US2022008418A1PendingUtilityA1
Aminoquinoline Derivatives and Uses Thereof
Est. expiryMar 7, 2032(~5.6 yrs left)· nominal 20-yr term from priority
Inventors:Diwan S. RawatSunny ManoharUmmadisetty Chinna RajeshDeepak KumarAnuj ThakurMohit TripathiPanyala Linga ReddyShamseer Kulangara KandiSatyapavan VardhineniKwang Soo KimChun-Hyung Kim
C07D 401/14C07D 401/12A61P 29/00A61P 31/00A61K 31/5377A61K 31/506A61K 31/5355A61P 25/28C12N 5/0619Y02A50/30A61K 45/06C12N 2506/02
59
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Claims
Abstract
Described herein are aminoquinoline and aminoacridine based hybrids, pharmaceutical compositions and medicaments that include such aminoquinoline and aminoacridine based hybrids, and methods of using such compounds for diagnosing and/or treating infections, neurodegerative diseases or disorders, inflammation, inflammation associated diseases and disorders, and/or diseases or disorders that are treatable with dopamine agonists such as the restless leg syndrome.
Claims
exact text as granted — not AI-modified1 . A method of ameliorating symptoms of Alzheimer's disease, the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound selected from the group consisting of Formula (I)-Formula(X) and any pharmaceutically acceptable salt, hydrate, solvate, ester, stereoisomer mixture, or enantiomer thereof, where
wherein:
X, Y, and Z are independently CR 18 , N, O, or S;
one of Z 1 and Z 2 is N and the other is CR 14 ;
R 10 -R 18 are each independently H, linear or branched alkyl, linear or branched alkenyl, linear or branched alkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halogen, trifluoromethyl, alkoxy, nitro, cyano, carbonyl, hydroxyl, phenoxy, amino, alkylamino, thiol, or alkylthio, each of which can be optionally substituted; and
L is a linker
wherein:
X and Y are independently CR 18 , N, O, or S;
one of Z 1 and Z 2 is N and the other is CR 14 ;
R 11 -R 18 are independently H, linear or branched alkyl, linear or branched alkenyl, linear or branched alkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halogen, trifluoromethyl, alkoxy, nitro, cyano, carbonyl, hydroxyl, phenoxy, amino, alkylamino, thiol, or alkylthio, each of which can be optionally substituted;
----- forms a cyclyl, heterocyclyl, aryl, or heteroaryl, each of which can be optionally substituted; and
L is a linker;
wherein:
A and B are independently CR 18 or N;
one of Z 1 and Z 2 is N and the other is CR 14 ;
R and R 10 -R 18 are independently H, linear or branched alkyl, linear or branched alkenyl, linear or branched alkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halogen, trifluoromethyl, -alkoxy, nitro, cyano, carbonyl, hydroxyl, phenoxy, amino, alkylamino, thiol, or alkylthio, each of which can be optionally substituted; and
L is a linker;
wherein:
X and Z are independently CR 18 , N, O, or S;
one of Z 1 and Z 2 is N and the other is CR 14 ;
R 11 -R 18 are independently H, linear or branched alkyl, linear or branched alkenyl, linear or branched alkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halogen, trifluoromethyl, alkoxy, nitro, cyano, carbonyl, hydroxyl, phenoxy, amino, alkylamino, thiol, or alkylthio, each of which can be optionally substituted;
----- forms a cyclyl, heterocyclyl, aryl, or heteroaryl, each of which can be optionally substituted; and
L is a linker;
wherein:
X, Y, and Z are independently CR 18 , N, O, or S;
one of Z 1 and Z 2 is N and the other is CR 14 ;
R 10 -R 18 are independently H, linear or branched alkyl, linear or branched alkenyl, linear or branched alkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halogen, trifluoromethyl, -alkoxy, nitro, cyano, carbonyl, hydroxyl, phenoxy, amino, alkylamino, thiol, or alkylthio, each of which can be optionally substituted; and
----- forms a cyclyl, heterocyclyl, aryl, or heteroaryl, each of which can be optionally substituted;
wherein:
X, Y, and Z are independently CR 18 , N, O, or S;
R 10 , R 11 , R 18 and R 21 -R 28 are independently H, linear or branched alkyl, linear or branched alkenyl, linear or branched alkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halogen, trifluoromethyl, alkoxy, nitro, cyano, carbonyl, hydroxyl, phenoxy, amino, alkylamino, thiol, or alkylthio, each of which can be optionally substituted;
----- forms a cyclyl, heterocyclyl, aryl, or heteroaryl, each of which can be optionally substituted; and
L is a linker;
wherein:
X, Y, and Z are independently CR 18 , N, O, or S;
one of Z 1 and Z 2 is N and the other is CR 14 ;
R 10 -R 22 are independently H, linear or branched alkyl, linear or branched alkenyl, linear or branched alkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halogen, trifluoromethyl, alkoxy, nitro, cyano, carbonyl, hydroxyl, phenoxy, amino, alkylamino, thiol, or alkylthio, each of which can be optionally substituted.
