公开(公告)号：US20080200445A1

公开(公告)日：2008-08-21

申请号：US11710582

申请日：2007-02-23

申请人： Zhaoning Zhu ,  Brian McKittrick ,  Zhong-Yue Sun ,  Yuanzan Ye ,  Johannes Voigt ,  Corey Strickland ,  Elizabeth Smith ,  Andrew Stamford ,  William Greenlee ,  Robert Mazzola ,  John Caldwell ,  Jared Cumming ,  Lingyan Wang ,  Yusheng Wu ,  Ulrich Iserloh ,  Xiaoxiang Liu ,  Tao Guo ,  Thuy Le ,  Kurt Saionz ,  Suresh Babu ,  Rachael Hunter ,  Michelle Morris ,  Huizhong Gu ,  Gang Qian ,  Dawit Tadesse ,  Ying Huang ,  Guoqing Li ,  Jianping Pan ,  Jeffrey Misiaszek ,  Gaifa Lai ,  Jingqi Duo ,  Chuanxing Qu ,  Yuefei Shao

发明人： Zhaoning Zhu ,  Brian McKittrick ,  Zhong-Yue Sun ,  Yuanzan Ye ,  Johannes Voigt ,  Corey Strickland ,  Elizabeth Smith ,  Andrew Stamford ,  William Greenlee ,  Robert Mazzola ,  John Caldwell ,  Jared Cumming ,  Lingyan Wang ,  Yusheng Wu ,  Ulrich Iserloh ,  Xiaoxiang Liu ,  Tao Guo ,  Thuy Le ,  Kurt Saionz ,  Suresh Babu ,  Rachael Hunter ,  Michelle Morris ,  Huizhong Gu ,  Gang Qian ,  Dawit Tadesse ,  Ying Huang ,  Guoqing Li ,  Jianping Pan ,  Jeffrey Misiaszek ,  Gaifa Lai ,  Jingqi Duo ,  Chuanxing Qu ,  Yuefei Shao

IPC分类号： A61K31/506 ,  A61K31/4178 ,  A61K31/4245 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/541 ,  A61P31/00 ,  C07D233/02 ,  C07D271/00 ,  C07D413/14 ,  C07D409/14 ,  C07D409/04 ,  C07D403/06 ,  C07D401/14 ,  C07D401/12 ,  C07D401/10 ,  C07D401/06 ,  C07D239/04 ,  A61P9/00 ,  A61P25/00 ,  A61K31/5377 ,  A61K31/4545 ,  A61K31/4709 ,  A61K31/498

CPC分类号： C07D233/88 ,  A61K31/4168 ,  A61K31/4178 ,  C07D239/22 ,  C07D401/06 ,  C07D401/10 ,  C07D403/06 ,  C07D409/04 ,  C07D409/14 ,  C07D413/04 ,  C07D417/10 ,  C07D417/14 ,  C07D495/10

摘要： Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein W is a bond, —C(═S)—, —S(O)—, —S(O)2—, —C(═O)—, —O—, —C(R6)(R7)—, —N(R5)— or —C(═N(R5))—; X is —O—, —N(R5)— or —C(R6)(R7)—; provided that when X is —O—, U is not —O—, —S(O)—, —S(O)2—, —C(═O)— or —C(═NR5)—; U is a bond, —S(O)—, —S(O)2—, —C(O)—, —O—, —P(O)(OR15)—, —C(═NR5)—, —(C(R6)(R7))b— or —N(R5)—; wherein b is 1 or 2; provided that when W is —S(O)—, —S(O)2—, —O—, or —N(R5)—, U is not —S(O)—, —S(O)2—, —O—, or —N(R5)—; provided that when X is —N(R5)— and W is —S(O)—, —S(O)2—, —O—, or —N(R5)—, then U is not a bond; and R1, R2, R3, R4, R5, R6, and R7 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula 1. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of Human Immunodeficiency Virus, plasmepins, cathepsin D and protozoal enzymes. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic m1 agonist or m2 antagonist.

