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    GLYCOPEPTIDE ANTIBIOTIC ANALOGS EFFECTIVE AGAINST VANCOMYCIN-RESISTANT BACTERIAL STRAINS
    2.
    发明申请
    GLYCOPEPTIDE ANTIBIOTIC ANALOGS EFFECTIVE AGAINST VANCOMYCIN-RESISTANT BACTERIAL STRAINS 有权
    抗乙型脑炎抗生素类抗生素类抗生素

    公开(公告)号：US20160272682A1

    公开(公告)日：2016-09-22

    申请号：US14236876

    申请日：2012-08-03

    申请人： Dale L. Boger

    发明人： Dale L. Boger

    IPC分类号： C07K9/00 ,  C07K7/06

    CPC分类号： C07K9/008 ,  A61K38/00 ,  A61K38/14 ,  C07K7/06

    摘要： The invention is directed to glycopeptide antibiotics and their aglycones that are engineered to overcome bacterial resistance by replacement of a single, specific peptide carboxamide group in the core peptide of the glycopeptide antibiotic with an amidine group. The amidine pseudopeptide analog of the glycopeptide is effective in killing vancomycin-resistant bacteria at therapeutically achievable concentrations in a patient. For example, a [ψ[C(═NH)NH]Tpg4]- vancomycin aglycon designed to exhabit the dual binding to D-Ala-D-Ala and D-Ala-D-Lac needed to reinstate activity against vancomycin-resistant bacteria has been shown to overcome a common mode of bacterial resistance to the “last resort” antibiotics of the glycopeptide class. The pseudopeptide amidine analogs can be prepared from corresponding pseudopeptide thioamide analogs, which can be prepared synthetically, semi-synthetically, or biosynthetically.

    摘要翻译： 本发明涉及糖肽抗生素及其糖苷配基，其被工程化以通过用脒基团替代糖肽抗生素的核心肽中的单个特异性肽羧酰胺基来克服细菌耐药性。 糖肽的脒假肽类似物在患者中以治疗可达到的浓度杀死万古霉素抗性细菌是有效的。 例如，设计用于排除与D-Ala-D-Ala和D-Ala-D-Lac的双重结合的[ψ[C（= N NH）NH] Tpg4]万古霉素苷元需要恢复对万古霉素抗性细菌的活性 已被证明可克服对糖肽类的“最后手段”抗生素的细菌耐药性的共同模式。 假肽脒类似物可以由相应的假肽硫代酰胺类似物制备，其可以合成，半合成或生物合成制备。

    10′-fluorinated Vinca alkaloids provide enhanced biological activity against MDR cancer cells
    3.
    发明授权
    10′-fluorinated Vinca alkaloids provide enhanced biological activity against MDR cancer cells 有权
    10'氟化长春花生物碱提供增强的抗MDR癌细胞的生物活性

    公开(公告)号：US08940754B2

    公开(公告)日：2015-01-27

    申请号：US13580340

    申请日：2011-02-09

    申请人： Dale L. Boger

    发明人： Dale L. Boger

    IPC分类号： A01N43/42 ,  A61K31/44 ,  C07D487/00 ,  C07D491/00 ,  C07D513/00 ,  C07D519/04

    CPC分类号： C07D519/04

    摘要： A 10′-fluoro-vinca alkaloid compound or its pharmaceutically acceptable salt is disclosed, as are methods of its preparation and use. A disclosed 10′-fluoro-vinca alkaloid compound has better cytotoxic potency against leukemia and cancer cell lines, and is about 8-times more cytotoxic to a multiple drug resistant cancer cell line than is a parental 10′-unsubstituted vinca alkaloid.

    摘要翻译： 公开了10'-氟 - 长春花生物碱化合物或其药学上可接受的盐，以及其制备和使用的方法。 公开的10'-氟 - 长春花碱生物碱化合物对白血病和癌细胞系具有更好的细胞毒性效力，并且比无亲本的10'-未取代的长春花生物碱多数药物抗性癌细胞系的细胞毒性高约8倍。

    Methods for inhibiting angiogenesis and tumor growth
    4.
    发明授权
    Methods for inhibiting angiogenesis and tumor growth 有权
    抑制血管生成和肿瘤生长的方法

    公开(公告)号：US07368478B2

    公开(公告)日：2008-05-06

    申请号：US11439918

    申请日：2006-05-24

    申请人： Dale L. Boger ,  David A. Cheresh

    发明人： Dale L. Boger ,  David A. Cheresh

    IPC分类号： A01N47/10 ,  A61K31/27 ,  A61K31/21 ,  A61K31/235 ,  A61K31/16

    CPC分类号： A61K31/195 ,  A61K31/165 ,  A61K31/27

    摘要： Angiogenesis, tumor growth, and metalloproteinase 2 (MMP2) interaction with integrin-αvβ3 are inhibited by an inhibitor compound of formula: wherein G1 and G2 are each independently —NH—C(O)—O—(CH2)v—(C6H4)—X3 ; Y1 and Y2 are each independently —OH or C1-C4 alkoxy; X1 and X2 are each independently halo or C1-C4 alkoxy; X3 is fluoro, nitro, C1-C4 alkyl, C1-C4 alkoxy, or C1-C4 perfluoroalkyl; Z is —C≡C—, —C6H4—, cis-CH═CH—, trans-CH═CH—, cis-CH2—CH═CH—CH2—, trans-CH2—CH═CH—CH2—, 1,4-naphthyl, cis-1,3-cyclohexyl, trans-1,3-cyclohexyl, cis-1,4-cyclohexyl, or trans-1,4-cyclohexyl; A is H or a covalent bond; m and n are each 1; t is an integer having a value of 0 or 1; p and r are each 2, and v is 1; with the proviso that when A is H, t is 0, and when A is a covalent bond, t is 1.

