公开(公告)号：US07541465B2

公开(公告)日：2009-06-02

申请号：US11443174

申请日：2006-05-31

申请人： Nancy Lan ,  Yan Wang ,  Sui Xiong Cai

发明人： Nancy Lan ,  Yan Wang ,  Sui Xiong Cai

IPC分类号： C07D211/94 ,  C07D211/96 ,  C07D211/98 ,  A61K31/513

CPC分类号： C07C233/05 ,  A61K31/165 ,  C07C237/06 ,  C07C237/08 ,  C07C2601/14 ,  C07D211/46 ,  C07D213/65 ,  C07D213/68 ,  C07D215/20 ,  C07D239/34 ,  C07D241/08 ,  C07D309/12 ,  C07D317/64

摘要： The invention is directed to substituted 2-aminoacetamides represented by formula (II): and to pharmaceutically acceptable salts and prodrugs thereof, wherein the substituents are defined herein. The invention is also directed to the use of substituted 2-aminoacetamides in methods for the treatment of neuronal damage following global and focal ischemia, and for the treatment, prevention or amelioration of pain, as anticonvulsants, as antimanic depressants, 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（II）表示的取代的2-氨基乙酰胺及其药学上可接受的盐和前药，其中取代基在本文中定义。 本发明还涉及取代的2-氨基乙酰胺在治疗全球和局灶性缺血后的神经元损伤的方法中的用途，以及用作治疗，预防或改善疼痛的抗惊厥药作为抗痉挛剂，作为局部麻醉剂，如 抗心律失常药物和治疗或预防糖尿病性神经病变。

公开(公告)号：US06500825B2

公开(公告)日：2002-12-31

申请号：US09933203

申请日：2001-08-21

申请人： Nancy C. Lan ,  Yan Wang ,  Sui Xiong Cai

发明人： Nancy C. Lan ,  Yan Wang ,  Sui Xiong Cai

IPC分类号： A61K31445

CPC分类号： C07C233/05 ,  A61K31/165 ,  C07C237/06 ,  C07C237/08 ,  C07C2601/14 ,  C07D211/46 ,  C07D213/65 ,  C07D213/68 ,  C07D215/20 ,  C07D239/34 ,  C07D241/08 ,  C07D309/12 ,  C07D317/64

摘要： This invention is related to substituted 2-aminoacetamides represented by Formula II: or a pharmaceutically acceptable salt or prodrug thereof, wherein: R1, R2, R3 and R4 are independently hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, haloalkyl, aryl, aminoalkyl, hydroxyalkyl, alkoxyalkyl or carboxyalkyl; R5, R6 and R7 are independently hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, haloalkyl, aryl, aminoalkyl, hydroxyalkyl, alkoxyalkyl or carboxyalkyl, or R5, is defined as above, and R6 and R7 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 or O, S, NR8, CH2, C(O), NR8C(O), C(O)NR8, SO, SO2 or a covalent bond; where R8 is hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, haloalkyl, aryl, aminoalkyl, hydroxyalkyl, alkoxyalkyl or carboxyalkyl; n is 0, 1, 2 or 3. The invention also is directed to the use substituted 2-aminoacetamides 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 pain, as anticonvulsants, and as antimanic depressants, 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II表示的取代的2-氨基乙酰胺或其药学上可接受的盐或前药，其中：R 1，R 2，R 3和R 4独立地为氢，烷基，环烷基，烯基，炔基，卤代烷基，芳基，氨基烷基， 羟烷基，烷氧基烷基或羧基烷基; R5，R6和R7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R5如上所定义，R 6和R 7与它们所在的氮原子一起 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1或O，S，NR8，CH2，C（O），NR8C（O），C（O）NR8，SO，SO2或共价键; 其中R8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; 本发明还涉及使用取代的2-氨基乙酰胺用于治疗全身和局灶性缺血后的神经元损伤，用于治疗或预防神经变性病症如肌萎缩性侧索硬化（ALS） ，作为抗惊厥药，作为抗躁狂抑制剂，作为局部麻醉剂，作为抗心律失常药物和用于治疗或预防糖尿病性神经病变的治疗，预防或改善。

公开(公告)号：US06458843B1

公开(公告)日：2002-10-01

申请号：US09421403

申请日：1999-10-21

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

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

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; 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; 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。

公开(公告)号：US20090240053A1

公开(公告)日：2009-09-24

申请号：US12473887

申请日：2009-05-28

申请人： Nancy C. Lan ,  Yan Wang ,  Sui Xiong Cai

发明人： Nancy C. Lan ,  Yan Wang ,  Sui Xiong Cai

IPC分类号： C07D239/34 ,  C07D213/64 ,  C07D309/32

CPC分类号： C07C233/05 ,  A61K31/165 ,  C07C237/06 ,  C07C237/08 ,  C07C2601/14 ,  C07D211/46 ,  C07D213/65 ,  C07D213/68 ,  C07D215/20 ,  C07D239/34 ,  C07D241/08 ,  C07D309/12 ,  C07D317/64

