Photoreactive synthetic regulator of protein function and methods of use thereof
The present disclosure provides a photoreactive synthetic regulator of protein function. The present disclosure further provides a light-regulated polypeptide that includes a subject synthetic regulator. Also provided are cells and membranes comprising a subject light-regulated polypeptide. The present disclosure further provides methods of modulating protein function, involving use of light.
1. A compound of the Formula XI:
wherein Q 1 is —C(═O)—;
Q 2 is NR 3 R 4 ;
R 3 and R 4 are each C 2-8 alkyl;
R 1 is —NR 10 R 11 ;
x is 1;
y is 1;
R 2 is hydrogen;
R 6 is hydrogen;
R 10 is C 1-10 alkyl; and
R 11 is substituted C 1-10 alkyl;
or a pharmaceutically acceptable salt thereof.
2. A compound of the Formula XII:
wherein
each of R 1 are independently selected from —NR 10 R 11 , cyano, fluoro, bromo, iodo, —OR 10 , —C(O)OR 10 , —SR 10 , —S(O)R 10 , and —S(O) 2 R 10 ;
x is an integer from 1 to 5;
y is an integer from 1 to 4;
R 2 is selected from hydrogen, C 1-10 alkyl, substituted C 1-10 alkyl, C 2-10 alkenyl, substituted C 2-10 alkenyl, C 2-10 alkynyl, substituted C 2-10 alkynyl, C 6-20 aryl, substituted C 6-20 aryl, C 4-10 cycloalkyl, substituted C 4-10 cycloalkyl, C 4-10 cycloalkenyl, and substituted C 4-10 cycloalkenyl;
R 3 , R 4 , and R 5 are each independently selected from C 2-8 alkyl, substituted C 2-10 alkyl, C 2-10 alkenyl, substituted C 2-10 alkenyl, C 2-10 alkynyl, substituted C 2-10 alkynyl, C 6-20 aryl, substituted C 6-20 aryl, C 4-10 cycloalkyl, substituted C 4-10 cycloalkyl, C 4-10 cycloalkenyl, and substituted C 4-10 cycloalkenyl;
each of R 6 are independently selected from hydrogen, C 1 -C 10 alkyl, substituted C 1 -C 10 alkyl, —NR 10 R 11 , —NR 12 C(O)R 13 , C 2-10 alkenyl, substituted C 2-10 alkenyl, C 2-10 alkynyl, substituted C 2-10 alkynyl, C 6-20 aryl, substituted C 6-20 aryl, heteroaryl, heterocyclic, heterocyclooxy, heterocyclothio, heteroarylamino, heterocycloamino, C 4-10 cycloalkyl, substituted C 4-10 cycloalkyl, C 4-10 cycloalkenyl, substituted C 4-10 cycloalkenyl, cyano, halo, —OR 10 , —C(O)OR 10 , —SR 10 , —S(O)R 10 , and —S(O) 2 R 10 ;
R 10 and R 11 are each independently selected from C 1-10 alkyl, substituted C 1-10 alkyl, C 2-10 alkenyl, substituted C 2-10 alkenyl, C 2-10 alkynyl, substituted C 2-10 alkynyl, C 6-20 aryl, substituted C 6-20 aryl, C 4-10 cycloalkyl, substituted C 4-10 cycloalkyl, C 4-10 cycloalkenyl, and substituted C 4-10 cycloalkenyl;
R 12 is selected from hydrogen, C 1 -C 10 alkyl, substituted C 1 -C 10 alkyl, C 2-10 alkenyl, substituted C 2-10 alkenyl, C 2-10 alkynyl, substituted C 2-10 alkynyl, C 6-20 aryl, aryl, C 4-10 substituted C 6-20 cycloalkyl, substituted C 4-10 cycloalkyl, C 4-10 cycloalkenyl, and substituted C 4-10 cycloalkenyl; and
R 13 is selected from hydrogen, C 1-10 alkyl, substituted C 1-10 alkyl, —CH 2 CH 2 CH═CH 2 , substituted C 2-10 alkenyl, C 2-10 alkynyl, substituted C 2-10 alkynyl, C 6 -C 10 aryl, substituted C 6-20 aryl, C 4-10 cycloalkyl, substituted C 4-10 cycloalkyl, C 4-10 cycloalkenyl, substituted C 4-10 cycloalkenyl, —CH 2 —N(CH 2 CH 3 ) 3 + , and —CH 2 —SO 3 − ;
or a pharmaceutically acceptable salt thereof,
wherein one of R 1 is —NR 10 R 11 .
