公开(公告)号：US07223837B2

公开(公告)日：2007-05-29

申请号：US10472921

申请日：2002-03-25

Applicant: Franciscus Marinus Hendrikus De Groot ,  Patrick Henry Beusker ,  Johannes Wilhelm Scheeren ,  Dick De Vos ,  Leonardus Wilhelmus Adriaan Van Berkom ,  Guuske Frederike Busscher ,  Antoinette Eugenie Seelen ,  Ralph Koekkoek ,  Carsten Albrecht

Inventor： Franciscus Marinus Hendrikus De Groot ,  Patrick Henry Beusker ,  Johannes Wilhelm Scheeren ,  Dick De Vos ,  Leonardus Wilhelmus Adriaan Van Berkom ,  Guuske Frederike Busscher ,  Antoinette Eugenie Seelen ,  Ralph Koekkoek ,  Carsten Albrecht

IPC: C07K5/08

CPC classification number: B82Y5/00 ,  A61K47/65 ,  A61K47/67 ,  A61K47/6889 ,  A61K47/6899

Abstract: This invention is directed to prodrugs that can be activated at the preferred site of action in order to selectively deliver the corresponding therapeutic parent drugs to target cells or to the target site. This invention will therefore primarily but not exclusively relate to tumor cells as target cells. More specifically the prodrugs are compounds of the formula V—(W)k—(X)l—A—Z, wherein: V is a specifier; (W)k—(X)l—A is an elongated self-elimination spacer system; W and X are each a 1,(4+2n) electronic cascade spacer, being the same or different; A is either a spacer group of formula (Y)m wherein: Y is a 1,(4+2n) electronic cascade spacer, or a group of formula U being a cyclization elimination spacer; Z is a therapeutic drug; k, l and m are integers from 0 (included) to 5 (included); n is an integer of 0 (included) to 10 (included), with the provisos that: —when A is (Y)m: k+l+m≧1, and if k+l+m=1; —when A is U: k+l≧1.

Abstract translation: 本发明涉及可以在优选的作用位点被活化的前药，以便选择性地将相应的治疗性母体药物递送至靶细胞或靶位点。 因此，本发明主要但不完全涉及作为靶细胞的肿瘤细胞。 更具体地，前药是式V-（W） - （X）1-Z-Z的化合物，其中：V是说明符; （W） - （X）1 - A是细长的自消除间隔体系; W和X分别为1（4 + 2n）个电子级联间隔物，相同或不同; A是式（Y）的间隔基团其中：Y是1，（4 + 2n）电子级联间隔基，或者是一组式U是环化消除间隔基; Z是治疗药物; k，l和m是从0（包括）到5（包括）的整数; n是0（包括）到10（包括）的整数，条件是：当A是（Y）m：k + 1 + m> = 1时，如果k + 1 + m = 1; - 当A是U：k + l> = 1。

公开(公告)号：US20090325980A1

公开(公告)日：2009-12-31

申请号：US12446580

申请日：2007-10-22

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

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

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

CPC classification number: C07D241/20 ,  C07D211/58 ,  C07D295/10 ,  C07D401/12 ,  C07D401/14

Abstract: 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.

Abstract translation: 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：US20100016291A1

公开(公告)日：2010-01-21

申请号：US12446581

申请日：2007-10-22

Applicant: Lieven Meerpoel ,  Leo Jacobus Jozef Backx ,  Peter Ten Holte ,  Guuske Frederike Busscher

Inventor： Lieven Meerpoel ,  Leo Jacobus Jozef Backx ,  Peter Ten Holte ,  Guuske Frederike Busscher

IPC: A61K31/55 ,  C07D223/12 ,  C07D401/12 ,  A61K31/4439 ,  C07C233/00 ,  A61K31/165 ,  A61K31/5377 ,  C07D413/12

CPC classification number: C07C235/60 ,  C07C233/78 ,  C07C2602/10 ,  C07D207/14 ,  C07D213/82 ,  C07D223/12 ,  C07D265/30 ,  C07D401/12 ,  C07D413/12

Abstract: The present invention is concerned with novel 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. Formula (I).

Abstract translation: 本发明涉及具有apoB分泌/ MTP抑制活性和伴随降脂活性的新型四氢萘-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。 式（I）。

公开(公告)号：US08158783B2

公开(公告)日：2012-04-17

申请号：US12446581

申请日：2007-10-22

Applicant: Lieven Meerpoel ,  Leo Jacobus Jozef Backx ,  Peter Ten Holte ,  Guuske Frederike Busscher

Inventor： Lieven Meerpoel ,  Leo Jacobus Jozef Backx ,  Peter Ten Holte ,  Guuske Frederike Busscher

IPC: A61K31/55 ,  A61K31/4439 ,  A61K31/165 ,  A61K31/5377 ,  C07D223/12 ,  C07D401/12 ,  C07D413/12 ,  C07C233/00

CPC classification number: C07C235/60 ,  C07C233/78 ,  C07C2602/10 ,  C07D207/14 ,  C07D213/82 ,  C07D223/12 ,  C07D265/30 ,  C07D401/12 ,  C07D413/12

Abstract: The present invention is concerned with novel 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. Formula (I).

Abstract translation: 本发明涉及具有apoB分泌/ MTP抑制活性和伴随降脂活性的新型四氢萘-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。 式（I）。

公开(公告)号：US08114880B2

公开(公告)日：2012-02-14

申请号：US12446580

申请日：2007-10-22

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

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

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

CPC classification number: C07D241/20 ,  C07D211/58 ,  C07D295/10 ,  C07D401/12 ,  C07D401/14

Abstract: 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.

Abstract translation: 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。