公开(公告)号：US20200270216A1

公开(公告)日：2020-08-27

申请号：US16647364

申请日：2018-09-14

Applicant: Tina BILOUSOVA ,  Barbara JAGODZINSKA ,  Varghese JOHN ,  The Regents of the University of California

Inventor： Tina Bilousova ,  Barbara Jagodzinska ,  Varghese John

IPC: C07D239/56 ,  C07D239/54 ,  C07D401/12 ,  C07D239/36 ,  C07D405/06 ,  A61P25/16 ,  A61P25/28

Abstract: Provided herein are compounds of Formula (I) and (II) and their salts, and compositions comprising such compounds that are useful for useful for modulating neutral sphingomyelinase 2 (n-SMase2) in cells. Also disclosed herein are methods of using the disclosed compounds and compositions for inhibiting the spread of Tau seeds from donor cells to recipient cells. Moreover, disclosed herein are methods of using the disclosed compounds and compositions for treating or preventing a neurodegenerative disorder, such as a tauopathy, Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Lewy body dementia, frontotemporal dementia, and amyotrophic lateral sclerosis (ALS).

公开(公告)号：US10449177B2

公开(公告)日：2019-10-22

申请号：US13213960

申请日：2011-08-19

Applicant: Varghese John ,  Dale E. Bredesen

Inventor： Varghese John ,  Dale E. Bredesen

IPC: A61K31/4035 ,  A61K31/05 ,  A61K31/145 ,  A61K31/5513

Abstract: The invention provides compositions and methods for the treatment of mild cognitive impairment (MCI), and for inhibiting, reducing, delaying and/or preventing the progression of MCI to Alzheimer's disease. The methods entail administering an effective amount of one or more compounds selected from the group consisting of tropisetron, disulfuram, honokiol and nimetazepam. The methods also are useful for prophylactic and therapeutic treatment of amyloidogenic diseases, including Alzheimer's disease.

公开(公告)号：US20120071468A1

公开(公告)日：2012-03-22

申请号：US13213960

申请日：2011-08-19

Applicant: Varghese John ,  Dale E. Bredesen

Inventor： Varghese John ,  Dale E. Bredesen

IPC: A61K31/5513 ,  A61K31/27 ,  A61P25/28 ,  C12N5/071 ,  A61P25/00 ,  A61K31/46 ,  A61K31/05

CPC classification number: A61K31/4035 ,  A61K31/05 ,  A61K31/145 ,  A61K31/5513

Abstract: The invention provides compositions and methods for the treatment of mild cognitive impairment (MCI), and for inhibiting, reducing, delaying and/or preventing the progression of MCI to Alzheimer's disease. The methods entail administering an effective amount of one or more compounds selected from the group consisting of tropisetron, disulfuram, honokiol and nimetazepam. The methods also are useful for prophylactic and therapeutic treatment of amyloidogenic diseases, including Alzheimer's disease.

Abstract translation: 本发明提供了用于治疗轻度认知障碍（MCI）以及用于抑制，减少，延迟和/或预防MCI进展为阿尔茨海默病的组合物和方法。 所述方法需要施用有效量的一种或多种选自托烷司琼，二硫酚，和厚朴酚和尼米西泮的化合物。 所述方法还可用于预防和治疗淀粉样变性疾病，包括阿尔茨海默氏病。

公开(公告)号：US20110281752A1

公开(公告)日：2011-11-17

申请号：US13070413

申请日：2011-03-23

Applicant: John P. Anderson ,  Guriqbal Basi ,  Minh Tam Doan ,  Normand Frigon ,  Varghese John ,  Michael Power ,  Sukanto Sinha ,  Gwen Tatsuno ,  Jay Tung ,  Shuwen Wang ,  Lisa McConlogue

Inventor： John P. Anderson ,  Guriqbal Basi ,  Minh Tam Doan ,  Normand Frigon ,  Varghese John ,  Michael Power ,  Sukanto Sinha ,  Gwen Tatsuno ,  Jay Tung ,  Shuwen Wang ,  Lisa McConlogue

IPC: C40B30/04 ,  C07K16/40 ,  C40B30/08 ,  C12N9/50 ,  G01N33/573

CPC classification number: C12N9/6478 ,  A01K2217/075 ,  A61K38/00 ,  H01Q1/364 ,  H01Q1/38 ,  H01Q3/44 ,  H01Q9/0407 ,  H01Q9/0442 ,  H01Q15/02

Abstract: Disclosed are various forms of an active, isolated β-secretase enzyme in purified and recombinant form. This enzyme is implicated in the production of amyloid plaque components which accumulate in the brains of individuals afflicted with Alzheimer's disease. Recombinant cells that produce this enzyme either alone or in combination with some of its natural substrates (β-APPwt and β-APPsw) are also disclosed, as are antibodies directed to such proteins. These compositions are useful for use in methods of selecting compounds that modulate β-secretase. Inhibitors of β-secretase are implicated as therapeutics in the treatment of neurodegenerative diseases, such as Alzheimer's disease.

