Compositions for sleeping disorders

• US 20050261167A1
• Filed: 05/13/2005
• Published: 11/24/2005
• Est. Priority Date: 05/18/2004
• Status: Active Grant

• Current Assignee: Bright Future Pharmaceutical Laboratories Ltd.
• Original Assignee: Bright Future Pharmaceutical Laboratories Ltd.
• Inventors: Rowlands, Dewi Kenneth, Chan, Hsiao Chang, Gou, Yu Lin, Chung, Yiu Wa
• Granted Patent: US 7,935,714 B2
• Time in Patent Office: Days
• US Class Current: 514/312
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/352 condensed with carbocyclic rings, e.g. methantheline cannabinoids A61K31/658
• CPC Class Codes: A61K 31/353 3,4-Dihydrobenzopyrans, e.g. chroman, catechin
• CPC Class Codes: A61K 31/452 Piperidinium derivatives pancuronium A61K31/58
• CPC Class Codes: A61K 31/4709 Non-condensed quinolines and containing further heterocyclic rings
• CPC Class Codes: A61K 31/7048 having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin , digitoxin or digoxin
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 21/02 Muscle relaxants, e.g. for tetanus or cramps
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics

Abstract

Provided herein is a composition that contains an effective amount of one or more compounds for treating, preventing, or ameliorating a disorder such as insomnia or another sleeping disorder and using the composition.

Claims

6. A composition comprising an effective amount of at least two compounds as defined in formulae I, II, or IV,

wherein the composition is effective for treating a disorder selected from the group consisting of insomnia, depression-related disease, stress-related disease, depression-related sleep disorder, neurodegeneration diseases, Alzheimer'"'"'s disease, Pick'"'"'s disease, spinocerbellar degeneration, Parkinson'"'"'s disease, chorea, glaucoma, amyotrophic lateral sclerosis, senile macular degeneration, hepatic encephalopathy, demyelinating diseases, Lewy body dementia, multi-infarct dementia, multiple sclerosis and combinations thereof,

wherein the compound of formulae I or II has a structure of

in which:

R₁, R₂, and R₁₂ taken independently can be absence, hydrogen, halo, alkyl, substituted alkyl, alkoxy, cycloalkyl, heterocyclic, alkenyl alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, phenyl, substituted phenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, hydroxyl, alkoxy, substituted alkoxy, phenoxy, substituted phenoxy, aroxy, substituted aroxy, thiol, alkylthio, substituted alkylthio, phenylthio, substituted phenylthio, arylthio, substituted arylthio, cyano, isocyano, substituted isocyano, carbonyl, substituted carbonyl, carboxyl, substituted carboxyl, amino, substituted amino, amido, substituted amido, fulfonyl, substituted sulfonyl, polyaryl, substituted polyaryl, C1-C20 cyclic, substituted C1-C20 cyclic, heterocyclic, substituted heterocyclic, amino acid, peptide, polyether, polyester, polypeptide, protein, polyphosphazene, polyalkylene oxide, polyalkylene glycol, polyethylene glycol, polyalkylene, a bioactive agent, or a drug molecule;

R₃, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀, R₁₁, R₁₃ and R₂₀ taken independently can be hydrogen, halo, alkyl, substituted alkyl, alkoxy, cycloalkyl, heterocyclic, alkenyl alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, phenyl, substituted phenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, hydroxyl, alkoxy, substituted alkoxy, phenoxy, substituted phenoxy, aroxy, substituted aroxy, thiol, alkylthio, substituted alkylthio, phenylthio, substituted phenylthio, arylthio, substituted arylthio, cyano, isocyano, substituted isocyano, carbonyl, substituted carbonyl, carboxyl, substituted carboxyl, amino, substituted amino, amido, substituted amido, fulfonyl, substituted sulfonyl, polyaryl, substituted polyaryl, C1-C20 cyclic, substituted C1-C20 cyclic, heterocyclic, substituted heterocyclic, amino acid, peptide, polyether, polyester, polypeptide, protein, polyphosphazene, polyalkylene oxide, polyalkylene glycol, polyethylene glycol, polyalkylene, a bioactive agent, or a drug molecule;

