IP Library Granted Patent US 8,053,440
Granted Patent B2
US 8,053,440 · App. 11/670,238 · Granted Nov 8, 2011

Compounds for the prevention and treatment of cardiovascular diseases

View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 8,053,440
App. No.
11/670,238
Granted
Nov 8, 2011
Kind
B2
Abstract

The present disclosure relates to compounds, which are useful for regulating the expression of apolipoprotein A-I (ApoA-I), and their use for treatment and prevention of cardiovascular disease and related disease states, including cholesterol- or lipid-related disorders, such as, for example, atherosclerosis.

Claims (223)

1. A compound of Formula II:

wherein:

X is N;

Y is CO;

R 1 and R 3 are each independently selected from alkoxy, alkyl, amino, halogen, and hydrogen;

R 2 is selected from alkoxy, alkyl, alkenyl, alkynyl, amide, amino, halogen, and hydrogen;

R 6 and R 8 are each independently selected from alkyl, alkoxy, amino, halogen, and hydrogen;

R 5 and R 9 are each hydrogen;

R 7 is selected from amino, amide, alkyl, hydroxyl, and alkoxy;

R 10 is hydrogen;

each W is independently selected from C and N, wherein if W is N, then p is 0 or 1, and if W is C, then p is 1;

for W—(R 10 ) p , W is N and p is 1;

for W—(R 7 ) p , W is C and p is 1;

for W—(R 4 ) p , W is C, p is 1 and R 4 is H, or W is N and p is 0;

Z 1 is a double bond, and Z 2 and Z 3 are each a single bond;

with the proviso that if R 1 is hydrogen, then R 3 is alkoxy;

with the proviso that if R 3 is hydrogen, then R 1 is selected from amino and alkoxy;

with the proviso that if R 7 is selected from alkyl, hydroxyl, and alkoxy, then at least one of R 6 and R 8 is independently selected from alkyl, alkoxy, amino, and halogen;

and pharmaceutically acceptable salts thereof.

2. The compound according to claim 1 , wherein R 7 is amino.

3. The compound according to claim 2 , wherein the compound of Formula II is 2-(4-(bis(2-hydroxyethyl)amino)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one.

4. The compound according to claim 1 , wherein R 7 is selected from hydroxyl and alkoxy.

5. The compound according to claim 4 , wherein the compound of Formula II is selected from:

N-(2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl)methanesulfonamide;

2-(4-hydroxy-3-methylphenyl)-5,7-dimethoxyquinazolin-4(3H)-one;

2-(4-(2-hydroxyethoxy)-3-methylphenyl)-5,7-dimethoxyquinazolin-4(3H)-one; and

2-(3,5-dimethyl-4-(2-morpholinoethoxy)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one.

6. The compound according to claim 4 , wherein R 6 and R 8 are each independently alkyl;

R 2 is hydrogen; and

R 7 is selected from hydroxyl and alkoxy substituted with a hydroxyl.

7. The compound according to claim 6 , wherein the compound of Formula II is 2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-5,7-dimethoxyquinazolin-4(3H)-one.

8. The compound according to claim 1 , wherein R 7 is an amino or an alkoxy selected from the group represented by Formula III:

wherein:

A is selected from O and N;

n is selected from 0, 1, 2, 3, 4 and 5;

B is selected from —C(O)N(R h ) 2 —, —S(O) 2 N(R h ) 2 —, —C(O)—, S(O) 2 —, —C(O)O—, wherein each R h is selected from alkyl, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl, haloalkyl, heteroaryl, heterocyclyl, and hydrogen; and

R 20 is selected from (C 1 -C 6 ) alkyl, (C 1 -C 6 ) alkenyl, (C 1 -C 6 ) alkynyl, aryl, arylalkyl, cycloalkyl, haloalkyl, heteroaryl, heterocyclyl, and hydrogen.

9. The compound according to claim 8 , wherein the compound of Formula II is selected from:

2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl cyclohexylcarbamate;

N-(2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl)acetamide;

N-(2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl)isobutyramide;

1-(2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl)-3-phenylurea; and

3-(2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl)-1,1-dimethylurea.

