Fused Pentacyclic Polyethers
AssigneeUniversity of North Carolina at Wilmington
InventorsDaniel Baden, William Abraham, Andrea Bourdelais
Life of this patent
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Abstract
Disclosed are polycyclic polyether compounds of formula I and pharmaceutical compositions comprising such compounds. wherein R, OR1, and R2 are as defined herein. Also disclosed are methods of regulating mucus clearance in a cell, and methods of treating decreased mucus clearance or mucociliary dysfunction.
Claims13
1-6. (canceled)
A method of treating mucociliary dysfunction in a subject comprising administering to a subject in need of such treatment a therapeutically effective amount of a compound or pharmaceutically acceptable salts, solvates, esters, amides, or isomers thereof ;
- wherein the compound has the formula:
- wherein
- R is C1-C12 alkyl, C2-C12 alkenyl, C1-C12 alkyl esters,
- C1-C12 alkyl amides, C4-C22 alkenyl esters,
- C1-C12 alkylaryl esters, C4-C12 alkenylaryl esters,
- C4-C12 alkenyl amides, C1-C12 alkoxy, formylC1-C12alkyl,
- formylC2-C12alkenyl, alkanoylC1-C12alkyl,
- alkanoylC2-C12alkenyl, carboxyC1-C12alkyl, or
- carboxyC2-C12alkenyl, wherein the alkyl and alkenyl groups are optionally substituted with 1-6 substituent groups selected from the group consisting of:
- C3-C12 cycloalkyl, C3-C12 heterocyclyl, aryl, heteroaryl, C1-C6 alkyl, C1-C6 alkoxy, halogen,
- C2-C6 alkenyl, OH,
- aryl esters, cycloalkyl esters, cycloalkenyl esters, and
- OR1 is OH or —O(CO)CH3;
- R2 is —CH═CHCH═CH2, —CH2-phenyl, or —CH2-pyridyl, wherein the phenyl and pyridyl groups are optionally substituted at each substitutable position with a group that is independently C1-C6 alkyl, C1-C6 alkoxy, haloalkyl, haloalkoxy, hydroxy, hydroxyalkyl, halogen, —CO2H,
- C1-C6 alkoxycarbonyl, —C(O)NH2, —C(O)NH(C1-C6 alkyl), or
- —C(O)N(C1-C6 alkyl) (C1-C6 alkyl).
(canceled)
A method of treating, preventing, or treating and preventing diseases associated with decreased mucus clearance in a mammal comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound, or pharmaceutically acceptable salts, solvates, esters, amides, or isomers thereof ;
- wherein the compound has the formula:
- wherein
- R is C1-C12 alkyl, C2-C12 alkenyl, C1-C12 alkyl esters,
- C1-C12 alkyl amides, C4-C22 alkenyl esters,
- C1-C12 alkylaryl esters, C4-C12 alkenylaryl esters,
- C4-C12 alkenyl amides, C1-C12 alkoxy, formylC1-C12alkyl,
- formylC2-C12alkenyl, alkanoylC1-C12alkyl,
- alkanoylC2-C12alkenyl, carboxyC1-C12alkyl, or
- carboxyC2-C12alkenyl, wherein the alkyl and alkenyl groups are optionally substituted with 1-6 substituent groups selected from the group consisting of:
- C3-C12 cycloalkyl, C3-C12 heterocyclyl, aryl,
- heteroaryl, C1-C6 alkyl, C1-C6 alkoxy, halogen,
- C2-C6 alkenyl, OH,
- aryl esters, cycloalkyl esters, cycloalkenyl esters, and
- OR1 is OH or —O(CO)CH3;
- R2 is —CH═CHCH═CH2, —CH2-phenyl, or —CH2-pyridyl, wherein the phenyl and pyridyl groups are optionally substituted at each substitutable position with a group that is independently C1-C6 alkyl, C1-C6 alkoxy, haloalkyl, haloalkoxy, hydroxy, hydroxyalkyl, halogen, —CO2H,
- C1-C6 alkoxycarbonyl, —C(O)NH2, —C(O)NH(C1-C6 alkyl), or
- —C(O)N(C1-C6 alkyl) (C1-C6 alkyl).
