Azacyclic compounds

• US 6,756,393 B2
• Filed: 04/07/2003
• Issued: 06/29/2004
• Est. Priority Date: 03/06/2000
• Status: Expired due to Term

• Current Assignee: Acadia Pharmaceuticals Inc.
• Original Assignee: Acadia Pharmaceuticals Inc.
• Inventors: Croston, Glenn, Hansen, Eva L., Andersson, Carl-Magnus A., Uldam, Allan Kjaersgaard
• Primary Examiner(s): Shah, Mukund J.
• Assistant Examiner(s): Patel, Sudhaker B.
• Application Number:
  US10/409,782
• Publication Number:
  US 20030220316A1
• Time in Patent Office: 449 Days
• Field of Search: 514/183, 514/352, 514/357, 514/358, 546/244, 546/246, 546/248
• US Class Current: 514/352
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/08 Vasodilators for multiple indications
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 Antihypertensives
• CPC Class Codes: C07D 207/14 Nitrogen atoms not forming part of a nitro radical
• CPC Class Codes: C07D 211/26 with hydrocarbon radicals, substituted by nitrogen atoms
• CPC Class Codes: C07D 211/58 attached in position 4
• CPC Class Codes: C07D 401/06 : linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 401/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 407/06 : linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 407/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 409/06 : linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 409/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 451/02 : containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
• CPC Class Codes: C07D 451/06 : Oxygen atoms
• CPC Class Codes: C07D 487/08 : Bridged systems

Abstract

Compounds and methods are provided for the treatment of disease conditions in which modification of serotonergic receptor activity has a beneficial effect. In the method, an effective amount of a compound is adminstered to a patient in need of such treatment.

Claims

1. A compound of formula (I)

wherein

Z is

 

wherein R is a lower alkyl group, wherein said lower alkyl group is a methyl; and

n is 1;

X₁ is methylene, vinylene, or an NH or N(lower alkyl) group; and

X₂ is methylene;

or, when X₁ is methylene or vinylene, X₂ is methylene or a bond;

or when X₁ is methylene, X₂ is O, S, NH, or N(lower alkyl) or a bond;

Y₁ is methylene and Y₂ is methylene, vinylene, ethylene, propylene, or a bond;

or

Y₁ is a bond and Y₂ is vinylene;

or

Y₁ is ethylene and Y₂ is O, S, NH, or N(lower alkyl);

Ar₁ and Ar₂ independently are unsubstituted or substituted aryl or heteroaryl groups, provided that Ar₁ and Ar₂ are not simultaneously unsubstituted phenyl; and

W is oxygen;

or

a pharmaceutically acceptable salt or prodrug thereof.

2. A compound of formula (I)

wherein

Z is

 

wherein R is a hydrogen, a cyclic or straight-chained or branched acyclic organyl group, a lower hydroxyalkyl group, a lower aminoalkyl group, or an aralkyl or heteroaralkyl group; and

n is 1;

X₁ is an NH, and X₂ is methylene;

Y₁ is methylene and Y₂ is methylene, vinylene, ethylene, propylene, or a bond;

or

Y₁ is a bond and Y₂ is vinylene;

or

Y₁ is ethylene and Y₂ is O, S, NH, or N(lower alkyl);

Ar₁ and Ar₂ independently are unsubstituted or substituted aryl or heteroaryl groups, provided that Ar₁ and Ar₂ are not simultaneously unsubstituted phenyl; and

W is oxygen;

or

a pharmaceutically acceptable salt or prodrug thereof.

3. A compound of formula (I)

wherein

Z is

 

wherein R is a hydrogen, a cyclic or straight-chained or branched acyclic organyl group, a lower hydroxyalkyl group, a lower aminoalkyl group, or an aralkyl or heteroaralkyl group; and

n is 1;

X₁ is methylene, vinylene, or an NH or N(lower alkyl) group; and

X₂ is methylene, or, when X₁ is methylene or vinylene, X₂ is methylene or a bond;

or when X₁ is methylene, X₂ is O, S, NH, or N(lower alkyl) or a bond;

Y₁ is methylene and Y₂ is a bond;

Ar₁ and Ar₂ independently are unsubstituted or substituted aryl or heteroaryl groups, provided that Ar₁ and Ar₂ are not simultaneously unsubstituted phenyl; and

W is oxygen;

or

a pharmaceutically acceptable salt or prodrug thereof.

4. A compound of formula (I)

wherein

Z is

 

wherein R is a hydrogen, a cyclic or straight-chained or branched acyclic organyl group, a lower hydroxyalkyl group, a lower aminoalkyl group, or an aralkyl or heteroaralkyl group; and

n is 1;

X₁ is methylene, vinylene, or an NH or N(lower alkyl) group; and

X₂ is methylene, or, when X₁ is methylene or vinylene, X₂ is methylene or a bond;

or when X₁ is methylene, X₂ is O, S, NH, or N(lower alkyl) or a bond;

Y₁ is methylene and Y₂ is methylene, vinylene, ethylene, propylene, or a bond;

or

Y₁ is a bond and Y₂ is vinylene;

or

Y₁ is ethylene and Y₂ is O, S, NH, or N(lower alkyl);

Ar₁ is a 4-haloaryl, wherein said aryl is phenyl and said halo is a fluoro;

Ar₂ is a 4-substituted aryl, wherein said aryl is phenyl, and said phenyl is substituted with a lower alkoxy group, wherein the alkyl group of said lower alkoxy group is an isobutyl; and

W is oxygen;

or

a pharmaceutically acceptable salt or prodrug thereof.

5. A tartrate salt of a compound of formula (I)

wherein

Z is

 

wherein R is a hydrogen, a cyclic or straight-chained or branched acyclic organyl group, a lower hydroxyalkyl group, a lower aminoalkyl group, or an aralkyl or heteroaralkyl group; and

n is 1;

X₁ is methylene, vinylene, or an NH or N(lower alkyl) group; and

X₂ is methylene, or, when X₁ is methylene or vinylene, X₂ is methylene or a bond;

or when X₁ is methylene, X₂ is O, S, NH, or N(lower alkyl) or a bond;

Y₁ is methylene and Y₂ is methylene, vinylene, ethylene, propylene, or a bond;

or

Y₁ is a bond and Y₂ is vinylene;

or

Y₁ is ethylene and Y₂ is O, S, NH, or N(lower alkyl);

Ar₁ and Ar₂ independently are unsubstituted or substituted aryl or heteroaryl groups, provided that Ar₁ and Ar₂ are not simultaneously unsubstituted phenyl; and

W is oxygen.