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1. 发明授权

US08119806B2 Cicletanine derivatives 失效
标题翻译：花氨酸衍生物
公开(公告)号：US08119806B2
公开(公告)日：2012-02-21
申请号：US12509698
申请日：2009-07-27
申请人： Amjad Ali , Iyassu K. Sebhat , Christopher L. Franklin , Kathleen M. Rupprecht , Robert K. Baker , Ravi P. Nargund , Lin Yan , Pei Huo , Dong-Ming Shen , Nicoletta Almirante , Stefano Biondi , Massimiliano Ferrario , Alessia Nicotra
发明人： Amjad Ali , Iyassu K. Sebhat , Christopher L. Franklin , Kathleen M. Rupprecht , Robert K. Baker , Ravi P. Nargund , Lin Yan , Pei Huo , Dong-Ming Shen , Nicoletta Almirante , Stefano Biondi , Massimiliano Ferrario , Alessia Nicotra
IPC分类号： A61K31/4355 , C07D491/048
CPC分类号： C07D491/04 , C07D519/00
摘要： A compound having the structure wherein X is selected from the group consisting of: a bond, —NHCH2(CH2)nCH2OC(O)—, —CH2NHC(O)CH2NHC(O)—, —CH2OC(O)—, —OCH(CH3)OC(O)—, —OCH2OC(O)—, —O—, —NR1—, —CR1R3—, —(CH2)p—, —(CH2)qNR1C(O)—, —CHR5NR2C(O)—, —(CH2)qC(O)—, —(CH2)qC(O)NR1—, or a pharmaceutically acceptable salt thereof, and methods of using the compounds for treating hypertension.
摘要翻译：具有结构的化合物，其中X选自：-NHCH 2（CH 2）n CH 2 OC（O） - ， - CH 2 NHC（O）CH 2 NHC（O） - ， - CH 2 OC（O） - ， - OCH CH 3）OC（O） - ， - OCH 2 OC（O） - ， - O - ， - NR 1 - ，CR 1 R 3 - ， - （CH 2）p - ， - （CH 2）q NR1C ， - （CH 2）q C（O） - ， - （CH 2）q C（O）NR 1 - 或其药学上可接受的盐，以及使用该化合物治疗高血压的方法。

2. 发明申请

US20100029678A1 DIURETICS 失效
公开(公告)号：US20100029678A1
公开(公告)日：2010-02-04
申请号：US12509698
申请日：2009-07-27
申请人： Amjad ALI , Iyassu K. Sebhat , Cristopher L. Franklin , Kathleen M. Rupprecht , Robert K. Baker , Ravi P. Nargund , Lin Yan , Pei Huo , Dong-Ming Shen , Nicoletta Almirante , Stefano Biondi , Massimiliano Ferrario , Alessia Nicotra
发明人： Amjad ALI , Iyassu K. Sebhat , Cristopher L. Franklin , Kathleen M. Rupprecht , Robert K. Baker , Ravi P. Nargund , Lin Yan , Pei Huo , Dong-Ming Shen , Nicoletta Almirante , Stefano Biondi , Massimiliano Ferrario , Alessia Nicotra
IPC分类号： A61K31/496 , C07D491/02 , A61K31/4355 , C07D241/04 , A61P9/12
CPC分类号： C07D491/04 , C07D519/00
摘要： A compound having the structure wherein X is selected from the group consisting of: a bond, —NHCH2(CH2)nCH2OC(O)—, —CH2NHC(O)CH2NHC(O)—, —CH2OC(O)—, —OCH(CH3)OC(O)—, —OCH2OC(O)—, —O—, —NR1—, —CR1R3—, —(CH2)p—, —(CH2)qNR1C(O)—, —CHR5NR2C(O)—, —(CH2)qC(O)—, —(CH2)qC(O)—, —(CH2)qC(O)NR1—, or a pharmaceutically acceptable salt thereof, and methods of using the compounds for treating, hypertension.
摘要翻译：具有结构的化合物，其中X选自：-NHCH 2（CH 2）n CH 2 OC（O） - ， - CH 2 NHC（O）CH 2 NHC（O） - ， - CH 2 OC（O） - ， - OCH CH 3）OC（O） - ， - OCH 2 OC（O） - ， - O - ， - NR 1 - ，CR 1 R 3 - ， - （CH 2）p - ， - （CH 2）q NR1C ， - （CH2）qC（O） - ， - （CH2）qC（O） - ， - （CH2）qC（O）NR1-或其药学上可接受的盐，以及使用该化合物治疗高血压的方法。

