Disubstituted Octahydropyrrolo[3,4-C]Pyrroles As Orexin Receptor Modulators

Disubstituted octahydropyrrolo[3,4-c]pyrrole compounds are described, which are useful as orexin receptor modulators. Such compounds may be useful in pharmaceutical compositions and methods for the treatment of diseased states, disorders, and conditions mediated by orexin activity, such as insomnia. 2. The chemical entity of claim 1 , wherein Ris (1-methylethyl)-2-(2H-1 claim 1 ,2 claim 1 ,3-triazol-2-yl)phenyl claim 1 , 2-(1H-1 claim 1 ,2 claim 1 ,3-triazol-1-yl)phenyl claim 1 , 2-(2H-1 claim 1 ,2 claim 1 ,3-triazol-2-yl)phenyl claim 1 , 2-fluoro-6-(2H-1 claim 1 ,2 claim 1 ,3-triazol-2-yl)phenyl claim 1 , 2-methyl-6-(2H-1 claim 1 ,2 claim 1 ,3-triazol-2-yl)phenyl claim 1 , 3-fluoro-2-(2H-1 claim 1 ,2 claim 1 ,3-triazol-2-yl)phenyl claim 1 , 3-fluoro-2-(1H-1 claim 1 ,2 claim 1 ,3-triazol-1-yl)phenyl claim 1 , 3-methoxy-2-(1H-1 claim 1 ,2 claim 1 ,3-triazol-1-yl)phenyl claim 1 , 3-methoxy-2-(2H-1 claim 1 ,2 claim 1 ,3-triazol-2-yl)phenyl claim 1 , 3-methyl-2-(2H-1 claim 1 ,2 claim 1 ,3-triazol-2-yl)phenyl claim 1 , 3-methyl-2-(1H-1 claim 1 ,2 claim 1 ,3-triazol-1-yl)phenyl claim 1 , 4-fluoro-2-(2H-1 claim 1 ,2 claim 1 ,3-triazol-2-yl)phenyl claim 1 , 4-methoxy-2-(2H-1 claim 1 ,2 claim 1 ,3-triazol-2-yl)phenyl claim 1 , 4-methoxy-2-(1H-1 claim 1 ,2 claim 1 ,3-triazol-2-yl)phenyl claim 1 , 4 claim 1 ,5-dimethoxy-2-[1 claim 1 ,2 claim 1 ,3]triazol-1-yl-phenyl claim 1 , 4 claim 1 ,5-dimethoxy-2-[2 claim 1 ,3]triazol-2-yl-phenyl claim 1 , 5-chloro-2-(2H-1 claim 1 ,2 claim 1 ,3-triazol-2-yl)phenyl claim 1 , 5-fluoro-2-(2H-1 claim 1 ,2 claim 1 ,3-triazol-2-yl)phenyl claim 1 , 5-iodo-2-(2H-1 claim 1 ,2 claim 1 ,3-triazol-2-yl)phenyl claim 1 , 5-methoxy-2-(2H-1 claim 1 ,2 claim 1 ,3-triazol-2-yl)phenyl claim 1 , 5-methyl-2-(2H-1 claim 1 ,2 claim 1 ,3-triazol-2-yl)phenyl claim 1 , 2-(1H-1 claim 1 ,2 claim 1 ,4-triazol-1-yl)phenyl claim 1 , 2-(1H-1 claim 1 ,2 claim 1 ,4-triazol-5-yl)phenyl claim 1 , 2-(1-methyl-1H-1 claim 1 ,2 claim 1 ,4-triazol-5-yl)phenyl claim 1 , 2-(1- ...

Heteroaryl amides as inhibitors of protein aggregation

The present invention relates to certain heteroaryl amide compounds, pharmaceutical compositions containing them, and methods of using them, including methods for preventing, reversing, slowing, or inhibiting protein aggregation, and methods of treating diseases that are associated with protein aggregation, including neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Lewy body disease, Parkinson's disease with dementia, fronto-temporal dementia, Huntington's Disease, amyotrophic lateral sclerosis, and multiple system atrophy, and cancer and melanoma.

DISUBSTITUTED OCTAHYDROPYRROLO[3,4-c]PYRROLES AS OREXIN RECEPTOR MODULATORS

Disubstituted octahydropyrrolo[3,4-c]pyrrole compounds are described, which are useful as orexin receptor modulators. Such compounds may be useful in pharmaceutical compositions and methods for the treatment of diseased states, disorders, and conditions mediated by orexin activity, such as insomnia. 3. A chemical entity defined in claim 1 , wherein Ris phenyl claim 1 , where Ris a member independently selected from the group consisting of —F claim 1 , —I claim 1 , —Cl claim 1 , —OCH claim 1 , —OCHCH claim 1 , —CH claim 1 , —CH(CH) claim 1 , —C(CH)and —NO.4. A chemical entity defined in claim 1 , wherein Ris phenyl wherein Ris a member selected from the group consisting of —Br claim 1 , —F claim 1 , —I claim 1 , —Calkyl claim 1 , —OCH claim 1 , —OCHCH claim 1 , —CN claim 1 , —OF claim 1 , and —OCF.5. A chemical entity defined in claim 1 , wherein Ris phenyl claim 1 , where Ris selected from the group consisting of —H claim 1 , —F claim 1 , —Cl claim 1 , —CH claim 1 , —C(CH) claim 1 , —OCH claim 1 , and —OCHCH claim 1 , and Ris selected from the group consisting of —Br claim 1 , —F claim 1 , —I claim 1 , —Calkyl claim 1 , —OCH claim 1 , —OCHCH claim 1 , —CN claim 1 , —CF claim 1 , and —OCF.6. A chemical entity defined in claim 1 , wherein Ris phenyl claim 1 , where Ris 2-thiophen-2-yl or 2-furan-2-yl.7. A chemical entity defined in claim 1 , wherein Ris phenyl claim 1 , where Ris selected from the group consisting of phenyl claim 1 , 3-chlorophenyl claim 1 , 4-fluorophenyl claim 1 , 3-fluorophenyl claim 1 , 4-methylphenyl claim 1 , and 4-trifluoromethylphenyl.8. A chemical entity defined in claim 1 , wherein Ris phenyl claim 1 , where Ris a member selected from the group consisting of 1H-pyrrol-1-yl claim 1 , 1H-pyrazol-1-yl claim 1 , 1H-pyrazol-5-yl claim 1 , 1H-imidazol-2-yl claim 1 , 1-methyl-1H-imidazol-2-yl claim 1 , 1H-1 claim 1 ,2 claim 1 ,3-triazol-1-yl claim 1 , 2H-1 claim 1 ,2 claim 1 ,3-triazol-2-yl claim 1 , 2H-1 claim 1 ,2 claim 1 ,3-triazol-1-yl claim 1 ...