Z₁, Z₂ and Z₃ taken independently can be oxygen (O), sulphur (S), or NH;

Z₁ and R₁ taken together can be a moiety of formula III;

where

R₁₄, R₁₅, R₁₆, R₁₇, R₁₈ and R₁₉ taken independently can be hydrogen, halo, alkyl, substituted alkyl, alkoxy, cycloalkyl, heterocyclic, alkenyl alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, phenyl, substituted phenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, hydroxyl, alkoxy, substituted alkoxy, phenoxy, substituted phenoxy, aroxy, substituted aroxy, thiol, alkylthio, substituted alkylthio, phenylthio, substituted phenylthio, arylthio, substituted arylthio, cyano, isocyano, substituted isocyano, carbonyl, substituted carbonyl, carboxyl, substituted carboxyl, amino, substituted amino, amido, substituted amido, fulfonyl, substituted sulfonyl, polyaryl, substituted polyaryl, C1-C20 cyclic, substituted C1-C20 cyclic, heterocyclic, substituted heterocyclic, amino acid, peptide, polyether, polyester, polypeptide, protein, polyphosphazene, polyalkylene oxide, polyalkylene glycol, polyethylene glycol, polyalkylene, a bioactive agent, or a drug molecule; and

Z₄ can be oxygen (O), sulphur (S), or NH,

wherein the compound of Formula IV has a structure of

in which;

R₁, R₆, and R₈ taken independently can be absence, hydrogen, halo, alkyl, substituted alkyl, alkoxy, cycloalkyl, heterocyclic, alkenyl alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, phenyl, substituted phenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, hydroxyl, alkoxy, substituted alkoxy, phenoxy, substituted phenoxy, aroxy, substituted aroxy, thiol, alkylthio, substituted alkylthio, phenylthio, substituted phenylthio, arylthio, substituted arylthio, cyano, isocyano, substituted isocyano, carbonyl, substituted carbonyl, carboxyl, substituted carboxyl, amino, substituted amino, amido, substituted amido, fulfonyl, substituted sulfonyl, polyaryl, substituted polyaryl, C1-C20 cyclic, substituted C1-C20 cyclic, heterocyclic, substituted heterocyclic, amino acid, peptide, polyether, polyester, polypeptide, protein, polyphosphazene, polyalkylene oxide, polyalkylene glycol, polyethylene glycol, polyalkylene, a bioactive agent, or a drug molecule;

R₂, R₃, R₄, R₅, R₇, R₉, R₁₀, R₁₁, R₁₂ and R₁₃ taken independently can be hydrogen, halo, alkyl, substituted alkyl, alkoxy, cycloalkyl, heterocyclic, alkenyl alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, phenyl, substituted phenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, hydroxyl, alkoxy, substituted alkoxy, phenoxy, substituted phenoxy, aroxy, substituted aroxy, thiol, alkylthio, substituted alkylthio, phenylthio, substituted phenylthio, arylthio, substituted arylthio, cyano, isocyano, substituted isocyano, carbonyl, substituted carbonyl, carboxyl, substituted carboxyl, amino, substituted amino, amido, substituted amido, fulfonyl, substituted sulfonyl, polyaryl, substituted polyaryl, C1-C20 cyclic, substituted C1-C20 cyclic, heterocyclic, substituted heterocyclic, amino acid, peptide, polyether, polyester, polypeptide, protein, polyphosphazene, polyalkylene oxide, polyalkylene glycol, polyethylene glycol, polyalkylene, a bioactive agent, or a drug molecule;

Z₁, Z₂ and Z₃ taken independently can be oxygen (O), sulphur (S), or NH; and

Z₁ and R₁ taken together can be a moiety of formula III;

in which

R₁₃, R₁₄, R₁₅, R₁₆, R₁₇, and R₁₈ taken independently can be hydrogen, halo, alkyl, substituted alkyl, alkoxy, cycloalkyl, heterocyclic, alkenyl alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, phenyl, substituted phenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, hydroxyl, alkoxy, substituted alkoxy, phenoxy, substituted phenoxy, aroxy, substituted aroxy, thiol, alkylthio, substituted alkylthio, phenylthio, substituted phenylthio, arylthio, substituted arylthio, cyano, isocyano, substituted isocyano, carbonyl, substituted carbonyl, carboxyl, substituted carboxyl, amino, substituted amino, amido, substituted amido, fulfonyl, substituted sulfonyl, polyaryl, substituted polyaryl, C1-C20 cyclic, substituted C1-C20 cyclic, heterocyclic, substituted heterocyclic, amino acid, peptide, polyether, polyester, polypeptide, protein, polyphosphazene, polyalkylene oxide, polyalkylene glycol, polyethylene glycol, polyalkylene, a bioactive agent, or a drug molecule.

