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    Glucokinase activators and methods of using same
    1.
    发明授权
    Glucokinase activators and methods of using same 有权
    葡糖激酶活化剂及其使用方法

    公开(公告)号：US07888504B2

    公开(公告)日：2011-02-15

    申请号：US11769799

    申请日：2007-06-28

    申请人： Sean Chen ,  Peter T. W. Cheng ,  Rebecca A. Smirk

    发明人： Sean Chen ,  Peter T. W. Cheng ,  Rebecca A. Smirk

    IPC分类号： C07D277/34 ,  C07D277/36 ,  C07D277/38 ,  C07D417/12 ,  C07D403/12 ,  A61K31/427 ,  A61K31/506 ,  A61P3/10

    CPC分类号： C07D417/14 ,  C07D277/46 ,  C07D417/12

    摘要： Compounds are provided which are glucokinase activators and thus are useful in treating diabetes and related diseases and have the structure wherein in the ring represents one or two double bonds; R1 is aryl or heteroaryl; R2 is halogen, cycloalkyl, heterocyclyl, aryl, or heteroaryl; R5 is as defined herein; Z is O, S, S(O), S(O)2, or NR5a; X is S, O, N, NR3, or CR3; Y is NCR4 or N4; R3, R4, and R5 are as defined herein; R8 is aryl or heteroaryl; R6 and R7 are independently H, halogen, or alkyl; m is 0 or 1; and n is 0 to 3, or a pharmaceutically acceptable salt thereof. A method for treating diabetes and related diseases employing the above compounds is also provided.

    摘要翻译： 提供作为葡糖激酶活化剂的化合物，因此可用于治疗糖尿病和相关疾病，并且具有其中在环中表示一个或两个双键的结构; R1是芳基或杂芳基; R2是卤素，环烷基，杂环基，芳基或杂芳基; R5如本文所定义; Z是O，S，S（O），S（O）2或NR5a; X是S，O，N，NR 3或CR 3; Y是NCR4或NR4; R3，R4和R5如本文所定义; R8是芳基或杂芳基; R6和R7独立地是H，卤素或烷基; m为0或1; 和n为0至3，或其药学上可接受的盐。 还提供了使用上述化合物治疗糖尿病和相关疾病的方法。

    1,3-dihydroxy substituted phenylamide glucokinase activators
    2.
    发明授权
    1,3-dihydroxy substituted phenylamide glucokinase activators 有权
    1,3-二羟基取代苯酰胺葡糖激酶活化剂

    公开(公告)号：US08222285B2

    公开(公告)日：2012-07-17

    申请号：US12663807

    申请日：2008-06-11

    申请人： Sean Chen ,  Peter T. W. Cheng ,  Rebecca A. Smirk

    发明人： Sean Chen ,  Peter T. W. Cheng ,  Rebecca A. Smirk

    IPC分类号： A01N43/78 ,  A61K31/425

    CPC分类号： C07D277/56 ,  C07D417/12 ,  C07D417/14 ,  C07F9/6539

    摘要： Compounds are provided which are glucokinase activators and thus are useful in treating diabetes and related diseases and have the structure wherein in the ring represents one or two double bonds; R1 is alkyl, aryl, arylalkyl, heteroaryl, or heteroarylalkyl; R2 is alkyl, aryl, arylalkyl, heteroaryl, or heteroarylalkyl; R5 is as defined herein; Z is O, S, S(O), S(O)2, or NR5a; X is S, O, N, NR3, or CR3; Y is NCR4 or NR4; R3, R4, and R5 are as defined herein; R8 is aryl, heteroaryl, —PO(OR9)(OR10), —PO(OR9)R10 or —P(O)(R9)R10 (wherein R9 and R10 are as defined herein)/R6 and R7 are independently H, halogen, or alkyl; m is 0 or 1; and n is 0 to 3, or a pharmaceutically acceptable salt thereof. A method for treating diabetes and related diseases employing the above compounds is also provided.

