US 2008/0176829 A1Published application

Compounds

AssigneeProximagen Limited

InventorsPeter Brandt, Erik Ringberg, Berts Wei, Rune Ringom, Kristin Hammer, Sofia Henriksson, Bengt Lindqvist

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Abstract

The present invention relates to compounds of the formula (I) wherein A, X and R1 to R9 are as described herein; to pharmaceutical compositions comprising the said compounds; to processes for their preparation; and to the use of the compounds as medicaments against 5-HT6 receptor-related disorders.

Claims22

Dependent claims

The compound of the formula (I):

wherein:
represents a single bond or a double bond;
A is N or NR5;
X is O, S, N—H or N—C1-6-alkyl;
R1 is a group selected from:
(a) C1-6-alkyl,
(b) C3-7-cycloalkyl,
(c) C3-6-alkenyl,
(d) aryl,
(e) aryl-C2-6-alkenyl,
(f) aryl-C1-6-alkyl,
(g) heteroaryl,
(h) heteroaryl-C2-6-alkenyl, and
(i) heteroaryl-C1-6-alkyl,
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) fluoro-C1-6-alkyl,
(d) C3-7-cycloalkyl,
(e) methyl-C3-7-cycloalkyl,
(f) fluoro-C3-7-cycloalkyl,
(g) C2-6-alkenyl,
(h) fluoro-C2-6-alkenyl,
(i) ethynyl;
(j) hydroxy-C1-4-alkyl,
(k) hydroxy,
(l) C1-6-alkoxy
(m) fluoro-C1-6-alkoxy
(n) C3-7-cycloalkoxy
(o) methyl-C3-7-cycloalkoxy
(p) fluoro-C3-7-cycloalkoxy
(q) —SCF3,
(r) —SCF2H,
(s) —SO2NR10R10,
(t) —S(O)eR11, wherein e is 0, 1, 2 or 3,
(u) —CN,
(v) —NR10R10,
(w) —NHSO2R11,
(x) —NR12COR11,
(y) —NO2,
(z) —CONR10R10,
(aa) —CO—R11,
(bb) —COOH,
(cc) C1-6-alkoxycarbonyl,
(dd) aryl,
(ee) heteroaryl,
(ff) aryloxy, and
(gg) heteroaryloxy,
wherein any (dd) aryl or (ee) 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-alkylthio,
(d) C1-4-alkoxy,
(e) —CF3,
(f) —CN, and
(g) hydroxymethyl;
R2 is a group selected from:
(a) hydrogen
(b) halogen,
(C) C1-6-alkyl,
(d) fluoro-C1-6-alkyl,
(e) C3-7-cycloalkyl,
(f) methyl-C3-7-cycloalkyl,
(g) fluoro-C3-7-cycloalkyl,
(h) C2-6-alkenyl,
(i) fluoro-C2-6-alkenyl,
(j) ethynyl,
(k) hydroxy-C1-4-alkyl,
(l) hydroxy,
(m) C1-6-alkoxy,
(n) fluoro-C1-6-alkoxy,
(o) C3-7-cycloalkoxy,
(p) methyl-C3-7-cycloalkoxy,
(q) fluoro-C3-7-cycloalkoxy,
(r) —SCF3,
(s) —SCF2H,
(t) —SO2NR10R10,
(u) —S(O)eR11, wherein e is 0, 1, 2 or 3,
(v) —CN,
(w) —NR10R10,
(x) —NR12SO2R11,
(y) —NR12COR11,
(z) —NO2,
(aa) —CONR10R10,
(bb) —OCONR10R10,
(cc) —CO—R11,
(dd) —COOH, and
(ee) C1-6-alkoxycarbonyl;
R3is a group selected from:
(a) hydrogen,
(b) halogen,
(c) C1-6-alkyl,
(d) C3-7-cycloalkyl,
(e) hydroxy-C1-4-alkyl,
(f) C3-7-cycloalkyl-hydroxy-C1-4-alkyl
(g) C1-2-alkoxy-C1-4-alkyl
(h) —COOR12,
(i) —CONR10R10,
(j) —CO—R11,
(k) —CN,
(l) aryl, and
(m) 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-alkylthio,
(d) C1-4-alkoxy,