1. A composition comprising an effective amount of a compound as defined in formulae I, II, or IV,

wherein the composition is effective for treating a disorder selected from the group consisting of insomnia, depression-related disease, stress-related disease, depression-related sleep disorder, neurodegeneration diseases, Alzheimer'"'"'s disease, Pick'"'"'s disease, spinocerbellar degeneration, Parkinson'"'"'s disease, chorea, glaucoma, amyotrophic lateral sclerosis, senile macular degeneration, hepatic encephalopathy, demyelinating diseases, Lewy body dementia, multi-infarct dementia, multiple sclerosis and combinations thereof,

wherein the compound of formulae I or II has a structure of

in which:

R₁, R₂, and R₁₂ taken independently can be absence, hydrogen, halo, alkyl, substituted alkyl, alkoxy, cycloalkyl, heterocyclic, alkenyl alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, phenyl, substituted phenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, hydroxyl, alkoxy, substituted alkoxy, phenoxy, substituted phenoxy, aroxy, substituted aroxy, thiol, alkylthio, substituted alkylthio, phenylthio, substituted phenylthio, arylthio, substituted arylthio, cyano, isocyano, substituted isocyano, carbonyl, substituted carbonyl, carboxyl, substituted carboxyl, amino, substituted amino, amido, substituted amido, fulfonyl, substituted sulfonyl, polyaryl, substituted polyaryl, C1-C20 cyclic, substituted C1-C20 cyclic, heterocyclic, substituted heterocyclic, amino acid, peptide, polyether, polyester, polypeptide, protein, polyphosphazene, polyalkylene oxide, polyalkylene glycol, polyethylene glycol, polyalkylene, a bioactive agent, or a drug molecule;

R₃, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀, R₁₁, R₁₃ and R₂₀ taken independently can be hydrogen, halo, alkyl, substituted alkyl, alkoxy, cycloalkyl, heterocyclic, alkenyl alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, phenyl, substituted phenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, hydroxyl, alkoxy, substituted alkoxy, phenoxy, substituted phenoxy, aroxy, substituted aroxy, thiol, alkylthio, substituted alkylthio, phenylthio, substituted phenylthio, arylthio, substituted arylthio, cyano, isocyano, substituted isocyano, carbonyl, substituted carbonyl, carboxyl, substituted carboxyl, amino, substituted amino, amido, substituted amido, fulfonyl, substituted sulfonyl, polyaryl, substituted polyaryl, C1-C20 cyclic, substituted C1-C20 cyclic, heterocyclic, substituted heterocyclic, amino acid, peptide, polyether, polyester, polypeptide, protein, polyphosphazene, polyalkylene oxide, polyalkylene glycol, polyethylene glycol, polyalkylene, a bioactive agent, or a drug molecule;

Z₁, Z₂ and Z₃ taken independently can be oxygen (O), sulphur (S), or NH;

Z₁ and R₁ taken together can be a moiety of formula III;

where

R₁₄, R₁₅, R₁₆, R₁₇, R₁₈ and R₁₉ taken independently can be hydrogen, halo, alkyl, substituted alkyl, alkoxy, cycloalkyl, heterocyclic, alkenyl alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, phenyl, substituted phenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, hydroxyl, alkoxy, substituted alkoxy, phenoxy, substituted phenoxy, aroxy, substituted aroxy, thiol, alkylthio, substituted alkylthio, phenylthio, substituted phenylthio, arylthio, substituted arylthio, cyano, isocyano, substituted isocyano, carbonyl, substituted carbonyl, carboxyl, substituted carboxyl, amino, substituted amino, amido, substituted amido, fulfonyl, substituted sulfonyl, polyaryl, substituted polyaryl, C1-C20 cyclic, substituted C1-C20 cyclic, heterocyclic, substituted heterocyclic, amino acid, peptide, polyether, polyester, polypeptide, protein, polyphosphazene, polyalkylene oxide, polyalkylene glycol, polyethylene glycol, polyalkylene, a bioactive agent, or a drug molecule; and