3. 发明申请

US20180110863A1 GLUCOSE-RESPONSIVE INSULIN CONJUGATES 审中-公开
公开(公告)号：US20180110863A1
公开(公告)日：2018-04-26
申请号：US15564805
申请日：2016-04-04
申请人： Danqing FENG , Erin N. GUIDRY , Pei HUO , Niels C. KAARSHOLM , Songnian LIN , Ravi P. NARGUND , Lin YAN , Merck Sharp & Dohme Corp.
发明人： Danqing Feng , Erin N. Guidry , Pei Huo , Niels C. Kaarsholm , Songnian Lin , Ravi P. Nargund , Lin Yan
IPC分类号： A61K47/54 , A61K38/28 , A61P3/10
摘要： Insulin conjugates comprising an insulin analog molecule covalently attached to at least one bi-dentate linker having two arms, each arm independently attached to a ligand comprising a saccharide and wherein the saccharide for at least one ligand of the linker is fucose are disclosed. The insulin conjugates display a pharmacokinetic (PK) and/or pharmacodynamic (PD) profile that is responsive to the systemic concentrations of a saccharide such as glucose or alpha-methylmannose even when administered to a subject in need thereof in the absence of an exogenous multivalent saccharide-binding molecule such as Con A.

4. 发明申请

US20160251407A1 GLUCOSE-RESPONSIVE INSULIN CONJUGATES 有权
标题翻译：葡萄糖反应性胰岛素结合
公开(公告)号：US20160251407A1
公开(公告)日：2016-09-01
申请号：US15025912
申请日：2014-10-02
申请人： Songnian LIN , Lin YAN , Ahmet KEKEC , Yuping ZHU , David N. HUNTER , Pei HUO , Danqing FENG , Ravi P. NARGUND , Christopher R. MOYES , Zhiqiang ZHAO , Brenda PIPIK , Dimitri PISSARNITSKI , Joseph L. DUFFY , Erin N. GUIDRY , MERCK SHARP & DOHME CORP.
发明人： Songnian Lin , Lin Yan , Ahmet Kekec , Yuping Zhu , David N. Hunter , Pei Huo , Danqing Feng , Ravi P. Nargund , Christopher R. Moyes , Zhiqiang Zhao , Brenda Pipik , Dmitri Pissarnitski , Joseph L. Duffy , Erin Guidry
IPC分类号： C07K14/62 , A61K38/28 , A61K47/48
CPC分类号： A61K47/61 , A61K38/28 , A61K47/549 , A61K47/64 , C07K14/62
摘要： Insulin conjugates comprising an insulin molecule covalently attached to at least one bi-dentate linker having two arms, each arm independently attached to a ligand comprising a saccharide and wherein at least one ligand of the linker is fucose are disclosed. The insulin conjugates display a pharmacokinetic (PK) and/or pharmacodynamic (PD) profile that is responsive to the systemic concentrations of a saccharide such as glucose or alpha-methylmannose even when administered to a subject in need thereof in the absence of an exogenous multivalent saccharide-binding molecule such as Con A.
摘要翻译：胰岛素缀合物包含共价连接到具有两个臂的至少一个双齿连接体的胰岛素分子，每个臂独立地连接到包含糖的配体，并且其中至少一个连接体的配体是岩藻糖。胰岛素缀合物显示药代动力学（PK）和/或药效学（PD）谱，其对糖类如葡萄糖或α-甲基甘露糖的全身浓度有反应，即使在不存在外源多价的情况下施用于有需要的受试者时糖结合分子如Con A.