wherein:
X, Y, and Z are independently CR 18 , N, O, or S;
one of Z 1 and Z 2 is N and the other is CR 14 ;
R 10 -R 21 are independently H, linear or branched alkyl, linear or branched alkenyl, linear or branched alkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halogen, trifluoromethyl, alkoxy, nitro, cyano, carbonyl, hydroxyl, phenoxy, amino, alkylamino, thiol, or alkylthio, each of which can be optionally substituted;
wherein:
X, Y, and Z are independently CR 18 , N, O, or S;
one of Z 1 and Z 2 is N and the other is CR 14 ;
R 10 -R 22 are independently H, linear or branched alkyl, linear or branched alkenyl, linear or branched alkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halogen, trifluoromethyl, alkoxy, nitro, cyano, carbonyl, hydroxyl, phenoxy, amino, alkylamino, thiol, or alkylthio, each of which can be optionally substituted;
wherein:
R is hydrogen, CH 3 , Cl, CF 3 or CN;
R 1 is cyclic or acyclic amine; and
L is an optionally substituted C 2 -C 30 alkyl, optionally substituted aromatic ring, optionally substituted heteroaryl ring, saturated cyclic ring; amino acid, or peptide.
2 . (canceled)
3 . A method of treating inflammation or inflammation associated disease or disorder in a subject, the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound selected from the group consisting of Formula (I)-Formula(X) and any pharmaceutically acceptable salt, hydrate, solvate, ester, stereoisomer mixture, or enantiomer thereof, where
wherein:
X, Y, and Z are independently CR 18 , N, O, or S;
one of Z 1 and Z 2 is N and the other is CR 14 ;
R 10 -R 18 are independently H, linear or branched alkyl, linear or branched alkenyl, linear or branched alkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halogen, trifluoromethyl, alkoxy, nitro, cyano, carbonyl, hydroxyl, phenoxy, amino, alkylamino, thiol, or alkylthio, each of which can be optionally substituted; and
L is a linker
wherein:
X and Y are independently CR 18 , N, O, or S;
one of Z 1 and Z 2 is N and the other is CR 14 ;
R 11 -R 18 are independently H, linear or branched alkyl, linear or branched alkenyl, linear or branched alkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halogen, trifluoromethyl, alkoxy, nitro, cyano, carbonyl, hydroxyl, phenoxy, amino, alkylamino, thiol, or alkylthio, each of which can be optionally substituted;
----- forms a cyclyl, heterocyclyl, aryl, or heteroaryl, each of which can be optionally substituted; and
L is a linker;
wherein:
A and B are independently CR 18 or N;
one of Z 1 and Z 2 is N and the other is CR 14 ;
R 10 -R 18 are independently H, linear or branched alkyl, linear or branched alkenyl, linear or branched alkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halogen, trifluoromethyl, alkoxy, nitro, cyano, carbonyl, hydroxyl, phenoxy, amino, alkylamino, thiol, or alkylthio, each of which can be optionally substituted; and
L is a linker;
wherein:
X and Z are independently CR 18 , N, O, or S;
one of Z 1 and Z 2 is N and the other is CR 14 ;
R 11 -R 18 are independently H, linear or branched alkyl, linear or branched alkenyl, linear or branched alkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halogen, trifluoromethyl, alkoxy, nitro, cyano, carbonyl, hydroxyl, phenoxy, amino, alkylamino, thiol, or alkylthio, each of which can be optionally substituted;
----- forms a cyclyl, heterocyclyl, aryl, or heteroaryl, each of which can be optionally substituted; and
L is a linker;
wherein:
X, Y, and Z are independently CR 18 , N, O, or S;
one of Z 1 and Z 2 is N and the other is CR 14 ;
R 10 -R 18 are independently H, linear or branched alkyl, linear or branched alkenyl, linear or branched alkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halogen, trifluoromethyl, alkoxy, nitro, cyano, carbonyl, hydroxyl, phenoxy, amino, alkylamino, thiol, or alkylthio, each of which can be optionally substituted; and
----- forms a cyclyl, heterocyclyl, aryl, or heteroaryl, each of which can be optionally substituted;
wherein:
X, Y, and Z are independently CR 18 , N, O, or S;
R 10 , R 11 , R 18 and R 21 -R 28 are independently H, linear or branched alkyl, linear or branched alkenyl, linear or branched alkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halogen, trifluoromethyl, alkoxy, nitro, cyano, carbonyl, hydroxyl, phenoxy, amino, alkylamino, thiol, or alkylthio, each of which can be optionally substituted;
----- forms a cyclyl, heterocyclyl, aryl, or heteroaryl, each of which can be optionally substituted; and
L is a linker;
wherein:
X, Y, and Z are independently CR 18 , N, O, or S;
one of Z 1 and Z 2 is N and the other is CR 14 ;
R 10 -R 22 are independently H, linear or branched alkyl, linear or branched alkenyl, linear or branched alkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halogen, trifluoromethyl, alkoxy, nitro, cyano, carbonyl, hydroxyl, phenoxy, amino, alkylamino, thiol, or alkylthio, each of which can be optionally substituted.