(e) —CF3,
(f) —CN, and
(g) hydroxymethyl;
R4 is a group selected from:
(a) hydrogen,
(b) C1-4-alkyl,
(c) fluoro-C1-4-alkyl,
(d) C3-5-cycloalkyl,
(e) fluoro-C3-5-cycloalkyl,
(f) hydroxy-C1-4-alkyl, and
(g) cyano;
R5 is a group selected from:
(a) hydrogen,
(b) C1-4-alkyl,
(c) fluoro-C1-4-alkyl,
(d) 2-cyanoethyl,
(e) hydroxy-C2-4-alkyl,
(f) C3-4-alkenyl,
(g) C3-4-alkynyl,
(h) C3-7-cycloalkyl,
(i) methyl-C3-7-cycloalkyl
(j) fluoro-C3-7-cycloalkyl,
(k) C3-4-cycloalkyl-C1-4-alkyl, and
(l) C1-4-alkoxy-C2-4-alkyl, or
R5 and one of R6, R7, R8, or R9 groups together with the atoms to which they are attached form a heterocyclic ring and the other three of R6, R7, R8 or R9 are hydrogen;
R6, R7, R8, and R9 are each independently selected from:
(a) hydrogen,
(b) C1-6-alkyl,
(c) fluoro-C1-6-alkyl,
(d) C3-7-cycloalkyl, and
(e) hydroxy-C1-4-alkyl,
with the proviso that three of R6, R7, R8 and R9 are hydrogen unless at least two of R6, R7, R8 and R9 are methyl and the remainder of them are hydrogen,
two of the R6, R7, R8, or R9 groups together with the atoms to which they are attached form a carbocyclic or heterocyclic ring and the other two of R6, R7, R8or R9 are hydrogen, or
one of R6, R7, R8, or R9 groups and R5 together with the atoms to which they are attached form a heterocyclic ring and the other three of R6, R7, R8 or R9 are hydrogen;
R10 is each independently a group selected from:
(a) hydrogen,
(b) C1-6-alkyl,
(c) fluoro-C2-6-alkyl, and
(d) C3-7-cycloalkyl, or
two R10 groups together with the nitrogen to which they are attached form a heterocyclic ring optionally substituted with methyl;
R11 is each independently a group selected from:
(a) hydrogen,
(b) C1-6-alkyl,
(c) fluoro-C1-6-alkyl,
(d) C3-7-cycloalkyl,
(e) methyl-C3-7-cycloalkyl,
(f) aryl, and
(g) 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-alkylthio,
(d) C1-4-alkoxy,
(e) —CF3,
(f) —CN, and
(g) hydroxymethyl,
R12 is each independently a group selected from:
(a) hydrogen,
(b) C1-6-alkyl,
(c) fluoro-C1-6-alkyl,
(d) C3-7-cycloalkyl, and
(e) hydroxy-C1-4-alkyl,
or R11 and R12 together with the atoms to which they are attached form a lactam ring when present in the group NR2COR11, or R11 and R12 together with the atoms to which they are attached form a sultam ring when present in the group NR12SO2R11;
and
pharmaceutically acceptable salts, hydrates, solvates, geometrical isomers, tautomers, optical isomers, and prodrug forms thereof.

169 more elements

Dependencies are inferred from the claim text.

Facts

Application: 11/980,114Filed 30 Oct 2007
Priority: SE 0602283-430 Oct 2006
Published: 24 Jul 2008
Term ends: Not estimatedThe source records don’t support an estimate.

