公开(公告)号：US20070185061A1

公开(公告)日：2007-08-09

申请号：US11556944

申请日：2006-11-06

申请人： David Campbell ,  David Winn ,  Juan Betancort ,  Kevin Shreder ,  Yi Hu ,  Bei Li ,  Melissa Wong ,  Lifu Ma ,  William Ripka ,  Min Wu

发明人： David Campbell ,  David Winn ,  Juan Betancort ,  Kevin Shreder ,  Yi Hu ,  Bei Li ,  Melissa Wong ,  Lifu Ma ,  William Ripka ,  Min Wu

IPC分类号： A61K31/69 ,  C07F5/02

CPC分类号： C07F5/025

摘要： Dipeptidyl peptidase IV (DPP-IV)-inhibiting compounds are provided that have formula I: wherein n is 1 to 3; X is CH2; S; O; CF2 or C(CH3)2; Z is H; halogen; hydroxyl; (C1-6)alkoxy; (C1-12)alkyl; (C3-12)cycloalkyl; phenyl; or heteroaryl; where the phenyl and heteroaryl groups are optionally mono- or independently plurisubstituted with R7; optionally, X together with an adjacent ring carbon and Z form a fused cyclopropyl; and optionally, one of the bonds in the ring containing X is a double bond; and CRiRii, R1, R2, R3, R4 and R5 are as described herein.

摘要翻译： 提供二肽基肽酶IV（DPP-IV）抑制化合物，其具有式I：其中n为1至3; X是CH 2 2; S; O; CF 2或C（CH 3）2）2。 Z是H; 卤素; 羟; （C 1-6）烷氧基; （C 1-12）烷基; （C 3-12）环烷基; 苯基; 或杂芳基; 其中苯基和杂芳基任选被R 7独立或独立地取代; 任选地，X与相邻的环碳一起形成稠合的环丙基; 并且任选地，含有X的环中的一个键是双键; 和R 1，R 2，R 2，R 3，R 3， R 4和R 5如本文所述。

公开(公告)号：US20070299036A1

公开(公告)日：2007-12-27

申请号：US11833063

申请日：2007-08-02

申请人： David Campbell ,  David Winn ,  Juan Betancort

发明人： David Campbell ,  David Winn ,  Juan Betancort

IPC分类号： A61K31/69 ,  A61P3/10 ,  C12N9/99

CPC分类号： C07F5/025

摘要： The present invention is directed to a method of treatment of a malcondition that can be regulated or normalized via inhibition of DPP-IV. The method involves administration of an effective amount of a pyrrolidine compound of the invention, such as would be present in a pharmaceutical composition of the invention, to mammals, especially humans, to affect a malcondition that can be regulated or normalized via inhibition of DPP-IV.

摘要翻译： 本发明涉及一种通过抑制DPP-IV来调节或归一化的病症的方法。 该方法包括将有效量的本发明的吡咯烷化合物（例如将存在于本发明的药物组合物中）施用于哺乳动物，特别是人，以影响可通过抑制DPP-1调节或归一化的病症， 四，

公开(公告)号：US20070060547A1

公开(公告)日：2007-03-15

申请号：US10514575

申请日：2004-11-12

申请人： David Campbell ,  David Winn ,  Juan Betancort

发明人： David Campbell ,  David Winn ,  Juan Betancort

IPC分类号： C07F5/02 ,  A61K31/69

CPC分类号： C07F5/025

摘要： Dipeptidyl peptidase IV (DPP-IV)-inhibiting compounds are provided that have formula I: wherein n is 1 to 3; X is CH2; S; O; CF2 or C(CH3)2; Z is H; halogen; hydroxyl; (C1-6)alkoxy; (C1-12)alkyl; (C3-12)cycloalkyl; phenyl; or heteroaryl; where the phenyl and heteroaryl groups are optionally mono- or independently plurisubstituted with R7; optionally, X together with an adjacent ring carbon and Z form a fused cyclopropyl; and optionally, one of the bonds in the ring containing X is a double bond; and CriRii, R1, R1, R3, R4 and R5 are as described herein. Methods for preparing these compounds, and methods for treating diabetes, especially Type II diabetes, and other related diseases are described using the compounds of formula I in pharmaceutical compositions which contain these compounds. Pharmaceutical compositions which contain combinations of these compounds with other antidiabetic agents are also described herein.

