公开(公告)号：WO2005020987A1

公开(公告)日：2005-03-10

申请号：PCT/GB2004/003648

申请日：2004-08-27

Applicant: ASTRAZENECA AB ,  ASTRAZENECA UK LIMITED ,  BIRCH, Alan, Martin ,  SIMPSON, Iain ,  STOCKER, Andrew ,  WHITTAMORE, Paul, Robert, Owen

Inventor： BIRCH, Alan, Martin ,  SIMPSON, Iain ,  STOCKER, Andrew ,  WHITTAMORE, Paul, Robert, Owen

IPC: A61K31/407

CPC classification number: C07D471/04 ,  C07D495/04

Abstract: Heterocyclic amides of formula (1) wherein: B is selected from R4 and R 5 together are either -S-C(R 6)=C(R 7)_ or _C(R7)=C(R6)_S_; A is a pyridylene ring; m is 0, 1 or 2; n is 0 or 1; R 2 is for example selected from (I -4C)alkyl, hydroxy(l -4C)alkyl, dihydroxy(2-4C)alkyl and (1 -4C)aIkoxy(1 -4C)alkyl. or a pharmaceutically acceptable salt possess glycogen phosphorylase inhibitory activity and accordingly have value in the treatment of disease states associated with increased glycogen phosphorylase activity. Processes for the manufacture of said heterocyclic amide derivatives, intermediates in said processes and pharmaceutical compositions containing the heterocyclic amide derivatives are described.

Abstract translation: 式（1）的杂环酰胺其中：B选自R4和R5一起是-S-C（R 6）= C（R 7）或-C（R 7）= C（R 6） A是吡啶环; m为0,1或2; n为0或1; R 2例如选自（I-4c）烷基，羟基（1-4C）烷基，二羟基（2-4C）烷基和（1-4C）烷氧基（1-4C）烷基。 或药学上可接受的盐具有糖原磷酸化酶抑制活性，因此在治疗与增加的糖原磷酸化酶活性相关的疾病状态方面具有价值。 描述了制备所述杂环酰胺衍生物的方法，所述方法中的中间体和含有杂环酰胺衍生物的药物组合物。

公开(公告)号：WO2009060232A1

公开(公告)日：2009-05-14

申请号：PCT/GB2008/051029

申请日：2008-11-05

Applicant: ASTRAZENECA AB ,  ASTRAZENECA UK LIMITED ,  PACKER, Martin ,  SCOTT, James, Stewart ,  STOCKER, Andrew ,  WHITTAMORE, Paul, Robert, Owen

Inventor： PACKER, Martin ,  SCOTT, James, Stewart ,  STOCKER, Andrew ,  WHITTAMORE, Paul, Robert, Owen

IPC: A61K31/415 ,  C07D231/14 ,  A61P3/00

CPC classification number: C07D231/14

Abstract: 4-[4-(2-Adamantylcarbamoyl)-5-tert-butyl-pyrazol- 1 -yl]benzoic acid and pharmaceutically-acceptable salts thereof and a particular crystalline form of the Agent (Form 1); their use in the inhibition of 11 βHSD1, processes for making them and pharmaceutical compositions comprising them are also described.

Abstract translation: 4- [4-（2-金刚烷基氨基甲酰基）-5-叔丁基 - 吡唑-1-基]苯甲酸及其药学上可接受的盐和特定结晶形式的试剂（形式1）; 还描述了其在抑制11βHSD1中的应用，其制备方法和包含它们的药物组合物。

公开(公告)号：WO2004031194A1

公开(公告)日：2004-04-15

申请号：PCT/GB2003/004217

申请日：2003-09-29

Applicant: ASTRAZENECA AB ,  ASTRAZENECA UK LIMITED ,  MURRAY, Paul, Michael ,  PARKER, Jeremy, Stephen ,  SCHOFIELD, Paul ,  STOCKER, Andrew

Inventor： MURRAY, Paul, Michael ,  PARKER, Jeremy, Stephen ,  SCHOFIELD, Paul ,  STOCKER, Andrew

