IP Library › Granted Patent US 9,499,574
Granted Patent B2
US 9,499,574 · App. 14/421,982 · Granted Nov 22, 2016

Arsenoplatin anti-cancer agents

Inventors: Denana U. Miodragovic (Chicago, IL); Thomas V. O'Halloran (Chicago, IL)
Assignee: Northwestern University
C07F19/005C07F9/70C07F9/902C07F9/94C07F15/0013C07F15/0066C07F15/045
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Quick Facts
Patent No.
US 9,499,574
App. No.
14/421,982
Granted
Nov 22, 2016
Kind
B2
Abstract

Disclosed are compound having the structure of formula (I): wherein M is Pt, Pd or Ni; Q is As, Sb or Bi; Z 1 is N; Z 2 is O or S; L 1 and L 2 are independently C(O), C—R 1 or C—R 2 ; X is a Lewis base and Y 1 and Y 2 are independently oxygen- or sulfur-containing substituents, conjugates containing compounds of formula (I) and their use as chemotherapy agents.

Claims (64)

1. A compound having the structure of formula (I)

wherein M is Pt, Pd or Ni; Q is As, Sb or Bi; Z 1 is N; Z 2 is O or S; L 1 and L 2 are independently C(O), C—R 1 or C—R 2 ; X is a Lewis base; Y 1 and Y 2 are independently selected from —OR 3 , —SR 3 and —SR 4 , wherein R 1 and R 2 are independently selected from hydrogen, halogen, cyano, keto, ester, ether, thiol, thioether, thioester, imino, C 1 -C 10 alkyl, C 1 -C 10 alkenyl, alkynyl, alkoxyl, amino, amidyl, immino, sulfonyl, sulfoxyl, phosphoryl, phosphoryl ester, glycosyl, aryl, C 3 -C 15 cycloalkyl, heteroaryl, and C 3 -C 15 heterocycloalkyl;

wherein R 3 and R 4 are independently selected from hydrogen, C 1 -C 10 alkyl, C 1 -C 10 alkenyl, alkynyl, alkoxyl, amino, amidyl, immino, sulfonyl, sulfoxyl, phosphoryl, phosphoryl ester, glycosyl, aryl, C 3 -C 15 cycloalkyl, heteroaryl, and C 3 -C 15 heterocycloalkyl;

wherein the Lewis base can be halogen, N-bonded cyano, nitroso, nitroxyl, N-bonded C 1 -C 10 alkyl, alkenyl, N-bonded C 3 -C 10 cycloalkyl, N-bonded heteroalkyl, N-bonded C 1 -C 10 heteroalkenyl, N-bonded aryl, N-bonded heteroaryl, N-bonded C 3 -C 15 heterocycloalkyl, —NR 5 R 6 , N-bonded ligand, S-bonded cyano, sulfonyl, sulfoxyl, thiol, S-bonded thioether, S-bonded thioester, S-bonded C 1 -C 10 alkyl, C 1 -C 10 alkenyl, S-bonded C 3 -C 10 cycloalkyl, S-bonded C 1 -C 10 heteroalkyl, S-bonded C 1 -C 10 heteroalkenyl, S-bonded aryl, S-bonded heteroaryl, S-bonded C 3 -C 15 heterocycloalkyl, —SR 5 , S-bonded ligand, O-bonded C 3 -C 10 cycloalkyl, O-bonded C 1 -C 10 heteroalkyl, O-bonded C 1 -C 10 heteroalkenyl, O-bonded aryl, O-bonded heteroaryl, O-bonded C 3 -C 15 heterocycloalkyl, —OR 5 , O-bonded carboxylato, O-bonded polycarboxylato, O-bonded ligand, or P-bonded phosphine having formula P(R 7 ) 3-x (R 8 ) x , where x is 0, 1, 2 or 3;

wherein R 5 and R 6 are independently selected from hydrogen, O, —CO 2 R 9 , —COR 9 , C 1 -C 10 alkyl, C 1 -C 10 alkenyl, aryl, heteroaryl, C 3 -C 15 cycloalkyl and C 3 -C 15 heterocycloalkyl;

