公开(公告)号：US07439374B2

公开(公告)日：2008-10-21

申请号：US11029910

申请日：2005-01-05

申请人： Andrew Thurkauf ,  Dawei Chen ,  Avinash Phadke ,  Shouming Li ,  Milind Deshpande

发明人： Andrew Thurkauf ,  Dawei Chen ,  Avinash Phadke ,  Shouming Li ,  Milind Deshpande

IPC分类号： C07D401/02 ,  A61K31/44

CPC分类号： A61K31/00 ,  A61K31/4355 ,  C07D491/04

摘要： The present invention provides compounds of Formula 1, wherein the variables Ar, A1, A2, A3, A4, R5, R6, R7, V, W, X, and Y are defined herein. Certain compounds of Formula 1 described herein possess potent antiviral activity. The invention also provides compounds of Formula 1 that are potent and/or selective inhibitors of Hepatitis C virus replication. The invention also provides pharmaceutical compositions containing one or more compounds of Formula 1, or a salt, solvate, or acylated prodrug of such compounds, and one or more pharmaceutically acceptable carriers, excipients, or diluents. The invention further comprises methods of treating patients suffering from certain infectious diseases by administering to such patients an amount of a compound of Formula 1 effective to reduce signs or symptoms of the disease. These infectious diseases include viral infections, particularly HCV infections. The invention is particularly includes methods of treating human patients suffering from an infectious disease, but also encompasses methods of treating other animals, including livestock and domesticated companion animals, suffering from an infectious disease.Methods of treatment include administering a compound of Formula 1 as a single active agent or administering a compound of Formula 1 in combination with on or more other therapeutic agent.

摘要翻译： 本发明提供式1的化合物，其中变量Ar，A 1，A 2，A 3，A 4， R 5，R 6，R 7，V，W，X和Y在本文中定义。 某些本文所述的式1的化合物具有有效的抗病毒活性。 本发明还提供了作为丙型肝炎病毒复制的有效和/或选择性抑制剂的式1化合物。 本发明还提供含有一种或多种式1化合物或这些化合物的盐，溶剂化物或酰化前药以及一种或多种药学上可接受的载体，赋形剂或稀释剂的药物组合物。 本发明还包括通过向这些患者施用一定量的有效减少疾病体征或症状的式1化合物来治疗患有某些感染性疾病的患者的方法。 这些传染病包括病毒感染，特别是HCV感染。 本发明特别包括治疗患有感染性疾病的人类患者的方法，还包括治疗其它动物（包括患有传染病的家畜和驯养的伴侣动物）的方法。 治疗方法包括施用作为单一活性剂的式1化合物或与一种或多种其它治疗剂组合施用式1的化合物。

公开(公告)号：US20070208048A1

公开(公告)日：2007-09-06

申请号：US11680865

申请日：2007-03-01

申请人： George Luke ,  George Maynard ,  Scott Mitchell ,  Andrew Thurkauf ,  Linghong Xie ,  LuYan Zhang ,  Suoming Zhang ,  He Zhao ,  Bertrand Chenard ,  Yang Gao ,  Bingsong Han ,  Xiao He

发明人： George Luke ,  George Maynard ,  Scott Mitchell ,  Andrew Thurkauf ,  Linghong Xie ,  LuYan Zhang ,  Suoming Zhang ,  He Zhao ,  Bertrand Chenard ,  Yang Gao ,  Bingsong Han ,  Xiao He

IPC分类号： A61K31/505 ,  A61K31/415 ,  A61K31/44 ,  A61K31/50

CPC分类号： C07D233/64 ,  A61K31/4164 ,  C07D233/68 ,  C07D235/02 ,  C07D235/30 ,  C07D237/12 ,  C07D401/04 ,  C07D401/12 ,  C07D403/06 ,  C07D403/12 ,  C07D405/12 ,  C07D405/14 ,  C07D409/04 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14

摘要： The invention provides Aryl substituted imidazoles, pyrazoles, pyridizines and related compounds of the Formula where the ring system represented by is a 5 membered heteroaryl ring system, in which x is 0, A is chosen from carbon and heteroatoms nitrogen, oxygen, and sulfur, and E and G are independently carbon or nitrogen provided that the 5 membered heteroaryl ring system does not contain more than 3 heteroatoms or more than 1 oxygen or sulfur atom, or a 6 membered heteroaryl ring system, in which x is 1, A, B, E, and G are independently chosen from carbon and nitrogen, provided that the 6 membered heteroaryl ring system does not contain more than 3 nitrogen atoms. The remaining variables, Ar1, Ar2, R, R1, R2, R3, R4, R5, R6, y and z are defined herein Such compounds are ligands of C5a receptors. Preferred compounds of the invention act bind to C5a receptors with high affinity and exhibit neutral antagonist or inverse agonist activity at C5a receptors. This invention also relates to pharmaceutical compositions comprising such compounds. It further relates to the use of such compounds in treating a variety of inflammatory and immune system disorders.

