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68 条记录 (耗时 0.034 秒)

    Methods for designing inhibitors of serine/threonine-kinases and tyrosine kinases
    22.
    发明授权
    Methods for designing inhibitors of serine/threonine-kinases and tyrosine kinases 失效
    设计丝氨酸/苏氨酸激酶和酪氨酸激酶抑制剂的方法

    公开(公告)号：US6162613A

    公开(公告)日：2000-12-19

    申请号：US25580

    申请日：1998-02-18

    申请人： Michael Shin-San Su ,  Ted Fox ,  Keith Philip Wilson ,  Ursula A. Germann

    发明人： Michael Shin-San Su ,  Ted Fox ,  Keith Philip Wilson ,  Ursula A. Germann

    IPC分类号： C12N15/09 ,  C12N9/12 ,  C12N9/99 ,  C12N15/54 ,  C12Q1/48 ,  G06F19/00

    CPC分类号： C12N9/1205 ,  G01N2333/9121

    摘要： The invention relates to methods for designing inhibitors of serine/threonine kinases and tyrosine kinases, particularly MAP kinases, through the use of ATP-binding site mutants of those kinases. The methods of this invention take advantage of the fact that the mutant kinases are capable of binding inhibitory compounds of other kinases with greater affinity than the corresponding wild-type kinase. The invention further relates to the mutant kinases themselves and crystallizable co-complexes of the mutant kinase and the inhibitory compound.

    摘要翻译： 本发明涉及通过使用这些激酶的ATP结合位点突变体设计丝氨酸/苏氨酸激酶和酪氨酸激酶抑制剂，特别是MAP激酶的方法。 本发明的方法利用突变体激酶能够以比相应的野生型激酶更大的亲和力结合其它激酶的抑制性化合物的事实。 本发明还涉及突变型激酶本身和突变型激酶与抑制性化合物的可结晶共配合物。

    Pyridazines as interleukin-1.beta. converting enzyme inhibitors
    23.
    发明授权
    Pyridazines as interleukin-1.beta. converting enzyme inhibitors 失效
    哒嗪作为白细胞介素-1β转换酶抑制剂

    公开(公告)号：US6121266A

    公开(公告)日：2000-09-19

    申请号：US444984

    申请日：1995-05-19

    申请人： Roland E. Dolle ,  Denton W. Hoyer ,  Tina Morgan Ross ,  James M. Rinker ,  Stanley J. Schmidt ,  Mark A. Ator

    发明人： Roland E. Dolle ,  Denton W. Hoyer ,  Tina Morgan Ross ,  James M. Rinker ,  Stanley J. Schmidt ,  Mark A. Ator

    IPC分类号： A61K31/50 ,  A61P29/00 ,  A61P35/00 ,  A61P43/00 ,  C07D237/24 ,  C07D401/04 ,  C07D403/04 ,  A61K31/4965 ,  A61K31/497

    CPC分类号： C07D401/04 ,  C07D237/24 ,  C07D403/04

    摘要： Disclosed are compounds of the formula (I) and pharmaceutically acceptable salts thereof: ##STR1## wherein R.sub.1 is a halogen, or an oxygen linked leaving group including an aromatic ether, an alkyl sulfonate, an aryl sulfonate, an alkyl phosphonate, an aryl phosphonate, an alkyl phosphate or aryl phosphate;R.sub.2 is COOR.sub.5, C(.dbd.O)NH(CHR.sub.5).sub.m --COOR.sub.5, NH(CHR.sub.5).sub.m CON(R.sub.5)R.sub.6, C(.dbd.O)N(R.sub.5)R.sub.6 or NH(CHR.sub.5).sub.m OH;R.sub.3 is H or alkyl;R.sub.4 is H, substituted or unsubstituted aryl, heteroaryl or alkyl;R.sub.5 and R.sub.6 are independently H, lower alkyl, aryl, hydroxy alkyl, amino alkyl, heteroaryl, lower alkylene-aryl, lower alkylene-heteroaryl or lower cycloalkyl; and m=0-6; pharmaceutical compositions containing the compounds; and a method for inhibiting interleukin-1.beta. protease activity in a mammal utilizing the compounds and compositions.