wherein R 7 and R 8 are independently selected from C 1 -C 10 alkyl, C 1 -C 10 alkenyl, aryl, heteroaryl, C 3 -C 15 cycloalkyl and C 3 -C 15 heterocycloalkyl; and

wherein R 9 is selected from hydrogen, hydroxyl, halogen, amine, thiol, ether, C 1 -C 10 alkyl, C 1 -C 10 alkenyl, aryl, heteroaryl, C 3 -C 15 cycloalkyl and C 3 -C 15 heterocycloalkyl.

2. The compound of claim 1 , wherein the compound has the structure of formula (II):

wherein M is Pt, Pd or Ni; Q is As, Sb or Bi; X is a Lewis base;

wherein R 1 and R 2 are independently selected from hydrogen, halogen, cyano, keto, ester, ether, thiol, thioether, thioester, imino, C 1 -C 10 alkyl, C 1 -C 10 alkenyl, alkynyl, alkoxyl, amino, amidyl, immino, sulfonyl, sulfoxyl, phosphoryl, phosphoryl ester, glycosyl, aryl, C 3 -C 15 cycloalkyl, heteroaryl, and C 3 -C 15 heterocycloalkyl;

wherein R 3 and R 4 are independently selected from hydrogen, C 1 -C 10 alkyl, C 1 -C 10 alkenyl, alkynyl, alkoxyl, amino, amidyl, immino, sulfonyl, sulfoxyl, phosphoryl, phosphoryl ester, glycosyl, aryl, C 3 -C 15 cycloalkyl, heteroaryl and C 3 -C 15 heterocycloalkyl;

wherein the Lewis base can be halogen, N-bonded cyano, nitroso, nitroxyl, N-bonded C 1 -C 10 alkyl, alkenyl, N-bonded C 3 -C 10 cycloalkyl, N-bonded heteroalkyl, N-bonded C 1 -C 10 heteroalkenyl, N-bonded aryl, N-bonded heteroaryl, N-bonded C 3 -C 15 heterocycloalkyl, —NR 5 R 6 , N-bonded ligand, S-bonded cyano, sulfonyl, sulfoxyl, thiol, S-bonded thioether, S-bonded thioester, S-bonded C 1 -C 10 alkyl, C 1 -C 10 alkenyl, S-bonded C 3 -C 10 cycloalkyl, S-bonded C 1 -C 10 heteroalkyl, S-bonded C 1 -C 10 heteroalkenyl, S-bonded aryl, S-bonded heteroaryl, S-bonded C 3 -C 15 heterocycloalkyl, —SR 5 , S-bonded ligand, O-bonded C 3 -C 10 cycloalkyl, O-bonded C 1 -C 10 heteroalkyl, O-bonded C 1 -C 10 heteroalkenyl, O-bonded aryl, O-bonded heteroaryl, O-bonded C 3 -C 15 heterocycloalkyl, —OR 5 , O-bonded carboxylato, O-bonded polycarboxylato, O-bonded ligand, or P-bonded phosphine having formula P(R 7 ) 3-x (R 8 ) x , where x is 0, 1, 2 or 3;

wherein R 5 and R 6 are independently selected from hydrogen, O, —CO 2 R 9 , —COR 9 , C 1 -C 10 alkyl, C 1 -C 10 alkenyl, aryl, heteroaryl, C 3 -C 15 cycloalkyl and C 3 -C 15 heterocycloalkyl;

wherein R 7 and R 8 are independently selected from C 1 -C 10 alkyl, C 1 -C 10 alkenyl, aryl, heteroaryl, C 3 -C 15 cycloalkyl and C 3 -C 15 heterocycloalkyl; and

wherein R 9 is selected from hydrogen, hydroxyl, halogen, amine, thiol, ether, C 1 -C 10 alkyl, C 1 -C 10 alkenyl, aryl, heteroaryl, C 3 -C 15 cycloalkyl and C 3 -C 15 heterocycloalkyl.

