公开(公告)号：US07638531B2

公开(公告)日：2009-12-29

申请号：US11641175

申请日：2006-12-19

Applicant: Mwangi W. Mutahi ,  Robert G. Aslanian ,  Michael Y. Berlin ,  Christopher W. Boyce ,  Manuel de Lera Ruiz ,  Kevin D. McCormick ,  Daniel M. Solomon ,  Henry A. Vaccaro ,  Junying Zheng ,  Purakkattle Biju ,  Younong Yu ,  Wei Zhou ,  Xiaohong Zhu

Inventor： Mwangi W. Mutahi ,  Robert G. Aslanian ,  Michael Y. Berlin ,  Christopher W. Boyce ,  Manuel de Lera Ruiz ,  Kevin D. McCormick ,  Daniel M. Solomon ,  Henry A. Vaccaro ,  Junying Zheng ,  Purakkattle Biju ,  Younong Yu ,  Wei Zhou ,  Xiaohong Zhu

IPC: A01N43/42 ,  A61K31/44 ,  A01N43/40 ,  C07D471/02 ,  C07D491/02 ,  C07D498/02 ,  C07D211/68 ,  C07D211/80 ,  C07D213/02

CPC classification number: C07D471/04 ,  C07D213/38 ,  C07D213/73 ,  C07D277/40 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D409/12 ,  C07D417/06 ,  C07D417/14 ,  C07D473/00

Abstract: Disclosed are compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein: M is CH or N; U and W are each CH, or one of U and W is CH and the other is N; X is a bond, alkylene, —C(O)—, —C(N—OR5)—, —C(N—OR5)—CH(R6)—, —CH(R6)—C(N—OR5)—, —O—, —OCH2—, —CH2O— or —S(O)0-2—; Y is —O—, —(CH2)2—, —C(═O)—, —C(═NOR7)— or —SO0-2—; Z is a bond, optionally substituted alkylene or alkylene interrupted by a heteroatom or heterocyclic group; R1 is optionally substituted alkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heterocycloalkyl, or benzimidazolyl or a derivative thereof; R2 is optionally substituted alkyl, alkenyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl or heterocycloalkyl; and the remaining variables are as defined in the specification; compositions and methods for treating an allergy-induced airway response, congestion, diabetes, obesity, an obesity-related disorder, metabolic syndrome and a cognition deficit disorder using said compounds, alone or in combination with other agents.

Abstract translation: 公开了下式的化合物或其药学上可接受的盐或溶剂化物，其中：M是CH或N; U和W各自为CH，或U和W中的一个为CH，另一个为N; X是键，亚烷基，-C（O） - ， - C（N-OR 5） - ， - C（N-OR 5）-CH（R 6） - ， - CH（R 6）-C（N-OR 5） ，-O - ， - OCH 2 - ， - CH 2 O-或-S（O）0-2-; Y是-O - ， - （CH 2）2 - ， - C（-O） - ， - C（-NOR 7） - 或-SOO 2 - ; Z是一个键，任选取代的被杂原子或杂环基中断的亚烷基或亚烷基; R1是任选取代的烷基，环烷基，芳基，芳烷基，杂芳基，杂环烷基或苯并咪唑基或其衍生物; R 2是任选取代的烷基，烯基，芳基，芳基烷基，杂芳基，杂芳基烷基，环烷基或杂环烷基; 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，糖尿病，肥胖，肥胖相关病症，代谢综合征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

Applicant: 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

Inventor： 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: A61K31/4545 ,  C07D401/14

CPC classification number: C07D295/185 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  Y02P20/582

Abstract: 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.

Abstract translation: 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

Applicant: 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

Inventor： 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: A61K31/4545

CPC classification number: C07D295/185 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  Y02P20/582

Abstract: 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.