Disubstituted Octahydropyrrolo[3,4-C]Pyrroles As Orexin Receptor Modulators

Disubstituted octahydropyrrolo[3,4-c]pyrrole compounds are described, which are useful as orexin receptor modulators. Such compounds may be useful in pharmaceutical compositions and methods for the treatment of diseased states, disorders, and conditions mediated by orexin activity, such as insomnia. 2. The chemical entity of claim 1 , wherein Ris (1-methylethyl)-2-(2H-1 claim 1 ,2 claim 1 ,3-triazol-2-yl)phenyl claim 1 , 2-(1H-1 claim 1 ,2 claim 1 ,3-triazol-1-yl)phenyl claim 1 , 2-(2H-1 claim 1 ,2 claim 1 ,3-triazol-2-yl)phenyl claim 1 , 2-fluoro-6-(2H-1 claim 1 ,2 claim 1 ,3-triazol-2-yl)phenyl claim 1 , 2-methyl-6-(2H-1 claim 1 ,2 claim 1 ,3-triazol-2-yl)phenyl claim 1 , 3-fluoro-2-(2H-1 claim 1 ,2 claim 1 ,3-triazol-2-yl)phenyl claim 1 , 3-fluoro-2-(1H-1 claim 1 ,2 claim 1 ,3-triazol-1-yl)phenyl claim 1 , 3-methoxy-2-(1H-1 claim 1 ,2 claim 1 ,3-triazol-1-yl)phenyl claim 1 , 3-methoxy-2-(2H-1 claim 1 ,2 claim 1 ,3-triazol-2-yl)phenyl claim 1 , 3-methyl-2-(2H-1 claim 1 ,2 claim 1 ,3-triazol-2-yl)phenyl claim 1 , 3-methyl-2-(1H-1 claim 1 ,2 claim 1 ,3-triazol-1-yl)phenyl claim 1 , 4-fluoro-2-(2H-1 claim 1 ,2 claim 1 ,3-triazol-2-yl)phenyl claim 1 , 4-methoxy-2-(2H-1 claim 1 ,2 claim 1 ,3-triazol-2-yl)phenyl claim 1 , 4-methoxy-2-(1H-1 claim 1 ,2 claim 1 ,3-triazol-2-yl)phenyl claim 1 , 4 claim 1 ,5-dimethoxy-2-[1 claim 1 ,2 claim 1 ,3]triazol-1-yl-phenyl claim 1 , 4 claim 1 ,5-dimethoxy-2-[1 claim 1 ,2 claim 1 ,3]triazol-2-yl-phenyl claim 1 , 5-chloro-2-(2H-1 claim 1 ,2 claim 1 ,3-triazol-2-yl)phenyl claim 1 , 5-fluoro-2-(2H-1 claim 1 ,2 claim 1 ,3-triazol-2-yl)phenyl claim 1 , 5-iodo-2-(2H-1 claim 1 ,2 claim 1 ,3-triazol-2-yl)phenyl claim 1 , 5-methoxy-2-(2H-1 claim 1 ,2 claim 1 ,3-triazol-2-yl)phenyl claim 1 , 5-methyl-2-(2H-1 claim 1 ,2 claim 1 ,3-triazol-2-yl)phenyl claim 1 , 2-(1H-1 claim 1 ,2 claim 1 ,4-triazol-1-yl)phenyl claim 1 , 2-(1H-1 claim 1 ,2 claim 1 ,4-triazol-5-yl)phenyl claim 1 , 2-(1-methyl-1H-1 claim 1 ,2 claim 1 ,4-triazol-5-yl)phenyl claim 1 , ...

Heteroaryl amides as inhibitors of protein aggregation

The present invention relates to certain heteroaryl amide compounds, pharmaceutical compositions containing them, and methods of using them, including methods for preventing, reversing, slowing, or inhibiting protein aggregation, and methods of treating diseases that are associated with protein aggregation, including neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Lewy body disease, Parkinson's disease with dementia, fronto-temporal dementia, Huntington's Disease, amyotrophic lateral sclerosis, and multiple system atrophy, and cancer and melanoma.

DISUBSTITUTED OCTAHYDROPYRROLO[3,4-c]PYRROLES AS OREXIN RECEPTOR MODULATORS

Disubstituted octahydropyrrolo[3,4-c]pyrrole compounds are described, which are useful as orexin receptor modulators. Such compounds may be useful in pharmaceutical compositions and methods for the treatment of diseased states, disorders, and conditions mediated by orexin activity, such as insomnia. 2. (canceled)3. The method of claim 1 , wherein Ris phenyl claim 1 , where Ris a member independently selected from the group consisting of —F claim 1 , —I claim 1 , —Cl claim 1 , —OCH claim 1 , —OCHCH claim 1 , —CH claim 1 , —CH(CH) claim 1 , —C(CH)and —NO.4. (canceled)5. (canceled)6. (canceled)7. (canceled)9. (canceled)10. (canceled)12. The method of claim 1 , wherein Ris (1-methylethyl)-2-(2H-1 claim 1 ,2 claim 1 ,3-triazol-2-yl)phenyl claim 1 , 2-(1H-1 claim 1 ,2 claim 1 ,3-triazol-1-yl)phenyl claim 1 , 2-(2H-1 claim 1 ,2 claim 1 ,3-triazol-2-yl)phenyl claim 1 , 2-fluoro-6-(2H-1 claim 1 ,2 claim 1 ,3-triazol-2-yl)phenyl claim 1 , 2-methyl-6-(2H-1 claim 1 ,2 claim 1 ,3-triazol-2-yl)phenyl claim 1 , 3-fluoro-2-(2H-1 claim 1 ,2 claim 1 ,3-triazol-2-yl)phenyl claim 1 , 3-fluoro-2-(1H-1 claim 1 ,2 claim 1 ,3-triazol-1-yl)phenyl claim 1 , 3-methoxy-2-(1H-1 claim 1 ,2 claim 1 ,3-triazol-1-yl)phenyl claim 1 , 3-methoxy-2-(2H-1 claim 1 ,2 claim 1 ,3-triazol-2-yl)phenyl claim 1 , 3-methyl-2-(2H-1 claim 1 ,2 claim 1 ,3-triazol-2-yl)phenyl claim 1 , 3-methyl-2-(1H-1 claim 1 ,2 claim 1 ,3-triazol-1-yl)phenyl claim 1 , 4-fluoro-2-(2H-1 claim 1 ,2 claim 1 ,3-triazol-2-yl)phenyl claim 1 , 4-methoxy-2-(2H-1 claim 1 ,2 claim 1 ,3-triazol-2-yl)phenyl claim 1 , 4-methoxy-2-(1H-1 claim 1 ,2 claim 1 ,3-triazol-2-yl)phenyl claim 1 , 4 claim 1 ,5-dimethoxy-2-[1 claim 1 ,2 claim 1 ,3]triazol-1-yl-phenyl claim 1 , 4 claim 1 ,5-dimethoxy-2-[1 claim 1 ,2 claim 1 ,3]triazol-2-yl-phenyl claim 1 , 5-[1 claim 1 ,2 claim 1 ,3]triazol-2-yl-benzo[1 claim 1 ,3]dioxol-4-yl claim 1 , 5-chloro-2-(2H-1 claim 1 ,2 claim 1 ,3-triazol-2-yl)phenyl claim 1 , 5-fluoro-2-(2H-1 claim 1 ,2 claim 1 ,3-triazol-2-yl) ...