摘要： The invention is directed to substituted 2-aminoacetamides represented by formula (II): and to pharmaceutically acceptable salts and prodrugs thereof, wherein the substituents are defined herein. The invention is also directed to the use of substituted 2-aminoacetamides in methods for the treatment of neuronal damage following global and focal ischemia, and for the treatment, prevention or amelioration of pain, as anticonvulsants, as antimanic depressants, 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（II）表示的取代的2-氨基乙酰胺及其药学上可接受的盐和前药，其中取代基在本文中定义。 本发明还涉及取代的2-氨基乙酰胺在治疗全球和局灶性缺血后的神经元损伤的方法中的用途，以及用作治疗，预防或改善疼痛的抗惊厥药作为抗痉挛剂，作为局部麻醉剂，如 抗心律失常药物和治疗或预防糖尿病性神经病变。

公开(公告)号：US5891871A

公开(公告)日：1999-04-06

申请号：US821638

申请日：1997-03-20

申请人： Haiji Xia ,  Sui Xiong Cai ,  George Field ,  Nancy C. Lan ,  Yan Wang

发明人： Haiji Xia ,  Sui Xiong Cai ,  George Field ,  Nancy C. Lan ,  Yan Wang

IPC分类号： A61K31/00 ,  A61K31/55 ,  A61K31/551 ,  A61P25/08 ,  A61P25/16 ,  A61P25/28 ,  C07D243/02 ,  C07D243/04 ,  C07D243/10 ,  C07D491/04 ,  C07D491/056

CPC分类号： C07D491/04 ,  C07D243/02 ,  C07D243/10

摘要： The invention relates to substituted 2,3-benzodiazepin-4-ones which are antagonists or positive modulators of AMPA receptors, and the use thereof for treating, preventing or ameliorating neuronal loss associated with stroke, global and focal ischemia, CNS trauma, hypoglycemia and surgery, as well as treating or ameliorating neurodegenerative diseases including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease and Down's syndrome, treating, preventing or ameliorating the adverse consequences of the overstimulation of the excitatory amino acids, treating or ameliorating anxiety, psychosis, convulsions, chronic pain, glaucoma, CMV retinitis, urinary incontinence, muscular spasm and inducing anesthesia, as well as for treating or ameliorating the adverse consequences of excitatory amino acid deficiency such as schizophrenia, Alzheimer's disease and malnutrition and neural maldevelopment, and as cognition enhancers. The invention also is directed to the process for the preparation of the substituted 2,3-benzodiazepin-4-ones.

摘要翻译： 本发明涉及作为AMPA受体的拮抗剂或阳性调节剂的取代2,3-苯并二氮杂-4-酮及其用于治疗，预防或改善与中风，全身和局灶性缺血，CNS创伤，低血糖和 手术，以及治疗或改善神经变性疾病，包括阿尔茨海默病，肌萎缩性侧索硬化，亨廷顿病，帕金森病和唐氏综合症，治疗，预防或改善兴奋性氨基酸过度刺激的不良后果，治疗或改善焦虑，精神病 ，抽搐，慢性疼痛，青光眼，CMV视网膜炎，尿失禁，肌肉痉挛和诱导麻醉，以及治疗或改善兴奋性氨基酸缺乏症如精神分裂症，阿尔茨海默病和营养不良以及神经发育不良的不良后果以及认知 增强剂。 本发明还涉及制备取代的2,3-苯并二氮杂-4-酮的方法。

公开(公告)号：US07872127B2

公开(公告)日：2011-01-18

申请号：US12473887

申请日：2009-05-28

申请人： Nancy C. Lan ,  Yan Wang ,  Sui Xiong Cai

发明人： Nancy C. Lan ,  Yan Wang ,  Sui Xiong Cai

IPC分类号： C07D211/94 ,  C07D211/96 ,  C07D211/98

CPC分类号： C07C233/05 ,  A61K31/165 ,  C07C237/06 ,  C07C237/08 ,  C07C2601/14 ,  C07D211/46 ,  C07D213/65 ,  C07D213/68 ,  C07D215/20 ,  C07D239/34 ,  C07D241/08 ,  C07D309/12 ,  C07D317/64

摘要： The invention is directed to substituted 2-aminoacetamides represented by formula (II): and to pharmaceutically acceptable salts and prodrugs thereof, wherein the substituents are defined herein. The invention is also directed to the use of substituted 2-aminoacetamides in methods for the treatment of neuronal damage following global and focal ischemia, and for the treatment, prevention or amelioration of pain, as anticonvulsants, as antimanic depressants, 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（II）表示的取代的2-氨基乙酰胺及其药学上可接受的盐和前药，其中取代基在本文中定义。 本发明还涉及取代的2-氨基乙酰胺在治疗全球和局灶性缺血后的神经元损伤的方法中的用途，以及用作治疗，预防或改善疼痛的抗惊厥药作为抗痉挛剂，作为局部麻醉剂，如 抗心律失常药物和治疗或预防糖尿病性神经病变。

