US 8,138,333 B2Granted

Sulfonyl-indole derivatives

AssigneeProximagen Limited

InventorsJohan Angbrant, Peter Brandt, Rune Ringom, Bengt Lindqvist

Life of this patent

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Abstract

The present invention relates to novel compounds of formula (I): wherein R1, R2, R3, R4, and R5 are as described herein, to pharmaceutical compositions comprising the compounds, to processes for their preparation, as well as to the use of the compounds for the preparation of a medicament against 5-HT6 receptor-related disorders.

Claims17

Dependent claims

A compound of the Formula (I)

including pharmaceutically acceptable salts, geometrical isomers, tautomers, and optical isomers thereof, wherein:
represents a double bond;
m and n are each independently selected from 1 and 2,
provided that m+n≦3;
R1 is a group selected from:
(a) aryl, and
(b) heteroaryl;
wherein any heteroaryl or aryl residue, alone or as part of another group, is optionally independently substituted in one or more positions with a substituent selected from:
(a) halogen,
(b) C1-6-alkyl,
(c) hydroxy-C1-6-alkyl,
(d) fluoro-C1-6-alkyl,
(e) C3-7-cycloalkyl,
(f) hydroxy-C3-7-cycloalkyl,
(g) fluoro-C3-7-cycloalkyl,
(h) methyl-C3-7-cycloalkyl,
(i) C3-4-cycloalkyl-C1-3-alkyl,
(j) C3-4-cycloalkyl(hydroxy)-C1-3-alkyl,
(k) C1-6-alkoxy,
(l) fluoro-C1-6-alkoxy,
(m) C1-2-alkoxy-C1-4-alkyl,
(n) C3-7-cycloalkoxy,
(o) fluoro-C3-7-cycloalkoxy,
(p) methyl-C3-7-cycloalkoxy,
(q) C2-6-alkenyl,
(r) fluoro-C2-6-alkenyl,
(s) C2-6-alkynyl,
(t) hydroxy,
(u) —SCF3,
(v) —SCF2H,
(w) —SO2NR6R6,
(x) —S(O)eR7, wherein e is 0, 1, 2 or 3,
(y) —OSO2R7,
(z) —CN,
(aa) —NR6R6,
(ab) —NHSO2R7,
(ac) —NR8COR7,
(ad) —NO2,
(ae) —CONR6R6,
(af) —CO—R7,
(ag) —COOH,
(ah) C1-6-alkoxycarbonyl,
(ai) aryl,
(aj) heteroaryl,
(ak) aryloxy, and
(al) heteroaryloxy;
wherein any (ai) aryl or (aj) heteroaryl, alone or as part of another group, is optionally substituted in one or more positions with a substituent selected from:
(a) halogen,
(b) C1-4-alkyl,
(c) C1-4-alkoxy,
(d) —CF3, and
(e) —CN;
q is selected from 0, 1 and 2;
each R2 is independently selected from:
(a) C1-6-alkoxy,
(b) hydroxy, and
(c) —OSO2—CF3,
R3 is hydrogen;
each R4 is independently selected from:
(a) hydrogen,
(b) C1-4-alkyl,
(c) hydroxy, and
(d) oxo,
provided that when R4 is hydroxy or oxo, then either m or n is 2, and R4 is
not attached on a carbon in alpha position to the ring nitrogen atom;
R5 is a group selected from:
(a) hydrogen, and
(b) C1-4-alkyl,
each R6 is a group independently selected from:
(a) hydrogen,
(b) C1-6-alkyl,
(c) fluoro-C2-6-alkyl, and
(d) C3-7-cycloalkyl, or
two R6 groups together with the nitrogen to which they are attached form a heterocyclic ring optionally substituted with methyl;
each R7 is a group independently selected from:
(a) hydrogen,
(b) C1-6-alkyl,
(c) fluoro-C1-6-alkyl,
(d) C3-7-cycloalkyl,
(e) methyl-C3-7-cycloalkyl,
(f) C3-4-cycloalkyl-C1-3-alkyl,
(g) aryl, and
(h) heteroaryl;
wherein any heteroaryl or aryl residue is optionally independently substituted in one or more positions with a substituent selected from:
(a) halogen,
(b) C1-4-alkyl,
(c) C1-4-alkoxy,
(d) —CF3, and
(e) —CN;
each R8 is independently a group selected from:
(a) hydrogen,
(b) C1-6-alkyl,
(c) fluoro-C1-6-alkyl, and
(d) C3-7-cycloalkyl,
or R7 and R8 together with the atoms to which they are attached form a lactam ring when present in the group NR8COR7, or R7 and R8 together with the atoms to which they are attached form a sultam ring when present in the group NR8SO2R7;
provided that the said compound of Formula (I) is not 1-[(4-methylphenyl)sulfonyl]-3,4,5,6-tetrahydro-1H-azepino[5,4,3-cd]indole.

93 more elements

Dependencies are inferred from the claim text.

Facts

Application: 12/075,979Filed 13 Mar 2008 · us provisional application
Priority: SE 070061113 Mar 2007
Published: US 2008/0293694 A127 Nov 2008
Granted: 20 Mar 2012
Term ends: Not estimatedThe source records don’t support an estimate.

