公开(公告)号：US20100190789A1

公开(公告)日：2010-07-29

申请号：US12663013

申请日：2008-06-06

申请人： Jean-Pierre Andre Marc Bongartz ,  Joannes Theodorus Maria Linders ,  Lieven Meerpoel ,  Guy Rosalia Eugeen Van Lommen ,  Erwin Coesemans ,  Mirielle Braeken ,  Christophe Francis Robert Nestor Buyck ,  Monique Jenny Marie Berwaer ,  Katharina Antonia Germania J.M De Waepenaert ,  Peter Walter Maria Roevens ,  Gustaaf Maria Boeckx ,  Peter Vladimirivich Davidenko

发明人： Jean-Pierre Andre Marc Bongartz ,  Joannes Theodorus Maria Linders ,  Lieven Meerpoel ,  Guy Rosalia Eugeen Van Lommen ,  Erwin Coesemans ,  Mirielle Braeken ,  Christophe Francis Robert Nestor Buyck ,  Monique Jenny Marie Berwaer ,  Katharina Antonia Germania J.M De Waepenaert ,  Peter Walter Maria Roevens ,  Gustaaf Maria Boeckx ,  Peter Vladimirivich Davidenko

IPC分类号： A61K31/5377 ,  C07D241/04 ,  A61K31/495 ,  C07D401/12 ,  A61K31/496 ,  C07D403/10 ,  C07D405/12 ,  C07D403/12 ,  C07D413/12 ,  C07D211/34 ,  A61K31/451 ,  A61P3/04 ,  A61P3/06 ,  A61P3/10 ,  A61P1/16

CPC分类号： C07D295/205 ,  C07D207/09 ,  C07D211/26 ,  C07D211/38 ,  C07D213/40 ,  C07D213/56 ,  C07D213/61 ,  C07D213/75 ,  C07D233/18 ,  C07D295/192 ,  C07D295/21 ,  C07D295/215 ,  C07D295/24 ,  C07D295/26 ,  C07D307/52 ,  C07D307/79 ,  C07D309/04 ,  C07D317/58 ,  C07D333/24

摘要： 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 —C(═O)—; —O—C(═O)—; C(═O)—C(═O)—; —NRx—C(═O)—; —Z1—C(O)—; —Z1—NRx—C(═O)—; —C(═O)—Z1—; —NRx—C(═O)—Z1—; —S(═O)p-; —C(═S)—; —NRx—C(═S)—; —Z1—C(═S)—; —Z1—NRx—C(═S)—; —C(═S)—Z1-; NRx—C(═S)—Z—; Y represents NRx—C(=0)-Z2—; —NRx—C(=0)-Z2—NRy—; —NRx—C(=0)-Z 2—NRy—C(=0)—; —NRx—C(=0)-Z2—NRy—C(=0)-; O—; —NRx—C(=0)-Z2-0-; —NRx—C(=0)-Z2-0-C(=0)-; —NRx—C(=0)-Z2—C(=0)-; —NRx—C(=0)-Z2—C(=0)-; —NRx—C(=0)-0-Z2—C(=0)-; —NRx—C(=0)-0-Z2—C(=0)-0-; —NRx—C(═O)—O—Z2—O—C(═O)—; —NRx—C(═O)—Z2—C(═O)—NRy—; —NRx—C(═O)—Z2—NRy—C(=0)-NRy—; —C(═O)—Z2—; —C(═O)—Z2—O—; —C(=0)-NRx—Z2—; —C(=0)-NRx—Z2-0-; —C(=0)-NRx—Z2—C(=0)-0-; —C(=0)-NRx—Z2-0-C(=0)-; —C(=0)-NRx—Z2—NRy—; —C(=0)—NRx—Z2—NRy—C(=0)-; —C(=0)-NRx—Z2—NRy—C(=0)-0-; R1 represents C1-12alkyl optionally substituted with cyano, C1-4alkyloxy, C1-4alkyl-oxyC1-4alkyloxy, C3-6Cycloalkyl or aryl; C2-6alkenyl; C2-6alkynyl; C3-6cycloalkyl; adamantanyl; aryl1; aryl1C1-6alkyl; Het1; or Het1C1-6alkyl; provided that when Y represents —NRx—C(═O)—Z2—; —NRx—C(=0)-Z2—NRy; —NRx—C(═O)—Z2—C(═O)—NRy—; —C(═O)—Z2—; —NRx—C(=0)-Z2—NRy—C(=0)—NRy—; —C(═O)—NR—Z2—; —C(═O)—NR—O—Z2—; or —C(=0)-NRx—Z2—NRy—; then R1 may also represent hydrogen; R2 represents hydrogen, C1-12alkyl, C2-6alkenyl or R3; provided that if X represents —O—C(═O)—; the R2 O represents R3; 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.

