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    Carbocyclic and heterocyclic substituted semicarbazones and thiosemicarbazones and the use thereof
    11.
    发明授权
    Carbocyclic and heterocyclic substituted semicarbazones and thiosemicarbazones and the use thereof 失效
    碳环和杂环取代的缩氨基脲和缩氨基硫脲和其用途

    公开(公告)号：US06696442B2

    公开(公告)日：2004-02-24

    申请号：US10178477

    申请日：2002-06-25

    申请人： Yan Wang ,  Sui Xiong Cai ,  Nancy C. Lan ,  John F. W. Keana ,  Victor I. Ilyin

    发明人： Yan Wang ,  Sui Xiong Cai ,  Nancy C. Lan ,  John F. W. Keana ,  Victor I. Ilyin

    IPC分类号： A61K3117

    CPC分类号： C07D213/643 ,  A61K31/17 ,  A61K31/175 ,  A61K31/44 ,  A61K31/445 ,  A61K31/47 ,  A61K31/505 ,  C07C281/12 ,  C07C281/14 ,  C07C2601/14 ,  C07D209/14 ,  C07D211/46 ,  C07D213/68 ,  C07D215/12 ,  C07D307/91 ,  C07D309/12 ,  C07D317/50 ,  C07D317/58 ,  C07D317/62 ,  C07D317/64 ,  C07D319/18

    摘要： This invention is related to carbocyclic and heterocyclic substituted semicarbazones and thiosemicarbazones represented by Formula I: or a pharmaceutically acceptable salt or prodrug thereof, wherein: Y is oxygen or sulfur; R1, R21, R22 and R23 are independently hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, haloalkyl, aryl, aminoalkyl, hydroxyalkyl, alkoxyalkyl or carboxyalkyl-82-; or R22 and R23, together with the N, form a heterocycle; A1 and A2 are independently aryl, heteroaryl, saturated or partially unsaturated carbocycle or saturated or partially unsaturated heterocycle, any of which is optionally substituted; X is one or O, S, NR24, CR25R26, C(O), NR24C(O), C(O)NR24, SO, SO2 or a covalent bond; where R24, R25 and R26 are independently hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, haloalkyl, aryl, aminoalkyl, hydroxyalkyl, alkoxyalkyl or carboxyalkyl. The invention also is directed to the use of carbocycle and heterocycle substituted semicarbazones and thiosemicarbazones for the treatment of neuronal damage following global and focal ischemia, for the treatment or prevention of neurodegenerative conditions such as amyotrophic lateral sclerosis (ALS), for the treatment and prevention of otoneurotoxicity and eye diseases involving glutamate toxicity and for the treatment, prevention or amelioration of pain, as anticonvulsants, and as antimanic depressants, as local anesthetics, as antiarrhythmics and for the treatment or prevention of diabetic neuropathy and urinary incontinence.

    摘要翻译： 本发明涉及由式I表示的碳环和杂环取代的缩氨基脲和缩氨基硫脲或其药学上可接受的盐或前药，其中：Y是氧或硫; R1，R21，R22和R23独立地是氢，烷基，环烷基，烯基，炔基，卤代烷基，芳基，氨基烷基，羟基烷基，烷氧基烷基或羧基烷基-82-。 或R 22和R 23与N一起形成杂环; A1和A2独立地是芳基，杂芳基，饱和或部分不饱和的碳环或饱和或部分不饱和的杂环，其中任何一个任选被取代; X是1或O，S，NR 24，CR 25 R 26，C（O），NR 24 C（O），C（O）NR 24，SO，SO 2或共价键; 其中R 24，R 25和R 26独立地是氢，烷基，环烷基，烯基，炔基，卤代烷基，芳基，氨基烷基，羟基烷基，烷氧基烷基或羧基烷基。 本发明还涉及使用碳环和杂环取代的缩氨基脲和缩氨基硫脲来治疗全身和局部缺血后的神经元损伤，用于治疗或预防神经变性疾病如肌萎缩性侧索硬化（ALS），用于治疗和预防 涉及谷氨酸毒性和治疗，预防或改善疼痛，作为抗惊厥药，以及作为局部麻醉剂，作为抗心律失常药物和用于治疗或预防糖尿病性神经病和尿失禁的抗疟药抑制剂。

