利索-全球专利检索

  1. 登录
  2. 注册

搜索结果

76 条记录 (耗时 0.035 秒)

    Akt inhibitors, pharmaceutical compositions, and uses thereof
    53.
    发明授权
    Akt inhibitors, pharmaceutical compositions, and uses thereof 有权

    公开(公告)号：US07378403B2

    公开(公告)日：2008-05-27

    申请号：US10526851

    申请日：2003-09-03

    申请人： Alan P. Kozikowski ,  Phillip Dennis ,  Haiying Sun ,  John Brognard

    发明人： Alan P. Kozikowski ,  Phillip Dennis ,  Haiying Sun ,  John Brognard

    IPC分类号： A61K31/662 ,  A61K31/683 ,  C07F9/09 ,  C07F9/30

    CPC分类号： C07C43/196 ,  C07C2601/14 ,  C07F9/117

    摘要： Disclosed are inhibitors of the serine/threonine kinase Akt, pharmaceutical compositions comprising such inhibitors, and a method of preventing or treating a disease or condition in an animal by the use of such inhibitors. The Akt inhibitors have the formula (I) wherein X and Y are independently selected from the group consisting of O, CF2, CH2, and CHF; wherein A is independently selected from the group consisting of P(O)OH, CH2000H, and CH(COOH)2; R2 is selected from the group consisting of H, OH, isosteres of OH, C1-C25 alkyloxy, C6-C10 aryloxy, C3-C8 cycloalkyloxy, C3-C8 cycloalkyl C1-C6 alkoxy, C2-C22 alkenyloxy, C3-C8 cycloalkenyloxy, C7-C32 aralkyloxy, C7-C32 alkylaryloxy, C9-C32 aralkenyloxy, and C9-C32 alkenylaryloxy; R3-R6 are independently selected from the group consisting of H, OH, isosteres of OH; and R1 and R7 are independently selected from the group consisting of C1-C25 alkyl, C6-C10 aryl, C3-C8 cycloalkyl, C2-C22 alkenyl, C3-C8 cycloalkenyl, C7-C32 aralkyl, C7-C32 alkylaryl, C9-C32 aralkenyl, and C9-C32 alkenylaryl; with the provisos that (i) when X is O, Y is O or CH2, and R3 is H, at least one of R2 and R4-R6 is not OH; (ii) when A is CH2COOH or CH(COOH)2, X and Y cannot be simultaneously O; and (iii) all of R2-R6 are not simultaneously H. The inhibitors can be in the form of a salt also

    Synthesis of dimeric, trimeric, tetrameric pentameric, and higher oligomeric epicatechin-derived procyanidins having 4,8-interflavan linkages and their use to inhibit cancer cell growth through cell cycle arrest
    54.
    发明授权
    Synthesis of dimeric, trimeric, tetrameric pentameric, and higher oligomeric epicatechin-derived procyanidins having 4,8-interflavan linkages and their use to inhibit cancer cell growth through cell cycle arrest 失效
    二聚体，三聚体，四聚体五聚体和更高级低聚表儿茶素衍生的原花青素具有4,8-间氯联的合成及其通过细胞周期停滞抑制癌细胞生长的用途

    公开(公告)号：US07067679B2

    公开(公告)日：2006-06-27

    申请号：US10658241

    申请日：2003-09-09

    申请人： Alan P. Kozikowski ,  Werner Tückmantel ,  Leo J. Romanczyk, Jr.

    发明人： Alan P. Kozikowski ,  Werner Tückmantel ,  Leo J. Romanczyk, Jr.

    IPC分类号： C07D311/26

    CPC分类号： C07D311/62 ,  C07D417/12 ,  C07D417/14

    摘要： Various processes are disclosed for preparing protected epicatechin oligomers having (4β,8)-interflavan linkages. In one process, a tetra-O-protected epicatechin monomer or oligomer is coupled with a protected, C-4 activated epicatechin monomer in the presence of an acidic clay such as a mortmorillonite clay. In another process, a 5,7,3′,4′-benzyl protected or a 3-acetyl-, 5,7,3′,4′-benzyl protected epicatechin or catechin monomer or oligomer is reacted with 3-O-acetyl-4-[(2-benzothiazolyl)thio]-5,7,3′,4′-tetra-O-benzylepicatechin in the presence of silver tetrafluoroborate. In another process, two 5,7,3′,4′-benzyl protected epicatechin monomers activated with 2-(benzothiazolyl)thio groups at the C-4 positions are cross-coupled in the presence of silver tetrofluoroborate. A process is also disclosed for reacting an unprotected epicatechin or catechin monomer with 4-(benzylthio)epicatechin or catechin. The use of naturally-derived and synthetically-prepared procyanidin (4β,8)4-pentamers to treat cancer is also disclosed.

