公开(公告)号：US07265128B2

公开(公告)日：2007-09-04

申请号：US10542214

申请日：2004-01-13

申请人： Wallace T. Ashton ,  Charles G. Caldwell ,  Robert J. Mathvink ,  Hyun O. Ok ,  Leah Bitalac Reigle ,  Ann E. Weber

发明人： Wallace T. Ashton ,  Charles G. Caldwell ,  Robert J. Mathvink ,  Hyun O. Ok ,  Leah Bitalac Reigle ,  Ann E. Weber

IPC分类号： A61K31/4365 ,  C07D513/04

CPC分类号： C07D498/04 ,  C07D471/04 ,  C07D495/04 ,  C07D513/04

摘要： The present invention is directed to 3-amino-4-phenylbutanoic acid derivatives of structural formula (I) which are inhibitors of the dipeptidyl peptidase-IV enzyme (“DP-IV inhibitors”) and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.

摘要翻译： 本发明涉及作为二肽基肽酶-IV酶（“DP-IV抑制剂”）的抑制剂的结构式（I）的3-氨基-4-苯基丁酸衍生物，其可用于治疗或预防疾病 其中涉及二肽基肽酶-IV酶，如糖尿病，特别是2型糖尿病。 本发明还涉及包含这些化合物的药物组合物以及这些化合物和组合物在预防或治疗涉及二肽基肽酶-IV酶的疾病中的用途。

公开(公告)号：US07388019B2

公开(公告)日：2008-06-17

申请号：US10542694

申请日：2004-01-27

申请人： Wallace T. Ashton ,  Charles G. Caldwell ,  Joseph L. Duffy ,  Robert J. Mathvink ,  Liping Wang ,  Ann E. Weber

发明人： Wallace T. Ashton ,  Charles G. Caldwell ,  Joseph L. Duffy ,  Robert J. Mathvink ,  Liping Wang ,  Ann E. Weber

IPC分类号： C07D471/04 ,  A61K31/4375 ,  A61P3/10 ,  C07D487/04 ,  A61K31/4985 ,  A61K31/5025 ,  A61K31/519 ,  A61K31/53

CPC分类号： C07D471/04 ,  C07D217/06 ,  C07D217/26

摘要： The present invention is directed to 3-amino-4-phenylbutanoic acid derivatives which are inhibitors of the dipeptidyl peptidase-IV enzyme (“DP-IV inhibitors”) and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.

摘要翻译： 本发明涉及作为二肽基肽酶-IV酶（“DP-IV抑制剂”）的抑制剂的3-氨基-4-苯基丁酸衍生物，其可用于治疗或预防其中二肽基肽酶 - 涉及IV酶，如糖尿病，特别是2型糖尿病。 本发明还涉及包含这些化合物的药物组合物以及这些化合物和组合物在预防或治疗涉及二肽基肽酶-IV酶的疾病中的用途。

公开(公告)号：US5451677A

公开(公告)日：1995-09-19

申请号：US168105

申请日：1993-12-15

申请人： Michael H. Fisher ,  Robert J. Mathvink ,  Hyun O. Ok ,  Emma R. Parmee ,  Ann E. Weber

发明人： Michael H. Fisher ,  Robert J. Mathvink ,  Hyun O. Ok ,  Emma R. Parmee ,  Ann E. Weber

IPC分类号： A61K31/18 ,  A61K31/335 ,  A61K31/34 ,  A61K31/343 ,  A61K31/38 ,  A61K31/381 ,  A61K31/40 ,  A61K31/403 ,  A61K31/415 ,  A61K31/42 ,  A61K31/423 ,  A61K31/425 ,  A61K31/428 ,  A61K31/433 ,  A61K31/44 ,  A61K31/4406 ,  A61K31/4433 ,  A61K31/47 ,  A61K31/496 ,  A61K31/505 ,  A61K31/63 ,  A61K31/635 ,  A61P3/04 ,  A61P3/08 ,  A61P3/10 ,  C07C311/02 ,  C07C311/10 ,  C07C311/13 ,  C07C311/14 ,  C07C311/21 ,  C07C311/29 ,  C07C311/44 ,  C07C311/46 ,  C07C311/47 ,  C07D209/02 ,  C07D209/08 ,  C07D209/12 ,  C07D209/34 ,  C07D213/65 ,  C07D213/71 ,  C07D213/73 ,  C07D213/75 ,  C07D215/36 ,  C07D233/54 ,  C07D239/34 ,  C07D261/20 ,  C07D277/64 ,  C07D277/74 ,  C07D285/10 ,  C07D285/14 ,  C07D307/78 ,  C07D307/79 ,  C07D307/82 ,  C07D311/08 ,  C07D317/62 ,  C07D319/18 ,  C07D333/34 ,  C07D333/54 ,  C07D333/62 ,  C07D401/12 ,  C07D405/12 ,  C07D409/04 ,  C07D409/12 ,  C07D413/12 ,  C07D417/12 ,  C07D455/00 ,  C07C311/01 ,  C07D307/10