3. The compound of claim 1 , wherein the compound has the structure of formula (VI):

wherein M is Pt, Pd or Ni; Q is As or Sb; X is a Lewis base;

wherein R 1 and R 2 are independently selected from hydrogen, halogen, cyano, keto, ester, ether, thiol, thioether, thioester, imino, C 1 -C 10 alkyl, C 1 -C 10 alkenyl, alkynyl, alkoxyl, amino, amidyl, immino, sulfonyl, sulfoxyl, phosphoryl, phosphoryl ester, glycosyl, aryl, C 3 -C 15 cycloalkyl, heteroaryl, and C 3 -C 15 heterocycloalkyl; and

wherein the Lewis base can be halogen, N-bonded cyano, nitroso, nitroxyl, N-bonded C 1 -C 10 alkyl, alkenyl, N-bonded C 3 -C 10 cycloalkyl, N-bonded heteroalkyl, N-bonded C 1 -C 10 heteroalkenyl, N-bonded aryl, N-bonded heteroaryl, N-bonded C 3 -C 15 heterocycloalkyl, —NR 5 R 6 , N-bonded ligand, S-bonded cyano, sulfonyl, sulfoxyl, thiol, S-bonded thioether, S-bonded thioester, S-bonded C 1 -C 10 alkyl, C 1 -C 10 alkenyl, S-bonded C 3 -C 10 cycloalkyl, S-bonded C 1 -C 10 heteroalkyl, S-bonded C 1 -C 10 heteroalkenyl, S-bonded aryl, S-bonded heteroaryl, S-bonded C 3 -C 15 heterocycloalkyl, —SR 5 , S-bonded ligand, O-bonded C 3 -C 10 cycloalkyl, O-bonded C 1 -C 10 heteroalkyl, O-bonded C 1 -C 10 heteroalkenyl, O-bonded aryl, O-bonded heteroaryl, O-bonded C 3 -C 15 heterocycloalkyl, —OR 5 , O-bonded carboxylato, O-bonded polycarboxylato, O-bonded ligand, or P-bonded phosphine having formula P(R 7 ) 3-x (R 8 ) x , where x is 0, 1, 2 or 3;

wherein R 5 and R 6 are independently selected from hydrogen, O, —CO 2 R 9 , —COR 9 , C 1 -C 10 alkyl, C 1 -C 10 alkenyl, aryl, heteroaryl, C 3 -C 15 cycloalkyl and C 3 -C 15 heterocycloalkyl;

wherein R 7 and R 8 are independently selected from C 1 -C 10 alkyl, C 1 -C 10 alkenyl, aryl, heteroaryl, C 3 -C 15 cycloalkyl and C 3 -C 15 heterocycloalkyl; and

wherein R 9 is selected from hydrogen, hydroxyl, halogen, amine, thiol, ether, C 1 -C 10 alkyl, C 1 -C 10 alkenyl, aryl, heteroaryl, C 3 -C 15 cycloalkyl and C 3 -C 15 heterocycloalkyl.

4. The compound of claim 3 , wherein the compound is selected from the group consisting of compounds (11)-(19):

5. The compound of claim 1 , wherein the compound has the structure of formula (VII):

wherein X is a Lewis base;

wherein R 1 and R 2 are independently selected from hydrogen, halogen, cyano, keto, ester, ether, thiol, thioether, thioester, imino, C 1 -C 10 alkyl, C 1 -C 10 alkenyl, alkynyl, alkoxyl, amino, amidyl, immino, sulfonyl, sulfoxyl, phosphoryl, phosphoryl ester, glycosyl, aryl, C 3 -C 15 cycloalkyl, heteroaryl, and C 3 -C 15 heterocycloalkyl; and

