Janssen Pharmaceutica Nv

Jean-Pierre André Marc Bongartz

Guy Rosalia Eugeen Van Lommen

Christophe Francis Robert Nestor Buyck

Lieven Meerpoel

Gustaaf Maria Boeckx

Erwin Coesemans

Daniel Obrecht

Anatol Luther

Philipp Ermert

Joannes Theodorus Maria Linders

Peter Walter Maria Roevens

Mirielle Braeken

Monique Jenny Marie Berwaer

Katharina Antonia Germania J M De Waepenaert

Petr Vladimirivich Davidenko

Ludwig Paul Cooymans

Christopher John Love

Peter Jacobus Johannes Antonius Buijnsters

Marcel Jozef Maria Van Der Aa

Julien Georges Pierre-Olivier Doyon

Nele Vandermaesen

Robert Jozef Maria Hendrickx

Christopher A Teleha

Kenneth Jerome Wilson

Alfred Elisabeth Stappers

Koen Johan Herman Weerts

Katharina Antonia Germania JM De Waepenaert

Julien Georgespierre-Olivier Doyon

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 &#x2014;NR&#x2014;C(&#x2550;O)&#x2014;; &#x2014;Z&#x2014;C(&#x2550;O)&#x2014;; &#x2014;Z&#x2014;NR&#x2014;C(&#x2550;O)&#x2014;; &#x2014;S(&#x2550;O)p-; &#x2014;C(&#x2550;S)&#x2014;; &#x2014;NR&#x2014;C(&#x2550;S)&#x2014;; &#x2014;Z&#x2014;C(&#x2550;S)&#x2014;; &#x2014;Z&#x2014;NR&#x2014;C(&#x2550;S)&#x2014;; &#x2014;O&#x2014;C(&#x2550;O)&#x2014;; &#x2014;C(&#x2550;O)&#x2014;C(&#x2550;O)&#x2014;; Rrepresents 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; Rrepresents R; Rrepresents Ccycloalkyl, 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 Ccycloalkyl, 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.

Piperidine/piperazine derivatives

The present invention is directed to a process for the preparation of heterocyclic ester derivatives of formula I wherein A, SEM, and Ware as defined herein. Such compounds are useful as intermediates in the synthesis of derivatives useful as protein tyrosine kinase inhibitors, more particularly inhibitors of c-fms kinase.

Process for the preparation of heterocyclic ester derivatives

The invention 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 &#x2014;O&#x2014;C(&#x2550;O)&#x2014;; &#x2014;C(&#x2550;O)&#x2014;C(&#x2550;O)&#x2014;; &#x2014;NR&#x2014;C(&#x2550;O)&#x2014;; &#x2014;Z&#x2014;C(&#x2550;O)&#x2014;; &#x2014;Z&#x2014;NR&#x2014;C(&#x2550;O)&#x2014;; &#x2014;C(&#x2550;O)&#x2014;Z&#x2014;; &#x2014;NR&#x2014;C(&#x2550;O)&#x2014;Z&#x2014;; &#x2014;C(&#x2550;S)&#x2014;; &#x2014;NR&#x2014;C(&#x2550;S)&#x2014;; &#x2014;Z&#x2014;C(&#x2550;S)&#x2014;; &#x2014;Z&#x2014;NR&#x2014;C(&#x2550;S)&#x2014;; &#x2014;C(&#x2550;S)&#x2014;Z&#x2014;; &#x2014;NR&#x2014;C(&#x2550;S)&#x2014;Z&#x2014;; Z represents a bivalent radical selected from Calkanediyl, Calkenediyl or Calkynediyl; wherein each of said Calkanediyl, Calkenediyl or Calkynediyl may optionally be substituted; and wherein two hydrogen atoms attached to the same carbon atom in Calkanediyl may optionally be replaced by Calkanediyl; Y represents &#x2014;C(&#x2550;O)&#x2014;NR&#x2014; or &#x2014;NR&#x2014;C(&#x2550;O)&#x2014;; Rrepresents adamantanyl, Ccycloalkyl; arylor Het; Rrepresents Ccycloalkyl, 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 Ccycloalkyl, phenyl, naphtalenyl, 2,3-dihydro-1,4-benzodioxinyl, 1,3-benzodioxolyl or heterocycle may optionally be substituted; Rrepresents hydrogen, halo, Calkyl, Calkyl substituted with hydroxyl;provided that the following compounds are excluded;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, as a DGAT inhibitor, of said compounds.

