Degradable carbamate-containing bis(acryloyl) crosslinkers, and degradable crosslinked hydrogels comprising them
View Patent ↗One aspect of the present invention relates to base-labile, carbamate-containing crosslinkers. A second aspect of the present invention relates to degradable crosslinked polymers and hydrogels comprising a base-labile, carbamate-containing crosslinker. The present invention also relates to methods of preparing base-labile, carbamate-containing crosslinkers. Another aspect of the present invention relates to methods of preparing cross-linked polymers and hydrogels comprising a base-labile, carbamate-containing crosslinker.
1. A compound represented by 1:
wherein
X represents independently for each occurrence O or S;
L represents independently for each occurrence —O—NH—Q;
Q represents independently for each occurrence acryloyl, 2-alkylacryloyl, 3-alkylacryloyl, 2,3-dialkylacryloyl, 3,3-dialkylacryloyl, 2,3,3-trialkylacryloyl, acryloylO(CR 2 ) n C(O)—, 2-alkylacryloylO(CR 2 ) n C(O)—, 3-alkylacryloylO(CR 2 ) n C(O)—, 2,3-dialkylacryloylO(CR 2 ) n C(O)—, 3,3-dialkylacryloylO(CR 2 ) n C(O)—, 2,3,3-trialkylacryloylO(CR 2 ) n C(O)—, (diene)C(O)—, (vinyl)(CR 2 ) n C(O)—, or (vinyl)ArC(O)—;
R represents independently for each occurrence H or alkyl;
Z represents —NH(CR 2 ) n NH—, or —NH(CR 2 ) n J(CR 2 ) m NH—;
Ar represents independently for each occurrence aryl or heteroaryl;
J represents independently for each occurrence O, S, NR, cycloalkyl, heterocyclyl, (CH 2 CH 2 O) n , or (CH 2 CH 2 N(R)) n ;
n represents independently for each occurrence an integer in the range 1-10; and
m represents independently for each occurrence an integer in the range 0-10.
2. The compound of claim 1 , wherein X represents O.
3. The compound of claim 1 , wherein Q represents acryloyl, or 2-methacryloyl.
4. The compound of claim 1 , wherein R represents H.
5. The compound of claim 1 , wherein Z represents —NH(CR 2 ) n NH—.
6. The compound of claim 1 , wherein X represents O; and L represents —O—NH—Q.
7. The compound of claim 1 , wherein X represents O; L represents —O—NH—Q; and Q represents acryloyl, or 2-methacryloyl.
8. The compound of claim 1 , wherein X represents O; L represents —O—NH—Q; Q represents acryloyl, or 2-methacryloyl; and R represents H.
9. The compound of claim 1 , wherein X represents O; L represents —O—NH—Q; Q represents acryloyl, or 2-methacryloyl; R represents H; and Z represents —NH(CR 2 ) n NH—.
10. A compound represented by 2:
wherein
X represents independently for each occurrence O or S;
M represents independently for each occurrence —O—NH—Q;
Q represents independently for each occurrence acryloyl, 2-alkylacryloyl, 3-alkylacryloyl, 2,3-dialkylacryloyl, 3,3-dialkylacryloyl, 2,3,3-trialkylacryloyl, acryloylO(CR 2 ) n C(O)—, 2-alkylacryloylO(CR 2 ) n C(O)—, 3-alkylacryloylO(CR 2 ) n C(O)—, 2,3-dialkylacryloylO(CR 2 ) n C(O)—, 3,3-dialkylacryloylO(CR 2 ) n C(O)—, 2,3,3-trialkylacryloylO(CR 2 ) n C(O)—, (diene)C(O)—, (vinyl)(CR 2 ) n C(O)—, or (vinyl)ArC(O)—;
R represents independently for each occurrence H or alkyl;
Z represents —NH(CR 2 ) n NH—, or —NH(CR 2 ) n J(CR 2 ) m NH—;
Ar represents independently for each occurrence aryl or heteroaryl;
J represents independently for each occurrence O, S, NR, cycloalkyl, heterocyclyl, (CH 2 CH 2 O) n , or (CH 2 CH 2 N(R)) n ;
G represents (CR (4−t) ), aryl, or heteroaryl;
n represents independently for each occurrence an integer in the range 1-10;
m represents independently for each occurrence an integer in the range 0-10; and
t represents 3 or 4.
