公开(公告)号：US20110275719A1

公开(公告)日：2011-11-10

申请号：US13145190

申请日：2010-01-29

Applicant: Matthew Daniels ,  Jed Hubbs ,  Thomas Miller

Inventor： Matthew Daniels ,  Jed Hubbs ,  Thomas Miller

IPC: A61K31/18 ,  A61P25/28 ,  C07C305/18

CPC classification number: C07D233/42 ,  C07C317/30 ,  C07C2601/14 ,  C07D295/185

Abstract: The present invention is directed to a novel trifluoromethylsulfonamide derivative which inhibits the processing of APP by the putative γ-secretase and thus is useful in the treatment or prevention of Alzheimer's disease. This compound possesses favorable pharmacokinetic properties in higher species (rhesus) and thus can be dosed on an intermittent dosing regiment (e.g., once weekly). When dosed on such a regiment the compound exhibits significant and continuous Aβ lowering without the manifestation of Notch associated gastrointestinal toxicity for extended periods, e.g., 7 days. Pharmaceutical compositions and methods of use are also included.

Abstract translation: 本发明涉及一种新的三氟甲基磺酰胺衍生物，其抑制通过推定的γ-分泌酶处理APP，因此可用于治疗或预防阿尔茨海默氏病。 该化合物在较高种类（恒河猴）中具有有利的药代动力学性质，因此可以间歇给药剂量（例如每周一次）给药。 当这样一个团体配合时，该化合物显示出显着和连续的A＆Bgr; 降低Notch相关胃肠道毒性长期持续的表现，例如7天。 还包括药物组合物和使用方法。

公开(公告)号：US20100010041A1

公开(公告)日：2010-01-14

申请号：US12439010

申请日：2007-08-31

Applicant: Matthew G. Stanton ,  Benito Munoz ,  David L. Sloman ,  Jed Hubbs ,  Christopher Hamblett

Inventor： Matthew G. Stanton ,  Benito Munoz ,  David L. Sloman ,  Jed Hubbs ,  Christopher Hamblett

IPC: A61K31/445 ,  C07D211/38

CPC classification number: C07D211/38

Abstract: Compounds of formula (I). Selectively inhibit production of Aβ(1-42) and hence find use in treatment of diseases associated with deposition of β-amyloid in the brain.

Abstract translation: 式（I）化合物。 选择性地抑制Abeta（1-42）的产生，因此可用于治疗与脑中沉淀β-淀粉样蛋白相关的疾病。

公开(公告)号：US20100093665A1

公开(公告)日：2010-04-15

申请号：US12520132

申请日：2007-12-14

Applicant: Benito Munoz ,  Jed Hubbs ,  Christopher L. Hamblett ,  Hua Zhou ,  Michelle Martinez

Inventor： Benito Munoz ,  Jed Hubbs ,  Christopher L. Hamblett ,  Hua Zhou ,  Michelle Martinez

IPC: A61K31/695 ,  C07F7/10

CPC classification number: C07F7/0812

Abstract: Compounds of formula I: I wherein at least one of R4 and R5 comprises Si(R6)3 as a substituent selectively attenuate production of Aβ(1-42) and hence find use in treatment of Alzheimer's disease and related conditions.

Abstract translation: 式I化合物其中R 4和R 5中的至少一个包含Si（R 6）3作为取代基选择性地减弱Aβ的产生（1-42），因此可用于治疗阿尔茨海默病和相关病症。

公开(公告)号：US08420622B2

公开(公告)日：2013-04-16

申请号：US12520132

申请日：2007-12-14

Applicant: Benito Munoz ,  Jed Hubbs ,  Christopher L. Hamblett ,  Hua Zhou ,  Michelle Martinez

Inventor： Benito Munoz ,  Jed Hubbs ,  Christopher L. Hamblett ,  Hua Zhou ,  Michelle Martinez

IPC: A61K31/445 ,  C07F7/10

CPC classification number: C07F7/0812

Abstract: Compounds of formula I: I wherein at least one of R4 and R5 comprises Si(R6)3 as a substituent selectively attenuate production of Aβ(1-42) and hence find use in treatment of Alzheimer's disease and related conditions.

Abstract translation: 式I化合物其中R 4和R 5中的至少一个包含Si（R 6）3作为取代基选择性地减弱Aβ的产生（1-42），因此可用于治疗阿尔茨海默病和相关病症。

公开(公告)号：US08609897B2

公开(公告)日：2013-12-17

申请号：US13145190

申请日：2010-01-29

Applicant: Matthew Daniels ,  Jed Hubbs ,  Thomas Miller

Inventor： Matthew Daniels ,  Jed Hubbs ,  Thomas Miller

IPC: C07C311/01 ,  A61K31/18

CPC classification number: C07D233/42 ,  C07C317/30 ,  C07C2601/14 ,  C07D295/185

Abstract: The present invention is directed to a novel trifluoromethylsulfonamide derivative which inhibits the processing of APP by the putative γ-secretase and thus is useful in the treatment or prevention of Alzheimer's disease. This compound possesses favorable pharmacokinetic properties in higher species (rhesus) and thus can be dosed on an intermittent dosing regiment (e.g., once weekly). When dosed on such a regiment the compound exhibits significant and continuous Aβ lowering without the manifestation of Notch associated gastrointestinal toxicity for extended periods, e.g., 7 days. Pharmaceutical compositions and methods of use are also included.

Abstract translation: 本发明涉及一种新的三氟甲基磺酰胺衍生物，其抑制由推定的γ-分泌酶处理APP，因此可用于治疗或预防阿尔茨海默氏病。 该化合物在较高种类（恒河猴）中具有有利的药代动力学性质，因此可以间歇给药剂量（例如每周一次）给药。 当给予这样一个团体时，该化合物显示出显着和连续的Abeta降低，而不延长Notch相关的胃肠道毒性的表现，例如7天。 还包括药物组合物和使用方法。