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1. (WO2008070350) METHODS AND COMPOSITIONS RELATED TO WRAPPING OF DEHYDRONS
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CLAIMS

1. A protein ligand represented by the following structural formula:


and stereoisomers, pharmaceutically acceptable salts, solvates, and hydrates thereof , wherein:
(a) Rl is hydrogen, alkyl, methyl, ethyl, n-propyl, isopropyl, n- butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, isopentyl, aryl, heteroaryl, furanyl, indolyl, thiophenyl, thiazolyl,
imidazolyl, isoxazoyl, oxazoyl, pyrazoyl, pyrrolyl, pyrazinyl, pyridyl, pyrimidyl, pyrimidinyl, purinyl, cinnolinyl,
benzofuranyl, benzothienyl, benzotriazolyl, benzoxazolyl,
quinoline, isoxazolyl, isoquinoline cycloalkyl, alkenyl,
cycloalkenyl, phenyl, or pyridyl;
(b) R2 is hydrogen, alkyl, methyl, ethyl, n-propyl, isopropyl, n- butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, isopentyl, aryl, heteroaryl, furanyl, indolyl, thiophenyl, thiazolyl,
imidazolyl, isoxazoyl, oxazoyl, pyrazoyl, pyrrolyl, pyrazinyl, pyridyl, pyrimidyl, pyrimidinyl, purinyl, cinnolinyl,
benzofuranyl, benzothienyl, benzotriazolyl, benzoxazolyl,
quinoline, isoxazolyl, isoquinoline cycloalkyl, alkenyl,
cycloalkenyl, phenyl, or pyridyl;
(c) R3 is hydrogen, alkyl, methyl, ethyl, n-propyl, isopropyl, n- butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, isopentyl, aryl, heteroaryl, furanyl, indolyl, thiophenyl, thiazolyl,
imidazolyl, isoxazoyl, oxazoyl, pyrazoyl, pyrrolyl, pyrazinyl, pyridyl, pyrimidyl, pyrimidinyl, purinyl, cinnolinyl,
benzofuranyl, benzothienyl, benzotriazolyl, benzoxazolyl,
quinoline, isoxazolyl, isoquinoline cycloalkyl, alkenyl,
cycloalkenyl, phenyl, or pyridyl; and
(d) R4 is hydrogen, alkyl, methyl, ethyl, n-propyl, isopropyl, n- butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, isopentyl, aryl, heteroaryl, furanyl, indolyl, thiophenyl, thiazolyl,
imidazolyl, isoxazoyl, oxazoyl, pyrazoyl, pyrrolyl, pyrazinyl, pyridyl, pyrimidyl, pyrimidinyl, purinyl, cinnolinyl,
benzofuranyl, benzothienyl, benzotriazolyl, benzoxazolyl,
quinoline, isoxazolyl, isoquinoline cycloalkyl, alkenyl,
cycloalkenyl, phenyl, or pyridyl.
2. The ligand of claim 1, wherein:
(a) Rl is alkyl, methyl, ethyl, n-propyl, isopropyl, n-butyl,
isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, isopentyl, aryl, heteroaryl, furanyl, indolyl, thiophenyl, thiazolyl, imidazolyl, isoxazoyl, oxazoyl, pyrazoyl, pyrrolyl, pyrazinyl, pyridyl,
pyrimidyl, pyrimidinyl, purinyl, cinnolinyl, benzofuranyl,
benzothienyl, benzotriazolyl, benzoxazolyl, quinoline,
isoxazolyl, isoquinoline cycloalkyl, alkenyl, cycloalkenyl,
phenyl, or pyridyl;
(b) R2 is hydrogen;
(c) R3 is hydrogen; and
(d) R4 is hydrogen.
3. The ligand of claim 1, wherein:
(a) Rl is hydrogen;
(b) R2 is alkyl, methyl, ethyl, n-propyl, isopropyl, n-butyl,
isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, isopentyl, aryl, heteroaryl, furanyl, indolyl, thiophenyl, thiazolyl, imidazolyl, isoxazoyl, oxazoyl, pyrazoyl, pyrrolyl, pyrazinyl, pyridyl,
pyrimidyl, pyrimidinyl, purinyl, cinnolinyl, benzofuranyl,
benzothienyl, benzotriazolyl, benzoxazolyl, quinoline, isoxazolyl, isoquinoline cycloalkyl, alkenyl, cycloalkenyl,
phenyl, or pyridyl;
(c) R3 is hydrogen; and
(d) R4 is hydrogen.
4. The ligand of claim 1, wherein:
(a) Rl is hydrogen;
(b) R2 is hydrogen;
(c) R3 is alkyl, methyl, ethyl, n-propyl, isopropyl, n-butyl,
isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, isopentyl, aryl, heteroaryl, furanyl, indolyl, thiophenyl, thiazolyl, imidazolyl, isoxazoyl, oxazoyl, pyrazoyl, pyrrolyl, pyrazinyl, pyridyl,
pyrimidyl, pyrimidinyl, purinyl, cinnolinyl, benzofuranyl,
benzothienyl, benzotriazolyl, benzoxazolyl, quinoline,
isoxazolyl, isoquinoline cycloalkyl, alkenyl, cycloalkenyl,
phenyl, or pyridyl; and
(d) R4 is hydrogen.
5. The ligand of claim 1, wherein:
(a) Rl is hydrogen;
(b) R2 is hydrogen;
(c) R3 is hydrogen; and
(d) R4 is alkyl, methyl, ethyl, n-propyl, isopropyl, n-butyl,
isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, isopentyl, aryl, heteroaryl, furanyl, indolyl, thiophenyl, thiazolyl, imidazolyl, isoxazoyl, oxazoyl, pyrazoyl, pyrrolyl, pyrazinyl, pyridyl,
pyrimidyl, pyrimidinyl, purinyl, cinnolinyl, benzofuranyl,
benzothienyl, benzotriazolyl, benzoxazolyl, quinoline,
isoxazolyl, isoquinoline cycloalkyl, alkenyl, cycloalkenyl,
phenyl, or pyridyl.
6. The ligand of claim 1 , wherein the ligand is:
N- {5-[4-(4-methyl piperazine methyl)-benzoylamido]-2- methylphenyl} -4-[3-(4-methyl)-pyridyl]-2-pyrimidine amine; N-{5-[4-(4-methyl piperazine methyl)-benzoylamido]-2- methylphenyl} -4-[3-(4-ethyl)-pyridyl]-2-pyrimidine amine;

