公开(公告)号：US20070287743A1

公开(公告)日：2007-12-13

申请号：US11632195

申请日：2005-04-29

申请人： Libuse Jaroskova ,  Joannes Linders ,  Christophe Francis Buyck ,  Louis Jozef Van Der Veken

发明人： Libuse Jaroskova ,  Joannes Linders ,  Christophe Francis Buyck ,  Louis Jozef Van Der Veken

IPC分类号： A61K31/40 ,  A61P43/00 ,  C07D207/00

CPC分类号： C07D207/26 ,  C07D207/267 ,  C07D211/76 ,  C07D453/06

摘要： the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein n is 1 or 2; M represents a direct bond or a C1-3alkyl linker optionally substituted with one or two substituents selected from C1-4alkyl, C1-3alkyloxy-C1-4alkyl-, hydroxy-C1-4alkyl-, hydroxy, C1-3alkyloxy- or phenyl-C1-4alkyl-; R1 and R2 each independently represent hydrogen, halo, cyano, hydroxy, C1-4alkyl optionally substituted with halo, C1-4alkyloxy-optionally substituted with one or where possible two or three substituents selected from hydroxy, Ar1 and halo; R3 represents hydrogen, halo, C1-4alkyl, C1-4alkyloxy-, cyano or hydroxy; R4 represents hydrogen, halo, C1-4alkyl, hydroxy, cyano or C1-4alkyloxy-optionally substituted with one or where possible two or three substituents selected from hydroxy and halo; R5 represents hydrogen, C1-4alkyl or Ar2—C1-4alkyl-; R6 represents hydrogen, hydroxy, halo, C1-4alkyl or C1-4alkyoxy-; R7 represents hydrogen or R7 and R5 taken together with the carbon atom to which they are attached from a —C2-alkyl-linker; Ar1 and Ar2 each independently represent phenyl or naphtyl wherein said phenyl and naphtyl are optionally substituted with C1-4alkyl, C1-4alkyloxy-, or phenyl-C1-4alkyl.

公开(公告)号：US07816360B2

公开(公告)日：2010-10-19

申请号：US12341567

申请日：2008-12-22

申请人： Lieven Meerpoel ,  Leo Jacobus Jozef Backx ,  Libuse Jaroskova ,  Peter Walter Maria Roevens ,  Louis Jozef Elisabeth Van Der Veken ,  Marcel Viellevoye ,  Joannes Theodorus Maria Linders

发明人： Lieven Meerpoel ,  Leo Jacobus Jozef Backx ,  Libuse Jaroskova ,  Peter Walter Maria Roevens ,  Louis Jozef Elisabeth Van Der Veken ,  Marcel Viellevoye ,  Joannes Theodorus Maria Linders

IPC分类号： A61K31/496 ,  A61K31/454 ,  C07D401/04 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D405/12 ,  C07D417/12 ,  C07D487/04 ,  C07D233/74 ,  C07D249/12

CPC分类号： C07D233/54 ,  C07D249/08 ,  C07D401/04 ,  C07D401/14 ,  C07D403/10 ,  C07D413/12 ,  C07D417/10 ,  C07D417/12

摘要： The present invention is concerned with novel aryl piperidine or piperazine compounds substituted with certain 5-membered heterocycles having apoB secretion/MTP inhibiting activity and concomitant lipid lowering activity. The invention further relates to methods for preparing such compounds, pharmaceutical compositions comprising said compounds as well as the use of said compounds as a medicine for the treatment of hyperlipidemia, obesity and type II diabetes. The invention further relates to methods for preparing such compounds, pharmaceutical compositions comprising said compounds as well as the use of said compounds as a medicine for the treatment of atherosclerosis, pancreatitis, obesity, hypertriglyceridemia, hypercholesterolemia, hyperlipidemia, diabetes and type II diabetes.

