ALS-8176

• CAT Number: I001711
• CAS Number: 1445385-02-3
• Molecular Formula: C18H25ClFN3O6
• Molecular Weight: 433.86
• Purity: ≥95%
• Target: RSV
• Solubility: 36 mg/mL in CDCl3
• Storage: -20°C
• IUPAC Name: [(2R,3R,4R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-2-(chloromethyl)-4-fluoro-3-(2-methylpropanoyloxy)oxolan-2-yl]methyl 2-methylpropanoate
• InChI: InChI=1S/C18H25ClFN3O6/c1-9(2)15(24)27-8-18(7-19)13(28-16(25)10(3)4)12(20)14(29-18)23-6-5-11(21)22-17(23)26/h5-6,9-10,12-14H,7-8H2,1-4H3,(H2,21,22,26)/t12-,13+,14-,18-/m1/s1
• InChIKey: MJVKYGMNSQJLIN-KYZVSKTDSA-N
• SMILES: CC(C)C(=O)OC[C@@]1([C@H]([C@H]([C@@H](O1)N2C=CC(=NC2=O)N)F)OC(=O)C(C)C)CCl

ALS-8176（Cat No.:I001711）is a potent antiviral compound developed for the treatment of respiratory infections caused by human rhinoviruses (HRVs), particularly HRV infections linked to exacerbations of chronic obstructive pulmonary disease (COPD) and asthma. This selective inhibitor targets the viral 3C protease, crucial for viral replication. By inhibiting this enzyme, ALS-8176 prevents the replication of HRV, reducing viral load and mitigating associated respiratory symptoms. Its development holds promise as an effective therapeutic option for managing viral infections and improving respiratory health in patients with preexisting conditions such as COPD and asthma.

Reference

1:J Med Chem. 2015 Feb 26;58(4):1862-78. doi: 10.1021/jm5017279. Epub 2015 Feb 10. Discovery of 4/’-chloromethyl-2/’-deoxy-3/’,5/’-di-O-isobutyryl-2/’-fluorocytidine (ALS-8176), a first-in-class RSV polymerase inhibitor for treatment of human respiratory syncytial virus infection.Wang G,Deval J,Hong J,Dyatkina N,Prhavc M,Taylor J,Fung A,Jin Z,Stevens SK,Serebryany V,Liu J,Zhang Q,Tam Y,Chanda SM,Smith DB,Symons JA,Blatt LM,Beigelman L, PMID: 25667954 DOI: 10.1021/jm5017279 Abstract: Respiratory syncytial virus (RSV) is a leading pathogen of childhood and is associated with significant morbidity and mortality. To date, ribavirin is the only approved small molecule drug, which has limited use. The only other RSV drug is palivizumab, a monoclonal antibody, which is used for RSV prophylaxis. Clearly, there is an urgent need for small molecule RSV drugs. This article reports the design, synthesis, anti-RSV activity, metabolism, and pharmacokinetics of a series of 4/’-substituted cytidine nucleosides. Among tested compounds 4/’-chloromethyl-2/’-deoxy-2/’-fluorocytidine (2c) exhibited the most promising activity in the RSV replicon assay with an EC50 of 0.15 μM. The 5/’-triphosphate of 2c (2c-TP) inhibited RSV polymerase with an IC50 of 0.02 μM without appreciable inhibition of human DNA and RNA polymerases at 100 μM. ALS-8176 (71), the 3/’,5/’-di-O-isobutyryl prodrug of 2c, demonstrated good oral bioavailability and a high level of 2c-TP in vivo. Compound 71 is a first-in-class nucleoside RSV polymerase inhibitor that demonstrated excellent anti-RSV efficacy and safety in a phase 2 clinical RSV challenge study.