10. The compound according to claim 1 , wherein the compound of Formula II is selected from:

2-(3,5-dimethyl-4-(2-morpholinoethoxy)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one;

2-(3,5-di-tert-butyl-4-hydroxyphenyl)-5,7-dimethoxyquinazolin-4(3H)-one;

2-(4-hydroxy-3-methoxyphenyl)-5,7-dimethoxyquinazolin-4(3H)-one;

2-(3-chloro-4-hydroxyphenyl)-5,7-dimethoxyquinazolin-4(3H)-one;

5,7-dimethoxy-2-(4-(4-methylpiperazin-1-yl)phenyl)quinazolin-4(3H)-one;

2-(4-hydroxy-3,5-dimethylphenyl)-6,7-dimethoxyquinazolin-4(3H)-one;

2-(4-(6,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)acetamide;

2-(3-chloro-4-(2-hydroxyethoxy)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one;

2-(4-(2-hydroxyethoxy)-3-methoxyphenyl)-5,7-dimethoxyquinazolin-4(3H)-one;

2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-6,7-dimethoxyquinazolin-4(3H)-one;

N-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenyl)-2-hydroxyacetamide;

2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)acetic acid;

N-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)phenyl)-2-hydroxyacetamide;

2-(4-hydroxy-3,5-dimethylphenyl)-5,7-dimethoxypyrido[2,3-d]pyrimidin-4(3H) -one;

5,7-dimethoxy-2-(4-methoxy-3-(morpholinomethyl)phenyl)quinazolin-4(3H)-one;

2-(3,5-dimethyl-4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one;

2-(4-hydroxy-3-(2-hydroxyethyl)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one;

2-(4-(bis(2-hydroxyethyl)amino)phenyl)-5,7-dimethoxy-pyrido[2,3-d]pyrimidin-4(3H)one;

5,7-dimethoxy-2-(4-(2-methoxyethoxy)-3,5-dimethylphenyl)quinazolin-4(3H)-one;

2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-5-methoxyquinazolin-4(3H)-one;

(E)-N′-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenyl)-N,N-dimethylformimidamide;

2-(4-(benzyloxy)-3,5-dimethylphenyl)-5,7-dimethoxyquinazolin-4(3H)-one;

2-(4-(2-aminoethoxy)-3,5-dimethylphenyl)-5,7-dimethoxyquinazolin-4(3H)-one;

2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2-methoxyphenoxy)acetic acid;

2-(4-(5,7-Dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethyl-phenoxy)ethyl propylcarbamate;

2-(4-(5,7-Dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethyl-phenoxy)ethyl methylcarbamate;

N-(2-(4-(5,7-Dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl)-4-methylbenzamide;

N-(2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl)benzenesulfonamide;

N-(2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl-4-methylbenzenesulfonamide;

N-(2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl)-4-methoxybenzamide;

N-(2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl)benzamide;

1-(2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl)-3-methylurea; and

1-(2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl)-3-(4-methoxyphenyl)urea.

11. A compound selected from:

2-(3,5-dimethyl-4-(2-morpholinoethoxy)phenyl)quinazolin-4(3H)-one;

2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)quinazolin-4(3H)-one;

2-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)quinazolin-4(3H)-one;

2-(4-(4-oxo-3,4-dihydroquinazolin-2-yl)phenoxy)acetic acid;

2-(4-(dimethylamino)naphthalen-1-yl)quinazolin-4(3H)-one;

2-(4-(4-oxo-3,4-dihydroquinazolin-2-yl)phenoxy)acetamide;

2-(4-(bis(2-hydroxyethyl)amino)phenyl)quinazolin-4(3H)-one;

2-(4-(5,7-dimethoxyquinazolin-2-yl)-2,6-dimethylphenoxy)ethanol;

2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-5,7-dimethylquinazolin-4(3H)-one;

5,7-dichloro-2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)quinazolin-4(3H)-one;

6-bromo-2-(4-hydroxy-3,5-dimethylphenyl)quinazolin-4(3H)-one;

6-bromo-2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)quinazolin-4(3H)-one;

6-bromo-2-(4-(2-(tert-butyldimethylsilyloxy)ethoxy)-3,5-dimethylphenyl)quinazolin-4(3H)-one;

5,7-dimethoxy-2-(pyridin-4-yl)quinazolin-4(3H)-one;

2-(4-(dimethylamino)naphthalen-1-yl)-5,7-dimethoxyquinazolin-4(3H)-one;

2-(4-(dimethylamino)pyridin-1-yl)-6,7-dimethoxyquinazolin-4(3H)-one;

2-(4-hydroxy-3,5-dimethylphenyl)-5,7-dimethoxy-1-methylquinazolin-4(1H)-one;

2-(4-hydroxy-3,5-dimethylphenyl)-5,7-dimethoxy-6-(morphoinomethyl)quinazolin-4(3H)-one;

2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-6-methoxyquinazolin-4(3H)-one; and

5-hydroxy-2-(4-hydroxy-3,5-dimethylphenyl)-7-methoxyquinazolin-4(3H)-one.

12. A pharmaceutical composition comprising a compound according to any one of claims 1 - 11 and a pharmaceutically acceptable carrier.