摘要翻译： 本发明提供芳基取代的咪唑，吡唑，吡啶并且其中由其表示的环系是5元杂芳基环系的相关化合物，其中x为0，A选自碳和杂原子氮，氧和硫， 并且E和G独立地为碳或氮，条件是5元杂芳基环系不包含多于3个杂原子或多于1个氧或硫原子，或6元杂芳基环系，其中x为1，A，B E和G独立地选自碳和氮，条件是6元杂芳基环系不含3个以上的氮原子。 其余的变量Ar 1，R 2，R 1，R 1，R 2，R 2， 3，R 4，R 5，R 6，y和z在本文中定义。这些化合物是C5a受体的配体。 本发明优选的化合物作用以高亲和力结合C5a受体，在C5a受体上表现出中性拮抗剂或反向激动剂活性。 本发明还涉及包含这些化合物的药物组合物。 它还涉及这些化合物在治疗各种炎性和免疫系统疾病中的应用。

公开(公告)号：US20060154917A1

公开(公告)日：2006-07-13

申请号：US10563401

申请日：2004-06-30

申请人： Suoming Zhang ,  He Zhao ,  Yang Gao ,  Andrew Thurkauf ,  George Maynard ,  Bertrand Chenard ,  Robert Ohliger ,  John Peterson

发明人： Suoming Zhang ,  He Zhao ,  Yang Gao ,  Andrew Thurkauf ,  George Maynard ,  Bertrand Chenard ,  Robert Ohliger ,  John Peterson

IPC分类号： A61K31/55 ,  A61K31/496 ,  A61K31/454 ,  C07D417/02 ,  C07D413/02

CPC分类号： C07D405/14 ,  C07D233/68 ,  C07D401/06 ,  C07D401/14 ,  C07D403/06 ,  C07D409/14 ,  C07D413/06 ,  C07D413/14 ,  C07D417/14

摘要： (Heterocycloalkyl)methyl azole derivatives of Formula (I) are provided: Formula I wherein A is oxygen, sulfur, or NR; J and K and each L are independently oxygen, sulfur, NH, or CH2; and the remaining variables are defined herein. Such compounds are modulators of C5a receptors, and preferably bind to C5a receptors with high affinity and exhibit neutral antagonist or inverse agonist activity at C5a receptors. Also provided herein are pharmaceutical compositions comprising such compounds, as well as methods for using such compounds in treating a variety of inflammatory and immune system disorders.

摘要翻译： （I）的（杂环烷基）甲基唑衍生物：式I其中A是氧，硫或NR; J和K，每个L独立地是氧，硫，NH或CH 2; 并且其余的变量在本文中定义。 这些化合物是C5a受体的调节剂，优选以高亲和力结合C5a受体，并在C5a受体上显示中性拮抗剂或反向激动剂活性。 本文还提供了包含这些化合物的药物组合物，以及使用这些化合物治疗各种炎性和免疫系统疾病的方法。

公开(公告)号：US20060025416A1

公开(公告)日：2006-02-02

申请号：US11131013

申请日：2005-05-17

申请人： Avinash Phadke ,  Dawei Chen ,  Milind Deshpande ,  Andrew Thurkauf ,  Xiangzhu Wang ,  Yiping Shen ,  Cuixian Liu ,  Jesse Quinn ,  Junko Ohkanda ,  Shouming Li

发明人： Avinash Phadke ,  Dawei Chen ,  Milind Deshpande ,  Andrew Thurkauf ,  Xiangzhu Wang ,  Yiping Shen ,  Cuixian Liu ,  Jesse Quinn ,  Junko Ohkanda ,  Shouming Li

