Apricitabine

Base Information

• Chemical Name: Apricitabine
• CAS No.: 160707-69-7
• Molecular Formula: C₈H₁₁N₃O₃S
• Molecular Weight: 229.26
• UNII: K1YX059ML1,DND9Y3G72C
• DSSTox Substance ID: DTXSID60166974
• Nikkaji Number: J1.147.915D,J645.730D
• Wikipedia: Apricitabine
• Wikidata: Q621846
• NCI Thesaurus Code: C79871
• Metabolomics Workbench ID: 153757
• ChEMBL ID: CHEMBL210651
• Mol file: 160707-69-7.mol

Synonyms:apricitabine;AVX-754;BCH 10619;BCH-10619;BCH10619;SPD754

Chemical Property of Apricitabine

Chemical Property:

• Boiling Point: 475.4±55.0 °C(Predicted)
• PKA: 13.83±0.10(Predicted)
• PSA: 115.67000
• Density: 1.73
• LogP: -0.01290
• XLogP3: -1.2
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 2
• Exact Mass: 229.05211239
• Heavy Atom Count: 15
• Complexity: 331

Purity/Quality:

99%, ^*data from raw suppliers

(-)-2''-Deoxy-3''-oxa-4''-thiocytidine(Apricitabine) ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: C1C(SC(O1)CO)N2C=CC(=NC2=O)N
• Isomeric SMILES: C1[C@@H](S[C@@H](O1)CO)N2C=CC(=NC2=O)N
• Recent ClinicalTrials: Study of the Efficacy and Safety of Apricitabine, a New NRTI, to Treat Drug-resistant HIV Infection
• Recent EU Clinical Trials: A phase 2b/3, randomized, double blind, dose confirming study of the safety, efficacy and tolerability of apricitabine versus lamivudine in treatment-experienced HIV-1 infected patients with the M184V/I mutation in reverse transcriptase
• Description: Apricitabine (formerly known as BCH-10618, SPD754, and AVX754) is a deoxycytidine nucleoside reverse transcriptase inhibitor (NRTI) in clinical development for the treatment of HIV disease. Specifically, apricitabine is the (–)-enantiomer of the heterosubstituted analog 2udeoxy-3u-oxa-4u-thiocytidine and has the molecular formula C8H11N3O3S. Apricitabine is structurally similar to lamivudine, but differs in the inversion of the oxygen and sulfur in the furanosyl ring. Apricitabine has a molecular weight of 229.26 (1 mM = 0.229 mg/ml). In common with other NRTIs, apricitabine is activated by intra-cellular phosphorylation. The initial phosphorylation to apricitabine monophosphate is catalyzed by deoxycytidine kinase. After further phosphorylation, the triphosphate form of the molecule competes with endogenous deoxycytidine triphosphate for binding to HIV-1 reverse transcriptase. The subsequent incorporation of apricitabine triphosphate into nascent DNA by this enzyme interrupts viral replication by terminating the elongation of the DNA chain. Apricitabine triphosphate is a potent and highly selective inhibitor of HIV-1 reverse transcriptase in vitro. Its inhibitory constant (Ki) for reverse transcriptase from wild-type HIV-1 (0.08 mM) was half that of lamivudine triphosphate under the same conditions and 150- to 3750- fold lower than for human DNA polymerases, including the mitochondrial DNA polymerase γ .
• Uses: (-)-2''-Deoxy-3''-oxa-4''-thiocytidine (Apricitabine) is a drug that is used in the treatment of HIV aids. It as also been shown to be useful against lamivudine and zidovudine resistant virus strains
• Clinical Use: Apricitabine is an NRTI currently under clinical development that has a good safety profile, including a good mitochondrial toxicity profile. There may be a niche for apricitabine in the treatment of individuals infected with viral strains with reduced susceptibility to other nucleoside analogs, including strains with M184V and TAMs. NRTIs are recommended for clinical use in combination with other classes of antiretrovirals within highly active antiretroviral treatment (HAART) regimens for HIV infection. In light of its activity in vitro against HIV strains resistant to existing NRTIs, apricitabine is likely to be most useful for the treatment of antiretroviral-experienced patients failing therapy containing one of these agents. Investigating the efficacy, tolerability, and resistance selection properties of new antiretrovirals within combination HAART regimens is complicated by the confounding effects of the other prescribed agents. Therefore, developmental NRTIs are commonly evaluated first within short-term (r14 day) trials of monotherapy in antiretroviral naive HIV-infected patients. To date, apricitabine has shown efficacy in two phase II trials, one as monotherapy in antiretroviral-naive patients, and one within HAART for antiretroviral-experienced patients.

Technology Process of Apricitabine

There total 28 articles about Apricitabine which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 93.0%

Trans-2-benzoyloxymethyl-4-(n4'-acetyl-cytosin-1'-yl)-1,3-oxathiolane → Trans-2-hydroxymethyl-4-(cytosin-1'-yl)-1,3-oxathiolane (160707-69-7)

Guidance literature:

With ammonia; In methanol;

Reference yield: 91.0%

N-[1-((2R,4R)-2-Hydroxymethyl-[1,3]oxathiolan-4-yl)-2-oxo-1,2-dihydro-pyrimidin-4-yl]-acetamide → lamivudine (160707-69-7)

Guidance literature:

With potassium carbonate; In methanol; for 0.5h;

Reference yield: 90.0%

Cis-2-benzoyloxymethyl-4-(n4'-acetyl-cytosin-1'-yl)-1,3-oxathiolane → Cis-2-hydroxymethyl-4-(cytosin-1'-yl)-1,3-oxathiolane (160707-69-7)

Guidance literature:

With ammonia; In methanol; at 20 ℃; for 16h;

upstream raw materials:

2-[(phenylcarbonyloxy)methyl]-1,3-oxathiolane

Trans and Cis-2R-t-butyldiphenylsilyloxymethyl-4-acetoxy-1,3-oxathiolane

2R-t-butyldiphenylsilyloxymethyl-4S-(N-4'-acetylcytosin-1'-yl)-1,3-oxathiolane

Trans and Cis-2S-t-butyldiphenylsilyloxymethyl-4-acetoxy-1,3-oxathiolane

Refernces

• 1、 -. "ENANTIOMERIC RESOLUTION OF 2,4-DISUBSTITUTED 1,3-OXATHIOLANE NUCLEOSIDES". Paragraph 0070; 0071. . Retrieved 2011/08/07.
• 2、 -. "Enantiomeric resolution of 2-substituted 4-substituted 1,3-oxathiolanes nucleosides". Page/Page column 11. . Retrieved 2009/04/24.