13. A compound of Formula II:

wherein:

X is N;

Y is CO;

R 1 and R 3 are each independently selected from alkoxy and hydrogen;

R 2 is selected from alkoxy, alkyl, and hydrogen;

R 6 and R 8 are each independently selected from alkyl, alkoxy, chloride, and hydrogen;

R 5 and R 9 are each hydrogen;

R 7 is selected from amino, hydroxyl, alkoxy, and alkyl substituted with a heterocyclyl;

R 10 is hydrogen; or

two adjacent substituents selected from R 6 , R 7 , and R 8 are connected to form a heterocyclyl;

each W is independently selected from C and N, wherein if W is N, then p is 0 or 1, and if W is C, then p is 1;

for W—(R 10 ) p , W is N and p is 1;

for W—(R 4 ) p , W is C, p is 1 and R 4 is H, or W is N and p is 0;

Z 1 is a double bond, and Z 2 and Z 3 are each a single bond;

with the proviso that if R 2 is alkoxy or hydrogen, then least one of R 1 and R 3 is alkoxy;

with the proviso that if R 7 is selected from hydroxyl and alkoxy, then at least one of R 6 and R 8 are independently selected from alkyl, alkoxy, and chloride;

with the proviso that if for W—(R 7 ) p , W is N and p is 0, then at least one of R 6 and R 8 is selected from alkyl, alkoxy, and chloride;

and pharmaceutically acceptable salts thereof.

14. The compound according to claim 13 , wherein the compound of Formula II is selected from:

3-(4-hydroxy-3,5-dimethylphenyl)-6,8-dimethoxyisoquinolin-1(2H)-one;

3-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-6,8-dimethoxyisoquinolin-1(2H)-one;

2-(4-hydroxy-3,5-dimethylphenyl)-5,7-dimethoxyquinazolin-4(3H)-one;

2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-5,7-dimethoxyquinazolin-4(3H)-one);

2-(4-hydroxy-3-methoxyphenyl)-5,7-dimethoxyquinazolin-4(3H)-one;

2-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-5,7-dimethoxyquinazolin-4(3H)one;

2-(4-(bis(2-hydroxyethyl)amino)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one;

2-(4-(bis(2-hydroxyethyl)amino)phenyl)-6,7-dimethoxyquinazolin-4(3H)-one;

2-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-6,7-dimethoxyquinazolin-4(3H)-one;

2-(4-((4-ethylpiperazin-1-yl)methyl)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one;

2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-5,7-dimethoxypyrido[2,3-d]pyrimidin -4(3H)-one;

2-(2-chloro-6-methylpyridin-4-yl)-5,7-dimethoxyquinazolin-4(3H)-one;

5,7-dimethoxy-2-(4-methoxy-3,5-dimethylphenyl)quinazolin-4(3H)-one;

2-(4-amino-3,5-dimethylphenyl)-5,7-dimethoxyquinazolin-4(3H)-one;

N1-(2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl)-N2-methylphthalamide;

2-(4-(2-aminoethoxy)-3,5-dimethylphenyl)-5,7-dimethoxyquinazolin-4(3H)-one;

and 4-chloro-N-(2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl)benzenesulfonamide.

15. The compound according to claim 13 , wherein R 7 is selected from an amino or an alkoxy selected from the group represented by Formula III:

wherein:

A is selected from O and N;

n is selected from 0, 1, 2, 3, 4 and 5;

B is selected from —C(O)N(R h ) 2 —, —S(O) 2 N(R h ) 2 —, —C(O)—, —S(O) 2 —, and —C(O)O—, wherein each R h is independently selected from alkyl, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl, haloalkyl, heteroaryl, heterocyclyl, and hydrogen; and

R 20 is selected from (C 1 -C 6 ) alkyl, (C 1 -C 6 ) alkenyl, (C 1 -C 6 ) alkynyl, aryl, arylalkyl, cycloalkyl, haloalkyl, heteroaryl, heterocyclyl, and hydrogen.

16. The compound of claim 15 , wherein the compound of Formula II is selected from:

N1-(2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl)-N2-methylphthalamide;

2-(4-(2-aminoethoxy)-3,5-dimethylphenyl)-5,7-dimethoxyquinazolin-4(3H)-one; and

4-chloro-N-(2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl)benzenesulfonamide.

17. A pharmaceutical composition comprising a compound according to any one of claims 13 - 16 and a pharmaceutically acceptable carrier.