公开(公告)号：US06479484B1

公开(公告)日：2002-11-12

申请号：US09554739

申请日：2000-08-08

申请人： Nancy C. Lan ,  Yan Wang ,  Sui Xiong Cai

发明人： Nancy C. Lan ,  Yan Wang ,  Sui Xiong Cai

IPC分类号： A61K314965

CPC分类号： C07C233/05 ,  A61K31/165 ,  C07C237/06 ,  C07C237/08 ,  C07C2601/14 ,  C07D211/46 ,  C07D213/65 ,  C07D213/68 ,  C07D215/20 ,  C07D239/34 ,  C07D241/08 ,  C07D309/12 ,  C07D317/64

摘要： The invention is directed to substituted 2-aminoacetamides represented by formula (II): and to pharmaceutically acceptable salts and prodrugs thereof, wherein the substituents are defined herein. The invention is also directed to the use of substituted 2-aminoacetamides in methods for the treatment of neuronal damage following global and focal ischemia, and for the treatment, prevention or amelioration of pain, as anticonvulsants, as antimanic depressants, 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（II）表示的取代的2-氨基乙酰胺及其药学上可接受的盐和前药，其中取代基在本文中定义。 本发明还涉及取代的2-氨基乙酰胺在治疗全球和局灶性缺血后的神经元损伤的方法中的用途，以及用作治疗，预防或改善疼痛的抗惊厥药作为抗痉挛剂，作为局部麻醉剂，如 抗心律失常药物和治疗或预防糖尿病性神经病变。

公开(公告)号：US08426431B2

公开(公告)日：2013-04-23

申请号：US12986587

申请日：2011-01-07

申请人： Nancy C. Lan ,  Yan Wang ,  Sui Xiong Cai

发明人： Nancy C. Lan ,  Yan Wang ,  Sui Xiong Cai

IPC分类号： A61K31/505 ,  A61K31/47 ,  A61K31/165

CPC分类号： C07C233/05 ,  A61K31/165 ,  C07C237/06 ,  C07C237/08 ,  C07C2601/14 ,  C07D211/46 ,  C07D213/65 ,  C07D213/68 ,  C07D215/20 ,  C07D239/34 ,  C07D241/08 ,  C07D309/12 ,  C07D317/64

摘要： The invention is directed to substituted 2-aminoacetamides represented by formula (II): and to pharmaceutically acceptable salts and prodrugs thereof, wherein the substituents are defined herein. The invention is also directed to the use of substituted 2-aminoacetamides in methods for the treatment of neuronal damage following global and focal ischemia, and for the treatment, prevention or amelioration of pain, anxiety, or manic depression, as anticonvulsants, as antimanic depressants, 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（II）表示的取代的2-氨基乙酰胺及其药学上可接受的盐和前药，其中取代基在本文中定义。 本发明还涉及取代的2-氨基乙酰胺在治疗全球和局灶性缺血后的神经元损伤的方法中的用途，以及用作治疗，预防或改善作为抗惊厥药物的抗痉挛剂的疼痛，焦虑或躁狂抑郁症 ，作为局部麻醉剂，作为抗心律失常药物和治疗或预防糖尿病性神经病变。

公开(公告)号：US06716818B2

公开(公告)日：2004-04-06

申请号：US09987417

申请日：2001-11-14

申请人： Sui Xiong Cai ,  Eckard Weber ,  Yan Wang ,  Gordon B Mills ,  Douglas R Green

发明人： Sui Xiong Cai ,  Eckard Weber ,  Yan Wang ,  Gordon B Mills ,  Douglas R Green

IPC分类号： A61K3806

CPC分类号： C07D295/205 ,  C07C237/22 ,  C07C271/22 ,  C07C311/19 ,  C07C2601/08 ,  C07C2601/14 ,  C07D311/16 ,  C07D311/66

摘要： The present invention is directed to novel dipeptide thereof, represented by the general Formula I: where R1-R3, X and Y are defined herein. The present invention also relates to the discovery that compounds having Formula I are potent inhibitors of caspases and apoptotic cell death. Therefore, the inhibitors of this invention can retard or block cell death in a variety of clinical conditions in which the loss of cells, tissues or entire organs occurs.

摘要翻译： 本发明涉及由通式I表示的新型二肽：其中R1-R3，X和Y如本文所定义。 本发明还涉及发现具有式I的化合物是胱天蛋白酶的有效抑制剂和凋亡性细胞死亡。 因此，本发明的抑制剂可以在发生细胞，组织或整个器官的损失的各种临床病症中阻滞或阻断细胞死亡。

公开(公告)号：US06638947B2

公开(公告)日：2003-10-28

申请号：US10003249

申请日：2001-12-06

申请人： Yan Wang ,  Sui Xiong Cai ,  John F. W. Keana

发明人： Yan Wang ,  Sui Xiong Cai ,  John F. W. Keana

IPC分类号： A61K31175

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; 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.