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1. 发明申请

WO2011146618A1 INHIBITORS OF HUMAN 12-LIPOXYGENASE 审中-公开
标题翻译：人类12-LIPOXYGENASE的抑制剂
公开(公告)号：WO2011146618A1
公开(公告)日：2011-11-24
申请号：PCT/US2011/037000
申请日：2011-05-18
申请人： THE UNITED STATES OF AMERICA, as represented by the secretary, DEPARTMENT OF HEALTH AND HUMAN SERVICES , THE REGENTS OF THE UNIVERSITY OF CALIFORNIA , EASTERN VIRGINIA MEDICAL SCHOOL , THOMAS JEFFERSON UNIVERSITY , MALONEY, David J. , HOLMAN, Theodore , JADHAV, Ajit , SIMEONOV, Anton , BANTUKALLU, Ganesha Rai , NADLER, Jerry L. , HOLINSTAT, Michael
发明人： MALONEY, David J. , HOLMAN, Theodore , JADHAV, Ajit , SIMEONOV, Anton , BANTUKALLU, Ganesha Rai , NADLER, Jerry L. , HOLINSTAT, Michael
IPC分类号： C07D215/28 , C07D215/38 , C07D405/06 , C07D409/06 , A61K31/47 , A61K31/4709 , A61K31/496 , A61P3/10 , A61P9/00
CPC分类号： C07D409/04 , C07D215/28 , C07D215/38 , C07D405/06 , C07D409/06
摘要： Disclosed are inhibitors of human 12-lipoxygenase of Formula (I) or (II), wherein R 1 , R 2 , R 3 , and R 4 are as defined herein, that are useful in treating or preventing a 12-lipoxygenase mediated disease or disorder, e.g., diabetes. Also disclosed are a composition comprising a pharmaceutically acceptable carrier and at least one inhibitor of the invention, and a method of treating or preventing such disease or disorder in a mammal.
摘要翻译：公开了式（I）或（II）的人类12-脂肪氧合酶抑制剂，其中R1，R2，R3和R4如本文所定义，其可用于治疗或预防12-脂肪氧合酶介导的疾病或病症，糖尿病。还公开了包含药学上可接受的载体和本发明的至少一种抑制剂的组合物，以及治疗或预防哺乳动物中的这种疾病或病症的方法。

2. 发明申请

WO2011088322A1 TREATMENT OF DIABETES AND DISORDERS ASSOCIATED WITH VISCERAL OBESITY WITH INHIBITORS OF HUMAN ARACHIDONATE 12 LIPOXYGENASE AND ARACHIDONATE 15-LIPOXYGENASE 审中-公开
标题翻译：治疗与人类ARACHIDONATE抑制剂相关的糖尿病和糖尿病12 LIPOXYGENASE和ARACHIDONATE 15-LIPOXYGENASE
公开(公告)号：WO2011088322A1
公开(公告)日：2011-07-21
申请号：PCT/US2011/021300
申请日：2011-01-14
申请人： EASTERN VIRGINIA MEDICAL SCHOOL , NADLER, Jerry, L. , TAYLOR-FISHWICK, David , CHAKRABARTI, Swarup , DOBRIAN, Anca
发明人： NADLER, Jerry, L. , TAYLOR-FISHWICK, David , CHAKRABARTI, Swarup , DOBRIAN, Anca
IPC分类号： G01N33/53
CPC分类号： C12N15/1137 , C12Q1/025 , C12Q1/26 , G01N2333/90241 , G01N2800/042
摘要： A basis for understanding the arachidonate 12-lipoxygenase pathway, as well as and methods and kits for inhibiting the arachidonate 12-lipoxygenase pathway for the treatment, reversal, reduction, modulation or prevention of disease states and conditions related to type 1 or type 2 diabetes, are disclosed. Also disclosed are inflammatory forms of AL0X12 and 15, which are selectively expressed in omental adipose tissue of obese humans. Inhibitors of ALOX 12 and 15 can be used to treat, prevent, modulate or reduce complications associated with increased visceral obesity and inflammation, including type 2 diabetes. Also disclosed are methods for developing selective ALOX inhibitors for treating or reducing complications associated with increased visceral obesity and inflammation.
摘要翻译：了解花生四烯酸12脂氧合酶途径的基础，以及用于抑制花生四烯酸12-脂氧合酶途径用于治疗，逆转，减少，调节或预防与1型或2型糖尿病有关的疾病状态和病症的方法和试剂盒，被披露。还公开了AL0X12和15的炎性形式，其在肥胖人的网膜脂肪组织中选择性表达。 ALOX 12和15的抑制剂可用于治疗，预防，调节或减少与内脏肥胖和炎症（包括2型糖尿病）相关的并发症。还公开了用于开发用于治疗或减少与内脏肥胖和炎症增加相关的并发症的选择性ALOX抑制剂的方法。