18. A compound of Formula II:

wherein:

X is N;

Y is CO;

R 1 and R 3 are each independently selected from alkoxy, alkyl, amino, halogen, and hydrogen;

R 2 is selected from —N—C(O)—R 18 , —N—SO 2 —R 18 , —CH 2 —C(R 18 ) 3 , —CH 2 —N(R 18 ) 2 , and —CH 2 —O—R 18 , wherein each R 18 is independently selected from alkoxy, alkyl, alkenyl, amide, amino, aryl, arylalkyl, cycloalkyl, haloalkyl, halogen, heteroaryl, heterocyclyl, and hydrogen;

R 6 and R 8 are each independently selected from alkyl, alkoxy, amino, halogen, and hydrogen;

R 6 and R 9 are each hydrogen;

R 7 is selected from amino, amide, alkyl, hydroxyl, and alkoxy;

R 10 is hydrogen;

each W is independently selected from C and N, wherein if W is N, then p is 0 or 1, and if W is C, then p is 1;

for W—(R 10 ) p , W is N and p is 1;

for W—(R 7 ) p , W is C and p is 1;

for W—(R 4 ) p , W is C, p is 1 and R 4 is H, or W is N and p is 0;

Z 1 is a double bond, and Z 2 and Z 3 are each a single bond;

with the proviso that if R 7 is selected from alkyl, hydroxyl, and alkoxy, then at least one of R 6 and R 8 is independently selected from alkyl, alkoxy, amino, and halogen;

and pharmaceutically acceptable salts thereof.

19. The compound according to claim 18 , wherein the compound of Formula II is selected from:

N-(2-(4-hydroxy-3,5-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-6-yl)acetamide;

2-(4-hydroxy-3,5-dimethylphenyl)-6-(morpholinomethyl)quinazolin-4(3H)-one;

N-(2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-6-yl)acetamide; and

2-(4-hydroxy-3,5-dimethylphenyl)-5,7-dimethoxy-6-(morphoinomethyl)quinazolin-4(3H)-one.

20. The compound according to claim 18 , wherein R 6 and R 8 are each independently alkyl; and R 7 is selected from hydroxyl and alkoxy.

21. The compound according to claim 18 , wherein R 7 is selected from an amino or an alkoxy selected from the group represented by Formula III:

wherein:

A is selected from O and N;

n is selected from 0, 1, 2, 3, 4 and 5;

B is selected from —C(O)N(R h ) 2 —, —S(O) 2 N(R h ) 2 —, —C(O)—, —S(O) 2 —, —C(O)O—, wherein each R h is selected from alkyl, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl, haloalkyl, heteroaryl, heterocyclyl, and hydrogen; and

R 20 is selected from (C 1 -C 6 ) alkyl, (C 1 -C 6 ) alkenyl, (C 1 -C 6 ) alkynyl, aryl, arylalkyl, cycloalkyl, haloalkyl, heteroaryl, heterocyclyl, and hydrogen.

22. The compound according to claim 18 , wherein R 6 and R 8 are each independently alkyl.

23. A pharmaceutical composition comprising a compound according to any one of claim 18 , 19 , or 20 - 22 and a pharmaceutically acceptable carrier.

24. A compound of Formula II:

wherein:

X is N;

Y is CO;

R 1 is selected from alkoxy or amino;

R 3 is alkoxy;

R 2 is selected from alkoxy, alkyl, alkenyl, alkynyl, amide, amino, halogen, and hydrogen;

R 6 and R 8 are each independently selected from alkyl, alkoxy, amino, halogen, and hydrogen;

R 5 and R 9 are each hydrogen;

R 7 is selected from amino, amide, alkyl, hydroxyl, and alkoxy;

R 10 is hydrogen;

each W is independently selected from C and N, wherein if W is N, then p is 0 or 1, and if W is C, then p is 1;

for W—(R 10 ) p , W is N and p is 1;

for W—(R 7 ) p , W is C and p is 1;

for W—(R 4 ) p , W is C, p is 1 and R 4 is H, or W is N and p is 0;

Z 1 is a double bond, and Z 2 and Z 3 are each a single bond;

and pharmaceutically acceptable salts thereof.

25. The compound according to claim 24 , wherein R 7 is selected from hydroxyl and alkoxy.

26. The compound according to claim 25 , wherein the compound of Formula II is selected from:

2-(4-hydroxyphenyl)-5,7-dimethoxyquinazolin-4(3H)-one;

2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)phenoxy)acetic acid;

5,7-dimethoxy-2-(4-methoxyphenyl)quinazolin-4(3H)-one; and

2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)phenoxy)acetamide.