N-{5-[4-(4-methyl piperazine methyl)-benzoylamido]-2- methylphenyl} -4- [3 -(4-(2-propyl)-pyridyl)] -2-pyrimidine
amine;
N-{5-[4-(4-methyl piperazine methyl)-benzoylamido]-2- methylphenyl}-4-[3-(4-methyl)-pyridyl]-2-pyrimidine amine;

N-{5-[4-(4-methyl piperazine methyl)-benzoylamido]-2- methylphenyl} -4-[3-(5-phenyl)-pyridyl]-2-pyrimidine amine; N-{5-[4-(4-methyl piperazine methyl)-benzoylamido]-2- methylphenyl}-4-[3-(5-(4-pyridinyl)-pyridyl]-2-pyrimidine
amine; or
N-{5-[4-(4-methyl piperazine methyl)-benzoylamido]-2- methylphenyl} -6-methyl-4-(3-pyridyl)-2-pyrimidine amine.

7. The ligand of claim 1 , wherein the ligand is N- {5-[4-(4-methyl piperazine methyl)-benzoylamido] -2-methylphenyl } -4- [3 -(4-methyl)-pyridyl] -2-pyrimidine amine.
8. The ligand of claim 1 , wherein the ligand is N- {5-[4-(4-methyl piperazine methyl)-benzoylamido] -2-methylphenyl } -4- [3 -(4-ethyl)-pyridyl] -2-pyrimidine amine.
9. The ligand of claim 1 , wherein the ligand is N- {5-[4-(4-methyl piperazine methyl)-benzoylamido] -2-methylphenyl} -4-[3-(4-(2-propyl)-pyridyl)] -2-pyrimidine amine.
10. The ligand of claim 1 , wherein the ligand is N- {5-[4-(4-methyl piperazine methyl)-benzoylamido] -2-methylphenyl } -4- [3 -(4-methyl)-pyridyl] -2-pyrimidine amine.
11. The ligand of claim 1 , wherein the ligand is N- {5-[4-(4-methyl piperazine methyl)-benzoylamido] -2-methylphenyl } -4- [3 -(5 -phenyl)-pyridyl] -2-pyrimidine amine.
12. The ligand of claim 1 , wherein the ligand is N- {5-[4-(4-methyl piperazine methyl)-benzoylamido] -2-methylphenyl } -4- [3 -(5 -(4-pyridinyl)-pyridyl] -2-pyrimidine amine.
13. The ligand of claim 1 , wherein the ligand is N- {5-[4-(4-methyl piperazine methyl)-benzoylamido] -2-methylphenyl } -6-methyl-4-(3 -pyridyl)-2-pyrimidine amine.
14. The ligand of claim 1, further comprised in a lipid formulation.

