公开(公告)号：US06943171B2

公开(公告)日：2005-09-13

申请号：US10290011

申请日：2002-11-07

Applicant: Theodros Asberom ,  John W. Clader ,  Yueqing Hu ,  Dmitri A. Pissarnitski ,  Andrew W. Stamford ,  Ruo Xu

Inventor： Theodros Asberom ,  John W. Clader ,  Yueqing Hu ,  Dmitri A. Pissarnitski ,  Andrew W. Stamford ,  Ruo Xu

IPC: A61K31/519 ,  A61K31/55 ,  A61K31/551 ,  A61K45/00 ,  A61P1/00 ,  A61P3/10 ,  A61P9/00 ,  A61P9/04 ,  A61P9/12 ,  A61P11/00 ,  A61P13/00 ,  A61P13/02 ,  A61P13/12 ,  A61P15/00 ,  A61P15/10 ,  A61P27/06 ,  A61P35/00 ,  A61P37/02 ,  A61P43/00 ,  C07D487/14 ,  C07D487/20

CPC classification number: C07D487/14

Abstract: A compound having the formula (Ia) or (b), salt or solvate thereof, with the variables as defined herein, which can inhibit selectively phosphodiesterase V and can be useful for treating sexual dysfunction and other physiological disorders, symptoms and diseases:

公开(公告)号：US20110306593A1

公开(公告)日：2011-12-15

申请号：US13128316

申请日：2009-11-11

Applicant: Zhaoning Zhu ,  William J. Greenlee ,  Hongmei Li ,  Monica L. Vicarel ,  Jun Qin ,  Pawan Kumar Dhondi ,  Xianhai Huang ,  Anandan Palani ,  Xiaoxiang Liu ,  Zhong-Yue Sun ,  Hubert B. Josien ,  Ruo Xu ,  David James Cole ,  Duane A. Burnett ,  Chad E. Bennett ,  Troy McCracken ,  Malcolm MacCoss

Inventor： Zhaoning Zhu ,  William J. Greenlee ,  Hongmei Li ,  Monica L. Vicarel ,  Jun Qin ,  Pawan Kumar Dhondi ,  Xianhai Huang ,  Anandan Palani ,  Xiaoxiang Liu ,  Zhong-Yue Sun ,  Hubert B. Josien ,  Ruo Xu ,  David James Cole ,  Duane A. Burnett ,  Chad E. Bennett ,  Troy McCracken ,  Malcolm MacCoss

IPC: A61K31/553 ,  C07D498/10 ,  C07D498/04 ,  A61P25/28 ,  C07D413/14 ,  C07D498/14 ,  A61K31/5395 ,  C07D498/20 ,  C07D413/10

CPC classification number: C07D498/04 ,  C07D409/14 ,  C07D413/10 ,  C07D498/14 ,  C07D498/20

Abstract: In its many embodiments, the present invention provides a novel class of heterocyclic compounds of the formula: as modulators of gamma secretase, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more disease associated with the central nervous system using such compounds or pharmaceutical compostions.

Abstract translation: 在其许多实施方案中，本发明提供了一类新颖的下式杂环化合物：作为γ-分泌酶的调节剂，制备此类化合物的方法，含有一种或多种此类化合物的药物组合物，制备包含一种或多种这样的化合物的药物制剂的方法 化合物，以及使用这些化合物或药物组合物治疗，预防，抑制或改善与中枢神经系统相关的一种或多种疾病的方法。

公开(公告)号：US20110110948A1

公开(公告)日：2011-05-12

申请号：US12668550

申请日：2008-07-15

Applicant: Thavalakulamgara K. Sasikumar ,  Duane A. Burnett ,  Theodros Asberom ,  Wen-Lian Wu ,  Hongmei Li ,  Ruo Xu ,  Hubert B. Josien

Inventor： Thavalakulamgara K. Sasikumar ,  Duane A. Burnett ,  Theodros Asberom ,  Wen-Lian Wu ,  Hongmei Li ,  Ruo Xu ,  Hubert B. Josien

IPC: A61K39/395 ,  C07D513/04 ,  C07D493/04 ,  C07D491/052 ,  C07D491/147 ,  C07D513/14 ,  A61K31/542 ,  A61K31/352 ,  A61K31/407 ,  A61K31/436 ,  A61K31/4162 ,  A61K31/519 ,  A61K31/549 ,  A61P25/28 ,  A61P29/00 ,  A61P31/00

CPC classification number: C07D493/04 ,  C07D491/04 ,  C07D513/04 ,  C07D513/14

Abstract: Disclosed are novel gamma secretase inhibitors of the formula (I): or a pharmaceutically acceptable salt, solvate, or ester thereof, wherein L1, n, X, Ar, Y, Z, Q, and Q1 are as defined herein. Also disclosed are methods for inhibiting gamma secretase, methods for treating Alzheimer's disease, methods of treating one or more neurodegenerative diseases, and methods of inhibiting the deposition of amyloid protein (e.g., amyloid beta protein) in, on or around neurological tissue (e.g., the brain) using the compounds of formula 1.0.