公开(公告)号：US20100210618A1

公开(公告)日：2010-08-19

申请号：US12663011

申请日：2008-06-06

申请人： Jean-Pierre Andre Marc Bongartz ,  Joannes Theodorus Maria Linders ,  Lieven Mieerpoel ,  Guy Rosalia Eugeen Van Lommen ,  Erwin Coesemans ,  Mirielle Braeken ,  Christophe Francis Robert Nestor Buyck ,  Monique Jenny Marie Berwaer ,  Katharina Antonia Germania J.M. De Waepenaret ,  Peter Walter Maria Roevens ,  Petr Vladimirivich Davidenko

发明人： Jean-Pierre Andre Marc Bongartz ,  Joannes Theodorus Maria Linders ,  Lieven Mieerpoel ,  Guy Rosalia Eugeen Van Lommen ,  Erwin Coesemans ,  Mirielle Braeken ,  Christophe Francis Robert Nestor Buyck ,  Monique Jenny Marie Berwaer ,  Katharina Antonia Germania J.M. De Waepenaret ,  Peter Walter Maria Roevens ,  Petr Vladimirivich Davidenko

IPC分类号： A61K31/397 ,  C07D401/12 ,  C07D417/12 ,  A61K31/497 ,  A61K31/454 ,  C07D405/12 ,  C07D241/04 ,  A61K31/4965 ,  C07D211/78 ,  A61K31/451 ,  C07D403/12 ,  C07D413/12 ,  A61K31/5377 ,  C07D279/02 ,  A61K31/541 ,  C07D279/12 ,  A61P3/04 ,  A61P3/06 ,  A61P3/10 ,  A61P1/16

CPC分类号： A61K31/4523 ,  A61K31/451 ,  A61K31/454 ,  A61K31/495 ,  A61K31/496 ,  C07D207/277 ,  C07D207/323 ,  C07D211/26 ,  C07D211/60 ,  C07D231/12 ,  C07D233/54 ,  C07D233/64 ,  C07D235/18 ,  C07D249/08 ,  C07D257/04 ,  C07D263/34 ,  C07D277/56 ,  C07D279/02 ,  C07D279/12 ,  C07D295/20 ,  C07D295/205 ,  C07D295/21 ,  C07D295/215 ,  C07D307/54 ,  C07D319/18 ,  C07D401/12 ,  C07D417/12 ,  C07D417/14

摘要： 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 —O—C(═O)—; —C(═O)—C(═O)—; —NRX—C(═O)—; —Z—C(═O)—; —Z—NRX—C(═O)—; —C(═O)—Z—; —NRX—C(═O)—Z—; —C(═S)—; —NRX—C(═S)—; —Z—C(═S)—; —Z—NRX—C(═S)—; —C(═S)—Z—; —NRX—C(═S)—Z—; Z represents a bivalent radical selected from C1-6alkanediyl, C2-6alkenediyl or C2-6alkynediyl; wherein each of said C1-6alkanediyl, C2-6alkenediyl or C2-6alkynediyl may optionally be substituted; and wherein two hydrogen atoms attached to the same carbon atom in C1-6alkanediyl may optionally be replaced by C1-6alkanediyl; Y represents —C(═O)—NRX— or —NRX—C(═O)—; R1 represents adamantanyl, C3-6cycloalkyl; aryl1 or Het1; R2 represents C3-6cycloalkyl, 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 C3-6Cycloalkyl, phenyl, naphtalenyl, 2,3-dihydro-1,4-benzodioxinyl, 1,3-benzodioxolyl or heterocycle may optionally be substituted; R7 represents hydrogen, halo, C1-4alkyl, C1-4alkyl substituted with hydroxyl; provided that the following compounds (II), (III) 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.

