Therapeutic compounds
View Patent ↗The invention relates to protein binding interacting/binding compounds and methods of identifying and using them. The invention further relates to pharmaceutical compositions and methods for treating 5-HT2C disorders, including diseases and disorders mediated by GPCRs.
1. A method of treating a GPCR-mediated disorder in a subject comprising administering to the subject identified as in need thereof a compound, wherein the GPCR-mediated disorder is selected from a neuropsychiatric disorder, a neurodegenerative disorder, a neurological disorder, a cardiovascular disorder, a gastrointestinal disorder, or a genito-urinary tract disorder; and the compound is:
wherein,
R 1 is independently H, NH 2 , NH(alkyl), N(alkyl) 2 ;
R 2 is independently —(CH 2 )n-;
Each n is independently 1 or 2;
R 3 is independently H, OH, or halo;
R 4 is independently H, OH, or halo;
R 5 is alkyl or halo;
R 6 is independently H or alkyl;
R 7 independently H, N(alkyl) 2 ;
the neuropsychiatric disorder is selected from the group consisting of obesity, addiction, anxiety, depression, schizophrenia, and sleep disorders;
the neurodegenerative disorder is selected from the group consisting of Parkinson's Disease and Alzheimer's Disease;
the neurological disorder is epilepsy;
the cardiovascular disorder is hypertension;
the gastrointestinal disorder is irritable bowel syndrome; and
the genito-urinary tract disorder is bladder control.
2. The method of claim 1 , wherein the compound is a compound of the following table:
Config
R 1
R 2
R 3
R 4
R 5
R 6
R 7
(±)-trans
N(CH 3 ) 2
CH 2
H
H
p-Cl
H
H
(±)-trans
N(CH 3 ) 2
CH 2
H
H
p-F
H
H
(±)-trans
N(CH 3 ) 2
CH 2
H
H
p-CH 3
H
H
(±)-trans
N(CH 3 ) 2
CH 2
H
H
o-Cl
H
H
(±)-trans
N(CH 3 ) 2
CH 2
H
H
o-CH 3
H
H
(±)-trans
N(CH 3 ) 2
CH 2
H
H
m-OCH 3
H
H
(±)-trans
N(CH 3 ) 2
CH 2
H
H
m-F
H
H
(±)-trans
N(CH 3 ) 2
CH 2
H
H
m-Cl
H
H
(±)-trans
N(CH 3 ) 2
CH 2
H
H
m-Br
H
H
(±)-trans
N(CH 3 ) 2
CH 2
H
H
m-CH 3
H
H
(±)-trans
N(CH 3 ) 2
CH 2
H
H
p-C(CH 3 ) 3
H
H.
3. The method of claim 1 , wherein in the compound R 1 is —NMe 2 .
4. The method of claim 3 , wherein the-compound is (1R,3S)-(−)-Trans-1-(3-bromo-phenyl-3-N,N-dimethylamino-1,2,3,4-tetrahydronaphthalene.
5. The method of claim 1 , wherein the disorder is cocaine addiction.
6. The method of claim 1 , wherein the disorder is obesity.
7. A method of treating a GPCR-mediated disorder in a subject comprising administering to the subject identified as in need thereof a compound, wherein the GPCR-mediated disorder is selected from a neuropsychiatric disorder, a neurodegenerative disorder, a neurological disorder, a cardiovascular disorder, a gastrointestinal disorder, or a genito-urinary tract disorder; and the compound is:
wherein,
R 1 is independently H, NH 2 , NH(alkyl), N(alkyl) 2 ;
R 2 is independently —(CH 2 )n-;
Each n is independently 1 or 2;
R 3 is independently OH or halo;
R 4 is independently H, OH, or halo;
R 5 is H;
R 6 is independently H or alkyl;
R 7 independently H, N(alkyl) 2 ;
the neuropsychiatric disorder is selected from the group consisting of obesity, addiction, anxiety, depression, schizophrenia, and sleep disorders;
the neurodegenerative disorder is selected from the group consisting of Parkinson's Disease and Alzheimer's Disease;
the neurological disorder is epilepsy;
the cardiovascular disorder is hypertension;
the gastrointestinal disorder is irritable bowel syndrome; and
the genito-urinary tract disorder is bladder control.
