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1. 发明申请

WO2014007650A1 COMPOUNDS AND METHODS FOR SELECTIVE IMAGING AND/OR ABLATION 审中-公开
标题翻译：用于选择性成像和/或消除的化合物和方法
公开(公告)号：WO2014007650A1
公开(公告)日：2014-01-09
申请号：PCT/NZ2012/000243
申请日：2012-12-21
申请人： AUCKLAND UNISERVICES LIMITED , ANDERSON, Robert, Forbes , SMAILL, Jeffery, Bruce , PATTERSON, Adam, Vorn , ASHOORZADEH, Amir , ACKERLEY, David, Francis , COPP, Janine, Naomi , MOWDAY, Alexandra, Marie , WILLIAMS, Elsie, May , GUISE, Christopher, Paul , KOCH, Cameron , KACHUR, Alex , DOLBIER, William R. Jr
发明人： ANDERSON, Robert, Forbes , SMAILL, Jeffery, Bruce , PATTERSON, Adam, Vorn , ASHOORZADEH, Amir , ACKERLEY, David, Francis , COPP, Janine, Naomi , MOWDAY, Alexandra, Marie , WILLIAMS, Elsie, May , GUISE, Christopher, Paul , KOCH, Cameron , KACHUR, Alex , DOLBIER, William R. Jr
IPC分类号： A61K31/00 , A61K31/495 , A61K31/4188 , A61K38/00 , A61P9/06 , A61P9/10
CPC分类号： A61K51/0453 , A61B6/037 , A61K31/4196 , A61K31/454 , A61K49/0442 , C07C233/13 , C07D403/06 , C12Q1/26
摘要： The invention relates generally to compounds and methods for imaging and/or selective ablation of nitroreductase-expressing cells and/or biological agents. More particularly, although not exclusively, the invention provides compounds that are selectively metabolised by bacterial nitroreductases and are substantially insensitive to metabolism under oxic or hypoxic conditions by human nitroreductase enzymes.
摘要翻译：本发明一般涉及用于成像和/或选择性消融表达硝酸还原酶的细胞和/或生物制剂的化合物和方法。更具体地，尽管不是唯一地，本发明提供了由细菌硝基还原酶选择性代谢并且在氧或缺氧条件下通过人硝基还原酶对代谢基本上不敏感的化合物。

2. 发明申请

WO2010044686A1 AKR1C3 AS A BIOMARKER, METHODS OF SELECTING AND TREATING PATIENTS BASED UPON AN AKR1C3 PROFILE AND COMPOUNDS FOR USE THEREIN 审中-公开
标题翻译： AKR1C3作为生物标志物，选择和治疗患者的方法基于AKR1C3型态及其使用的化合物
公开(公告)号：WO2010044686A1
公开(公告)日：2010-04-22
申请号：PCT/NZ2009/000227
申请日：2009-10-19
申请人： AUCKLAND UNISERVICES LIMITED , PATTERSON, Adam, Vorn , GUISE, Christopher, Paul , ABBATTISTA, Maria, Rosaria , WILSON, William, Robert , SMAILL, Jeffrey, Bruce , SYDDALL, Sophie , DENNY, William, Alexander , ASHOORZADEH, Amir
发明人： PATTERSON, Adam, Vorn , GUISE, Christopher, Paul , ABBATTISTA, Maria, Rosaria , WILSON, William, Robert , SMAILL, Jeffrey, Bruce , SYDDALL, Sophie , DENNY, William, Alexander , ASHOORZADEH, Amir
IPC分类号： G01N33/50 , A61K31/661 , C07C311/40 , A61K31/136 , A61P35/00 , C07F9/09 , A61K31/145 , C07C237/32 , C12N9/06
CPC分类号： C07F9/091 , A61K31/00 , A61K31/136 , A61K31/145 , A61K31/166 , A61K31/661 , A61K45/06 , C07C237/32 , C07C309/66 , C12Q1/26 , G01N33/573 , G01N33/57484 , G01N2333/90209 , G01N2800/52 , A61K2300/00
摘要： The invention is based on the finding that the enzyme AKR1C3 is capable of exhibiting nitroreductase activity and activating nitroaromatic prodrugs to release the cytotoxic effector. AKR1C3-activated nitroaromatic prodrugs include dinitrobenzamide mustards such as 2-((2-bromoethyl)-2-{[(2-hydroxyethyl)amino]carbonyl}-4,6-dinitroanilino)ethyl methanesulfonate (PR-104A), and the corresponding pre-prodrug 2-[(2-(bromoethyl)-2,4-dinitro-6-[[[2- (phosphonooxy)ethyl]amino]carbonyl]anilino]ethyl methanesulfonate (PR-104). The invention provides methods and procedures to determine drug sensitivity in patients to allow the identification of individualized patient profiles which will aid in treating diseases and disorders, such as cancer. The invention also provides methods of treatment which are based upon such biomarker-related profiles, as well as compounds suitable for use in such methods and compositions comprising "such compounds.
摘要翻译：本发明基于以下发现：AKR1C3酶能够显示硝基还原酶活性并激活硝基芳族前药以释放细胞毒性效应物。 AKR1C3活化的硝基芳族前药包括二硝基苯甲酰胺芥末，例如2 - （（2-溴乙基）-2 - {[（2-羟乙基）氨基]羰基} -4,6-二硝基苯胺基）甲磺酸乙酯（PR-104A）前药前药2 - [（2-（溴乙基）-2,4-二硝基-6 - [[[2-（膦酰氧基）乙基]氨基]羰基]苯胺基]乙基甲磺酸酯（PR-104）确定患者药物敏感性的程序，以确定有助于治疗疾病和病症（例如癌症）的个体化患者概况。本发明还提供了基于这样的生物标记相关特征的治疗方法，以及适合的化合物用于包含“这种化合物”的这些方法和组合物中。

