公开(公告)号：US08999993B2

公开(公告)日：2015-04-07

申请号：US13640188

申请日：2011-04-06

申请人： Roger Francis Martin ,  Jonathan White ,  Pavel Lobachevsky ,  David Winkler ,  Colin Skene ,  Sebastian Marcuccio

发明人： Roger Francis Martin ,  Jonathan White ,  Pavel Lobachevsky ,  David Winkler ,  Colin Skene ,  Sebastian Marcuccio

IPC分类号： A61K31/496 ,  C07D235/20 ,  C07D401/14 ,  C07D235/18 ,  C07D403/14 ,  C07D405/14 ,  C07D413/04 ,  C07D413/14

CPC分类号： C07D401/14 ,  C07D235/18 ,  C07D403/14 ,  C07D405/14 ,  C07D413/04 ,  C07D413/14

摘要： The invention relates to novel compounds, processes for their preparation and their use in protecting biological materials from radiation damage (radioprotection). Preferred compounds of the invention are those of Formula II, as follows: wherein W represents —N(R1R2) where R1 and R2 are not both hydrogen and where they may together form a 5, 6 or 7 membered ring structure, —NHN(R1R2), —NHR3N(R1R2), —NHR3OR2, —N(R3)R3OR2, —N(R1)R3OR3OR3, —OR3NR1R2, —OR3 or W represents piperidyl, piperazinyl, morpholinyl, thiomorpholinyl or diazepanyl each of which may be optionally substituted by C1 to C4 alkyl, C2 to C4 alkenyl, —N(CO)N(R1R2), —N(CO)OR1, —N(CO)OR3OH, —(CO)NR1R2, —R3(CO)NR1R2, —R3OR1, —OR1, —N(R1R2) or —NH—; R1 and R2 are the same or different and are selected from hydrogen, C1 to C4 alkyl or C2 to C4 alkenyl; R3 is a C1 to C4 alkyl or C2 to C4 alkenyl group or chain; Z is the same or different and represents N or CH; Z′ is the same or different and represents N or C; X represents CH, N or NH, where is a double bond when X is CH or N and a single bond when X is NH; X′ represents N or NH, wherein when X is CH or NX′ is NH and wherein X and X′ are different and further where is a double bond when X′ is N and a single bond when X′ is NH; Q represents H, alkoxyl, —NR1R2, F or Cl; Q1 is absent when Z′ is N and when Z′ is C it represents H, alkoxyl, —NR1R2, F or Cl; A represents a five to ten membered single or multiple ring structure with heterocyclic N or O located at the ortho position, said ring including optional double bonds, substitutions and/or other heteroatoms and pharmaceutically acceptable derivatives thereof.

公开(公告)号：US20130109678A1

公开(公告)日：2013-05-02

申请号：US13640188

申请日：2011-04-06

申请人： Roger Francis Martin ,  Jonathan White ,  Pavel Lobachevsky ,  David Winkler ,  Colin Skene ,  Sebastian Maruccio

发明人： Roger Francis Martin ,  Jonathan White ,  Pavel Lobachevsky ,  David Winkler ,  Colin Skene ,  Sebastian Maruccio

IPC分类号： C07D401/14 ,  C07D413/14 ,  C07D403/14 ,  C07D405/14

CPC分类号： C07D401/14 ,  C07D235/18 ,  C07D403/14 ,  C07D405/14 ,  C07D413/04 ,  C07D413/14

摘要： The invention relates to novel compounds, processes for their preparation and their use in protecting biological materials from radiation damage (radioprotection). Preferred compounds of the invention are those of Formula II, as follows: wherein W represents —N(R1R2) where R1 and R2 are not both hydrogen and where they may together form a 5, 6 or 7 membered ring structure, —NHN(R1R2), —NHR3N(R1R2), —NHR3OR2, —N(R3)R3OR2, —N(R1)R3OR3OR3, —OR3NR1R2, —OR3 or W represents piperidyl, piperazinyl, morpholinyl, thiomorpholinyl or diazepanyl each of which may be optionally substituted by C1 to C4 alkyl, C2 to C4 alkenyl, —N(CO)N(R1R2), —N(CO)OR1, —N(CO)OR3OH, —(CO)NR1R2, —R3(CO)NR1R2, —R3OR1, —OR1, —N(R1R2) or —NH—; R1 and R2 are the same or different and are selected from hydrogen, C1 to C4 alkyl or C2 to C4 alkenyl; R3 is a C1 to C4 alkyl or C2 to C4 alkenyl group or chain; Z is the same or different and represents N or CH; Z′ is the same or different and represents N or C; X represents CH, N or NH, where is a double bond when X is CH or N and a single bond when X is NH; X′ represents N or NH, wherein when X is CH or NX′ is NH and wherein X and X′ are different and further where is a double bond when X′ is N and a single bond when X′ is NH; Q represents H, alkoxyl, —NR1R2, F or Cl; Q1 is absent when Z′ is N and when Z′ is C it represents H, alkoxyl, —NR1R2, F or Cl; A represents a five to ten membered single or multiple ring structure with heterocyclic N or O located at the ortho position, said ring including optional double bonds, substitutions and/or other heteroatoms and pharmaceutically acceptable derivatives thereof.