Classification6 codes

C07D 498/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61P 3/04
Drugs for disorders of the metabolism: anorexiants; Antiobesity agents
A61P 43/00
Drugs for specific purposes, not provided for in groups a61p1/00-a61p41/00
C07D 498/18
In which the condensed system contains three hetero rings: bridged systems

Family

Application60/872,209Us provisional application · filed 1 Dec 2006
US 7,960,374 B2Related patent
US 2008/0176829 A1This patent

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

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Abstract

The compound of the formula (I):

wherein:
represents a single bond or a double bond;
A is N or NR5;
X is O, S, N—H or N—C1-6-alkyl;
R1 is a group selected from:
(a) C1-6-alkyl,
(b) C3-7-cycloalkyl,
(c) C3-6-alkenyl,
(d) aryl,
(e) aryl-C2-6-alkenyl,
(f) aryl-C1-6-alkyl,
(g) heteroaryl,
(h) heteroaryl-C2-6-alkenyl, and
(i) heteroaryl-C1-6-alkyl,
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) fluoro-C1-6-alkyl,
(d) C3-7-cycloalkyl,
(e) methyl-C3-7-cycloalkyl,
(f) fluoro-C3-7-cycloalkyl,
(g) C2-6-alkenyl,
(h) fluoro-C2-6-alkenyl,
(i) ethynyl;
(j) hydroxy-C1-4-alkyl,
(k) hydroxy,
(l) C1-6-alkoxy
(m) fluoro-C1-6-alkoxy
(n) C3-7-cycloalkoxy
(o) methyl-C3-7-cycloalkoxy
(p) fluoro-C3-7-cycloalkoxy
(q) —SCF3,
(r) —SCF2H,
(s) —SO2NR10R10,
(t) —S(O)eR11, wherein e is 0, 1, 2 or 3,
(u) —CN,
(v) —NR10R10,
(w) —NHSO2R11,
(x) —NR12COR11,
(y) —NO2,
(z) —CONR10R10,
(aa) —CO—R11,
(bb) —COOH,
(cc) C1-6-alkoxycarbonyl,
(dd) aryl,
(ee) heteroaryl,
(ff) aryloxy, and
(gg) heteroaryloxy,
wherein any (dd) aryl or (ee) 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-alkylthio,
(d) C1-4-alkoxy,
(e) —CF3,
(f) —CN, and
(g) hydroxymethyl;
R2 is a group selected from:
(a) hydrogen
(b) halogen,
(C) C1-6-alkyl,
(d) fluoro-C1-6-alkyl,
(e) C3-7-cycloalkyl,
(f) methyl-C3-7-cycloalkyl,
(g) fluoro-C3-7-cycloalkyl,
(h) C2-6-alkenyl,
(i) fluoro-C2-6-alkenyl,
(j) ethynyl,
(k) hydroxy-C1-4-alkyl,
(l) hydroxy,
(m) C1-6-alkoxy,
(n) fluoro-C1-6-alkoxy,
(o) C3-7-cycloalkoxy,
(p) methyl-C3-7-cycloalkoxy,
(q) fluoro-C3-7-cycloalkoxy,
(r) —SCF3,
(s) —SCF2H,
(t) —SO2NR10R10,
(u) —S(O)eR11, wherein e is 0, 1, 2 or 3,
(v) —CN,
(w) —NR10R10,
(x) —NR12SO2R11,
(y) —NR12COR11,
(z) —NO2,
(aa) —CONR10R10,
(bb) —OCONR10R10,
(cc) —CO—R11,
(dd) —COOH, and
(ee) C1-6-alkoxycarbonyl;
R3is a group selected from:
(a) hydrogen,
(b) halogen,
(c) C1-6-alkyl,
(d) C3-7-cycloalkyl,
(e) hydroxy-C1-4-alkyl,
(f) C3-7-cycloalkyl-hydroxy-C1-4-alkyl
(g) C1-2-alkoxy-C1-4-alkyl
(h) —COOR12,
(i) —CONR10R10,
(j) —CO—R11,
(k) —CN,
(l) aryl, and
(m) 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-alkylthio,
(d) C1-4-alkoxy,
(e) —CF3,
(f) —CN, and
(g) hydroxymethyl;
R4 is a group selected from:
(a) hydrogen,
(b) C1-4-alkyl,
(c) fluoro-C1-4-alkyl,
(d) C3-5-cycloalkyl,
