Bromodomain binding reagents and uses thereof
The present invention provides compounds of the Formula (I) and (II), and salts thereof, wherein L 1 , L 2 , A, B, Z, and R O are as defined herein. The present invention also provides synthetic intermediates, methods of preparation and use, and kits comprising such compounds. Such compounds, when bound to a label or probe (B), may be useful in various assays for identifying bromodomain binding agents, for example, specific for the BET-family of bromodomains.
1. A compound of Formula (I):
or salt thereof;
wherein:
L 1 is a bond or a linking group selected from the group consisting of substituted or unsubstituted alkylene; substituted or unsubstituted alkenylene; substituted or unsubstituted alkynylene; substituted or unsubstituted heteroalkylene; substituted or unsubstituted heteroalkenylene; substituted or unsubstituted heteroalkynylene; substituted or unsubstituted heterocyclylene; substituted or unsubstituted carbocyclylene; substituted or unsubstituted arylene; substituted or unsubstituted heteroarylene; and combinations thereof;
L 2 is a linking group selected from the group consisting of substituted or unsubstituted alkylene; substituted or unsubstituted alkenylene; substituted or unsubstituted alkynylene; substituted or unsubstituted heteroalkylene; substituted or unsubstituted heteroalkenylene; substituted or unsubstituted heteroalkynylene; substituted or unsubstituted heterocyclylene; substituted or unsubstituted carbocyclylene; substituted or unsubstituted arylene; substituted or unsubstituted heteroarylene; and combinations thereof;
A is a bond, —NR W1 —, —NR W1 —NR W1 —, —S—, —O—, —S—S—
wherein is a single or double bond, W is —O—, —S—, or —NR W1 —, R W1 is hydrogen, substituted or unsubstituted alkyl, or an amino protecting group; and Q is —NR W1 —, —NR W1 —NR W1 —, —S—, —O—; and B is a detectable label.
2. The compound of claim 1 , wherein L 1 is a linker group comprising a combination of one or more groups of the formula:
wherein R L is hydrogen or substituted or unsubstituted alkyl, n is 0 or an integer between 1 to 10, inclusive.
3. The compound of claim 1 , wherein L 2 is a linker group comprising a combination of one or more groups of the formula:
wherein R L is hydrogen or substituted or unsubstituted alkyl, m is 0 or an integer between 1 to 10, inclusive.
4. The compound of claim 1 , wherein A is
5. The compound of claim 1 , wherein A is
6. The compound of claim 1 , wherein A is —NR W1 —, —NR W1 —NR W1 —, —S—, —O—, or —S—S—.
7. The compound of claim 1 , wherein A is:
8. The compound of claim 1 , wherein A is:
9. The compound of claim 1 , wherein A is:
10. The compound of claim 1 , wherein A is:
11. The compound of claim 1 , wherein the compound is of formula:
or a salt thereof.
12. The compound of claim 1 , wherein the compound is of formula:
or a salt thereof.
13. The compound of claim 1 , wherein the compound is of Formula:
or a salt thereof.