3. 发明申请

WO2008011518A2 ENCAPSULATION SYSTEM 审中-公开
标题翻译：封装系统
公开(公告)号：WO2008011518A2
公开(公告)日：2008-01-24
申请号：PCT/US2007/073893
申请日：2007-07-19
申请人： DIAKINE THERAPEUTICS, INC. , NADLER, Jerry, L.
发明人： NADLER, Jerry, L.
IPC分类号： A61K35/39
CPC分类号： A61K35/39
摘要： An encapsulation system for use in the treatment of diabetes (Types 1 or 2, and LADA) are provided. The system has (1 ) a delivery vehicle comprising a selectively permeable membrane that allows passage of glucose, insulin and other nutrients through the membrane, but prevents large molecules such as antibodies or inflammatory cells from passing through the membrane; (2) a population of islet cells or insulin producing cells encapsulated by said membrane; and (3) a biological response modifier that may be in contact with the membrane or encapsulated by the membrane. Generally, the biological response modifier is a compound, including resolved enantiomers, diastereomers, tautomers, salts and solvates thereof, having the following formula: wherein: X, Y and Z are independently selected from a member of the group consisting of C(R 3 ), N, N(R 3 ) and S; R 1 is selected from a member of the group consisting of hydrogen, methyl, C (5-9) alkyl, C (5-9) alkenyl, C (5-9) alkynyl, C (5-9) hydroxyalkyl, C (3-8) alkoxyl, C (5-9) alkoxyalkyl, the R 1 being optionally substituted; R 2 and R 3 are independently selected from a member of the group consisting of hydrogen, halo, oxo, C (1-20) alkyl, C (1-20) hydroxyalkyl, C (1-20) thioalkyl, C (1-20) alkylamino, C (1-20) alkylaminoalkyl, C (1-20) aminoalkyl, C (1-20) aminoalkoxyalkenyl, C (1-20) aminoalkoxyalkynyl, C (1-20) diaminoalkyl, C (1-20) triaminoalkyl, C (1-20) tetraaminoalkyl, C (5-15) aminothalkoxyamino, C (1-20) alkylamido, C (1-20) alkylamidoalkyl, C (1-20) amidoalkyl, C (1-20) acetamidoalkyl, C (1-20) alkenyl, C (1-20) alkynyl, C (3-8) alkoxyl, C (1-11) alkoxyalkyl, and C (1-20) dialkoxyalkyl.
摘要翻译：提供了一种用于治疗糖尿病的包封系统（1型或2型和LADA型）。该系统具有（1）包含选择性渗透膜的输送载体，其允许葡萄糖，胰岛素和其它营养物通过膜，但是阻止大分子例如抗体或炎性细胞通过膜; （2）由所述膜包封的胰岛细胞群体或产生胰岛素的细胞群; 和（3）可以与膜接触或被膜包封的生物反应调节剂。通常，生物反应调节剂是具有下列结构式的拆分的对映异构体，非对映异构体，互变异构体，盐和溶剂化物的化合物：其中：X，Y和Z独立地选自C（R' 3，N，N（R 3）和S; R 1选自氢，甲基，C（5-9） - 烷基，C（5-9）烷氧基烷基，R 1'是任选被取代的; R 2和R 3独立地选自氢，卤代，氧代，C 1〜（1-20）烷基，，（1-20）羟基烷基，C 1-20（1-20）个硫代烷基，C（1-20） - 烷基氨基，C 1 -C 20 - （1-20）烷基氨基烷基，C（1-20）氨基烷基，C（1-20）氨基烷氧基烯基，C 1-20（1-20）（1-20）二氨基烷基，C 1-20（1-20）三氨基烷基，C（1-20）四氨基烷基，（5-15）氨基硫烷基氨基，C 1-20（1-20）烷基酰氨基，C（1-20） - 烷基酰氨基烷基，C 1 -C 20 - （1-20）酰氨基烷基，C 1-20（1-20），酰胺基烷基，C 1-20（1-20）烯基，C 1-20（1-20）（1-3）烷氧基，C（1-11）烷氧基烷基和C（1-20） - 炔基，二烷氧基。