    摘要翻译： 提供作为葡糖激酶活化剂的化合物，因此可用于治疗糖尿病和相关疾病，并且具有其中在环中表示一个或两个双键的结构; R 1是烷基，芳基，芳烷基，杂芳基或杂芳基烷基; R2是烷基，芳基，芳基烷基，杂芳基或杂芳基烷基; R5如本文所定义; Z是O，S，S（O），S（O）2或NR5a; X是S，O，N，NR 3或CR 3; Y是NCR4或NR4; R3，R4和R5如本文所定义; R8是芳基，杂芳基，-PO（OR9）（OR10），-PO（OR9）R10或-P（O）（R9）R10（其中R9和R10如本文所定义）/ R6和R7独立地是H，卤素 ，或烷基; m为0或1; 和n为0至3，或其药学上可接受的盐。 还提供了使用上述化合物治疗糖尿病和相关疾病的方法。

    Phosphonate and phosphinate pyrazolylamide glucokinase activators
    4.
    发明授权
    Phosphonate and phosphinate pyrazolylamide glucokinase activators 有权
    膦酸酯和次膦酸吡唑基酰胺葡萄糖激酶激活剂

    公开(公告)号：US07910747B2

    公开(公告)日：2011-03-22

    申请号：US11769964

    申请日：2007-06-28

    申请人： Denis E. Ryono ,  Peter T. W. Cheng ,  Scott A. Bolton ,  Sean Chen ,  Yan Shi ,  Wei Meng ,  Joseph A. Tino

    发明人： Denis E. Ryono ,  Peter T. W. Cheng ,  Scott A. Bolton ,  Sean Chen ,  Yan Shi ,  Wei Meng ,  Joseph A. Tino

    IPC分类号： C07D231/00

    CPC分类号： C07F9/6539 ,  C07F9/58 ,  C07F9/65031 ,  C07F9/650952 ,  C07F9/6518

    摘要： Pyrazoloamides are provided which are phosphonate and phosphinate glucokinase activators that are useful in treating diabetes and related diseases and have the structure wherein is a pyrazoyl ring; R4 is —(CH2)n—Z—(CH2)m—PO(OR7)(OR8), —(CH2)nZ—(CH2)m—PO(OR7)R9, or —(CH2)nZ—(CH2)m—PO(R9)(R10); R5 and R6 are independently selected from H, alkyl and halogen; Y is R3(CH2)s, wherein R3 is aryl , s is 0, X is a bond; and n, Z, m, R4, R5, R6, and R7 are as defined herein; or a pharmaceutically acceptable salt thereof.

    摘要翻译： 提供了吡唑并酰胺，其是可用于治疗糖尿病和相关疾病的膦酸盐和次膦酸盐葡糖激酶活化剂，并且其结构是吡唑基环; R4是 - （CH2）n-Z-（CH2）m-PO（OR7）（OR8）， - （CH2）nZ-（CH2）m-PO（OR7）R9或 - （CH2）nZ-（CH2） m-PO（R9）（R10）; R5和R6独立地选自H，烷基和卤素; Y是R3（CH2）s，其中R3是芳基，s是0，X是一个键; 并且n，Z，m，R 4，R 5，R 6和R 7如本文所定义; 或其药学上可接受的盐。

    Substituted heterocyclic derivatives useful as antidiabetic and antiobesity agents and method
    6.
    发明授权
    Substituted heterocyclic derivatives useful as antidiabetic and antiobesity agents and method 有权
    用作抗糖尿病和抗肥胖剂的取代的杂环衍生物和方法

    公开(公告)号：US07279485B2

    公开(公告)日：2007-10-09

    申请号：US10616365

    申请日：2003-07-08

    申请人： Peter T. W. Cheng ,  Sean Chen ,  Pratik Devasthale ,  Charles Z. Ding ,  Timothy F. Herpin ,  Shung Wu ,  Hao Zhang ,  Wei Wang ,  Xiang-Yang Ye

    发明人： Peter T. W. Cheng ,  Sean Chen ,  Pratik Devasthale ,  Charles Z. Ding ,  Timothy F. Herpin ,  Shung Wu ,  Hao Zhang ,  Wei Wang ,  Xiang-Yang Ye

    IPC分类号： A01N43/54 ,  A01N43/76 ,  A61K31/505 ,  C07D239/02 ,  C07D413/00

    CPC分类号： C07D413/12 ,  C07D413/14

    摘要： Substituted heterocyclic derivatives are provided which have the structure wherein Z1 is (CH2)q or C═O; Z2 is (CH2)p or C═O; D is —CH═ or C═O or (CH2)m where m is 0, 1, 2 or 3; n=0, 1 or 2; p=1 or 2; q=0, 1 or 2; Q is C or N; X is CH or N; X2 is C, N, O or S; X3 is C, N, O or S; X4 is C, N, O or S; X5 is C, N, O or S; X6 is C, N, O or S; provided that at least one of X2, X3, X4, X5 and X6 is N; and at least one of X2, X3, X4, X5 and X6 is C; A, B, R1, R2, R2a, R2b, R4, R3, E, Z and Y are as defined herein. In addition, a method is provided for treating diabetes, Type 2 diabetes, insulin resistance, hyperglycemia, hyperinsulinemia, elevated blood levels of fatty acids or glycerol, hyperlipidemia, obesity, hypertriglyceridemia, Syndrome X, or atherosclerosis, wherein the substituted heterocyclic derivatives are administered in a therapeutically effective amount to a patient.