公开(公告)号：US20070072852A1

公开(公告)日：2007-03-29

申请号：US11010772

申请日：2004-12-13

申请人： Zhaoning Zhu ,  Brian McKittrick ,  Zhong-Yue Sun ,  Yuanzan Ye ,  Johannes Voigt ,  Corey Strickland ,  Elizabeth Smith ,  Andrew Stamford ,  William Greenlee ,  Robert Mazzola ,  John Caldwell ,  Jared Cumming ,  Lingyan Wang ,  Yusheng Wu ,  Ulrich Iserloh ,  Tao Guo ,  Thuy Le ,  Kurt Saionz ,  Suresh Babu ,  Rachael Hunter

发明人： Zhaoning Zhu ,  Brian McKittrick ,  Zhong-Yue Sun ,  Yuanzan Ye ,  Johannes Voigt ,  Corey Strickland ,  Elizabeth Smith ,  Andrew Stamford ,  William Greenlee ,  Robert Mazzola ,  John Caldwell ,  Jared Cumming ,  Lingyan Wang ,  Yusheng Wu ,  Ulrich Iserloh ,  Tao Guo ,  Thuy Le ,  Kurt Saionz ,  Suresh Babu ,  Rachael Hunter

IPC分类号： A61K31/549 ,  A61K31/5395 ,  A61K31/513

CPC分类号： C07D233/88 ,  A61K31/4168 ,  A61K31/4178 ,  A61K31/4184 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/4725 ,  A61K31/5377 ,  A61K31/655 ,  A61K45/06 ,  C07D233/46 ,  C07D233/70 ,  C07D235/02 ,  C07D239/22 ,  C07D239/70 ,  C07D271/07 ,  C07D273/00 ,  C07D295/15 ,  C07D401/04 ,  C07D401/06 ,  C07D401/08 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/06 ,  C07D403/08 ,  C07D403/10 ,  C07D403/12 ,  C07D405/06 ,  C07D405/10 ,  C07D405/14 ,  C07D407/06 ,  C07D409/04 ,  C07D409/06 ,  C07D409/10 ,  C07D409/14 ,  C07D413/10 ,  C07D413/12 ,  C07D417/06 ,  Y02A50/411

摘要： Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein W is a bond, —C(═S)—, —S(O)—, —S(O)2—, —C(═O)—, —O—, —C(R6)(R7)—, —N(R5)— or —C(═N(R5))—; X is —O—, —N(R5)— or —C(R6)(R7)—; provided that when X is —O—, U is not —O—, —S(O)—, —S(O)2—, —C(═O)— or —C(═NR5)—; U is a bond, —S(O)—, —S(O)2—, —C(O)—, —O—, —P(O)(OR15)—, —C(═NR5)—, —(C(R6)(R7))b— or —N(R5)—; wherein b is 1 or 2; provided that when W is —S(O)—, —S(O)2—, —O—, or —N(R5)—, U is not —S(O)—, —S(O)2—, —O—, or —N(R5)—; provided that when X is —N(R5)— and W is —S(O)—, —S(O)2—, —O—, or —N(R5)—, then U is not a bond; and R1, R2, R3, R4, R5, R6, and R7 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of Human Immunodeficiency Virus, plasmepins, cathepsin D and protozoal enzymes. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic antagonist.

公开(公告)号：US20060111370A1

公开(公告)日：2006-05-25

申请号：US11149027

申请日：2005-06-09

申请人： Zhaoning Zhu ,  Brian McKittrick ,  Zhong-Yue Sun ,  Yuanzan Ye ,  Johannes Voigt ,  Corey Strickland ,  Elizabeth Smith ,  Andrew Stamford ,  William Greenlee ,  Robert Mazzola ,  John Caldwell ,  Jared Cumming ,  Lingyan Wang ,  Yusheng Wu ,  Ulrich Iserloh ,  Tao Guo ,  Thuy Le ,  Kurt Saionz ,  Suresh Babu ,  Rachael Hunter ,  Michelle Morris ,  Huizhong Gu ,  Gang Qian ,  Dawit Tadesse

发明人： Zhaoning Zhu ,  Brian McKittrick ,  Zhong-Yue Sun ,  Yuanzan Ye ,  Johannes Voigt ,  Corey Strickland ,  Elizabeth Smith ,  Andrew Stamford ,  William Greenlee ,  Robert Mazzola ,  John Caldwell ,  Jared Cumming ,  Lingyan Wang ,  Yusheng Wu ,  Ulrich Iserloh ,  Tao Guo ,  Thuy Le ,  Kurt Saionz ,  Suresh Babu ,  Rachael Hunter ,  Michelle Morris ,  Huizhong Gu ,  Gang Qian ,  Dawit Tadesse

IPC分类号： A61K31/519 ,  A61K31/497 ,  A61K31/513 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/4245 ,  C07D413/02 ,  C07D403/02