IPC: C07D495/04

CPC classification number: C07D495/04 ,  C07D333/36 ,  Y02P20/55

Abstract: A process for preparing a compound of formula (I) where R 4 and R 5 are as defined in the specification; and R 6 is hydrogen or a protecting group, which process comprises cyclisation of a compound of formula (II) where R 4 , R 5 and R 6 are as defined in relation to formula (I) and R 7 is a nitrogen-protecting group, and removing protecting group R 7 -, and thereafter if desired or necessary, removing any protecting group R 6 to obtain the corresponding carboxylic acid. Novel intermediates and the use of the products in the preparation of pharmaceutical compounds is also described and claimed.

Abstract translation: 制备式（I）化合物的方法，其中R 4和R 5如说明书中所定义; 并且R 6是氢或保护基，该方法包括使式（II）化合物环化，其中R 4，R 5和R 6如关于式（I）所定义，和 R 7是氮保护基，除去保护基R 7，然后如果需要或必要的话，除去任何保护基团R 6，得到相应的羧酸。 还描述和要求保护新型中间体和制备药物化合物中产物的用途。

公开(公告)号：WO2003074532A1

公开(公告)日：2003-09-12

申请号：PCT/GB2003/000877

申请日：2003-03-04

Applicant: ASTRAZENECA AB ,  ASTRAZENECA UK LIMITED ,  BIRCH, Alan, Martin ,  MORLEY, Andrew, David ,  STOCKER, Andrew ,  WHITTAMORE, Paul, Robert, Owen

Inventor： BIRCH, Alan, Martin ,  MORLEY, Andrew, David ,  STOCKER, Andrew ,  WHITTAMORE, Paul, Robert, Owen

IPC: C07D495/04

CPC classification number: C07D495/04

Abstract: Heterocyclic amides of formula (1) wherein: X is N or CH; R 4 and R 5 together are either -S-C(R 6 )=C(R 7 )- or -C(R 7 )=C(R 6 )-S-; R 6 and R 7 are independently selected from, for example hydrogen, halo and C 1-4 alkyl; A is phenylene or heteroarylene; n is 0, 1 or 2; R 1 is selected from for example halo, nitro, cyano, hydroxy, carboxy; R 2 is hydrogen, hydroxy or carboxy; R 3 is selected from for example hydrogen, hydroxy, aryl, heterocyclyl and C 1-4 alkyl (optionally substituted by 1 or 2 R 8 groups); R 8 is selected from for example hydroxy, -COCOOR 9 , -C(O)N(R 9 )(R 10 ), -NHC(O)R 9 , (R 9 )(R 10 )N- and -COOR 9 ; R 9 and R 10 are selected from for example hydrogen, hydroxy, C 1-4 alkyl (optionally substituted by 1 or 2 R 13 ); R 13 is selected from hydroxy, halo, trihalomethyl and C 1-4 alkoxy; or a pharmaceutically acceptable salt or pro-drug thereof; possess glycogen phosphorylase inhibitory activity and accordingly have value in the treatment of disease states associated with increased glycogen phosphorylase activity. Processes for the manufacture of said heterocyclic amide derivatives and pharmaceutical compositions containing them are described.

Abstract translation: 式（1）的杂环酰胺其中：X是N或CH; R4和R5一起是-S-C（R6）= C（R7） - 或-C（R7）= C（R6）-S-; R 6和R 7独立地选自例如氢，卤素和C 1-4烷基; A是亚苯基或亚杂芳基; n为0,1或2; R 1选自例如卤素，硝基，氰基，羟基，羧基; R2是氢，羟基或羧基; R3选自例如氢，羟基，芳基，杂环基和C 1-4烷基（任选被1或2个R 8基团取代）; R8选自例如羟基，-COCOOR9，-C（O）N（R9）（R10），-NHC（O）R9，（R9）（R10）N-和-COOR9; R9和R10选自例如氢，羟基，C 1-4烷基（任选被1或2个R 13取代）; R 13选自羟基，卤代，三卤代甲基和C 1-4烷氧基; 或其药学上可接受的盐或前体药物; 具有糖原磷酸化酶抑制活性，因此具有与增加的糖原磷酸化酶活性相关的疾病状态的治疗价值。 描述了制备所述杂环酰胺衍生物和含有它们的药物组合物的方法。

