V2043   Click here for help

GtoPdb Ligand ID: 12587

Synonyms: 1-O-Octadecyl-2-O-benzyl-sn-glyceryl-3-phospho-GS-441524 | compound 5c [PMID: 34310217] | example 67 [WO2022081973A1] | ODBG-P-RVn
Compound class: Synthetic organic
Comment: V2043 is an orally bioavailable phospholipid analogue of remdesivir nucleoside (RVn; GS-441524) [1,3]. It is a prodrug that is metabolised first to RVn monophosphate (by sphingomyelin phosphodiesterase I), and then to the active metabolite RVn triphosphate. Mechanistically, RVn triphosphate inhibits the viral RNA-dependent RNA polymerase (RdRP). Antiviral activity against SARS-CoV-2 has been demonstrated in vitro and in a mouse model of SARS-CoV-2 infection. Structural modifications of V2043 have been reported to improve its antiviral activity [1].
2D Structure
Click here for help

2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

✖
Click here for structure editor
Physico-chemical Properties
Click here for help

Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

✖
Hydrogen bond acceptors 14
Hydrogen bond donors 4
Rotatable bonds 29
Topological polar surface area 211.49
Molecular weight 787.92
XLogP 6.39
No. Lipinski's rules broken 4
SMILES / InChI / InChIKey
Click here for help

SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

✖
Canonical SMILES CCCCCCCCCCCCCCCCCCOC[C@H](COP(=O)(O)OC[C@@H]1[C@H]([C@H]([C@](C#N)(C2=CC=C3C(=NC=NN32)N)O1)O)O)OCC4=CC=CC=C4
Isomeric SMILES P(=O)(OC[C@H]1O[C@@]([C@@H]([C@@H]1O)O)(C#N)C2=CC=C3C(=NC=NN32)N)(OC[C@@H](COCCCCCCCCCCCCCCCCCC)OCC4=CC=CC=C4)O
InChI InChI=1S/C40H62N5O9P/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-20-25-50-27-33(51-26-32-21-18-17-19-22-32)28-52-55(48,49)53-29-35-37(46)38(47)40(30-41,54-35)36-24-23-34-39(42)43-31-44-45(34)36/h17-19,21-24,31,33,35,37-38,46-47H,2-16,20,25-29H2,1H3,(H,48,49)(H2,42,43,44)/t33-,35-,37-,38-,40+/m1/s1
InChI Key JWTGVUMJEVOXGW-RTZKIGCUSA-N
References
1. Carlin AF, Beadle JR, Clark AE, Gully KL, Moreira FR, Baric RS, Graham RL, Valiaeva N, Leibel SL, Bray W et al.. (2023)
1-O-Octadecyl-2-O-benzyl-sn-glyceryl-3-phospho-GS-441524 (V2043). Evaluation of Oral V2043 in a Mouse Model of SARS-CoV-2 Infection and Synthesis and Antiviral Evaluation of Additional Phospholipid Esters with Enhanced Anti-SARS-CoV-2 Activity.
J Med Chem, 66 (8): 5802-5819. [PMID:37040439]
2. Lazerwith SE, Medley JW, Morganelli PA, Stratton TP, Wang P. (2022)
Phospholipid compounds and uses thereof.
Patent number: WO2022081973A1. Assignee: Gilead Sciences, Inc.. Priority date: 16/10/2020. Publication date: 21/04/2022.
3. Schooley RT, Carlin AF, Beadle JR, Valiaeva N, Zhang XQ, Clark AE, McMillan RE, Leibel SL, McVicar RN, Xie J et al.. (2021)
Rethinking Remdesivir: Synthesis, Antiviral Activity, and Pharmacokinetics of Oral Lipid Prodrugs.
Antimicrob Agents Chemother, 65 (10): e0115521. [PMID:34310217]