wherein the Lewis base can be halogen, N-bonded cyano, nitroso, nitroxyl, N-bonded C 1 -C 10 alkyl, C 1 -C 10 alkenyl, N-bonded C 3 -C 10 cycloalkyl, N-bonded heteroalkyl, N-bonded C 1 -C 10 heteroalkenyl, N-bonded aryl, N-bonded heteroaryl, N-bonded C 3 -C 15 heterocycloalkyl, —NR 5 R 6 , N-bonded ligand, S-bonded cyano, sulfonyl, sulfoxyl, thiol, S-bonded thioether, S-bonded thioester, S-bonded C 1 -C 10 alkyl, C 1 -C 10 alkenyl, S-bonded C 3 -C 10 cycloalkyl, S-bonded C 1 -C 10 heteroalkyl, S-bonded C 1 -C 10 heteroalkenyl, S-bonded aryl, S-bonded heteroaryl, S-bonded C 3 -C 15 heterocycloalkyl, —SR 5 , S-bonded ligand, O-bonded C 3 -C 10 cycloalkyl, O-bonded C 1 -C 10 heteroalkyl, O-bonded C 1 -C 10 heteroalkenyl, O-bonded aryl, O-bonded heteroaryl, O-bonded C 3 -C 15 heterocycloalkyl, —OR 5 , O-bonded carboxylato, O-bonded polycarboxylato, O-bonded ligand, or P-bonded phosphine having formula P(R 7 ) 3-x (R 8 ) x , where x is 0, 1, 2 or 3;

wherein R 5 and R 6 are independently selected from hydrogen, O, —CO 2 R 9 , —COR 9 , C 1 -C 10 alkyl, C 1 -C 10 alkenyl, aryl, heteroaryl, C 3 -C 15 cycloalkyl and C 3 -C 15 heterocycloalkyl;

wherein R 7 and R 8 are independently selected from C 1 -C 10 alkyl, C 1 -C 10 alkenyl, aryl, heteroaryl, C 3 -C 15 cycloalkyl and C 3 -C 15 heterocycloalkyl; and

wherein R 9 is selected from hydrogen, hydroxyl, halogen, amine, thiol, ether, C 1 -C 10 alkyl, C 1 -C 10 alkenyl, aryl, heteroaryl, C 3 -C 15 cycloalkyl and C 3 -C 15 heterocycloalkyl.

6. The compound of claim 5 , wherein the compound is selected from the group consisting of compounds (1)-(10):

7. A pharmaceutical composition comprising:

an excipient, and

a compound having the structure of formula (I)

wherein M is Pt, Pd or Ni; Q is As, Sb or Bi; Z 1 is N; Z 2 is O or S; L 1 and L 2 are independently C(O), C—R 1 or C—R 2 ; X is a Lewis base; Y 1 and Y 2 are independently selected from —OR 3 , —SR 3 and —SR 4 , wherein R 1 and R 2 are independently selected from hydrogen, halogen, cyano, keto, ester, ether, thiol, thioether, thioester, imino, C 1 -C 10 alkyl, C 1 -C 10 alkenyl, alkynyl, alkoxyl, amino, amidyl, immino, sulfonyl, sulfoxyl, phosphoryl, phosphoryl ester, glycosyl, aryl, C 3 -C 15 cycloalkyl, heteroaryl, and C 3 -C 15 heterocycloalkyl;

wherein R 3 and R 4 are independently selected from hydrogen, C 1 -C 10 alkyl, C 1 -C 10 alkenyl, alkynyl, alkoxyl, amino, amidyl, immino, sulfonyl, sulfoxyl, phosphoryl, phosphoryl ester, glycosyl, aryl, C 3 -C 15 cycloalkyl, heteroaryl, and C 3 -C 15 heterocycloalkyl;