3. 发明申请

WO2006043839A1 NITROBENZINDOLES AND THEIR USE IN CANCER THERAPY 审中-公开
标题翻译：硝酸锌及其在癌症治疗中的应用
公开(公告)号：WO2006043839A1
公开(公告)日：2006-04-27
申请号：PCT/NZ2005/000278
申请日：2005-10-21
申请人： AUCKLAND UNISERVICES LIMITED , DENNY, William, Alexander , WILSON, William, Robert , STEVENSON, Ralph, James , TERCEL, Moana , ATWELL, Graham, John , YANG, Shangjin , PATTERSON, Adam, Vorn , PRUIJN, Frederik, Bastiaan
发明人： DENNY, William, Alexander , WILSON, William, Robert , STEVENSON, Ralph, James , TERCEL, Moana , ATWELL, Graham, John , YANG, Shangjin , PATTERSON, Adam, Vorn , PRUIJN, Frederik, Bastiaan
IPC分类号： C07D209/60 , A61K31/405 , A61P35/04 , C07D403/06 , C07F9/09
CPC分类号： C07F9/5728 , C07D209/60 , C07D403/06 , C07F9/65583
摘要： The present invention relates generally to nitro-1,2-dihydro-3H-benzo[e]indoles and related analogues, to their preparation, and to their use as hypoxia-selective drugs and radiosensitizers for cancer therapy, both alone or in combination with radiation and/or other anticancer drugs.
摘要翻译：本发明一般涉及硝基-1,2-二氢-3H-苯并[e]吲哚及其相关类似物及其制备方法，以及它们作为用于癌症治疗的缺氧选择性药物和放射增敏剂的用途，其单独或与辐射和/或其他抗癌药物。

