公开(公告)号：US20090118160A1

公开(公告)日：2009-05-07

申请号：US12349239

申请日：2009-01-06

申请人： Andrew Thomas Bach ,  Prasad Koteswara Kapa ,  George Tien-San Lee ,  Eric M. Loeser ,  Michael Lloyd Sabio ,  James Lawrence Stanton ,  Thalaththani Ralalage Vedananda

发明人： Andrew Thomas Bach ,  Prasad Koteswara Kapa ,  George Tien-San Lee ,  Eric M. Loeser ,  Michael Lloyd Sabio ,  James Lawrence Stanton ,  Thalaththani Ralalage Vedananda

IPC分类号： A61K38/28 ,  C07D209/04 ,  A61K31/404 ,  C07D413/02 ,  A61K31/422 ,  C07D205/04 ,  A61K31/397 ,  A61P9/04 ,  C07D403/02 ,  A61P9/00 ,  C07D401/02 ,  A61K31/4709 ,  A61P9/12 ,  A61K31/423 ,  A61P19/02 ,  A61K31/538 ,  C07D417/02 ,  A61K31/427 ,  C07D263/30 ,  A61P3/04 ,  A61P35/00 ,  A61P25/28 ,  A61P1/00 ,  A61P3/10 ,  A61P17/00 ,  A61P11/00 ,  A61P27/02

CPC分类号： C07D205/04 ,  C07D207/16 ,  C07D209/42 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D413/12 ,  C07D417/12

摘要： Compounds of the formula provide pharmacological agents which are potent agonists of Peroxisome Proliferator-Activated Receptors (PPARs). Accordingly, the compounds of the instant invention are useful for the treatment of conditions mediated by the PPAR receptor activity in mammals. Such conditions include dyslipidemia, hyperlipidemia, hypercholesteremia, atherosclerosis, hypertriglyceridemia, heart failure, myocardial infarction, vascular diseases, cardiovascular diseases, hypertension, obesity, inflammation, arthritis, cancer, Alzheimer's disease, skin disorders, respiratory diseases, ophthalmic disorders, inflammatory bowel diseases, ulcerative colitis and Crohn's disease. The compounds of the present invention are particularly useful in mammals as hypoglycemic agents for the treatment and prevention of conditions in which impaired glucose tolerance, hyperglycemia and insulin resistance are implicated, such as type-1 and type-2 diabetes, and Syndrome X. Preferred are the compounds of the invention which are dual agonists of PPARα and PPARγ receptors.

摘要翻译： 配方的化合物提供作为过氧化物酶体增殖物激活受体（PPARs）的有效激动剂的药理学试剂。 因此，本发明的化合物可用于治疗由哺乳动物中的PPAR受体活性介导的病症。 这些病症包括血脂异常，高脂血症，高胆固醇血症，动脉粥样硬化，高甘油三酯血症，心力衰竭，心肌梗死，血管疾病，心血管疾病，高血压，肥胖症，炎症，关节炎，癌症，阿尔茨海默病，皮肤病，呼吸系统疾病，眼科疾病，炎症性肠病 ，溃疡性结肠炎和克罗恩病。 本发明的化合物在哺乳动物中特别可用作降血糖药，用于治疗和预防葡萄糖耐量降低，高血糖症和胰岛素抵抗等疾病，如1型和2型糖尿病，以及X综合征。 是本发明的化合物，它们是PPARα和PPARγ受体的双重激动剂。

公开(公告)号：US20080221336A1

公开(公告)日：2008-09-11

申请号：US11995261

申请日：2006-07-12

申请人： Christine E. Garrett ,  Guang-Pei Chen ,  George Tien-San Lee ,  Xinglong Jiang ,  Michael J. Girgis ,  James Anthony Vivelo ,  Beata Sweryda-Krawiec ,  Dimitris Papoutsakis ,  Piotr Karpinski ,  Prasad Koteswara Kapa ,  Ada Skorodinsky

发明人： Christine E. Garrett ,  Guang-Pei Chen ,  George Tien-San Lee ,  Xinglong Jiang ,  Michael J. Girgis ,  James Anthony Vivelo ,  Beata Sweryda-Krawiec ,  Dimitris Papoutsakis ,  Piotr Karpinski ,  Prasad Koteswara Kapa ,  Ada Skorodinsky