    摘要翻译： 公开了式（I）的化合物及其药学上可接受的盐：其中R1是卤素，或含有芳香族醚，烷基磺酸酯，芳基磺酸酯，烷基膦酸酯，芳基膦酸酯，烷基 磷酸盐或芳基磷酸盐; R2是COOR5，C（= O）NH（CHR5）m -COOR5，NH（CHR5）mCON（R5）R6，C（= O）N（R5）R6或NH（CHR5） R3是H或烷基; R4是H，取代或未取代的芳基，杂芳基或烷基; R5和R6独立地为H，低级烷基，芳基，羟基烷基，氨基烷基，杂芳基，低级亚烷基 - 芳基，低级亚烷基 - 杂芳基或低级环烷基; m = 0-6; 含有这些化合物的药物组合物; 以及利用该化合物和组合物抑制哺乳动物中白细胞介素-1β蛋白酶活性的方法。

    Biosensors, extracorporeal devices and methods for detecting substances using crosslinked protein crystals
    25.
    发明授权
    Biosensors, extracorporeal devices and methods for detecting substances using crosslinked protein crystals 失效
    生物传感器，体外装置和使用交联蛋白质晶体检测物质的方法

    公开(公告)号：US6004768A

    公开(公告)日：1999-12-21

    申请号：US484238

    申请日：1995-06-07

    申请人： Manuel A. Navia ,  Nancy L. St. Clair

    发明人： Manuel A. Navia ,  Nancy L. St. Clair

    IPC分类号： A61K38/43 ,  A61K38/46 ,  C07K1/107 ,  C07K5/072 ,  C12M1/40 ,  C12N9/14 ,  C12N9/20 ,  C12N9/36 ,  C12N9/54 ,  C12N9/66 ,  C12N9/80 ,  C12N9/82 ,  C12N11/00 ,  C12Q1/00 ,  C12Q1/37 ,  G01N33/531 ,  C12Q1/34 ,  C12M1/34

    CPC分类号： C12N9/2462 ,  C07K1/1077 ,  C07K5/0613 ,  C12N11/00 ,  C12N9/14 ,  C12N9/20 ,  C12N9/54 ,  C12N9/6448 ,  C12N9/80 ,  C12N9/82 ,  C12Q1/00 ,  C12Q1/003 ,  C12Q1/37 ,  G01N33/531 ,  A61K38/00 ,  Y10S435/817 ,  Y10S530/81

    摘要： Proteins such as enzymes and antibodies are immobilized by crosslinking crystals of the proteins such as microcrystals having a cross-section of 10.sup.-1 mm or less with a multifunctional crosslinking agent. The crosslinked protein crystals may be lyophilized for storage. Crystals of an enzyme such as thermolysin, elastase, asparaginase, lysozyme, lipase or urease may be crosslinked to provide crosslinked enzyme crystals that retain at least 91% activity after incubation for three hours in the presence of a concentration of Pronase.TM. that causes the soluble uncrosslinked form of the enzyme to lose at least 94% of its initial activity under the same conditions. A preferred Pronase.TM.:enzyme ratio is 1:40. Crosslinked enzyme or antibody crystals may be used in an assay, diagnostic kit or biosensor for detecting an analyte, in an extracorporeal device for altering a component of a fluid, in producing a product such as using crosslinked thermolysin crystals to produce aspartame, in separating a substance from a mixture, and in therapy.

    摘要翻译： 蛋白质如酶和抗体通过用多官能交联剂交联具有10-1mm或更小截面的微晶的蛋白质的晶体来固定。 交联的蛋白质晶体可以冻干以储存。 可以交联酶，例如嗜热菌蛋白酶，弹性蛋白酶，天冬酰胺酶，溶菌酶，脂肪酶或脲酶的晶体以提供交联的酶晶体，其在浓度为Pronase TM的浓度存在下孵育3小时后保持至少91％的活性，其导致可溶性 未交联形式的酶在相同条件下损失至少94％的初始活性。 Pronase TM：酶比为1:40。 交联的酶或抗体晶体可用于用于检测分析物的测定，诊断试剂盒或生物传感器，用于改变流体组分的体外装置中，用于在产生例如使用交联的嗜热溶蛋白晶体产生阿斯巴甜的产物时分离 物质从混合物和治疗。

    Butyrate prodrugs derived from lactic acid
    26.
    发明授权
    Butyrate prodrugs derived from lactic acid 失效
    丁酸酯前体药物衍生自乳酸

    公开(公告)号：US5880152A

    公开(公告)日：1999-03-09

    申请号：US814945

    申请日：1997-03-10

    申请人： Roger D. Tung ,  Bigin Li

    发明人： Roger D. Tung ,  Bigin Li

    IPC分类号： A61K31/00 ,  A61K31/215 ,  A61K31/22 ,  A61K48/00 ,  A61P1/00 ,  A61P7/00 ,  A61P7/06 ,  A61P17/14 ,  A61P35/00 ,  A61P43/00 ,  C07C69/66 ,  C07C69/68 ,  A01N37/02

