Inhibitors of adenosine 5′-nucleotidase
Compounds that modulate the conversion of AMP to adenosine by 5′-nucleotidase, ecto, and compositions containing the compounds and methods for synthesizing the compounds, are described herein. The use of such compounds and compositions for the treatment and/or prevention of a diverse array of diseases, disorders and conditions, including cancer- and immune-related disorders, that are mediated by 5′-nucleotidase, ecto is also provided.
1. A process for preparing a CD73 inhibitor, said process comprising:
a) contacting a compound of formula (i):
with a protected analog of ribofuranose to form a protected analog of compound of formula (iii):
and
b) contacting the protected analog of compound of formula (iii) with cyclopentyl amine to form a protected analog of compound of formula (iv):
2. The process of claim 1 , wherein each of the protected analog of ribofuranose, the protected analog of compound of formula (iii), and the protected analog of compound of formula (iv) are protected with one or more protecting groups.
3. The process of claim 2 , wherein the one or more protecting groups are independently selected from acyl and acetonide.
4. The process of claim 3 , wherein the acyl is an acetate.
5. The process of claim 1 , wherein the protected analog of ribofuranose is a compound of formula (ii):
6. The process of claim 1 , wherein the protected analog of compound of formula (iii) is a compound of formula (iii-a):
7. The process of claim 1 , wherein the protected analog of compound of formula (iv) is a compound of formula (iv-a):
8. The process of claim 1 , wherein step b) further comprises a base.
9. The process of claim 8 , wherein the base is an amine.
10. The process of claim 9 , wherein the amine is triethylamine.
11. The process of claim 1 , wherein step b) is conducted in a solvent.
12. The process of claim 11 , wherein the solvent is an alcohol.
13. The process of claim 12 , wherein the alcohol is methanol.
14. A process for preparing a CD73 inhibitor, said process comprising converting a compound of formula (i):
to a compound of formula (iv):
or a protected analog thereof.
15. The process of claim 14 , wherein converting the compound of formula (i) comprises contacting the compound of formula (i) with a protected analog of ribofuranose to form a protected analog of compound of formula (iii):
16. The process of claim 15 , wherein the protected analog of ribofuranose is a compound of formula (ii):
17. The process of claim 15 , wherein the protected analog of compound of formula (iii) has a structure of formula (iii-a):
18. The process of claim 15 , further comprising contacting the protected analog of compound of formula (iii) with cyclopentyl amine to form a protected analog of a compound of formula (iv):
19. The process of claim 18 , wherein the protected analog of a compound of formula (iv) is a compound of formula (iv-a):
20. A process for preparing a CD73 inhibitor, said process comprising: starting with a compound of formula (i):
and using a means for converting said compound of formula (i) to a compound of formula (iv):
or a protected form thereof.
21. The process of claim 20 , wherein the protected form of the compound of formula (iv) is a compound of formula (iv-a) or a compound of formula (iv-b):
22. A compound having the structure
or a protected form thereof.
23. The compound of claim 22 , having the structure
24. The compound of claim 22 , having the structure