Processes for intermediates for macrocyclic compounds
View Patent ↗The present invention is directed to novel macrocyclic compounds of formula (I) and their pharmaceutically acceptable salts, hydrates or solvates: wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , n 1 , m, p Z 1 , Z 2 , and Z 3 are as describe in the specification. The invention also relates to compounds of formula (I) which are antagonists of the motilin receptor and are useful in the treatment of disorders associated with this receptor and with or with motility dysfunction.
1. A compound having the following structure:
wherein:
W is selected from the group consisting of —NHPG and —NH 2 ,
X is —OH or —OPG; and
PG is a protecting group.
2. The compound of claim 1 , wherein W is —NHPG.
3. The compound of claim 1 , wherein the protecting group on the nitrogen is selected from the group consisting of benzothiazole-2-sulfonyl (Bts), t-butyloxycarbonyl (Boc), carbobenzyloxy (Cbz), α,α-dimethyl-3,5-dimethoxybenzyloxycarbonyl (Ddz), 9-fluorenylmethyloxycarbonyl (Fmoc) and allyloxycarbonyl (Alloc).
4. The compound of claim 1 , wherein the protecting group on the oxygen is selected from the group consisting of tetrahydropyranyl (THP), tert-butyldimethylsilyl (TBDMS), acetyl (Ac) and benzoyl (Bz).
5. The compound of claim 1 having the following structure:
6. The compound of claim 1 having the following structure:
7. The compound of claim 1 having the following structure:
8. The compound of claim 1 having the following structure:
9. The compound of claim 8 , wherein the protecting group is α,α-dimethyl-3,5-dimethoxybenzyloxycarbonyl (Ddz) or t-butyloxycarbonyl (Boc).
10. The compound of claim 9 having the following structure:
11. The compound of claim 9 having the following structure:
12. The compound of claim 9 having the following structure:
13. The compound of claim 9 having the following structure:
14. A compound having the following structure:
wherein:
W is —OPG,
X is —OH or —OPG; and
PG is a protecting group.
15. The compound of claim 14 , wherein the protecting group on the oxygen is selected from the group consisting of tetrahydropyranyl (THP), tert-butyldimethylsilyl (TBDMS), acetyl (Ac) and benzoyl (Bz).