({[({[(2R,3R,4R,5R)-5-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyloxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy](hydroxy)phosphoryl}oxy)phosphonic acid

ID: ALA486231

Chembl Id: CHEMBL486231

Cas Number: 1015073-42-3

PubChem CID: 23725128

Max Phase: Unknown

Molecular Formula: C10H16FN2O14P3

Molecular Weight: 500.16

Molecule Type: Small molecule

Names and Identifiers

Synonyms: Gs-461203 | Psi-7409 | PSI-7409 | PSI-7409|1015073-42-3|GS-461203|PSI-7409 sodium salt|CHEMBL486231|Dihydroxyphosphoryl (((2R,3R,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydrofuran-2-yl)methoxy-hydroxy-phosphoryl) hydrogen phosphate|T90A75S60M|Uridine 5'-(tetrahydrogen triphosphate), 2'-deoxy-2'-fluoro-2'-methyl-, (2'R)-|[[(2R,3R,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyloxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate|UNII-T90A75Show More⌵

Canonical SMILES:  C[C@@]1(F)[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/C10H16FN2O14P3/c1-10(11)7(15)5(25-8(10)13-3-2-6(14)12-9(13)16)4-24-29(20,21)27-30(22,23)26-28(17,18)19/h2-3,5,7-8,15H,4H2,1H3,(H,20,21)(H,22,23)(H,12,14,16)(H2,17,18,19)/t5-,7-,8-,10-/m1/s1

Standard InChI Key:  IPHULAIUXUVCHH-VPCXQMTMSA-N

Alternative Forms

1. Parent:

   

   ALA486231

   GS-461203

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: Yes

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 500.16

Molecular Weight (Monoisotopic): 499.9798

AlogP: -1.13

#Rotatable Bonds: 8

Polar Surface Area: 244.14

Molecular Species: ACID

HBA: 11

HBD: 6

#RO5 Violations: 3

HBA (Lipinski): 16

HBD (Lipinski): 6

#RO5 Violations (Lipinski): 3

CX Acidic pKa: 0.90

CX Basic pKa:

CX LogP: -2.21

CX LogD: -9.62

Aromatic Rings: 1

Heavy Atoms: 30

QED Weighted: 0.23

Np Likeness Score: 1.10

References

1. Ma H, Jiang WR, Robledo N, Leveque V, Ali S, Lara-Jaime T, Masjedizadeh M, Smith DB, Cammack N, Klumpp K, Symons J..  (2007)  Characterization of the metabolic activation of hepatitis C virus nucleoside inhibitor beta-D-2'-Deoxy-2'-fluoro-2'-C-methylcytidine (PSI-6130) and identification of a novel active 5'-triphosphate species.,  282  (41): [PMID:17698842] [10.1074/jbc.m705274200]

2. Murakami E, Niu C, Bao H, Micolochick Steuer HM, Whitaker T, Nachman T, Sofia MA, Wang P, Otto MJ, Furman PA..  (2008)  The mechanism of action of beta-D-2'-deoxy-2'-fluoro-2'-C-methylcytidine involves a second metabolic pathway leading to beta-D-2'-deoxy-2'-fluoro-2'-C-methyluridine 5'-triphosphate, a potent inhibitor of the hepatitis C virus RNA-dependent RNA polymerase.,  52  (2): [PMID:17999967] [10.1128/aac.01184-07]

3. Lam AM, Murakami E, Espiritu C, Steuer HM, Niu C, Keilman M, Bao H, Zennou V, Bourne N, Julander JG, Morrey JD, Smee DF, Frick DN, Heck JA, Wang P, Nagarathnam D, Ross BS, Sofia MJ, Otto MJ, Furman PA..  (2010)  PSI-7851, a pronucleotide of beta-D-2'-deoxy-2'-fluoro-2'-C-methyluridine monophosphate, is a potent and pan-genotype inhibitor of hepatitis C virus replication.,  54  (8): [PMID:20516278] [10.1128/aac.00399-10]

4. Zhen L, Dai L, Wen X, Yao L, Jin X, Yang XW, Zhao W, Yu SQ, Yuan H, Wang G, Sun H..  (2017)  Discovery of Novel Nucleotide Prodrugs with Improved Potency Against HCV Variants Carrying NS5B S282T Mutation.,  60  (14): [PMID:28650160] [10.1021/acs.jmedchem.7b00262]

5. Zhou S, Mahmoud S, Liu P, Zhou L, Ehteshami M, Bassit L, Tao S, Domaoal RA, Sari O, Schutter C, Amiralaei S, Khalil A, Ollinger Russell O, McBrayer T, Whitaker T, Abou-Taleb N, Amblard F, Coats SJ, Schinazi RF..  (2017)  2'-Chloro,2'-fluoro Ribonucleotide Prodrugs with Potent Pan-genotypic Activity against Hepatitis C Virus Replication in Culture.,  60  (13): [PMID:28595015] [10.1021/acs.jmedchem.7b00067]

6. 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]

7. Pinho P, Kalayanov G, Westerlind H, Rosenquist Å, Wähling H, Sund C, Almeida M, Ayesa S, Tejbrant J, Targett-Adams P, Eneroth A, Lindqvist A..  (2017)  Discovery of β-d-2'-deoxy-2'-dichlorouridine nucleotide prodrugs as potent inhibitors of hepatitis C virus replication.,  27  (15): [PMID:28622881] [10.1016/j.bmcl.2017.05.075]

8. 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]

9. 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]

10. 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]

11. Unpublished dataset, 

12. Wu YJ, Meanwell NA..  (2021)  Geminal Diheteroatomic Motifs: Some Applications of Acetals, Ketals, and Their Sulfur and Nitrogen Homologues in Medicinal Chemistry and Drug Design.,  64  (14.0): [PMID:34213340] [10.1021/acs.jmedchem.1c00790]

Source

Source(2):

• Scientific Literature
• Active Ingredient of a Prodrug