Z₄ can be oxygen (O), sulphur (S), or NH,

wherein the compound of Formula II is not myricetin,

wherein the compound of Formula IV has a structure of

in which;

R₁, R_6, and R₈ taken independently can be absence, hydrogen, halo, alkyl, substituted alkyl, alkoxy, cycloalkyl, heterocyclic, alkenyl alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, phenyl, substituted phenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, hydroxyl, alkoxy, substituted alkoxy, phenoxy, substituted phenoxy, aroxy, substituted aroxy, thiol, alkylthio, substituted alkylthio, phenylthio, substituted phenylthio, arylthio, substituted arylthio, cyano, isocyano, substituted isocyano, carbonyl, substituted carbonyl, carboxyl, substituted carboxyl, amino, substituted amino, amido, substituted amido, fulfonyl, substituted sulfonyl, polyaryl, substituted polyaryl, C1-C20 cyclic, substituted C1-C20 cyclic, heterocyclic, substituted heterocyclic, amino acid, peptide, polyether, polyester, polypeptide, protein, polyphosphazene, polyalkylene oxide, polyalkylene glycol, polyethylene glycol, polyalkylene, a bioactive agent, or a drug molecule;

R₂, R₃, R₄, R₅, R₇, R₉, R₁₀, R₁₁, R₁₂ and R₁₃ taken independently can be hydrogen, halo, alkyl, substituted alkyl, alkoxy, cycloalkyl, heterocyclic, alkenyl alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, phenyl, substituted phenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, hydroxyl, alkoxy, substituted alkoxy, phenoxy, substituted phenoxy, aroxy, substituted aroxy, thiol, alkylthio, substituted alkylthio, phenylthio, substituted phenylthio, arylthio, substituted arylthio, cyano, isocyano, substituted isocyano, carbonyl, substituted carbonyl, carboxyl, substituted carboxyl, amino, substituted amino, amido, substituted amido, fulfonyl, substituted sulfonyl, polyaryl, substituted polyaryl, C1-C20 cyclic, substituted C1-C20 cyclic, heterocyclic, substituted heterocyclic, amino acid, peptide, polyether, polyester, polypeptide, protein, polyphosphazene, polyalkylene oxide, polyalkylene glycol, polyethylene glycol, polyalkylene, a bioactive agent, or a drug molecule;

Z₁, Z₂ and Z₃ taken independently can be oxygen (O), sulphur (S), or NH; and

Z₁ and R₁ taken together can be a moiety of formula III;

in which

R₁₃, R₁₄, R₁₅, R₁₆, R₁₇, and R₁₈ taken independently can be hydrogen, halo, alkyl, substituted alkyl, alkoxy, cycloalkyl, heterocyclic, alkenyl alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, phenyl, substituted phenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, hydroxyl, alkoxy, substituted alkoxy, phenoxy, substituted phenoxy, aroxy, substituted aroxy, thiol, alkylthio, substituted alkylthio, phenylthio, substituted phenylthio, arylthio, substituted arylthio, cyano, isocyano, substituted isocyano, carbonyl, substituted carbonyl, carboxyl, substituted carboxyl, amino, substituted amino, amido, substituted amido, fulfonyl, substituted sulfonyl, polyaryl, substituted polyaryl, C1-C20 cyclic, substituted C1-C20 cyclic, heterocyclic, substituted heterocyclic, amino acid, peptide, polyether, polyester, polypeptide, protein, polyphosphazene, polyalkylene oxide, polyalkylene glycol, polyethylene glycol, polyalkylene, a bioactive agent, or a drug molecule.

2. The composition of claim 1, wherein the compound of Formula I is myricitrin.

3. The composition of claim 1, wherein the compound of formula II can be in a racemic form, a mixture of diastero isomers, or an enantiomer.

