US 2023/0055376 A1 · 5-HT2C RECEPTOR AGONISTS AND COMPOSITIONS AND METHODS OF USE

Abstract

Provided in some embodiments are compounds of Formula A, as defined herein, that modulate the activity of 5-HT2C receptor. Also provided in some embodiments are methods, such as, for weight management, inducing satiety, and decreasing food intake, and for preventing and treating obesity, antipsychotic-induced weight gain, type 2 diabetes, Prader-Willi syndrome, tobacco/nicotine dependence, drug addiction, alcohol addiction, pathological gambling, reward deficiency syndrome, and sex addiction), obsessive-compulsive spectrum disorders and impulse control disorders (including nail-biting and onychophagia), sleep disorders (including insomnia, fragmented sleep architecture, and disturbances of slow-wave sleep), urinary incontinence, psychiatric disorders (including schizophrenia, anorexia nervosa, and bulimia nervosa), Alzheimer disease, sexual dysfunction, erectile dysfunction, epilepsy, movement disorders (including parkinsonism and antipsychotic-induced movement disorder), hypertension, dyslipidemia, nonalcoholic fatty liver disease, obesity-related renal disease, and sleep apnea.

Claims25

Dependent claims

-50. (canceled)

A method selected from the group consisting of decreasing food intake in an individual in need thereof, inducing satiety in an individual in need thereof, treating obesity in an individual in need thereof, and weight management in an individual in need thereof, the method comprising administering to the individual a therapeutically acceptable amount of a compound selected from the following compounds and pharmaceutically acceptable salts, solvates, and hydrates thereof:

Com-
pound
No.
Chemical Structure
Chemical Name
102
6,6′-dimethyl-2′,3′,4′,4a′,5′,6′- hexahydro-1′H- spiro[cyclopropane-1,7′- naphtho[1,8-cd]azepine]
103
(S)-6,6′-dimethyl- 2′,3′,4′,4a′,5′,6′-hexahydro- 1′H-spiro[cyclopropane-1,7′- naphtho[1,8-cd]azepine]
104
(R)-6′,6′-dimethyl- 2′,3′,4′,4a′,5′,6′-hexahydro- 1′H-spiro[cyclopropane-1,7′- naphtho[1,8-cd]azepine]
105
8′-fluoro-2′,3′,4′,4a′,5′- pentahydro-1′H- dispiro[cyclopropane-1,6′- cyclopropane-7′,1″- naphtho[1,8-cd]-azepine]
110
(S)-7,7-dimethyl- 1,2,3,4,4a,5,6,7- octahydronaphtho[1,8- cd]azepine
113
(R)-2′,3′,4′,4a′,5′-pentahydro- 1′H-dispiro[cyclopropane-1,6′- cyclopropane-7′,1″- naphtho[1,8-cd]-azepine]
114
(S)-2′,3′,4′,4a′,5′-pentahydro- 1′H-dispiro[cyclopropane-1,6′- cyclopropane-7′,1″- naphtho[1,8-cd]-azepine]
122
(R)-7,7-dimethyl- 1,2,3,4,4a,5,6,7- octahydronaphtho[1,8- cd]azepine
123
(S)-2′,3′,4′,4a′,5′,6′- hexahydro-1′H- spiro[cyclopropane-1,7′- naphtho[1,8-cd]azepine]
128
2′,3′,4′,4a′,5′,6′- hexahydro-1′H- spiro[cyclopropane-1,7′- naphtho[1,8-cd]azepine]
130
2′,3′,4′,4a′,5′-pentahydro-1′H- dispiro[cyclopropane-1,6′- cyclopropane-7′,1″- naphtho[1,8-cd]-azepine]
133
(R)-8′-fluoro- 2′,3′,4′,4a′,5′-pentahydro-1′H- dispiro[cyclopropane-1,6′- cyclopropane-7′,1″- naphtho[1,8-cd]-azepine]
134
(S)-8′-fluoro- 2′,3′,4′,4a′,5′-pentahydro-1′H- dispiro[cyclopropane-1,6′- cyclopropane-7′,1″- naphtho[1,8-cd]-azepine]
135
7,7-dimethyl-1,2,3,4,4a,5,6,7- octahydronaphtho[1,8- cd]azepine
136
(R)-2′,3′,4′,4a′,5′,6′-hexahydro- 1′H-spiro[cyclopropane-1,7′- naphtho[1,8-cd]azepine].