27. The compound according to claim 24 , wherein R 7 is selected from amide and amino.

28. The compound according to claim 27 , wherein the compound of Formula II is selected from:

5,7-dimethoxy-2-(4-(4-methylpiperazin-1-yl)phenyl)quinazolin-4(3H)-one;

2-(4-(bis(2-hydroxyethyl)amino)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one;

5,7-dimethoxy-2-(4-morpholinophenyl)quinazolin-4(3H)-one;

N-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)phenyl)-2-hydroxyacetamide; and

2-(4-(bis(2-hydroxyethyl)amino)phenyl)-5,7-dimethoxy-pyrido[2,3-d]pyrimidin -4(3H)one.

29. The compound according to claim 24 , wherein R 7 is alkyl.

30. The compound according to claim 29 , wherein the compound of Formula II is selected from:

3-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)phenyl)propanoic acid;

5,7-dimethoxy-2-(4-((4-methylpiperazin-1-yl)methyl)phenyl)quinazolin-4(3H)-one;

5,7-dimethoxy-2-(4-(morpholinomethyl)phenyl)quinazolin-4(3H)-one; and

2-(4-((4-ethylpiperazin-1-yl)methyl)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one.

31. The compound according to claim 24 , wherein R 6 and R 8 are each independently alkyl.

32. The compound according to claim 24 , wherein R 7 is selected from an amino or an alkoxy selected from the group represented by Formula III:

wherein:

A is selected from O and N;

n is selected from 0, 1, 2, 3, 4 and 5;

B is selected from —C(O)N(R h ) 2 —, —S(O) 2 N(R h ) 2 —, —C(O)—, —S(O) 2 —, —C(O)O—, wherein each R h is selected from alkyl, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl, haloalkyl, heteroaryl, heterocyclyl, and hydrogen; and

R 20 is selected from (C 1 -C 6 ) alkyl, (C 1 -C 6 ) alkenyl, (C 1 -C 6 ) alkynyl, aryl, arylalkyl, cycloalkyl, haloalkyl, heteroaryl, heterocyclyl, and hydrogen.

33. The compound according to claim 32 , wherein R 6 and R 8 are each independently alkyl.

34. A pharmaceutical composition comprising a compound according to any one of claims 24 - 33 and a pharmaceutically acceptable carrier.

Assignments (11)
CORRECTIVE ASSIGNMENT TO CORRECT THE RECEIVING PARTY DATA PREVIOUSLY RECORDED ON REEL 058655 FRAME 0643. ASSIGNOR(S) HEREBY CONFIRMS THE SECURITY INTEREST. Recorded Jan 27, 2022
From: RESVERLOGIX CORP.
To: HEPALINK (HONG KONG) LIMITED
Reel/Frame 058887/0288 →
SECURITY INTEREST Recorded Jan 14, 2022
From: RESVERLOGIX CORP.
To: HEPALINK (HONG KONG) LIMITED
Reel/Frame 058655/0643 →
RELEASE OF SECURITY INTEREST Recorded Jan 12, 2021
From: VISION LEADER LIMITED
To: RESVERLOGIX CORP.
Reel/Frame 054888/0506 →
RELEASE OF SECURITY INTEREST Recorded Oct 17, 2019
From: THIRD EYE CAPITAL CORPORATION
To: RESVERLOGIX CORP.
Reel/Frame 050763/0175 →
SECURITY INTEREST Recorded Sep 27, 2019
From: RESVERLOGIX CORP.
To: VISION LEADER LIMITED
Reel/Frame 050518/0714 →
CHANGE OF ADDRESS Recorded Aug 28, 2019
From: RESVERLOGIX CORP.
To: RESVERLOGIX CORP.
Reel/Frame 050206/0465 →
SECURITY INTEREST Recorded Jun 14, 2018
From: RESVERLOGIX CORP.
To: THIRD EYE CAPITAL CORPORATION
Reel/Frame 046090/0103 →
RELEASE OF SECURITY INTEREST Recorded Dec 12, 2017
From: CAMBRIDGE BAY FINANCE LTD.
To: RESVERLOGIX CORP.
Reel/Frame 044368/0868 →
RELEASE OF SECURITY INTEREST Recorded Dec 12, 2017
From: EASTERN CAPITAL LIMITED
To: RESVERLOGIX CORP.
Reel/Frame 044368/0856 →
SECURITY INTEREST Recorded Sep 14, 2017
From: RESVERLOGIX CORP.
To: CAMBRIDGE BAY FINANCE LTD.
Reel/Frame 043592/0343 →
AMENDED AND RESTATED PATENT SECURITY AGREEMENT Recorded Jul 7, 2014
From: RESVERLOGIX CORP.
To: EASTERN CAPITAL LIMITED
Reel/Frame 033279/0137 →