摘要翻译： 提供二肽基肽酶IV（DPP-IV）抑制化合物，其具有式I：其中n为1至3; X是CH 2 2; S; O; CF 2或C（CH 3）2）2。 Z是H; 卤素; 羟; （C 1-6）烷氧基; （C 1-12）烷基; （C 3-12）环烷基; 苯基; 或杂芳基; 其中苯基和杂芳基任选被R7单取代或独立地被二取代; 任选地，X与相邻的环碳一起形成稠合的环丙基; 并且任选地，含有X的环中的一个键是双键; 和R i，R i，R i，R i，R i，R i，R i， R 4和R 5如本文所述。 使用含有这些化合物的药物组合物中的式I化合物来描述制备这些化合物的方法，以及治疗糖尿病，特别是II型糖尿病和其它相关疾病的方法。 含有这些化合物与其它抗糖尿病药物的组合的药物组合物也在本文中描述。

公开(公告)号：US20060276410A1

公开(公告)日：2006-12-07

申请号：US11420273

申请日：2006-05-25

申请人： David Campbell ,  David Winn ,  Juan Betancort

发明人： David Campbell ,  David Winn ,  Juan Betancort

IPC分类号： A61K38/04 ,  C07F5/02 ,  A61K31/69

CPC分类号： C07F5/025

摘要： Compounds that selectively inhibit dipeptidyl peptidase-IV over closely related dipeptidyl peptidases are those of Formula (I): as well as pharmaceutically acceptable salts thereof, cyclic isomers thereof, prodrugs thereof, and solvates thereof, where all the variables are defined herein. These compounds can be used, alone or in combination with other drugs, for the treatment of diabetes and related diseases.

摘要翻译： 选择性抑制二肽基肽酶-IV超过密切相关的二肽基肽酶的化合物是式（I）的化合物：及其药学上可接受的盐，其环状异构体，其前药和溶剂合物，其中所有变量均在本文中定义。 这些化合物可以单独使用或与其他药物组合使用，用于治疗糖尿病和相关疾病。

公开(公告)号：US20060258621A1

公开(公告)日：2006-11-16

申请号：US11381082

申请日：2006-05-01

申请人： David Campbell ,  David Winn ,  Juan Betancort

发明人： David Campbell ,  David Winn ,  Juan Betancort

IPC分类号： A61K31/69 ,  C07F5/02

CPC分类号： C07F5/025

摘要： The present invention is directed to pyrrolidinylaminoacetyl pyrrolidine boronic acid compounds that display selective, potent dipeptidyl peptidase IV (DPP-IV) inhibitory activity. These compounds are useful for the treatment of disorders that can be regulated or normalized via inhibition of DPP-IV including those characterized by impaired glycemic control such as Diabetes Mellitus and related conditions. The compounds can be administered alone or with another medicament that displays pharmacological activity for treatment of these and other diseases.

摘要翻译： 本发明涉及显示选择性，有效的二肽基肽酶IV（DPP-IV）抑制活性的吡咯烷基氨基乙酰基吡咯烷硼酸化合物。 这些化合物可用于治疗可以通过抑制DPP-IV调节或归一化的疾病，包括以血糖控制受损为特征的糖尿病和相关病症。 化合物可以单独施用或与另外一种显示用于治疗这些和其它疾病的药理活性的药物一起施用。

公开(公告)号：US20060009518A1

公开(公告)日：2006-01-12

申请号：US11179797

申请日：2005-07-12

申请人： David Campbell ,  Juan Betancort ,  David Winn

发明人： David Campbell ,  Juan Betancort ,  David Winn

IPC分类号： A61K31/277

CPC分类号： C07D513/04

摘要： Certain constrained cyano compounds are useful as inhibitors of post-proline/alanine cleaving amino-dipeptidases. Accordingly, these compounds can be employed, alone or with another therapeutic agent, to treat diabetes (especially, Type II diabetes), hyperglycemia, Syndrome X, diabetic complications, hyperinsulinemia, obesity, atherosclerosis and related diseases, as well as various immunomodulatory diseases and chronic inflammatory bowel disease.

摘要翻译： 某些受限的氰基化合物可用作后脯氨酸/丙氨酸切割氨基二肽酶的抑制剂。 因此，这些化合物可以单独或与另一种治疗剂一起用于治疗糖尿病（特别是II型糖尿病），高血糖症，X综合征，糖尿病并发症，高胰岛素血症，肥胖症，动脉粥样硬化和相关疾病以及各种免疫调节性疾病，以及 慢性炎性肠病。

公开(公告)号：US20060264401A1

公开(公告)日：2006-11-23

申请号：US11381090

申请日：2006-05-01

申请人： David Campbell ,  David Winn ,  Juan Betancort

发明人： David Campbell ,  David Winn ,  Juan Betancort

IPC分类号： A61K31/69 ,  C07F5/02

CPC分类号： C07F5/025

摘要： The present invention is directed to pyrrolidinylaminoacetyl pyrrolidine boronic acid compounds that display selective, potent dipeptidyl peptidase IV inhibitory activity. These compounds are useful for the treatment of disorders that can be regulated or normalized via inhibition of DPP-IV including those characterized by impaired glycemic control such as Diabetes Mellitus and related conditions. The compounds can be administered alone or with another medicament that displays pharmacological activity for treatment of these and other diseases.