wherein:
X, Y, and Z are independently CR 18 , N, O, or S;
one of Z 1 and Z 2 is N and the other is CR 14 ;
R 10 -R 21 are independently H, linear or branched alkyl, linear or branched alkenyl, linear or branched alkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halogen, trifluoromethyl, alkoxy, nitro, cyano, carbonyl, hydroxyl, phenoxy, amino, alkylamino, thiol, or alkylthio, each of which can be optionally substituted;
wherein:
X, Y, and Z are independently CR 18 , N, O, or S;
one of Z 1 and Z 2 is N and the other is CR 14 ;
R 10 -R 22 are independently H, linear or branched alkyl, linear or branched alkenyl, linear or branched alkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halogen, trifluoromethyl, alkoxy, nitro, cyano, carbonyl, hydroxyl, phenoxy, amino, alkylamino, thiol, or alkylthio, each of which can be optionally substituted;
wherein:
R is hydrogen, CH 3 , Cl, CF 3 or CN;
R 1 is cyclic or acyclic amine; and
L is an optionally substituted C 2 -C 30 alkyl, optionally substituted aromatic ring, optionally substituted heteroaryl ring, saturated cyclic ring; amino acid, or peptide.
4 - 9 . (canceled)
10 . A method for inducing differentiation of a stem cell into a dopaminergic neuron, the method comprising contacting said cell with a compound selected from the group consisting of Formula (I)-Formula(X) in an amount sufficient to cause differentiation of said stem cell, where
wherein:
X, Y, and Z are independently CR 18 , N, O, or S;
one of Z 1 and Z 2 is N and the other is CR 14 ;
R 10 -R 18 are independently H, linear or branched alkyl, linear or branched alkenyl, linear or branched alkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halogen, trifluoromethyl, alkoxy, nitro, cyano, carbonyl, hydroxyl, phenoxy, amino, alkylamino, thiol, or alkylthio, each of which can be optionally substituted; and
L is a linker
wherein:
X and Y are independently CR 18 , N, O, or S;
one of Z 1 and Z 2 is N and the other is CR 14 ;
R 11 -R 18 are independently H, linear or branched alkyl, linear or branched alkenyl, linear or branched alkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halogen, trifluoromethyl, alkoxy, nitro, cyano, carbonyl, hydroxyl, phenoxy, amino, alkylamino, thiol, or alkylthio, each of which can be optionally substituted;
----- forms a cyclyl, heterocyclyl, aryl, or heteroaryl, each of which can be optionally substituted; and
L is a linker;
wherein:
A and B are independently CR 18 or N;
one of Z 1 and Z 2 is N and the other is CR 14 ;
R 10 -R 18 are independently H, linear or branched alkyl, linear or branched alkenyl, linear or branched alkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halogen, trifluoromethyl, alkoxy, nitro, cyano, carbonyl, hydroxyl, phenoxy, amino, alkylamino, thiol, or alkylthio, each of which can be optionally substituted; and
L is a linker;
wherein:
X and Z are independently CR 18 , N, O, or S;
one of Z 1 and Z 2 is N and the other is CR 14 ;
R 11 -R 18 are independently H, linear or branched alkyl, linear or branched alkenyl, linear or branched alkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halogen, trifluoromethyl, alkoxy, nitro, cyano, carbonyl, hydroxyl, phenoxy, amino, alkylamino, thiol, or alkylthio, each of which can be optionally substituted;
----- forms a cyclyl, heterocyclyl, aryl, or heteroaryl, each of which can be optionally substituted; and
L is a linker;
wherein:
X, Y, and Z are independently CR 18 , N, O, or S;
one of Z 1 and Z 2 is N and the other is CR 14 ;
R 10 -R 18 are independently H, linear or branched alkyl, linear or branched alkenyl, linear or branched alkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halogen, trifluoromethyl, alkoxy, nitro, cyano, carbonyl, hydroxyl, phenoxy, amino, alkylamino, thiol, or alkylthio, each of which can be optionally substituted; and
----- forms a cyclyl, heterocyclyl, aryl, or heteroaryl, each of which can be optionally substituted;
wherein:
X, Y, and Z are independently CR 18 , N, O, or S;
R 10 , R 11 , R 18 and R 21 -R 28 are independently H, linear or branched alkyl, linear or branched alkenyl, linear or branched alkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halogen, trifluoromethyl, alkoxy, nitro, cyano, carbonyl, hydroxyl, phenoxy, amino, alkylamino, thiol, or alkylthio, each of which can be optionally substituted;
----- forms a cyclyl, heterocyclyl, aryl, or heteroaryl, each of which can be optionally substituted; and
L is a linker;
wherein:
X, Y, and Z are independently CR 18 , N, O, or S;
one of Z 1 and Z 2 is N and the other is CR 14 ;
R 10 -R 22 are independently H, linear or branched alkyl, linear or branched alkenyl, linear or branched alkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halogen, trifluoromethyl, alkoxy, nitro, cyano, carbonyl, hydroxyl, phenoxy, amino, alkylamino, thiol, or alkylthio, each of which can be optionally substituted.