The invention further relates to a DGAT inhibitor of formula including any stereochemically isomeric form thereof, wherein A represents CH or N; X represents &#x2014;NR&#x2014;C(&#x2550;O)&#x2014;; &#x2014;Z&#x2014;C(&#x2550;O)&#x2014;; &#x2014;Z&#x2014;NR&#x2014;C(&#x2550;O)&#x2014;; &#x2014;S(&#x2550;O)p-; &#x2014;C(&#x2550;S)&#x2014;; &#x2014;NR&#x2014;C(&#x2550;S)&#x2014;; &#x2014;Z&#x2014;C(&#x2550;S)&#x2014;; &#x2014;Z&#x2014;NR&#x2014;C(&#x2550;S)&#x2014;; &#x2014;O&#x2014;C(&#x2550;O)&#x2014;; &#x2014;C(&#x2550;O)&#x2014;C(&#x2550;O)&#x2014;; Rrepresents 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; Rrepresents R; Rrepresents Ccycloalkyl, 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 Ccycloalkyl, phenyl, naphtalenyl, 2,3-dihydro-1,4-benzo-dioxinyl, 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.

The invention relates to a DGAT inhibitor of formula (I): 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 &#x2014;C(&#x2550;O)&#x2014;; &#x2014;O&#x2014;C(&#x2550;O)&#x2014;; C(&#x2550;O)&#x2014;C(&#x2550;O)&#x2014;; &#x2014;NR&#x2014;C(&#x2550;O)&#x2014;; &#x2014;Z&#x2014;C(O)&#x2014;; &#x2014;Z&#x2014;NR&#x2014;C(&#x2550;O)&#x2014;; &#x2014;C(&#x2550;O)&#x2014;Z&#x2014;; &#x2014;NR&#x2014;C(&#x2550;O)&#x2014;Z&#x2014;; &#x2014;S(&#x2550;O)p-; &#x2014;C(&#x2550;S)&#x2014;; &#x2014;NR&#x2014;C(&#x2550;S)&#x2014;; &#x2014;Z&#x2014;C(&#x2550;S)&#x2014;; &#x2014;Z&#x2014;NR&#x2014;C(&#x2550;S)&#x2014;; &#x2014;C(&#x2550;S)&#x2014;Z1-; &#x2014;NR&#x2014;C(&#x2550;S)&#x2014;Z&#x2014;; Y represents NR&#x2014;C(=0)-Z&#x2014;; &#x2014;NR&#x2014;C(=0)-Z&#x2014;NR&#x2014;; &#x2014;NR&#x2014;C(=0)-Z&#x2014;NR&#x2014;C(=0)-; &#x2014;NR&#x2014;C(=0)-Z&#x2014;NR&#x2014;C(=0)-O&#x2014;; &#x2014;NR&#x2014;C(=0)-Z-0-; &#x2014;NR&#x2014;C(=0)-Z-0-C(=0)-; &#x2014;NR&#x2014;C(=0)-Z&#x2014;C(=0)-; &#x2014;NR&#x2014;C(=0)-Z&#x2014;C(=0)-; &#x2014;NR&#x2014;C(=0)-0-Z&#x2014;C(=0)-; &#x2014;NR&#x2014;C(=0)-0-Z&#x2014;C(=0)-0-; &#x2014;NR&#x2014;C(&#x2550;O)&#x2014;O&#x2014;Z&#x2014;O&#x2014;C(&#x2550;O)&#x2014;; &#x2014;NR&#x2014;C(&#x2550;O)&#x2014;Z&#x2014;C(&#x2550;O)&#x2014;NR&#x2014;; &#x2014;NR&#x2014;C(&#x2550;O)&#x2014;Z&#x2014;NR&#x2014;C(=0)-NR&#x2014;; &#x2014;C(&#x2550;O)&#x2014;Z&#x2014;; &#x2014;C(&#x2550;O)&#x2014;Z&#x2014;O&#x2014;; &#x2014;C(=0)-NR&#x2014;Z&#x2014;; &#x2014;C(=0)-NR&#x2014;Z-0-; &#x2014;C(=0)-NR&#x2014;Z&#x2014;C(=0)-0-; &#x2014;C(=0)-NR&#x2014;Z-0-C(=0)-; &#x2014;C(=0)-NR&#x2014;Z&#x2014;NR&#x2014;; &#x2014;C(=0)-NR&#x2014;Z&#x2014;NR&#x2014;C(=0)-; &#x2014;C(=0)-NR&#x2014;Z&#x2014;NR&#x2014;C(=0)-0-; Rrepresents