2'-C-Methyl-uridine-5'-triphosphate

ID: ALA521487

Chembl Id: CHEMBL521487

Cas Number: 125911-76-4

PubChem CID: 44586007

Max Phase: Preclinical

Molecular Formula: C10H17N2O15P3

Molecular Weight: 498.17

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  C[C@@]1(O)[C@H](O)[C@@H](COP(=O)(O)OP(=O)(O)OP(=O)(O)O)O[C@H]1n1ccc(=O)[nH]c1=O

Standard InChI:  InChI=1S/C10H17N2O15P3/c1-10(16)7(14)5(25-8(10)12-3-2-6(13)11-9(12)15)4-24-29(20,21)27-30(22,23)26-28(17,18)19/h2-3,5,7-8,14,16H,4H2,1H3,(H,20,21)(H,22,23)(H,11,13,15)(H2,17,18,19)/t5-,7-,8-,10-/m1/s1

Standard InChI Key:  JPNBLHSBLCCTEO-VPCXQMTMSA-N

Alternative Forms

1. Parent:

   

   ALA521487

   2''-C-Methyl-uridine-5''-triphosphate

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: 498.17

Molecular Weight (Monoisotopic): 497.9842

AlogP: -2.11

#Rotatable Bonds: 8

Polar Surface Area: 264.37

Molecular Species: ACID

HBA: 12

HBD: 7

#RO5 Violations: 2

HBA (Lipinski): 17

HBD (Lipinski): 7

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 0.90

CX Basic pKa: ┄

CX LogP: -3.10

CX LogD: -10.51

Aromatic Rings: 1

Heavy Atoms: 30

QED Weighted: 0.19

Np Likeness Score: 1.43

References

1. Ko H, Carter RL, Cosyn L, Petrelli R, de Castro S, Besada P, Zhou Y, Cappellacci L, Franchetti P, Grifantini M, Van Calenbergh S, Harden TK, Jacobson KA..  (2008)  Synthesis and potency of novel uracil nucleotides and derivatives as P2Y2 and P2Y6 receptor agonists.,  16  (12): [PMID:18514530] [10.1016/j.bmc.2008.05.013]

2. Alexandre FR, Badaroux E, Bilello JP, Bot S, Bouisset T, Brandt G, Cappelle S, Chapron C, Chaves D, Convard T, Counor C, Da Costa D, Dukhan D, Gay M, Gosselin G, Griffon JF, Gupta K, Hernandez-Santiago B, La Colla M, Lioure MP, Milhau J, Paparin JL, Peyronnet J, Parsy C, Pierra Rouvière C, Rahali H, Rahali R, Salanson A, Seifer M, Serra I, Standring D, Surleraux D, Dousson CB..  (2017)  The discovery of IDX21437: Design, synthesis and antiviral evaluation of 2'-α-chloro-2'-β-C-methyl branched uridine pronucleotides as potent liver-targeted HCV polymerase inhibitors.,  27  (18): [PMID:28835346] [10.1016/j.bmcl.2017.08.029]

3. Wang G, Lim SP, Chen YL, Hunziker J, Rao R, Gu F, Seh CC, Ghafar NA, Xu H, Chan K, Lin X, Saunders OL, Fenaux M, Zhong W, Shi PY, Yokokawa F..  (2018)  Structure-activity relationship of uridine-based nucleoside phosphoramidate prodrugs for inhibition of dengue virus RNA-dependent RNA polymerase.,  28  (13): [PMID:29801997] [10.1016/j.bmcl.2018.04.069]

4. Wang G, Dyatkina N, Prhavc M, Williams C, Serebryany V, Hu Y, Huang Y, Wan J, Wu X, Deval J, Fung A, Jin Z, Tan H, Shaw K, Kang H, Zhang Q, Tam Y, Stoycheva A, Jekle A, Smith DB, Beigelman L..  (2019)  Synthesis and Anti-HCV Activities of 4'-Fluoro-2'-Substituted Uridine Triphosphates and Nucleotide Prodrugs: Discovery of 4'-Fluoro-2'- C-methyluridine 5'-Phosphoramidate Prodrug (AL-335) for the Treatment of Hepatitis C Infection.,  62  (9): [PMID:30951311] [10.1021/acs.jmedchem.9b00143]

5. Mengshetti S, Zhou L, Sari O, De Schutter C, Zhang H, Cho JH, Tao S, Bassit LC, Verma K, Domaoal RA, Ehteshami M, Jiang Y, Ovadia R, Kasthuri M, Ollinger Russell O, McBrayer T, Whitaker T, Pattassery J, Pascual ML, Uher L, Lin BY, Lee S, Amblard F, Coats SJ, Schinazi RF..  (2019)  Discovery of a Series of 2'-α-Fluoro,2'-β-bromo-ribonucleosides and Their Phosphoramidate Prodrugs as Potent Pan-Genotypic Inhibitors of Hepatitis C Virus.,  62  (4): [PMID:30653317] [10.1021/acs.jmedchem.8b01300]

Source

Source(1):

• Scientific Literature