公开(公告)号：US06506756B2

公开(公告)日：2003-01-14

申请号：US09954867

申请日：2001-09-18

申请人： Neng-Yang Shih ,  Daniel M. Solomon ,  John J. Piwinski ,  Andrew T. Lupo, Jr. ,  Michael J. Green

发明人： Neng-Yang Shih ,  Daniel M. Solomon ,  John J. Piwinski ,  Andrew T. Lupo, Jr. ,  Michael J. Green

IPC分类号： C07D40112

CPC分类号： C07D401/12 ,  C07D401/14

摘要： The present invention discloses novel substituted imidazole compounds which have dual histamine-H1 and H3 receptor antagonist activity as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such imidazoles as well as methods of using them to treat allergy, inflammatory and CNS-related diseases and others.

公开(公告)号：US06762186B2

公开(公告)日：2004-07-13

申请号：US09955383

申请日：2001-09-18

申请人： Neng-Yang Shih ,  Robert G. Aslanian ,  Daniel M. Solomon ,  Stuart B. Rosenblum ,  Mwangi Wa Mutahi ,  Tom G. Wing ,  Kevin D. McCormick ,  John J. Piwinski ,  Ronald Wolin

发明人： Neng-Yang Shih ,  Robert G. Aslanian ,  Daniel M. Solomon ,  Stuart B. Rosenblum ,  Mwangi Wa Mutahi ,  Tom G. Wing ,  Kevin D. McCormick ,  John J. Piwinski ,  Ronald Wolin

IPC分类号： C07D21168

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

摘要： The present invention discloses novel substituted imidazole compounds which have H3 receptor antagonist or dual histamine-H1 and H3 receptor antagonist activity as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such imidazoles as well as methods of using them to treat allergy, nasal congestion, inflammatory and CNS-related diseases and others.

摘要翻译： 本发明公开了具有H3受体拮抗剂或双组胺H1和H3受体拮抗剂活性的新型取代咪唑化合物以及制备这些化合物的方法。 在另一个实施方案中，本发明公开了包含这种咪唑的药物组合物以及使用它们治疗过敏，鼻充血，炎性和CNS相关疾病等的方法。

公开(公告)号：US07105505B2

公开(公告)日：2006-09-12

申请号：US10417391

申请日：2003-04-16

申请人： Qingbei Zeng ,  Robert G. Aslanian ,  Michael Y. Berlin ,  Christopher W. Boyce ,  Jianhua Cao ,  Joseph A. Kozlowski ,  Pietro Mangiaracina ,  Kevin D. McCormick ,  Mwangi W. Mutahi ,  Stuart B. Rosenblum ,  Neng-Yang Shih ,  Daniel M. Solomon ,  Wing C. Tom

发明人： Qingbei Zeng ,  Robert G. Aslanian ,  Michael Y. Berlin ,  Christopher W. Boyce ,  Jianhua Cao ,  Joseph A. Kozlowski ,  Pietro Mangiaracina ,  Kevin D. McCormick ,  Mwangi W. Mutahi ,  Stuart B. Rosenblum ,  Neng-Yang Shih ,  Daniel M. Solomon ,  Wing C. Tom

IPC分类号： A61K31/495

CPC分类号： C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04

摘要： Disclosed are novel compounds of the formula wherein R1 is optionally substituted benzimidazolyl or a derivative thereof; R2 is optionally substituted aryl or heteroaryl; M1 and M2 are C(R3) or N; and the remaining variables are as defined in the specification; also disclosed are pharmaceutical compositions comprising the compounds of formula I and methods of treating various diseases or conditions, such as allergy, allergy-induced airway responses, and congestion (e.g., nasal congestion) using the compounds of formula I, as well as methods of treating said diseases or conditions using the compounds of formula I in combination with an H1 receptor antagonist.