Calkyl optionally substituted with cyano, Calkyloxy, Calkyl-oxyCalkyloxy, CCycloalkyl or aryl; Calkenyl; Calkynyl; Ccycloalkyl; adamantanyl; aryl; arylCalkyl; Het; or HetCalkyl; provided that when Y represents &#x2014;NR&#x2014;C(&#x2550;O)&#x2014;Z&#x2014;; &#x2014;NR&#x2014;C(=0)-Z&#x2014;NR; &#x2014;NR&#x2014;C(&#x2550;O)&#x2014;Z&#x2014;C(&#x2550;O)&#x2014;NR&#x2014;; &#x2014;C(&#x2550;O)&#x2014;Z&#x2014;; &#x2014;NR&#x2014;C(=0)-Z&#x2014;NR&#x2014;C(=0)-NR&#x2014;; &#x2014;C(&#x2550;O)&#x2014;NR&#x2014;Z&#x2014;; &#x2014;C(&#x2550;O)&#x2014;NR&#x2014;O&#x2014;Z&#x2014;; or &#x2014;C(=0)-NR&#x2014;Z&#x2014;NR&#x2014;; then Rmay also represent hydrogen; Rrepresents hydrogen, Calkyl, Calkenyl or R; provided that if X represents &#x2014;O&#x2014;C(&#x2550;O)&#x2014;; the Rrepresents R; and provided that (A) is excluded; 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. 

The invention relates to a DGAT inhibitor of formula (I),  including any stereochemically isomeric form thereof, a N-oxide thereof, a pharmaceutically acceptable salt thereof or a solvate thereof, and methods for preparing such compounds, pharmaceutical compositions comprising said compounds as well as the use as a medicine, as a DGAT inhibitor, of said compounds.

The invention further relates to a DGAT inhibitor of formula (I), 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 &#x2014;NR&#x2014;C(&#x2550;O)&#x2014;; &#x2014;Z&#x2014;C(&#x2550;O)&#x2014;; &#x2014;Z&#x2014;NR&#x2014;C(&#x2550;O)&#x2014;; &#x2014;S(&#x2550;O)p&#x2014;; C(&#x2550;S)&#x2014;; &#x2014;NR&#x2014;C(&#x2550;S)&#x2014;; &#x2014;Z&#x2014;C(&#x2550;S)&#x2014;; &#x2014;Z&#x2014;NR&#x2014;C(&#x2550;S)&#x2014;; &#x2014;O&#x2014;C(&#x2550;O)&#x2014;; &#x2014;C(&#x2550;O)&#x2014;C(&#x2550;O)&#x2014;; Rrepresents 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; Rrepresents R; Rrepresents Ccycloalkyl, phenyl, naphtalenyl, 2,3-dihydro-1,4-benzodioxinyl, 1,3-benzodioxlyl, 2,3-dihydrobenzofuranyl or a 6-membered aromatic heterocycle containing 1 or 2 N atoms, wherein said Ccycloalkyl, phenyl, naphtalenyl, 2,3-dihydro-1,4-benzo-dioxinyl, 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. 

