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    The synthesis of naturally occuring ecteinascidins and related compounds
    7.
    发明公开
    The synthesis of naturally occuring ecteinascidins and related compounds 有权
    Herstellung vonnatürlichvorkommenden Ecteinascidinen und verwandten Verbindungen

    公开(公告)号：EP2305689A1

    公开(公告)日：2011-04-06

    申请号：EP10181699.9

    申请日：2003-02-04

    申请人： Pharma Mar S.A.U.

    发明人： Menchaca, Roberto ,  Martinez, Valentin ,  Rodriguez, Alberto ,  Rodriguez, Natividad ,  Gallego, Pilar ,  Cuevas, Carmen ,  Munt, Simon ,  Manzanares, Ignacio

    IPC分类号： C07D515/22 ,  A61K31/50 ,  A61P35/00

    CPC分类号： C07D515/18 ,  C07D515/22

    摘要： The present invention provides compounds of formula:

    wherein
    R a and R b together with the carbon to which they are attached form a group of formula:

    where each X 1 is independently selected from hydrogen or substituted or unsubstituted R', OR', -(C=O)R', substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, and substituted or unsubstituted aralkyl; wherein R' is selected from the group consisting of H, OH, NO 2 NH 2 , SH, CN, halogen, C(=O)H, C(=O)CH 3 , CO 2 H, CO 2 CH 3 , C 1 -C 6 alkyl, alkenyl, alkynyl, aryl, aralkyl and heterocyclic;
    where R d is a substituted or unsubstituted R', OR',-(C=O)R', substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, or substituted or unsubstituted aralkyl; wherein R' is selected from the group consisting of OH, NO 2 , NH 2 , SH, CN, halogen, C(=O)H, C(=O)CH 3 , CO 2 H, CO 2 CH 3 , C 1 -C 6 alkyl, alkenyl, alkynyl, aryl, aralkyl and heterocyclic;
    R 7 is -OCH 3 and R 8 is -OH or R 7 and R 8 together form a group -O-CH 2 -O-;
    R 12a is hydrogen, acyl, alkenyl, or alkyl-O-CO-;
    R 21 is -H, OH or CN;
    X is -O- or -NH-;
    R 5 and R 18 are -OX 1 , wherein each X 1 is independently selected from hydrogen, substituted or unsubstituted C 1 -C 18 alkyl, substituted or unsubstituted C 2 -C 18 alkenyl, substituted or unsubstituted C 2 C 18 alkynyl, substituted or unsubstituted aryl, and -C(=O)R' wherein R' is selected from hydrogen, OH, NO 2 , NH 2 , SH, CN, halogen, C 1 -C 6 alkyl, alkenyl, alkynyl, aryl, aralkyl, and heterocyclic.

    摘要翻译： 本发明提供下式的化合物：其中R a和R b与它们所连接的碳一起形成下式：其中每个X 1独立地选自氢或取代或未取代的R'，OR'， - （ C = O）R'，取代或未取代的烷基，取代或未取代的烷氧基，取代或未取代的烯基，取代或未取代的炔基，取代或未取代的芳基和取代或未取代的芳烷基; 其中R'选自H，OH，NO 2 NH 2，SH，CN，卤素，C（= O）H，C（= O）CH 3，CO 2 H，CO 2 CH 3，C C 1 -C 6烷基，烯基，炔基，芳基，芳烷基和杂环基; 其中R d是取代或未取代的R'，OR'， - （C = O）R'，取代或未取代的烷基，取代或未取代的烷氧基，取代或未取代的烯基，取代或未取代的炔基，取代或未取代的芳基或取代的 或未取代的芳烷基; 其中R'选自OH，NO 2，NH 2，SH，CN，卤素，C（= O）H，C（= O）CH 3，CO 2 H，CO 2 CH 3，C 1 -C 6烷基，烯基，炔基，芳基，芳烷基和杂环基; R 7是-OCH 3，R 8是-OH或R 7和R 8一起形成-O-CH 2 -O-基团; R 12a是氢，酰基，烯基或烷基-O-CO-; R 21是-H，OH或CN; X是-O-或-NH-; R 5和R 18是-OX 1，其中每个X 1独立地选自氢，取代或未取代的C 1 -C 18烷基，取代或未取代的C 2 -C 18烯基，取代或未取代的C 2 C 18炔基，取代的 或未取代的芳基，和-C（= O）R'，其中R'选自氢，OH，NO 2，NH 2，SH，CN，卤素，C 1 -C 6烷基，烯基，炔基，芳基，芳烷基， 和杂环。

    ATAXIA TELENGIECTASIA AND RAD3-RELATED (ATR) PROTEIN KINASE INHIBITORS
    10.
    发明公开
    ATAXIA TELENGIECTASIA AND RAD3-RELATED (ATR) PROTEIN KINASE INHIBITORS 审中-公开
    ATAXIA TELENGIECTASIA和RAD3相关（ATR）蛋白激酶抑制剂

    公开(公告)号：EP3207031A1

    公开(公告)日：2017-08-23

    申请号：EP15850553.7

    申请日：2015-10-13

    申请人： Atrin Pharmaceuticals LLC

    发明人： BRESLIN, Henry, Joseph ,  GILAD, Oren

    IPC分类号： C07D241/04

    CPC分类号： C07D519/00 ,  A61K31/4985 ,  A61K31/5377 ,  A61K45/06 ,  C07D498/08 ,  C07D498/18 ,  C07D515/08 ,  C07D515/18

    摘要： A macrocyclic compound having the structure of Formula (A), wherein each of R1 and R2 is independently (i) a 5-6 membered monocyclic aromatic ring containing 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or (ii) an 8-10 membered bicyclic aromatic ring containing 0-6 heteroatoms independently selected from nitrogen, oxygen, or sulfur. Each R1 and R2 may independently be substituted by 0, 1, 2, 3, or 4 substituents. Z1 represents a covalent bond, an atom, or a functional group comprising a grouping of atoms, wherein the grouping of atoms includes at least one heteroatom selected from the group consisting of N, O, P, and S. Also, Z1 may represent (i) a 5-6 membered monocyclic aromatic ring containing 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or (ii) an 8-10 membered bicyclic aromatic ring containing 0-6 heteroatoms independently selected from nitrogen, oxygen, or sulfur. Z2 represents a covalent bond, an atom, or a functional group comprising a grouping of atoms, wherein the grouping of atoms includes at least one heteroatom selected from the group consisting of N, O, P, and S. Variable v is an integer having a value of 1 or 0. T is a carbon atom, a nitrogen atom, a sulfur atom, or an oxygen atom. L is a linking group covalently bonded to T when v has a value of 1 or L is covalently bonded to R1 when v has a value of 0. L is covalently bonded to Z2 when Z2 is an atom or a functional group comprising grouping of atoms and/or L is covalently bonded to R2 when Z2 is a covalent bond. Each of R3, R4 and R5 may be the same as or different from each other and each is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, heteroaryl, aralkyl, and heteraralkyl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, heteroaryl, aralkyl, and heteraralkyl is optionally substituted by one or more suitable substituents.

    摘要翻译： 其中R 1，R 2，R 3，R 4和R 5如本文所定义。 还提供了包含大环化合物的药物组合物和用于治疗患者癌症的方法，其包括向患者施用大环化合物。