    摘要翻译： 提供了取代的杂环衍生物，其具有其中Z 1是（CH 2 CH 2）q或C-O的结构; Z 2是（CH 2）2或C-O; D是-CH-或C-O或（CH 2 CH 2）m，其中m是0,1,2或3; n = 0,1或2; p = 1或2; q = 0,1或2; Q是C或N; X是CH或N; X 2是C，N，O或S; X 3是C，N，O或S; X 4是C，N，O或S; X 5是C，N，O或S; X 6是C，N，O或S; 条件是X 2，X 3，X 4，X 5和X 3中的至少一个， 6是N; 和X 2，X 3，X 4，X 5和X 6中的至少一个 是C; A，B，R 1，R 2，R 2a，R 2b，R 4， R 3，R 3，E，Z和Y如本文所定义。 另外，提供了一种治疗糖尿病，2型糖尿病，胰岛素抵抗，高血糖症，高胰岛素血症，升高的脂肪酸或甘油血糖水平，高脂血症，肥胖症，高甘油三酯血症，综合征X或动脉粥样硬化的方法，其中给予取代的杂环衍生物 以治疗有效量给予患者。

    Substituted pyrazolylamides useful as glucokinase activators
    7.
    发明授权
    Substituted pyrazolylamides useful as glucokinase activators 有权
    用作葡糖激酶活化剂的取代的吡唑基酰胺

    公开(公告)号：US08614332B2

    公开(公告)日：2013-12-24

    申请号：US13397123

    申请日：2012-02-15

    申请人： Denis E. Ryono ,  Peter T. W. Cheng ,  Scott A. Bolton ,  Sean Chen ,  Yan Shi ,  Wei Meng ,  Joseph A. Tino ,  Richard B. Sulsky

    发明人： Denis E. Ryono ,  Peter T. W. Cheng ,  Scott A. Bolton ,  Sean Chen ,  Yan Shi ,  Wei Meng ,  Joseph A. Tino ,  Richard B. Sulsky

    IPC分类号： C07D231/00

    CPC分类号： C07F9/6539 ,  C07F9/58 ,  C07F9/65031 ,  C07F9/650952 ,  C07F9/6518

    摘要： Compounds are provided which are phosphonate and phosphinate activators and thus are useful in treating diabetes and related diseases and have the structure is a heteroaryl ring; R4 is —(CH2)n—Z—(CH2)m—PO(OR7)(OR8), —(CH2)nZ—(CH2)m—PO(OR7)R9, —(CH2)n—Z—(CH2)m—OPO(OR7)R9, —(CH2)nZ—(CH2)m—OPO(R9)(R10), or —(CH2)nZ—(CH2)m—PO(R9)(R10); R5 and R6 are independently selected from H, alkyl and halogen; Y is R7(CH2)s or is absent; and X, n, Z, m, R4, R5, R6, R7, and s are as defined herein; or a pharmaceutically acceptable salt thereof. A method for treating diabetes and related diseases employing the above compounds is also provided.

    摘要翻译： 提供了膦酸酯和次膦酸酯活化剂的化合物，因此可用于治疗糖尿病和相关疾病，并且其结构是杂芳基环; R4是 - （CH2）nZ-（CH2）m-PO（OR7）（OR8）， - （CH2）nZ-（CH2）m-PO（OR7）R9， - （CH2）nZ-（CH2） （OR7）R9， - （CH2）nZ-（CH2）m-OPO（R9）（R10）或 - （CH2）nZ-（CH2）m-PO（R9）（R10） R5和R6独立地选自H，烷基和卤素; Y为R 7（CH 2）s或不存在; 并且X，n，Z，m，R 4，R 5，R 6，R 7和s如本文所定义; 或其药学上可接受的盐。 还提供了使用上述化合物治疗糖尿病和相关疾病的方法。

    Substituted pyrazolylamide compounds useful as glucokinase activators
    8.
    发明授权
    Substituted pyrazolylamide compounds useful as glucokinase activators 有权
    用作葡糖激酶活化剂的取代的吡唑基酰胺化合物