3. The compound of claim 2 , wherein R 2 is hydrogen.
4. The compound of claim 2 , wherein R 1 is —NR 10 R 11 , wherein each of R 10 and R 11 are selected from C 1-10 alkyl, and substituted C 1-10 alkyl.
5. The compound of claim 2 , wherein R 12 is hydrogen.
6. The compound of claim 2 , wherein R 13 is hydrogen or C 1-10 alkyl, substituted alkenyl, C 6 aryl or substituted C 6 aryl, —CH 2 —N(CH 2 CH 3 ) 3 + , or —CH 2 —SO 3 − .
7. A compound of Formula I:
wherein
each of R 1 are independently selected from —NR 10 R 11 , cyano, fluoro, bromo, iodo, —OR 10 , —C(O)OR 10 , —SR 10 , —S(O)R 10 , and —S(O) 2 R 10 ;
x is an integer from 1 to 5;
R 2 is hydrogen or C 1-10 alkyl;
R 3 , R 4 , and R 5 are each independently C 2-8 alkyl; and
R 10 and R 11 are each independently C 1-10 alkyl;
wherein one of R 1 is —NR 10 R 11 .
8. A compound of Formula III:
wherein
R 1 is —NR 10 R 11 ;
x is 1;
R 2 is hydrogen or C 1-10 alkyl;
R 3 , R 4 , and R 5 are each independently C 2-8 alkyl; and
R 10 and R 11 are each independently C 1-10 alkyl.
9. A compound of Formula IV:
wherein
R 1 is —NR 10 R 11 ;
x is 1;
R 2 is hydrogen or C 1-10 alkyl;
R 3 , R 4 , and R 5 are each independently C 2-8 alkyl; and
R 10 and R 11 are each independently C 1-10 alkyl.
10. A compound of the Formula VII:
wherein
R 1 is —NR 10 R 11 ;
x is an integer from 1 to 4;
R 2 is hydrogen or C 1-10 alkyl;
R 3 , R 4 , and R 5 are each independently C 2-8 alkyl;
each of R 6 and R 7 are independently selected from hydrogen, C 1-10 alkyl, substituted C 1-10 alkyl, —NR 10 R 11 , —NR 12 C(O)R 13 , C 2-10 alkenyl, substituted C 2-10 alkenyl, C 2-10 alkynyl, substituted C 2-10 alkynyl, C 6-20 aryl, substituted C 6-20 aryl, heteroaryl, heterocyclic, heterocyclooxy, heterocyclothio, heteroarylamino, heterocycloamino, C 4-10 cycloalkyl, substituted C 4-10 cycloalkyl, C 4-10 cycloalkenyl, substituted C 4-10 cycloalkenyl, cyano, halo, —OR 10 , —C(O)OR 10 , —SR 10 , —S(O)R 10 , and —S(O) 2 R 10 ;
R 10 and R 11 are each independently C 1-10 alkyl;
R 12 is hydrogen or C 1-10 alkyl; and
R 13 is selected from hydrogen, C 1-10 alkyl, C 1-8 alkenyl, C 6-10 aryl, and substituted C 1-10 alkyl,
or a pharmaceutically acceptable salt thereof.
