GS 441524
- CAS No.
- 1191237-69-0
- Chemical Name:
- GS 441524
- Synonyms
- GS-441524;GS-441;(2R,3R,4S,5R)-2-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-carbonitrile;(2R,3R,4S,5R)-2-(4-Aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-3,4-dihydroxy-5-(hydroxymethyl)oxolane-2-carbonitrile;(2R,3R,4S,5R)-2-(4-AMINOPYRROLO[2,1-F][1,2,4]TRIAZIN-7-YL)-3,4-DIHYDROXY-5-(HYDROXYMETHYL)OXOLANE-2-;NUC;Remdesivir intermediates;200-001-8;(2R,3R,4S,5R)-2-(4-aminopyrrolo[1,2-f][1,2,4]triazin-7-yl)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-carbonitrile;GS-4
- CBNumber:
- CB04808604
- Molecular Formula:
- C12H13N5O4
- Molecular Weight:
- 291.26
- MDL Number:
- MFCD32666994
- MOL File:
- 1191237-69-0.mol
- MSDS File:
- SDS
- TDS File:
- TDS
| Melting point | > 233° C (dec.) |
|---|---|
| Density | 1.84±0.1 g/cm3(Predicted) |
| storage temp. | -20°C |
| solubility | Soluble in DMSO (>25 mg/ml) |
| pka | 12.13±0.70(Predicted) |
| form | solid |
| color | Off-white |
| Stability | Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 1 month. |
| InChI | InChI=1/C12H13N5O4/c13-4-12(10(20)9(19)7(3-18)21-12)8-2-1-6-11(14)15-5-16-17(6)8/h1-2,5,7,9-10,18-20H,3H2,(H2,14,15,16)/t7-,9-,10-,12+/s3 |
| InChIKey | BRDWIEOJOWJCLU-QHRJDZJMNA-N |
| SMILES | C([C@]1(C2=CC=C3C(=NC=NN23)N)[C@@H]([C@H](O)[C@@H](CO)O1)O)#N |&1:1,12,13,15,r| |
| CAS DataBase Reference | 1191237-69-0 |
| FDA UNII | 1BQK176DT6 |
SAFETY
Risk and Safety Statements
| Symbol(GHS) |  GHS07 |
|||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Signal word | Warning | |||||||||
| Hazard statements | H302-H315-H319-H335 | |||||||||
| Precautionary statements | P261-P280-P301+P312-P302+P352-P305+P351+P338 | |||||||||
| REACH Registrations | Active | |||||||||
| NFPA 704 |
|
GS 441524 price More Price(67)
| Manufacturer | Product number | Product description | CAS number | Packaging | Price | Updated | Buy |
|---|---|---|---|---|---|---|---|
| Cayman Chemical | 30469 | GS-441524 ≥98% | 1191237-69-0 | 1mg | $29 | 2026-04-30 | Buy |
| Cayman Chemical | 30469 | GS-441524 ≥98% | 1191237-69-0 | 5mg | $50 | 2026-04-30 | Buy |
| Cayman Chemical | 30469 | GS-441524 ≥98% | 1191237-69-0 | 10mg | $85 | 2026-04-30 | Buy |
| Cayman Chemical | 30469 | GS-441524 ≥98% | 1191237-69-0 | 25mg | $176 | 2026-04-30 | Buy |
| TRC | TRC-A606090-500MG | (2R,3R,4S,5R)-2-(4-Aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-carbonitrile | 1191237-69-0 | 500mg | $535 | 2026-06-03 | Buy |
GS 441524 Chemical Properties, Uses, Production
Description
GS-441524 is the active prodrug of the broad-spectrum antiviral Remdesivir. GS-441524 is an adenosine nucleotide analog in viral RNA production. It is a nucleotide analog inhibitor of RNA-dependent RNA polymerases (RdRps). The compound interferes with the action of viral RNA polymerase and evades proofreading by viral exoribonuclease (ExoN), causing a decrease in viral RNA production (RNA synthesis arrest), either by terminating RNA chains or causing mutations. It inhibits MERS-CoV or SARS-CoV-infected HAE cultures (EC50=74nM and 69nM) and murine hepatitis virus (MHV) (EC50=30nM). In vivo, remdesivir (25 and 50 mg/kg) reduces lung viral titers and prevents weight loss in a mouse model of SARS-CoV infection. Remdesivir is used as a treatment for Ebola virus disease and Marburg virus infections and other single-stranded RNA viruses such as respiratory syncytial virus, Junin virus, Lassa fever virus, Nipah virus, Hendra virus and the coronaviruses (including MERS and SARS viruses). Remdesivir is effective in the control of 2019-nCoV (COVID-19) infection in vitro. It now also has been studied as a potential treatment for SARS-CoV-2 infections.