IPC分类号： A61K31/537 ,  A61K31/498 ,  A61K31/47 ,  A61K31/421 ,  A61K31/17

CPC分类号： C07D295/15 ,  C07C335/26 ,  C07D211/22 ,  C07D211/46 ,  C07D211/60 ,  C07D211/64 ,  C07D211/78 ,  C07D213/56 ,  C07D213/82 ,  C07D215/54 ,  C07D231/14 ,  C07D233/54 ,  C07D233/64 ,  C07D233/90 ,  C07D237/24 ,  C07D239/28 ,  C07D241/24 ,  C07D241/44 ,  C07D249/06 ,  C07D253/07 ,  C07D261/18 ,  C07D263/34 ,  C07D263/58 ,  C07D265/30 ,  C07D271/12 ,  C07D277/56 ,  C07D277/68 ,  C07D285/06 ,  C07D307/68 ,  C07D307/84 ,  C07D307/85 ,  C07D309/38 ,  C07D311/58 ,  C07D333/38 ,  C07D401/04 ,  C07D401/12 ,  C07D405/04 ,  C07D409/04 ,  C07D409/12 ,  C07D413/12 ,  C07D417/04 ,  C07D417/12 ,  C07D417/14 ,  C07D419/12 ,  C07D471/04 ,  C07D487/04 ,  C07D491/04 ,  C07D495/04 ,  C07D513/04

摘要： The invention provides compounds and pharmaceutically acceptable salts of Formula I wherein the variables A1, A2, R1, R2, V, W, X, Y, and Z are defined herein. Certain compounds of Formula I described herein which possess potent antiviral activity. The invention particularly provides compounds of Formula I that are potent and/or selective inhibitors of Hepatitis C virus replication. The invention also provides pharmaceutical compositions containing one or more compound of Formula I, or a salt, solvate, or acylated prodrug of such compounds, and one or more pharmaceutically acceptable carriers, excipients, or diluents. The invention further comprises methods of treating patients suffering from certain infectious diseases by administering to such patients an amount of a compound of Formula I effective to reduce signs or symptoms of the disease or disorder. These infectious diseases include viral infections, particularly HCV infections. The invention is particularly includes methods of treating human patients suffering from an infectious disease, but also encompasses methods of treating other animals, including livestock and domesticated companion animals, suffering from an infectious disease. Methods of treatment include administering a compound of Formula I as a single active agent or administering a compound of Formula I in combination with on or more other therapeutic agent.

摘要翻译： 本发明提供式I的化合物和药学上可接受的盐，其中变量A 1，A 2，R 1，R 2， / SUB>，V，W，X，Y和Z在本文中定义。 某些本文所述的具有强抗病毒活性的式I化合物。 本发明特别提供了作为丙型肝炎病毒复制的有效和/或选择性抑制剂的式I化合物。 本发明还提供含有一种或多种式I化合物或这些化合物的盐，溶剂化物或酰化前药以及一种或多种药学上可接受的载体，赋形剂或稀释剂的药物组合物。 本发明还包括通过向这些患者施用一定量的有效减少疾病或病症的体征或症状的式I化合物来治疗患有某些感染性疾病的患者的方法。 这些传染病包括病毒感染，特别是HCV感染。 本发明特别包括治疗患有感染性疾病的人类患者的方法，还包括治疗其它动物（包括患有传染病的家畜和驯养的伴侣动物）的方法。 治疗方法包括给予式I化合物作为单一活性剂或将一种式I化合物与一种或多种其它治疗剂组合施用。

公开(公告)号：US20050032849A1

公开(公告)日：2005-02-10

申请号：US10887227

申请日：2004-07-08

申请人： Avinash Phadke ,  Jesse Quinn ,  Junko Ohkanda ,  Andrew Thurkauf ,  Yiping Shen ,  Cuixian Liu ,  Dawei Chen ,  Shouming Li

发明人： Avinash Phadke ,  Jesse Quinn ,  Junko Ohkanda ,  Andrew Thurkauf ,  Yiping Shen ,  Cuixian Liu ,  Dawei Chen ,  Shouming Li

IPC分类号： A61K31/17 ,  A61K31/44 ,  C07C15/00 ,  C07C335/14 ,  C07C335/16 ,  C07D213/54

CPC分类号： C07D211/64 ,  C07C335/12 ,  C07C335/14 ,  C07C335/16 ,  C07C335/18 ,  C07C335/20 ,  C07C335/22 ,  C07C2601/08 ,  C07C2601/14 ,  C07C2602/08 ,  C07C2602/44 ,  C07D211/14 ,  C07D211/62 ,  C07D215/06 ,  C07D217/04 ,  C07D295/135 ,  C07D317/66

摘要： Substituted arylthiourea compounds of Formula I, and the pharmaceutically acceptable salts of such compounds, useful as antiviral agents, are provided herein. Certain substituted arylthioureas disclosed herein are potent and/or selective inhibitors of viral replication, particularly Hepatitis C virus replication. Pharmaceutical compositions containing one or more substituted arylthiourea compounds and one or more pharmaceutically acceptable carriers, excipients, or diluents are provided herein. Such pharmaceutical compositions may contain a substituted arylthiourea as the only active agent or may contain a combination of a substituted arylthiourea derivative and one or more other pharmaceutically active agents. Methods of treating Hepatitis C viral infections in mammals are also provided herein.