摘要翻译： 本发明涉及新化合物，其制备方法及其在保护生物材料免受辐射损伤（放射防护）中的应用。 本发明优选的化合物是式II的化合物，其如下：其中W表示-N（R 1 R 2），其中R 1和R 2不是氢并且它们可以一起形成5,6或7元环结构，-NHN（R 1 R 2 ），-NHR3N（R1R2），-NHR3OR2，-N（R3）R3OR2，-N（R1）R3OR3OR3，-OR3NR1R2，-OR3或W表示哌啶基，哌嗪基，吗啉基，硫代吗啉基或二氮杂环丁基， C 1 -C 4烷基，C 2〜C 4烯基，-N（CO）N（R 1 R 2），-N（CO）OR 1，-N（CO）OR 3 OH， - （CO）NR 1 R 2，-R 3（CO）NR 1 R 2，-R 3 OR 1， -OR1，-N（R1R2）或-NH-; R 1和R 2相同或不同，并且选自氢，C 1至C 4烷基或C 2至C 4链烯基; R3是C1-C4烷基或C2-C4链烯基或链; Z相同或不同，代表N或CH; Z'相同或不同，表示N或C; X表示CH，N或NH，当X为CH或N时为双键，当X为NH时为单键; X'表示N或NH，其中当X是CH或NX'是NH并且其中X和X'不同，并且当X'是N时是双键，当X'是NH时，是单键; Q表示H，烷氧基，-NR1R2，F或Cl; 当Z'为N时，Q1不存在，当Z'为C时，它代表H，烷氧基，-NR1R2，F或Cl; A表示具有位于邻位的杂环N或O的五至十元单环或多环结构，所述环包括任选的双键，取代和/或其它杂原子及其药学上可接受的衍生物。

公开(公告)号：US20070140970A1

公开(公告)日：2007-06-21

申请号：US10590784

申请日：2005-02-25

申请人： Roger Martin ,  Jonathan White ,  Pavel Lobachevsky ,  Thomas Karagiannis

发明人： Roger Martin ,  Jonathan White ,  Pavel Lobachevsky ,  Thomas Karagiannis

IPC分类号： A61K49/00 ,  A61K39/395 ,  C07K16/46

CPC分类号： A61K51/0459 ,  A61K31/4184 ,  C07C45/292 ,  C07D235/20 ,  C07C47/55

摘要： The present invention relates to cell targeting conjugates and in particular, but not exclusively, to methods of their use in selectively eliminating and in selectively imaging target cells. The invention also relates to processes for production of the conjugates and to intermediate compounds that may be used in production of a specific class of cell targeting conjugates. In one embodiment there is provided a cell targeting conjugate comprising the following components that are covalently conjugated via a linker that is degradable within the target cells: i) a DNA minor groove binding ligand incorporating an effective Auger electron-emitting and/or gamma-emitting and/or positron-emitting atom or photoactive moiety; ii) a target cell specific protein or peptide that is capable of internalisation by target cells.

摘要翻译： 本发明涉及细胞靶向缀合物，特别是但不排他地涉及它们用于选择性地消除和选择性地成像靶细胞的方法。 本发明还涉及可用于生产特定类别的细胞靶向缀合物的缀合物和中间体化合物的制备方法。 在一个实施方案中，提供了细胞靶向缀合物，其包含通过可在靶细胞内可降解的接头共价共轭的以下成分：i）掺入有效俄歇电子发射和/或γ发射的DNA小沟结合配体 和/或正电子发射原子或光活性部分; ii）能够靶细胞内化的靶细胞特异性蛋白质或肽。