CPC分类号： C07D233/46 ,  C07D233/70 ,  C07D233/88 ,  C07D239/22 ,  C07D239/70 ,  C07D271/07 ,  C07D273/00 ,  C07D401/04 ,  C07D401/08 ,  C07D401/10 ,  C07D401/12 ,  C07D403/04 ,  C07D403/06 ,  C07D403/08 ,  C07D403/10 ,  C07D403/12 ,  C07D405/10 ,  C07D409/04 ,  C07D409/10 ,  C07D409/14 ,  C07D413/10 ,  C07D413/12 ,  C07D417/06

摘要： Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein W is a bond, —C(═S)—, —S(O)—, —S(O)2—, —C(═O)—, —O—, —C(R6)(R7)—, —N(R5)— or —C(═N(R5))—; X is —O—, —N(R5)— or —C(R6)(R7)—; provided that when X is —O—, U is not —O—, —S(O)—, —S(O)2—, —C(═O)— or —C(═NR5)—; U is a bond, —S(O)—, —S(O)2—, —C(O)—, —O—, —P(O)(OR15)—, —C(═NR5)—, —(C(R6)(R7))b— or —N(R5)—; wherein b is 1 or 2; provided that when W is —S(O)—, —S(O)2—, —O—, or —N(R5)—, U is not —S(O)—, —S(O)2—, —O—, or —N(R5)—; provided that when X is —N(R5)— and W is —S(O)—, —S(O)2—, —O—, or —N(R5)—, then U is not a bond; and R1, R2, R3, R4, R5, R6, and R7 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of Human Immunodeficiency Virus, plasmepins, cathepsin D and protozoal enzymes. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic m1 agonist or m2 antagonist.

公开(公告)号：US20070010667A1

公开(公告)日：2007-01-11

申请号：US11451262

申请日：2006-06-12

申请人： Brian McKittrick ,  Zhaoning Zhu ,  Andrew Stamford ,  Elizabeth Smith

发明人： Brian McKittrick ,  Zhaoning Zhu ,  Andrew Stamford ,  Elizabeth Smith

IPC分类号： C07F9/6533 ,  C07F9/6512 ,  C07F9/6509

CPC分类号： C07D251/72 ,  C07D239/70 ,  C07F9/6584

摘要： Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein A is a bond, —C(O)—, or —C(R3′)(R4′)—; X is —N(R1)— or —C(R6)(R7)—; Y is —S(O)2—, —C(═O)—, —PO(OR9) or —C(R6′R7′)—; is a single or double bond and R, R1, R2, R3, R4, R3′, R4′, R5, R6, R6′, R7 and R7′ are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of Human Immunodeficiency Virus, plasmepins, cathepsin D and protozoal enzymes. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic antagonist.

摘要翻译： 公开了式I化合物或其立体异构体，互变异构体或其药学上可接受的盐或溶剂合物，其中A为键，-C（O） - 或-C（R 3' R 4'） - ; X是-N（R 1） - 或-C（R 6）（R 7） - ; Y是-S（O）2 - ， - C（-O） - ， - PO（OR 9）或-C（R 6' ）>; “img id =”custom-character-00001“he =”3.13mm“wi =”6.35mm“file =”US20070010667A1-20070111-P00001.TIF“alt =”custom character“img-content =”character“img-format =“tif”/>是单键或双键，R 1，R 2，R 2，R 3，R 4， R 3，R 4，R 4，R 5，R 6，R SUP， > 6'，R 7和R 7'如说明书中所定义; 以及包含式I化合物的药物组合物。还公开了抑制天冬氨酰蛋白酶的方法，特别是治疗心血管疾病，认知和神经变性疾病的方法以及抑制人类免疫缺陷病毒，plasmepins，组织蛋白酶D 和原生动物酶。 还公开了使用式I化合物与胆碱酯酶抑制剂或毒蕈碱拮抗剂组合来治疗认知或神经变性疾病的方法。

公开(公告)号：US20060281730A1

公开(公告)日：2006-12-14

申请号：US11451074

申请日：2006-06-12

申请人： Zhaoning Zhu ,  Brian McKittrick ,  Andrew Stamford ,  Ying Huang ,  Elizabeth Smith

发明人： Zhaoning Zhu ,  Brian McKittrick ,  Andrew Stamford ,  Ying Huang ,  Elizabeth Smith

IPC分类号： A61K31/553 ,  A61K31/551 ,  C07D491/04 ,  C07D487/04

CPC分类号： C07D487/04

摘要： Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein U, W, R, R1, R2, R3 and R4 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic m1 agonist or m2 antagonist.