    Substituted 5-oxo-5,6,7,8-tetrahydro-4H-1-benzopyrans and benzothiopyrans and the use thereof as potentiators of AMPA
    12.
    发明授权
    Substituted 5-oxo-5,6,7,8-tetrahydro-4H-1-benzopyrans and benzothiopyrans and the use thereof as potentiators of AMPA 失效
    取代的5-氧代-5,6,7,8-四氢-4H-1-苯并吡喃和苯并噻喃并将其作为AMPA的增效剂

    公开(公告)号：US06680332B1

    公开(公告)日：2004-01-20

    申请号：US09980628

    申请日：2002-05-20

    申请人： Christopher S. Konkoy ,  David B. Fick ,  Sui Xiong Cai ,  Nancy C. Lan ,  John F. W. Keana

    发明人： Christopher S. Konkoy ,  David B. Fick ,  Sui Xiong Cai ,  Nancy C. Lan ,  John F. W. Keana

    IPC分类号： A61K4364

    CPC分类号： C07D311/74

    摘要： Disclosed is a method for treating a disorder responsive to the positive modulation of AMPA receptors in animals suffering therefrom, comprising administering to an animal in need thereof a compound of Formula I: or a pharmaceutically acceptable salt or prodrug thereof, wherein: Y is NH2, NHR, and NHCOR; Z is O and S; and R1, R2, R3, R4, and X are defined herein. These compounds can be used as cognitive enhancers, for the treatment of neurodegenerative diseases, including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, AIDS associated dementia and Down's syndrome as well as for the treatment of schizophrenia and myoclonus. Also disclosed are pharmaceutical compositions useful for treating disorders responsive to the positive modulation of AMPA receptors, and novel compounds of Formula I.

    摘要翻译： 本发明公开了一种治疗患有AMPA受体AMPA受体阳性调节的病症的方法，其包括向有需要的动物施用式I化合物或其药学上可接受的盐或前药，其中：Y为NH 2， NHR和NHCOR; Z是O和S; 并且R1，R2，R3，R4和X在本文中定义。 这些化合物可用作认知增强剂，用于治疗神经变性疾病，包括阿尔茨海默病，肌萎缩性侧索硬化，亨廷顿舞蹈病，帕金森病，AIDS相关性痴呆和唐氏综合征，以及治疗精神分裂症和肌阵挛。 还公开了可用于治疗对AMPA受体的正调节起反应的病症的药物组合物和式I的新化合物。

    Substituted 5-oxo-5, 6, 7, 8-tetrahydro-4H-1-benzopyrans
    14.
    发明授权
    Substituted 5-oxo-5, 6, 7, 8-tetrahydro-4H-1-benzopyrans 失效
    取代的5-氧代-5,6,7,8-四氢-4H-1-苯并吡喃

    公开(公告)号：US06800657B2

    公开(公告)日：2004-10-05

    申请号：US10610871

    申请日：2003-07-02

    申请人： Christopher S. Konkoy ,  David B. Fick ,  Sui Xiong Cai ,  Nancy C. Lan ,  John F. W. Keana

    发明人： Christopher S. Konkoy ,  David B. Fick ,  Sui Xiong Cai ,  Nancy C. Lan ,  John F. W. Keana

    IPC分类号： A61K3138

    CPC分类号： C07D311/74

    摘要： Disclosed is a method for treating a disorder responsive to the positive modulation of AMPA receptors in animals suffering therefrom, comprising administering to an animal in need thereof a compound of Formula I: or a pharmaceutically acceptable salt or prodrug thereof, wherein: Y is NH2, NHR, and NHCOR; Z is O and S; and R1, R2, R3, R4, and X are defined herein. These compounds can be used as cognitive enhancers, for the treatment of neurodegenerative diseases, including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, AIDS associated dementia and Down's syndrome as well as for the treatment of schizophrenia and myoclonus. Also disclosed are pharmaceutical compositions useful for treating disorders responsive to the positive modulation of AMPA receptors, and novel compounds of Formula I.

