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

ID: ALA526928

PubChem CID: 135924031

Max Phase: Preclinical

Molecular Formula: C24H29N5O6

Molecular Weight: 483.53

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  Nc1nc2[nH]c(CCCCCCc3ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)cc3)cc2c(=O)[nH]1

Standard InChI:  InChI=1S/C24H29N5O6/c25-24-28-20-17(22(33)29-24)13-16(26-20)6-4-2-1-3-5-14-7-9-15(10-8-14)21(32)27-18(23(34)35)11-12-19(30)31/h7-10,13,18H,1-6,11-12H2,(H,27,32)(H,30,31)(H,34,35)(H4,25,26,28,29,33)/t18-/m0/s1

Standard InChI Key:  RPYYKEVLDNHRJX-SFHVURJKSA-N

Molfile:  

     RDKit          2D

 35 37  0  0  0  0  0  0  0  0999 V2000
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    3.6387  -12.1166    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.3507  -11.6986    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.3410  -10.8669    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.6157  -10.4637    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.9061  -10.8888    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.0530  -10.4465    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
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    7.1959   -9.1834    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
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    0.0752  -11.7489    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.7931  -12.1508    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
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    2.2193  -12.1320    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.7779  -10.8405    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    5.7680   -9.2045    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    8.6612  -11.6481    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -4.5370  -13.3528    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -2.1008  -13.0263    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -4.4797  -14.7559    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  2  0
  2  3  1  0
  3  4  2  0
  4  5  1  0
  5  6  2  0
  6  1  1  0
  4  7  1  0
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  9 10  1  6
 16 17  2  0
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 19 18  1  0
 19 20  2  0
 21 22  2  0
 22 19  1  0
 18 23  2  0
 21 24  1  0
 24 25  1  0
 25 26  1  0
 26 27  1  0
  9 11  1  0
 27 28  1  0
 11 12  2  0
 28 29  1  0
 29  1  1  0
 10 13  1  0
 13 14  1  0
 14 15  2  0
 14 32  1  0
 11 31  1  0
 33 16  1  0
 33 18  1  0
  7 30  1  0
 30  9  1  0
 20 34  1  0
 34 21  1  0
 16 35  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA526928

   ---

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: 483.53

Molecular Weight (Monoisotopic): 483.2118

AlogP: 2.23

#Rotatable Bonds: 13

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: 1.39

CX LogD: -3.71

Aromatic Rings: 3

Heavy Atoms: 35

QED Weighted: 0.20

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