15. The ligand of claim 14, wherein the lipid formulation comprises one or more cationic lipids.
16. The ligand of claim 15, wherein the cationic lipid is 1 ,2-dimyristoyl-sn-glycero-3 -phospocholine (DMPC), N,N-dioleyl-N,N-dimethyl ammonium chloride (DODAC); N-(2,3-d-ioleyloxy) propyl-N, N-N-triethylammonium chloride (DOTMA); N,N-distearyl-N,N-dimethylammonium bromide
(DDAB); N-(2,3-dioleoyloxy)propyl)-N,N,N-trimethylammonium chloride (DOTAP); 313-(N-(N',N'-dimethylaminoethane)- carbamoyl) cholesterol (DC-Chol), N-(I -(2,3- d ioleyloxy)propyl)-N-2-(sperminecarboxamido)ethyl)-N, N-dimethylammonium trifluoracetate (DOSPA), d-ioctadecylamidoglycyl carboxyspermine (DOGS), l,2-dileoyl-sn-3-phosphoethanolamine (DOPE), l,2-dioleoyl-3-dimethylammonium propane (tlDODAP), or N-(1, 2-dimyristyloxyprop-3-yl)-N,N-dimethyl-N-hydroxyethyl ammonium bromide (DMRIE).
17. The ligand of claim 15 further comprising cholesterol or cholesterol derivative.
18. A method of treating a hyperproliferative condition comprising providing an effective amount of a protein ligand to a subject having, suspected of having, or at risk of developing the hyperproliferative condition, wherein the protein ligand selectively inhibits a protein kinase, wherein the protein ligand is represented by the following structural formula:


and stereoisomers, pharmaceutically acceptable salts, solvates, and hydrates thereof , wherein: (a) Rl is hydrogen, alkyl, methyl, ethyl, n-propyl, isopropyl, n- butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, isopentyl, aryl, heteroaryl, furanyl, indolyl, thiophenyl, thiazolyl,
imidazolyl, isoxazoyl, oxazoyl, pyrazoyl, pyrrolyl, pyrazinyl, pyridyl, pyrimidyl, pyrimidinyl, purinyl, cinnolinyl,
benzofuranyl, benzothienyl, benzotriazolyl, benzoxazolyl,
quinoline, isoxazolyl, isoquinoline cycloalkyl, alkenyl,
cycloalkenyl, phenyl, or pyridyl;
(b) R2 is hydrogen, alkyl, methyl, ethyl, n-propyl, isopropyl, n- butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, isopentyl, aryl, heteroaryl, furanyl, indolyl, thiophenyl, thiazolyl,
imidazolyl, isoxazoyl, oxazoyl, pyrazoyl, pyrrolyl, pyrazinyl, pyridyl, pyrimidyl, pyrimidinyl, purinyl, cinnolinyl,
benzofuranyl, benzothienyl, benzotriazolyl, benzoxazolyl,
quinoline, isoxazolyl, isoquinoline cycloalkyl, alkenyl,
cycloalkenyl, phenyl, or pyridyl;
(c) R3 is hydrogen, alkyl, methyl, ethyl, n-propyl, isopropyl, n- butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, isopentyl, aryl, heteroaryl, furanyl, indolyl, thiophenyl, thiazolyl,
imidazolyl, isoxazoyl, oxazoyl, pyrazoyl, pyrrolyl, pyrazinyl, pyridyl, pyrimidyl, pyrimidinyl, purinyl, cinnolinyl,
benzofuranyl, benzothienyl, benzotriazolyl, benzoxazolyl,
quinoline, isoxazolyl, isoquinoline cycloalkyl, alkenyl,
cycloalkenyl, phenyl, or pyridyl; and
(d) R4 is hydrogen, alkyl, methyl, ethyl, n-propyl, isopropyl, n- butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, isopentyl, aryl, heteroaryl, furanyl, indolyl, thiophenyl, thiazolyl,
imidazolyl, isoxazoyl, oxazoyl, pyrazoyl, pyrrolyl, pyrazinyl, pyridyl, pyrimidyl, pyrimidinyl, purinyl, cinnolinyl,
benzofuranyl, benzothienyl, benzotriazolyl, benzoxazolyl,
quinoline, isoxazolyl, isoquinoline cycloalkyl, alkenyl,
cycloalkenyl, phenyl, or pyridyl.
19. The method of claim 18, wherein the protein kinase is associated with a hyperproliferative condition.

20. The method of claim 19, wherein the hyperproliferative condition is cancer.
21. The method claim 20, wherein the cancer is a blood borne cancer.

22. The method of claim 21 , wherein the cancer is leukemia.