摘要翻译： 公开了下式的新化合物，其中R 1是任选取代的苯并咪唑基或其衍生物; R 2是任选取代的芳基或杂芳基; M 1和M 2是C（R 3）或N; 剩余的变量如规范中所定义; 还公开了包含式I化合物的药物组合物和使用式I化合物治疗各种疾病或病症如过敏，过敏引起的气道反应和充血（例如，鼻塞）的方法，以及 使用式I化合物与H 1受体拮抗剂组合治疗所述疾病或病症。

公开(公告)号：US07238688B2

公开(公告)日：2007-07-03

申请号：US10974329

申请日：2004-10-27

申请人： Stuart B. Rosenblum ,  Qingbei Zeng ,  Mwangi Wa Mutahi ,  Robert G. Aslanian ,  Pauline C. Ting ,  Neng-Yang Shih ,  Daniel M. Solomon ,  Jianhua Cao ,  Henry A. Vaccaro ,  Kevin D. McCormick ,  John J. Baldwin ,  Ge Li

发明人： Stuart B. Rosenblum ,  Qingbei Zeng ,  Mwangi Wa Mutahi ,  Robert G. Aslanian ,  Pauline C. Ting ,  Neng-Yang Shih ,  Daniel M. Solomon ,  Jianhua Cao ,  Henry A. Vaccaro ,  Kevin D. McCormick ,  John J. Baldwin ,  Ge Li

IPC分类号： A61K31/55 ,  C07D243/08 ,  C07D241/02 ,  C07D401/06 ,  C07D403/06

CPC分类号： C07D401/14 ,  C07D211/26 ,  C07D211/38 ,  C07D211/62 ,  C07D211/96 ,  C07D243/08 ,  C07D401/06 ,  C07D407/12 ,  C07D407/14 ,  C07D409/14 ,  C07D413/06 ,  C07D413/14 ,  C07D417/06 ,  C07D417/14 ,  C07D451/02 ,  C07D487/06

摘要： Disclosed are novel compounds of the formula Also disclosed are pharmaceutical compositions comprising the compounds of Formula I.Also disclosed are methods of treating various diseases or conditions, such as, for example, allergy, allergy-induced airway responses, and congestion (e.g., nasal congestion) using the compounds of Formula I.Also disclosed are methods of treating various diseases or conditions, such as, for example, allergy, allergy-induced airway responses, and congestion (e.g., nasal congestion) using the compounds of Formula I in combination with a H1 receptor antagonist.

摘要翻译： 公开的是式的新化合物还公开了包含式I化合物的药物组合物。还公开了治疗各种疾病或病症的方法，例如过敏，过敏诱发的气道反应和充血（例如，鼻 拥塞）。还公开了使用组合式I化合物来治疗各种疾病或病症的方法，例如过敏，过敏诱发的气道反应和充血（例如，鼻塞） 具有H 1受体拮抗剂。

公开(公告)号：US07846946B2

公开(公告)日：2010-12-07

申请号：US12507563

申请日：2009-07-22

申请人： Robert G. Aslanian ,  Michael Y. Berlin ,  Christopher W. Boyce ,  Jianhua Chao ,  Manuel de Lera Ruiz ,  Pietro Mangiaracina ,  Kevin D. McCormick ,  Mwangi W. Mutahi ,  Stuart B. Rosenblum ,  Neng-Yang Shih ,  Daniel M. Solomon ,  Wing C. Tom ,  Henry A. Vaccaro ,  Junying Zheng ,  Xiaohong Zhu

发明人： Robert G. Aslanian ,  Michael Y. Berlin ,  Christopher W. Boyce ,  Jianhua Chao ,  Manuel de Lera Ruiz ,  Pietro Mangiaracina ,  Kevin D. McCormick ,  Mwangi W. Mutahi ,  Stuart B. Rosenblum ,  Neng-Yang Shih ,  Daniel M. Solomon ,  Wing C. Tom ,  Henry A. Vaccaro ,  Junying Zheng ,  Xiaohong Zhu

IPC分类号： A61K31/4545 ,  C07D401/14

CPC分类号： C07D295/185 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  Y02P20/582