IPC分类号： C07D263/32

CPC分类号： C07D413/12

摘要： This invention provides a method for preparing compounds having the structure [Formula (I)] wherein L is [Formula (A)] or [Formula (B)] in which R1 is hydrogen or optionally substituted alkyl, n is zero or 1 and m is 1; wherein R is H, halogen, optionally substituted C1-6alkyl or C1-6alkoxy; wherein Z is a bond, O or S; wherein p is an integer from 1 to 5; wherein Q is a bond provided that Z is not a bond when p is 1; or Q is O, S or —C(O)NR6— in which R6 is hydrogen, optionally substituted alkyl or cycloalkyl; or Q is —NR6—, —NR5C(O)NH— or —NR5C(O)O— in which R5 is hydrogen, alkyl or aralkyl provided that p is not 1; wherein W is cycloalkyl, aryl or heterocyclyl; or W and R6 form a 9- to 10-membered bicyclic ring, which may be optionally substituted or may contain oxygen, nitrogen or sulfur.

摘要翻译： 本发明提供了制备具有结构[式（I）]的化合物的方法，其中L是[式（A）]或[式（B）]，其中R 1是氢或任选取代的烷基 ，n为0或1，m为1; 其中R是H，卤素，任选取代的C 1-6烷基或C 1-6烷氧基; 其中Z是键，O或S; 其中p是1至5的整数; 其中Q是键，条件是当p是1时Z不是键; 或Q是O，S或-C（O）NR 6 - ，其中R 6是氢，任选取代的烷基或环烷基; 或Q是-NR 6 - ， - NR 5 C（O）NH-或-NR 5 C（O）O-，其中 R 5是氢，烷基或芳烷基，条件是p不是1; 其中W是环烷基，芳基或杂环基; 或W和R 6形成9至10元双环，其可任选被取代或可含有氧，氮或硫。

公开(公告)号：US20110251171A1

公开(公告)日：2011-10-13

申请号：US13166663

申请日：2011-06-22

申请人： Andrew Thomas Bach ,  Prasad Koteswara Kapa ,  George Tien-San Lee ,  Eric M. Loeser ,  Michael Lloyd Sabio ,  James Lawrence Stanton ,  Thalaththani Ralalage Vedananda

发明人： Andrew Thomas Bach ,  Prasad Koteswara Kapa ,  George Tien-San Lee ,  Eric M. Loeser ,  Michael Lloyd Sabio ,  James Lawrence Stanton ,  Thalaththani Ralalage Vedananda

IPC分类号： A61K31/397 ,  A61K31/5415 ,  A61K31/4725 ,  C07D417/12 ,  A61K31/422 ,  A61K31/404 ,  A61K31/427 ,  A61K31/40 ,  A61P3/10 ,  A61K31/538 ,  C07D401/12 ,  C07D411/12 ,  C07D413/12 ,  C07D209/30 ,  C07D207/48 ,  C07D205/04 ,  A61P9/12 ,  A61P9/00 ,  A61P11/00 ,  A61P27/02 ,  A61P25/28 ,  A61P1/00 ,  A61P17/00 ,  A61P3/06

CPC分类号： C07D205/04 ,  C07D207/16 ,  C07D209/42 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D413/12 ,  C07D417/12

摘要： Compounds of the formula provide pharmacological agents which are potent agonists of Peroxisome Proliferator-Activated Receptors (PPARs). Accordingly, the compounds of the instant invention are useful for the treatment of conditions mediated by the PPAR receptor activity in mammals. Such conditions include dyslipidemia, hyperlipidemia, hypercholesteremia, atherosclerosis, hypertriglyceridemia, heart failure, myocardial infarction, vascular diseases, cardiovascular diseases, hypertension, obesity, inflammation, arthritis, cancer, Alzheimer's disease, skin disorders, respiratory diseases, ophthalmic disorders, inflammatory bowel diseases, ulcerative colitis and Crohn's disease. The compounds of the present invention are particularly useful in mammals as hypoglycemic agents for the treatment and prevention of conditions in which impaired glucose tolerance, hyperglycemia and insulin resistance are implicated, such as type-1 and type-2 diabetes, and Syndrome X. Preferred are the compounds of the invention which are dual agonists of PPARα and PPARγ receptors.