4. 发明申请

WO2012008860A2 BACTERIAL NITROREDUCTASE ENZYMES AND METHODS RELATING THERETO 审中-公开
标题翻译：细菌氮氧化酶酶及其相关方法
公开(公告)号：WO2012008860A2
公开(公告)日：2012-01-19
申请号：PCT/NZ2011/000137
申请日：2011-07-18
申请人： AUCKLAND UNISERVICES LIMITED , VICTORIA LINK LIMITED , GUISE, Christopher Paul , ACKERLEY, David Francis , ASHOORZADEH, Amir , COPP, Janine Naomi , FLANAGAN, Jack Urquhart , MOWDAY, Alexandra Marie , PATTERSON, Adam Vorn , PROSSER, Gareth Adrian , SMAILL, Jeffrey Bruce , SYDDALL, Sophie Phillipa , WILLIAMS, Elsie May
发明人： GUISE, Christopher Paul , ACKERLEY, David Francis , ASHOORZADEH, Amir , COPP, Janine Naomi , FLANAGAN, Jack Urquhart , MOWDAY, Alexandra Marie , PATTERSON, Adam Vorn , PROSSER, Gareth Adrian , SMAILL, Jeffrey Bruce , SYDDALL, Sophie Phillipa , WILLIAMS, Elsie May
IPC分类号： G01N33/60
CPC分类号： C12N9/0028 , A61K38/44 , A61K47/556 , A61K51/0495 , C12N9/0036 , C12Q1/26
摘要： The invention relates generally to bacterial nitroreductase enzymes and methods of use thereof: More particularly, although not exclusively, said enzymes have use in non-invasise imaging techniques, monitoring of therapeutic cell populations and gene-directed enzyme prodrug therapy. The invention also relates to the use of bacterial nitroreductase enzymes in radioimaging and/or ablation of biological agents and to compositions of use in such methods.
摘要翻译：本发明一般涉及细菌硝基还原酶及其使用方法：更具体地，尽管不是唯一地，所述酶可用于非侵入成像技术，监测治疗性细胞群体和基因定向酶前药治疗。本发明还涉及细菌硝基还原酶在生物制剂的放射成像和/或消融中的用途以及在这些方法中使用的组合物。

5. 发明申请

WO2010104406A8 PRODRUG FORMS OF KINASE INHIBITORS AND THEIR USE IN THERAPY 审中-公开
公开(公告)号：WO2010104406A8
公开(公告)日：2010-09-16
申请号：PCT/NZ2010/000040
申请日：2010-03-11
申请人： AUCKLAND UNISERVICES LIMITED , SMAILL, Jeffrey, Bruce , PATTERSON, Adam Vorn , HAY, Michael Patrick , DENNY, William, Alexander , WILSON, William Robert , LU, Guo-Liang , ANDERSON, Robert, Forbes , LEE, Ho Huat , ASHOORZADEH, Amir
发明人： SMAILL, Jeffrey, Bruce , PATTERSON, Adam Vorn , HAY, Michael Patrick , DENNY, William, Alexander , WILSON, William Robert , LU, Guo-Liang , ANDERSON, Robert, Forbes , LEE, Ho Huat , ASHOORZADEH, Amir
IPC分类号： C07D471/04 , A61K31/519 , C07D403/14 , A61K31/4178 , A61P35/00 , C07D405/14 , A61K31/4709 , C07D239/94 , A61K31/517 , C07D403/12
摘要： The invention provides novel prodrug compounds comprising a kinase inhibitor and a reductively-activated fragmenting aromatic nitroheterocycle or aromatic nitrocarbocycle trigger, where the compound carries a positive charge. In preferred embodiments, the compounds are of Formula I: where: X is any negatively charged counterion; R 1 is a group of the formula —(CH 2 ) n Tr, where Tr is an aromatic nitroheterocycle or aromatic nitrocarbocycle and —(CH 2 ) n Tr acts as a reductively-activated fragmenting trigger; and n is an integer from 0 to 6; R 2 , R 3 and R 4 may each independently be selected from aliphatic or aromatic groups of a tertiary amine kinase inhibitor (R 2 )(R 3 )(R 4 )N, or two of R 2 , R 3 , and R 4 may form an aliphatic or aromatic heterocyclic amine ring of a kinase inhibitor, or one of R 2 , R 3 and R 4 may be absent and two of R 2 , R 3 and R 4 form an aromatic heterocyclic amine ring of a kinase inhibitor. The compounds of the invention are useful in treating proliferative diseases such as cancer.

6. 发明申请

WO9945127A3 ENHANCED PRODRUG ACTIVATION 审中-公开
标题翻译：加强PRODRUG激活
公开(公告)号：WO9945127A3
公开(公告)日：2000-02-24
申请号：PCT/GB9900674
申请日：1999-03-05
申请人： OXFORD BIOMEDICA LTD , STRATFORD IAN JAMES , PATTERSON ADAM VORN , KINGSMAN SUSAN MARY , KAN ON , GRIFFITHS LEIGH , MITROPHANOUS KYRIACOS
发明人： STRATFORD IAN JAMES , PATTERSON ADAM VORN , KINGSMAN SUSAN MARY , KAN ON , GRIFFITHS LEIGH , MITROPHANOUS KYRIACOS
IPC分类号： C12N15/09 , A61K35/12 , A61K35/76 , A61K38/44 , A61K45/00 , A61K47/48 , A61K48/00 , A61P9/10 , A61P29/00 , A61P35/00 , A61P43/00 , C12N5/10 , C12N7/00 , C12N9/02 , C12N15/62 , C12N7/01 , C12N15/86
CPC分类号： B82Y5/00 , A61K35/12 , A61K38/44 , A61K47/62 , A61K47/6899 , A61K48/00 , C07K2319/00 , C12N9/0077 , C12N2799/022 , C12N2799/027 , C12Y114/14001
摘要： A prodrug activating agent comprising: a) a localisation domain and b) a prodrug activation domain for activating a prodrug in a target cell.
摘要翻译：一种前药活化剂，其包含：a）定位结构域和b）用于在靶细胞中活化前药的前体药物活化结构域。