摘要： Disclosed are novel compounds of the formula or a pharmaceutically acceptable salt thereof, wherein: M1 and M3 are CH or N; M2 is CH, CF or N; Y is —C(═O)—, —C(═S)—, —(CH2)q—, —C(═NOR7)— or —SO1-2—; Z is a bond or optionally substituted alkylene or alkenylene; R1 is H, or alkyl, cycloalkyl, aryl, heteroaryl, heterocycloalkyl, all optionally substituted, or a group of the formula: where ring A is a heteroaryl ring; R2 is optionally substituted alkyl, alkenyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl; R3 is H, —C(O)NH2, or alkyl, aryl, cycloalkyl, heterocycloalkyl or heteroaryl, all optionally substituted; and the remaining variables are as defined in the specification; compositions and methods of treating allergy-induced airway responses, congestion, obesity, metabolic syndrome, alcoholic fatty liver disease, hepatic steatosis, nonalcoholic steatohepatitis, cirrhosis, hepatacellular carcinoma and cognition deficit disorders using said compounds, alone or in combination with other agents.

摘要翻译： 公开了下式的新化合物或其药学上可接受的盐，其中：M1和M3是CH或N; M2是CH，CF或N; Y是-C（= O） - ， - C（= S） - ， - （CH 2）q - ， - C（= NOR 7） - 或-SO 1 2- Z是键或任选取代的亚烷基或亚烯基; R 1是H或烷基，环烷基，芳基，杂芳基，杂环烷基，全部被取代，或下式的基团：其中环A是杂芳基环; R 2是任选取代的烷基，烯基，芳基，杂芳基，环烷基或杂环烷基; R 3是H，-C（O）NH 2或烷基，芳基，环烷基，杂环烷基或杂芳基，全部被取代; 剩余的变量如规范中所定义; 使用所述化合物单独或与其它试剂组合治疗过敏引起的气道反应，充血，肥胖，代谢综合征，酒精性脂肪肝疾病，肝脂肪变性，非酒精性脂肪性肝炎，肝硬化，肝细胞癌和认知缺陷障碍的组合物和方法。

公开(公告)号：US07635705B2

公开(公告)日：2009-12-22

申请号：US11455625

申请日：2006-06-19

申请人： Robert G. Aslanian ,  Michael Y. Berlin ,  Christopher W. Boyce ,  Jianhua Chao ,  Manuel de Lera Ruiz ,  Pietro Mangiaracina ,  Kevin D. McCormick ,  Stuart B. Rosenblum ,  Neng-Yang Shih ,  Daniel M. Solomon ,  Wing C. Tom ,  Henry A. Vaccaro ,  Junying Zheng ,  Xiaohong Zhu ,  Mwangi W. Mutahi

发明人： Robert G. Aslanian ,  Michael Y. Berlin ,  Christopher W. Boyce ,  Jianhua Chao ,  Manuel de Lera Ruiz ,  Pietro Mangiaracina ,  Kevin D. McCormick ,  Stuart B. Rosenblum ,  Neng-Yang Shih ,  Daniel M. Solomon ,  Wing C. Tom ,  Henry A. Vaccaro ,  Junying Zheng ,  Xiaohong Zhu ,  Mwangi W. Mutahi

IPC分类号： A61K31/4545 ,  C07D401/14

CPC分类号： C07D295/185 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  Y02P20/582

摘要： Disclosed are novel compounds of the formula or a pharmaceutically acceptable salt thereof, wherein: M1 and M3 are CH or N; M2 is CH, CF or N; Y is —C(═O)—, —C(═S)—, —(CH2)q—, —C(═NOR7)— or —SO1-2—; Z is a bond or optionally substituted alkylene or alkenylene; R1 is H, or alkyl, cycloalkyl, aryl, heteroaryl, heterocycloalkyl, all optionally substituted, or a group of the formula: where ring A is a heteroaryl ring; R2 is optionally substituted alkyl, alkenyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl; R3 is H, —C(O)NH2, or alkyl, aryl, cycloalkyl, heterocycloalkyl or heteroaryl, all optionally substituted; and the remaining variables are as defined in the specification; compositions and methods of treating allergy-induced airway responses, congestion, obesity, metabolic syndrome, alcoholic fatty liver disease, hepatic steatosis, nonalcoholic steatohepatitis, cirrhosis, hepatacellular carcinoma and cognition deficit disorders using said compounds, alone or in combination with other agents.