    CPC分类号： C07C69/68 ,  A61K31/22

    摘要： This invention relates to butyrate prodrugs derived from lactic acid and pharmaceutical compositions and methods employing them, either alone or in combination with other agents, for increasing gamma globin and fetal hemoglobin in a patient. These compounds, compositions and methods are particularly effective in treating .beta.-hemoglobinopathies, including sickle cell syndromes and .beta.-thalassemia syndromes. This invention relates to the use of these prodrugs, alone or in combination with other agents, to stimulate cell differentiation which prevents proliferation of malignant cells. These methods are particularly useful in treating cancer, especially malignant hematological disorders. In addition, this invention relates to the use of these prodrugs in treating inflammatory bowel diseases.

    摘要翻译： 本发明涉及由乳酸衍生的丁酸酯前药以及使用它们的单独或与其它试剂组合的药物组合物和方法，用于增加患者中的γ珠蛋白和胎儿血红蛋白。 这些化合物，组合物和方法在治疗β-血红蛋白病，包括镰状细胞综合征和β-地贫综合征中特别有效。 本发明涉及这些前药单独使用或与其它试剂组合来刺激细胞分化，其可防止恶性细胞的增殖。 这些方法特别适用于治疗癌症，特别是恶性血液病。 此外，本发明涉及这些前药在治疗炎症性肠病中的用途。

    Crosslinked enzyme crystals
    27.
    发明授权
    Crosslinked enzyme crystals 失效
    交联酶晶体

    公开(公告)号：US5618710A

    公开(公告)日：1997-04-08

    申请号：US17510

    申请日：1993-02-12

    申请人： Manuel A. Navia ,  Nancy L. St. Clair

    发明人： Manuel A. Navia ,  Nancy L. St. Clair

    IPC分类号： A61K38/43 ,  A61K38/46 ,  C07K1/107 ,  C07K5/072 ,  C12M1/40 ,  C12N9/14 ,  C12N9/20 ,  C12N9/36 ,  C12N9/54 ,  C12N9/66 ,  C12N9/80 ,  C12N9/82 ,  C12N11/00 ,  C12Q1/00 ,  C12Q1/37 ,  G01N33/531 ,  C12N1/00 ,  C07K17/00 ,  C12P1/00 ,  G01N33/543

    CPC分类号： C12N9/2462 ,  C07K1/1077 ,  C07K5/0613 ,  C12N11/00 ,  C12N9/14 ,  C12N9/20 ,  C12N9/54 ,  C12N9/6448 ,  C12N9/80 ,  C12N9/82 ,  C12Q1/00 ,  C12Q1/003 ,  C12Q1/37 ,  G01N33/531 ,  A61K38/00 ,  Y10S435/817 ,  Y10S530/81

    摘要： A protein such as an enzyme of antibody is immobilized by crosslinking crystals of the protein with a multifunctional crosslinking agent. The crosslinked protein crystals may be lyophilized for storage. A preferred protein is an enzyme such as thermolysin, elastase, asparaginase, lysozyme, lipase or urease. Crosslinked enzyme crystals preferably retain at least 91% activity after incubation for three hours in the presence of a concentration of Pronase.TM. that causes the soluble uncrosslinked form of the enzyme to lose at least 94% of its initial activity under the same conditions. A preferred enzyme:Pronase.TM. ratio is 1:40. Enzyme crystals that are crosslinked may be microcrystals having a cross-section of 10.sup.-1 mm or less. Crosslinked enzyme or antibody crystals may be used in an assay, diagnostic kit or biosensor for detecting an analyte, in an extracorporeal device for altering a component of a fluid, in producing a product such as using crosslinked thermolysin crystals to produce aspartame, in separating a substance from a mixture, and in therapy.

    摘要翻译： 通过用多官能交联剂交联蛋白质的晶体来固定蛋白质如抗体的酶。 交联的蛋白质晶体可以冻干以储存。 优选的蛋白质是酶，例如嗜热菌蛋白酶，弹性蛋白酶，天冬酰胺酶，溶菌酶，脂肪酶或脲酶。 交联的酶晶体优选保持在Termase TM浓度存在下温育3小时后的至少91％的活性，其导致可溶性的未交联形式的酶在相同条件下损失至少94％的初始活性。 优选的酶：Pronase TM比为1:40。 交联的酶晶体可以是横截面为10-1mm或更小的微晶。 交联的酶或抗体晶体可用于用于检测分析物的测定，诊断试剂盒或生物传感器，用于改变流体组分的体外装置中，用于在产生例如使用交联的嗜热溶蛋白晶体产生阿斯巴甜的产物时分离 物质从混合物和治疗。

    Systems and methods for inline sampling
    29.
    发明授权
    Systems and methods for inline sampling 有权
    用于在线抽样的系统和方法

    公开(公告)号：US09038488B2

    公开(公告)日：2015-05-26

    申请号：US13776563

    申请日：2013-02-25

    申请人： Vertex Pharmaceuticals, Inc.

