ANALOGS OF ADAMANTYLUREAS AS SOLUBLE EPOXIDE HYDROLASE INHIBITORS
    81.
    发明申请
    ANALOGS OF ADAMANTYLUREAS AS SOLUBLE EPOXIDE HYDROLASE INHIBITORS 审中-公开
    ADAMANTYLUREAS作为可溶性环氧化物水解酶抑制剂的模拟物

    公开(公告)号:WO2017017048A1

    公开(公告)日:2017-02-02

    申请号:PCT/EP2016/067620

    申请日:2016-07-25

    Abstract: N-(2-oxaadamantan-1-yl)ureas of formula I, where R3 is H, C 1 -C 3 alkyl, cyclohexyl or phenyl; R is -[CH 2 ] n -Y; n is 0-15; in -[CH 2 ] n - 0-n/3 of the methylene groups are optionally replaced by non adjacent oxygen atoms; and Y is a 3- or 4-substituted phenyl, a 3- or 4-substituted cyclohexyl, a N-substituted piperidin-4-yl, a N-substituted piperidin-3-yl, a di- or tri-fluorosubstituted phenyl, 4-chloro-3-trifluoromethylphenyl, 3-chloro-4-trifluoromethylphenyl, 4-fluoro-3-trifluoromethylphenyl, or 3-fluoro-4-trifluoromethylphenyl; have epoxide hydrolase (sEH) inhibitory activities similar to those of their N-(adamantan-1-yl)urea analogs. Thus, compounds I are useful as API for the treatment of sEH mediated diseases. Besides, in general, compounds (I) have higher water solubilities and lower melting points, what make them more promising from the point of view of pharmacokinetics and formulation.

    Abstract translation: 式I的N-(2-氧杂金刚烷-1-基)脲,其中R 3是H,C 1 -C 3烷基,环己基或苯基; R是 - [CH 2] n -Y; n为0-15; 亚甲基的 - [CH 2] n -O-N / 3任选被不相邻的氧原子取代; 并且Y是3-或4-取代的苯基,3-或4-取代的环己基,N-取代的哌啶-4-基,N-取代的哌啶-3-基,二或三氟取代的苯基, 4-氯-3-三氟甲基苯基,3-氟-4-三氟甲基苯基或3-氟-4-三氟甲基苯基; 具有与其N-(金刚烷-1-基)脲类似物类似的环氧化物水解酶(sEH)抑制活性。 因此,化合物I可用作治疗sEH介导的疾病的API。 此外,通常化合物(I)具有较高的水溶性和较低的熔点,从药代动力学和制剂的观点来看,它们更有希望。

    BACTERIAL EXOPOLYSACCHARIDE
    86.
    发明申请
    BACTERIAL EXOPOLYSACCHARIDE 审中-公开
    细菌异丙醇

    公开(公告)号:WO2015117985A1

    公开(公告)日:2015-08-13

    申请号:PCT/EP2015/052249

    申请日:2015-02-04

    CPC classification number: C12R1/38 A61K8/60 A61K8/73 A61K8/99 A61Q19/08 C12P19/04

    Abstract: Pseudomonas sp. CECT8437 is a cold-adapted bacterium isolated from a marine sediment sample collected from Deception Island (South Shetland Islands, Antarctica) that is noted for the highly mucous appearance of its colonies. An exopolysaccharide (EPS) is produced by this strain, which comprises glucose, galactose, fucose and uronic acid in a molar ratio of 2:1:1:0.3 approximately. The EPS shows the following weight percentages, approximately: 37.29% C, 6.17% H, 2.25% N, and 0.41 % S. Its molecular weight (MW) is higher than 2 x 10 6 Da. The EPS is useful for the following purposes: (i) cryoprotectant agent; (ii) emulsifier agent; (iii) thickening, stabilizing or structural agent; (iv) dermoprotective agent; and (v) agent for increasing skin elasticity. The EPS can be used in cosmetic compositions.