8. The method of claim 7 , wherein the compound is a compound of the following table:
Config
R 1
R 2
R 3
R 4
R 5
R 6
R 7
(±)-trans
N(CH 3 ) 2
CH 2
Cl
OH
H
H
H
(±)-cis
N(CH 3 ) 2
CH 2
Cl
OH
H
H
H
(±)-trans
N(CH 3 ) 2
CH 2
OH
OH
H
H
H
(±)-cis
N(CH 3 ) 2
CH 2
OH
OH
H
H
H
(±)-trans
NH 2
CH 2
OH
OH
H
H
H
(±)-cis
NH 2
CH 2
OH
OH
H
H
H.
9. A method of treating a GPCR-mediated disorder in a subject comprising administering to the subject identified as in need thereof a compound, wherein the GPCR-mediated disorder is selected from a neuropsychiatric disorder, a neurodegenerative disorder, a neurological disorder, a cardiovascular disorder, a gastrointestinal disorder, or a genito-urinary tract disorder; and the compound is:
wherein,
R 1 is independently H, NH 2 , NH(alkyl), N(alkyl) 2 ;
R 2 is independently —(CH 2 )n-;
Each n is independently 1 or 2;
R 3 is independently H, OH, or halo;
R 4 is independently OH or halo;
R 5 is H;
R 6 is independently H or alkyl;
R 7 independently H, N(alkyl) 2 ;
the neuropsychiatric disorder is selected from the group consisting of obesity, addiction, anxiety, depression, schizophrenia, and sleep disorders;
the neurodegenerative disorder is selected from the group consisting of Parkinson's Disease and Alzheimer's Disease;
the neurological disorder is epilepsy;
the cardiovascular disorder is hypertension;
the gastrointestinal disorder is irritable bowel syndrome; and
the genito-urinary tract disorder is bladder control.
10. The method of claim 3 , wherein the compound is (−)-(trans)-4-(4-chlorophenyl)-N,N-dimethyl-1,2,3,4-tetrahydronaphthalen-2-amine, (−)-(trans)-4-(4-fluorophenyl)-N,N-dimethyl-1,2,3,4-tetrahydronaphthalen-2-amine, (−)-(trans)-4-(4-methylphenyl)-N,N-dimethyl-1,2,3,4-tetrahydronaphthalen-2-amine, or (−)-(trans)-4-(2-chlorophenyl)-N,N-dimethyl-1,2,3,4-tetrahydronaphthalen-2-amine.
11. A method of treating a GPCR-mediated disorder in a subject comprising administering to the subject identified as in need thereof a compound, wherein the GPCR-mediated disorder is selected from a neuropsychiatric disorder, a neurodegenerative disorder, a neurological disorder, a cardiovascular disorder, a gastrointestinal disorder, or a genito-urinary tract disorder; and the compound is:
wherein,
R 1 is independently N(C 2 H 5 ) 2 , N(C 3 H 5 ) 2 , NCH 3 (C 3 H 5 ), or NH(C 3 H 5 );
R 2 is independently —(CH 2 )n-;
Each n is independently 1 or 2;
R 3 is independently H, OH, or halo;
R 4 is independently H, OH or halo;
R 5 is H;
R 6 is independently H or alkyl;
R 7 independently H, N(alkyl) 2 ;
the neuropsychiatric disorder is selected from the group consisting of obesity, addiction, anxiety, depression, schizophrenia, and sleep disorders;
the neurodegenerative disorder is selected from the group consisting of Parkinson's Disease and Alzheimer's Disease;
the neurological disorder is epilepsy;
the cardiovascular disorder is hypertension;
the gastrointestinal disorder is irritable bowel syndrome; and
the genito-urinary tract disorder is bladder control.
12. The method of claim 11 , wherein the compound is a compound of the following table:
Config
R 1
R 2
R 3
R 4
R 5
R 6
R 7
(±)-trans
N(C 2 H 5 ) 2
CH 2
H
H
H
H
H
(±)-trans
N(C 3 H 5 ) 2
CH 2
H
H
H
H
H
(±)-trans
NCH 3 (C 3 H 5 )
CH 2
H
H
H
H
H
(±)-trans
NH(C 3 H 5 )
CH 2
H
H
H
H
H.