    摘要翻译： 公开了用于制备具有（4beta，8） - 间连环的保护的表儿茶素低聚物的各种方法。 在一个方法中，四氧化物保护的表儿茶素单体或低聚物在保护的C-4活化的表儿茶素单体的存在下，在酸性粘土如失
    桑土粘土的存在下偶合。 在另一种方法中，将5,7,3'，4'-苄基保护或3-乙酰基，5,7,3'，4'-苄基保护的表儿茶素或儿茶素单体或低聚物与3-O-乙酰基 -4 - [（2-苯并噻唑基）硫基] -5,7,3'，4'-四-O-苯甲酸酯在四氟硼酸银的存在下反应。 在另一种方法中，在C-4位上用2-（苯并噻唑基）硫基活化的两个5,7,3'，4'-苄基保护的表儿茶素单体在四氟硼酸银的存在下交联。 还公开了使未保护的表儿茶素或儿茶素单体与4-（苄硫基）表儿茶素或儿茶素反应的方法。 还公开了使用天然衍生的和合成制备的原花青素（4beta，8）4质子以治疗癌症。

    Inhibitors of phosphatidyl myo-inositol cycle
    55.
    发明授权
    Inhibitors of phosphatidyl myo-inositol cycle 失效
    磷脂酰肌醇周期抑制剂

    公开(公告)号：US06667340B1

    公开(公告)日：2003-12-23

    申请号：US09879765

    申请日：2001-06-12

    申请人： Alan P. Kozikowski ,  Lixin Qiao ,  Garth Powis

    发明人： Alan P. Kozikowski ,  Lixin Qiao ,  Garth Powis

    IPC分类号： A61K31215

    CPC分类号： C07F9/117 ,  C07C69/013 ,  C07C69/96 ,  C07C2601/14 ,  C07F9/4081

    摘要： The present invention relates to the preparation and biological activity of 3-deoxy-Dmyo-inositol ether lipid analogs as inhibitors of phosphatidylinositol-3-kinase signaling and cancer cell growth. The compounds of the present invention are useful as anti-tumor 5 agents which effectively inhibit the growth of mammalian cells.

    摘要翻译： 本发明涉及作为磷脂酰肌醇-3-激酶信号传导和癌细胞生长抑制剂的3-脱氧-Dmyo-inositol醚脂质类似物的制备和生物学活性。 本发明的化合物可用作有效抑制哺乳动物细胞生长的抗肿瘤剂5。

    Synthesis of 4&agr;-arylepicatechins
    56.
    发明授权
    Synthesis of 4&agr;-arylepicatechins 失效
    4α-芳基葡聚糖的合成

    公开(公告)号：US06476241B1

    公开(公告)日：2002-11-05

    申请号：US09655360

    申请日：2000-09-05

    申请人： Alan P. Kozikowski ,  Leo J. Romanczyk, Jr. ,  Werner Tückmantel

    发明人： Alan P. Kozikowski ,  Leo J. Romanczyk, Jr. ,  Werner Tückmantel

    IPC分类号： C07D31158

    CPC分类号： C07D311/74 ,  C07D311/62 ,  Y02P20/55

    摘要： Oligomeric procyanidins containing 4&agr;-linked epicatechin units are rare in nature and have hitherto not been accessible through stereoselective synthesis. Provided herein is the preparation of the prototypical dimer, epicatechin-4&agr;,8-epicatechin, by reaction of the protected 4-ketones with aryllithium reagents derived by halogen/metal exchange from the aryl bromides. Removal of the 4-hydroxyl group from the resulting tertiary benzylic alcohols is effected by tri-n-butyltin hydride and trifluoroacetic acid in a completely stereoselective manner, resulting in hydride delivery exclusively from the &bgr; face.