摘要翻译： 公开了下式的新化合物或其药学上可接受的盐，其中：M1和M3是CH或N; M2是CH，CF或N; Y是-C（-O） - ， - C（-S） - ， - （CH 2）q - ， - C（-NOR 7） - 或-SO 1 - Z是键或任选取代的亚烷基或亚烯基; R 1是H或烷基，环烷基，芳基，杂芳基，杂环烷基，全部被取代，或下式的基团：其中环A是杂芳基环; R 2是任选取代的烷基，烯基，芳基，杂芳基，环烷基或杂环烷基; R 3是H，-C（O）NH 2或烷基，芳基，环烷基，杂环烷基或杂芳基，全部被取代; 剩余的变量如规范中所定义; 使用所述化合物单独或与其它试剂组合治疗过敏引起的气道反应，充血，肥胖，代谢综合征，酒精性脂肪肝疾病，肝脂肪变性，非酒精性脂肪性肝炎，肝硬化，肝细胞癌和认知缺陷障碍的组合物和方法。

公开(公告)号：US20090286830A1

公开(公告)日：2009-11-19

申请号：US12507563

申请日：2009-07-22

申请人： Robert G. Aslanian ,  Michael Y. Berlin ,  Christopher W. Boyce ,  Jianhua Chao ,  Manuel de Lera Ruiz ,  Pietro Mangiaracina ,  Kevin D. McCormick ,  Stuart B. Rosenblum ,  Neng-Yang Shih ,  Daniel M. Solomon ,  Wing C. Tom ,  Henry A. Vaccaro ,  Junying Zheng ,  Xiaohong Zhu ,  Mwangi W. Mutahi

发明人： Robert G. Aslanian ,  Michael Y. Berlin ,  Christopher W. Boyce ,  Jianhua Chao ,  Manuel de Lera Ruiz ,  Pietro Mangiaracina ,  Kevin D. McCormick ,  Stuart B. Rosenblum ,  Neng-Yang Shih ,  Daniel M. Solomon ,  Wing C. Tom ,  Henry A. Vaccaro ,  Junying Zheng ,  Xiaohong Zhu ,  Mwangi W. Mutahi

IPC分类号： A61K31/4545

CPC分类号： C07D295/185 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  Y02P20/582

摘要： Disclosed are novel compounds of the formula or a pharmaceutically acceptable salt thereof, wherein: M1 and M3 are CH or N; M2 is CH, CF or N; Y is —C(═O)—, —C(═S)—, —(CH2)q—, —C(═NOR7)— or —SO1-2—; Z is a bond or optionally substituted alkylene or alkenylene; R1 is H, or alkyl, cycloalkyl, aryl, heteroaryl, heterocycloalkyl, all optionally substituted, or a group of the formula: where ring A is a heteroaryl ring; R2 is optionally substituted alkyl, alkenyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl; R3 is H, —C(O)NH2, or alkyl, aryl, cycloalkyl, heterocycloalkyl or heteroaryl, all optionally substituted; and the remaining variables are as defined in the specification; compositions and methods of treating allergy-induced airway responses, congestion, obesity, metabolic syndrome, alcoholic fatty liver disease, hepatic steatosis, nonalcoholic steatohepatitis, cirrhosis, hepatacellular carcinoma and cognition deficit disorders using said compounds, alone or in combination with other agents.