32 more elements

A method selected from the group consisting of treating type 2 diabetes in an individual in need thereof, treating drug and alcohol addiction in an individual in need thereof, and treating a seizure disorder in an individual in need thereof, wherein said seizure disorder is epilepsy or Dravet syndrome, the method comprising administering to the individual a therapeutically effective amount of a compound selected from the following compounds and pharmaceutically acceptable salts, solvates, and hydrates thereof:

Com-
pound
No.
Chemical Structure
Chemical Name
102
6,6′-dimethyl-2′,3′,4′,4a′,5′,6′- hexahydro-1′H- spiro[cyclopropane-1,7′- naphtho[1,8-cd]azepine]
103
(S)-6,6′-dimethyl- 2′,3′,4′,4a′,5′,6′-hexahydro- 1′H-spiro[cyclopropane-1,7′- naphtho[1,8-cd]azepine]
104
(R)-6′,6′-dimethyl- 2′,3′,4′,4a′,5′,6′-hexahydro- 1′H-spiro[cyclopropane-1,7′- naphtho[1,8-cd]azepine]
105
8′-fluoro-2′,3′,4′,4a′,5′- pentahydro-1′H- dispiro[cyclopropane-1,6′- cyclopropane-7′,1″- naphtho[1,8-cd]-azepine]
110
(S)-7,7-dimethyl- 1,2,3,4,4a,5,6,7- octahydronaphtho[1,8- cd]azepine
113
(R)-2′,3′,4′,4a′,5′-pentahydro- 1′H-dispiro[cyclopropane-1,6′- cyclopropane-7′,1″- naphtho[1,8-cd]-azepine]
114
(S)-2′,3′,4′,4a′,5′-pentahydro- 1′H-dispiro[cyclopropane-1,6′- cyclopropane-7′,1″- naphtho[1,8-cd]-azepine]
122
(R)-7,7-dimethyl- 1,2,3,4,4a,5,6,7- octahydronaphtho[1,8- cd]azepine
123
(S)-2′,3′,4′,4a′,5′,6′-hexahydro-1′H-spiro[cyclopropane-1,7′- naphtho[1,8-cd]azepine]
128
2′,3′,4′,4a′,5′,6′-hexahydro- 1′H-spiro[cyclobutane-1,7′-naphtho[1,8-cd]azepine]
130
2′,3′,4′,4a′,5′-pentahydro-1′H- dispiro[cyclopropane-1,6′- cyclopropane-7′,1″- naphtho[1,8-cd]-azepine]
133
(R)-8′-fluoro-2′,3′,4′,4a′,5′- pentahydro-1′H- dispiro[cyclopropane-1,6′- cyclopropane-7′,1″- naphtho[1,8-cd]-azepine]
134
(S)-8′-fluoro-2′,3′,4′,4a′,5′- pentahydro-1′H- dispiro[cyclopropane-1,6′- cyclopropane-7′,1″- naphtho[1,8-cd]-azepine]
135
7,7-dimethyl-1,2,3,4,4a,5,6,7- octahydronaphtho[1,8- cd]azepine
136
(R)-2′,3′,4′,4a′,5′,6′-hexahydro- 1′H-spiro[cyclopropane-1,7′- naphtho[1,8-cd]azepine].

32 more elements

Dependencies are inferred from the claim text.

Facts

Application

17/837,622Filed 10 Jun 2022

Priority

31 Jul 2015

Published

23 Feb 2023

Term ends

Not estimatedThe source records don’t support an estimate.

Classification12 codes

A61K 31/55
Having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins: having seven-membered rings, e.g. azelastine, pentylenetetrazole
A61P 3/04
Drugs for disorders of the metabolism: anorexiants; Antiobesity agents
A61P 3/10
For glucose homeostasis: for hyperglycaemia, e.g. antidiabetics
A61P 25/08
Drugs for disorders of the nervous system: antiepileptics; Anticonvulsants

Family

Application62/199,382Us provisional application · filed 31 Jul 2015

Application15/748,205Continuation · filed 29 Jan 2018

Application16/299,880Continuation · filed 12 Mar 2019

Application16/848,013Continuation · filed 14 Apr 2020

Application17/837,622Continuation

US 10,272,094 B2Related patent

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US 11,395,824 B2Related patent

US 2018/0214455 A1Published application

US 2020/0078368 A1Published application

US 2020/0383993 A1Published application

US 2023/0055376 A1This patent

From the US filing history. Foreign family members aren’t listed.

5-ht2c receptor agonists and compositions and methods of use

Life of this patent

5-ht2c receptor agonists and compositions and methods of use

Life of this patent

Abstract

Claims25