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    CONJUGATE BASED SYSTEMS FOR CONTROLLED INSULIN DELIVERY
    5.
    发明申请
    CONJUGATE BASED SYSTEMS FOR CONTROLLED INSULIN DELIVERY 有权

    公开(公告)号：US20210198339A1

    公开(公告)日：2021-07-01

    申请号：US16771818

    申请日：2018-12-13

    申请人： Lin YAN ,  Pei HUO ,  Ahmet KEKEC ,  Danqing D. FENG ,  Yuping ZHU ,  Dmitri PISSARNITSKI ,  Chris MOYES ,  Songnian LIN ,  Merck Sharp & Dohme Corp.

    发明人： Lin Yan ,  Pei Huo ,  Ahmet Kekec ,  Danqing D. Feng ,  Yuping Zhu ,  Dmitri Pissarnitski ,  Chris Moyes ,  Songnian Lin

    IPC分类号： C07K14/62 ,  A61K47/54 ,  A61K47/61

    摘要： The present disclosure provides conjugates that comprise an insulin molecule conjugated via a conjugate framework to two or more separate ligands that each include a saccharide, wherein the framework, ligand, saccharide and insulin molecule optionally comprise a fatty chain (e.g., a C8-30 fatty chain), wherein when said insulin molecule is conjugated both to a C8-30 fatty chain and one or more separate ligands that each include a saccharide, said C8-30 fatty chain is linked to insulin molecule only, and wherein when the framework or ligand comprises a fatty chain the insulin molecule is conjugated to two or more separate ligands. In certain embodiments, a conjugate is characterized in that, when the conjugate is administered to a mammal, at least one pharmacokinetic (PK) and/or pharmacodynamic (PD) property of the conjugate is sensitive to serum concentration of a second saccharide. In certain embodiments, a conjugate is also characterized by having a protracted PK profile. Exemplary conjugates and sustained release formulations are provided in addition to methods of use and preparation.

    Substituted pyrano[2,3-B]pyridine derivatives as cannabinoid-1 receptor modulators
    8.
    发明授权
    Substituted pyrano[2,3-B]pyridine derivatives as cannabinoid-1 receptor modulators 失效
    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。

    Substituted pyrano[2,3-B]pyridine derivatives as cannabinoid-1 receptor modulators
    9.
    发明申请
    Substituted pyrano[2,3-B]pyridine derivatives as cannabinoid-1 receptor modulators 失效
    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：US20080207666A1

    公开(公告)日：2008-08-28

    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： A61K31/527 ,  C07D471/10 ,  A61K31/4433 ,  C07D471/04 ,  A61P25/28

    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。