摘要翻译： 本文提供了式I的取代的芳基硫脲化合物和可用作抗病毒剂的这类化合物的药学上可接受的盐。 本文公开的某些取代的芳基硫脲是有效和/或选择性的病毒复制抑制剂，特别是丙型肝炎病毒复制。 本文提供了含有一种或多种取代的芳基硫脲化合物和一种或多种药学上可接受的载体，赋形剂或稀释剂的药物组合物。 这样的药物组合物可以含有取代的芳基硫脲作为唯一的活性剂，或者可以含有取代的芳基硫脲衍生物和一种或多种其它药物活性剂的组合。 本文还提供了治疗哺乳动物中丙型肝炎病毒感染的方法。

公开(公告)号：US06569861B2

公开(公告)日：2003-05-27

申请号：US09900679

申请日：2001-07-06

申请人： Rajagopal Bakthavatchalam ,  Andrew Thurkauf ,  Alan Hutchison

发明人： Rajagopal Bakthavatchalam ,  Andrew Thurkauf ,  Alan Hutchison

IPC分类号： A61K31495

CPC分类号： C07D295/096

摘要： Disclosed are compounds of the formula: and the pharmaceutically acceptable salts thereof wherein Q, X, Y, Z, and R1 R9, and R12-R19 are defined herein. These compounds are selective modulators of MCH 1 receptors that are, therefore, useful in the treatment of a variety of metabolic, feeding, and sexual disorders. Methods of treatment of such disorders and well as packaged pharmaceutical compositions are also disclosed.

摘要翻译： 公开了下式的化合物及其药学上可接受的盐，其中Q，X，Y，Z和R 1 R 9和R 12 -R 19如本文所定义。这些化合物是MCH 1受体的选择性调节剂，因此其可用于 治疗各种代谢，喂养和性功能障碍。 还公开了治疗这种病症以及包装的药物组合物的方法。

公开(公告)号：US06436941B1

公开(公告)日：2002-08-20

申请号：US09783476

申请日：2001-02-14

申请人： Jun Yuan ,  Andrew Thurkauf

发明人： Jun Yuan ,  Andrew Thurkauf

IPC分类号： A61K31495

摘要： Disclosed are 5,6-Dihydro-napth[1,2-d]-imidazoles, Naphth[1,2-d]imidazoles, and Chromane[3,4-d]imidazoles compounds having the formula: and the pharmaceutically acceptable salts thereof, wherein, A represents ethenylene, or A represents —X—CH2—; where X is CH2 or oxygen, provided that when X is oxygen, the oxygen is adjacent the 6-membered ring; R1, R2, R3 and R4 are inorganic or organic substituents; and R5 and R6 is are optionally substituted organic substituents; or NR5R6 represents a carbocyclic or heterocyclic six membered ring optionally substituted with various organic or inorganic groups. Such compounds are useful in the treatment of neuropsychological disorders.

公开(公告)号：US6121260A

公开(公告)日：2000-09-19

申请号：US109558

申请日：1998-07-02

申请人： Andrew Thurkauf ,  Jun Yuan ,  Alan Hutchison ,  Charles A. Blum ,  Richard L. Elliot ,  Marlys Hammond

发明人： Andrew Thurkauf ,  Jun Yuan ,  Alan Hutchison ,  Charles A. Blum ,  Richard L. Elliot ,  Marlys Hammond

IPC分类号： A61K31/40 ,  A61K31/4164 ,  A61K31/4178 ,  A61K31/4427 ,  A61K31/443 ,  A61K31/4433 ,  A61K31/4439 ,  A61K31/495 ,  A61K31/538 ,  A61K31/5415 ,  A61P3/04 ,  A61P9/00 ,  A61P43/00 ,  C07D233/54 ,  C07D233/64 ,  C07D401/04 ,  C07D403/04 ,  C07D405/04 ,  C07D405/14 ,  C07D409/04 ,  C07D413/04 ,  C07D417/04 ,  A61K31/54 ,  A61K31/4166 ,  A61K31/5377 ,  A61K31/541

CPC分类号： C07D233/64 ,  C07D401/04 ,  C07D405/04 ,  C07D405/14 ,  C07D409/04 ,  C07D413/04 ,  C07D417/04

摘要： Certain diaryl imidazoles act as partial agonists or antagonists for NPY receptors, in particular NPY 5 receptors. They are of use, for example in treating loss of appetite. Such compounds bear aryl groups in the 2 position. Many of the compounds are novel.

