[(4R,5R,6R,8R)-8-(2,4-dioxopyrimidin-1-yl)-5-hydroxy-3,7-dioxaspiro[3.4]octan-6-yl]methyl dihydrogen phosphate

ID: ALA3827609

PubChem CID: 118084894

Max Phase: Preclinical

Molecular Formula: C11H15N2O9P

Molecular Weight: 350.22

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  O=c1ccn([C@@H]2O[C@H](COP(=O)(O)O)[C@@H](O)[C@]23CCO3)c(=O)[nH]1

Standard InChI:  InChI=1S/C11H15N2O9P/c14-7-1-3-13(10(16)12-7)9-11(2-4-20-11)8(15)6(22-9)5-21-23(17,18)19/h1,3,6,8-9,15H,2,4-5H2,(H,12,14,16)(H2,17,18,19)/t6-,8-,9-,11-/m1/s1

Standard InChI Key:  IIGNQSAZLWVQBB-PNHWDRBUSA-N

Molfile:  

     RDKit          2D

 23 25  0  0  0  0  0  0  0  0999 V2000
    2.1400   -2.2700    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.0000   -1.1200    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.0000   -2.2000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.0000   -3.3700    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.5154   -7.5146    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.0823   -6.1259    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.1583   -4.9420    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.6770   -5.1439    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.1100   -6.5326    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.0292   -7.7179    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.8300   -3.6000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.3400   -3.3500    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    4.5100   -1.8000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.1200   -1.1200    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0581   -4.1953    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.5756   -8.8289    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    5.8226   -1.0781    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.1070   -1.8544    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    2.8757    0.0549    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    8.4220   -1.1310    0.0000 P   0  0  0  0  0  0  0  0  0  0  0  0
    8.4465    0.0687    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    9.4732   -0.5522    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    9.4490   -1.7518    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  6
  2  3  1  0
  3  4  1  0
  4  1  1  0
  5  6  2  0
  5 10  1  0
  6  7  1  0
  7  8  1  0
  8  9  1  0
  9 10  1  0
 11 12  1  0
 12 13  1  0
 13 14  1  0
 14  1  1  0
  1 11  1  0
 11  7  1  1
  8 15  2  0
 10 16  2  0
 13 17  1  1
 17 18  1  0
 14 19  1  6
 18 20  1  0
 20 21  1  0
 20 22  1  0
 20 23  2  0
M  END

Alternative Forms

1. Parent:

   

   ALA3827609

   [(4R,5R,6R,8R)-8-(2,4-dioxopyrimidin-1-yl)-5-hydroxy-1,7-dioxaspiro[3.4]octan-6-yl]methyl dihydrogen phosphate

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: 350.22

Molecular Weight (Monoisotopic): 350.0515

AlogP: -1.94

#Rotatable Bonds: 4

Polar Surface Area: 160.31

Molecular Species: ACID

HBA: 8

HBD: 4

#RO5 Violations: ┄

HBA (Lipinski): 11

HBD (Lipinski): 4

#RO5 Violations (Lipinski): 1

CX Acidic pKa: 1.22

CX Basic pKa: ┄

CX LogP: -2.08

CX LogD: -5.62

Aromatic Rings: 1

Heavy Atoms: 23

QED Weighted: 0.45

Np Likeness Score: 1.29

References

1. Jonckers TH, Tahri A, Vijgen L, Berke JM, Lachau-Durand S, Stoops B, Snoeys J, Leclercq L, Tambuyzer L, Lin TI, Simmen K, Raboisson P..  (2016)  Discovery of 1-((2R,4aR,6R,7R,7aR)-2-Isopropoxy-2-oxidodihydro-4H,6H-spiro[furo[3,2-d][1,3,2]dioxaphosphinine-7,2'-oxetan]-6-yl)pyrimidine-2,4(1H,3H)-dione (JNJ-54257099), a 3'-5'-Cyclic Phosphate Ester Prodrug of 2'-Deoxy-2'-Spirooxetane Uridine Triphosphate Useful for HCV Inhibition.,  59  (12): [PMID:27181575] [10.1021/acs.jmedchem.6b00382]

Source

Source(1):

• Scientific Literature