Substituted phenyl sulfonyl phenyl triazole thiones and uses thereof

The present disclosure relates to substituted phenyl sulfonyl phenyl triazole thiones, pharmaceutical compositions containing them, and methods of using them.

TRI-SUBSTITUTED ARYL AND HETEROARYL DERIVATIVES AS MODULATORS OF PI3-KINASE AND AUTOPHAGY PATHWAYS

The present disclosure relates to tri-substituted aryl and heteroaryl derivatives, pharmaceutical compositions containing them, and methods of using them, including methods for modulating autophagy or preventing, reversing, slowing or inhibiting the PI3K-AKT-MTOR pathway, and methods of treating diseases that are associated with autophagy or the PI3K-AKT-MTOR pathway. 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —(CRR)-aryl.3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris (CRR)-heteroaryl.4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris (CRR)-heterocycloalkyl or (CRR)-cycloalkyl.5. The compound of any one of - claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein L is —S(O)—.6. The compound of any one of - claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein L is —C(O)— claim 1 , —CH— claim 1 , —CF— claim 1 , C(CH) claim 1 , —C(═CH)— claim 1 , or —CRR.7. The compound of any one of - claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein L is absent.10. The compound of any one of - claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Y claim 1 , Y claim 1 , and Yare each CH.11. The compound of any one of - claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Yis N and Yand Yare each CH.12. The compound of any one of - claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Yis N and Yand Yare each CH.13. The compound of any one of - claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Yis N and Yand Yare each CH.14. The compound of any one of - claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein X is O.15. The compound of any one of - claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein X is NH claim 1 , N(COCalkyl) claim 1 , N(SOCalkyl) ...

Morpholine derivates as inhibitors of vps34

The present disclosure relates to thiazole- or diathiazole-substituted aryl and heteroaryl compounds (I), pharmaceutical compositions containing them, and methods of using them, including treatment of disorders or disease related to regulation of the Vps34/PI3K III signaling pathway.

COMPOUNDS AND COMPOSITIONS AS MODULATORS OF TLR SIGNALING

The present disclosure relates to compounds, pharmaceutical compositions comprising such compounds, and use of such compounds in methods of treatment or in medicaments for treatment of inflammatory diseases and certain neurological disorders that are related to inflammatory signaling processes, including but not limited to misfolded proteins. 192-. (canceled)94. The method of claim 93 , wherein the disease or condition is selected from the group consisting of: Alzheimer's disease claim 93 , Parkinson's disease claim 93 , fronto-temporal dementia claim 93 , dementia with Lewy bodies (Lewy body disease) claim 93 , Parkinson's disease with dementia claim 93 , multiple system atrophy claim 93 , amyotrophic lateral sclerosis claim 93 , Huntington's disease claim 93 , Progressive Supranuclear Palsy (PSP) claim 93 , Niemann-Pick disease type C claim 93 , inflammatory diseases claim 93 , asthma claim 93 , chronic obstructive pulmonary disease (COPD) claim 93 , chronic peptic ulcers claim 93 , irritable bowel disease claim 93 , tuberculosis claim 93 , rheumatoid arthritis claim 93 , osteoarthritis claim 93 , chronic sinusitis claim 93 , hepatitis claim 93 , hepatitis B claim 93 , hepatitis C claim 93 , gout claim 93 , lupus claim 93 , pleurisy claim 93 , eczema claim 93 , gastritis claim 93 , psoriasis claim 93 , psoriatic arthritis claim 93 , vasculitis claim 93 , laryngitis claim 93 , allergic reactions claim 93 , multiple sclerosis claim 93 , Crohn's disease claim 93 , traumatic brain injury claim 93 , CIDP (chronic inflammatory demyelinating polyneuropathy) claim 93 , stroke claim 93 , ischemic heart disease claim 93 , atopic dermatitis claim 93 , acne vulgaris claim 93 , rosacea claim 93 , non-alcoholic fatty liver disease claim 93 , non-alcoholic steatohepatisis claim 93 , corneal wounds claim 93 , corneal disorders claim 93 , corneal HSV claim 93 , Stargardt disease (Juvenile macular degeneration) claim 93 , age-related macular degeneration claim 93 , sepsis claim 93 ...