Uses
GS-441524 is originally identified as an active metabolite of Remdesivir that is an antiviral drug, a novel nucleotide analog prodrug.
Definition
ChEBI: GS-441524 is a C-nucleoside analog that is (2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-carbonitrile substituted by a 4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl group at position 2. It is the active metabolite of remdesivir and exhibits a broad range of inhibitory activity against various RNA viruses including HCV, parainfluenza and SARS-CoV. It has a role as a drug metabolite, an antiviral agent and an anticoronaviral agent. It is a pyrrolotriazine, a nitrile, a C-nucleoside and an aromatic amine.
Acquired resistance
Resistance to GS-441524 can exist at the time of diagnosis, but this is uncommon. Rather, it tends to occur during treatment and is often partial at first and necessitates a higher dosage to accommodate for it. It can become total in some cats. Resistance is the biggest problem in cats with neurological disease, especially those that present with neurological disease or develop brain infections during treatment or during a relapse after what appears to have been a successful treatment. Many cats with partial drug resistance can be treated for their disease signs but will relapse as soon as the treatment is stopped. There have been cats "treated" for FIP for over a year with no cure, but ultimately resistance becomes worse or the owner runs out of money.
Biological Activity
GS 441524 is a viral RNA-dependent RNA polymerase (RdRp) inhibitor and broad spectrum antiviral nucleotide; active metabolite of Remdesivir. Competes with natural nucleoside triphosphates, blocking viral RNA synthesis. Exhibits antiviral activity against viruses from Coronaviridae family including SARS-CoV-2 in vitro, and SARS-CoV and feline infectious peritonitis virus (FIPV) in vitro and in vivo. Inhibits SARS-CoV and MERS-CoV- infected HAE cultures (EC50 values are 0.18 and 0.86 μM, respectively) and inhibits murine hepatitis virus (MHV) (EC50 = 1.1 μM).
Pharmacokinetics
GS-441524 is a nucleoside analogue that terminates the RNA chain of viral RNA-dependent RNA polymerase. It was developed by Gilead Sciences, Inc as part of their research into human RNA virus disease such as Ebola. GS-441524 is a small molecule that exhibits potent antiviral activity against a number of RNA viruses, including the zoonotic severe acute respiratory syndrome (SARS) coronavirus ( Cho et al., 2012). GS-5734 is a phosphoramidate prodrug of GS-441524 that has been previously shown to inhibit the replication of several taxonomically diverse RNA viruses such as Middle East respiratory syndrome virus, Ebola virus, Lassa fever virus, Junin virus and respiratory syncytial virus, while having low cytotoxicity in a wide-range of cell lines ( Sheahan et al., 2017 ). GS-5734 has also been shown to protect rhesus monkeys from experimental Ebola virus infection ( Warren et al., 2016 ).
Side effects
GS-441524 treatment is amazingly free of systemic side effects. It can cause minor kidney damage in some cats, but this does not progress to overt renal disease. Systemic drug reactions of the vasculitis type have been seen in a few cats and can be confused with injection site reactions. However, these drug reactions are at non-injection sites and are often self-limiting or respond well to a short-term low dose of steroids. The major side-effect of GS treatment is pain at the injection sites, which varies from cat to cat and according to the injection prowess of the person doing the treatment (usually the owner). Injection site sores are a problem with some owners and usually occur when the injection site is not moved around the body (stay away from between the shoulders) and not given into the muscle and nerve layers below the subcutis. I recommend selecting sites starting an inch behind the shoulder blades, down the back to 1-2 inches before the tailhead, and one third to one-half of the way down the chest and abdomen. Many people use gabapentin before injections to help ease the pain. Injection site sores are cleared of surrounding hair and gently cleaned 4 or more times a day with sterile cotton balls soaked in 1:5 dilution of household hydrogen peroxide. They usually do not require any more sophisticated treatment and heal within 2 weeks or so.
