N-{4-[4-(2-Amino-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-6-yl)-butyl]benzoyl}-L-glutamic Acid

ID: ALA491104

PubChem CID: 24771725

Max Phase: Preclinical

Molecular Formula: C22H24N4O6S

Molecular Weight: 472.52

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  Nc1nc2sc(CCCCc3ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)cc3)cc2c(=O)[nH]1

Standard InChI:  InChI=1S/C22H24N4O6S/c23-22-25-19(30)15-11-14(33-20(15)26-22)4-2-1-3-12-5-7-13(8-6-12)18(29)24-16(21(31)32)9-10-17(27)28/h5-8,11,16H,1-4,9-10H2,(H,24,29)(H,27,28)(H,31,32)(H3,23,25,26,30)/t16-/m0/s1

Standard InChI Key:  KVBZUTNKUVNMNN-INIZCTEOSA-N

Molfile:  

     RDKit          2D

 33 35  0  0  0  0  0  0  0  0999 V2000
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    0.9226   -4.9682    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.6370   -5.3807    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.6370   -3.7216    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.3561   -4.1387    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.3606   -4.9692    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.1521   -5.2216    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
    3.6366   -4.5469    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.1446   -3.8777    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.4616   -4.5423    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
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    5.7030   -5.2499    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.1195   -5.9620    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
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    1.6358   -2.8966    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.2081   -5.3807    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    7.3577   -6.6687    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.1819   -6.6645    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.5912   -5.9472    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.1704   -5.2326    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.3475   -5.2404    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.4162   -5.9415    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.8337   -6.6530    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    9.8238   -5.2242    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   10.6586   -6.6474    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.0760   -7.3590    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.6685   -8.0763    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.0858   -8.7879    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.6782   -9.5052    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   11.9108   -8.7822    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   11.0662   -5.9301    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.8911   -5.9244    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   10.6488   -5.2186    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
  2 16  1  0
  6  7  1  0
 14 17  2  0
  7  8  1  0
 17 18  1  0
  8  9  2  0
 18 19  2  0
  9  5  1  0
 19 20  1  0
  5  4  1  0
 20 21  2  0
 21 14  1  0
  8 10  1  0
 19 22  1  0
  5  6  2  0
 22 23  1  0
 10 11  1  0
 22 24  2  0
 25 23  1  6
 11 12  1  0
 25 26  1  0
  1  2  1  0
 26 27  1  0
 12 13  1  0
 27 28  1  0
  1  4  1  0
 28 29  1  0
 13 14  1  0
 28 30  2  0
  2  3  2  0
 25 31  1  0
  4 15  2  0
 31 32  1  0
  3  6  1  0
 31 33  2  0
M  END

Alternative Forms

1. Parent:

   

   ALA491104

   N-{4-[4-(2-Amino-4-Oxo-1,4-Dihydrothieno[2,3-D]pyrimidin-6-Yl)butyl]benzoyl}-L-Glutamic Acid

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: 472.52

Molecular Weight (Monoisotopic): 472.1417

AlogP: 2.18

#Rotatable Bonds: 11

Polar Surface Area: 175.47

Molecular Species: ACID

HBA: 7

HBD: 5

#RO5 Violations: ┄

HBA (Lipinski): 10

HBD (Lipinski): 6

#RO5 Violations (Lipinski): 1

CX Acidic pKa: 3.34

CX Basic pKa: 3.75

CX LogP: 1.93

CX LogD: -3.72

Aromatic Rings: 3

Heavy Atoms: 33

QED Weighted: 0.26

Np Likeness Score: -0.53

References

1. Deng Y, Zhou X, Kugel Desmoulin S, Wu J, Cherian C, Hou Z, Matherly LH, Gangjee A..  (2009)  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.,  52  (9): [PMID:19371039] [10.1021/jm8011323]

2. Wang L, Cherian C, Desmoulin SK, Polin L, Deng Y, Wu J, Hou Z, White K, Kushner J, Matherly LH, Gangjee A..  (2010)  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.,  53  (3): [PMID:20085328] [10.1021/jm9015729]

3. Wallace-Povirk A,Tong N,Wong-Roushar J,O'Connor C,Zhou X,Hou Z,Bao X,Garcia GE,Li J,Kim S,Dann CE,Matherly LH,Gangjee A.  (2021)  Discovery of 6-substituted thieno[2,3-d]pyrimidine analogs as dual inhibitors of glycinamide ribonucleotide formyltransferase and 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase in de novo purine nucleotide biosynthesis in folate receptor expressing human tumors.,  37  [PMID:33773393] [10.1016/j.bmc.2021.116093]

Source

Source(1):

• Scientific Literature