ARYL- AND HETEROARYL-SUBSTITUTED BENZENE DERIVATIVES AS MODULATORS OF PI3-KINASE SIGNALLING PATHWAYS

The present disclosure relates to certain aryl- or heteroaryl-substituted benzene derivatives, pharmaceutical compositions containing them, and methods of using them, including methods for modulating autophagy or preventing, reversing, slowing or inhibiting the PI3K-AKT-MTOR pathway, and methods of treating diseases that are associated with autophagy or the PI3K-AKT-MTOR pathway. 4. The compound of claim 3 , wherein X is —SO—.5. The compound of claim 3 , wherein Gand Gare each CH.6. The compound of claim 3 , wherein n is zero.8. A pharmaceutical composition comprising (a) at least one compound of Formula (I) in claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and (b) a pharmaceutically acceptable excipient.9. A method of treating a disease or medical condition associated with autophagy or the PI3K-AKT-MTOR pathway claim 1 , comprising administering to a subject in need of such treatment an effective amount of at least one compound of Formula I as in claim 1 , or a pharmaceutically acceptable salt thereof.10. The method of claim 9 , wherein the disease or medical condition is Alzheimer's Disease claim 9 , Parkinson's Disease claim 9 , fronto-temporal dementia claim 9 , dementia with Lewy Bodies claim 9 , PD dementia claim 9 , multiple system atrophy claim 9 , Huntington's disease claim 9 , Amyotrophic lateral sclerosis claim 9 , cancer claim 9 , infection claim 9 , Crohn's disease claim 9 , heart disease claim 9 , and aging. This application claims priority to U.S. Provisional Patent Application No. 61/681,585, filed Aug. 9, 2012, which is incorporated herein in its entirety.The present disclosure relates to aryl- and heteroaryl-substituted benzene compounds, pharmaceutical compositions containing them, and methods of using them, including methods for modulating the PI3K-AKT-MTOR pathway, methods for activating, increasing or stimulating autophagy by preventing, reversing, slowing or inhibiting the PI3K-AKT-MTOR pathway, and methods for treating ...

HETEROARYL AMIDES AS INHIBITORS OF PROTEIN AGGREGATION

The present invention relates to certain heteroaryl amide compounds, pharmaceutical compositions containing them, and methods of using them, including methods for preventing, reversing, slowing, or inhibiting protein aggregation, and methods of treating diseases that are associated with protein aggregation, including neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Lewy body disease, Parkinson's disease with dementia, fronto-temporal dementia, Huntington's Disease, amyotrophic lateral sclerosis, and multiple system atrophy, and cancer and melanoma. 2. The compound of claim 1 , wherein Ris H claim 1 , fluoro claim 1 , chloro claim 1 , bromo claim 1 , methyl claim 1 , ethyl claim 1 , propyl claim 1 , isopropyl claim 1 , butyl claim 1 , isobutyl claim 1 , sec-butyl claim 1 , or tert-butyl.3. The compound of claim 1 , wherein Ris H or fluoro.4. The compound of claim 1 , wherein Ris —CFor is Calkyl optionally substituted with halo or —CF.5. The compound of claim 1 , wherein Ris Calkyl claim 1 , unsubstituted or substituted with fluoro or —CF.6. The compound of claim 1 , wherein Ris butyl.7. The compound of claim 1 , wherein Ris in an “R” stereochemical configuration.8. The compound of claim 1 , wherein Ris in an “S” stereochemical configuration.9. The compound of claim 1 , wherein Ris substantially an “R” or substantially an “S” stereochemical configuration.10. The compound of claim 1 , wherein A is a 5-membered heteroaryl ring with two or three heteroatom ring atoms.11. The compound of claim 1 , wherein A is a 5-membered heteroaryl ring with two non-adjacent heteroatom ring atoms.12. The compound of claim 1 , wherein A is thiazole claim 1 , thiadiazole claim 1 , oxazole claim 1 , imidazole claim 1 , or triazole.13. The compound of claim 1 , wherein A is thiazole or thiadiazole.14. The compound of claim 1 , wherein A is thiazole.15. The compound of claim 1 , wherein Y is absent.16. The compound of claim 1 , wherein Y is —CH— claim 1 , —CHCH— ...

Method of treating a condition associated with neurodegeneration using inhibitors of oat3

The present disclosure relates to therapeutic agents that may be useful intreatment and prophylaxis of neurodegenerative disorders and/or neural inflammation.

Substituted phenyl sulfonyl phenyl triazole thiones and uses thereof

The present disclosure relates to substituted phenyl sulfonyl phenyl triazole thiones, pharmaceutical compositions containing them, and methods of using them.

HETEROARYL AMIDES AS INHIBITORS OF PROTEIN AGGREGATION

The present invention relates to certain heteroaryl amide compounds, pharmaceutical compositions containing them, and methods of using them, including methods for preventing, reversing, slowing, or inhibiting protein aggregation, and methods of treating diseases that are associated with protein aggregation, including neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Lewy body disease, Parkinson's disease with dementia, fronto-temporal dementia, Huntington's Disease, amyotrophic lateral sclerosis, and multiple system atrophy, and cancer and melanoma. 2: The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris H claim 1 , fluoro claim 1 , chloro claim 1 , bromo claim 1 , methyl claim 1 , ethyl claim 1 , propyl claim 1 , isopropyl claim 1 , butyl claim 1 , isobutyl claim 1 , sec-butyl claim 1 , or tert-butyl.3: The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris H or fluoro.4: The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —CF claim 1 , or is methyl claim 1 , ethyl claim 1 , propyl claim 1 , isopropyl claim 1 , butyl claim 1 , isobutyl claim 1 , sec-butyl claim 1 , or tert-butyl claim 1 , each unsubstituted or substituted with fluoro claim 1 , chloro claim 1 , bromo claim 1 , or —CF.5: The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —CFor is Calkyl optionally substituted with halo or —CF.6: The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris Calkyl claim 1 , unsubstituted or substituted with fluoro or —CF.7: The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris butyl.8: The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris propyl substituted with —CF.9: The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris in an “R ...

COMPOUNDS AND COMPOSITIONS AS MODULATORS OF TLR SIGNALING

The present disclosure relates to compounds, pharmaceutical compositions comprising such compounds, and use of such compounds in methods of treatment or in medicaments for treatment of inflammatory diseases and certain neurological disorders that are related to inflammatory signaling processes, including but not limited to misfolded proteins. 26-. (canceled)811-. (canceled)13. (canceled)14. The compound of claim 1 , or a tautomer thereof claim 1 , or a pharmaceutically acceptable salt of any of the foregoing claim 1 , wherein Ris selected from the group consisting of —CH claim 1 , —OCH claim 1 , Cl and F.1619-. (canceled)20. The compound of claim 1 , or a tautomer thereof claim 1 , or a pharmaceutically acceptable salt of any of the foregoing claim 1 , wherein n is 0.2124-. (canceled)2737-. (canceled)38. The compound of claim 25 , or a tautomer thereof claim 25 , or a pharmaceutically acceptable salt of any of the foregoing claim 25 , wherein one or more of R claim 25 , R claim 25 , R claim 25 , and Ris selected from the group consisting of C-Calkyl claim 25 , C-Calkoxy claim 25 , halo claim 25 , —OH claim 25 , —NRR claim 25 , aryl claim 25 , heterocyclyl claim 25 , heteroaryl claim 25 , —C-Calkyl-heterocyclyl claim 25 , —OC(O)-heterocyclyl claim 25 , —C(O)R claim 25 , —S(O)NRR claim 25 , —S(O)R claim 25 , or —NRS(O)R.3941-. (canceled)42. The compound of claim 1 , or a tautomer thereof claim 1 , or a pharmaceutically acceptable salt of any of the foregoing claim 1 , wherein Gis CH and Gis CH.43. The compound of claim 1 , or a tautomer thereof claim 1 , or a pharmaceutically acceptable salt of any of the foregoing claim 1 , wherein Gis N and Gis CH.4445-. (canceled)46. A compound of Table 1A claim 1 , or a tautomer thereof claim 1 , or a pharmaceutically acceptable salt of any of the foregoing.48. (canceled)49. The compound of claim 47 , or a tautomer thereof claim 47 , or a pharmaceutically acceptable salt of any of the foregoing claim 47 , wherein Yand Yare each CH ...