    发明人： James E. Sinclair ,  B. Albert Griffin ,  Minh Vuong

    IPC分类号： G01N1/20 ,  G01N9/02

    CPC分类号： G01N9/02 ,  G01N1/20

    摘要： Methods and devices for inline sampling of a bulk material, such as a powder, are provided. The material's bulk density can be determined from samples drawn using methods and devices described herein. One embodiment of a method of sampling a material allows the material to flow through a sampling compartment, closes off the flow of material below the sampling compartment, builds up a column of material through the sampling compartment, shifts the sampling compartment to remove a slice of material in the column, and places the slice of material into a sample container. A device for sampling a material is provided in another embodiment. The device includes an inlet, an outlet aligned with the inlet, and a sample collector. The sample collector can include at least one through hole and be configured to move such that the at least one through hole can be moved into and out of alignment with the inlet and the outlet.

    摘要翻译： 提供了散装材料如粉末的在线取样方法和装置。 可以使用本文所述的方法和装置绘制的样品来确定材料的体积密度。 采样材料的方法的一个实施例允许材料流过采样室，封闭采样室下方的材料流，通过采样室建立一列材料，移动采样室以移除一片 柱中的材料，并将切片材料放入样品容器中。 在另一个实施例中提供用于取样材料的装置。 该装置包括入口，与入口对准的出口和样品收集器。 样品收集器可以包括至少一个通孔，并且被配置为移动，使得至少一个通孔可以移动进入和离开与入口和出口对齐。

    Aminopyridine derivatives having aurora a selective inhibitory action
    30.
    发明授权
    Aminopyridine derivatives having aurora a selective inhibitory action 有权
    具有极光选择性抑制作用的氨基吡啶衍生物

    公开(公告)号：US08367690B2

    公开(公告)日：2013-02-05

    申请号：US13259620

    申请日：2010-03-15

    申请人： Hayley Binch ,  Masaya Hashimoto ,  Michael Mortimore ,  Mitsuru Ohkubo ,  Tomoko Sunami

    发明人： Hayley Binch ,  Masaya Hashimoto ,  Michael Mortimore ,  Mitsuru Ohkubo ,  Tomoko Sunami

    IPC分类号： A01N43/54 ,  A61K31/505

    CPC分类号： A61K31/535 ,  C07D401/14 ,  C07D417/14

    摘要： The present invention relates to a compound of Formula (I): wherein: R1 is H, —NHCOOR1a, C5-6 cycloalkyl, or phenyl; where the cycloalkyl and phenyl each independently may be substituted with one to three of the same or different substituents selected from R10; R1a is C1-3 alkyl which may be substituted with one to three of the same or different substituents selected from F and Cl; R2 is H, —COOH, —CH2 COOH, —COOR2a, or —CH2COOR2a; R2a is C1-2 alkyl, where the alkyl may be substituted with one to three of the same or different substituents selected from halogen atoms; R3 is H, C1-6 alkyl, where the alkyl may be substituted with one to three of the same or different substituents selected from R11; R10 is F, Cl, CF3, or C1-2 alkyl; R11 is halogen atom, hydroxy, or cyano; W is selected from: W2a is H, halogen atom, cyano, C1-2 alkyl, or C3-5 cycloalkyl, or a pharmaceutically acceptable salt or ester thereof.

    摘要翻译： 本发明涉及式（I）的化合物：其中：R1是H，-NHCOOR1a，C5-6环烷基或苯基; 其中环烷基和苯基各自独立地可以被一至三个相同或不同的选自R 10的取代基取代; R 1a是可以被一至三个相同或不同的选自F和Cl的取代基取代的C 1-3烷基; R2是H，-COOH，-CH2COOH，-COOR2a或-CH2COOR2a; R2a是C1-2烷基，其中烷基可以被一至三个相同或不同的选自卤素原子的取代基取代; R3是H，C1-6烷基，其中烷基可以被一至三个相同或不同的选自R11的取代基取代; R 10是F，Cl，CF 3或C 1-2烷基; R11是卤素原子，羟基或氰基; W选自：W2a是H，卤素原子，氰基，C1-2烷基或C3-5环烷基，或其药学上可接受的盐或酯。