CPC分类号： C07D213/73 ,  C07C311/13 ,  C07C311/14 ,  C07C311/21 ,  C07C311/29 ,  C07C311/44 ,  C07C311/46 ,  C07C311/47 ,  C07D209/08 ,  C07D209/12 ,  C07D209/34 ,  C07D213/65 ,  C07D213/71 ,  C07D215/36 ,  C07D261/20 ,  C07D277/74 ,  C07D285/14 ,  C07D307/79 ,  C07D307/82 ,  C07D311/08 ,  C07D317/62 ,  C07D319/18 ,  C07D333/34 ,  C07D333/54 ,  C07D333/62 ,  C07D401/12 ,  C07D405/12 ,  C07D409/04 ,  C07D409/12 ,  C07D413/12 ,  C07D417/12 ,  C07C2102/08 ,  C07C2102/10

摘要： Substituted phenylsulfonamides are selective .beta..sub.3 adrenergic receptor agonists with very little .beta..sub.1 and .beta..sub.2 adrenergic receptor activity and as such the compounds are capable of increasing lipolysis and energy expenditure in cells. The compounds thus have potent activity in the treatment of Type II diabetes and obesity. The compounds can also be used to lower triglyceride levels and cholesterol levels or raise high density lipoprotein levels or to decrease gut motility. In addition, the compounds can be used to reduced neurogenic inflammation or as antidepressant agents. The compounds are prepared by coupling an aminoalkylphenyl-sulfonamide with an appropriately substituted alkyl epoxide. Compositions and methods for the use of the compounds in the treatment of diabetes and obesity and for lowering triglyceride levels and cholesterol levels or raising high density lipoprotein levels or for increasing gut motility are also disclosed.

摘要翻译： 取代的苯基磺酰胺是具有非常少的β1和β2肾上腺素能受体活性的选择性β3肾上腺素能受体激动剂，因此化合物能够增加细胞中的脂肪分解和能量消耗。 因此，这些化合物在治疗II型糖尿病和肥胖中具有有效的活性。 该化合物也可用于降低甘油三酯水平和胆固醇水平或提高高密度脂蛋白水平或降低肠道运动性。 此外，该化合物可用于减少神经源性炎症或作为抗抑郁剂。 通过将氨基烷基苯基磺酰胺与适当取代的烷基环氧化物偶联制备化合物。 还公开了用于治疗糖尿病和肥胖以及降低甘油三酯水平和胆固醇水平或提高高密度脂蛋白水平或增加肠蠕动的组合物和方法。

公开(公告)号：US6011048A

公开(公告)日：2000-01-04

申请号：US7363

申请日：1998-01-15

申请人： Robert J. Mathvink ,  Emma R. Parmee ,  Samuel Tolman ,  Ann E. Weber

发明人： Robert J. Mathvink ,  Emma R. Parmee ,  Samuel Tolman ,  Ann E. Weber

IPC分类号： C07D20060101 ,  C07D417/12 ,  C07D417/14 ,  C07D417/10 ,  A61K31/44

CPC分类号： B05D1/305 ,  C07D417/12 ,  C07D417/14 ,  B05D3/044

摘要： Thiazole substituted benzenesulfonamides are .beta..sub.3 adrenergic receptor agonists with very little .beta..sub.1 and .beta..sub.2 adrenergic receptor activity and as such the compounds are capable of increasing lipolysis and energy expenditure in cells. The compounds thus have potent activity in the treatment of Type II diabetes and obesity. The compounds can also be used to lower triglyceride levels and cholesterol levels or raise high density lipoprotein levels or to decrease gut motility. In addition, the compounds can be used to reduced neurogenic inflammation or as antidepressant agents. The compounds are prepared by coupling an aminoalkylphenyl-sulfonamide with an appropriately substituted epoxide. Compositions and methods for the use of the compounds in the treatment of diabetes and obesity and for lowering triglyceride levels and cholesterol levels or raising high density lipoprotein levels or for decreasing gut motility are also disclosed.