Abstract translation: 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：US07531660B2

公开(公告)日：2009-05-12

申请号：US11837248

申请日：2007-08-10

Applicant: Manuel de Lera Ruiz ,  Robert G. Aslanian ,  Michael Y. Berlin ,  Kevin D. McCormick ,  Chander S. Celly

Inventor： Manuel de Lera Ruiz ,  Robert G. Aslanian ,  Michael Y. Berlin ,  Kevin D. McCormick ,  Chander S. Celly

IPC: C07D498/02 ,  A01N43/42

CPC classification number: C07D471/04

Abstract: The present invention discloses the compound of Formula I and pharmaceutically acceptable salts and solvates thereof. The invention also relates to pharmaceutical compositions comprising the Compound of Formula I and its use in treating obesity, metabolic syndrome, diabetes, hepatic lipidosis or nonalcoholic fatty liver disease. The invention also relates to the use of a combination of the Compound of Formula I with additional therapeutic agents for treating obesity, metabolic syndrome, diabetes, hepatic lipidosis or nonalcoholic fatty liver disease.

Abstract translation: 本发明公开了式I化合物及其药学上可接受的盐和溶剂化物。 本发明还涉及包含式I化合物及其在治疗肥胖，代谢综合征，糖尿病，肝脏脂质沉积或非酒精性脂肪性肝病中的用途的药物组合物。 本发明还涉及式I化合物与用于治疗肥胖，代谢综合征，糖尿病，肝脏脂质沉积或非酒精性脂肪性肝病的其它治疗剂的组合的用途。

公开(公告)号：US07332604B2

公开(公告)日：2008-02-19

申请号：US11523489

申请日：2006-09-19

Applicant: Manuel de Lera Ruiz ,  Robert G. Aslanian ,  Michael Y. Berlin ,  Kevin D. McCormick

Inventor： Manuel de Lera Ruiz ,  Robert G. Aslanian ,  Michael Y. Berlin ,  Kevin D. McCormick

IPC: C07D498/02

CPC classification number: C07D471/04

Abstract: The present invention discloses the compound of Formula I and pharmaceutically acceptable salts and solvates thereof. The invention also relates to pharmaceutical compositions comprising the Compound of Formula I and its use in treating obesity, metabolic syndrome, diabetes, hepatic lipidosis or nonalcoholic fatty liver disease. The invention also relates to the use of a combination of the Compound of Formula I with additional therapeutic agents for treating obesity, metabolic syndrome, diabetes, hepatic lipidosis or nonalcoholic fatty liver disease.

Abstract translation: 本发明公开了式I化合物及其药学上可接受的盐和溶剂化物。 本发明还涉及包含式I化合物及其在治疗肥胖，代谢综合征，糖尿病，肝脏脂质沉积或非酒精性脂肪性肝病中的用途的药物组合物。 本发明还涉及式I化合物与用于治疗肥胖，代谢综合征，糖尿病，肝脏脂质沉积或非酒精性脂肪性肝病的其它治疗剂的组合的用途。

公开(公告)号：US20070167435A1

公开(公告)日：2007-07-19

申请号：US11641175

申请日：2006-12-19

Applicant: Mwangi Mutahi ,  Robert Aslanian ,  Michael Berlin ,  Christopher Boyce ,  Manuel de Lera Ruiz ,  Kevin McCormick ,  Daniel Solomon ,  Henry Vaccaro ,  Junying Zheng ,  Purakkattle Biju ,  Younong Yu ,  Wei Zhou ,  Xiaohong Zhu

Inventor： Mwangi Mutahi ,  Robert Aslanian ,  Michael Berlin ,  Christopher Boyce ,  Manuel de Lera Ruiz ,  Kevin McCormick ,  Daniel Solomon ,  Henry Vaccaro ,  Junying Zheng ,  Purakkattle Biju ,  Younong Yu ,  Wei Zhou ,  Xiaohong Zhu