4. 发明申请

WO2009099582A2 COMPOSITIONS AND METHODS FOR TREATING DIABETES USING LISOFYLLINE ANALOGS AND ISLET NEOGENESIS ASSOCIATED PEPTIDE 审中-公开
标题翻译：用类似的方法治疗糖尿病的组合物和方法和血小板生成相关肽
公开(公告)号：WO2009099582A2
公开(公告)日：2009-08-13
申请号：PCT/US2009/000664
申请日：2009-02-02
申请人： DIAKINE THERAPEUTICS, INC. , NADLER, Mary Ann, Latona , NADLER, Jerry, L.
发明人： NADLER, Mary Ann, Latona , NADLER, Jerry, L.
IPC分类号： A61K31/522
CPC分类号： A61K38/10 , A61K31/502 , A61K31/522 , A61K31/5377 , A61K31/695 , A61K38/1709 , A61K2300/00
摘要： Pharmaceutical compositions and methods are provided for treating diabetes and/or restoring β-cell mass and function in a mammal in need thereof. Type 1 diabetes mellitus (T1 DM) is an autoimmune disorder characterized by immune damage to pancreatic beta- cells. Lisofylline analogs (LSF analogs) are immunomodulators that reduce interlukin 12 signaling and reduce the onset of T1 DM in non-obese diabetic (NOD) mice. A combination therapy with both LSF analog (pretreatment) and INGAP provides protection from autoimmune destruction. The concomitant or combination of an LSF analog and INGAP after pre-treatment with an LSF analog is an effective therapy for a disease or condition resulting from the loss of pancreatic islet cells or insulin production in a mammal.
摘要翻译：提供药物组合物和方法用于治疗有需要的哺乳动物的糖尿病和/或恢复β细胞团块和功能。 1型糖尿病（T1DM）是以胰腺β细胞免疫损伤为特征的自身免疫性疾病。赖索丝线类似物（LSF类似物）是免疫调节剂，其减少非肥胖性糖尿病（NOD）小鼠中IL-12信号并减少T1DM的发生。使用LSF类似物（预处理）和INGAP的联合治疗可以防止自身免疫破坏。与LSF类似物预处理后的LSF类似物和INGAP的伴随或组合是由哺乳动物胰岛细胞或胰岛素产生丧失导致的疾病或病症的有效治疗方法。

5. 发明申请

WO2009097155A1 COMPOSITIONS AND METHODS FOR TREATING DIABETES USING LISOFYLLINE AND ISLET NEOGENESIS ASSOCIATED PEPTIDE 审中-公开
标题翻译：使用LISOFYLLINE和ISLET NEOGENESIS相关肽治疗糖尿病的组合物和方法
公开(公告)号：WO2009097155A1
公开(公告)日：2009-08-06
申请号：PCT/US2009/000661
申请日：2009-02-02
申请人： DIAKINE THERAPEUTICS, INC. , NADLER, Mary Ann, Latona , NADLER, Jerry, L.
发明人： NADLER, Mary Ann, Latona , NADLER, Jerry, L.
IPC分类号： A61K39/38
CPC分类号： A61K38/10 , A61K31/502 , A61K31/522 , A61K31/5377 , A61K31/695 , A61K38/1709 , A61K2300/00
摘要： Pharmaceutical compositions and methods are provided for treating diabetes and/or restoring β-cell mass and function in a mammal in need thereof. Type 1 diabetes mellitus (T1 DM) is an autoimmune disorder characterized by immune damage to pancreatic beta- cells. Lisofylline (LSF) is an immunomodulator that reduces cytokine signaling and reduces the onset of T1 DM in non-obese diabetic (NOD) mice. A combination therapy with both LSF (pretreatment) and INGAP provides protection from autoimmune destruction. The concomitant or combination of LSF and INGAP after pre-treatment with LSF is an effective therapy for a disease or condition resulting from the loss of pancreatic islet cells or insulin production in a mammal.
摘要翻译：提供药物组合物和方法用于治疗有需要的哺乳动物的糖尿病和/或恢复β细胞团块和功能。 1型糖尿病（T1DM）是一种以胰腺β细胞免疫损伤为特征的自身免疫性疾病。利福舍线（LSF）是一种免疫调节剂，可减少细胞因子信号并减少非肥胖型糖尿病（NOD）小鼠中T1DM的发生。与LSF（预处理）和INGAP的联合治疗可以保护免受自身免疫破坏。 LSF预处理后的LSF和INGAP的伴随或组合是对哺乳动物胰岛细胞或胰岛素产生丧失导致的疾病或病症的有效治疗方法。

