Prodrugs of secondary amine compounds
View Patent ↗The present invention relates to compounds of Formula I:
1. A compound selected from:
wherein R 1 is —C(O)OC(R 4 )(R 5 )—OC(O)(G 12 ) m R 6 ;
R 4 and R 5 are from hydrogen;
G 12 is selected from absent, NH, CH 2 , —S— or —O—;
m is 0 or 1;
R 6 is selected from C 13 -C 26 -alkyl, substituted C 13 -C 26 -alkyl, C 13 -C 26 -alkenyl, substituted C 13 -C 26 -alkenyl, C 13 -C 26 -alkynyl, substituted C 13 -C 26 -alkynyl, C 13 -C 26 -cycloalkyl, and substituted C 13 -C 26 -cycloalkyl.
2. A compound according to claim 1 , wherein R 6 is selected from C 13 -C 25 -alkyl, and substituted C 13 -C 25 -alkyl.
3. A compound according to claim 1 , wherein R 6 is selected from C 17 -C 21 -alkyl, and substituted C 17 -C 21 -alkyl.
4. A method for sustained delivery of a secondary amine-containing parent drug to a patient comprising administering a compound according to claim 1 .
5. The method according to claim 4 , wherein the parent drug is present in the blood stream of the patient for at least 12 hours.
6. An injectable depot formulation comprising a compound according to claim 1 .
7. The injectable depot formulation of claim 6 , wherein said compound is released over a period of more than one week.
8. The injectable depot formulation of claim 6 , wherein said compound is released over a period of at least four weeks.
9. A compound selected from table below, or a pharmaceutically acceptable salt thereof:
No.
Structure
1.
2.
3.
4.
5.
6.
7.
8.
9.
15.
16.
17.
18.
19.
31.
32.
33.
34.
35.
36.
55.
56.
57.
58.
59.
60.
61.
111.
112.
113.
114.
115.
116.
117.
118.
119.
120.
121.
122.
123.
124.
125.
126.
127.
128.
141.
142.
143.
144.
145.
146.
10. A compound of formula:
or a pharmaceutically acceptable salt thereof;
wherein R 1 is —C(O)OC(R 4 )(R 5 )—OC(O)(G 12 ) m R 6 ;
each R 4 and R 5 is hydrogen;
G 12 is selected from absent, NH, CH 2 , —S— or —O—;
m is 0 or 1;
R 6 is selected from C 13 -C 26 -alkyl and substituted C 13 -C 26 -alkyl.
11. A compound selected from the table below or a pharmaceutically acceptable salt thereof:
No.
Structure
1.
2.
3.
4.
5.
6.
7.
8.
9.
16.
17.
18.
19.
113.
114.
115.
116.
117.
12. A compound according to claim 1 wherein R 1 is selected from Table 2:
TABLE 2
wherein each j is independently 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25; and
each k is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 with the proviso that the total of j and k does not exceed a 26 carbon chain.
13. A compound according to claim 1 wherein R 1 is selected from Table 3:
TABLE 3
wherein each j is independently 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25; and
each k is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 with the proviso that the total of j and k does not exceed a 26 carbon chain.