公开(公告)号：WO1998021188A1

公开(公告)日：1998-05-22

申请号：PCT/GB1997003033

申请日：1997-11-04

Applicant: ZENECA LIMITED ,  PRESTON, John ,  STOCKER, Andrew ,  TURNER, Paul ,  SMITHERS, Michael, James ,  RAYNER, John, Wall

Inventor： ZENECA LIMITED

IPC: C07D239/26

CPC classification number: C07D213/73 ,  A61K31/44 ,  A61K31/505 ,  C07D213/56 ,  C07D213/61 ,  C07D213/84 ,  C07D213/89 ,  C07D237/08 ,  C07D239/26

Abstract: The invention relates to heterocyclic derivatives of the formula (I): A-B-X -T (R )-L -T (R )-X -Q or pharmaceutically acceptable salts thereof, which possess antithrombotic and anticoagulant properties due to their inhibition of Factor Xa and are accordingly useful in methods of treatment of humans or animals. The invention also relates to processes for the preparation of the heterocyclic derivatives, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments for use in the production of an antithrombotic or anticoagulant effect.

Abstract translation: 本发明涉及式（I）的杂环衍生物：ABX 1 -T 1（R 2）-L 1 -T 2（R 3）-X 2 - Q或其药学上可接受的盐，由于其对因子Xa的抑制而具有抗血栓形成和抗凝血性质，因此可用于治疗人或动物的方法。 本发明还涉及制备杂环衍生物的方法，含有它们的药物组合物及其在制备用于产生抗血栓形成或抗凝血作用的药物中的用途。

公开(公告)号：WO1996010022A1

公开(公告)日：1996-04-04

申请号：PCT/GB1995002285

申请日：1995-09-25

Applicant: ZENECA LIMITED ,  FAULL, Alan, Wellington ,  MAYO, Colette, Marie ,  PRESTON, John ,  STOCKER, Andrew

Inventor： ZENECA LIMITED

IPC: C07D401/04

CPC classification number: C07D213/74 ,  C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14

Abstract: The invention concerns compounds of formula (I), wherein each of G , G and G is CH or N; m is 1 or 2; R includes hydrogen, halogeno and (1-4C)alkyl; M is a group of formula: NR -L -T R , in which R and R together form a (1-4C)alkylene group, L includes (1-4C)alkylene, and T is CH or N; A may be a direct link; M is a group of the formula: (T R )r-L -T R in which R is 0 or 1, each of T and T is CH or N, each of R and R is hydrogen or (1-4C)alkyl, or R and R together form a (1-4C)alkylene group, and L includes (1-4C)alkylene; M may be a direct link to X; X includes sulphonyl; and Q includes naphthyl and a heterocyclic moiety; or a pharmaceutically-acceptable salt thereof; processes for their preparation, pharmaceutical compositions containing them and their use as antithrombotic or anticoagulant agents.

Abstract translation: 本发明涉及式（I）化合物，其中G 1，G 2和G 3各自为CH或N; m为1或2; R 1包括氢，卤素和（1-4C）烷基; M 1是下式的基团：NR 2 -L 1 -T 1 R 3，其中R 2和R 3一起形成（1-4C）亚烷基 ，L 1包括（1-4C）亚烷基，T 1是CH或N; A可能是直接链接; M 2是下式的基团：（T 2 R 4）r L 2 -T 3 R 5其中R是0或1，每个T 2和T R 3和R 5分别是氢或（1-4C）烷基，或者R 4和R 5一起形成（1-4C）亚烷基， 和L 2包括（1-4C）亚烷基; M 3可以直接连接到X; X包括磺酰基; 且Q包括萘基和杂环部分; 或其药学上可接受的盐; 其制备方法，含有它们的药物组合物及其作为抗血栓形成或抗凝血剂的用途。