DISUBSTITUTED OCTAHYDROPYRROLO[3,4-c]PYRROLES AS OREXIN RECEPTOR MODULATORS

Disubstituted octahydropyrrolo[3,4-c]pyrrole compounds are described, which are useful as orexin receptor modulators. Such compounds may be useful in pharmaceutical compositions and methods for the treatment of diseased states, disorders, and conditions mediated by orexin activity, such as insomnia. 1. A compound selected from[5-(4,6-Dimethyl-pyrimidin-2-yl)-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl]-(2-fluoro-6-[1,2,3]triazol-2-yl-phenyl)-methanone;and pharmaceutically acceptable salts thereof.234.-. (canceled)35. The compound of claim 1 , selected from:[5-(4,6-Dimethyl-pyrimidin-2-yl)-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl]-(2-fluoro-6-[1,2,3]triazol-2-yl-phenyl)-methanone; and[5-(4,6-Dimethyl-pyrimidin-2-yl)-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl]-(2-fluoro-6-[1,2,3]triazol-2-yl-phenyl)-methanone•HCl.36. A compound which is [5-(4 claim 1 ,6-Dimethyl-pyrimidin-2-yl)-hexahydro-pyrrolo[3 claim 1 ,4-c]pyrrol-2-yl]-(2-fluoro-6-[1 claim 1 ,2 claim 1 ,3]triazol-2-yl-phenyl)-methanone.37. A pharmaceutical composition comprising a compound selected from:[5-(4,6-Dimethyl-pyrimidin-2-yl)-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl]-(2-fluoro-6-[1,2,3]triazol-2-yl-phenyl)-methanone, and pharmaceutically acceptable salts thereof;and a pharmaceutically acceptable excipient.38. A pharmaceutical composition comprising the compound of and a pharmaceutically acceptable excipient.39. A method of treating a subject suffering from or diagnosed with a sleep disorder selected from the group consisting of sleep-wake transition disorders claim 36 , insomnia claim 36 , restless legs syndrome claim 36 , jet-lag claim 36 , disturbed sleep claim 36 , and sleep disorders secondary to neurological disorders claim 36 , comprising administering to a subject in need of such treatment an effective amount of a compound selected from [5-(4 claim 36 ,6-Dimethyl-pyrimidin-2-yl)-hexahydro-pyrrolo[3 claim 36 ,4-c]pyrrol-2-yl]-(2-fluoro-6-[1 claim 36 ,2 claim 36 ,3]triazol-2-yl-phenyl)methanone claim 36 , and ...

HETEROARYL AMIDES AS PROTEIN AGGREGATION INHIBITORS

AMIDAS DE HETEROARIL COMO INIBIDORES DE AGREGAÇÃO DE PROTEÍNAS. A presente invenção refere-se a certos compostos de heteroaril amida, composições farmacêuticas contendo estes, e métodos de utilização deles, incluindo métodos para prevenir, inverter, retardar, ou inibir à agregação da proteína, e métodos de tratamento de doenças que estão associadas à agregação de proteínas, incluindo as doenças neurodegenerativas, tais como a doença de Parkinson, doença de Alzheimer, doença do corpo de Lewy, doença de Parkinson com demência, demência fronto-temporal, doença de Huntington, esclerose lateral amiotrófica, atrofia múltipla dos sistemas, e câncer e melanoma.

Substituted aminomethyl benzamide compounds

Certain substituted aminomethyl benzamide compounds are histamine H3 receptor and/or serotonin transporter modulators useful in the treatment of histamine H3 receptor- and/or serotonin-mediated diseases.

HETEROARYLAMIDES AS INHIBITORS OF PROTEIN AGGREGATION

Heteroaryl amides as inhibitors of protein aggregation

The present invention relates to certain heteroaryl amide compounds, pharmaceutical compositions containing them, and methods of using them, including methods for preventing, reversing, slowing, or inhibiting protein aggregation, and methods of treating diseases that are associated with protein aggregation, including neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Lewy body disease, Parkinson's disease with dementia, frontotemporal dementia, Huntington's Disease, amyotrophic lateral sclerosis, and multiple system atrophy, and cancer and melanoma.

Disubstituted octahydropyrrolo[3,4-c]pyrroles as orexin receptor modulators

Disubstituted octahydropyrrolo[3,4-c]pyrrole compounds are described, which are useful as orexin receptor modulators. Such compounds may be useful in pharmaceutical compositions and methods for the treatment of diseased states, disorders, and conditions mediated by orexin activity, such as insomnia.

Heteroaryl amides as inhibitors of protein aggregation

Cycloalkyloxy-and hetîžrocycloalky- loxypyridine compounds as modulators of the histamine h3 receptor.

Ciertos compuestos de cicloalquiloxi y heterocicloalquiloxipiridin a son moduladores del receptor H3 de histamina útiles en el tratamiento de las enfermedades mediadas por el receptor H3 de histamina.

Disubstituted octahydropyrrolo[3,4-c]pyrroles as orexin receptor modulators

Abstract Disubstituted octahydropyrrolo[3,4-c]pyrrole compounds are described, which are useful as orexin receptor modulators. Such compounds may be 5 useful in pharmaceutical compositions and methods for the treatment of diseased states, disorders, and conditions mediated by orexin activity, such as insomnia.

Heteroaryl amides as inhibitors of protein aggregation

Tri-substituted aryl and heteroaryl derivatives as modulators of pi3-kinase and autophagy pathways

The present disclosure relates to tri-substituted aryl and heteroaryl derivatives, pharmaceutical compositions containing them, and methods of using them, including methods for modulating autophagy or preventing, reversing, slowing or inhibiting the PI3K-AKT-MTOR pathway, and methods of treating diseases that are associated with autophagy or the PI3K-AKT-MTOR pathway.