Synthesis
N-(7-lodopyrrolo[2,1-f][1,2,4]triazin-4-yl)-N,N-dimethylformimidamide (12) was prepared by heated 7-lodopyrrolo[2,1-f][1,2,4]triazin-4-amine (2) and N,N-dimethylformamide dimethyl acetal (DMF-DMA) in ethanol with >90% isolated yield. Compound 12 was firstly treated with tt-PrMgCl at −20~−10 °C, then reacted with ribonolactone 3 to give the product 4 after quenched by ammonium chloride aqueous solution to remove the protecting group, in 60% yield by recrystallization from MTBE and heptane. The active amino group in compound 2 will block the Grignard reaction, so the protection methods of NH₂ has been widely examined. The reported protective groups included -TMS, 1,2-bis(dimethylsilyl)ethane, -Boc, and so on. The N-Si bond is unstable and it should be partly destroyed during the Grignard reaction and the residual NH will consume Grignard reagent, as well as gives side products. The N,N-dimethylformimidamide group used as the protective group has advantages. There is no NH group in compound 12 so the side product was lower, and the protective group can be deprotected easily during the work-up operation to give 4 directly. Compound 4 should be a mixture of 1’-isomers, while we had not established the method or identified the ratio by HPLC. It was taken into the subsequent 1’-cyanation reaction to give compound 5, by reacted with TFA, TMSOTf and TMSCN in CH₂Cl₂ respectively at −40~−30 °C in 81% yield and >99% anomeric ratio after purified from toluene. At the last step, compound 5 was added into BCl3 in CH2Cl2 solution at −40~−30 °C to give the final GS-441524 in 83% yield and >99% purity (HPLC). [13]
storage
Store at -20°C
Mode of action
GS-441524 undergoes intracellular phosphorylation by cellular kinases, first to a nucleoside monophosphate and then to an active triphosphate metabolite (NTP)( Cho et al., 2012; Sheahan et al., 2017; Warren et al., 2016). This active NTP analog competes with natural nucleoside triphosphates to inhibit viral RNA synthesis. Specifically, the active form of GS-441524 inhibits RNA-dependent RNA polymerase-mediated transcription by terminating nascent viral transcript prematurely. We hypothesized that, once activated in feline cells, GS-441524 would attenuate FIPV replication with minimal cytotoxicity in vitro and effectively treat cats with experimentally induced FIP.
Preparation and handling
GS-441524 is supplied as a solid. A stock solution may be made by dissolving the GS-441524 in the solvent of choice, which should be purged with an inert gas. It is soluble in organic solvents such as DMSO and dimethyl formamide. The solubility of GS-441524 in these solvents is approximately 10 mg/ml.
GS-441524 is sparingly soluble in aqueous buffers. For maximum solubility in aqueous buffers, It should first be dissolved in DMSO and then diluted with the aqueous buffer of choice. It has a solubility of approximately 0.16 mg/ml in a 1:5 solution of DMSO:PBS (pH 7.2) using this method. We do not recommend storing the aqueous solution for more than one day.
