Integrated photoactive agents for real-time monitoring of hemostasis
View Patent ↗The present invention discloses a number of photoactive compounds designed to bind and inhibit serine proteases. Compounds disclosed herein may be utilized in a number of appropriate medical diagnostic and/or therapeutic procedures such as the monitoring of hemostasis, imaging and/or treatment of vulnerable plaques, and/or tumor imaging and/or treatment.
1. A compound of Formula 1, wherein:
each of R 1 , R 2 , R 3 , R 4 , X 1 , and X 2 is independently hydrogen, —OH, C1-C6 alkyl, C1-C6 acyl, C1-C6 alkoxycarbonyl, C1-C6 hydroxyalkyl, C1-C6 polyhydroxyalkyl, C1-C6 carboxyalkyl, C1-C6 aminoalkyl, C5-C10 aryl, —(CH 2 ) m —Y—C(═NH)NH 2 , —(CH 2 ) m (CHR 5 ) n —Y—C(═NH)NH 2 , —(CH 2 ) m (CHR 5 ) n —Y—NHC(═NH)NH 2 , —(CH 2 ) m —Y—NHC(═NH)NH 2 , —O—(CHR 5 )n-Y—C(═NH)NH 2 , —O—(CHR 5 )n-Y—NHC(═NH)NH 2 , —N(R 6 )—(CH 2 ) m (CHR 5 ) n —Y—C(═NH)NH 2 , or —N(R 7 )—(CH 2 ) m (CHR 5 ) n —Y—NHC(═NH)NH 2 ;
Y is
with the proviso that at least one of R 1 , R 2 , R 3 , R 4 , X 1 , or X 2 is —(CH 2 ) m —Y—C(═NH)NH 2 , —(CH 2 ) m (CHR 5 ) n —Y—C(═NH)NH 2 , —(CH 2 ) m (CHR 5 ) n —Y—NHC(═NH)NH 2 , —(CH 2 ) m —Y—NHC(═NH)NH 2 , —O—(CHR 5 )n-Y—C(═NH)NH 2 , —O—(CHR 5 ) n —Y—NHC(═NH)NH 2 , —N(R 6 )—(CH 2 ) m (CHR 5 ) n —Y—C(═NH)NH 2 , or —N(R 7 )—(CH 2 ) m (CHR 5 ) n —Y—NHC(═NH)NH 2 ;
each of ‘m,’ ‘n,’ and ‘p’ is independently 0, 1, 2, 3, 4, 5, or 6;
R 5 is hydroxyl, C1-C6 hydroxyalkyl, carboxyl, C1-C6 carboxyalkyl, amino, or C1-C6 aminoalkyl; and
each of R 6 and R 7 is independently hydrogen, C1-C6 alkyl, C1-C6 acyl, C1-C6 alkoxycarbonyl, C1-C6 hydroxyalkyl, C1-C6 polyhydroxyalkyl, C1-C6 carboxyalkyl, C1-C6 aminoalkyl, or C5-C10 aryl.
2. The compound of claim 1 , wherein:
each of R 1 , R 2 , R 3 , and R 4 is hydrogen; and
X 1 is —OH; and
X 2 is —O—(CHR 5 ) n —Y—C(═NH)NH 2 , —O—(CHR 5 ) n —Y—NHC(═NH)NH 2 , —N(R 6 )—(CH 2 ) m (CHR 5 ) n —Y—C(═NH)NH 2 , or —N(R 7 )—(CH 2 ) m (CHR 5 ) n —Y—NHC(═NH)NH 2 .
3. The compound of claim 2 , wherein X 2 —N(R 6 )—(CH 2 ) m (CHR 5 ) n —Y—C(═NH)NH 2 , or —N(R 7 )—(CH 2 ) m (CHR 5 ) n —Y—NHC(═NH)NH 2 .
4. The compound of claim 1 , wherein:
each of R 1 , R 2 , R 3 , and R 4 is hydrogen; and
each of X 1 and X 2 is independently —O—(CHR 5 ) n —Y—C(═NH)NH 2 , —O—(CHR 5 ) n —Y—NHC(═NH)NH 2 , —N(R 6 )—(CH 2 ) m (CHR 5 ) n —Y—C(═NH)NH 2 , or —N(R 7 )—(CH 2 ) m (CHR 5 ) n —Y—NHC(═NH)NH 2 .
5. The compound of claim 4 , wherein each of X 1 and X 2 is independently —N(R 6 )—(CH 2 ) m (CHR 5 ) n —Y—C(═NH)NH 2 , or —N(R 7 )—(CH 2 ) m (CHR 5 ) n —Y—NHC(═NH)NH 2 .
6. The compound of claim 1 , wherein R 6 is hydrogen.
7. The compound of claim 1 , wherein:
each of R 2 , R 3 , and R 4 is hydrogen; and
each of X 1 , and X 2 is —OH; and
R 1 is —(CH 2 ) m —Y—C(═NH)NH 2 , —(CH 2 ) m —Y—NHC(═NH)NH 2 , —(CH 2 ) m (CHR 5 ) n —Y—C(═NH)NH 2 , or —(CH 2 ) m (CHR 5 ) n —Y—NHC(═NH)NH 2 .
8. The compound of claim 7 , wherein R 1 is —(CH 2 ) m —Y—C(═NH)NH 2 or —(CH 2 ) m (CHR 5 ) n —Y—NHC(═NH)NH 2 .
9. The compound of claim 1 , wherein:
each of R 2 and R 4 is hydrogen; and
each of X 1 and X 2 is —OH; and
each of R 1 and R 3 is independently —(CH 2 ) m —Y—C(═NH)NH 2 , —(CH 2 ) m —Y—NHC(═NH)NH 2 , —(CH 2 ) m (CHR 5 ) n —Y—C(═NH)NH 2 , or —(CH 2 ) m (CHR 5 ) n —Y—NHC(═NH)NH 2 .
10. The compound of claim 9 , wherein each of R 1 and R 3 is independently —(CH 2 ) m —Y—C(═NH)NH 2 or —(CH 2 ) m (CHR 5 ) n —Y—NHC(═NH)NH 2 .
11. The compound of claim 1 , wherein ‘m’ is 0, 1, 2, or 3.
12. The compound of claim 1 , wherein ‘n’ is 0, 1, 2, or 3.
13. The compound of claim 1 , wherein ‘p’ is 1.
14. The compound of claim 1 , wherein Y is —(CH 2 ) p — or
15. The compound of claim 1 , wherein R 5 is carboxyl.
16. The compound of claim 1 , where the compound is any of the Compounds 2-6 below: