US 7,678,800 B2Granted

2-(1H-indolylsulfanyl)-aryl amine derivatives for use in the treatment of affective disorders, pain, ADHD and stress urinary incontinence

AssigneeH. Lundbeck A/S

InventorsJan Kehler, Friedrich Kroll, Karsten Juhl

Life of this patent

Estimating the term…

Abstract

The present invention relates to 2-(1H-indolylsulfanyl)-aryl amine derivatives of the general formula I as the free base or salts thereof and their use for the treatment of affective disorders, pain, attention deficit hyperactivity disorder (ADHD) and stress urinary incontinence.

Claims29

Dependent claims

A compound having the general formula I as the free base or salts thereof

wherein
the dotted line represents an optional bond;
each of R1-R4 is independently selected from the group consisting of hydrogen, halogen, cyano, nitro, C1-6-alk(en/yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en/yn)yl, amino, C1-6-alk(en/yn)ylamino, di-(C1-6-alk(en/yn)yl)amino, C1-6-alk(en/yn)ylcarbonyl, aminocarbonyl, C1-6-alk(en/yn)ylaminocarbonyl, di-(C1-6-alk(en)yl)aminocarbonyl, hydroxy, C1-6-alk(en/yn)yloxy, C1-6-alk(en/yn)ylsulfanyl, halo-C1-6-alk(en/yn)yl, halo-C1-6-alk(en/yn)ylsulfonyl, halo-C1-6-alk(en/yn)ylsulfanyl and C1-6-alk(en/yn)ylsulfonyl;
R5 is selected from the group consisting of hydrogen, halogen, cyano, C1-6-alk(en/yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en/yn)yl, amino, C1-6-alk(en/yn)ylamino, di-(C1-6-alk(en/yn)yl)amino, C1-6-alk(en/yn)ylcarbonyl, aminocarbonyl, C1-6-alk(en/yn)ylaminocarbonyl, di-(C1-6-alk(en)yl)aminocarbonyl, hydroxy, C1-6-alk(en/yn)yloxy, C1-6-alk(en/yn)ylsulfanyl, halo-C1-6-alk(en/yn)yl, halo-C1-6-alk(en/yn)ylsulfonyl, halo-C1-6-alk(en/yn)ylsulfanyl and C1-6-alk(en/yn)ylsulfonyl;
each of R6-R9 is independently selected from the group consisting of hydrogen, halogen, cyano, nitro, C1-6-alk(en/yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en/yn)yl, amino, C1-6-alk(en/yn)ylamino, di-(C1-6-alk(en/yn)yl)amino, C1-6-alk(en/yn)ylcarbonyl, aminocarbonyl, C1-6-alk(en/yn)ylaminocarbonyl, di-(C1-6-alk(en)yl)aminocarbonyl, hydroxy, C1-6-alk(en/yn)yloxy, C1-6-alk(en/yn)ylsulfanyl, halo-C1-6-alk(en/yn)yl, halo-C1-6-alk(en/yn)ylsulfonyl, halo-C1-6-alk(en/yn)ylsulfanyl, C1-6-alk(en/yn)ylsulfonyl and C1-6-alk(en/yn)yl-O—CO—;
R10 is selected from the group consisting of hydrogen, C1-6-alk(en/yn)yl, C3-8-cycloalk(en)yl and C3-8-cycloalk(en)yl-C1-6-alk(en/yn)yl;
Z is selected from the group consisting of N, CH and C, with the proviso that the dotted line represents a bond when Z is C and the dotted line does not represent a bond when Z is CH or N.

4 more elements

A compound selected from the group consisting of:

3-(2-piperazin-1-yl-phenylsulfanyl)-1H-indole,
4-Methoxy-3-(2-piperazin-1-yl-phenylsulfanyl)-1H-indole,
3-(2-piperazin-1-yl-phenylsulfanyl)-1H-indole-7-carboxylic acid methyl ester,
5-Nitro-3-(2-piperazin-1-yl-phenylsulfanyl)-1H-indole,
6-Chloro-3-(2-piperazin-1-yl-phenylsulfanyl)-1H-indole,
6-Methoxy-3-(2-piperazin-1-yl-phenylsulfanyl)-1H-indole,
6-Fluoro-3-(2-piperazin-1-yl-phenylsulfanyl)-1H-indole,
7-Methyl-3-(2-piperazin-1-yl-phenylsulfanyl)-1H-indole,
3-[2-(1,2,3,6-Tetrahydro-pyridin-4-yl)-phenylsulfanyl]-1H-indole,
6-Methyl-3-(2-piperazin-1-yl-phenylsulfanyl)-1H-indole,
4-Fluoro-3-(2-piperazin-1-yl-phenylsulfanyl)-1H-indole,
5-Fluoro-3-(2-piperazin-1-yl-phenylsulfanyl)-1H-indole,
4-Methyl-3-(4-methyl-2-piperazin-1-yl-phenylsulfanyl)-1H-indole,
6-Fluoro-3-(4-methyl-2-piperazin-1-yl-phenylsulfanyl)-1H-indole,
4-Fluoro-3-(4-methyl-2-piperazin-1-yl-phenylsulfanyl)-1H-indole,
7-Fluoro-3-(4-methyl-2-piperazin-1-yl-phenylsulfanyl)-1H-indole,
5-Methoxy-4-methyl-3-(4-methyl-2-piperazin-1-yl-phenylsulfanyl)-1H-indole,
5-Methoxy-3-(4-methyl-2-piperazin-1-yl-phenylsulfanyl)-1H-indole,
7-Methoxy-3-(4-methyl-2-piperazin-1-yl-phenylsulfanyl)-1H-indole,
4-Methoxy-3-(4-methyl-2-piperazin-1-yl-phenylsulfanyl)-1H-indole,
4-Chloro-3-(4-methyl-2-piperazin-1-yl-phenylsulfanyl)-1H-indole,
7-Chloro-3-(4-methyl-2-piperazin-1-yl-phenylsulfanyl)-1H-indole,
1-Methyl-3-(4-methyl-2-piperazin-1-yl-phenylsulfanyl)-1H-indole,
3-Methyl-2-(4-methyl-2-piperazin-1-yl-phenylsulfanyl)-1H-indole,
2-Methyl-3-(2-piperazin-1-yl-phenylsulfanyl)-1H-indole,
5-Methyl-3-(2-piperazin-1-yl-phenylsulfanyl)-1H-indole,
4-Methyl-3-(2-piperazin-1-yl-phenylsulfanyl)-1H-indole,
7-Fluoro-3-(2-piperazin-1-yl-phenylsulfanyl)-1H-indole,
7-Ethyl-3-(2-piperazin-1-yl-phenylsulfanyl)-1H-indole,
5-Methoxy-4-methyl-3-(2-piperazin-1-yl-phenylsulfanyl)-1H-indole,
5-Methoxy-3-(2-piperazin-1-yl-phenylsulfanyl)-1H-indole,
7-Methoxy-3-(2-piperazin-1-yl-phenylsulfanyl)-1H-indole,
5-Fluoro-2-methyl-3-(2-piperazin-1-yl-phenylsulfanyl)-1H-indole,
5-Chloro-3-(2-piperazin-1-yl-phenylsulfanyl)-1H-indole,
4-Chloro-3-(2-piperazin-1-yl-phenylsulfanyl)-1H-indole,
7-Chloro-3-(2-piperazin-1-yl-phenylsulfanyl)-1H-indole,
1-Methyl-3-(2-piperazin-1-yl-phenylsulfanyl)-1H-indole,
3-Methyl-2-(2-piperazin-1-yl-phenylsulfanyl)-1H-indole,
6-Methyl-3-(4-methyl-2-piperazin-1-yl-phenylsulfanyl)-1H-indole,
2-Methyl-3-(4-methyl-2-piperazin-1-yl-phenylsulfanyl)-1H-indole,
5-Methyl-3-(4-methyl-2-piperazin-1-yl-phenylsulfanyl)-1H-indole,
7-Methyl-3-(4-methyl-2-piperazin-1-yl-phenylsulfanyl)-1H-indole,
3-(2-Piperidin-4-yl-phenylsulfanyl)-1H-indole,
2-Methyl-3-(2-piperidin-4-yl-phenylsulfanyl)-1H-indole,
1-Methyl-3-(2-piperidin-4-yl-phenylsulfanyl)-1H-indole,
5-Methyl-3-(2-piperidin-4-yl-phenylsulfanyl)-1H-indole,
7-Fluoro-3-(2-piperidin-4-yl-phenylsulfanyl)-1H-indole,
6-Fluoro-3-(2-piperidin-4-yl-phenylsulfanyl)-1H-indole,
5-Methoxy-4-methyl-3-(2-piperidin-4-yl-phenylsulfanyl)-1H-indole,
4-Fluoro-3-(2-piperidin-4-yl-phenylsulfanyl)-1H-indole,
7-Methyl-3-(2-piperidin-4-yl-phenylsulfanyl)-1H-indole,
4-Methyl-3-(2-piperidin-4-yl-phenylsulfanyl)-1H-indole,
4-Chloro-3-(2-piperidin-4-yl-phenylsulfanyl)-1H-indole,
6-Chloro-3-(2-piperidin-4-yl-phenylsulfanyl)-1H-indole,
5-Fluoro-3-(2-piperidin-4-yl-phenylsulfanyl)-1H-indole,
5-Methoxy-3-(2-piperidin-4-yl-phenylsulfanyl)-1H-indole,
5-Chloro-3-(2-piperidin-4-yl-phenylsulfanyl)-1H-indole,
7-Methoxy-3-(2-piperidin-4-yl-phenylsulfanyl)-1H-indole,
7-Chloro-3-(2-piperidin-4-yl-phenylsulfanyl)-1H-indole,
7-Ethyl-3-(2-piperidin-4-yl-phenylsulfanyl)-1H-indole,
3-Methyl-2-(2-piperidin-4-yl-phenylsulfanyl)-1H-indole,
6-Methyl-3-(2-piperidin-4-yl-phenylsulfanyl)-1H-indole, and
5-Fluoro-2-methyl-3-(2-piperidin-4-yl-phenylsulfanyl)-1H-indole;
or a pharmaceutically acceptable salt thereof.