IPC: A61K31/551 ,  A61K31/501 ,  A61K31/506 ,  A61K31/4745 ,  C07D471/02

CPC classification number: C07D471/04 ,  C07D213/38 ,  C07D213/73 ,  C07D277/40 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D409/12 ,  C07D417/06 ,  C07D417/14 ,  C07D473/00

Abstract: Disclosed are compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein: M is CH or N; U and W are each CH, or one of U and W is CH and the other is N; X is a bond, alkylene, —C(O)—, —C(N—OR5)—, —C(N—OR5)—CH(R6)—, —CH(R6)—C(N—OR5)—, —O—, —OCH2—, —CH2O— or —S(O)0-2—; Y is —O—, —(CH2)2—, —C(═O)—, —C(═NOR7)— or —SO0-2—; Z is a bond, optionally substituted alkylene or alkylene interrupted by a heteroatom or heterocyclic group; R1 is optionally substituted alkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heterocycloalkyl, or benzimidazolyl or a derivative thereof; R2 is optionally substituted alkyl, alkenyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl or heterocycloalkyl; and the remaining variables are as defined in the specification; compositions and methods for treating an allergy-induced airway response, congestion, diabetes, obesity, an obesity-related disorder, metabolic syndrome and a cognition deficit disorder using said compounds, alone or in combination with other agents.

Abstract translation: 公开了下式的化合物或其药学上可接受的盐或溶剂化物，其中：M是CH或N; U和W各自为CH，或U和W中的一个为CH，另一个为N; X是键，亚烷基，-C（O） - ， - C（N-OR 5） - ， - （N -OR 5）-CH（R - （CH 3） - ， - CH（R 6） - ， - （N-OR 5） - ， - O - ， - 2 - ， - CH 2 O-或-S（O）0-2 - 。 Y是-O-， - （CH 2）2 - ， - C（-O） - ， - C（-NOR 7） - 或-SO <0-2 - ; - Z是一个键，任选取代的被杂原子或杂环基中断的亚烷基或亚烷基; R 1是任选取代的烷基，环烷基，芳基，芳基烷基，杂芳基，杂环烷基或苯并咪唑基或其衍生物; R 2是任选取代的烷基，烯基，芳基，芳基烷基，杂芳基，杂芳基烷基，环烷基或杂环烷基; 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，糖尿病，肥胖，肥胖相关病症，代谢综合征和认知缺陷障碍的组合物和方法。

公开(公告)号：US20070015807A1

公开(公告)日：2007-01-18

申请号：US11455625

申请日：2006-06-19

Applicant: Robert Aslanian ,  Michael Berlin ,  Christopher Boyce ,  Jianhua Chao ,  Manuel de Lera Ruiz ,  Pietro Mangiaracina ,  Kevin McCormick ,  Mwangi Mutahi ,  Stuart Rosenblum ,  Neng-Yang Shih ,  Daniel Solomon ,  Wing Tom ,  Henry Vaccaro ,  Junying Zheng ,  Xiaohong Zhu

Inventor： Robert Aslanian ,  Michael Berlin ,  Christopher Boyce ,  Jianhua Chao ,  Manuel de Lera Ruiz ,  Pietro Mangiaracina ,  Kevin McCormick ,  Mwangi Mutahi ,  Stuart Rosenblum ,  Neng-Yang Shih ,  Daniel Solomon ,  Wing Tom ,  Henry Vaccaro ,  Junying Zheng ,  Xiaohong Zhu

IPC: C07D403/02 ,  A61K31/4178 ,  A61K31/4025

CPC classification number: C07D295/185 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  Y02P20/582

Abstract: 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.