wherein the Lewis base can be halogen, N-bonded cyano, nitroso, nitroxyl, N-bonded C 1 -C 10 alkyl, alkenyl, N-bonded C 3 -C 10 cycloalkyl, N-bonded heteroalkyl, N-bonded heteroalkenyl, N-bonded aryl, N-bonded heteroaryl, N-bonded C 3 -C 15 heterocycloalkyl, —NR 5 R 6 , N-bonded ligand, S-bonded cyano, sulfonyl, sulfoxyl, thiol, S-bonded thioether, S-bonded thioester, S-bonded C 1 -C 10 alkyl, C 1 -C 10 alkenyl, S-bonded C 3 -C 10 cycloalkyl, S-bonded C 1 -C 10 heteroalkyl, S-bonded C 1 -C 10 heteroalkenyl, S-bonded aryl, S-bonded heteroaryl, S-bonded C 3 -C 15 heterocycloalkyl, —SR 5 , S-bonded ligand, O-bonded C 3 -C 10 cycloalkyl, O-bonded C 1 -C 10 heteroalkyl, O-bonded C 1 -C 10 heteroalkenyl, O-bonded aryl, O-bonded heteroaryl, O-bonded C 3 -C 15 heterocycloalkyl, —OR 5 , O-bonded carboxylato, O-bonded polycarboxylato, O-bonded ligand, or P-bonded phosphine having formula P(R 7 ) 3-x (R 8 ) x , where x is 0, 1, 2 or 3;

wherein R 5 and R 6 are independently selected from hydrogen, O, —CO 2 R 9 , —COR 9 , C 1 -C 10 alkyl, C 1 -C 10 alkenyl, aryl, heteroaryl, C 3 -C 15 cycloalkyl and C 3 -C 15 heterocycloalkyl;

wherein R 7 and R 8 are independently selected from C 1 -C 10 alkyl, C 1 -C 10 alkenyl, aryl, heteroaryl, C 3 -C 15 cycloalkyl and C 3 -C 15 heterocycloalkyl; and

wherein R 9 is selected from hydrogen, hydroxyl, halogen, amine, thiol, ether, C 1 -C 10 alkyl, C 1 -C 10 alkenyl, aryl, heteroaryl, C 3 -C 15 cycloalkyl and C 3 -C 15 heterocycloalkyl.

8. The pharmaceutical composition of claim 7 , wherein the compound has the structure of formula (II):

wherein M is Pt, Pd or Ni; Q is As, Sb or Bi; X is a Lewis base;

wherein R 1 and R 2 are independently selected from hydrogen, halogen, cyano, keto, ester, ether, thiol, thioether, thioester, imino, C 1 -C 10 alkyl, C 1 -C 10 alkenyl, alkynyl, alkoxyl, amino, amidyl, immino, sulfonyl, sulfoxyl, phosphoryl, phosphoryl ester, glycosyl, aryl, C 3 -C 15 cycloalkyl, heteroaryl, and C 3 -C 15 heterocycloalkyl;

wherein R 3 and R 4 are independently selected from hydrogen, C 1 -C 10 alkyl, C 1 -C 10 alkenyl, alkynyl, alkoxyl, amino, amidyl, immino, sulfonyl, sulfoxyl, phosphoryl, phosphoryl ester, glycosyl, aryl, C 3 -C 15 cycloalkyl, heteroaryl and C 3 -C 15 heterocycloalkyl;

wherein the Lewis base can be halogen, N-bonded cyano, nitroso, nitroxyl, N-bonded C 1 -C 10 alkyl, alkenyl, N-bonded C 3 -C 10 cycloalkyl, N-bonded heteroalkyl, N-bonded C 1 -C 10 heteroalkenyl, N-bonded aryl, N-bonded heteroaryl, N-bonded C 3 -C 15 heterocycloalkyl, —NR 5 R 6 , N-bonded ligand, S-bonded cyano, sulfonyl, sulfoxyl, thiol, S-bonded thioether, S-bonded thioester, S-bonded C 1 -C 10 alkyl, C 1 -C 10 alkenyl, S-bonded C 3 -C 10 cycloalkyl, S-bonded C 1 -C 10 heteroalkyl, S-bonded C 1 -C 10 heteroalkenyl, S-bonded aryl, S-bonded heteroaryl, S-bonded C 3 -C 15 heterocycloalkyl, —SR 5 , S-bonded ligand, O-bonded C 3 -C 10 cycloalkyl, O-bonded C 1 -C 10 heteroalkyl, O-bonded C 1 -C 10 heteroalkenyl, O-bonded aryl, O-bonded heteroaryl, O-bonded C 3 -C 15 heterocycloalkyl, —OR 5 , O-bonded carboxylato, O-bonded polycarboxylato, O-bonded ligand, or P-bonded phosphine having formula P(R 7 ) 3-x (R 8 ) x , where x is 0, 1, 2 or 3;