4. The composition of claim 3, wherein the enantiomer has a structure as shown in formulae IIa, IIb, IIc and IId:

in which;

R₁, R₂, and R₁₂ taken independently can be absence, hydrogen, halo, alkyl, substituted alkyl, alkoxy, cycloalkyl, heterocyclic, alkenyl alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, phenyl, substituted phenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, hydroxyl, alkoxy, substituted alkoxy, phenoxy, substituted phenoxy, aroxy, substituted aroxy, thiol, alkylthio, substituted alkylthio, phenylthio, substituted phenylthio, arylthio, substituted arylthio, cyano, isocyano, substituted isocyano, carbonyl, substituted carbonyl, carboxyl, substituted carboxyl, amino, substituted amino, amido, substituted amido, fulfonyl, substituted sulfonyl, polyaryl, substituted polyaryl, C1-C20 cyclic, substituted C1-C20 cyclic, heterocyclic, substituted heterocyclic, amino acid, peptide, polyether, polyester, polypeptide, protein, polyphosphazene, polyalkylene oxide, polyalkylene glycol, polyethylene glycol, polyalkylene, a bioactive agent, or a drug molecule;

R₃, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀, R₁₁, R₁₃ and R₂₀ taken independently can be hydrogen, halo, alkyl, substituted alkyl, alkoxy, cycloalkyl, heterocyclic, alkenyl alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, phenyl, substituted phenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, hydroxyl, alkoxy, substituted alkoxy, phenoxy, substituted phenoxy, aroxy, substituted aroxy, thiol, alkylthio, substituted alkylthio, phenylthio, substituted phenylthio, arylthio, substituted arylthio, cyano, isocyano, substituted isocyano, carbonyl, substituted carbonyl, carboxyl, substituted carboxyl, amino, substituted amino, amido, substituted amido, fulfonyl, substituted sulfonyl, polyaryl, substituted polyaryl, C1-C20 cyclic, substituted C1-C20 cyclic, heterocyclic, substituted heterocyclic, amino acid, peptide, polyether, polyester, polypeptide, protein, polyphosphazene, polyalkylene oxide, polyalkylene glycol, polyethylene glycol, polyalkylene, a bioactive agent, or a drug molecule;

Z₁, Z₂ and Z₃ taken independently can be oxygen (O), sulphur (S), or NH;

Z₁ and R₁ taken together can be a moiety of formula III;

where

R₁₄, R₁₅, R₁₆, R₁₇, R₁₈ and R₁₉ taken independently can be hydrogen, halo, alkyl, substituted alkyl, alkoxy, cycloalkyl, heterocyclic, alkenyl alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, phenyl, substituted phenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, hydroxyl, alkoxy, substituted alkoxy, phenoxy, substituted phenoxy, aroxy, substituted aroxy, thiol, alkylthio, substituted alkylthio, phenylthio, substituted phenylthio, arylthio, substituted arylthio, cyano, isocyano, substituted isocyano, carbonyl, substituted carbonyl, carboxyl, substituted carboxyl, amino, substituted amino, amido, substituted amido, fulfonyl, substituted sulfonyl, polyaryl, substituted polyaryl, C1-C20 cyclic, substituted C1-C20 cyclic, heterocyclic, substituted heterocyclic, amino acid, peptide, polyether, polyester, polypeptide, protein, polyphosphazene, polyalkylene oxide, polyalkylene glycol, polyethylene glycol, polyalkylene, a bioactive agent, or a drug molecule; and

Z₄ can be oxygen (O), sulphur (S), or NH.

5. The composition of claim 1, wherein the compound of formula II can be a compound of formula IIe:

in which R₁ can be hydrogen, halo, alkyl, substituted alkyl, alkoxy, cycloalkyl, heterocyclic, alkenyl alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, phenyl, substituted phenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, hydroxyl, alkoxy, substituted alkoxy, phenoxy, substituted phenoxy, aroxy, substituted aroxy, thiol, alkylthio, substituted alkylthio, phenylthio, substituted phenylthio, arylthio, substituted arylthio, cyano, isocyano, substituted isocyano, carbonyl, substituted carbonyl, carboxyl, substituted carboxyl, amino, substituted amino, amido, substituted amido, fulfonyl, substituted sulfonyl, polyaryl, substituted polyaryl, C1-C20 cyclic, substituted C1-C20 cyclic, heterocyclic, substituted heterocyclic, amino acid, peptide, polyether, polyester, polypeptide, protein, polyphosphazene, polyalkylene oxide, polyalkylene glycol, polyethylene glycol, polyalkylene, a bioactive agent, or a drug molecule.