Abstract translation: 公开了各种形式的纯化和重组形式的活性，分离和分泌的酶。 这种酶涉及积聚在患有阿尔茨海默病的个体的脑中的淀粉样蛋白斑块成分的产生。 产生该酶单独或与其一些天然底物（＆bgr; -APPwt和＆bgr-APPsw）组合的重组细胞也被公开，以及针对这种蛋白质的抗体。 这些组合物可用于选择调节和分泌酶的化合物的方法。 抑制剂与分泌酶作为治疗神经变性疾病如阿尔茨海默氏病的治疗剂有牵连作用。

公开(公告)号：US20100099609A1

公开(公告)日：2010-04-22

申请号：US12510831

申请日：2009-07-28

Applicant: VARGHESE JOHN ,  CLARE PETERS-LIBEU ,  DALE E. BREDESEN

Inventor： VARGHESE JOHN ,  CLARE PETERS-LIBEU ,  DALE E. BREDESEN

IPC: A61K38/16 ,  A61K38/10 ,  A61P25/28

CPC classification number: A61K38/1716 ,  A61K47/58 ,  A61K47/59 ,  A61K47/60 ,  A61K47/61

Abstract: This invention provides methods of reducing levels of amyloid beta (Aβ) protein and/or netrin-1 in a mammal. In certain embodiments the methods involve administering to the mammal a fragment of an amyloid precursor protein, or a mutant amyloid precursor protein, in an amount sufficient to decrease circulating levels of free Aβ protein in said mammal, wherein said fragment is a fragment of the extracellular domain of APP or a mutant thereof that binds amyloid beta protein and/or netrin-1.

Abstract translation: 本发明提供降低哺乳动物中淀粉样蛋白β（A＆bgr））蛋白和/或netrin-1水平的方法。 在某些实施方案中，所述方法包括给予哺乳动物淀粉样蛋白前体蛋白片段或突变型淀粉样蛋白前体蛋白，其量足以降低游离A和Bgr的循环水平; 蛋白质，其中所述片段是APP的细胞外结构域的片段或其结合淀粉样蛋白β蛋白和/或netrin-1的突变体。

公开(公告)号：US07459476B2

公开(公告)日：2008-12-02

申请号：US10519793

申请日：2003-06-27

Applicant: Varghese John

Inventor： Varghese John

IPC: A61K31/4172

CPC classification number: A61K31/4172 ,  A61K31/4174

Abstract: Disclosed are methods for treating Alzheimer's disease, and other diseases, and/or inhibiting beta-secretase enzyme, and/or inhibiting deposition of A beta peptide in a mammal, by use of compounds of formula (I) wherein X, R1, and R2 are defined herein.

Abstract translation: 公开了通过使用其中X，R 1和R 2的式（I）化合物治疗阿尔茨海默病和/或抑制β-分泌酶，和/或抑制Aβ肽在哺乳动物中的沉积的方法 在本文中定义。

公开(公告)号：US07456007B1

公开(公告)日：2008-11-25

申请号：US09471669

申请日：1999-12-24

Applicant: John P. Anderson ,  Guriqbal Basi ,  Minh Tam Doan ,  Normand Frigon ,  Varghese John ,  Michael Power ,  Sukanto Sinha ,  Gwen Tatsuno ,  Jay Tung ,  Shuwen Wang ,  Lisa McConlogue

Inventor： John P. Anderson ,  Guriqbal Basi ,  Minh Tam Doan ,  Normand Frigon ,  Varghese John ,  Michael Power ,  Sukanto Sinha ,  Gwen Tatsuno ,  Jay Tung ,  Shuwen Wang ,  Lisa McConlogue

IPC: C12N9/64 ,  C12N15/00 ,  C12N5/00 ,  C12P21/06 ,  C12Q1/68

CPC classification number: C12N9/6421 ,  C07K14/8142 ,  C12Q1/6883 ,  C12Y304/23046

Abstract: Disclosed is an active, isolated β-secretase enzyme in purified and recombinant form. This enzyme is implicated in the production of amyloid plaque components which accumulate in the brains of individuals afflicted with Alzheimer's disease. Recombinant cells that produce this enzyme either alone or in combination with some of its natural substrates (APP and APPsw) are also disclosed. These compositions are useful for use in methods of selecting compounds that modulate β-secretase. Inhibitors of β-secretase are implicated as therapeutics in the treatment of neurodegenerative diseases, such as Alzheimer's disease.