摘要翻译： 本发明涉及用具有apoB分泌/ MTP抑制活性和伴随的降脂活性的某些5-元杂环取代的新的芳基哌啶或哌嗪化合物。 本发明还涉及制备这些化合物的方法，包含所述化合物的药物组合物以及所述化合物作为治疗高脂血症，肥胖症和II型糖尿病的药物的用途。 本发明还涉及制备这些化合物的方法，包含所述化合物的药物组合物以及所述化合物作为治疗动脉粥样硬化，胰腺炎，肥胖症，高甘油三酯血症，高胆固醇血症，高脂血症，糖尿病和II型糖尿病的药物的用途。

公开(公告)号：US20090325980A1

公开(公告)日：2009-12-31

申请号：US12446580

申请日：2007-10-22

申请人： Lieven Meerpoel ,  Joannes Theodorus Maria Linders ,  Libuse Jaroskova ,  Marcel Viellevoye ,  Leo Jacobus Jozef Backx ,  Didier Jean-Claude Berthelot ,  Guuske Frederike Busscher

发明人： Lieven Meerpoel ,  Joannes Theodorus Maria Linders ,  Libuse Jaroskova ,  Marcel Viellevoye ,  Leo Jacobus Jozef Backx ,  Didier Jean-Claude Berthelot ,  Guuske Frederike Busscher

IPC分类号： A61K31/4468 ,  A61K31/4965 ,  A61K31/4545 ,  C07D295/10 ,  C07D401/14 ,  C07D401/12 ,  C07D211/58 ,  A61P3/00

CPC分类号： C07D241/20 ,  C07D211/58 ,  C07D295/10 ,  C07D401/12 ,  C07D401/14

摘要： The present invention is concerned with novel piperidine or piperazine substituted tetrahydro-naphthalene-1-carboxylic acid derivatives having apoB secretion/MTP inhibiting activity and concomitant lipid lowering activity. The invention further relates to methods for preparing such compounds, pharmaceutical compositions comprising said compounds as well as the use of said compounds as a medicine for the treatment of atherosclerosis, pancreatitis, obesity, hypertriglyceridemia, hypercholesterolemia, hyperlipidemia, diabetes and type II diabetes.

摘要翻译： 本发明涉及具有apoB分泌/ MTP抑制活性和伴随的降脂活性的新型哌啶或哌嗪取代的四氢 - 萘-1-羧酸衍生物。 本发明还涉及制备这些化合物的方法，包含所述化合物的药物组合物以及所述化合物作为治疗动脉粥样硬化，胰腺炎，肥胖症，高甘油三酯血症，高胆固醇血症，高脂血症，糖尿病和II型糖尿病的药物的用途。

公开(公告)号：US07504400B2

公开(公告)日：2009-03-17

申请号：US10589515

申请日：2005-03-07

申请人： Lieven Meerpoel ,  Leo Jacobus Jozef Backx ,  Libuse Jaroskova ,  Peter Walter Maria Roevens ,  Louis Jozef Elisabeth Van Der Veken ,  Marcel Viellevoye ,  Joannes Theodorus Maria Linders

发明人： Lieven Meerpoel ,  Leo Jacobus Jozef Backx ,  Libuse Jaroskova ,  Peter Walter Maria Roevens ,  Louis Jozef Elisabeth Van Der Veken ,  Marcel Viellevoye ,  Joannes Theodorus Maria Linders

IPC分类号： A61K31/496 ,  A61K31/454 ,  C07D295/15 ,  C07D401/04 ,  C07D401/10 ,  C07D401/12 ,  C07D417/121

CPC分类号： C07D233/54 ,  C07D249/08 ,  C07D401/04 ,  C07D401/14 ,  C07D403/10 ,  C07D413/12 ,  C07D417/10 ,  C07D417/12

摘要： The present invention is concerned with novel aryl piperidine or piperazine compounds substituted with certain 5-membered heterocycles having apoB secretion/MTP inhibiting activity and concomitant lipid lowering activity. The invention further relates to methods for preparing such compounds, pharmaceutical compositions comprising said compounds as well as the use of said compounds as a medicine for the treatment of hyperlipidemia, obesity and type II diabetes. The invention further relates to methods for preparing such compounds, pharmaceutical compositions comprising said compounds as well as the use of said compounds as a medicine for the treatment of atherosclerosis, pancreatitis, obesity, hyper-triglyceridemia, hypercholesterolemia, hyperlipidemia, diabetes and type II diabetes.