摘要翻译： 公开了下式的新化合物或其药学上可接受的盐，其中：M1和M3是CH或N; M2是CH，CF或N; Y是-C（-O） - ， - C（-S） - ， - （CH 2）q - ， - C（-NOR 7） - 或-SO 1 - Z是键或任选取代的亚烷基或亚烯基; R 1是H或烷基，环烷基，芳基，杂芳基，杂环烷基，全部被取代，或下式的基团：其中环A是杂芳基环; R 2是任选取代的烷基，烯基，芳基，杂芳基，环烷基或杂环烷基; R 3是H，-C（O）NH 2或烷基，芳基，环烷基，杂环烷基或杂芳基，全部被取代; 剩余的变量如规范中所定义; 使用所述化合物单独或与其它试剂组合治疗过敏引起的气道反应，充血，肥胖，代谢综合征，酒精性脂肪肝疾病，肝脂肪变性，非酒精性脂肪性肝炎，肝硬化，肝细胞癌和认知缺陷障碍的组合物和方法。

公开(公告)号：US07220735B2

公开(公告)日：2007-05-22

申请号：US10414943

申请日：2003-04-16

申请人： Pauline C. Ting ,  Robert G. Aslanian ,  Michael Y. Berlin ,  Christopher W. Boyce ,  Jianhua Cao ,  Pietro Mangiaracina ,  Kevin D. McCormick ,  Mwangi W. Mutahi ,  Stuart B. Rosenblum ,  Neng-Yang Shih ,  Daniel M. Solomon ,  Wing C. Tom ,  Qingbei Zeng

发明人： Pauline C. Ting ,  Robert G. Aslanian ,  Michael Y. Berlin ,  Christopher W. Boyce ,  Jianhua Cao ,  Pietro Mangiaracina ,  Kevin D. McCormick ,  Mwangi W. Mutahi ,  Stuart B. Rosenblum ,  Neng-Yang Shih ,  Daniel M. Solomon ,  Wing C. Tom ,  Qingbei Zeng

IPC分类号： A61K31/495

CPC分类号： C07D471/04 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14

摘要： Disclosed are novel compounds of the formula wherein R1 is benzimidazolone derivative, M1 and M2 are optionally substituted carbon or nitrogen, R2 includes optionally substituted aryl or heteroaryl, and the remaining variables are as defined in the specification, and the remaining variables are as defined in the specification; also disclosed are pharmaceutical compositions comprising the compounds of formula I and methods of treating various diseases or conditions, such as allergy, allergy-induced airway responses, and congestion (e.g., nasal congestion) using the compounds of formula I, as well as methods of treating said diseases or conditions using the compounds of formula I in combination with an H1 receptor antagonist.

摘要翻译： 公开了下式的新化合物其中R 1是苯并咪唑酮衍生物，M 1和M 2是任选取代的碳或氮，R SUP > 2 包括任选取代的芳基或杂芳基，其余变量如说明书中所定义，其余变量如说明书中所定义; 还公开了包含式I化合物的药物组合物和使用式I化合物治疗各种疾病或病症如过敏，过敏引起的气道反应和充血（例如，鼻塞）的方法，以及 使用式I化合物与H 1受体拮抗剂组合治疗所述疾病或病症。

公开(公告)号：US06849621B2

公开(公告)日：2005-02-01

申请号：US10095134

申请日：2002-03-11

申请人： Stuart B. Rosenblum ,  Qingbei Zeng ,  Mwangi Wa Mutahi ,  Robert G. Aslanian ,  Pauline C. Ting ,  Neng-Yang Shih ,  Daniel M. Solomon ,  Jianhua Cao ,  Henry A. Vaccaro ,  Kevin D. McCormick ,  John J. Baldwin ,  Ge Li

发明人： Stuart B. Rosenblum ,  Qingbei Zeng ,  Mwangi Wa Mutahi ,  Robert G. Aslanian ,  Pauline C. Ting ,  Neng-Yang Shih ,  Daniel M. Solomon ,  Jianhua Cao ,  Henry A. Vaccaro ,  Kevin D. McCormick ,  John J. Baldwin ,  Ge Li