(e) fluoro-C3-5-cycloalkyl,
(f) hydroxy-C1-4-alkyl, and
(g) cyano;
R5 is a group selected from:
(a) hydrogen,
(b) C1-4-alkyl,
(c) fluoro-C1-4-alkyl,
(d) 2-cyanoethyl,
(e) hydroxy-C2-4-alkyl,
(f) C3-4-alkenyl,
(g) C3-4-alkynyl,
(h) C3-7-cycloalkyl,
(i) methyl-C3-7-cycloalkyl
(j) fluoro-C3-7-cycloalkyl,
(k) C3-4-cycloalkyl-C1-4-alkyl, and
(l) C1-4-alkoxy-C2-4-alkyl, or
R5 and one of R6, R7, R8, or R9 groups together with the atoms to which they are attached form a heterocyclic ring and the other three of R6, R7, R8 or R9 are hydrogen;
R6, R7, R8, and R9 are each independently selected from:
(a) hydrogen,
(b) C1-6-alkyl,
(c) fluoro-C1-6-alkyl,
(d) C3-7-cycloalkyl, and
(e) hydroxy-C1-4-alkyl,
with the proviso that three of R6, R7, R8 and R9 are hydrogen unless at least two of R6, R7, R8 and R9 are methyl and the remainder of them are hydrogen,
two of the R6, R7, R8, or R9 groups together with the atoms to which they are attached form a carbocyclic or heterocyclic ring and the other two of R6, R7, R8or R9 are hydrogen, or
one of R6, R7, R8, or R9 groups and R5 together with the atoms to which they are attached form a heterocyclic ring and the other three of R6, R7, R8 or R9 are hydrogen;
R10 is each independently a group selected from:
(a) hydrogen,
(b) C1-6-alkyl,
(c) fluoro-C2-6-alkyl, and
(d) C3-7-cycloalkyl, or
two R10 groups together with the nitrogen to which they are attached form a heterocyclic ring optionally substituted with methyl;
R11 is each independently a group selected from:
(a) hydrogen,
(b) C1-6-alkyl,
(c) fluoro-C1-6-alkyl,
(d) C3-7-cycloalkyl,
(e) methyl-C3-7-cycloalkyl,
(f) aryl, and
(g) 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-alkylthio,
(d) C1-4-alkoxy,
(e) —CF3,
(f) —CN, and
(g) hydroxymethyl,
R12 is each independently a group selected from:
(a) hydrogen,
(b) C1-6-alkyl,
(c) fluoro-C1-6-alkyl,
(d) C3-7-cycloalkyl, and
(e) hydroxy-C1-4-alkyl,
or R11 and R12 together with the atoms to which they are attached form a lactam ring when present in the group NR2COR11, or R11 and R12 together with the atoms to which they are attached form a sultam ring when present in the group NR12SO2R11;
and
pharmaceutically acceptable salts, hydrates, solvates, geometrical isomers, tautomers, optical isomers, and prodrug forms thereof.

169 more elements

Facts

Application

11/980,114Filed 30 Oct 2007

Priority

SE 0602283-430 Oct 2006

Published

24 Jul 2008

Term ends

Not estimatedThe source records don’t support an estimate.

Classification6 codes

C07D 498/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61P 3/04
Drugs for disorders of the metabolism: anorexiants; Antiobesity agents
A61P 43/00
Drugs for specific purposes, not provided for in groups a61p1/00-a61p41/00
C07D 498/18
In which the condensed system contains three hetero rings: bridged systems