摘要翻译： 本发明涉及用具有apoB分泌/ MTP抑制活性和伴随的降脂活性的某些5-元杂环取代的新的芳基哌啶或哌嗪化合物。 本发明还涉及制备这些化合物的方法，包含所述化合物的药物组合物以及所述化合物作为治疗高脂血症，肥胖症和II型糖尿病的药物的用途。 本发明还涉及制备这些化合物的方法，包含所述化合物的药物组合物以及所述化合物作为治疗动脉粥样硬化，胰腺炎，肥胖症，高甘油三酯血症，高胆固醇血症，高脂血症，糖尿病和II型糖尿病的药物的用途 。

公开(公告)号：US20080139625A1

公开(公告)日：2008-06-12

申请号：US11632675

申请日：2005-04-29

申请人： Libuse Jaroskova ,  Joannes Theodorus Maria Linders ,  Christophe Francis Robert Nestor Buyck ,  Louis Jozef Elizabeth Van Der Veken ,  Vladimir Dimichev Dimitrov ,  Theo Teofanov Nikiforov

发明人： Libuse Jaroskova ,  Joannes Theodorus Maria Linders ,  Christophe Francis Robert Nestor Buyck ,  Louis Jozef Elizabeth Van Der Veken ,  Vladimir Dimichev Dimitrov ,  Theo Teofanov Nikiforov

IPC分类号： A61K31/4015 ,  C07D207/12 ,  C07D405/10 ,  A61P3/00 ,  A61K31/4412 ,  C07D211/40

CPC分类号： C07D211/76 ,  C07D207/26 ,  C07D207/267 ,  C07D405/06

摘要： Formula (I), the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein n is 1 or 2; L represents a C1-3alkyl linker optionally substituted with one or two substituents selected from C1-4alkyl, C1-3alkyloxy-C1-4alkyl-, hydroxy-C1-4alkyl, hydroxy, C1-3alkyloxy- or phenyl-C1-4alkyl; M represents a direct bond or a C1-3alkyl linker optionally substituted with one or two substituents selected from hydroxy, C1-4alkyl or C1-4alkyloxy; R1 and R2 each independently represent hydrogen, halo, cyano, hydroxy, C1-4alkyl optionally substituted with halo, C1-4alkyloxy- optionally substituted with one or where possible two or three substituents selected from hydroxy, Ar1 and halo; or R1 and R2 taken together with the phenyl ring to which they are attached form naphtyl or 1,3-benzodioxolyl, wherein said naphtyl or 1,3-benzodioxolyl are optionally substituted with halo; R3 represents hydrogen, halo, C1-4alkyl, C1-4alkyloxy-, cyano or hydroxy; R4 represents hydrogen, halo, C1-4alkyl, C1-4alkyloxy-, cyano or hydroxy; R5 represents hydrogen, C1-4alkyl or Ar2-C1-4alky-; R6 represents hydrogen, halo, C1-4alkyl Or C1-4alkyoxy-; Ar1 and Ar2 each independently represent phenyl or naphtyl wherein said phenyl and naphtyl are optionally substituted with C1-4alkyl, C1-4alkyloxy-, or phenyl-C1-4alkyl; for use as a medicine.