7. The composition of claim 6, wherein the compound of Formula I is myricitrin, and

wherein the compound of Formula II is myricetin.

8. The composition of claim 6, wherein the compound of formula II can be in a racemic form, a mixture of diastero isomers, or an enantiomer.

9. The composition of claim 8, wherein the enantiomer has a structure as shown in formulae IIa, IIb, IIc and IId:

in which;

R₆, R₂, and R₁₂ taken independently can be absence, hydrogen, halo, alkyl, substituted alkyl, alkoxy, cycloalkyl, heterocyclic, alkenyl alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, phenyl, substituted phenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, hydroxyl, alkoxy, substituted alkoxy, phenoxy, substituted phenoxy, aroxy, substituted aroxy, thiol, alkylthio, substituted alkylthio, phenylthio, substituted phenylthio, arylthio, substituted arylthio, cyano, isocyano, substituted isocyano, carbonyl, substituted carbonyl, carboxyl, substituted carboxyl, amino, substituted amino, amido, substituted amido, fulfonyl, substituted sulfonyl, polyaryl, substituted polyaryl, C1-C20 cyclic, substituted C1-C20 cyclic, heterocyclic, substituted heterocyclic, amino acid, peptide, polyether, polyester, polypeptide, protein, polyphosphazene, polyalkylene oxide, polyalkylene glycol, polyethylene glycol, polyalkylene, a bioactive agent, or a drug molecule;

R₃, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀, R₁₁, R₁₃ and R₂₀ taken independently can be hydrogen, halo, alkyl, substituted alkyl, alkoxy, cycloalkyl, heterocyclic, alkenyl alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, phenyl, substituted phenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, hydroxyl, alkoxy, substituted alkoxy, phenoxy, substituted phenoxy, aroxy, substituted aroxy, thiol, alkylthio, substituted alkylthio, phenylthio, substituted phenylthio, arylthio, substituted arylthio, cyano, isocyano, substituted isocyano, carbonyl, substituted carbonyl, carboxyl, substituted carboxyl, amino, substituted amino, amido, substituted amido, fulfonyl, substituted sulfonyl, polyaryl, substituted polyaryl, C1-C20 cyclic, substituted C1-C20 cyclic, heterocyclic, substituted heterocyclic, amino acid, peptide, polyether, polyester, polypeptide, protein, polyphosphazene, polyalkylene oxide, polyalkylene glycol, polyethylene glycol, polyalkylene, a bioactive agent, or a drug molecule;

Z₁, Z₂ and Z₃ taken independently can be oxygen (O), sulphur (S), or NH;

Z₁ and R₁ taken together can be a moiety of formula III;

where

R₁₄, R₁₅, R₁₆, R₁₇, R₁₈ and R₁₉ taken independently can be hydrogen, halo, alkyl, substituted alkyl, alkoxy, cycloalkyl, heterocyclic, alkenyl alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, phenyl, substituted phenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, hydroxyl, alkoxy, substituted alkoxy, phenoxy, substituted phenoxy, aroxy, substituted aroxy, thiol, alkylthio, substituted alkylthio, phenylthio, substituted phenylthio, arylthio, substituted arylthio, cyano, isocyano, substituted isocyano, carbonyl, substituted carbonyl, carboxyl, substituted carboxyl, amino, substituted amino, amido, substituted amido, fulfonyl, substituted sulfonyl, polyaryl, substituted polyaryl, C1-C20 cyclic, substituted C1-C20 cyclic, heterocyclic, substituted heterocyclic, amino acid, peptide, polyether, polyester, polypeptide, protein, polyphosphazene, polyalkylene oxide, polyalkylene glycol, polyethylene glycol, polyalkylene, a bioactive agent, or a drug molecule; and

Z₄ can be oxygen (O), sulphur (S), or NH.