摘要翻译： 公开了式I化合物或其立体异构体，互变异构体或其药学上可接受的盐或溶剂合物，其中U，W，R，R 1，R 2，R 2， SUP＆gt; 3＆gt;和＆lt; 4＆gt;如本说明书中所定义的; 以及包含式I化合物的药物组合物。还公开了抑制天冬氨酰蛋白酶的方法，特别是治疗心血管疾病，认知和神经变性疾病的方法。 还公开了使用式I化合物与胆碱酯酶抑制剂或毒蕈碱m 1激动剂或m 2 H 2拮抗剂组合治疗认知或神经变性疾病的方法。

公开(公告)号：US20080076750A1

公开(公告)日：2008-03-27

申请号：US11854738

申请日：2007-09-13

申请人： Robert Aslanian ,  Tin-Yau Chan ,  Joel Harris ,  Brian McKittrick ,  Bernard Neustadt ,  Anandan Palani ,  Tony Priestley ,  Elizabeth Smith ,  Andrew Stamford ,  Henry Vaccaro ,  Dong Xiao

发明人： Robert Aslanian ,  Tin-Yau Chan ,  Joel Harris ,  Brian McKittrick ,  Bernard Neustadt ,  Anandan Palani ,  Tony Priestley ,  Elizabeth Smith ,  Andrew Stamford ,  Henry Vaccaro ,  Dong Xiao

IPC分类号： A61K31/397 ,  A61P25/04 ,  A61P3/00

CPC分类号： A61K31/4427 ,  C07D471/10 ,  C07D519/00

摘要： The present invention relates to methods for treating or preventing a disorder of lipid metabolism, pain, diabetes, a vascular condition, demyelination or nonalcoholic fatty liver disease, comprising administering a compound having the formula or a pharmaceutically acceptable salt, solvate, ester, prodrug or stereoisomer thereof, wherein: R1 and R2 are defined in Tables 1-6 herein, and R3 is -phenyl, -4-chlorophenyl, -2-pyridyl, or -3-pyridyl.

摘要翻译： 本发明涉及治疗或预防脂质代谢紊乱，疼痛，糖尿病，血管病症，脱髓鞘或非酒精性脂肪性肝病的方法，包括给予具有下式的化合物或其药学上可接受的盐，溶剂合物，酯，前药或 其中：R 1和R 2在本文的表1-6中定义，R 3是 - 苯基， 氯苯基，-2-吡啶基或-3-吡啶基。

公开(公告)号：US20080076751A1

公开(公告)日：2008-03-27

申请号：US11854754

申请日：2007-09-13

申请人： Robert Aslanian ,  Chad Bennett ,  Duane Burnett ,  Tin-Yau Chan ,  Eugenia Kiselgof ,  Chad Knutson ,  Joel Harris ,  Brian McKittrick ,  Anandan Palani ,  Elizabeth Smith ,  Henry Vaccaro ,  Dong Xiao ,  Hyunjin Kim

发明人： Robert Aslanian ,  Chad Bennett ,  Duane Burnett ,  Tin-Yau Chan ,  Eugenia Kiselgof ,  Chad Knutson ,  Joel Harris ,  Brian McKittrick ,  Anandan Palani ,  Elizabeth Smith ,  Henry Vaccaro ,  Dong Xiao ,  Hyunjin Kim

IPC分类号： A61K31/397 ,  A61P25/04 ,  A61P3/00 ,  C07D471/10

CPC分类号： C07D471/10

摘要： The present invention relates to Azetidinone Derivatives, compositions comprising an Azetidinone Derivative and methods for treating or preventing a disorder of lipid metabolism, pain, diabetes, a vascular condition, demyelination or nonalcoholic fatty liver disease, comprising administering to a patient an effective amount of an Azetidinone Derivative.

摘要翻译： 本发明涉及氮杂环丁酮衍生物，包含氮杂环丁酮衍生物的组合物和用于治疗或预防脂质代谢紊乱，疼痛，糖尿病，血管病症，脱髓鞘或非酒精性脂肪性肝病的方法，包括向患者施用有效量的 氮杂环丁酮衍生物。

公开(公告)号：US20080070888A1

公开(公告)日：2008-03-20

申请号：US11854620

申请日：2007-09-13

申请人： Brian McKittrick ,  Elizabeth Smith ,  Chad Bennett ,  Duane Burnett ,  Chad Knutson

发明人： Brian McKittrick ,  Elizabeth Smith ,  Chad Bennett ,  Duane Burnett ,  Chad Knutson

IPC分类号： A61K31/397 ,  A61K31/438 ,  A61K31/506 ,  A61P25/04 ,  C07D239/42 ,  C07D471/10

CPC分类号： C07D471/10 ,  C07D487/10

摘要： Disclosed are compounds of the formula wherein Z1 is —CH2— or —C(O)—, R4 and R5 are carbon chains (and optionally, together can form a C2 bridge), u and v are independently an integer of 0-3 such that there sum is from 3 to 5, and R2 is heteroaryl, and R1 and R3 are as defined herein. Also disclosed are methods of treating pain using a compound of formula I.