6. 发明申请

WO2008108842A1 LISOFYLLINE ANALOGS AND METHODS FOR USE 审中-公开
标题翻译： LISOFYLLINE模拟和使用方法
公开(公告)号：WO2008108842A1
公开(公告)日：2008-09-12
申请号：PCT/US2007/062968
申请日：2007-02-28
申请人： UNIVERSITY OF VIRGINIA PATENT FOUNDATION , MACDONALD, Timothy, L. , NADLER, Jerry, L. , CUI, Peng
发明人： MACDONALD, Timothy, L. , NADLER, Jerry, L. , CUI, Peng
IPC分类号： C07D237/32 , A61K31/502
CPC分类号： C07D237/32
摘要： Analogs of a Lisofylline (LSF), and synthetic methods for the preparation of such analogs are provided. The analogs of LSF provided have the ability to protect cell viability, particularly the ability to protect pancreatic β-cells.
摘要翻译：提供了莱索菲线（LSF）的类似物，以及制备此类类似物的合成方法。所提供的LSF的类似物具有保护细胞活力的能力，特别是保护胰腺β细胞的能力。

7. 发明申请

WO2007027719A2 LISOFYLLINE ANALOGS AND METHODS FOR USE 审中-公开
标题翻译： LISOFYLLINE模拟和使用方法
公开(公告)号：WO2007027719A2
公开(公告)日：2007-03-08
申请号：PCT/US2006/033777
申请日：2006-08-29
申请人： UNIVERSITY OF VIRGINIA PATENT FOUNDATION , MACDONALD, Timothy, L. , NADLER, Jerry, L. , CUI, Peng
发明人： MACDONALD, Timothy, L. , NADLER, Jerry, L. , CUI, Peng
IPC分类号： C07D209/08 , C07D209/80 , C07D221/08 , C07D223/22
CPC分类号： A61K31/538 , A61K31/404 , A61K31/405 , A61K31/4196 , A61K31/495 , A61K31/502 , A61K31/53 , C07C215/68 , C07C219/32 , C07D209/08 , C07D209/80 , C07D221/08 , C07D223/22 , C07D241/08 , C07D241/18 , C07D249/12 , C07D253/04 , C07D265/26 , C07D265/36 , C07D265/38 , C07D275/04 , C07D279/22 , C07D487/04
摘要： The present invention provides analogs of a Lysofylline (LSF), and synthetic methods for the preparation of such analogs. The have the active side chain moiety (5-R-hydroxyhexyl) of LSF and can have greater potency and oral bioavailability than LSF.
摘要翻译：本发明提供了类似物溶血素（LSF）的类似物，以及制备这类类似物的合成方法。具有LSF的活性侧链部分（5-R-羟基己基），并且可以具有比LSF更大的效力和口服生物利用度。

8. 发明申请

WO1994005777A1 INHIBITION OF THE FORMATION OR ACTIVITY OF HUMAN LEUKOCYTE 12-LIPOXYGENASE PATHWAY 审中-公开
标题翻译：人类白细胞介素12-LIPOXYGENASE PATHWAY的形成或活性的抑制
公开(公告)号：WO1994005777A1
公开(公告)日：1994-03-17
申请号：PCT/US1993008106
申请日：1993-08-26
申请人： CITY OF HOPE , NADLER, Jerry, L. , NATARAJAN, Rama, Devi , GU, Jiali
发明人： CITY OF HOPE
IPC分类号： C12N09/02
CPC分类号： C12N9/0069 , A61K31/00 , A61K31/045 , A61K31/05 , A61K31/155 , A61K31/195 , A61K31/20 , A61K31/35 , A61K31/44 , A61K31/575 , A61K38/08 , C12Y113/11012 , C12Y113/11031 , G01N33/573
摘要： The discovery of a new form of 12-lipoxygenase RNA and protein in human adrenal, mononuclear, vascular smooth muscle and endothelial cells is disclosed. Activation of this 12-LO pathway mediates angiotensin II and glucose induced vascular and renal actions. A rationale for the development of pharmaceutical or molecular methods to inhibit this newly discovered lipoxygenase pathway is described.
摘要翻译：公开了在人肾上腺，单核，血管平滑肌和内皮细胞中发现新形式的12-脂氧合酶RNA和蛋白质。这种12-LO途径的激活介导血管紧张素II和葡萄糖诱导的血管和肾脏作用。描述了开发用于抑制这种新发现的脂氧合酶途径的药物或分子方法的理由。

