N-{4-[5-(2-Amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)pentyl]benzoyl}-L-glutamic Acid

ID: ALA502528

PubChem CID: 135745092

Max Phase: Preclinical

Molecular Formula: C23H27N5O6

Molecular Weight: 469.50

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  Nc1nc2[nH]c(CCCCCc3ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)cc3)cc2c(=O)[nH]1

Standard InChI:  InChI=1S/C23H27N5O6/c24-23-27-19-16(21(32)28-23)12-15(25-19)5-3-1-2-4-13-6-8-14(9-7-13)20(31)26-17(22(33)34)10-11-18(29)30/h6-9,12,17H,1-5,10-11H2,(H,26,31)(H,29,30)(H,33,34)(H4,24,25,27,28,32)/t17-/m0/s1

Standard InChI Key:  VGLCUJLZYVTUKW-KRWDZBQOSA-N

Molfile:  

     RDKit          2D

 34 36  0  0  0  0  0  0  0  0999 V2000
   15.9872   -6.7309    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.7072   -7.1302    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.4150   -6.7080    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.4012   -5.8816    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.6737   -5.4795    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.9689   -5.9082    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.1089   -5.4536    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.8319   -5.8552    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   18.0935   -4.6283    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   19.5395   -5.4270    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.2626   -5.8286    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   19.5242   -4.6017    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.2277   -4.1778    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   18.8012   -4.2043    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   20.2780   -6.6539    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.9968   -7.0513    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   21.0121   -7.8766    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   21.7045   -6.6273    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    9.5517   -5.1358    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    9.1535   -5.8583    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.5763   -6.5618    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   10.3771   -5.1168    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.8000   -5.8275    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.3971   -6.5509    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.9620   -7.1524    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   11.7116   -6.8050    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.6114   -5.9846    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.7795   -4.3943    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    8.3281   -5.8738    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   12.4341   -7.2032    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.1424   -6.7803    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.8607   -7.1785    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.5648   -6.7556    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.2831   -7.1538    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
 16 17  2  0
 16 18  1  0
 19 20  1  0
  7  9  2  0
  4  5  1  0
  8 10  1  0
  2  3  1  0
 19 22  1  0
 20 21  2  0
 21 24  1  0
 23 22  1  0
 23 24  2  0
 10 11  1  6
  5  6  2  0
 10 12  1  0
  6  1  1  0
 12 13  2  0
 24 25  1  0
 25 26  1  0
 26 27  2  0
 27 23  1  0
  1  2  2  0
 22 28  2  0
 12 14  1  0
 20 29  1  0
  4  7  1  0
 26 30  1  0
 11 15  1  0
 30 31  1  0
  3  4  2  0
 31 32  1  0
 15 16  1  0
 32 33  1  0
  7  8  1  0
 33 34  1  0
 34  1  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA502528

   ---

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: 469.50

Molecular Weight (Monoisotopic): 469.1961

AlogP: 1.84

#Rotatable Bonds: 12

Polar Surface Area: 191.26

Molecular Species: ACID

HBA: 6

HBD: 6

#RO5 Violations: 1

HBA (Lipinski): 11

HBD (Lipinski): 7

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 3.33

CX Basic pKa: 4.91

CX LogP: 0.94

CX LogD: -4.15

Aromatic Rings: 3

Heavy Atoms: 34

QED Weighted: 0.22

Np Likeness Score: 0.09

References

1. Deng Y, Wang Y, Cherian C, Hou Z, Buck SA, Matherly LH, Gangjee A..  (2008)  Synthesis and discovery of high affinity folate receptor-specific glycinamide ribonucleotide formyltransferase inhibitors with antitumor activity.,  51  (16): [PMID:18680275] [10.1021/jm8003366]

2. Wang Y, Cherian C, Orr S, Mitchell-Ryan S, Hou Z, Raghavan S, Matherly LH, Gangjee A..  (2013)  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.,  56  (21): [PMID:24111942] [10.1021/jm401139z]

3. Mitchell-Ryan S, Wang Y, Raghavan S, Ravindra MP, Hales E, Orr S, Cherian C, Hou Z, Matherly LH, Gangjee A..  (2013)  Discovery of 5-substituted pyrrolo[2,3-d]pyrimidine antifolates as dual-acting inhibitors of glycinamide ribonucleotide formyltransferase and 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase in de novo purine nucleotide biosynthesis: implications of inhibiting 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase to ampk activation and antitumor activity.,  56  (24): [PMID:24256410] [10.1021/jm401328u]

Source

Source(1):

• Scientific Literature