11. The compound of claim 10 , wherein X represents O.
12. The compound of claim 10 , wherein Q represents acryloyl, or 2-methacryloyl.
13. The compound of claim 10 , wherein R represents H.
14. The compound of claim 10 , wherein X represents O; and M represents —O—NH—Q.
15. The compound of claim 10 , wherein X represents O; M represents —O—NH—Q; and Q represents acryloyl, or 2-methacryloyl.
16. The compound of claim 10 , wherein X represents O; M represents —O—NH—Q; Q represents acryloyl, or 2-methacryloyl; and R represents H.
17. A method of preparing a compound represented by 1:
wherein
X represents independently for each occurrence O or S;
L represents independently for each occurrence —O—NH—Q;
Q represents independently for each occurrence acryloyl, 2-alkylacryloyl, 3-alkylacryloyl, 2,3-dialkylacryloyl, 3,3-dialkylacryloyl, 2,3,3-trialkylacryloyl, acryloylO(CR 2 ) n C(O)—, 2-alkylacryloylO(CR 2 ) n C(O)—, 3-alkylacryloylO(CR 2 ) n C(O)—, 2,3-dialkylacryloylO(CR 2 ) N C(O)—, 3,3-dialkylacryloylO(CR 2 ) n C(O)—, 2,3,3-trialkylacryloylO(CR 2 ) n C(O)—, (diene)C(O)—, (vinyl)(CR 2 ) n C(O)—, or (vinyl)ArC(O)—;
R represents independently for each occurrence H or alkyl;
Z represents —NH(CR 2 ) n NH—, or —NH(CR 2 ) n J(CR 2 ) m NH—;
Ar represents independently for each occurrence aryl or heteroaryl;
J represents independently for each occurrence O, S, NR, cycloalkyl, heterocyclyl, (CH 2 CH 2 O) n , or (CH 2 CH 2 N(R)) n ;
n represents independently for each occurrence an integer in the range 1-10; and
m represents independently for each occurrence an integer in the range 0-10.
(a) reacting a hydroxylamine with an acrylate, thereby forming an acrylic hydroxamic acid; and
(b) reacting said acrylic hydroxamic acid with a diisocyanate.
18. A method of preparing a compound represented by 2:
wherein
X represents independently for each occurrence O or S;
M represents independently for each occurrence —O—NH—Q;
Q represents independently for each occurrence acryloyl, 2-alkylacryloyl, 3-alkylacryloyl, 2,3-dialkylacryloyl, 3,3-dialkylacryloyl, 2,3,3-trialkylacryloyl, acryloylO(CR 2 ) n C(O)—, 2-alkylacryloylO(CR 2 ) n C(O)—, 3-alkylacryloylO(CR 2 ) n C(O)—, 2,3-dialkylacryloylO(CR 2 ) n C(O)—, 3,3-dialkylacryloylO(CR 2 ) n C(O)—, 2,3,3-trialkylacryloylO(CR 2 ) n C(O)—, (diene)C(O)—, (vinyl)(CR 2 ) n C(O)—, or (vinyl)ArC(O)—;
R represents independently for each occurrence H or alkyl;
Z represents —NH(CR 2 ) n NH—, or —NH(CR 2 ) n J(CR 2 ) m NH—;
Ar represents independently for each occurrence aryl or heteroaryl;
J represents independently for each occurrence O, S, NR, cycloalkyl, heterocyclyl, (CH 2 CH 2 O) n , or (CH 2 CH 2 N(R)) n ;
G represents (CR (4−t) ), aryl, or heteroaryl;
n represents independently for each occurrence an integer in the range 1-10;
m represents independently for each occurrence an integer in the range 0-10; and
t represents 3 or 4;
comprising:
(a) reacting a hydroxylamine with an acrylate, thereby forming a hydroxamic acid; and
(b) reacting said hydroxamic acid with a triisocyanate or tetraisocyanate.