Classification22 codes

C07D 471/06
In which the condensed system contains two hetero rings: peri-condensed systems
A61P 1/14
Drugs for disorders of the alimentary tract or the digestive system: prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics,…
A61P 3/04
Drugs for disorders of the metabolism: anorexiants; Antiobesity agents
A61P 3/10
For glucose homeostasis: for hyperglycaemia, e.g. antidiabetics

Family

Application61/002,029Us provisional application · filed 5 Nov 2007
US 2008/0293694 A1Pre-grant publication · published 27 Nov 2008
US 8,138,333 B2This patent

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

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Abstract

A compound of the Formula (I)

including pharmaceutically acceptable salts, geometrical isomers, tautomers, and optical isomers thereof, wherein:
represents a double bond;
m and n are each independently selected from 1 and 2,
provided that m+n≦3;
R1 is a group selected from:
(a) aryl, and
(b) heteroaryl;
wherein any heteroaryl or aryl residue, alone or as part of another group, is optionally independently substituted in one or more positions with a substituent selected from:
(a) halogen,
(b) C1-6-alkyl,
(c) hydroxy-C1-6-alkyl,
(d) fluoro-C1-6-alkyl,
(e) C3-7-cycloalkyl,
(f) hydroxy-C3-7-cycloalkyl,
(g) fluoro-C3-7-cycloalkyl,
(h) methyl-C3-7-cycloalkyl,
(i) C3-4-cycloalkyl-C1-3-alkyl,
(j) C3-4-cycloalkyl(hydroxy)-C1-3-alkyl,
(k) C1-6-alkoxy,
(l) fluoro-C1-6-alkoxy,
(m) C1-2-alkoxy-C1-4-alkyl,
(n) C3-7-cycloalkoxy,
(o) fluoro-C3-7-cycloalkoxy,
(p) methyl-C3-7-cycloalkoxy,
(q) C2-6-alkenyl,
(r) fluoro-C2-6-alkenyl,
(s) C2-6-alkynyl,
(t) hydroxy,
(u) —SCF3,
(v) —SCF2H,
(w) —SO2NR6R6,
(x) —S(O)eR7, wherein e is 0, 1, 2 or 3,
(y) —OSO2R7,
(z) —CN,
(aa) —NR6R6,
(ab) —NHSO2R7,
(ac) —NR8COR7,
(ad) —NO2,
(ae) —CONR6R6,
(af) —CO—R7,
(ag) —COOH,
(ah) C1-6-alkoxycarbonyl,
(ai) aryl,
(aj) heteroaryl,
(ak) aryloxy, and
(al) heteroaryloxy;
wherein any (ai) aryl or (aj) heteroaryl, alone or as part of another group, is optionally substituted in one or more positions with a substituent selected from:
(a) halogen,
(b) C1-4-alkyl,
(c) C1-4-alkoxy,
(d) —CF3, and
(e) —CN;
q is selected from 0, 1 and 2;
each R2 is independently selected from:
(a) C1-6-alkoxy,
(b) hydroxy, and
(c) —OSO2—CF3,
R3 is hydrogen;
each R4 is independently selected from:
(a) hydrogen,
(b) C1-4-alkyl,
(c) hydroxy, and
(d) oxo,
provided that when R4 is hydroxy or oxo, then either m or n is 2, and R4 is
not attached on a carbon in alpha position to the ring nitrogen atom;
R5 is a group selected from:
(a) hydrogen, and
(b) C1-4-alkyl,
each R6 is a group independently selected from:
(a) hydrogen,
(b) C1-6-alkyl,
(c) fluoro-C2-6-alkyl, and
(d) C3-7-cycloalkyl, or
two R6 groups together with the nitrogen to which they are attached form a heterocyclic ring optionally substituted with methyl;
each R7 is a group independently selected from:
(a) hydrogen,
(b) C1-6-alkyl,
(c) fluoro-C1-6-alkyl,
(d) C3-7-cycloalkyl,
(e) methyl-C3-7-cycloalkyl,
(f) C3-4-cycloalkyl-C1-3-alkyl,
(g) aryl, and
(h) heteroaryl;
wherein any heteroaryl or aryl residue is optionally independently substituted in one or more positions with a substituent selected from:
(a) halogen,
(b) C1-4-alkyl,
(c) C1-4-alkoxy,
(d) —CF3, and
(e) —CN;
each R8 is independently a group selected from:
(a) hydrogen,
(b) C1-6-alkyl,
(c) fluoro-C1-6-alkyl, and
(d) C3-7-cycloalkyl,
or R7 and R8 together with the atoms to which they are attached form a lactam ring when present in the group NR8COR7, or R7 and R8 together with the atoms to which they are attached form a sultam ring when present in the group NR8SO2R7;
provided that the said compound of Formula (I) is not 1-[(4-methylphenyl)sulfonyl]-3,4,5,6-tetrahydro-1H-azepino[5,4,3-cd]indole.

93 more elements

Facts

Application

12/075,979Filed 13 Mar 2008 · us provisional application

Priority

SE 070061113 Mar 2007

Published

US 2008/0293694 A127 Nov 2008

Granted

20 Mar 2012

Term ends

Not estimatedThe source records don’t support an estimate.

Classification22 codes

C07D 471/06
In which the condensed system contains two hetero rings: peri-condensed systems
A61P 1/14
Drugs for disorders of the alimentary tract or the digestive system: prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics,…
A61P 3/04
Drugs for disorders of the metabolism: anorexiants; Antiobesity agents
A61P 3/10
For glucose homeostasis: for hyperglycaemia, e.g. antidiabetics