公开(公告)号：US07332524B2

公开(公告)日：2008-02-19

申请号：US10540616

申请日：2003-12-16

申请人： Joannes Theodorus Maria Linders ,  Gustaaf Henri Maria Willemsens ,  Ronaldus Arnodus Hendrika Joseph Gilissen ,  Christophe Francis Robert Nestor Buyck ,  Greta Constantia Peter Vanhoof ,  Louis Jozef Elisabeth Van Der Veken ,  Libuse Jaroskova

发明人： Joannes Theodorus Maria Linders ,  Gustaaf Henri Maria Willemsens ,  Ronaldus Arnodus Hendrika Joseph Gilissen ,  Christophe Francis Robert Nestor Buyck ,  Greta Constantia Peter Vanhoof ,  Louis Jozef Elisabeth Van Der Veken ,  Libuse Jaroskova

IPC分类号： A61K31/165 ,  C07C233/57

CPC分类号： C07D207/27 ,  C07C233/11 ,  C07C233/14 ,  C07C233/22 ,  C07C233/23 ,  C07C233/32 ,  C07C233/41 ,  C07C233/58 ,  C07C235/36 ,  C07C235/40 ,  C07C237/20 ,  C07C237/22 ,  C07C255/41 ,  C07C255/57 ,  C07C271/22 ,  C07C2601/02 ,  C07C2601/14 ,  C07C2601/18 ,  C07C2601/20 ,  C07C2602/06 ,  C07C2602/08 ,  C07C2602/10 ,  C07C2602/12 ,  C07C2602/18 ,  C07C2602/42 ,  C07C2602/46 ,  C07C2603/62 ,  C07C2603/66 ,  C07C2603/70 ,  C07C2603/74 ,  C07D209/08 ,  C07D209/18 ,  C07D213/56 ,  C07D215/08 ,  C07D215/48 ,  C07D217/06 ,  C07D217/26 ,  C07D243/08 ,  C07D257/04 ,  C07D277/40 ,  C07D277/48 ,  C07D295/088 ,  C07D295/155 ,  C07D295/185 ,  C07D309/12 ,  C07D311/58 ,  C07D311/64 ,  C07D317/60 ,  C07D317/72 ,  C07D333/24 ,  C07D333/68 ,  C07D335/06

摘要： the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein n represents an integer being 1 or 2; R1 and R2 each independently represents hydrogen C1-4alkyl, NR9R10, C1-4alkyloxy; or R1 and R2 taken together with the carbon atom with which they are attached form a C3-6cycloalkyl; and where n is 2, either R1 or R2 may be absent to form an unsaturated bond; R3 represents a C6-12cycloalkyl, preferably selected from cylo-octanyl and cyclohexyl or R3 represents a monovalent radical having one of the following formulae wherein said C6-12cycloalkyl or monovalent radical may optionally be substituted with one, or where possible two, three or more substituents selected from the group consisting of C1-4alkyl, C1-4alkyloxy, halo or hydroxy; Q represents Het1 or Ar2 wherein said C3-8cycloalkyl, Het1 or Ar2 are optionally substituted with one or where possible two or more substituents selected from halo, C1-4alkyl, C1-4alkyloxy, hydroxy, nitro, NR5R6, C1-4alkyloxy substituted with one or where possible two, three or more substituents each independently selected from hydroxycarbonyl, Het2 and NR7R8, and C1-4alkyl substituted with one or where possible two or three halo substituents, preferably trifluoromethyl; R5 and R6 each independently represent hydrogen, C1-4alkyl, or C1-4alkyl substituted with phenyl; R7 and R8 each independently represent hydrogen or C1-4alkyl; R9 and R10 each independently represent hydrogen, C1-4alkyl or C1-4alkyloxycarbonyl; L represents C1-4alkyl; Het1 represents a heterocycle selected from pyridinyl, thiophenyl, or 1,3-benzodioxolyl; Het2 represents piperidinyl, pyrrolidinyl or morpholinyl; Ar2 represents phenyl, naphtyl or indenyl.