wherein R 5 and R 6 are independently selected from hydrogen, O, —CO 2 R 9 , C 1 -C 10 alkyl, C 1 -C 10 alkenyl, aryl, heteroaryl, C 3 -C 15 cycloalkyl and C 3 -C 15 heterocycloalkyl;

wherein R 7 and R 8 are independently selected from C 1 -C 10 alkyl, C 1 -C 10 alkenyl, aryl, heteroaryl, C 3 -C 15 cycloalkyl and C 3 -C 15 heterocycloalkyl; and

wherein R 9 is selected from hydrogen, hydroxyl, halogen, amine, thiol, ether, C 1 -C 10 alkyl, C 1 -C 10 alkenyl, aryl, heteroaryl, C 3 -C 15 cycloalkyl and C 3 -C 15 heterocycloalkyl.

9. The pharmaceutical composition of claim 7 , wherein the compound has the structure of formula (VI):

wherein M is Pt, Pd or Ni; Q is As or Sb; X is a Lewis base;

wherein R 1 and R 2 are independently selected from hydrogen, halogen, cyano, keto, ester, ether, thiol, thioether, thioester, imino, C 1 -C 10 alkyl, C 1 -C 10 alkenyl, alkynyl, alkoxyl, amino, amidyl, immino, sulfonyl, sulfoxyl, phosphoryl, phosphoryl ester, glycosyl, aryl, C 3 -C 15 cycloalkyl, heteroaryl, and C 3 -C 15 heterocycloalkyl; and

wherein the Lewis base can be halogen, N-bonded cyano, nitroso, nitroxyl, N-bonded C 1 -C 10 alkyl, alkenyl, N-bonded C 3 -C 10 cycloalkyl, N-bonded heteroalkyl, N-bonded C 1 -C 10 heteroalkenyl, N-bonded aryl, N-bonded heteroaryl, N-bonded C 3 -C 15 heterocycloalkyl, —NR 5 R 6 , N-bonded ligand, S-bonded cyano, sulfonyl, sulfoxyl, thiol, S-bonded thioether, S-bonded thioester, S-bonded C 1 -C 10 alkyl, C 1 -C 10 alkenyl, S-bonded C 3 -C 10 cycloalkyl, S-bonded C 1 -C 10 heteroalkyl, S-bonded C 1 -C 10 heteroalkenyl, S-bonded aryl, S-bonded heteroaryl, S-bonded C 3 -C 15 heterocycloalkyl, —SR 5 , S-bonded ligand, O-bonded C 3 -C 10 cycloalkyl, O-bonded C 1 -C 10 heteroalkyl, O-bonded C 1 -C 10 heteroalkenyl, O-bonded aryl, O-bonded heteroaryl, O-bonded C 3 -C 15 heterocycloalkyl, —OR 5 , O-bonded carboxylato, O-bonded polycarboxylato, O-bonded ligand, or P-bonded phosphine having formula P(R 7 ) 3-x (R 8 ) x , where x is 0, 1, 2 or 3;

wherein R 5 and R 6 are independently selected from hydrogen, O, —CO 2 R 9 , C 1 -C 10 alkyl, C 1 -C 10 alkenyl, aryl, heteroaryl, C 3 -C 15 cycloalkyl and C 3 -C 15 heterocycloalkyl;

wherein R 7 and R 8 are independently selected from C 1 -C 10 alkyl, C 1 -C 10 alkenyl, aryl, heteroaryl, C 3 -C 15 cycloalkyl and C 3 -C 15 heterocycloalkyl; and

wherein R 9 is selected from hydrogen, hydroxyl, halogen, amine, thiol, ether, C 1 -C 10 alkyl, C 1 -C 10 alkenyl, aryl, heteroaryl, C 3 -C 15 cycloalkyl and C 3 -C 15 heterocycloalkyl.