9. 发明申请

WO2009099582A3 COMPOSITIONS AND METHODS FOR TREATING DIABETES USING LISOFYLLINE ANALOGS AND ISLET NEOGENESIS ASSOCIATED PEPTIDE 审中-公开
标题翻译：用类似的方法治疗糖尿病的组合物和方法和血小板生成相关肽
公开(公告)号：WO2009099582A3
公开(公告)日：2010-01-07
申请号：PCT/US2009000664
申请日：2009-02-02
申请人： DIAKINE THERAPEUTICS INC , NADLER MARY ANN LATONA , NADLER JERRY L
发明人： NADLER MARY ANN LATONA , NADLER JERRY L
IPC分类号： A61K38/00
CPC分类号： A61K38/10 , A61K31/502 , A61K31/522 , A61K31/5377 , A61K31/695 , A61K38/1709 , A61K2300/00
摘要： Pharmaceutical compositions and methods are provided for treating diabetes and/or restoring ß-cell mass and function in a mammal in need thereof. Type 1 diabetes mellitus (T1 DM) is an autoimmune disorder characterized by immune damage to pancreatic beta- cells. Lisofylline analogs (LSF analogs) are immunomodulators that reduce interlukin 12 signaling and reduce the onset of T1 DM in non-obese diabetic (NOD) mice. A combination therapy with both LSF analog (pretreatment) and INGAP provides protection from autoimmune destruction. The concomitant or combination of an LSF analog and INGAP after pre-treatment with an LSF analog is an effective therapy for a disease or condition resulting from the loss of pancreatic islet cells or insulin production in a mammal.
摘要翻译：提供药物组合物和方法用于治疗有需要的哺乳动物的糖尿病和/或恢复β细胞团块和功能。 1型糖尿病（T1DM）是以胰腺β细胞免疫损伤为特征的自身免疫性疾病。赖索丝线类似物（LSF类似物）是免疫调节剂，其减少非肥胖性糖尿病（NOD）小鼠中IL-12信号并减少T1DM的发生。使用LSF类似物（预处理）和INGAP的联合治疗可以防止自身免疫破坏。与LSF类似物预处理后的LSF类似物和INGAP的伴随或组合是由哺乳动物胰岛细胞或胰岛素产生丧失导致的疾病或病症的有效治疗方法。

10. 发明申请

WO2007027719A3 LISOFYLLINE ANALOGUES AND THEIR PHARMEACUETICAL USES 审中-公开
标题翻译： LISOFYLLINE类似物及其药理学用途
公开(公告)号：WO2007027719A3
公开(公告)日：2007-05-18
申请号：PCT/US2006033777
申请日：2006-08-29
申请人： UNIV VIRGINIA , MACDONALD TIMOTHY L , NADLER JERRY L , CUI PENG
发明人： MACDONALD TIMOTHY L , NADLER JERRY L , CUI PENG
IPC分类号： C07D209/08 , C07C215/16 , C07D209/80 , C07D221/08 , C07D223/22 , C07D241/08 , C07D241/18 , C07D249/12 , C07D253/04 , C07D265/26 , C07D265/36 , C07D265/38 , C07D275/04 , C07D279/22 , C07D487/04
CPC分类号： A61K31/538 , A61K31/404 , A61K31/405 , A61K31/4196 , A61K31/495 , A61K31/502 , A61K31/53 , C07C215/68 , C07C219/32 , C07D209/08 , C07D209/80 , C07D221/08 , C07D223/22 , C07D241/08 , C07D241/18 , C07D249/12 , C07D253/04 , C07D265/26 , C07D265/36 , C07D265/38 , C07D275/04 , C07D279/22 , C07D487/04
摘要： The present invention provides analogs of formula (I) of a Lysofylline (LSF), and synthetic methods for the preparation of such analogs. The have the active side chain moiety (5-R-hydroxyhexyl) of LSF and can have greater potency and oral bioavailability than LSF. The compounds (II) are used to treat diabetes, inflammatory and autoimmune conditions. wherein R 1 is hydrogen or a group having the formula -C(=O)R 3 , wherein R is lower alkyl, and R 2 is selected from the group consisting of.
摘要翻译：本发明提供了溶血素基（LSF）的式（I）的类似物，以及制备这类类似物的合成方法。具有LSF的活性侧链部分（5-R-羟基己基），并且可以具有比LSF更大的效力和口服生物利用度。化合物（II）用于治疗糖尿病，炎症和自身免疫病症。其中R 1是氢或具有式-C（= O）R 3的基团，其中R是低级烷基，R 2，选自由以下组成的组。

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