    Abstract translation: 假单胞菌属 CECT8437是从海岛沉积物样品中分离得到的一种冷适应细菌,该海洋沉积物样品是从其殖民地高度粘稠的外观上被认为是从南非的南部设得兰德群岛(South Shetland Islands,南极洲)收集的。 通过该菌株产生外多糖(EPS),其包含葡萄糖,半乳糖,岩藻糖和糖醛酸,摩尔比约为2:1:1:0.3。 EPS显示以下重量百分比,约:37.29%C,6.17%H,2.25%N和0.41%S.其分子量(MW)高于2×10 6 Da。 EPS用于以下目的:(i)冷冻保护剂; (ii)乳化剂; (iii)增稠剂,稳定剂或结构剂; (iv)皮肤保护剂; 和(v)增加皮肤弹性的药剂。 EPS可用于化妆品组合物中。

    AUTOMATIC QUALITY CONTROL OF FORCED SPIROMETRY
    87.
    发明申请
    AUTOMATIC QUALITY CONTROL OF FORCED SPIROMETRY 审中-公开
    强迫螺旋自动质量控制

    公开(公告)号:WO2015036013A1

    公开(公告)日:2015-03-19

    申请号:PCT/EP2013/068732

    申请日:2013-09-10

    CPC classification number: A61B5/7221 A61B5/087 A61B5/7239 A61B5/746

    Abstract: The invention provides a method, and corresponding system and apparatus, for assessing the acceptability of an individual forced spirometry manoeuvre as well as an indication of the quality of a full spirometry test, comprising more than one manoeuvre. An automatic validation of the spirometry measurements are provided by identifying wrong/flawed tests, or acceptable/valid tests. Hence an indication is provided regarding the quality of the measurements performed, and feedback or indication is provided regarding the reliability, or confidence level, of the manoeuvre or set of manoeuvres. Preferably no expert intervention is necessary, however a minimum intervention might be considered useful in order to rule out any doubtful manoeuvres and dissipate ambiguities.

    Abstract translation: 本发明提供了一种用于评估个体强制肺量计操作的可接受性的方法和相应的系统和装置,以及包括多于一个动作的完整肺量计测试的质量的指示。 通过识别错误/有缺陷的测试或可接受/有效的测试来提供肺量计测量的自动验证。 因此,提供关于所执行的测量的质量的指示,并且提供关于机动或一组动作的可靠性或置信水平的反馈或指示。 最好不需要专家干预,但是最低限度的干预措施可能被认为是有用的,以排除任何可疑的动作并消除歧义。

    METHOD OF MEASURING ATTENTION
    88.
    发明申请
    METHOD OF MEASURING ATTENTION 审中-公开
    测量方法

    公开(公告)号:WO2013159841A1

    公开(公告)日:2013-10-31

    申请号:PCT/EP2012/076654

    申请日:2012-12-21

    Inventor: SUPER, Hans

    CPC classification number: A61B5/168 A61B3/02 A61B3/113 G08B21/06

    Abstract: In a first aspect, the present invention provides a method of measuring attention of a person comprising presenting one or more stimulus aimed at attracting attention of the person; and obtaining positions of the eyes of the person. The method further comprises detecting one or more eye fixations from the obtained positions of the eyes; and measuring the angle of convergence of the eyes over time from the obtained positions of the eyes during one or more of the detected eye fixations.

    Abstract translation: 在第一方面,本发明提供了一种衡量人的注意力的方法,包括呈现一种或多种旨在吸引人的注意的刺激; 并获得该人的眼睛的位置。 该方法还包括从所获得的眼睛位置检测一个或多个眼睛定位; 并且在一个或多个检测到的眼睛固定期间从所获得的眼睛位置测量眼睛随时间的会聚的角度。

    METHOD OF BINDING SITE AND BINDING ENERGY DETERMINATION BY MIXED EXPLICIT SOLVENT SIMULATIONS
    89.
    发明申请
    METHOD OF BINDING SITE AND BINDING ENERGY DETERMINATION BY MIXED EXPLICIT SOLVENT SIMULATIONS 审中-公开
    混合显式溶剂模拟确定场地和结合能的方法