摘要翻译： 配方的化合物提供作为过氧化物酶体增殖物激活受体（PPARs）的有效激动剂的药理学试剂。 因此，本发明的化合物可用于治疗由哺乳动物中的PPAR受体活性介导的病症。 这些病症包括血脂异常，高脂血症，高胆固醇血症，动脉粥样硬化，高甘油三酯血症，心力衰竭，心肌梗死，血管疾病，心血管疾病，高血压，肥胖症，炎症，关节炎，癌症，阿尔茨海默病，皮肤病，呼吸系统疾病，眼科疾病，炎症性肠病 ，溃疡性结肠炎和克罗恩病。 本发明的化合物在哺乳动物中特别可用作降血糖药，用于治疗和预防葡萄糖耐量降低，高血糖症和胰岛素抵抗等疾病，如1型和2型糖尿病，以及X综合征。 是PPARα和PPARγ受体的双重激动剂的本发明化合物。

公开(公告)号：US07183304B2

公开(公告)日：2007-02-27

申请号：US10495992

申请日：2002-11-20

申请人： Andrew Thomas Bach ,  Prasad Koteswara Kapa ,  George Tien-San Lee ,  Eric M. Loesser ,  Michael Lloyd Sabio ,  James Lawrence Stanton ,  Thalaththani Ralalage Vedananda

发明人： Andrew Thomas Bach ,  Prasad Koteswara Kapa ,  George Tien-San Lee ,  Eric M. Loesser ,  Michael Lloyd Sabio ,  James Lawrence Stanton ,  Thalaththani Ralalage Vedananda

IPC分类号： A61K31/422 ,  A61K31/405 ,  C07D263/32 ,  C07D209/30

CPC分类号： C07D205/04 ,  C07D207/16 ,  C07D209/42 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D413/12 ,  C07D417/12

摘要： Compounds of the formula provide pharmacological agents which are potent agonists of Peroxisome Proliferator-Activated Receptors (PPARs). Accordingly, the compounds of the instant invention are useful for the treatment of conditions mediated by the PPAR receptor activity in mammals. Such conditions include dyslipidemia, hyperlipidemia, hypercholesteremia, atherosclerosis, hypertriglyceridemia, heart failure, myocardial infarction, vascular diseases, cardiovascular diseases, hypertension, obesity, inflammation, arthritis, cancer, Alzheimer's disease, skin disorders, respiratory diseases, ophthalmic disorders, inflammatory bowel diseases, ulcerative colitis and Crohn's disease. The compounds of the present invention are particularly useful in mammals as hypoglycemic agents for the treatment and prevention of conditions in which impaired glucose tolerance, hyperglycemia and insulin resistance are implicated, such as type-1 and type-2 diabetes, and Syndrome X. Preferred are the compounds of the invention which are dual agonists of PPARα and PPARγ receptors.

摘要翻译： 配方的化合物提供作为过氧化物酶体增殖物激活受体（PPARs）的有效激动剂的药理学试剂。 因此，本发明的化合物可用于治疗由哺乳动物中的PPAR受体活性介导的病症。 这些病症包括血脂异常，高脂血症，高胆固醇血症，动脉粥样硬化，高甘油三酯血症，心力衰竭，心肌梗塞，血管疾病，心血管疾病，高血压，肥胖症，炎症，关节炎，癌症，阿尔茨海默病，皮肤病，呼吸系统疾病，眼科疾病，炎症性肠病 ，溃疡性结肠炎和克罗恩病。 本发明的化合物在哺乳动物中特别可用作降血糖药，用于治疗和预防葡萄糖耐量降低，高血糖症和胰岛素抵抗等疾病，如1型和2型糖尿病，以及X综合征。 是本发明的化合物，它们是PPARα和PPARγ受体的双重激动剂。

公开(公告)号：US07589216B2

公开(公告)日：2009-09-15

申请号：US10527628

申请日：2003-09-18

申请人： Prasad Koteswara Kapa ,  Xinglong Jiang ,  Eric M. Loeser ,  Joel Slade ,  Mahavir Prashad ,  George Tien-San Lee

发明人： Prasad Koteswara Kapa ,  Xinglong Jiang ,  Eric M. Loeser ,  Joel Slade ,  Mahavir Prashad ,  George Tien-San Lee

IPC分类号： C07D277/04 ,  C07D207/16

CPC分类号： C07D401/12 ,  C07C259/06 ,  C07D205/08 ,  C07D207/16 ,  Y02P20/55

摘要： The present invention is directed to a process for preparing intermediates that are useful to prepare certain antibacterial N-formyl hydroxylamine compounds which are peptide deformylase inhibitors. The process makes use α β-lactarn intermediate. Certain optically pure intermediates are also claimed.

摘要翻译： 本发明涉及一种制备中间体的方法，其可用于制备作为肽去甲酰化酶抑制剂的某些抗菌N-甲酰基羟胺化合物。 该过程使用αβ-内酰胺中间体。 还要求某些光学纯中间体。