公开(公告)号：WO2008099145A1

公开(公告)日：2008-08-21

申请号：PCT/GB2008/000454

申请日：2008-02-11

Applicant: ASTRAZENECA AB ,  ASTRAZENECA UK LIMITED ,  PACKER, Martin, John ,  SCOTT, James, Stewart ,  STOCKER, Andrew ,  WHITTAMORE, Paul, Robert, Owen

Inventor： PACKER, Martin, John ,  SCOTT, James, Stewart ,  STOCKER, Andrew ,  WHITTAMORE, Paul, Robert, Owen

IPC: A61K31/415 ,  C07D231/14 ,  C07D231/18 ,  C07D403/06 ,  C07D405/12 ,  A61P3/00

CPC classification number: C07D231/18 ,  C07D231/14 ,  C07D403/06 ,  C07D405/12

Abstract: A compound of formula (I): and pharmaceutically -acceptable salts thereof wherein the variable groups are defined within; their use in the inhibition of 11βHSD1, processes for making them and pharmaceutical compositions comprising them are also described.

Abstract translation: 式（I）化合物及其药学上可接受的盐，其中所述可变基团定义在其内; 还描述了其在抑制11βHSD1中的用途，其制备方法和包含它们的药物组合物。

公开(公告)号：WO2003074517A1

公开(公告)日：2003-09-12

申请号：PCT/GB2003/000924

申请日：2003-03-04

Applicant: ASTRAZENECA AB ,  ASTRAZENECA UK LIMITED ,  STOCKER, Andrew ,  WHITTAMORE, Paul, Robert, Owen

Inventor： STOCKER, Andrew ,  WHITTAMORE, Paul, Robert, Owen

IPC: C07D413/12

CPC classification number: C07D413/12 ,  C07D209/42

Abstract: Heterocyclic amides of formula (1), wherein: m is 0, 1 or 2; n is 0, 1 or 2; B is phenyl or heterocyclyl; R 1 is selected from for example halo, nitro, cyano, hydroxy, carboxy; R 2 and R 3 are independently selected from, for example, C 5-7 cycloalkyl, cyano(C 1-4 )alkyl, C 1-4 alkyl (optionally substituted with 1 or 2 R 8 groups), -OR 8 and R 8 ; R 4 is independently selected from for example hydrogen, halo, nitro, cyano, hydroxy, C 1-4 alkyl, and C 1-4 alkanoyl; R 8 is selected from for example hydroxy, heterocyclyl, aryl, -COCOOR 9 , -C(O)N(R 9 )(R 10 ), (R 9 )(R 10 )N- and -COOR 9 ; R 9 and R 10 are selected from for example hydrogen, hydroxy, C 1-4 alkyl (optionally substituted by 1 or 2 R 13 ); R 13 is selected from for example, hydroxy, C 1-4 alkoxy, heterocyclyl and C 1-4 alkanoyl; R 14 is selected from for example, hydrogen, halo, C 1-4 alkyl, C 5-7 cycloalkyl, C 1-4 alkoxy, cyano, cyano(C 1-4 )alkyl, -COR 3 , (R 2 )(R 3 )NCO-, and (R 2 )(R 3 )NSO 2- ; or a pharmaceutically acceptable salt or pro-drug thereof; possess glycogen phosphorylase inhibitory activity and accordingly have value in the treatment of disease states associated with increased glycogen phosphorylase activity. Processes for the manufacture of said heterocyclic amide derivatives and pharmaceutical compositions containing them are described.