(canceled)
A method of treating diseases associated with decreased mucus clearance in a mammal comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound, or pharmaceutically acceptable salts, solvates, esters, amides, or isomers thereof;
- wherein the compound has the formula:
- wherein
- R is C1-C12 alkyl, C2-C12 alkenyl, C1-C12 alkyl esters,
- C1-C12 alkyl amides, C4-C22 alkenyl esters,
- C1-C12 alkylaryl esters, C4-C12 alkenylaryl esters,
- C4-C12 alkenyl amides, C1-C12 alkoxy, formylC1-C12alkyl,
- formylC2-C12alkenyl, alkanoylC1-C12alkyl,
- alkanoylC2-C12alkenyl, carboxyC1-C12alkyl, or
- carboxyC2-C12alkenyl, wherein the alkyl and alkenyl groups are optionally substituted with 1-6 substituent groups selected from the group consisting of:
- C3-C12 cycloalkyl, C3-C12 heterocyclyl, aryl, heteroaryl, C1-C6 alkyl, C1-C6 alkoxy, halogen,
- C2-C6 alkenyl, OH,
- aryl esters, cycloalkyl esters, cycloalkenyl esters, and
- OR1 is OH or —O(CO)CH3;
- R2 is —CH═CHCH═CH2, —CH2-phenyl, or —CH2-pyridyl, wherein the phenyl and pyridyl groups are optionally substituted at each substitutable position with a group that is independently C1-C6 alkyl, C1-C6 alkoxy, haloalkyl, haloalkoxy, hydroxy, hydroxyalkyl, halogen, —CO2H,
- C1-C6 alkoxycarbonyl, —C(O)NH2, —C(O)NH(C1-C6 alkyl), or
- —C(O)N(C1-C6 alkyl) (C1-C6 alkyl).
(canceled)
A method of treating a subject who has, or is at increased risk of developing chronic obstructive pulmonary disease, asthma, pulmonary disease, pulmonary infection, or cystic fibrosis, comprising administering to a subject in need of such treatment a therapeutically effective amount of a compound, or pharmaceutically acceptable salts, solvates, esters, amides, or isomers thereof;
- wherein the compound has the formula:
- wherein
- R is C1-C12 alkyl, C2-C12 alkenyl, C1-C12 alkyl esters,
- C1-C12 alkyl amides, C4-C22 alkenyl esters,
- C1-C12 alkylaryl esters, C4-C12 alkenylaryl esters,
- C4-C12 alkenyl amides, C1-C12 alkoxy, formylC1-C12alkyl,
- formylC2-C12alkenyl, alkanoylC1-C12alkyl,
- alkanoylC2-C12alkenyl, carboxyC1-C12alkyl, or
- carboxyC2-C12alkenyl, wherein the alkyl and alkenyl groups are optionally substituted with 1-6 substituent groups selected from the group consisting of:
- C3-C12 cycloalkyl, C3-C12 heterocyclyl, aryl, heteroaryl, C1-C6 alkyl, C1-C6 alkoxy, halogen,
- C2-C6 alkenyl, OH,
- aryl esters, cycloalkyl esters, cycloalkenyl esters, and
- OR1 is OH or —O(CO)CH3;
- R2 is —CH═CHCH═CH2, —CH2-phenyl, or —CH2-pyridyl, wherein the phenyl and pyridyl groups are optionally substituted at each substitutable position with a group that is independently C1-C6 alkyl, C1-C6 alkoxy, haloalkyl, haloalkoxy, hydroxy, hydroxyalkyl, halogen, —CO2H,
- C1-C6 alkoxycarbonyl, —C(O)NH2, —C(O)NH(C1-C6 alkyl), or
- —C(O)N(C1-C6 alkyl) (C1-C6 alkyl).
16-22. (canceled)
A method of treatment according to claim 24, wherein the method is for treating an industrial disease, and the industrial disease is caused or exacerbated by inhaling gases, particles of textiles, grit, or other industrial particles or fumes.
A method of treating brevetoxin or ciguatoxin poisoning, an industrial disease, or a disease or condition that results from inhalation of bacterial or other pathogenic particles comprising administering a pharmaceutically acceptable amount of a compound, or pharmaceutically acceptable salts, solvates, esters, amides, or isomers thereof, to a subject in need of such treatment;
- wherein the compound has the formula:
- wherein
- R is C1-C12 alkyl, C2-C12 alkenyl, C1-C12 alkyl esters,
- C1-C12 alkyl amides, C4-C22 alkenyl esters,
- C1-C12 alkylaryl esters, C4-C12 alkenylaryl esters,
- C4-C12 alkenyl amides, C1-C12 alkoxy, formylC1-C12alkyl,
- formylC2-C12alkenyl, alkanoylC1-C12alkyl,
- alkanoylC2-C12alkenyl, carboxyC1-C12alkyl, or
- carboxyC2-C12alkenyl, wherein the alkyl and alkenyl groups are optionally substituted with 1-6 substituent groups selected from the group consisting of:
- C3-C12 cycloalkyl, C3-C12 heterocyclyl, aryl, heteroaryl, C1-C6 alkyl, C1-C6 alkoxy, halogen,
- C2-C6 alkenyl, OH,
- aryl esters, cycloalkyl esters, cycloalkenyl esters, and
- OR1 is OH or —O(CO)CH3;
- R2 is —CH═CHCH═CH2, —CH2-phenyl, or —CH2-pyridyl, wherein the phenyl and pyridyl groups are optionally substituted at each substitutable position with a group that is independently C1-C6 alkyl, C1-C6 alkoxy, haloalkyl, haloalkoxy, hydroxy, hydroxyalkyl, halogen, —CO2H,
- C1-C6 alkoxycarbonyl, —C(O)NH2, —C(O)NH(C1-C6 alkyl), or
- —C(O)N(C1-C6 alkyl) (C1-C6 alkyl).
Dependencies are inferred from the claim text.