Substituted benzyl amine compounds

Certain substituted benzyl amine compounds are histamine H3 receptor and/or serotonin transporter modulators useful in the treatment of histamine H3 receptor- and/or serotonin-mediated diseases.

OCTAHYDROPIRROLO [3,4-C] DISUSTITUTED PYROROLS AS MODULATORS OF THE OREXIN RECEPTOR

SE REFIERE A UN COMPUESTO DE FORMULA (I) Y (II) DONDE R1 ES UN DERIVADO DE FENILO, DERIVADO DE PIRIDINA, HETEROARILO DE 5 MIEMBROS CON HETEROATOMOS SELECCIONADOS ENTRE N, S Y O, ENTRE OTROS; R2 ES HETEROARILO DE 6 MIEMBROS CON DOS N COMO HETEROATOMOS, DERIVADO DE PIRIDINA, HETEROARILO DE 9 MIEMBROS CON HETEROATOMOS SELECCIONADOS ENTRE N, S Y O, ENTRE OTROS; R3 ES DERIVADO DE FENILO; R4 ES (5-TRIFLUOROMETIL)-PIRIDIN-2-ILO, (5-TRIFLUOROMETIL)-PIRIMIDIN-2-ILO, 4,6-DIMETILPIRIMIDIN-2-ILO, Y QUINOXALIN-2-ILO. SON COMPUESTOS PREFERIDOS: 4-[5-{[2-FLUORO-6-(2H-1,2,3-TRIAZOL-2-IL)FENIL]CARBONIL}HEXAHIDROPIRROLO[3,4-c]PIRROL-2(1H)-IL]-6-METOXI-N,N-DIMETILPIRIMIDIN-2-AMINA; N,N-DIMETIL-6-[5-{[2-(2H-1,2,3-TRIAZOL-2-IL)FENIL]CARBONIL}HEXAHIDROPIRROLO[3,4-c]PIRROL-2(1H)-IL]-2-(TRIFLUOROMETIL)PIRIMIDIN-4-AMINA; 6-[5-{[2-FLUORO-6-(2H-1,2,3-TRIAZOL-2-IL)FENIL]CARBONIL}HEXAHIDROPIRROLO[3,4-c]PIRROL-2(1H)-IL]-6-METOXI-N,N-DIMETIL-2-(TRIFLUOROMETIL)PIRIMIDIN-4-AMINA; ENTRE OTROS. SE REFIERE TAMBIEN A UNA COMPOSICION FARMACEUTICA. DICHO COMPUESTO ES UN MODULADOR DE RECEPTOR DE OREXINA UTIL EN EL TRATAMIENTO DEL INSOMNIO, DESFASE HORARIO, SUENO INTERRUMPIDO, ENTRE OTROS REFERS TO A COMPOUND OF FORMULA (I) AND (II) WHERE R1 IS A DERIVATIVE OF PHENYL, DERIVED FROM PYRIDINE, HETEROARYL OF 5 MEMBERS WITH HETEROATOMS SELECTED FROM N, S AND O, AMONG OTHERS; R2 IS 6-MEMBER HETEROARYL WITH TWO N AS HETEROATOMS, DERIVED FROM PYRIDINE, 9-MEMBER HETEROARYL WITH HETEROATOMS SELECTED FROM N, S AND O, AMONG OTHERS; R3 IS DERIVED FROM PHENYL; R4 IS (5-TRIFLUORomethyl) -PYRIDIN-2-ILO, (5-TRIFLUOROMETHYL) -PYRIMIDIN-2-ILO, 4,6-DIMETHYLPYRIMIDIN-2-ILO, AND QUINOXALIN-2-ILO. THE PREFERRED COMPOUNDS ARE: 4- [5 - {[2-FLUORO-6- (2H-1,2,3-TRIAZOL-2-IL) PHENYL] CARBONYL} HEXAHYDROPYRROLO [3,4-c] PYRROL-2 (1H) -IL] -6-METOXY-N, N-DIMETHYLPYRIMIDIN-2-AMINE; N, N-DIMETHYL-6- [5 - {[2- (2H-1,2,3-TRIAZOL-2-IL) PHENYL] CARBONYL} HEXAHYDROPYRROLO [3,4-c] PYRROL-2 (1H) -IL ] -2- (TRIFLUORomethyl) PYRIMIDIN-4-AMINE; 6- ...

Disubstituted octahy - dropyrrolo [3,4-c] pyrroles as orexin receptor modulators

Disubstituted octahydropyrrolo[3,4-c]pyrrole compounds are described, which are useful as orexin receptor modulators. Such compounds may be useful in pharmaceutical compositions and methods for the treatment of diseased states, disorders, and conditions mediated by orexin activity, such as insomnia.

Heteroaryl amides as inhibitors of protein aggregation

Cycloalkyloxy-and heterocycloalkyloxypyridine compounds as modulators of the histamine h3 receptor

Substituted benzyl amine compounds

Certain substituted benzyl amine compounds are histamine H 3 receptor and/or serotonin transporter modulators useful in the treatment of histamine H 3 receptor- and/or serotonin-mediated diseases.

Substituted benzyl amine compounds

Certain substituted benzyl amine compounds are histamine H3 receptor and/or serotonin transporter modulators useful in the treatment of histamine H3 receptor- and/or serotonin-mediated diseases.

Substituted pyrrolidine amides as modulators of the histamine H3 receptor

Compounds and compositions as tlr signaling modulators

La presente descripción se refiere a compuestos, composiciones farmacéuticas que comprenden dichos compuestos, y el uso de dichos compuestos en métodos de tratamiento o en medicamentos para el tratamiento de enfermedades inflamatorias y determinados trastornos neurológicos que están relacionados con procesos de señalización inflamatoria, lo que incluye, de modo no taxativo, el mal plegamiento de proteínas. The present description relates to compounds, pharmaceutical compositions comprising said compounds, and the use of said compounds in methods of treatment or in medicaments for the treatment of inflammatory diseases and certain neurological disorders that are related to inflammatory signaling processes, including , but not limited to, protein misfolding.

Heteroaryl amides as inhibitors of protein aggregation

The present invention relates to certain heteroaryl amide compounds, pharmaceutical compositions containing them, and methods of using them, including methods for preventing, reversing, slowing, or inhibiting protein aggregation, and methods of treating diseases that are associated with protein aggregation, including neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Lewy body disease, Parkinson's disease with dementia, fronto-temporal dementia, Huntington's Disease, amyotrophic lateral sclerosis, and multiple system atrophy, and cancer and melanoma.

