecular Weight: 479.42

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  Nc1nc(N)c(CCCC(C(=O)C(F)(F)F)c2ccc(C(=O)NCc3nn[nH]n3)cc2)c(O)n1

Standard InChI:  InChI=1S/C19H20F3N9O3/c20-19(21,22)14(32)11(2-1-3-12-15(23)26-18(24)27-17(12)34)9-4-6-10(7-5-9)16(33)25-8-13-28-30-31-29-13/h4-7,11H,1-3,8H2,(H,25,33)(H,28,29,30,31)(H5,23,24,26,27,34)

Standard InChI Key:  AWYPXHGWECVZMX-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 34 36  0  0  0  0  0  0  0  0999 V2000
   -2.3431    0.6542    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.3443   -0.1732    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.6294   -0.5860    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.9130   -0.1727    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.9159    0.6578    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.6312    1.0670    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.0577    1.0665    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.1979   -0.5841    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.1966   -1.4091    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.5159   -0.1704    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.2311   -0.5818    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.9449   -0.1682    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.0579    1.8915    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.7720    0.6539    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.3435    2.3042    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.6289    1.8919    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.9146    2.3045    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2048    1.8893    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.5091    2.3013    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.5094    3.1272    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2102    3.5394    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -0.9212    3.1250    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.2232    3.5408    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.6381    3.5332    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2072    1.0643    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -4.4866    1.0662    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.7718   -0.1711    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -5.2042    1.4792    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   -4.0747    1.7810    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   -4.8960    0.3499    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    2.0315    0.6473    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    2.7124   -0.5095    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    3.2525    0.0999    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    2.8410    0.8142    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
 16 17  1  0
 17 18  1  0
  8  9  2  0
 18 19  2  0
  4  5  1  0
 19 20  1  0
  8 10  1  0
 20 21  2  0
  2  3  1  0
 21 22  1  0
 22 17  2  0
 10 11  1  0
 20 23  1  0
  5  6  2  0
 22 24  1  0
 11 12  1  0
 18 25  1  0
  6  1  1  0
 14 26  1  0
  7 13  1  0
 14 27  2  0
  1  2  2  0
 26 28  1  0
  7 14  1  0
 26 29  1  0
  1  7  1  0
 26 30  1  0
 13 15  1  0
  3  4  2  0
 15 16  1  0
  4  8  1  0
 31 12  1  0
 12 32  2  0
 32 33  1  0
 33 34  1  0
 34 31  2  0
M  END

Alternative Forms

1. Parent:

   

   ALA381706

   ---

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: 479.42

Molecular Weight (Monoisotopic): 479.1641

AlogP: 1.03

#Rotatable Bonds: 9

Polar Surface Area: 198.68

Molecular Species: ACID

HBA: 10

HBD: 5

#RO5 Violations: ┄

HBA (Lipinski): 12

HBD (Lipinski): 7

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 4.75

CX Basic pKa: 4.10

CX LogP: 2.85

CX LogD: 1.44

Aromatic Rings: 3

Heavy Atoms: 34

QED Weighted: 0.30

Np Likeness Score: -0.94

References

1. DeMartino JK, Hwang I, Xu L, Wilson IA, Boger DL..  (2006)  Discovery of a potent, nonpolyglutamatable inhibitor of glycinamide ribonucleotide transformylase.,  49  (10): [PMID:16686541] [10.1021/jm0601147]

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