摘要翻译： 本发明涉及显示选择性，有效的二肽基肽酶IV抑制活性的吡咯烷基氨基乙酰基吡咯烷硼酸化合物。 这些化合物可用于治疗可以通过抑制DPP-IV调节或归一化的疾病，包括以血糖控制受损为特征的糖尿病和相关病症。 化合物可以单独施用或与另外一种显示用于治疗这些和其它疾病的药理活性的药物一起施用。

公开(公告)号：US20060264400A1

公开(公告)日：2006-11-23

申请号：US11381085

申请日：2006-05-01

申请人： David Campbell ,  David Winn ,  Juan Betancort

发明人： David Campbell ,  David Winn ,  Juan Betancort

IPC分类号： A61K31/69 ,  C07F5/02

CPC分类号： C07F5/025

摘要： The present invention is directed to pyrrolidinylaminoacetyl pyrrolidine boronic acid compounds that display selective, potent dipeptidyl peptidase IV inhibitory activity. These compounds are useful for the treatment of disorders that can be regulated or normalized via inhibition of DPP-IV including those characterized by impaired glycemic control such as Diabetes Mellitus and related conditions. The compounds can be administered alone or with another medicament that displays pharmacological activity for treatment of these and other diseases.

摘要翻译： 本发明涉及显示选择性，有效的二肽基肽酶IV抑制活性的吡咯烷基氨基乙酰基吡咯烷硼酸化合物。 这些化合物可用于治疗可以通过抑制DPP-IV调节或归一化的疾病，包括以血糖控制受损为特征的糖尿病和相关病症。 化合物可以单独施用或与另外一种显示用于治疗这些和其它疾病的药理活性的药物一起施用。

公开(公告)号：US07923433B2

公开(公告)日：2011-04-12

申请号：US10530646

申请日：2003-10-08

申请人： David Winn ,  David Alan Campbell

发明人： David Winn ,  David Alan Campbell

IPC分类号： A61K38/05

CPC分类号： C07D311/90 ,  C07D311/82 ,  C12Q1/37

摘要： The present invention provides compositions and methods for assessing profiles of catalytically active enzymes in compositions containing a plurality of proteins. In preferred embodiments, the enzyme is a hydrolase, most preferably a cysteine protease. The methods described herein use activity based probes (“ABPs”) that have an affinity moiety for directing the binding of the ABP to one or more catalytically active target enzymes, a reactive group for forming a covalent bond at an active site of the target enzyme(s), and a TAG (e.g., a detectable label, preferably a fluorophore). One or more ABPs may be combined with a protein-containing sample under conditions for binding and reaction of the ABP(s) with target enzyme(s) that are present in the sample. The resulting products may then be used to assess the active enzyme profile of the sample, and can be correlated to the presence, amount, or activity of one or more target enzyme(s) present in the original complex protein mixture.

摘要翻译： 本发明提供了用于在含有多种蛋白质的组合物中评估催化活性酶的谱的组合物和方法。 在优选的实施方案中，酶是水解酶，最优选半胱氨酸蛋白酶。 本文描述的方法使用具有亲和部分的活性基探针（“ABP”），该亲和部分用于引导ABP与一种或多种催化活性靶酶的结合，用于在靶酶的活性位点形成共价键的反应性基团 （例如，可检测标记，优选荧光团）。 可以在ABP与样品中存在的目标酶的结合和反应的条件下，将一种或多种ABP与含蛋白质的样品组合。 然后可以将所得产物用于评估样品的活性酶谱，并且可与存在于原始复合蛋白​​混合物中的一种或多种目标酶的存在，量或活性相关。

公开(公告)号：US20070141624A1

公开(公告)日：2007-06-21

申请号：US10530646

申请日：2003-10-08

申请人： David Winn

发明人： David Winn

IPC分类号： C40B30/06 ,  C40B40/04 ,  C12Q1/37 ,  C07D311/88

CPC分类号： C07D311/90 ,  C07D311/82 ,  C12Q1/37

摘要： The present invention provides compositions and methods for assessing profiles of catalytically active enzymes in compositions containing a plurality of proteins. In preferred embodiments, the enzyme is a hydrolase, most preferably a cysteine protease. The methods described herein use activity based probes (“ABPs”) that have an affinity moiety for directing the binding of the ABP to one or more catalytically active target enzymes, a reactive group for forming a covalent bond at an active site of the target enzyme(s), and a TAG (e.g., a detectable label, preferably a fluorophore). One or more ABPs may be combined with a protein-containing sample under conditions for binding and reaction of the ABP(s) with target enzyme(s) that are present in the sample. The resulting products may then be used to assess the active enzyme profile of the sample, and can be correlated to the presence, amount, or activity of one or more target enzyme(s) present in the original complex protein mixture.

摘要翻译： 本发明提供了用于在含有多种蛋白质的组合物中评估催化活性酶的谱的组合物和方法。 在优选的实施方案中，酶是水解酶，最优选半胱氨酸蛋白酶。 本文描述的方法使用具有亲和部分的活性基探针（“ABP”），该亲和部分用于引导ABP与一种或多种催化活性靶酶的结合，用于在靶酶的活性位点形成共价键的反应性基团 （例如，可检测标记，优选荧光团）。 可以在ABP与样品中存在的目标酶的结合和反应的条件下，将一种或多种ABP与含蛋白质的样品组合。 然后可以将所得产物用于评估样品的活性酶谱，并且可与存在于原始复合蛋白​​混合物中的一种或多种目标酶的存在，量或活性相关。