The invention relates to a DGAT inhibitor of formula including any stereochemically isomeric form thereof, a N-oxide thereof, a pharmaceutically acceptable salt thereof or a solvate thereof, and methods for preparing such compounds, pharmaceutical compositions comprising said compounds as well as the use as a medicine of said compounds.

This invention concerns the use of a compound of formula (I') a N-oxide, a pharmaceutically acceptable addition salt, a quaternary amine and a stereochemically isomeric form thereof, wherein Z is halo; Calkyl; Calkylcarbonyl; Calkyloxycarbonyl; aminocarbonyl; Calkyl substituted with hydroxy, carboxyl, cyano, amino, amino substituted with piperidinyl, amino substituted with Calkyl substituted piperidinyl, mono- or di(Calkyl)amino, aminocarbonyl, mono- or di(Calkyl)aminocarbonyl, Calkyloxycarbonyl, Calkyloxy, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl; polyhaloCalkyl; cyano; amino; mono- or di(Calkyl)aminocarbonyl; Calkyloxycarbonyl; Calkylcarbonyloxy; aminoS(&#x2550;O)&#x2014;; mono- or di(Calkyl)aminoS(&#x2550;O); &#x2014;C(&#x2550;N&#x2014;R)NRR; Q is optionally substituted Ccycloalkyl, phenyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, benzthiazolyl, benzoxazolyl, benzimidazolyl, indazolyl, or imidazopyridyl, or Q is a radical of formula L is optionally substituted phenyl or an optionally substituted monocyclic 5 or 6-membered partially saturated or aromatic heterocycle or a bicyclic partially saturated or aromatic heterocycle; aryl is optionally substituted phenyl; for the manufacture of a medicament for the prevention or the treatment of inflammatory and/or auto-immune diseases mediated through TNF-&#x3b1; and/or IL-12.

2-amino-4,5-trisubstituted thiazolyl derivatives

This invention concerns the use of a compound of formula (I'), a N-oxide, a pharmaceutically acceptable addition salt, a quaternary amine and a stereochemically isomeric form thereof, wherein Z is halo; Calkyl; Calkylcarbonyl; Calkyloxy -carbonyl; aminocarbonyl; Calkyl substituted with hydroxy, carboxyl, cyano, amino, amino substituted with piperidinyl, amino substituted with Calkyl substituted piperidinyl, mono- or di(Calkyl)amino, aminocarbonyl, mono- or di(Calkyl)aminocarbonyl, Calkyloxycarbonyl, Calkyloxy, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl; polyhaloCalkyl; cyano; amino; mono- or di(Calkyl)aminocarbonyl; Calkyloxycarbonyl; Calkylcarbonyloxy; aminoS(&#x2550;O)&#x2014;; mono- or di(Calkyl)aminoS(&#x2550;O); &#x2014;C(&#x2550;N&#x2014;R)NRR; Q is optionally substituted Ccycloalkyl, phenyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, benzthiazolyl, benzoxazolyl, benzimidazolyl, indazolyl, or imidazopyridyl, or Q is a radical of formula (b-1), (b-2), or (b-3), L is optionally substituted phenyl or an optionally substituted monocyclic 5 or 6-membered partially saturated or aromatic heterocycle or a bicyclic partially saturated or aromatic heterocycle; aryl is optionally substituted phenyl; for the manufacture of a medicament for the prevention or the treatment of inflammatory and/or auto-immune diseases mediated through TNF-&#x3b1; and/or IL-12 

Growing community of inventors

Turnhout, Belgium

Jean-Pierre André Marc Bongartz