wherein:
X, Y, and Z are independently CR 18 , N, O, or S;
one of Z 1 and Z 2 is N and the other is CR 14 ;
R 10 -R 21 are independently H, linear or branched alkyl, linear or branched alkenyl, linear or branched alkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halogen, trifluoromethyl, alkoxy, nitro, cyano, carbonyl, hydroxyl, phenoxy, amino, alkylamino, thiol, or alkylthio, each of which can be optionally substituted;
wherein:
X, Y, and Z are independently CR 18 , N, O, or S;
one of Z 1 and Z 2 is N and the other is CR 14 ;
R 10 -R 22 are independently H, linear or branched alkyl, linear or branched alkenyl, linear or branched alkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halogen, trifluoromethyl, alkoxy, nitro, cyano, carbonyl, hydroxyl, phenoxy, amino, alkylamino, thiol, or alkylthio, each of which can be optionally substituted;
wherein:
R is hydrogen, CH 3 , Cl, CF 3 or CN;
R 1 is cyclic or acyclic amine; and
L is an optionally substituted C 2 -C 30 alkyl, optionally substituted aromatic ring, optionally substituted heteroaryl ring, saturated cyclic ring; amino acid, or peptide.
11 . (canceled)
12 . The method of claim 1 , wherein the compound is selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
13 . The method of claim 1 , comprising co-administering to the subject a composition comprising stem cells, wherein an amount of the compound is sufficient to induce differentiation of the stem cells.
14 . The method of claim 13 , wherein the stem cells are human embryonic stem cells.
15 . The method of claim 1 , wherein the compound is selected from any one of the following compounds
or any pharmaceutically acceptable salt, hydrate, solvate, ester, stereoisomer mixture, or enantiomer thereof.
16 . The method of claim 15 , wherein the compound has formula:
or any pharmaceutically acceptable salt, hydrate, solvate, ester, stereoisomer mixture, or enantiomer thereof.
17 . The method of claim 15 , wherein the compound has formula:
or any pharmaceutically acceptable salt, hydrate, solvate, ester, stereoisomer mixture, or enantiomer thereof.
18 . The method of claim 15 , wherein the compound has formula:
or any pharmaceutically acceptable salt, hydrate, solvate, ester, stereoisomer mixture, or enantiomer thereof.
19 . The method of claim 15 , wherein the compound has formula:
or any pharmaceutically acceptable salt, hydrate, solvate, ester, stereoisomer mixture, or enantiomer thereof.
20 . The method of claim 15 , wherein the compound has formula:
or any pharmaceutically acceptable salt, hydrate, solvate, ester, stereoisomer mixture, or enantiomer thereof.
21 . A compound selected from the group consisting of:
or any pharmaceutically acceptable salt, hydrate, solvate, ester, stereoisomer mixture, or enantiomer thereof.
22 . The compound of claim 21 , having formula:
or any pharmaceutically acceptable salt, hydrate, solvate, ester, stereoisomer mixture, or enantiomer thereof.
23 . The compound of claim 21 , having formula:
or any pharmaceutically acceptable salt, hydrate, solvate, ester, stereoisomer mixture, or enantiomer thereof.
24 . The compound of claim 21 , having formula:
or any pharmaceutically acceptable salt, hydrate, solvate, ester, stereoisomer mixture, or enantiomer thereof.
25 . The compound of claim 21 , having formula:
or any pharmaceutically acceptable salt, hydrate, solvate, ester, stereoisomer mixture, or enantiomer thereof.Cited by (0)
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