Cycloalkyloxy-and heterocycloalkyloxypyridine compounds as modulators of the histamine h3 receptor

Heteroaryl amides as inhibitors of protein aggregation

The present invention relates to certain heteroaryl amide compounds, pharmaceutical compositions containing them, and methods of using them, including methods for preventing, reversing, slowing, or inhibiting protein aggregation, and methods of treating diseases that are associated with protein aggregation, including neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Lewy body disease, Parkinson's disease with dementia, fronto-temporal dementia, Huntington's Disease, amyotrophic lateral sclerosis, and multiple system atrophy, and cancer and melanoma.

Compuestos y composiciones como moduladores de señalización tlr

La presente descripción se refiere a compuestos, composiciones farmacéuticas que comprenden dichos compuestos, y el uso de dichos compuestos en métodos de tratamiento o en medicamentos para el tratamiento de enfermedades inflamatorias y determinados trastornos neurológicos que están relacionados con procesos de señalización inflamatoria, lo que incluye, de modo no taxativo, el mal plegamiento de proteínas.

Morpholine derivates as inhibitors of Vps34

The present disclosure relates to thiazole- or diathiazole- substituted aryl and heteroaryl compounds (I), pharmaceutical compositions containing them, and methods of using them, including treatment of disorders or disease related to regulation of the Vps34/ PI3K III signaling pathway.

Bis-heteroaryl derivatives as modulators of protein aggregation

The present invention relates to certain bis-heteroaryl compounds, pharmaceutical compositions containing them, and methods of using them, including methods for preventing, reversing, slowing, or inhibiting protein aggregation, and methods of treating diseases that are associated with protein aggregation, including neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Lewy body disease, Parkinson's disease with dementia, fronto- temporal dementia, Huntington's Disease, amyotrophic lateral sclerosis, and multiple system atrophy, and cancer including melanoma.

Compuestos y composiciones como moduladores de señalización tlr

La presente descripción se refiere a compuestos, composiciones farmacéuticas que comprenden dichos compuestos, y el uso de dichos compuestos en métodos de tratamiento o en medicamentos para el tratamiento de enfermedades inflamatorias y determinados trastornos neurológicos que están relacionados con procesos de señalización inflamatoria, lo que incluye, de modo no taxativo, el mal plegamiento de proteínas. Un compuesto de fórmula (1), o un tautómero de este, o una sal farmacéuticamente aceptable de cualquiera de los anteriores, en donde R¹ es R¹A y R² es R²A, o R¹ es R²A y R² es R¹A, en donde R¹A es -OH, -OPO₃H₂, -OCH₂OPO₃H₂, -OC(O)R¹A¹, -OC(O)OR¹A¹, -OC(O)NHR¹A¹, -OC(O)NR¹A¹R¹A², o -OR¹A³, en donde R¹A¹ y R¹A² son cada uno independientemente hidrógeno, alquilo opcionalmente sustituido, alquenilo opcionalmente sustituido, alquinilo opcionalmente sustituido, cicloalquilo opcionalmente sustituido, cicloalquenilo opcionalmente sustituido, arilo opcionalmente sustituido, heterociclilo opcionalmente sustituido, o -O₀₋₁(CH₂)ₘO(CH₂)ₙOH, en donde m y n son cada uno independientemente 1 ó 2, y R¹A³ es heteroarilo opcionalmente sustituido; R²A es -CHO o -CH=NR²A¹, en donde R²A¹ es heterociclilo opcionalmente sustituido, alquilo opcionalmente sustituido, alquenilo opcionalmente sustituido, alquinilo opcionalmente sustituido, -NR²A¹AC(O)R²A¹B, -NR²A¹AS(O)₂R²A¹B, -NR²A¹AR²A¹B, -OR²A¹A, o -NR²A¹AC(NR²A¹B)NR²A¹CR²A¹D, y en donde R²A¹A, R²A¹B, R²A¹C, y R²A¹D son cada uno independientemente hidrógeno, alquilo opcionalmente sustituido, cicloalquilo opcionalmente sustituido, heteroarilo opcionalmente sustituido, arilo opcionalmente sustituido, o amino opcionalmente sustituido; o R¹A y R²A tomados juntos con el resto de fórmula (2), al que están unidos forman un compuesto de fórmula (3) opcionalmente sustituido; R³ es halo, hidrógeno, alquilo opcionalmente sustituido o alcoxi opcionalmente sustituido; G¹ y G² son cada uno independientemente CH o N; L es un enlace, -C(O)NH-*, -NHC(O)-*, ...

Pirrolidin amidas sustituidas como moduladores del receptor histamina h3

REFERIDA A UN DERIVADO DE PIRROLIDINAMIDA DE FORMULA (I), DONDE R1 Y R2 JUNTO AL ATOMO DE NITROGENO AL QUE ESTAN UNIDOS FORMAN UN GRUPO (a) O (b); Ra ES H, ALQUILO C1-C6, CICLOALQUILO C3-C10, ENTRE OTROS; Rb Y Rc SON H, ALQUILO C1-C4, ENTRE OTROS; R3 ES H, F, ALQUILO C1-C6, ENTRE OTROS; R4 Y R5 SON H O -X-Rd; R6 ES CH2-Re O H; X ES O, S O CH2; Rd ES H, ALQUILO C1-C6, FENILO, BENCILO, ENTRE OTROS; Re ES FENILO O HETEROARILO MONOCICLICO OPCIONALMENTE SUSTITUIDO CON Rf; Rf ES OH, F, -O-ALQUILO C1-C4, ENTRE OTROS. SON COMPUESTOS PREFERIDOS: ESTER TER-BUTILICO DE ACIDO (2S,4R)-2-(4-CICLOBUTIL-[1,4]DIAZEPAN-1-CARBONIL)-4-HIDROXI-PIRROLIDIN-1-CARBOXILICO, ESTER TER-BUTILICO DE ACIDO (2S,4R)-2-(4-CICLOBUTIL-PIPERAZIN-1-CARBONIL)-4-HIDROXI-PIRROLIDIN-1-CARBOXILICO, ESTER TER-BUTILICO DE ACIDO (2S,3S)-2-(4-CICLOBUTIL-[1,4]DIAZEPAN-1-CARBONIL)-3-HIDROXI-PIRROLIDIN-1-CARBOXILICO, ENTRE OTROS. TAMBIEN ESTA REFERIDA A UNA COMPOSICION FARMACEUTICA. DICHOS COMPUESTOS SON MODULADORES DEL RECEPTOR H3 Y SON UTILES EN EL TRATAMIENTO DE LA ENFERMEDAD DE ALZHEIMER, SINDROME DE DOWN, ENTRE OTROS

Substituted phenyl sulfonyl phenyl triazole thiones and uses thereof

The present disclosure relates to substituted phenyl sulfonyl phenyl triazole thiones, pharmaceutical compositions containing them, and methods of using them.