    公开(公告)号:WO2013092922A2

    公开(公告)日:2013-06-27

    申请号:PCT/EP2012/076500

    申请日:2012-12-20

    CPC classification number: G06F19/706 G06F19/16 G06F19/701 G06F19/702

    Abstract: It is described a method of binding site and binding energy determination by mixed explicit solvent all-atoms molecular dynamics simulations. The macromolecular target for which high affinity binders are sought is simulated in several mixed solvent environments comprising water and at least one amphiphilic organic co-solvent. The simulations are run so that the mixture of solvents are free to react to the presence of the target without the addition of any forces other than those found in the original potential. A correction is applied that helps dissociating the distribution of the different chemical groups found in the amphiphilic organic solvents when calculating their free energies of binding. Additionally, a second correction can be applied accounting for the aggregation of said solvents. The correction helps determining more meaningful absolute, and more accurate relative free energies of binding that can be applied in the rational design of new binders to macromolecular targets.

    Abstract translation: 描述了通过混合显式溶剂全原子分子动力学模拟来确定结合位点和结合能确定的方法。 在包含水和至少一种两亲性有机共溶剂的几种混合溶剂环境中模拟寻求高亲和力粘合剂的大分子靶。 进行模拟,以便溶剂混合物自由地对目标物的存在作出反应,而不会增加原始电位以外的任何力。 在计算它们的结合自由能时,应用修正来帮助分离在两亲有机溶剂中发现的不同化学基团的分布。 此外,考虑到所述溶剂的聚集,可以应用第二次校正。 校正有助于确定更有意义的绝对和更准确的相对结合自由能,可用于合理设计新结合物到大分子靶标。

    INDOLENINAS FLUORADAS ÚTILES PARA EL TRATAMIENTO DEL CÁNCER
    90.
    发明申请
    INDOLENINAS FLUORADAS ÚTILES PARA EL TRATAMIENTO DEL CÁNCER 审中-公开
    用于治疗癌症的氟化吲哚

    公开(公告)号:WO2013079754A1

    公开(公告)日:2013-06-06

    申请号:PCT/ES2012/070830

    申请日:2012-11-27

    CPC classification number: C07D209/30

    Abstract: Los compuestos de fórmula (I) o sus sales farmacéuticamente aceptables, o sus estereoisómeros o mezcla de estereoisómeros, donde:R 1 , R 2 , R 4, R 5 , y R 7 , son independientemente seleccionados del grupo que consiste en H, Cl,C(=O)O(C 1 -C 4 )alquilo, O(C 1 -C 4 )alquilo; y (C 1 -C 4 )alquilo; R 3 se selecciona del grupo que consiste en H 1 , Cl, C(=O)O(C 1 -C 4 )alquilo, O(C 1 -C 4 )alquilo, (C 1 -C 4 )alquilo, pirrolidinil-1-carbonil, and morfolin-1-carbonil; R 6 es seleccionado del grupo que consiste en H and (C 1 -C 4 )alquilo; y R 8 es seleccionado del grupo que consiste en H, F, Br, (C 1 -C 4 )alquilo, y fenilo; inhiben la proliferación celular de células tumorales independientemente de la proteína p53 y también pueden inducir apoptosis en varias células tumorales independientemente de la proteína p53, siendo útiles para el tratamiento de varios tipos de cáncer.

    Abstract translation: 式(I)化合物或其药学上可接受的盐或其立体异构体或其立体异构体的混合物,其中:R 1,R 2,R 4,R 5和R 7独立地选自H,Cl,C(= O)(C 1 -C 4)烷基,O(C 1 -C 4)烷基; 和(C 1 -C 4)烷基; R 3选自H1,Cl,C(= O)O(C1-C4)烷基,O(C1-C4)烷基,(C1-C4)烷基,吡咯烷基-1-羰基和吗啉 -羰; R 6选自H和(C 1 -C 4)烷基; 并且R 8选自H,F,Br,(C 1 -C 4)烷基和苯基; 所述化合物独立于p53蛋白质抑制肿瘤细胞的细胞增殖,并且能够独立于p53蛋白诱导各种肿瘤细胞的凋亡,这使得它们可用于治疗各种类型的癌症。

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