Abstract translation: 式（1）的杂环酰胺，其中：m为0,1或2; n为0,1或2; B是苯基或杂环基; R 1选自例如卤素，硝基，氰基，羟基，羧基; R 2和R 3独立地选自例如C 5-7环烷​​基，氰基（C 1-4）烷基，C 1-4烷基（任选被1或2个R 8基团取代），-OR 8和R 8; R 4独立地选自例如氢，卤素，硝基，氰基，羟基，C 1-4烷基和C 1-4烷酰基; R8选自例如羟基，杂环基，芳基，-COCOOR9，-C（O）N（R9）（R10），（R9）（R10）N-和-COOR9; R9和R10选自例如氢，羟基，C 1-4烷基（任选被1或2个R 13取代）; R 13选自例如羟基，C 1-4烷氧基，杂环基和C 1-4烷酰基; R 14选自例如氢，卤素，C 1-4烷基，C 5-7环烷​​基，C 1-4烷氧基，氰基，氰基（C 1-4）烷基，-COR 3，（R 2）（R 3）NCO-和（R 2） R3）NSO 2; 或其药学上可接受的盐或前体药物; 具有糖原磷酸化酶抑制活性，因此具有与增加的糖原磷酸化酶活性相关的疾病状态的治疗价值。 描述了制备所述杂环酰胺衍生物和含有它们的药物组合物的方法。

公开(公告)号：WO2004031193A1

公开(公告)日：2004-04-15

申请号：PCT/GB2003/004211

申请日：2003-09-29

Applicant: ASTRAZENECA AB ,  ASTRAZENECA UK LIMITED ,  BUTTERS, Michael ,  SCHOFIELD, Paul ,  STOCKER, Andrew

Inventor： BUTTERS, Michael ,  SCHOFIELD, Paul ,  STOCKER, Andrew

IPC: C07D495/04

CPC classification number: C07D495/04 ,  C07D333/36 ,  Y02P20/55

Abstract: Novel Process and Intermediates. A process for preparing a compound of formula (I) where R 4 and R 5 are as defined in the specification; and R 6 is hydrogen or a protecting group, which process comprises cyclisation of a compound of formula (II) where R 4 , R 5 and R 6 are as defined in relation to formula (I), and R 7 is a nitrogen protecting group, and removing the group R 7 , and thereafter if desired, removing any protecting group R 6 . Novel intermediates and the use of these in the formation of pharmaceutical compounds is also described and claimed.

Abstract translation: 新工艺和中间体。 制备式（I）化合物的方法，其中R 4和R 5如说明书中所定义; 并且R 6是氢或保护基，该方法包括使式（II）化合物环化，其中R 4，R 5和R 6如关于式（I）所定义， R 7为氮保护基，除去基团R 7，然后如果需要，除去任何保护基R 6。 还描述和要求保护新型中间体及其在药物化合物形成中的用途。

公开(公告)号：WO1997028129A1

公开(公告)日：1997-08-07

申请号：PCT/GB1997000284

申请日：1997-01-31

Applicant: ZENECA LIMITED ,  SMITHERS, Michael, James ,  PRESTON, John ,  STOCKER, Andrew

Inventor： ZENECA LIMITED

IPC: C07D213/74

CPC classification number: C07D401/14 ,  C07D213/74 ,  C07D237/20 ,  C07D239/42 ,  C07D401/04 ,  C07D401/12

Abstract: Compounds of formula (I), wherein G is CH or N; G is CH or N; R is a variety of optional substituents; L is (1-4C)alkylene; T is CH or N; R and R are independently hydrogen or (1-4C)alkyl or are joined to form a ring; X and X represent various linking groups; Ar is phenylene or certain heteroaryl rings and Q represents a variety of aromatic or heterocyclic rings systems, and pharmaceutically acceptable salts thereof are described as useful antithrombotic and anticoagulant agents, and are selective Factor Xa inhibitors. Processes for their preparation and pharmaceutical compositions containing them are also described.

Abstract translation: 式（I）的化合物，其中G 1是CH或N; G 2是CH或N; R 1是各种任选的取代基; L 1为（1-4C）亚烷基; T 1是CH或N; R 2和R 3独立地是氢或（1-4C）烷基或连接形成环; X 1和X 2代表各种连接基团; Ar是亚苯基或某些杂芳基环，Q表示各种芳族或杂环体系，其药学上可接受的盐被描述为有用的抗血栓形成和抗凝血剂，并且是选择性因子Xa抑制剂。 还描述了其制备方法和含有它们的药物组合物。