References
1) Remdesivir and GS-441524 Retain Antiviral Activity against Delta, Omicron, and Other Emergent SARS-CoV-2 Variants DOI:10.1128/aac.00222-22
2) Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys: T.K. Warren, et al.; Nature 531, 381 (2016) DOI:10.1038/nature17180
3) Late Ebola virus relapse causing meningoencephalitis: a case report: M. Jacobs, et al.; Lancet 388, 498 (2016) DOI:10.1016/S0140-6736(16)30386-5
4) Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses: T.P. Sheahan, et al.; Sci. Transl. Med. 9, eaal3653 (2017) DOI:10.1126/scitranslmed.aal3653
5) Discovery and Synthesis of a Phosphoramidate Prodrug of a Pyrrolo[2,1-f][triazin-4- amino] Adenine C-Nucleoside (GS-5734) for the Treatment of Ebola and Emerging Viruses; D. Siegel, et al.; J. Med. Chem. 60, 1648 (2017) DOI:10.1021/acs.jmedchem.6b01594
6) Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease: M.L. Agostini, et al.; mBio 9, e00221 (2018) DOI: 10.1128/mBio.00221-18
7) Mechanism of Inhibition of Ebola Virus RNA-Dependent RNA Polymerase by Remdesivir: E.P. Tchesnokov, et al.; Viruses 11, E326 (2019) DOI:10.3390/v11040326
8) Remdesivir (GS-5734) protects African green monkeys from Nipah virus challenge: M.K. Lo, et al.; Sci. Transl. Med. 11, eaau9242 (2019) DOI:10.1126/scitranslmed.aau9242
9) Broad spectrum antiviral remdesivir inhibits human endemic and zoonotic deltacoronaviruses with a highly divergent RNA dependent RNA polymerase: A.J. Brown, et al.; Antiviral Res. 169, 104541 (2019) DOI:10.1016/j.antiviral.2019.104541
10) Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection: R. de Wit, et al.; PNAS (Epub ahead of print) (2020) DOI:10.1073/pnas.1922083117
11) Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro: M. Wang, et al.; Cell Res. 30, 269 (2020) DOI:10.1038/s41422-020-0282-0
12) The nucleoside analog GS-441524 strongly inhibits feline infectious peritonitis (FIP) virus in tissue culture and experimental cat infection studies DOI: 10.1016/j.vetmic.2018.04.026
13) HAN WANG. New and Practical Synthesis of GS-441524, the Key Intermediate of Remdesivir[J]. Heterocycles, 2021, 1 1. DOI:10.3987/com-21-14499.
GS 441524 Preparation Products And Raw materials
| Supplier | Tel | Country | ProdList | Advantage | |
|---|---|---|---|---|---|
| Changzhou Huihan Biotechnology Co., Ltd. | 15380463325 15380463325 | 819573646@qq.com | China | 73 | 55 |
| Jinan Hongkangda Chemical Co., Ltd | 0531-88901705 18753193522 | 810353473@qq.com | China | 156 | 58 |
| INTERCHEMIE NANJING PHARMATECH CO., LTD | 13656237714 13656237714; | xiaokunfu@kyyykj.com | China | 297 | 55 |
| Suzhou Muyuanda Biotechnology Co., Ltd | 021-37318802 18616909727 | liangpanpan@sh-jiaoze.com | China | 124 | 58 |
| Jinan Cen Ben Medical Technology Co., Ltd | 14793566 | info@cenpharm.com | China | 785 | 58 |
| Shandong Mingfeng Pharmaceutical and Technology Co. Ltd | 053155551677 15315114555 | 1345456643@qq.com | China | 298 | 58 |
| NANJING ZENJI PHARMACEUTICALS | 0512-62750571 | marketing@zenjipharma.com | China | 416 | 58 |
| Shaoguan Mingtu Chemical Co., Ltd | 13411131983 | 2407385074@qq.com | China | 2046 | 58 |
| Anhui nuoquan pharmaceutical co. LTD | 15705561919 | chunli.yi@nuozhanchem.com | China | 90 | 55 |
| Hangzhou Beishengyuan Biotechnology Co., Ltd | 15700194842 15700194842 | 1289372011@qq.com | China | 156 | 58 |
Related articles
- What is GS-441524 do for cats?
- Safe and effective antiviral therapies for cats with feline infectious peritonitis (FIP) have been identified, and the nucleos....
- Jun 25,2024
- GS-441524: Introduction; Side effects and antiviral against ASFV
- GS-441524, predominant metabolite of Remdesivir and superior to Remdesivir against Covid-19 , shows comparable efficacy in cel....
- Dec 19,2023
View Latest Price from GS 441524 manufacturers
| Image | Update time | Product | Price | Min. Order | Purity | Supply Ability | Manufacturer | |
|---|---|---|---|---|---|---|---|---|
 |
2026-09-15 | GS-441524
1191237-69-0
|
1kg | 99.9% | 500 KG | Jinan Hong Kongda Chemical Co.,LTD | ||
 |
2026-09-14 | GS-441524
1191237-69-0
|
$10.00 | 1ASSAYS | 99% | 10 ton | RongNa Biotechnology Co.,Ltd | |
 |
2026-08-25 | GS-441524
1191237-69-0
|
10gram | 98% | 2000 | Xi an Biohorlden Industry Trade Co Ltd |