11. A compound of the Formula VIII:
wherein
R 1 is —NR 10 R 11 ;
x is an integer from 1 to 4;
R 2 is hydrogen or C 1-10 alkyl;
R 3 and R 4 are each independently C 2-8 alkyl;
each of R 6 and R 7 are independently selected from hydrogen, C 1-10 alkyl, substituted C 1-10 alkyl, —NR 10 R 11 , —NR 12 C(O)R 13 , C 2-10 alkenyl, substituted C 2-10 alkenyl, C 2-10 alkynyl, substituted C 2-10 alkynyl, C 6-20 aryl, substituted C 6-20 aryl, heteroaryl, heterocyclic, heterocyclooxy, heterocyclothio, heteroarylamino, heterocycloamino, C 4-10 cycloalkyl, substituted C 4-10 cycloalkyl, C 4-10 cycloalkenyl, substituted C 4-10 cycloalkenyl, cyano, halo, —OR 10 , —C(O)OR 10 , —SR 10 , —S(O)R 10 , and —S(O) 2 R 10 ;
R 10 and R 11 are each independently C 1 -C 10 alkyl;
R 12 is hydrogen or C 1-10 alkyl;
R 13 is selected from hydrogen, C 1-10 alkyl, C 1-8 alkenyl, C 6-10 aryl, and substituted C 1-10 alkyl,
or a pharmaceutically acceptable salt thereof.
12. A compound of the Formula IX
wherein
R 1 is —NR 10 R 11 ;
x is an integer from 1 to 4;
y is an integer from 1 to 4;
R 2 is hydrogen or C 1-10 alkyl;
R 3 , R 4 , and R 5 are each independently C 2-8 alkyl;
each of R 6 and R 7 are independently selected from hydrogen, C 1-10 alkyl, substituted C 1-10 alkyl, NR 10 R 11 , —NR 12 C(O)R 13 , C 2-10 alkenyl, substituted C 2-10 alkenyl, C 2-10 alkynyl, substituted C 2-10 alkynyl, C 6-20 aryl, substituted C 6-20 aryl, heteroaryl, heterocyclic, heterocyclooxy, heterocyclothio, heteroarylamino, heterocycloamino, C 4-10 cycloalkyl, substituted C 4-10 cycloalkyl, C 4-10 cycloalkenyl, substituted C 4-10 cycloalkenyl, cyano, halo, —OR 10 , —C(O)OR 10 , —SR 10 , —S(O)R 10 , and —S(O) 2 R 10 ;
R 10 and R 11 are each independently C 1-10 alkyl;
R 12 is hydrogen or C 1-10 alkyl; and
R 13 is selected from hydrogen, C 1-10 alkyl, C 1-8 alkenyl, C 6-10 aryl, and substituted C 1-10 alkyl,
or a pharmaceutically acceptable salt thereof.
13. A compound of the Formula X
wherein
R 1 is —NR 10 R 11 ;
x is an integer from 1 to 4;
y is an integer from 1 to 4;
R 2 is hydrogen or C 1-10 alkyl;
R 3 and R 4 are each independently C 2-8 alkyl;
each of R 6 and R 7 are independently selected from hydrogen, C 1-10 alkyl, substituted C 1-10 alkyl, —NR 10 R 11 , —NR 12 C(O)R 13 , C 2-10 alkenyl, substituted C 2-10 alkenyl, C 2-10 alkynyl, substituted C 2-10 alkynyl, C 6-20 aryl, substituted C 6-20 aryl, heteroaryl, heterocyclic, heterocyclooxy, heterocyclothio, heteroarylamino, heterocycloamino, C 4-10 cycloalkyl, substituted C 4-10 cycloalkyl, C 4-10 cycloalkenyl, substituted C 4-10 cycloalkenyl, cyano, halo, —OR 10 , —C(O)OR 10 , —SR 10 , —S(O)R 10 , and —S(O) 2 R 10 ;
R 10 and R 11 are each independently C 1-10 alkyl;
R 12 is hydrogen or C 1-10 alkyl;
R 13 is selected from hydrogen, C 1-10 alkyl, C 1-8 alkenyl, C 6-10 aryl, and substituted C 1-10 alkyl,
or a pharmaceutically acceptable salt thereof.
14. A compound having a structure selected from:
15. The compound of claim 2 , wherein x is 1 and y is 1.