Abstract translation: 公开了式（I）的新型γ-分泌酶抑制剂：或其药学上可接受的盐，溶剂化物或酯，其中L 1，n，X，Ar，Y，Z，Q和Q 1如本文所定义。 还公开了抑制γ分泌酶的方法，治疗阿尔茨海默氏病的方法，治疗一种或多种神经变性疾病的方法，以及抑制淀粉样蛋白（例如，淀粉样β蛋白）沉积在神经组织内或周围的方法（例如， 大脑）使用式1.0化合物。

公开(公告)号：US20100255005A1

公开(公告)日：2010-10-07

申请号：US12600910

申请日：2008-05-28

Applicant: Zhaoning Zhu ,  William J. Greenlee ,  Zhong-Yue Sun ,  Gioconda Gallo ,  Ruo Xu ,  Xianhai Huang ,  Xiaohong Zhu

Inventor： Zhaoning Zhu ,  William J. Greenlee ,  Zhong-Yue Sun ,  Gioconda Gallo ,  Ruo Xu ,  Xianhai Huang ,  Xiaohong Zhu

IPC: A61K39/395 ,  C07D498/04 ,  A61K31/437 ,  A61P25/28 ,  A61P29/00 ,  A61K39/00 ,  A61P27/06 ,  A61P9/10 ,  A61P27/00 ,  A61K31/5383 ,  C07D413/10 ,  A61K31/423 ,  A61K31/5025 ,  A61K31/4245 ,  A61K31/4439 ,  C07D498/14 ,  A61K31/445 ,  A61K31/473 ,  A61K38/17

CPC classification number: C07D498/04 ,  C07D413/10

Abstract: In its many embodiments, the present invention provides a novel class of heterocyclic compounds as modulators of gamma secretase, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the central nervous system using such compounds or pharmaceutical compositions.

公开(公告)号：US20100093695A1

公开(公告)日：2010-04-15

申请号：US12633311

申请日：2009-12-08

Applicant: Hubert B. Josien ,  John W. Clader ,  Thomas A. Bara ,  Ruo Xu ,  Hongmei Li ,  Dmitri A. Pissarnitski ,  Zhiqiang Zhao

Inventor： Hubert B. Josien ,  John W. Clader ,  Thomas A. Bara ,  Ruo Xu ,  Hongmei Li ,  Dmitri A. Pissarnitski ,  Zhiqiang Zhao

IPC: A61K31/438 ,  C07D413/14 ,  A61K31/5377 ,  C07D413/12 ,  C07D487/04 ,  A61K31/55 ,  A61K31/551

CPC classification number: C07D265/30 ,  C07D413/12 ,  C07D451/02 ,  C07D487/08

Abstract: This invention discloses novel gamma secretase inhibitors of the formula: wherein: L is —O—, —N(R6)—, —S—, —S(O)—, or —S(O2)—; R1 is selected from the group consisting of aryl and heteroaryl; R2 is selected from the group consisting of alkyl, —C(O)—Y, —X—C(O)—Y, -alkylene-X—C(O)—Y, -alkylene-C(O)—Y, -alkylene-cycloalkylene-X—C(O)—Y, -alkylene-cycloalkylene-C(O)—Y, -cycloalkylene-alkylene-X—C(O)—Y, -cycloalkylene-alkylene-C(O)—Y, -cycloalkylene-X—C(O)—Y, -cycloalkylene-C(O)—Y, -alkylene-cycloalkylene-alkylene-X—C(O)—Y, -alkylene-cycloalkylene-alkylene-C(O)—Y, aryl, and heteroaryl; R3 is selected from the group consisting of aryl, heteroaryl, alkyl, cycloalkyl, arylalkyl, arylcycloalkyl, heteroarylalkyl, heteroarylcycloalkyl, arylheterocycloalkyl, and alkoxyalkyl; each R4 and R5 is independently selected from the group consisting of H and alkyl; and Y is selected from the group consisting of —NR8R9, —N(R6)—(CH2)b—NR8R9, aryl, heteroaryl, alkyl, cycloalkyl, arylalkyl, arylcycloalkyl, heteroarylalkyl, heteroarylcycloalkyl, and arylheterocycloalkyl; or Y is selected from the group consisting of: One or more compounds of formula I, or formulations comprising such compounds, may be useful, e.g. in treating Alzheimer's Disease.

Abstract translation: 本发明公开了下式的新型γ-分泌酶抑制剂：其中：L是-O - ， - N（R6） - ， - S - ， - S（O） - 或-S（O 2） - ; R 1选自芳基和杂芳基; R 2选自烷基，-C（O）-Y，-X-C（O）-Y， - 亚烷基-X-C（O）-Y， - 亚烷基-C（O）-Y， - 亚烷基 - 亚环烷基-X-C（O）-Y-亚烷基 - 亚环烷基-C（O）-Y-亚烷基 - 亚烷基-X-C（O）-Y-亚烷基 - 亚烷基-C（O） （O）-Y-亚烷基-C（O）-Y-亚烷基 - 亚环烷基 - 亚烷基-X-C（O）-Y-亚烷基 - 亚环烷基 - 亚烷基-C（O ）-Y，芳基和杂芳基; R 3选自芳基，杂芳基，烷基，环烷基，芳基烷基，芳基环烷基，杂芳基烷基，杂芳基环烷基，芳基杂环烷基和烷氧基烷基; 每个R 4和R 5独立地选自H和烷基; 并且Y选自-NR 8 R 9，-N（R 6） - （CH 2）b -NR 8 R 9，芳基，杂芳基，烷基，环烷基，芳基烷基，芳基环烷基，杂芳基烷基，杂芳基环烷基和芳基杂环烷基。 或Y选自：一种或多种式I化合物或包含该化合物的制剂可用于，例如， 治疗阿尔茨海默病。