Compuestos y composiciones como moduladores de señalización tlr.

La presente descripción se refiere a compuestos, composiciones farmacéuticas que comprenden dichos compuestos, y el uso de dichos compuestos en métodos de tratamiento o en medicamentos para el tratamiento de enfermedades inflamatorias y determinados trastornos neurológicos que están relacionados con procesos de señalización inflamatoria, lo que incluye, de modo no taxativo, el mal plegamiento de proteínas.

Compuestos y composiciones como moduladores de señalización tlr

La presente descripción se refiere a compuestos, composiciones farmacéuticas que comprenden dichos compuestos, y el uso de dichos compuestos en métodos de tratamiento o en medicamentos para el tratamiento de enfermedades inflamatorias y determinados trastornos neurológicos que están relacionados con procesos de señalización inflamatoria, lo que incluye, de modo no taxativo, el mal plegamiento de proteínas.

Compounds and compositions as modulators of tlr signaling

The present disclosure relates to compounds, pharmaceutical compositions comprising such compounds, and use of such compounds in methods of treatment or in medicaments for treatment of inflammatory diseases and certain neurological disorders that are related to inflammatory signaling processes, including but not limited to misfolded proteins.

Substituted phenyl sulfonyl phenyl triazole thiones and uses thereof

The present disclosure relates to substituted phenyl sulfonyl phenyl triazole thiones, pharmaceutical compositions containing them, and methods of using them.

Aryl-and heteroaryl-substituted benzene derivatives as modulators of pi3-kinase signalling pathways

The present disclosure relates to certain aryl- or heteroaryl-substituted benzene derivatives, pharmaceutical compositions containing them, and methods of using them, including methods for modulating autophagy or preventing, reversing, slowing or inhibiting the PI3K-AKT-MTOR pathway, and methods of treating diseases that are associated with autophagy or the PI3K-AKT-MTOR pathway.

Bis-heteroaryl derivatives as modulators of protein aggregation

The present invention relates to certain bis-heteroaryl compounds, pharmaceutical compositions containing them, and methods of using them, including methods for preventing, reversing, slowing, or inhibiting protein aggregation, and methods of treating diseases that are associated with protein aggregation, including neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Lewy body disease, Parkinson's disease with dementia, fronto-temporal dementia, Huntington's Disease, amyotrophic lateral sclerosis, and multiple system atrophy, and cancer including melanoma.

Aryl-and heteroaryl-substituted benzene derivatives as modulators of pi3-kinase signalling pathways -- pi3-

Tri-substituted aryl and heteroaryl derivatives as modulators of PI3-kinase and autophagy pathways

The present disclosure relates to tri-substituted aryl and heteroaryl derivatives. pharmaceutical compositions containing them, and methods of using them, including methods for modulating autophagy or preventing, reversing, slowing or inhibiting the PI3K-AKT-MTOR pathway, and methods of treating diseases that are associated with autophagy or the PI3K-AKT-MTOR pathway.

Αμιδια ετεροαρυλιου ως αναστολεις της συσσωματωσης πρωτεϊνων

Η παρούσα εφεύρεση σχετίζεται με ορισμένες ενώσεις αμιδίων ετεροαρυλίου, φαρμακευτικές συνθέσεις περιέχοντας αυτές, και μεθόδους χρήσεις αυτών, που συμπεριλαμβάνουν μεθόδους για πρόληψη, αντιστροφή, επιβράδυνση ή αναστολή συσσωμάτωσης πρωτεϊνών, και μεθόδους αγωγής παθήσεων που συσχετίζονται με συσσωμάτωση πρωτεϊνών, που συμπεριλαμβάνουν νευροεκφυλιστικές παθήσεις όπως είναι η νόσος του Πάρκινσον, η νόσος του Αλτσχάϊμερ, η πάθηση σωμάτων Lewy, η νόσος του Πάρκινσον με άνοια, η κροταφομετωπιαία άνοια, η Νόσος του Χάντινγκτον, η αμυοτροφική πλευρική σκλήρυνση, και η ατροφία πολλαπλών συστημάτων, και ο καρκίνος και το μελάνωμα.

بيرولات [3، 4-سي] اوكتاهيدروبيرولو ثنائية الاستبدال كمعدلات لمستقبل اوريكسين

وصفت في هذا الاختراع مركبات ثامن هيدروبيرولو[3، 4-andrlm;candrlm;]بيرولات ثنائية الاستبدال، والتي تكون مفيدة كمعدلات لمستقبل الأوركسين. وقد تكون تلك المركبات مفيدة في التركيبات الصيدلانية وطرق معالجة الحالات المرضية والاضطرابات والحالات الطبية التي تحدث نتيجة نشاط الأوركسين، مثل القلق.

Διυποκατεστημενα οκταϋδροπυρρολο [3,4-c]πυρρολια ως ρυθμιστες υποδοχεα ορεξινης

Περιγράφονται ενώσεις διυποκατεστημένου οκταϋδροπυρρολο[3,4-c]πυρρολίου, που είναι χρήσιμες ως ρυθμιστές υποδοχέα ορεξίνης. Τέτοιες ενώσεις μπορεί να είναι χρήσιμες σε φαρμακευτικές συνθέσεις και μεθόδους για τη θεραπεία καταστάσεων ασθένειας, διαταραχών και καταστάσεων που προκαλούνται με δραστικότητα ορεξίνης, όπως αϋπνίας.

fenil sulfonil fenil triazol tionas substituídas e usos destas

A presente revelação está relacionada às fenil sulfonil fenil triazol tionas substituídas, às composições farmacêuticas que as contêm e aos métodos de sua utilização.

Disubstituted octahydropyrrolo[3,4-c]pyrroles as orexin receptor modulators

Disubstituted octahydropyrrolo[3,4-c]pyrrole compounds are described, which are useful as orexin receptor modulators. Such compounds may be useful in pharmaceutical compositions and methods for the treatment of diseased states, disorders, and conditions mediated by orexin activity, such as insomnia.