Abstract translation: 公开了下式的新化合物或其药学上可接受的盐，其中：M 1和M 3是CH或N; M 2是CH，CF或N; Y是-C（-O） - ， - C（-S） - ， - （CH 2 CH 2）q - ， - C（-NOR 7） / SO 2 - ） - 或-SO 2 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，全部是任选取代的，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，全部任选被取代; 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：US20240131028A1

公开(公告)日：2024-04-25

申请号：US18263551

申请日：2022-02-02

Applicant: Justin A. BODDEY ,  David B. OLSEN ,  Ryan STEEL ,  John A. MCCAULEY ,  Manuel DE LERA RUIZ ,  Merck Sharp & Dohme LLC ,  The Walter and Eliza Hall Institute of Medical Research

Inventor： Justin A. Boddey ,  David B. Olsen ,  Ryan Steel ,  John A. McCauley ,  Manuel De Lera Ruiz

IPC: A61K31/513 ,  A61K39/015 ,  A61K45/06 ,  A61P33/06

CPC classification number: A61K31/513 ,  A61K39/015 ,  A61K45/06 ,  A61P33/06 ,  A61K2039/522

Abstract: The present invention relates to a method of chemovaccination against Plasmodium infection comprising administering to a patient an effective amount of a selective inhibitor of plasmepsin X, or a pharmaceutically acceptable salt thereof.

公开(公告)号：US20210260082A1

公开(公告)日：2021-08-26

申请号：US17260619

申请日：2019-07-15

Applicant: Manuel De Lera RUIZ ,  Izzat RAHEEM ,  Michael T. RUDD ,  Merck Sharp & Dohme Corp.

Inventor： Manuel De Lera Ruiz ,  Izzat Raheem ,  Michael T. Rudd

IPC: A61K31/675 ,  C07F9/6561 ,  A61P31/18 ,  A61K31/52 ,  A61K31/7068 ,  A61K31/7072 ,  A61K31/341 ,  A61K31/496 ,  A61K31/513 ,  A61K31/427 ,  A61K31/635 ,  A61K31/4439 ,  A61K31/536

Abstract: Compounds of Formula I: I and their pharmaceutically acceptable salts are useful for the inhibition of HIV reverse transcriptase. The compounds may also be useful for the prophylaxis or treatment of infection by HIV and in the prophylaxis, delay in the onset or progression, and treatment of AIDS. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antiviral agents, immunomodulators, antibiotics or vaccines.

公开(公告)号：US20130079271A1

公开(公告)日：2013-03-28

申请号：US13499071

申请日：2010-09-22

Applicant: Kevin D. McCormick ,  Ning Shao ,  Younong Yu ,  Xianhai Huang ,  Manuel De Lera Ruiz ,  Anandan Palani ,  Junying Zheng ,  Christopher W. Boyce ,  Robert G. Aslanian ,  Jianhua Chao

Inventor： Kevin D. McCormick ,  Ning Shao ,  Younong Yu ,  Xianhai Huang ,  Manuel De Lera Ruiz ,  Anandan Palani ,  Junying Zheng ,  Christopher W. Boyce ,  Robert G. Aslanian ,  Jianhua Chao

IPC: C07D413/10 ,  A61K31/537 ,  A61K31/4245 ,  A61K38/02 ,  A61K31/423 ,  A61K31/4439 ,  A61K31/56 ,  A61K31/506 ,  C07D263/52

CPC classification number: C07D413/10 ,  A61K31/42 ,  A61K31/423 ,  A61K31/4245 ,  A61K31/4439 ,  A61K31/506 ,  A61K31/537 ,  A61K31/56 ,  A61K38/02 ,  A61K45/06 ,  C07D263/52 ,  C07D413/04 ,  C07D417/04 ,  A61K2300/00

Abstract: In its many embodiments, the present invention provides a novel class of biaryl spiroaminooxazoline analogues as modulators of α2C adrenergic receptor agonists, 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 conditions associated with the α2C adrenergic receptors using such compounds or pharmaceutical compositions.

Abstract translation: 在其许多实施方案中，本发明提供了一类新颖的联芳基螺氨基恶唑啉类似物作为α2C肾上腺素能受体激动剂的调节剂，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类化合物的药物制剂的方法 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α2C肾上腺素能受体相关的一种或多种病症的方法。