10. The pharmaceutical composition of claim 9 , wherein the compound is selected from the group consisting of compounds (11)-(19):

11. The pharmaceutical composition of claim 7 , wherein the compound has the structure of formula (VII):

wherein X is a Lewis base;

wherein R 1 and R 2 are independently selected from hydrogen, halogen, cyano, keto, ester, ether, thiol, thioether, thioester, imino, C 1 -C 10 alkyl, C 1 -C 10 alkenyl, alkynyl, alkoxyl, amino, amidyl, immino, sulfonyl, sulfoxyl, phosphoryl, phosphoryl ester, glycosyl, aryl, C 3 -C 15 cycloalkyl, heteroaryl, and C 3 -C 15 heterocycloalkyl; and

wherein the Lewis base can be halogen, N-bonded cyano, nitroso, nitroxyl, N-bonded C 1 -C 10 alkyl, C 1 -C 10 alkenyl, N-bonded C 3 -C 10 cycloalkyl, N-bonded heteroalkyl, N-bonded C 1 -C 10 heteroalkenyl, N-bonded aryl, N-bonded heteroaryl, N-bonded C 3 -C 15 heterocycloalkyl, —NR 5 R 6 , N-bonded ligand, S-bonded cyano, sulfonyl, sulfoxyl, thiol, S-bonded thioether, S-bonded thioester, S-bonded C 1 -C 10 alkyl, C 1 -C 10 alkenyl, S-bonded C 3 -C 10 cycloalkyl, S-bonded C 1 -C 10 heteroalkyl, S-bonded C 1 -C 10 heteroalkenyl, S-bonded aryl, S-bonded heteroaryl, S-bonded C 3 -C 15 heterocycloalkyl, —SR 5 , S-bonded ligand, O-bonded C 3 -C 10 cycloalkyl, O-bonded C 1 -C 10 heteroalkyl, O-bonded C 1 -C 10 heteroalkenyl, O-bonded aryl, O-bonded heteroaryl, O-bonded C 3 -C 15 heterocycloalkyl, —OR 5 , O-bonded carboxylato, O-bonded polycarboxylato, O-bonded ligand, or P-bonded phosphine having formula P(R 7 ) 3-x (R 8 ) x , where x is 0, 1, 2 or 3;

wherein R 5 and R 6 are independently selected from hydrogen, O, —CO 2 R 9 , —COR 9 , C 1 -C 10 alkyl, C 1 -C 10 alkenyl, aryl, heteroaryl, C 3 -C 15 cycloalkyl and C 3 -C 15 heterocycloalkyl;

wherein R 7 and R 8 are independently selected from C 1 -C 10 alkyl, C 1 -C 10 alkenyl, aryl, heteroaryl, C 3 -C 15 cycloalkyl and C 3 -C 15 heterocycloalkyl; and

wherein R 9 is selected from hydrogen, hydroxyl, halogen, amine, thiol, ether, C 1 -C 10 alkyl, C 1 -C 10 alkenyl, aryl, heteroaryl, C 3 -C 15 cycloalkyl and C 3 -C 15 heterocycloalkyl.

12. The pharmaceutical composition of claim 11 , wherein the compound is selected from the group consisting of compounds (1)-(10):

Assignments (2)
CONFIRMATORY LICENSE Recorded Jun 30, 2015
From: NORTHWESTERN UNIVERSITY
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 036041/0041 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 18, 2015
From: O'HALLORAN, THOMAS V.; MIODRAGOVIC, DENANA U.
To: NORTHWESTERN UNIVERSITY
Reel/Frame 035025/0132 →
Continuity (2)
Provisional Application 61683031 · Aug 14, 2012
Related Publication 20150218195A1 · Aug 6, 2015