Abstract translation: 公开了纯化和重组形式的活性，分离的β-分泌酶。 这种酶涉及积聚在患有阿尔茨海默病的个体的脑中的淀粉样蛋白斑块成分的产生。 也公开了单独或与其一些天然底物（APP和APPsw）组合产生该酶的重组细胞。 这些组合物可用于选择调节β-分泌酶的化合物的方法。 β-分泌酶的抑制剂涉及作为治疗神经变性疾病如阿尔茨海默病的治疗剂。

公开(公告)号：US07432389B2

公开(公告)日：2008-10-07

申请号：US11370073

申请日：2006-03-07

Applicant: Lawrence Fang ,  Varghese John

Inventor： Lawrence Fang ,  Varghese John

IPC: C07C261/00

CPC classification number: C07D295/13 ,  C07C215/28 ,  C07C233/78 ,  C07C235/84 ,  C07C239/20 ,  C07C243/22 ,  C07C243/28 ,  C07C271/16 ,  C07C271/18 ,  C07C275/24 ,  C07C311/03 ,  C07C311/05 ,  C07C311/08 ,  C07C311/13 ,  C07C311/16 ,  C07C311/37 ,  C07C317/44 ,  C07C323/60 ,  C07D211/60 ,  C07D215/12 ,  C07D277/04 ,  C07D303/36 ,  C07D307/52 ,  C07D307/54 ,  C07D333/24

Abstract: The present invention is substituted amine s of formula (XV) useful in treating Alzheimer's ease and other similar disease.

Abstract translation: 本发明是用于治疗阿尔茨海默病易感性和其它类似疾病的式（ⅩⅤ）的取代胺。

公开(公告)号：US20070293483A1

公开(公告)日：2007-12-20

申请号：US11447789

申请日：2006-06-06

Applicant: Varghese John ,  Michel Maillard ,  James Beck ,  Eric Baldwin ,  Robert Hughes ,  Shon Pulley ,  Ruth TenBrink

Inventor： Varghese John ,  Michel Maillard ,  James Beck ,  Eric Baldwin ,  Robert Hughes ,  Shon Pulley ,  Ruth TenBrink

IPC: A61K31/54 ,  A61P25/28 ,  C07D279/04

CPC classification number: C07C233/36 ,  C07C235/10 ,  C07C235/74 ,  C07C271/24 ,  C07C311/05 ,  C07C327/30 ,  C07C2601/02 ,  C07C2601/08 ,  C07C2601/14 ,  C07C2602/10 ,  C07D209/14 ,  C07D213/38 ,  C07D213/64 ,  C07D215/233 ,  C07D215/38 ,  C07D215/42 ,  C07D215/46 ,  C07D217/22 ,  C07D233/61 ,  C07D233/64 ,  C07D237/08 ,  C07D237/14 ,  C07D239/26 ,  C07D239/38 ,  C07D241/12 ,  C07D249/08 ,  C07D261/08 ,  C07D265/02 ,  C07D277/28 ,  C07D295/135 ,  C07D307/52 ,  C07D309/14 ,  C07D311/68 ,  C07D311/74 ,  C07D333/20 ,  C07D333/22 ,  C07D335/06 ,  C07D405/04 ,  C07D407/06 ,  C07D409/12 ,  C07D495/04

Abstract: Disclosed are compounds of the formula: where variables Z, X, R15, R2, R3, and Rc are defined herein. Compounds disclosed herein are inhibitors of the beta-secretase enzyme and are therefore useful in the treatment of Alzheimer's disease and other diseases characterized by deposition of A beta peptide in a mammal.

Abstract translation: 公开了下式的化合物：其中变量Z，X，R 15，R 2，R 3和R c， / SUB>。 本文公开的化合物是β-分泌酶的抑制剂，因此可用于治疗阿尔茨海默氏病和以哺乳动物中Aβ肽沉积为特征的其它疾病。

公开(公告)号：US07276484B2

公开(公告)日：2007-10-02

申请号：US11075232

申请日：2005-03-08

Applicant: Varghese John ,  Jay Tung ,  Roy Hom ,  Ashley Guinn ,  Lawrence Fang ,  Andrea Gailunas ,  Shumeye S. Mamo

Inventor： Varghese John ,  Jay Tung ,  Roy Hom ,  Ashley Guinn ,  Lawrence Fang ,  Andrea Gailunas ,  Shumeye S. Mamo

IPC: C07K5/06

CPC classification number: C07K5/101 ,  C07K5/0205

Abstract: Dipeptide derived inhibitors of the β-secretase enzyme are provided which are useful in the treatment of Alzheimer's disease and other diseases characterized by deposition of Aβ peptide in a mammal. The compounds of the invention provide useful methods of treatment by administration of these inhibitors to reduce Aβ peptide formation and in pharmaceutical compositions.

Abstract translation: 提供了二肽衍生的β-分泌酶的抑制剂，其可用于治疗阿尔茨海默病和以哺乳动物中Abeta肽沉积为特征的其它疾病。 本发明的化合物提供了通过施用这些抑制剂以减少Aβ肽形成和药物组合物治疗的有用方法。