    摘要翻译： 本发明公开了一种治疗患有AMPA受体AMPA受体阳性调节的病症的方法，其包括向有需要的动物施用式I化合物或其药学上可接受的盐或前药，其中：Y为NH 2， NHR和NHCOR; Z是O和S; 并且R1，R2，R3，R4和X在本文中定义。 这些化合物可用作认知增强剂，用于治疗神经变性疾病，包括阿尔茨海默病，肌萎缩性侧索硬化，亨廷顿舞蹈病，帕金森病，AIDS相关性痴呆和唐氏综合症，以及治疗精神分裂症和肌阵挛。 还公开了可用于治疗对AMPA受体的正调节起反应的病症的药物组合物和式I的新化合物。

    Substituted semicarbazides and the use thereof
    16.
    发明授权
    Substituted semicarbazides and the use thereof 有权
    取代氨基脲及其用途

    公开(公告)号：US06281211B1

    公开(公告)日：2001-08-28

    申请号：US09601698

    申请日：2000-09-21

    申请人： Sui Xiong Cai ,  Nancy C. Lan ,  Soo Hong-Bae

    发明人： Sui Xiong Cai ,  Nancy C. Lan ,  Soo Hong-Bae

    IPC分类号： A61K31535

    CPC分类号： C07D317/64 ,  C07C281/06 ,  C07C2601/14 ,  C07C2601/18 ,  C07C2602/08 ,  C07C2602/10 ,  C07C2602/42 ,  C07D209/08

    摘要： This invention is related to substituted semicarbazides represented by Formula (I) or a pharmaceutically acceptable salt or prodrug thereof, wherein: R1 and R2 are independently hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, haloalkyl, aryl, aminoalkyl, hydroxyalkyl, alkoxyalkyl or carboxyalkyl; R3, R4, R5 and R6 are independently hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, haloalkyl, aryl, aminoalkyl, hydroxyalkyl, alkoxyalkyl or carboxyalkyl, or R3 and R4 is defined as above, and R5 and R6 together with the nitrogen atom to which they are attached form a heterocycle, including piperidine, piperazine, morpholine; A1 and A2 are independently aryl, heteroaryl, saturated or partially unsaturated carbocycle or saturated or partially unsaturated heterocycle, any of which is optionally substituted; X is one of O, S, NR7, CH2, C(O), NR7C(O), C(O)NR7, SO, SO2 or a covalent bond; where R7 is hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, haloalkyl, aryl, aminoalkyl, hydroxyalkyl, alkoxyalkyl or carboxyalkyl; n is 0, 1, 2 or 3. m is 0, 1, 2 or 3. The invention also is directed to the use of substituted semi-carbazides for the treatment of neuronal damage following global and focal ischemia, for the treatment or prevention of neurodegenerative conditions such as amyotrophic lateral sclerosis (ALS), and for the treatment, prevention or amelioration of both acute or chronic pain, as anticonvulsants, and as antimanic depressants, as anti-nigraine agents, as local anesthetics, as antiarrhythmics and for the treatment or prevention of diabetic neuropathy.

    摘要翻译： 本发明涉及由式（I）表示的取代氨基脲或其药学上可接受的盐或前药，其中：R 1和R 2独立地为氢，烷基，环烷基，烯基，炔基，卤代烷基，芳基，氨基烷基，羟基烷基，烷氧基烷基或羧基烷基 ; R3，R4，R5和R6独立地是氢，烷基，环烷基，烯基，炔基，卤代烷基，芳基，氨基烷基，羟基烷基，烷氧基烷基或羧基烷基，或R3和R4定义如上，R5和R6连同氮原子 它们连接形成杂环，包括哌啶，哌嗪，吗啉; A1和A2独立地是芳基，杂芳基，饱和或部分不饱和的碳环或饱和或部分不饱和的杂环，其中任何一个任选被取代; X是O，S，NR7，CH2，C（O），NR7C（O），C（O）NR7，SO，SO2或共价键之一; 其中R 7是氢，烷​​基，环烷基，烯基，炔基，卤代烷基，芳基，氨基烷基，羟基烷基，烷氧基烷基或羧基烷基; n为0,1,2或3.m为0,1,2或3.本发明还涉及用于治疗全身和局灶性缺血后的神经元损伤的治疗或预防的替代半卡巴肼的用途 的神经退行性疾病如肌萎缩性侧索硬化（ALS），以及用作治疗，预防或改善急性或慢性疼痛的抗惊厥药，作为抗躁狂抑制剂，作为局部麻醉剂作为抗心律失常药物， 治疗或预防糖尿病性神经病变。