10. The composition of claim 6, wherein the compound of formula II can be a compound of formula IIe:

in which R₁ can be hydrogen, halo, alkyl, substituted alkyl, alkoxy, cycloalkyl, heterocyclic, alkenyl alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, phenyl, substituted phenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, hydroxyl, alkoxy, substituted alkoxy, phenoxy, substituted phenoxy, aroxy, substituted aroxy, thiol, alkylthio, substituted alkylthio, phenylthio, substituted phenylthio, arylthio, substituted arylthio, cyano, isocyano, substituted isocyano, carbonyl, substituted carbonyl, carboxyl, substituted carboxyl, amino, substituted amino, amido, substituted amido, fulfonyl, substituted sulfonyl, polyaryl, substituted polyaryl, C1-C20 cyclic, substituted C1-C20 cyclic, heterocyclic, substituted heterocyclic, amino acid, peptide, polyether, polyester, polypeptide, protein, polyphosphazene, polyalkylene oxide, polyalkylene glycol, polyethylene glycol, polyalkylene, a bioactive agent, or a drug molecule.

11. The composition of claim 1, further comprising a pharmaceutically acceptable carrier.

12. The composition of claim 6, further comprising a pharmaceutically acceptable carrier.

13. The composition of claim 1, further comprising an agent selected from the group consisting of antiviral agent, antibiotics, anti-depression agent, anti-cancer agents, immunosuppressant, anti-fungal, and a combination thereof.

14. The composition of claim 6, further comprising an agent selected from the group consisting of antiviral agent, antibiotics, anti-depression agent, anti-cancer agents, immunosuppressant, anti-fungal, and a combination thereof.

15. The composition of claim 11, wherein the pharmaceutically acceptable carrier is a carrier suitable for oral delivery, parenteral delivery, topical delivery, mucosal delivery, intradermal delivery, intravenous injection, subcutaneous injection, intramedullary injection, administration by inhalation, and intranasal delivery.

16. The composition of claim 12, wherein the pharmaceutically acceptable carrier is a carrier suitable for oral delivery, parenteral delivery, topical delivery, mucosal delivery, intradermal delivery, intravenous injection, subcutaneous injection, intramedullary injection, administration by inhalation, and intranasal delivery.

17. The composition of claim 15 in a dosage form selected from the group consisting of a solution, a suspension, a syrup, a tablet, a capsule, microparticles, an ointment, a cream, and a lozenge.

18. The composition of claim 16 in a dosage form selected from the group consisting of a solution, a suspension, a syrup, a tablet, a capsule, microparticles, an ointment, a cream, and a lozenge.

19. The composition of claim 1, which is a pharmaceutical composition.

20. The composition of claim 6, which is a pharmaceutical composition.

21. The composition of claim 1, which is a nutraceutical composition or dietary supplement composition.

22. A method of treating, preventing, or ameliorating insomnia or another sleeping disorder in a human subject, comprising:

administering to the subject a composition as defined in claim 1,

wherein the compound is effective for treating a disorder selected from the group consisting of insomnia, depression-related disease, stress-related disease, depression-related sleep disorder, neurodegeneration diseases, Alzheimer'"'"'s disease, Pick'"'"'s disease, spinocerbellar degeneration, Parkinson'"'"'s disease, chorea, glaucoma, amyotrophic lateral sclerosis, senile macular degeneration, hepatic encephalopathy, demyelinating diseases, Lewy body dementia, multi-infarct dementia, multiple sclerosis and combinations thereof.

23. A method of treating, preventing, or ameliorating insomnia or another sleeping disorder in a human subject, comprising:

administering to the subject a composition as defined in claim 6,

wherein the compound is effective for treating a disorder selected from the group consisting of insomnia, depression-related disease, stress-related disease, depression-related sleep disorder, neurodegeneration diseases, Alzheimer'"'"'s disease, Pick'"'"'s disease, spinocerbellar degeneration, Parkinson'"'"'s disease, chorea, glaucoma, amyotrophic lateral sclerosis, senile macular degeneration, hepatic encephalopathy, demyelinating diseases, Lewy body dementia, multi-infarct dementia, multiple sclerosis and combinations thereof.

21-1. The composition of claim 6, which is a nutraceutical composition or dietary supplement composition.