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    • 5. 发明申请
    • INDOLINE SCAFFOLD SHP-2 INHIBITORS AND CANCER TREATMENT METHOD
    • INDOLINE SCAFFOLD SHP-2抑制剂和癌症治疗方法
    • WO2010011666A3
    • 2010-04-22
    • PCT/US2009051276
    • 2009-07-21
    • UNIV SOUTH FLORIDAWU JIELAWRENCE NICHOLAS JSEBTI SAID M
    • WU JIELAWRENCE NICHOLAS JSEBTI SAID M
    • C07D403/12A61K31/496A61P35/00
    • C07D405/06C07D209/08C07D215/36
    • The subject invention concerns methods and compounds for inhibiting Shp2. In one embodiment, a compound of the invention has a chemical structure as shown in formula I or II: wherein X, Y, and Z are independently N or S; R1 is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, any of which can be optionally substituted with one or more of halogen; alkyl; heteroalkyl; -COOH; -C(R3)3, wherein R3 can independently be any of -H or halogen; or -OR4, wherein R4 can be any of H, alkyl. or heteroalkyl; R2 is alkyl, alkylcarbonyl, heteroalkylcarbonyl, aryl, arylcarbonyl, heterocycloalkylcarbonyl, cycloalkylcarbonyl, or -C(O)NR6R7, any of which can be optionally substituted with one or more of halogen; alkyl; heteroalkyl; carbonyl; -OR4, wherein R4 can be -H, alkyl, or heteroalkyl; -OH; -C(RO3)3, wherein R3 can independently be any of -H or halogen; aryl, which can be substituted with one or more of halogen or - OR4; heterocycloalkyl; or -C(O)OR5, wherein R5 can be -H or alkyl; R6 and R7 are independently -H, alkyl, heteroalkyl, aryl, or heteroaryl; and R1 is H or alkyl; or a pharmaceutically acceptable salt or hydrate thereof.
    • 本发明涉及用于抑制Shp2的方法和化合物。 在一个实施方案中,本发明的化合物具有如式I或II所示的化学结构:其中X,Y和Z独立地为N或S; R 1是环烷基,杂环烷基,芳基或杂芳基,它们中的任何一个可以任选地被一个或多个卤素取代; 烷基; 杂; -COOH; -C(R 3)3,其中R 3可以独立地为-H或卤素中的任何一个; 或-OR 4,其中R 4可以是H,烷基中的任何一个。 或杂烷基; R 2是烷基,烷基羰基,杂烷基羰基,芳基,芳基羰基,杂环烷基羰基,环烷基羰基或-C(O)NR 6 R 7,它们中的任何一个可以任选地被一个或多个卤素取代; 烷基; 杂; 羰; -OR 4,其中R 4可以是-H,烷基或杂烷基; -哦; -C(RO 3)3,其中R 3可以独立地为-H或卤素中的任何一个; 芳基,其可以被一个或多个卤素或-OR 4取代; 杂环; 或-C(O)OR 5,其中R 5可以是-H或烷基; R6和R7独立地为-H,烷基,杂烷基,芳基或杂芳基; 并且R1是H或烷基; 或其药学上可接受的盐或水合物。
    • 9. 发明申请
    • METHOD FOR DECREASING NICOTINE AND OTHER SUBSTANCE USE IN HUMANS
    • 降低人类免疫球蛋白和其他物质使用的方法
    • WO2004069144A3
    • 2005-10-27
    • PCT/IB2004002083
    • 2004-02-09
    • ARIZONA HEALTH CONSULTING GROUWU JIE
    • WU JIE
    • A61K20060101A61K36/00A61K36/185A61K35/78
    • A61K36/185
    • A method for decreasing nicotine and other substance use in humans is disclosed. Tetrahydroberberine (THB) and its analogs, l-Tetrahydropalmatine (1­THP) and l-Stepholidine (l-SPD), are present in and can be isolated from several plants in the Magnoliidae superorder. According to the disclosed method, THB and its analogs are used to block nicotine-induced DA release, and modulate heterologous or homoeric expression of human nicotinic acetylcholine receptors (nAChR) in humans. Specifically, THB exhibits bi-directory modulation of a4ß2-nAChR-mediated currents induced by nicotine. THB also shows predominant inhibition on homologously expressed alpha7-nAChR function. Thus, according to the disclosed method, THB is used to simultaneous blockade midbrain DA system function, the brain reward center, and neuronal a4ß2- and a7-nAChR function, the major nicotine targets in the brain. Therefore, THB and its analogs serve as a novel class of natural compounds to decrease nicotine dependence in humans. Furthermore, other substances such as alcohol, cocaine, and opiates, also operate by triggering the brain reward center, resulting in a cycle of substance or alcohol abuse. THB and its analogs can be used to decrease use of substances such as alcohol, cocaine, and opiates. Finally, because THB and its analogs are DA antagonists, THB and its analogs can also be used as a treatment for Parkinson's Disease, Alzheimer's Disease and schizophrenia.
    • 公开了一种减少人体中尼古丁和其他物质使用的方法。 四氢小檗碱(THB)及其类似物1-四氢al嗪(1THP)和1- Step hol啶(1-SPD)存在于并可以从Magnoliidae超级序列中的几种植物中分离出来。 根据所公开的方法,泰铢及其类似物用于阻断尼古丁诱导的DA释放,并调节人类烟碱乙酰胆碱受体(nAChR)的异源或同源性表达。 具体来说,泰铢表现了由尼古丁诱导的a4β2-nAChR介导的电流的双目录调制。 THB也显示出对同源表达的α7-nAChR功能的主要抑制作用。 因此,根据所公开的方法,泰铢用于同时封锁中脑DA系统功能,脑回报中心和神经元a4ß2-和a7-nAChR功能,大脑中主要的尼古丁目标。 因此,泰铢及其类似物作为一类新型天然化合物,可以减少人体尼古丁依赖。 此外,其他物质如酒精,可卡因和阿片剂也可以通过触发脑回报中心进行操作,导致物质或酒精滥用的循环。 泰铢及其类似物可用于减少酒精,可卡因和阿片剂等物质的使用。 最后,由于泰铢及其类似物是DA拮抗剂,泰铢及其类似物也可用作帕金森病,阿尔茨海默病和精神分裂症的治疗。