5. 发明授权

US08354394B2 Diuretics 有权
标题翻译：利尿剂
公开(公告)号：US08354394B2
公开(公告)日：2013-01-15
申请号：US13504581
申请日：2010-10-22
申请人： Amjad Ali , Christopher Franklin , Ravi Nargund , Michael Man-Chu Lo , Lin Yan , Pei Huo
发明人： Amjad Ali , Christopher Franklin , Ravi Nargund , Michael Man-Chu Lo , Lin Yan , Pei Huo
IPC分类号： A61K31/655 , C07D491/06 , A61P9/12
CPC分类号： C07D491/048
摘要： A compound having the structure (I) wherein R is selected from the group consisting of 1) and 2), or a pharmaceutically acceptable salt thereof, and methods of using the compounds for treating hypertension.
摘要翻译：具有结构（I）的化合物，其中R选自1）和2）或其药学上可接受的盐，以及使用该化合物治疗高血压的方法。

6. 发明申请

US20130059823A1 Diazeniumdiolate Cyclohexyl Derivatives 有权
标题翻译：二氮烯二硫代环己基衍生物
公开(公告)号：US20130059823A1
公开(公告)日：2013-03-07
申请号：US13698444
申请日：2011-05-16
申请人： Amjad Ali , Lin Yan , Pei Huo , Ravi Nargund
发明人： Amjad Ali , Lin Yan , Pei Huo , Ravi Nargund
IPC分类号： A61K31/655 , A61P9/12 , C07C245/02
CPC分类号： C07C291/02 , C07B59/001 , C07C2601/14
摘要： A compound having the structure (I) or a pharmaceutically acceptable salt thereof, wherein R3 is hydrogen, deuterium, —OH, —OC1-6alkyl, or halogen; R8 is hydrogen, deuterium, or C1-6alkyl; R11 and R12 are independently hydrogen, —C1-6alkyl, —OH, —OC1-6alkyl, or halogen; R13 and R14 are independently —C1-6alkyl, —(CH2)1-2OH, or —OC1-6alkyl, or, together with the nitrogen atom to which they are attached, form a 4- to 7-membered heterocyclic ring containing one nitrogen atom and 0 or 1 oxygen atoms, wherein said ring is unsubstituted or mono-, di- or tri-substituted with halogen or —C1-6alkyl; R15 is (CR1R2)nC(O)OR16, wherein n is 0, 1 or 2, —C(O)NHCH(R17)OR16, or —C(O)NHCH(R17)C(O)NHCH(R18)C(O)OR16; R16 is hydrogen, C1-6alkyl, or (CH2)1-2N+R19R20R21; R1, R2, R4, R5, R6, R7, R9, R10, R17, R18, R19, R20, and R21 are independently hydrogen or —C1-6alkyl; and stereoisomers thereof, and pharmaceutically acceptable salts thereof, and pharmaceutically acceptable salts of stereoisomers thereof.
摘要翻译：具有结构（I）的化合物或其药学上可接受的盐，其中R 3是氢，氘，-OH，-OC 1-6烷基或卤素; R8是氢，氘或C1-6烷基; R 11和R 12独立地是氢，-C 1-6烷基，-OH，-OC 1-6烷基或卤素; R 13和R 14独立地为C 1-6烷基， - （CH 2）1-2 OH或-OC 1-6烷基，或者与它们所连接的氮原子一起形成含有一个氮的4-至7-元杂环原子和0或1个氧原子，其中所述环是未取代的或被卤素或-C 1-6烷基单取代，二取代或三取代; R15是（CR1R2）nC（O）OR16，其中n是0,1或2，-C（O）NHCH（R17）OR16或-C（O）NHCH（R17）C（O）NHCH（R18）（O）OR16; R16是氢，C1-6烷基或（CH2）1-2N + R19R20R21; R 1，R 2，R 4，R 5，R 6，R 7，R 9，R 10，R 17，R 18，R 19，R 20和R 21独立地为氢或-C 1-6烷基; 其立体异构体及其药学上可接受的盐及其立体异构体的药学上可接受的盐。