摘要翻译： 噻唑取代的苯磺酰胺是具有非常少的β1和β2肾上腺素能受体活性的β3肾上腺素能受体激动剂，因此化合物能够增加细胞中的脂肪分解和能量消耗。 因此，这些化合物在治疗II型糖尿病和肥胖中具有有效的活性。 该化合物也可用于降低甘油三酯水平和胆固醇水平或提高高密度脂蛋白水平或降低肠道运动性。 此外，该化合物可用于减少神经源性炎症或作为抗抑郁剂。 通过将氨基烷基苯基磺酰胺与适当取代的环氧化物偶合来制备化合物。 还公开了使用该化合物治疗糖尿病和肥胖以及降低甘油三酯水平和胆固醇水平或提高高密度脂蛋白水平或降低肠蠕动的组合物和方法。

公开(公告)号：US07309714B2

公开(公告)日：2007-12-18

申请号：US10537476

申请日：2003-11-26

申请人： Joseph L. Duffy ,  Robert J. Mathvink ,  Ann E. Weber ,  Jinyou Xu

发明人： Joseph L. Duffy ,  Robert J. Mathvink ,  Ann E. Weber ,  Jinyou Xu

IPC分类号： A61K31/426 ,  A61K31/40 ,  A61K31/397 ,  A61K31/4453 ,  C07D277/04 ,  C07D207/08 ,  C07D205/04

CPC分类号： C07D295/185 ,  A61K31/40 ,  C07D207/10 ,  C07D207/16 ,  C07D277/04

摘要： The present invention is directed to phenylalanine derivatives which are inhibitors of the dipeptidyl peptidase-IV enzyme (“DP-IV inhibitors”) and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.

摘要翻译： 本发明涉及作为二肽基肽酶-IV酶（“DP-IV抑制剂”）的抑制剂的苯丙氨酸衍生物，其可用于治疗或预防涉及二肽基肽酶-IV酶的疾病，例如 糖尿病，特别是2型糖尿病。 本发明还涉及包含这些化合物的药物组合物以及这些化合物和组合物在预防或治疗涉及二肽基肽酶-IV酶的疾病中的用途。

公开(公告)号：US07157490B2

公开(公告)日：2007-01-02

申请号：US10481352

申请日：2003-11-03

申请人： Vincent J. Colandrea ,  Scott D. Edmondson ,  Robert J. Mathvink ,  Anthony Mastracchio ,  Ann E. Weber ,  Jinyou Xu

发明人： Vincent J. Colandrea ,  Scott D. Edmondson ,  Robert J. Mathvink ,  Anthony Mastracchio ,  Ann E. Weber ,  Jinyou Xu

IPC分类号： C07D277/04 ,  C07D207/04 ,  A61K31/40 ,  A61K31/426

CPC分类号： C07D205/04 ,  C07D207/10 ,  C07D211/38 ,  C07D213/64 ,  C07D295/185 ,  C07D401/10 ,  C07D401/12 ,  C07D403/06 ,  C07D403/10 ,  C07D403/12 ,  C07D413/10 ,  C07D413/12 ,  C07D417/10 ,  C07D471/04 ,  C07D487/04

摘要： The present invention is directed to phenylalanine derivatives which are inhibitors of the dipeptidyl peptidase-IV enzyme (“DP-IV inhibitors”) and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.

公开(公告)号：US07208498B2

公开(公告)日：2007-04-24

申请号：US10520839

申请日：2003-07-11

申请人： Robert J. Mathvink ,  Scott D. Edmondson ,  Ann E. Weber

发明人： Robert J. Mathvink ,  Scott D. Edmondson ,  Ann E. Weber

IPC分类号： C07D239/72 ,  A61K31/519 ,  A61P3/10 ,  A61P3/06 ,  A61P3/04 ,  A61P5/28 ,  A61P35/00

CPC分类号： C07D471/04

摘要： The present invention is directed to compounds which are inhibitors of the dipeptidyl peptidase-IV enzyme (“DP-IV inhibitors”) and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly Type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.

摘要翻译： 本发明涉及作为二肽基肽酶-IV酶（“DP-IV抑制剂”）抑制剂的化合物，其可用于治疗或预防涉及二肽基肽酶-IV酶的疾病，例如糖尿病 特别是2型糖尿病。 本发明还涉及包含这些化合物的药物组合物以及这些化合物和组合物在预防或治疗涉及二肽基肽酶-IV酶的疾病中的用途。