公开(公告)号：US20100184776A1

公开(公告)日：2010-07-22

申请号：US12663007

申请日：2008-06-05

申请人： Jean-Pierre Andre Marc Bongartz ,  Guy Rosalia Eugeen Van Lommen ,  Erwin Coesemans ,  Christophe Francis Robert Nestor Buyck

发明人： Jean-Pierre Andre Marc Bongartz ,  Guy Rosalia Eugeen Van Lommen ,  Erwin Coesemans ,  Christophe Francis Robert Nestor Buyck

IPC分类号： A61K31/496 ,  C07D241/04 ,  A61K31/495 ,  C07D403/12 ,  A61P3/04 ,  A61P3/06 ,  A61P1/16

CPC分类号： C07D295/215 ,  C07D231/12

摘要： The invention relates to a DGAT inhibitor of formula (I) including any stereochemically isomeric form thereof, wherein A represents CH or N; X represents O or NRx; the dotted line represents an optional bond in case A represents a carbon atom; Y represents a direct bond; —NRx—C(═O)—; —C(═O)—NRx—; —NRx—C(═O)—Z—; —NRx—C(═O)—Z—NRy—; —NRx—C(═O)—Z—NRy—C(═O)—; —NRx—C(═O)—Z—NRy—C(═O)—O—; —NRx—C(═O)—Z—O—; —NRx—C(═O)—Z—O—C(═O)—; —NRx—C(═O)—Z—C(═O)—; —NRx—C(═O)—Z—C(═O)—O—; —NRx—C(═O)—O—Z—C(═O)—; —NRx—C(═O)—O—Z—C(═O)—O—; —NRx—C(═O)—O—Z—O—C(═O)—; —NRx—C(═O)—Z—C(═O)—NRy—; —NRx—C(═O)—Z—NRy—C(═O)—NRy—; —C(═O)—Z—; —C(═O)—Z—O—; —C(═O)—NRx—Z—; —C(═O)—NRx—Z—O—; —C(═O)—NRx—Z—C(═O)—O—; —C(═O)—NRx—Z—O—C(═O)—; —C(═O)—NRx—O—Z—; —C(═O)—NRx—Z—NRy—; —C(═O)—NRx—Z—NRy—C(═O)—; —C(═O)—NRx—Z—NRy—C(═O)—O—; R1 represents optionally substituted C1-12alkyl; C2-6alkenyl; C2-6alkynyl; C3-6cycloalkyl; aryl1; aryl1C1-6alkyl; Het1; or Het1C1-6alkyl; provided that when Y represents —NRx—C(═O)—Z—; —NRx—C(═O)—Z—NRy; —NRx—C(═O)—Z—C(═O)—NRy—; —C(═O)—Z—; —NRx—C(═O)—Z—NRy—C(═O)—NRy—; —C(═O)—NRx—Z—; —C(═O)—NRx—O—Z—; or —C(═O)—NRx—Z—NRy—; then R1 may also represent hydrogen; R2 and R3 each independently represent hydrogen; hydroxyl; carboxyl; halo; C1-6alkyl; polyhaloC1-6alkyl; C1-6alkyloxyoptionally substituted with C1-4alkyloxy; C1-6alkylthio; polyhaloC1-6alkyloxy; C1-6alkyloxycarbonyl; cyano; aminocarbonyl; mono- or di(C1-4alkyl)aminocarbonyl; C1-6alkylcarbonyl; nitro; amino; mono- or di(C1-4alkyl)amino; —S(═O)p-C1-4alkyl; R4 represents hydrogen; hydroxyl; carboxyl; halo; C1-6alkyl; polyhaloC1-6alkyl; optionally substituted C1-6alkyloxy; C1-6alkylthio; polyhalo-C1-6alkyloxy; C1-6alkyloxycarbonyl wherein C1-6alkyl may optionally be substituted; cyano; C1-6alkylcarbonyl; nitro; amino; mono- or di(C1-4alkyl)amino; C1-4alkylcarbonylamino; —S(═O)p-C1-4alkyl; R6R5N—C(═O)—; R6R5N—C1-6alkyl; C3-6cycloalkyl aryl; aryloxy; arylC1-4alkyl; aryl-C(═O)—C1-4alkyl; aryl-C(═O)—; Het; HetC1-4alkyl; Het-C(═O)—C1-4alkyl; Het-C(═O)—; Het-O—; R9 represents hydrogen, halo, C1-4alkyl, C1-4alkyl substituted with hydroxyl; 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.

