Piperidine/piperazine derivatives

Patent metadata

Field	Value
Publication number	US-9499567-B2
Application number	US-201514803275-A
Country	US
Kind code	B2
Filing date	Jul 20, 2015
Priority date	Jun 8, 2007
Publication date	Nov 22, 2016
Grant date	Nov 22, 2016

Abstract

The invention further relates to a DGAT inhibitor of formula

including any stereochemically isomeric form thereof, wherein A represents CH or N; the dotted line represents an optional bond in case A represents a carbon atom; X represents —NR x —C(═O)—; —Z—C(═O)—; —Z—NR x —C(═O)—; —S(═O)p-; —C(═S)—; —NR x —C(═S)—; —Z—C(═S)—; —Z—NR x —C(═S)—; —O—C(═O)—; —C(═O)—C(═O)—; R 1 represents a 5-membered monocyclic heterocycle containing at least 2 heteroatoms; a 6-membered aromatic monocyclic heterocycle; or a 5-membered heterocycle containing at least 2 heteroatoms fused with phenyl, cyclohexyl or a 5- or 6-membered heterocycle; wherein each of said heterocycles may optionally be substituted; R 2 represents R 3 ; R 3 represents C 3-6 cycloalkyl, phenyl, naphtalenyl, 2,3-dihydro-1,4-benzodioxinyl, 1,3-benzodioxolyl, 2,3-dihydrobenzofuranyl or a 6-membered aromatic heterocycle containing 1 or 2 N atoms, wherein said C 3-6 cycloalkyl, phenyl, naphtalenyl, 2,3-dihydro-1,4-benzodioxinyl, 1,3-benzodioxolyl, 2,3-dihydrobenzofuranyl or 6-membered aromatic heterocycle may optionally be substituted; a N-oxide thereof, a pharmaceutically acceptable salt thereof or a solvate thereof.

The invention further relates to methods for preparing such compounds, pharmaceutical compositions comprising said compounds as well as the use as a medicine of said compounds.

First claim

The invention claimed is:

1. A compound of formula

including any stereochemically isomeric form thereof, wherein
A represents N;
X represents —NR x —C(═O)—; —Z—C(═O)—; or —Z—NR x —C(═O)—;
Z represents a bivalent radical selected from C 1-6 alkanediyl,
R x represents hydrogen;
R 1 represents a 5-membered monocyclic heterocycle selected from the group consisting of 1,3-dioxolanyl, imidazolidinyl, thiazolidinyl, dihydrooxazolyl, isothiazolidinyl, isoxazolidinyl, oxadiazolidinyl, triazolidinyl, thiadiazolidinyl, pyrazolidinyl, imidazolinyl, pyrazolinyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, triazolyl, thiadiazolyl, oxadiazolyl, tetrazolyl; wherein each of said heterocycles may optionally be substituted with one or two substituents, each substituent independently being selected from the group consisting of C 1-6 alkyl optionally substituted with C 1-4 alkyl oxycarbonyl; hydroxyC 1-6 alkyl optionally substituted with aryl; mono- or di(C 1-6 alkyl)-amino; R 5 R 4 N—C 1-6 alkyl; Het-NR x —; arylC 1-4 alkyl-NR x —; C 3-6 cycloalkyl; C 3-6 cyclo-alkylC 1-4 alkyl; aryl; arylC 1-4 alkyl; aryl-C(═O)—C 1-4 alkyl; and Het;
R 2 represents R 3 ;
R 3 represents C 3-6 cycloalkyl, phenyl, naphthalenyl, 1,3-benzodioxolyl, or a 6-membered aromatic heterocycle containing 1 or 2 N atoms, wherein said C 3-6 cycloalkyl, phenyl, naphthalenyl, 1,3-benzodioxolyl or 6-membered aromatic heterocycle may optionally be substituted with at least one substituent, each substituent independently selected from the group consisting of hydroxyl; carboxyl; halo; C 1-6 alkyl optionally substituted with hydroxy; polyhaloC 1-6 alkyl; C 1-6 alkyloxy; C 1-6 alkylthio; C 1-6 alkyloxycarbonyl; mono- or di(C 1-4 alkyl)amino; C 1-4 alkylcarbonylamino Het; and HetC 1-4 alkyl;
R 4 represents hydrogen; or C 1-4 alkyl;
R 5 represents hydrogen or C 1-4 alkyl;
R 8 represents hydrogen;
aryl represents phenyl or phenyl substituted with at least one substituent, each substituent independently being selected from the group consisting of halo; C 1-6 alkyl and C 1-6 alkyloxy;
Het represents piperidinyl, morpholinyl, piperazinyl or pyrrolidinyl; said piperidinyl, morpholinyl, piperazinyl or pyrrolidinyl, optionally being substituted with C1-6alkyloxycarbonyl;
p represents 1 or 2;
provided that the following compounds

X
R 1
R 2

Assignees

• Janssen Pharmaceutica Nv
• Janssen Pharmaceutica Nv

Inventors

• Bongartz Jean-Pierre Andre Marc
• Meerpoel Lieven
• Boeckx Gustaaf Maria
• Van Lommen Guy Rosalia Eugeen
• Buyck Christophe Francis Robert Nestor
• Obrecht Daniel
• Ermert Philipp
• Luther Anatol

Classifications

• A61P3/04

  Anorexiants; Antiobesity agents · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P3/08

  for glucose homeostasis (pancreatic hormones A61P5/48) · CPC title

• A61P3/06

  Antihyperlipidemics · CPC title

• A61P3/00

  Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00) · CPC title