    摘要翻译： 含有4α-连接的表儿茶素单元的低聚原花青素在自然界中是罕见的，并且迄今尚未通过立体选择性合成进行。 本文提供了通过将受保护的4-酮与芳基溴化物的卤素/金属交换衍生的芳基锂试剂反应制备原型二聚体，表儿茶素-4α，8-表儿茶素。 从所得叔苄醇中除去4-羟基由三正丁基锡氢化物和三氟乙酸以完全立体选择的方式进行，从而产生仅从β面产生的氢化物。

    Analogs of cocaine
    57.
    发明授权
    Analogs of cocaine 失效
    可卡因类似物

    公开(公告)号：US06472422B2

    公开(公告)日：2002-10-29

    申请号：US09769774

    申请日：2001-01-25

    申请人： Alan P. Kozikowski ,  Gian Luca Araldi

    发明人： Alan P. Kozikowski ,  Gian Luca Araldi

    IPC分类号： A61K3135

    CPC分类号： C07D211/60 ,  C07B59/002 ,  C07B2200/07 ,  C07D211/12 ,  C07D211/14 ,  C07D211/20 ,  C07D211/22

    摘要： The invention provides a compound of formula (I): wherein R1, R2, R3, and Y have any of the meanings defined in the specification; as well a pharmaceutical composition comprising a compound of formula I; intermediates and methods useful for preparing a compound of formula I; and therapeutic methods for treating drug addiction, Parkinson's disease or depression comprising administering a compound of formula I, to a mammal in need of such treatment.

    摘要翻译： 本发明提供式（I）化合物：其中R1，R2，R3和Y具有本说明书中定义的任何含义; 以及包含式I化合物的药物组合物; 用于制备式I化合物的中间体和方法; 以及用于治疗药物成瘾，帕金森病或抑郁症的治疗方法，包括向需要这种治疗的哺乳动物施用式I化合物。

    Intermediates useful for the synthesis of huperzine A
    58.
    发明授权
    Intermediates useful for the synthesis of huperzine A 有权
    用于合成石杉碱甲的中间体

    公开(公告)号：US06271379B1

    公开(公告)日：2001-08-07

    申请号：US09520497

    申请日：2000-03-08

    申请人： Werner Tückmantel ,  Alan P. Kozikowski

    发明人： Werner Tückmantel ,  Alan P. Kozikowski

    IPC分类号： C07D22122

    CPC分类号： C07D213/64 ,  C07D221/22

    摘要： Intermediates useful for the synthesis of huperzine A represented by the structures below, and methods for their synthesis, wherein: R1 is lower alkyl, benzyl, or substituted benzyl; X is a suitable leaving group; Y is an electron withdrawing group that can subsequently be converted into an amino group; one broken line is present as a carbon—carbon bond and the other broken line is absent, where the broken line forms an unconjugated carbon—carbon double bond, which double bond may be endocyclic whereby n is 3 or the double bond may be exocyclic whereby n is 2.

    摘要翻译： 用于合成由以下结构表示的石杉碱甲的中间体及其合成方法，其中：R1为低级烷基，苄基或取代的苄基; X为合适的离去基团; Y为可以随后为 转化为氨基;一条虚线以碳 - 碳键存在，另一条虚线不存在，其中虚线形成非共轭碳 - 碳双键，该双键可为内环，由此n为3或 双键可以是环外，其中n是2。

    Cocaine analogs
    60.
    发明授权
    Cocaine analogs 失效
    可卡因类似物

    公开(公告)号：US5391744A

    公开(公告)日：1995-02-21

    申请号：US118140

    申请日：1993-09-08

    申请人： Alan P. Kozikowski

    发明人： Alan P. Kozikowski

    IPC分类号： C07D451/12 ,  C07F9/6561 ,  C07F7/02 ,  C07F9/40

    CPC分类号： C07F9/6561 ,  C07D451/12

    摘要： Bioactive cocaine analogs of the general formulae: ##STR1## are provided wherein X' is H or (C.sub.1 -C.sub.5)alkyl, X is H, halo, alkyl, alkoxy, perfluoroalkyl, nitro, alkoxycarbonyl, dialkoxyphosphonyl, acyl, perfluoroacyl, azido (substituted)silyl or (substituted)thio, and Y is H, halo, nitro, amino or (substituted)amino, alkoxycarbonyl, carboxy, alkyl or alkoxy; and the pharmaceutically acceptable salts thereof.

    摘要翻译： 提供以下通式的生物活性可卡因类似物：其中X'为H或（C1-C5）烷基，X为H，卤素，烷基，烷氧基，全氟烷基，硝基，烷氧基羰基，二烷氧基膦酰基，酰基，全氟酰基 （取代）甲硅烷基或（取代的）硫基，Y是H，卤素，硝基，氨基或（取代的）氨基，烷氧基羰基，羧基，烷基或烷氧基; 及其药学上可接受的盐。