    摘要翻译： 血管生成，肿瘤生长和金属蛋白酶2（MMP2）与整联蛋白α3β3的相互作用被下式的抑制剂化合物抑制：其中G 1， （O）-O-（CH 2）2 - （C 1 -C 6） 6 H 4）-X 3; Y 1和Y 2各自独立地为-OH或C 1 -C 4烷氧基; X 1和X 2各自独立地为卤素或C 1 -C 4烷氧基; X 3是氟，硝基，C 1 -C 4烷基，C 1 -C 4 烷氧基或C 1 -C 4全氟烷基; Z是-C≡C - ， - C 6 H 4 - ，顺式-CH-CH-，反式-CH-CH-，顺式-CH 2 -CH-CH-CH 2 - ，反式-CH 2 -CH-CH 2 CH 2 - ，1,4 顺式-1,3-环己基，反式-1,3-环己基，顺式-1,4-环己基或反式-1,4-环己基; A是H或共价键; m和n分别为1; t是值为0或1的整数; p和r各自为2，v为1; 条件是当A为H时，t为0，当A为共价键时，t为1。

    Inhibitors of fatty acid amide hydrolase
    5.
    发明授权
    Inhibitors of fatty acid amide hydrolase 有权
    脂肪酸酰胺水解酶抑制剂

    公开(公告)号：US06462054B1

    公开(公告)日：2002-10-08

    申请号：US09536842

    申请日：2000-03-27

    申请人： Dale L. Boger

    发明人： Dale L. Boger

    IPC分类号： A61K31435

    CPC分类号： A61K31/4196 ,  A61K31/415 ,  A61K31/42 ,  A61K31/424 ,  A61K31/4245 ,  A61K31/428 ,  A61K31/433 ,  A61K31/435 ,  A61K31/44 ,  A61K31/4965 ,  A61K31/503 ,  A61K31/519 ,  A61K31/53

    摘要： Potent inhibitors of fatty acid amide hydrolase (FAAH) are constructed having Ki's below 200 pM and activities 102-103 times more potent than the corresponding trifluoromethyl ketones. The potent inhibitors combine several features, viz.: 1.) an &agr;-keto heterocylic head group; 2.) a hydrocarbon linkage unit employing an optimal C12-C8 chain length; and 3.) a phenyl or other &pgr;-unsaturation corresponding to the arachidonyl &Dgr;8.9/&Dgr;11.12 and/or oleyl &Dgr;9.10 positions. A preferred &agr;-keto heterocylic head group is &agr;-keto N4 oxazolopyridine, with incorporation of a second weakly basic nitrogen. Fatty acid amide hydrolase is an enzyme responsible for the degradation of oleamide (an endogenous sleep-inducing lipid) and anandamide (an endogenous ligand for cannabinoid receptors).

    摘要翻译： 脂肪酸酰胺水解酶（FAAH）的强力抑制剂被构建为具有低于200pM的Ki，并且相对于相应的三氟甲基酮的活性为102-103倍。 有效的抑制剂结合了几个特征，即：1.）一个α-酮杂环头基; 2.）使用最佳C12-C8链长的烃链单元; 和3.）对应于花生四烯基DELTA8.9 / DELTA11.12和/或油基DELTA9.10位置的苯基或其它不饱和键。 优选的α-酮基杂环头基是α-酮基N4恶唑啉吡啶，并加入第二弱碱性氮。 脂肪酸酰胺水解酶是负责降解油酰胺（内源性睡眠诱导脂质）和anandamide（大麻素受体的内源性配体）的酶。

    TRICYCLIC INHIBITORS OF FATTY ACID AMIDE HYDROLASE
    10.
    发明申请
    TRICYCLIC INHIBITORS OF FATTY ACID AMIDE HYDROLASE 有权
    脂肪酸酰胺水解三元抑制剂

    公开(公告)号：US20100216750A1

    公开(公告)日：2010-08-26

    申请号：US12600736

    申请日：2008-05-30

    申请人： Dale L. Boger

    发明人： Dale L. Boger

    IPC分类号： A61K31/60 ,  C12N9/99 ,  C07D413/04 ,  C07D401/14 ,  A61K31/4427 ,  A61P25/22 ,  A61P25/28

    CPC分类号： C07D413/14 ,  C07D413/04

    摘要： A series of substituted oxazole compounds having an alpha keto side chain at the 2 position and an aromatic, heteroaromatic or heterocycle substituent at the 5 position are disclosed. These compounds exhibit inhibition of fatty acid amid hydrolase and arc useful for treatment of malconditions involving that enzyme.

    摘要翻译： 公开了一系列在2位具有α酮侧链的取代的恶唑化合物和5位上的芳族，杂芳族或杂环取代基。 这些化合物表现出对水解酶中的脂肪酸的抑制，并且可用于治疗涉及该酶的病态。