# US 8,541,437 B2 · Substituted 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoles, methods for the production and use thereof

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- Number: US 8,541,437 B2
- Document ID: US8541437B2
- Status: Granted
- Kind: B2
- Application number: 12/594,453
- Filed: 2008-04-01
- Published: 2010-05-13
- Granted: 2013-09-24
- Earliest claimed: 2007-04-05
- Assignees: Alla Chem, LLC
- Applicants: Andrey Alexandrovich Ivashchenko; Alexandre Vasilievich Ivachtchenko; Sergey Yevgenievich Tkachenko; Evgueni Borisovich Frolov; Oleg Dmitrievich Mitkin; Dmitri Vladimirovich Kravchenko; Ilya Matusovich Okun; Nikolay Filippovich Savchuk; Yan Lavrovsky
- Inventors: Andrey Alexandrovich Ivashchenko; Alexandre Vasilievich Ivachtchenko; Sergey Yevgenievich Tkachenko; Evgueni Borisovich Frolov; Oleg Dmitrievich Mitkin; Dmitri Vladimirovich Kravchenko; Ilya Matusovich Okun; Nikolay Filippovich Savchuk; Yan Lavrovsky
- Web page: https://patentgrep.com/patent/US8541437B2

## CPC

- A61K 31/437: the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
- A61P 3/04: Anorexiants; Antiobesity agents
- A61K 31/444: containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 25/08: Antiepileptics; Anticonvulsants
- A61P 25/14: for treating abnormal movements, e.g. chorea, dyskinesia
- A61P 25/16: Anti-Parkinson drugs
- A61P 25/18: Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A61P 25/22: Anxiolytics
- A61P 25/24: Antidepressants
- 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
- A61P 37/02: Immunomodulators
- A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14)
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 471/04: Ortho-condensed systems
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

The invention relates to antagonists of serotonin 5-HT6 receptors simultaneously regulating homeostasis of Ca+2 ions in cells, representing substituted 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoles of the general formula 1, pharmaceutically acceptable salts and/or hydrate thereof. In the general formula 1: R1 represents amino group substituent selected from optionally substituted C1-C5 alkyl; R2i is one or more substituents selected from hydrogen, halogen, C1-C3 alkyl, CF3, OCF3; Ar is phenyl optionally substituted with halogen, C1-C6 alkyl, C1-C6 alkoxy, substituted amino group, or CF3; or optionally substituted aromatic 6-membered heterocycle comprising 1-2 nitrogen atoms in the cycle; W represents ethylene group —CH2—CH2—, ethenyl group —CH═CH—, or ethynyl group —C≡C—. The invention also relates to the novel compounds selected from the compounds of the general formula 1, methods for their preparation, pharmaceutical compositions and methods of their use.

## Claims

### Claim 1

A compound of the formula 1; or a pharmaceutically acceptable salt, or hydrate thereof:
wherein R1 is C1-C5 alkyl;
R2i is independently hydrogen, halogen, C1-C3 alkyl, CF3, OCF3 or OCH3;
i is 1, 2, 3, or 4;
Ar is unsubstituted phenyl or substituted phenyl substituted with halogen, C1-C6 alkyl, C1-C6 alkoxy, a substituted amino group or trifluoromethyl; or Ar is a substituted or unsubstituted 6-membered aromatic heterocycle one or, with two nitrogen atoms in the heterocycle; and
W is an ethenyl group or ethynyl group.

### Claim 2 (depends on 1)

The compound according to claim 1, wherein W is an ethenyl group.

### Claim 3 (depends on 2)

The compound according to claim 2, wherein the compound is:
wherein R2 is hydrogen, F, CH3, CF3, OCF3 or OCH3; and
Ar is substituted phenyl or substituted pyridyl.

### Claim 4 (depends on 2)

The compound according to claim 2, wherein the compound is:
or a pharmaceutically acceptable salt or hydrate thereof.

### Claim 5 (depends on 1)

The compound according to claim 1, of the formula 1.3, or a pharmaceutically acceptable salt or hydrate thereof:

### Claim 6 (depends on 5)

The compound according to claim 5, wherein the compound is:
wherein R2 is hydrogen, F, CH3, CF3, OCF3 or OCH3.

### Claim 7 (depends on 6)

The compound according to claim 6, wherein the compound is:
or a pharmaceutically acceptable salt or hydrate thereof.

### Claim 8 (depends on 1)

A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt or hydrate thereof, of claim 1 and a pharmaceutically acceptable carrier.

### Claim 9 (depends on 8)

The pharmaceutical composition according to claim 8, which is in the form of a tablet, capsule or an injectable liquid.

### Claim 10 (depends on 1)

A method of antagonizing a 5-HT6 serotonin receptor and simultaneously regulating Ca+2 ion homeostasis in a cell, comprising administering to the cell a compound of claim 1; or a pharmaceutically acceptable salt or hydrate thereof.

### Claim 11 (depends on 1)

A pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt or hydrate thereof, and a drug substance selected from the group consisting of a non-steroidal anti-inflammatory drug, inhibitor of acetylcholinesterase, NMDA-receptor antagonist, nootropic drug, AMRA receptor modulator, monoaminooxidase MAO-B or MAO-A inhibitor, antiamiloidogen drug, substance lowering beta-amyloid neurotoxicity, antagonist of GAMK (B) receptor, monoclonal antibody, antioxidant, neurotrophic agent, antidepressant, anorexic drug, hormonal drug, statin, hypoglycemic drug, and inhibitor of enzymes of fatty acid synthesis in the form of a tablet, capsule or injection placed in a pharmaceutically acceptable packing.