摘要翻译： 公开了下式的化合物其中Z 1是-CH 2 - 或-C（O） - ，R 4和R 4， 5是碳链（并且可选地，一起可以形成C 2 H 2桥），u和v独立地是0-3的整数，使得总和为3至5，并且 R 2是杂芳基，R 1和R 3如本文所定义。 还公开了使用式I化合物治疗疼痛的方法。

公开(公告)号：US20080089858A1

公开(公告)日：2008-04-17

申请号：US11854600

申请日：2007-09-13

申请人： Brian McKittrick ,  Elizabeth Smith ,  Chad Bennett ,  Joel Harris ,  Eugenia Kiselgof ,  Chad Knutson ,  Peter Korakas ,  Deen Tulshian ,  Hyunjin Kim

发明人： Brian McKittrick ,  Elizabeth Smith ,  Chad Bennett ,  Joel Harris ,  Eugenia Kiselgof ,  Chad Knutson ,  Peter Korakas ,  Deen Tulshian ,  Hyunjin Kim

IPC分类号： A61K31/438 ,  A61K31/565 ,  A61K31/57 ,  A61K31/573 ,  A61K31/675 ,  A61K38/20 ,  A61P3/10 ,  C07D471/10

CPC分类号： C07D471/08

摘要： Disclosed are compounds of the formula: and compounds of the formula: wherein R1, R2, R3, R4, R5, u and v are as defined herein. Also disclosed are methods of treating pain (e.g., inflammatory pain, chronic pain, and neuropathic pain), methods of treating diabetes, and methods of inhibiting the absorption of cholesterol using compounds of formula I or IIA.

摘要翻译： 公开了下式的化合物和下式的化合物：其中R 1，R 2，R 3，R 4， u，v和u如本文所定义。 还公开了治疗疼痛（例如炎性疼痛，慢性疼痛和神经性疼痛）的方法，治疗糖尿病的方法，以及使用式I或IIA化合物抑制胆固醇吸收的方法。

公开(公告)号：US20060100427A1

公开(公告)日：2006-05-11

申请号：US11242337

申请日：2005-10-03

申请人： Dmitri Pissarnitski ,  Hubert Josien ,  Elizabeth Smith ,  John Clader ,  Theodros Asberom ,  Tao Guo ,  Douglas Hobbs

发明人： Dmitri Pissarnitski ,  Hubert Josien ,  Elizabeth Smith ,  John Clader ,  Theodros Asberom ,  Tao Guo ,  Douglas Hobbs

IPC分类号： A61K31/5377 ,  C07D413/02 ,  C07D401/14

CPC分类号： C07D401/12 ,  C07D211/96 ,  C07D401/14 ,  C07D409/12 ,  C07D471/10

摘要： This invention discloses novel gamma secretase inhibitors of the formula: wherein: R1 is a substituted aryl or substituted heteroaryl group; R2 is an R1 group, alkyl, —X(CO)Y, or alkylene-X(CO)Y wherein X and Y are as defined herein; each R3 and each R3A are independently H, or alkyl; R11 is aryl, heteroaryl, alkyl, cycloalkyl, arylalkyl, arylcycloalkyl, heteroarylalkyl, heteroarylcycloalkyl, arylheterocycloalkyl, or alkoxyalkyl. Also disclosed is a method of treating Alzheimer's Disease using one or more compounds of the invention.

摘要翻译： 本发明公开了下式的新型γ分泌酶抑制剂：其中：R 1是取代的芳基或取代的杂芳基; R 2是R 1基团，烷基，-X（CO）Y或亚烷基-X（CO）Y，其中X和Y如本文所定义; 每个R 3和R 3各自独立地为H或烷基; R 11是芳基，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，芳基杂环烷基或烷氧基烷基。 还公开了使用一种或多种本发明化合物治疗阿尔茨海默病的方法。