Viral inhibitors, the synthesis thereof, and intermediates thereto
The present disclosure discloses compositions comprising maribavir, methods of providing the same, and compositions providing intermediates useful in providing maribavir. Maribavir (((2S,3S,4R,5S)-2-(5,6-dichloro-2-(isopropylamino)-1H-benzo[d]imidazol-1-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol) is a benzimidazole riboside and is an orally available antiviral medication against cytomegalovirus (CMV).
1. A composition of maribavir, Compound 2, and Compound 4, the composition comprising maribavir, Compound 2, and Compound 4, having the following structures:
wherein Compound 2 is present in an amount of 0.1% w/w or less relative to maribavir and Compound 4 is present in an amount of 0.1% w/w or less relative to maribavir.
2. The composition of claim 1 , wherein Compound 4 is present in an amount of from 0.01% to 0.1% w/w relative to maribavir.
3. The composition of claim 2 , further comprising Compound 3,
wherein Compound 3 is present in an amount of from 0.01% to 0.1% w/w relative to maribavir.
4. The composition of claim 3 , wherein Compound 2 is present in an amount of from 0.01% to 0.1% w/w relative to maribavir.
5. The composition of claim 4 , further comprising D-maribavir, wherein D-maribavir is present in an amount of 0.1% w/w or less relative to maribavir.
6. A pharmaceutical composition comprising a composition of claim 5 and one or more pharmaceutically acceptable excipients.
7. A pharmaceutical composition comprising a composition of claim 4 and one or more pharmaceutically acceptable excipients.
8. A pharmaceutical composition comprising a composition of claim 3 and one or more pharmaceutically acceptable excipients.
9. The composition of claim 2 , wherein Compound 2 is present in an amount of from 0.01% to 0.1% w/w relative to maribavir.
10. A pharmaceutical composition comprising a composition of claim 2 and one or more pharmaceutically acceptable excipients.
11. The composition of claim 1 , wherein Compound 4 is present in an amount of 0.05% w/w or less relative to maribavir.
12. The composition of claim 11 , wherein Compound 4 is present in an amount of from 0.01% to 0.05% w/w relative to maribavir.
13. The composition of claim 1 , further comprising Compound 3,
wherein Compound 3 is present in an amount of 0.1% w/w or less relative to maribavir.
14. The composition of claim 1 , further comprising D-maribavir, wherein D-maribavir is present in an amount of 0.1% w/w or less relative to maribavir.
15. The composition of claim 1 , wherein the maribavir has a particle size distribution (PSD) with a d (50) of between about 170 and about 350 μm.
16. The composition of claim 15 , wherein the d (50) is between about 170 and about 226 μm.
17. The composition of claim 15 , wherein the d (50) is between about 227 and about 280 μm.
18. The composition of claim 15 , wherein the d (50) is between about 281 and about 336 μm.
19. A pharmaceutical composition comprising a composition of claim 15 and one or more pharmaceutically acceptable excipients.
20. A pharmaceutical composition comprising a composition of claim 1 and one or more pharmaceutically acceptable excipients.