61 more elements

Dependencies are inferred from the claim text.

Facts

Application: 11/629,043Filed 13 Jul 2005
Priority: DK 2004 0112116 Jul 2004
Published: US 2008/0027074 A131 Jan 2008
Granted: 16 Mar 2010
Term ends: Not estimatedThe source records don’t support an estimate.

Classification17 codes

C07D 209/30
Indoles; Hydrogenated indoles: with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen,…
A61P 13/02
Drugs for disorders of the urinary system: of urine or of the urinary tract, e.g. urine acidifiers
A61P 21/00
Drugs for disorders of the muscular or neuromuscular system
A61P 25/00
Drugs for disorders of the nervous system

Family

US 2008/0027074 A1Pre-grant publication · published 31 Jan 2008
US 7,678,800 B2This patent

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

Timeline

Citations

Open elsewhere

patentgrep

Loading patent…

Abstract

A compound having the general formula I as the free base or salts thereof

wherein
the dotted line represents an optional bond;
each of R1-R4 is independently selected from the group consisting of hydrogen, halogen, cyano, nitro, C1-6-alk(en/yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en/yn)yl, amino, C1-6-alk(en/yn)ylamino, di-(C1-6-alk(en/yn)yl)amino, C1-6-alk(en/yn)ylcarbonyl, aminocarbonyl, C1-6-alk(en/yn)ylaminocarbonyl, di-(C1-6-alk(en)yl)aminocarbonyl, hydroxy, C1-6-alk(en/yn)yloxy, C1-6-alk(en/yn)ylsulfanyl, halo-C1-6-alk(en/yn)yl, halo-C1-6-alk(en/yn)ylsulfonyl, halo-C1-6-alk(en/yn)ylsulfanyl and C1-6-alk(en/yn)ylsulfonyl;
R5 is selected from the group consisting of hydrogen, halogen, cyano, C1-6-alk(en/yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en/yn)yl, amino, C1-6-alk(en/yn)ylamino, di-(C1-6-alk(en/yn)yl)amino, C1-6-alk(en/yn)ylcarbonyl, aminocarbonyl, C1-6-alk(en/yn)ylaminocarbonyl, di-(C1-6-alk(en)yl)aminocarbonyl, hydroxy, C1-6-alk(en/yn)yloxy, C1-6-alk(en/yn)ylsulfanyl, halo-C1-6-alk(en/yn)yl, halo-C1-6-alk(en/yn)ylsulfonyl, halo-C1-6-alk(en/yn)ylsulfanyl and C1-6-alk(en/yn)ylsulfonyl;
each of R6-R9 is independently selected from the group consisting of hydrogen, halogen, cyano, nitro, C1-6-alk(en/yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en/yn)yl, amino, C1-6-alk(en/yn)ylamino, di-(C1-6-alk(en/yn)yl)amino, C1-6-alk(en/yn)ylcarbonyl, aminocarbonyl, C1-6-alk(en/yn)ylaminocarbonyl, di-(C1-6-alk(en)yl)aminocarbonyl, hydroxy, C1-6-alk(en/yn)yloxy, C1-6-alk(en/yn)ylsulfanyl, halo-C1-6-alk(en/yn)yl, halo-C1-6-alk(en/yn)ylsulfonyl, halo-C1-6-alk(en/yn)ylsulfanyl, C1-6-alk(en/yn)ylsulfonyl and C1-6-alk(en/yn)yl-O—CO—;
R10 is selected from the group consisting of hydrogen, C1-6-alk(en/yn)yl, C3-8-cycloalk(en)yl and C3-8-cycloalk(en)yl-C1-6-alk(en/yn)yl;
Z is selected from the group consisting of N, CH and C, with the proviso that the dotted line represents a bond when Z is C and the dotted line does not represent a bond when Z is CH or N.

4 more elements

Facts

Application

11/629,043Filed 13 Jul 2005

Priority

DK 2004 0112116 Jul 2004

Published

US 2008/0027074 A131 Jan 2008

Granted

16 Mar 2010

Term ends

Not estimatedThe source records don’t support an estimate.

Classification17 codes

C07D 209/30
Indoles; Hydrogenated indoles: with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen,…
A61P 13/02
Drugs for disorders of the urinary system: of urine or of the urinary tract, e.g. urine acidifiers
A61P 21/00
Drugs for disorders of the muscular or neuromuscular system
A61P 25/00
Drugs for disorders of the nervous system