摘要翻译： 某些二芳基咪唑作为NPY受体特别是NPY 5受体的部分激动剂或拮抗剂。 它们是有用的，例如用于治疗食欲不振。 这种化合物在2位上带有芳基。 许多化合物是新颖的。

公开(公告)号：US6084098A

公开(公告)日：2000-07-04

申请号：US259239

申请日：1999-02-26

申请人： Renata Xavier Kover ,  Silva Terdjanian ,  Jennifer Tran ,  Andrew Thurkauf

发明人： Renata Xavier Kover ,  Silva Terdjanian ,  Jennifer Tran ,  Andrew Thurkauf

IPC分类号： C07D209/08 ,  C07D295/15 ,  C07D401/06 ,  C07D403/06

CPC分类号： C07D295/15 ,  C07D209/08 ,  C07D401/06

摘要： Disclosed are compounds of the formula: ##STR1## or pharmaceutically acceptable addition salts thereof wherein: Y represents oxygen or sulfur; Z is nitrogen or CH;R.sub.1, R.sub.2 and R.sub.3 independently represent organic or inorganic substituents;R.sub.4 and R.sub.4 ' independently represent hydrogen, alkyl or form a ring with the atom to which they are attached;R.sub.5 represents hydrogen, alkyl, alkoxy, or alkylthio, and R.sub.6 represents hydrogen or alkyl; or R.sub.5 and R.sub.6 form a ring together with the atoms to which they are attached; andR.sub.7, R.sub.8, R.sub.9, R.sub.10 and R.sub.11 independently represent hydrogen or alkyl,which compounds are useful for the treatment and/or prevention of neuropsychological disorders including, but not limited to, schizophrenia, mania, dementia, depression, anxiety, compulsive behavior, substance abuse, Parkinson-like motor disorders and motion disorders related to the use of neuroleptic agents.

摘要翻译： 公开了下式的化合物或其药学上可接受的加成盐，其中：Y表示氧或硫; Z是氮或CH; R1，R2和R3独立地表示有机或无机取代基; R4和R4'独立地表示氢，烷基或与它们所连接的原子形成环; R5代表氢，烷基，烷氧基或烷硫基，R6代表氢或烷基; 或R 5和R 6与它们所连接的原子一起形成环; 并且R 7，R 8，R 9，R 10和R 11独立地表示氢或烷基，该化合物可用于治疗和/或预防神经心理障碍，包括但不限于精神分裂症，躁狂症，痴呆，抑郁，焦虑，强迫行为， 药物滥用，帕金森样运动障碍和与使用精神安定药有关的运动障碍。

公开(公告)号：US6069251A

公开(公告)日：2000-05-30

申请号：US859861

申请日：1997-05-21

申请人： Andrew Thurkauf ,  Raymond F. Horvath ,  Jun Yuan ,  John M. Peterson

发明人： Andrew Thurkauf ,  Raymond F. Horvath ,  Jun Yuan ,  John M. Peterson

IPC分类号： C07D233/54 ,  C07D233/64 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D403/06 ,  C07D403/04

CPC分类号： C07D233/64 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12

摘要： Disclosed are compounds of the formula: ##STR1## wherein R.sub.1 represents optionally substituted aryl, heteroaryl, arylalkyl, or cycloalkyl groups; X, Z, and Y are optionally substituted nitrogen or carbon atoms; R.sub.3 and R.sub.4 are organic or inorganic substituents which may together form ring structures; m is zero, one or two; and R.sub.5 and R.sub.6 are are organic or inorganic substituents; and the pharmaceutically acceptable addition salts thereof, which compounds are highly selective partial agonists or antagonists at brain dopamine receptor subtypes or prodrugs thereof and are useful in the diagnosis and treatment of affective disorders such as schizophrenia and depression as well as certain movement disorders such as Parkinsonism.

摘要翻译： 公开了下式的化合物：其中R 1表示任选取代的芳基，杂芳基，芳烷基或环烷基; X，Z和Y任选被取代的氮或碳原子; R3和R4是可以一起形成环结构的有机或无机取代基; m为零，一或二; R5和R6是有机或无机取代基; 和其药学上可接受的加成盐，该化合物是脑多巴胺受体亚型或其前药的高选择性部分激动剂或拮抗剂，并且可用于诊断和治疗情感障碍如精神分裂症和抑郁症以及某些运动障碍如帕金森综合征 。