7. 发明授权

US08623846B2 Diazeniumdiolate cyclohexyl derivatives 有权
标题翻译：二氮烯二硫代环己基衍生物
公开(公告)号：US08623846B2
公开(公告)日：2014-01-07
申请号：US13698444
申请日：2011-05-16
申请人： Amjad Ali , Lin Yan , Pei Huo , Ravi Nargund
发明人： Amjad Ali , Lin Yan , Pei Huo , Ravi Nargund
IPC分类号： A61K31/655 , C07C245/02 , C09B44/02
CPC分类号： C07C291/02 , C07B59/001 , C07C2601/14
摘要： A compound having the structure (I) or a pharmaceutically acceptable salt thereof, wherein R3 is hydrogen, deuterium, —OH, —OC1-6alkyl, or halogen; R8 is hydrogen, deuterium, or C1-6alkyl; R11 and R12 are independently hydrogen, —C1-6alkyl, —OH, —OC1-6alkyl, or halogen; R13 and R14 are independently —C1-6alkyl, —(CH2)1-2OH, or —OC1-6alkyl, or, together with the nitrogen atom to which they are attached, form a 4- to 7-membered heterocyclic ring containing one nitrogen atom and 0 or 1 oxygen atoms, wherein said ring is unsubstituted or mono-, di- or tri-substituted with halogen or —C1-6alkyl; R15 is —C(O)OH, —C(O)OCH2CH2N+CH3)3 wherein n is 0, 1 or 2, —C(O)NHCH(R17)OR16, or —C(O)NHCH(R17)C(O)NHCH(R18)C(O)OR16; R16 is hydrogen, C1-6alkyl, or (CH2)1-2N+R19R20R21; R1, R2, R4, R5, R6, R7, R9, R10, R17, R18, R19, R20, and R21 are independently hydrogen or —C1-6alkyl; and stereoisomers thereof, and pharmaceutically acceptable salts thereof, and pharmaceutically acceptable salts of stereoisomers thereof.
摘要翻译：具有结构（I）的化合物或其药学上可接受的盐，其中R 3是氢，氘，-OH，-OC 1-6烷基或卤素; R8是氢，氘或C1-6烷基; R 11和R 12独立地是氢，-C 1-6烷基，-OH，-OC 1-6烷基或卤素; R 13和R 14独立地为C 1-6烷基， - （CH 2）1-2 OH或-OC 1-6烷基，或者与它们所连接的氮原子一起形成含有一个氮的4-至7-元杂环原子和0或1个氧原子，其中所述环是未取代的或被卤素或-C 1-6烷基单取代，二取代或三取代; R 15是-C（O）OH，-C（O）OCH 2 CH 2 N + CH 3）3，其中n是0,1或2，-C（O）NHCH（R 17）OR 16或-C（O）NHCH（R 17）C （O）NHCH（R 18）C（O）OR 16; R16是氢，C1-6烷基或（CH2）1-2N + R19R20R21; R 1，R 2，R 4，R 5，R 6，R 7，R 9，R 10，R 17，R 18，R 19，R 20和R 21独立地为氢或-C 1-6烷基; 其立体异构体及其药学上可接受的盐及其立体异构体的药学上可接受的盐。

8. 发明申请

US20120208838A1 DIURETICS 有权
公开(公告)号：US20120208838A1
公开(公告)日：2012-08-16
申请号：US13504581
申请日：2010-10-22
申请人： Amjad Ali , Christopher Franklin , Ravi Nargund , Michael Man-Chu Lo , Lin Yan , Pei Huo
发明人： Amjad Ali , Christopher Franklin , Ravi Nargund , Michael Man-Chu Lo , Lin Yan , Pei Huo
IPC分类号： A61K31/4355 , A61P9/12 , C07D491/048
CPC分类号： C07D491/048
摘要： A compound having the structure (I) wherein R is selected from the group consisting of 1) and 2), or a pharmaceutically acceptable salt thereof, and methods of using the compounds for treating hypertension.
摘要翻译：具有结构（I）的化合物，其中R选自1）和2）或其药学上可接受的盐，以及使用该化合物治疗高血压的方法。