    公开(公告)号：US08153677B2

    公开(公告)日：2012-04-10

    申请号：US13012351

    申请日：2011-01-24

    申请人： Denis E. Ryono ,  Peter T. W. Cheng ,  Scott A. Bolton ,  Sean Chen ,  Yan Shi ,  Wei Meng ,  Joseph A. Tino ,  Richard B. Sulsky

    发明人： Denis E. Ryono ,  Peter T. W. Cheng ,  Scott A. Bolton ,  Sean Chen ,  Yan Shi ,  Wei Meng ,  Joseph A. Tino ,  Richard B. Sulsky

    IPC分类号： A61K31/415

    CPC分类号： C07F9/6539 ,  C07F9/58 ,  C07F9/65031 ,  C07F9/650952 ,  C07F9/6518

    摘要： Compounds are provided which are phosphonate and phosphinate activators and thus are useful in treating diabetes and related diseases and have the structure wherein is a heteroaryl ring; R4 is —(CH2)n—Z—(CH2)m—PO(OR7)(OR8), —(CH2)nZ—(CH2)m—OPO(OR7)R9, —(CH2)nZ—(CH2)m—OPO(R9)(R10), or —(CH2)nZ—(CH2)m—PO(R9)(R10); R5 and R6 are independently selected from hydrogen, alkyl and halogen; Y is R7(CH2)s or is absent; and X, n, Z, m, R4, R5, R6, R7, and s are as defined herein; or a pharmaceutically acceptable salt thereof. A method for treating diabetes and related diseases employing the above compounds is also provided.

    摘要翻译： 提供了膦酸酯和次膦酸酯活化剂的化合物，因此可用于治疗糖尿病和相关疾病，并且其结构是杂芳基环; R4是 - （CH2）n-Z-（CH2）m-PO（OR7）（OR8）， - （CH2）nZ-（CH2）m-OPO（OR7）R9， - （CH2）nZ-（CH2） -OPO（R9）（R10）或 - （CH2）nZ-（CH2）m-PO（R9）（R10）; R5和R6独立地选自氢，烷基和卤素; Y为R 7（CH 2）s或不存在; 并且X，n，Z，m，R 4，R 5，R 6，R 7和s如本文所定义; 或其药学上可接受的盐。 还提供了使用上述化合物治疗糖尿病和相关疾病的方法。

    Substituted heterocyclic derivatives useful as antidiabetic and antiobesity agents and method
    9.
    发明授权
    Substituted heterocyclic derivatives useful as antidiabetic and antiobesity agents and method 有权
    用作抗糖尿病和抗肥胖剂的取代的杂环衍生物和方法

    公开(公告)号：US07507757B2

    公开(公告)日：2009-03-24

    申请号：US11016183

    申请日：2004-12-17

    申请人： Peter T. W. Cheng ,  Sean Chen ,  Charles Z. Ding ,  Timothy F. Herpin

    发明人： Peter T. W. Cheng ,  Sean Chen ,  Charles Z. Ding ,  Timothy F. Herpin

    IPC分类号： A61K31/4164 ,  C07D233/56

    CPC分类号： C07D233/64 ,  C07D249/06 ,  C07D263/32 ,  C07D271/06 ,  C07D413/12

    摘要： Compounds are provided which are useful as antidiabetic agents and antiobesity agents and have the structure wherein m is 0, 1 or 2; n is 0, 1 or 2; Q is C or N; A is (CH2)x where x is 1 to 5, or A is (CH2)x1 where x1 is 1 to 5 with an alkenyl bond or an alkynyl bond embedded anywhere in the chain, or A is —(CH2)x2—O—(CH2)x3— where x2 is 0 to 5 and x3 is 0 to 5, provided that at least one of x2 and x3 is other than 0; B is a bond or is (CH2)x4 where x4 is 1 to 5; X is CH; X2 is N; X3 is C; X4 is N; X5 is C; X6 is C.

    摘要翻译： 提供可用作抗糖尿病剂和抗肥胖剂并具有其中m为0,1或2的结构的化合物; n为0,1或2; Q是C或N; A是（CH 2）x，其中x是1至5，或A是（CH 2）x1，其中x1是1至5，其中烯基键或链烯基嵌入链中的任何位置，或A是 - （CH 2）x 2 -O - （CH 2）x3-，其中x2为0至5，x3为0至5，条件是x2和x3中的至少一个不为0; B是键或是（CH 2）x 4，其中x 4是1至5; X是CH; X2是N; X3是C; X4是N; X5是C; X6是C.