US 2003/0125345 A1 · Compounds capable of activating cholinergic receptors

Abstract

The present invention generally relates to nicotinic compounds, in the form of aryl substituted olefinic compounds, as well as pro-drug, N-oxide, metabolite and pharmaceutically acceptable salt forms thereof. Methods of modulating neurotransmitter release via administration of the compounds, pro-drugs, N-oxides and/or pharmaceutically acceptable salts are also disclosed.

Claims49

Dependent claims

A compound of the formula:

8
wherein each X and X′ is individually selected from the group consisting of N, NO, C—H, C—F, C—Cl, C—Br, C—I, C—R′, C—NR′R″, C—CF3, C—OH, C—CN, C—NO2, C—C2R′, C—SH, C—SCH3, C—N3, C—SO2CH3, C—OR′, C—SR′, C—C(═O)NR′R″, C—NR′C(═O)R′, C—C(═O)R′, C—C(═O)OR′, C(CH2)qOR′, C—OC(═O)R′, COC(═O)NR′R″ and C—NR′C(═O)OR′,
q is an integer from 1 to 6;
each A, A1 and A11 individually is a substituent selected from the group consisting of H, F, Cl, Br, I, R′, —NR′R″, —CF3, —OH, —CN, —NO2, —C2R′, —SH, —SCH3, —N3, —SO2CH3, —OR′, —SR′, —C(═O)NR′R″, —NR′C(═O)R′, —C(═O)R′, —C(═O)OR′, —(CH2)qOR′, —OC(═O)R′, —OC(═O)NR′R″ and —NR′C(═O)OR′,
m and n are integers such that the sum of m and n is an integer from 1 to 8 and n is at least 1;
each EI, EII, EIII, EIV, EV, EVI individually is hydrogen, C1-10 alkyl or halo-substituted lower alkyl, with the provision that at least one of EV and EVI is C1-10 alkyl;
each Z′ and Z″ individually is hydrogen, lower alkyl, —C(═O)R′, —C(═O)OR′, —C(═O)NR′R″, —C(═S)R′, —C(═S)OR′, —C(═S)NR′R″, —C(═NR′)R′, —C(═NR′)OR′, or —C(═NR′)NR′R″;
and
R′ and R″ are, individually, hydrogen, C1-C10 alkyl, an aromatic group-containing species or a substituted aromatic group-containing species, or R′ and R″ form a cycloalkyl group,
wherein the aromatic group-containing species is pyridyl, quinolinyl, pyrimidinyl, phenyl, or benzyl and the substituents are as defined above with respect to A, A′, A″ and A′″,
and pharmaceutically acceptable salts thereof.

8 more elements

Dependencies are inferred from the claim text.

Facts

Application

10/263,083Filed 2 Oct 2002

Priority

23 Apr 1996

Published

3 Jul 2003

Term ends

Not estimatedThe source records don’t support an estimate.

Classification19 codes

C07D 239/26
Having three or more double bonds between ring members or between ring members and non-ring members: with only hydrogen atoms, hydrocarbon or…
A61K 31/44
Having six-membered rings with one nitrogen as the only ring hetero atom: non condensed pyridines; Hydrogenated derivatives thereof
A61K 31/505
Having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines: pyrimidines; Hydrogenated…
A61P 25/00
Drugs for disorders of the nervous system

Family

Application08/631,761Continuation in part · filed 23 Apr 1996

Application09/098,285Continuation · filed 16 Jun 1998

Application09/522,117Continuation · filed 9 Mar 2000

Application09/641,496Continuation · filed 18 Aug 2000

Application09/973,411Continuation in part · filed 9 Oct 2001

Application10/263,083Continuation in part · filed 2 Oct 2002

Application10/263,083Continuation · filed 2 Oct 2002

US 2002/0052497 A1Published application

US 6,979,695 B2Related patent

US 2003/0125345 A1This patent

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

Abstract

Claims49

Dependent claims

A compound of the formula:

8
wherein each X and X′ is individually selected from the group consisting of N, NO, C—H, C—F, C—Cl, C—Br, C—I, C—R′, C—NR′R″, C—CF3, C—OH, C—CN, C—NO2, C—C2R′, C—SH, C—SCH3, C—N3, C—SO2CH3, C—OR′, C—SR′, C—C(═O)NR′R″, C—NR′C(═O)R′, C—C(═O)R′, C—C(═O)OR′, C(CH2)qOR′, C—OC(═O)R′, COC(═O)NR′R″ and C—NR′C(═O)OR′,
q is an integer from 1 to 6;
each A, A1 and A11 individually is a substituent selected from the group consisting of H, F, Cl, Br, I, R′, —NR′R″, —CF3, —OH, —CN, —NO2, —C2R′, —SH, —SCH3, —N3, —SO2CH3, —OR′, —SR′, —C(═O)NR′R″, —NR′C(═O)R′, —C(═O)R′, —C(═O)OR′, —(CH2)qOR′, —OC(═O)R′, —OC(═O)NR′R″ and —NR′C(═O)OR′,
m and n are integers such that the sum of m and n is an integer from 1 to 8 and n is at least 1;
each EI, EII, EIII, EIV, EV, EVI individually is hydrogen, C1-10 alkyl or halo-substituted lower alkyl, with the provision that at least one of EV and EVI is C1-10 alkyl;
each Z′ and Z″ individually is hydrogen, lower alkyl, —C(═O)R′, —C(═O)OR′, —C(═O)NR′R″, —C(═S)R′, —C(═S)OR′, —C(═S)NR′R″, —C(═NR′)R′, —C(═NR′)OR′, or —C(═NR′)NR′R″;
and
R′ and R″ are, individually, hydrogen, C1-C10 alkyl, an aromatic group-containing species or a substituted aromatic group-containing species, or R′ and R″ form a cycloalkyl group,
wherein the aromatic group-containing species is pyridyl, quinolinyl, pyrimidinyl, phenyl, or benzyl and the substituents are as defined above with respect to A, A′, A″ and A′″,
and pharmaceutically acceptable salts thereof.

8 more elements

Dependencies are inferred from the claim text.

Compounds capable of activating cholinergic receptors

Life of this patent

Abstract

Claims49

Compounds capable of activating cholinergic receptors

Life of this patent

Abstract

Claims49