公开(公告)号：US20060079506A1

公开(公告)日：2006-04-13

申请号：US10540616

申请日：2003-12-16

申请人： Joannes Linders ,  Gustaaf Willemsens ,  Ronaldus Gilissen ,  Christophe Francis Buyck ,  Greta Vanhoof ,  Louis Van Der Veken ,  Libuse Jaroskova

发明人： Joannes Linders ,  Gustaaf Willemsens ,  Ronaldus Gilissen ,  Christophe Francis Buyck ,  Greta Vanhoof ,  Louis Van Der Veken ,  Libuse Jaroskova

IPC分类号： A61K31/55 ,  A61K31/5377 ,  A61K31/502 ,  A61K31/501 ,  A61K31/497 ,  A61K31/4965 ,  A61K31/4172 ,  A61K31/4745

CPC分类号： C07D207/27 ,  C07C233/11 ,  C07C233/14 ,  C07C233/22 ,  C07C233/23 ,  C07C233/32 ,  C07C233/41 ,  C07C233/58 ,  C07C235/36 ,  C07C235/40 ,  C07C237/20 ,  C07C237/22 ,  C07C255/41 ,  C07C255/57 ,  C07C271/22 ,  C07C2601/02 ,  C07C2601/14 ,  C07C2601/18 ,  C07C2601/20 ,  C07C2602/06 ,  C07C2602/08 ,  C07C2602/10 ,  C07C2602/12 ,  C07C2602/18 ,  C07C2602/42 ,  C07C2602/46 ,  C07C2603/62 ,  C07C2603/66 ,  C07C2603/70 ,  C07C2603/74 ,  C07D209/08 ,  C07D209/18 ,  C07D213/56 ,  C07D215/08 ,  C07D215/48 ,  C07D217/06 ,  C07D217/26 ,  C07D243/08 ,  C07D257/04 ,  C07D277/40 ,  C07D277/48 ,  C07D295/088 ,  C07D295/155 ,  C07D295/185 ,  C07D309/12 ,  C07D311/58 ,  C07D311/64 ,  C07D317/60 ,  C07D317/72 ,  C07D333/24 ,  C07D333/68 ,  C07D335/06

摘要： the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein n represents an integer being 1 or 2; R1 and R2 each independently represents hydrogen C1-4alkyl, NR9R10, C1-4alkyloxy; or R1 and R2 taken together with the carbon atom with which they are attached form a C3-6cycloalkyl; and where n is 2, either R1 or R2 may be absent to form an unsaturated bond; R3 represents a C6-12cycloalkyl, preferably selected from cylo-octanyl and cyclohexyl or R3 represents a monovalent radical having one of the following formulae wherein said C6-12cycloalkyl or monovalent radical may optionally be substituted with one, or where possible two, three or more substituents selected from the group consisting of C1-4alkyl, C1-4alkyloxy, halo or hydroxy; Q represents Het1 or Ar2 wherein said C3-8cycloalkyl, Het1 or Ar2 are optionally substituted with one or where possible two or more substituents selected from halo, C1-4alkyl, C1-4alkyloxy, hydroxy, nitro, NR5R6, C1-4alkyloxy substituted with one or where possible two, three or more substituents each independently selected from hydroxycarbonyl, Het2 and NR7R8, and C1-4alkyl substituted with one or where possible two or three halo substituents, preferably trifluoromethyl; R5 and R6 each independently represent hydrogen, C1-4alkyl, or C1-4alkyl substituted with phenyl; R7 and R8 each independently represent hydrogen or C1-4alkyl; R9 and R10 each independently represent hydrogen, C1-4alkyl or C1-4alkyloxycarbonyl; L represents C1-4alkyl; Het1 represents a heterocycle selected from pyridinyl, thiophenyl, or 1,3-benzodioxolyl; Het2 represents piperidinyl, pyrrolidinyl or morpholinyl; Ar2 represents phenyl, naphtyl or indenyl.