9. 发明申请

US20190175744A1 INSULIN-INCRETIN CONJUGATES 审中-公开
公开(公告)号：US20190175744A1
公开(公告)日：2019-06-13
申请号：US16083201
申请日：2017-03-13
申请人： Anandan PALANI , Chunhui HUANG , Zhiqiang YANG , Lin YAN , Songnian LIN , Pei HUO , Qiaolin DENG , Elisabetta BIANCHI , Federica ORVIETO , Merck Sharp & Dohme Corp.
发明人： Anandan Palani , Chunhui Huang , Zhiqiang Yang , Lin Yan , Songnian Lin , Pei Huo , Qiaolin Deng , Elisabetta Bianchi , Federica Orvieto
IPC分类号： A61K47/64 , A61K38/28 , A61K38/26
摘要： Insulin-incretin conjugates comprising a peptide having agonist activity at the glucagon-like 1 (GLP-1) receptor, the glucagon (GCG) receptor, and/or the gastric inhibitory protein (GIP) receptor conjugated to an insulin molecule having agonist activity at the insulin receptor and use of the conjugates for treatment of metabolic diseases, for example, Type 2 diabetes, are described.

10. 发明授权

US07999107B2 Substituted pyrano[2,3-B]pyridine derivatives as cannabinoid-1 receptor modulators 失效
标题翻译：取代的吡喃并[2,3-B]吡啶衍生物作为大麻素-1受体调节剂
公开(公告)号：US07999107B2
公开(公告)日：2011-08-16
申请号：US12009114
申请日：2008-01-16
申请人： John S. Debenham , Jeffrey J. Hale , Pei Huo , Christina B. Madsen-Duggan , Thomas F. Walsh , Lin Yan
发明人： John S. Debenham , Jeffrey J. Hale , Pei Huo , Christina B. Madsen-Duggan , Thomas F. Walsh , Lin Yan
IPC分类号： C07D491/052 , A61K31/436
CPC分类号： C07D491/052 , C07D491/16 , C07D495/16
摘要： Novel compounds of the structural formula (I) are antagonists and/or inverse agonists of the Cannabinoid-1 (CB1) receptor and are useful in the treatment, prevention and suppression of diseases mediated by the CB1 receptor. The compounds of the present invention are useful as centrally acting drugs in the treatment of psychosis, memory deficits, cognitive disorders, Alzheimer's disease, migraine, neuropathy, neuro-inflammatory disorders including multiple sclerosis and Guillain-Barre syndrome and the inflammatory sequelae of viral encephalitis, cerebral vascular accidents, and head trauma, anxiety disorders, stress, epilepsy, Parkinson's disease, Huntington's disease movement disorders, and schizophrenia. The compounds are also useful for the treatment of substance abuse disorders, the treatment of obesity or eating disorders, as well as the treatment of asthma, constipation, chronic intestinal pseudo-obstruction, cirrhosis of the liver, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and the promotion of wakefulness.
摘要翻译：结构式（I）的新型化合物是大麻素-1（CB1）受体的拮抗剂和/或反向激动剂，可用于治疗，预防和抑制由CB1受体介导的疾病。本发明的化合物可用作治疗精神病，记忆缺陷，认知障碍，阿尔茨海默病，偏头痛，神经病，包括多发性硬化症和神经 - 巴利综合征的神经炎症性疾病以及病毒性脑炎的炎症性后遗症的中枢作用药物脑血管意外，头部创伤，焦虑障碍，压力，癫痫，帕金森病，亨廷顿病运动障碍和精神分裂症。这些化合物还可用于治疗药物滥用障碍，治疗肥胖或进食障碍，以及治疗哮喘，便秘，慢性肠假性梗阻，肝硬化，非酒精性脂肪性肝病（NAFLD ），非酒精性脂肪性肝炎（NASH），以及促进觉醒。

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