公开(公告)号：US20090030039A1

公开(公告)日：2009-01-29

申请号：US12278719

申请日：2007-02-06

申请人： Erwin Coesemans ,  Jean-Pierre Andre Marc Bongartz ,  Guy Rosali Eugeen Van Lommen ,  Jean Pierre Frans Van Wauwe ,  Mieke Buntinx

发明人： Erwin Coesemans ,  Jean-Pierre Andre Marc Bongartz ,  Guy Rosali Eugeen Van Lommen ,  Jean Pierre Frans Van Wauwe ,  Mieke Buntinx

IPC分类号： A61K31/4545 ,  C07D401/04

CPC分类号： C07D401/04 ,  C07D401/14

摘要： The present invention relates to a compound of formula (I) a N-oxide thereof, a pharmaceutically acceptable salt thereof, a stereochemically isomeric form thereof or a solvate thereof, wherein X represents N or CH; Y and Z each independently represent C(═O) or CH2 provided that at least one of Y and Z represents C(═O); R1 represents CH(R4)-aryl or CH(R4)-heteroaryl; R2 represents aryl2 or heteroaryl; R3 represents hydrogen; C1-4alkylcarbonyl; C1-6alkyl optionally substituted with C1-6alkyloxy, C1-6alkylthio, C1-6alkyloxycarbonyl or aryl1; provided that when Y and Z each represent C(═O), X represents CH, R3 represents hydrogen, R4 represents hydrogen, and R2 represents unsubstituted pyridyl or phenyl optionally substituted with one halo or with one C1-4alkyloxy or with one or two C1-4alkyl, then aryl in the definition of R1 is other than phenyl substituted with one halo or with one or two C1-4alkyl; and provided that when Y and Z each represent C(═O), X represents CH, R3 represents hydrogen, and R2 represents unsubstituted pyridyl or phenyl optionally substituted with one halo or with one C1-4alkyloxy or with one or two C1-4alkyl, then heteroaryl in the definition of R1 is other than unsubstituted thienyl or unsubstituted pyridyl. The present invention also relates to the use of a compound of formula (I) for the manufacture of a medicament for preventing or treating a disease mediated through activation of the CXCR3 receptor; to processes for preparing the compounds of formula (I) and pharmaceutical compositions comprising them.

摘要翻译： 本发明涉及式（I）的化合物，其N-氧化物，其药学上可接受的盐，其立体化学异构形式或其溶剂合物，其中X表示N或CH; Y和Z各自独立地表示C（-O）或CH 2，条件是Y和Z中的至少一个表示C（-O）; R 1表示CH（R 4） - 芳基或CH（R 4） - 杂芳基; R 2表示芳基2或杂芳基; R3表示氢; C 1-4烷基羰基; 任选被C 1-6烷氧基，C 1-6烷硫基，C 1-6烷氧基羰基或芳基取代的C 1-6烷基; 条件是当Y和Z各自表示C（-O）时，X表示CH，R 3表示氢，R 4表示氢，R 2表示未取代的吡啶基或任选被一个卤素或一个C 1-4烷氧基取代的苯基或与一个或两个C 1 -4-烷基，则R1定义中的芳基不同于被一个卤素或一个或两个C 1-4烷基取代的苯基; 并且条件是当Y和Z各自表示C（-O）时，X表示CH，R 3表示氢，R 2表示未取代的吡啶基或任选被一个卤素或一个C 1-4烷氧基取代或与一个或两个C 1-4烷基取代的苯基， 那么R1的定义中的杂芳基不是未取代的噻吩基或未取代的吡啶基。 本发明还涉及式（I）化合物在制备用于预防或治疗通过活化CXCR3受体介导的疾病的药物中的用途; 制备式（I）化合物的方法和包含它们的药物组合物。