IPC分类号： C07D211/34 ,  A61K31/496 ,  A61P1/00 ,  A61P1/04 ,  A61P3/04 ,  A61P9/00 ,  A61P9/04 ,  A61P11/00 ,  A61P25/00 ,  A61P25/06 ,  A61P25/18 ,  A61P25/20 ,  A61P25/28 ,  A61P37/08 ,  A61P43/00 ,  C07D211/26 ,  C07D211/38 ,  C07D211/62 ,  C07D211/96 ,  C07D243/08 ,  C07D401/06 ,  C07D401/14 ,  C07D405/14 ,  C07D407/12 ,  C07D407/14 ,  C07D409/14 ,  C07D413/06 ,  C07D413/14 ,  C07D417/06 ,  C07D417/14 ,  C07D451/02 ,  C07D487/06 ,  A61K31/4545 ,  C07D403/06

CPC分类号： C07D401/14 ,  C07D211/26 ,  C07D211/38 ,  C07D211/62 ,  C07D211/96 ,  C07D243/08 ,  C07D401/06 ,  C07D407/12 ,  C07D407/14 ,  C07D409/14 ,  C07D413/06 ,  C07D413/14 ,  C07D417/06 ,  C07D417/14 ,  C07D451/02 ,  C07D487/06

摘要： Disclosed are novel compounds of the formula Also disclosed are pharmaceutical compositions comprising the compounds of Formula I.Also disclosed are methods of treating various diseases or conditions, such as, for example, allergy, allergy-induced airway responses, and congestion (e.g., nasal congestion) using the compounds of Formula I.Also disclosed are methods of treating various diseases or conditions, such as, for example, allergy, allergy-induced airway responses, and congestion (e.g., nasal congestion) using the compounds of Formula I in combination with a H. receptor antagonist.

摘要翻译： 所公开的新化合物还公开了包含式I化合物的药物组合物。还公开了治疗各种疾病或病症的方法，例如过敏，过敏诱发的气道反应和充血（例如，鼻充血 ）。还公开了使用式I化合物与下列化合物组合治疗各种疾病或病症的方法，例如过敏，过敏诱发的气道反应和充血（例如，鼻塞） H.受体拮抗剂。

公开(公告)号：US06211182B1

公开(公告)日：2001-04-03

申请号：US09264615

申请日：1999-03-08

申请人： Wayne Vaccaro ,  John J. Piwinski ,  Wing C. Tom ,  Daniel M. Solomon ,  Robert G. Aslanian

发明人： Wayne Vaccaro ,  John J. Piwinski ,  Wing C. Tom ,  Daniel M. Solomon ,  Robert G. Aslanian

IPC分类号： A61K31496

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

摘要： This invention discloses novel imidazoles substituted with a six or seven membered heterocyclic ring which contains two nitrogen atoms as part of the heterocyclic ring structure. These compounds have excellent histamine-H3 receptor antagonist activity. Also disclosed are methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such imidazoles as well as methods of using them to treat allergy (for example asthma), inflammation, hypertension, raised intraocular pressure (such as glaucoma)—i.e., a method of lowering intraocular pressure, sleeping disorders, states of hyper and hypomotility and acidic secretion of the gastrointestinal tract, hypo and hyperactivity of the central nervous system (for example, agitation and depression) and other CNS disorders (such as Alzheimer's Disease, schizophrenia, and migraine). An illustrative inventive imidazole is shown below:

摘要翻译： 本发明公开了用含有两个氮原子作为杂环结构的一部分的六元或七元杂环取代的新型咪唑。 这些化合物具有优异的组胺H3受体拮抗剂活性。 还公开了制备这些化合物的方法。 在另一个实施方案中，本发明公开了包含这种咪唑的药物组合物以及使用它们治疗过敏（例如哮喘），炎症，高血压，升高的眼内压（如青光眼）的方法，降低眼内压的方法， 睡眠障碍，超低运动性和胃肠道酸性分泌状态，中枢神经系统（例如，激动和抑郁）和其他CNS疾病（如阿尔茨海默病，精神分裂症和偏头痛）的低反应和多动症。 本发明的咪唑如下所示：