7. 发明申请

WO2008033040A1 COMBINATION APPROACHES TO CANCER TREATMENT 审中-公开
标题翻译：癌症治疗的组合方法
公开(公告)号：WO2008033040A1
公开(公告)日：2008-03-20
申请号：PCT/NZ2007/000267
申请日：2007-09-11
申请人： AUCKLAND UNISERVICES LIMITED , PATTERSON, Adam Vorn , WILSON, William Robert
发明人： PATTERSON, Adam Vorn , WILSON, William Robert
IPC分类号： A61K31/661 , A61K31/095 , A61K31/337 , A61K31/69 , A61P35/00
CPC分类号： A61K31/66 , A61K31/095 , A61K31/337 , A61K31/661 , A61K31/69 , A61K2300/00
摘要： The invention relates to a combination therapy for cancer treatment. In particular, the invention relates to a method for the treatment of cancer in a warm-blooded animal such as a human, which comprises administering to the animal an effective amount of a compound of Formula (I) refer to Formula I on page 43 of the specification wherein: X represents at any available ring position -CONH-, -SO2NH-, -O-, -CH2-, -NHCO- or -NHSO2-; R represents a lower C1-6 alkyl optionally substituted with one or more groups including hydroxyl, amino and N-oxides therefrom or dialkylamino and N-oxides therefrom; Y represents at any available ring position -N-aziridinyl, -N(CH2CH2W)2 or -N(CH2CHMeW)2, where each W is independently selected from halogen or -OSO2Me; Z represents at any available ring position -NO2, -halogen, -CN, -CF3 or -SO2Me; or a pharmaceutically acceptable salt or derivative thereof, before, after or simultaneously with an effective amount of docetaxel.
摘要翻译：本发明涉及癌症治疗的联合疗法。特别地，本发明涉及一种在温血动物如人中治疗癌症的方法，其包括向动物施用有效量的式（I）化合物，其指示第43页上的式I的化合物其中：X表示任何可用的环位置-CONH-，-SO 2 NH - ， - O - ， - CH 2 - ， - NHCO-或-NHSO 2 - ; R表示任选被一个或多个基团取代的低级C 1-6烷基，包括羟基，氨基和N-氧化物，或二烷基氨基和N-氧化物; Y表示任何可用的环位置-N-吖丙啶基，-N（CH 2 CH 2 W）2或-N（CH 2 CHMeW）2，其中各W独立地选自卤素或-OSO 2 Me; Z表示任何可用的环位置-NO 2， - 卤素，-CN，-CF 3或-SO 2 Me; 或其药学上可接受的盐或衍生物，在有效量的多西紫杉醇之前，之后或同时。

8. 发明申请

WO2008033039A1 CANCER TREATMENT 审中-公开
标题翻译：癌症治疗
公开(公告)号：WO2008033039A1
公开(公告)日：2008-03-20
申请号：PCT/NZ2007/000266
申请日：2007-09-11
申请人： PATTERSON, Adam Vorn , WILSON, William Robert
发明人： PATTERSON, Adam Vorn , WILSON, William Robert
IPC分类号： A61K31/661 , A61K31/095 , A61K31/506 , A61K31/69 , A61P35/00
CPC分类号： A61K31/095 , A61K31/505 , A61K31/506 , A61K31/661 , A61K31/69 , A61K2300/00
摘要： The invention relates to a combination therapy for cancer treatment. In particular, the invention relates to a method for the treatment of cancer in a warm-blooded animal such as a human, which comprises administering to the animal an effective amount of a compound of Formula (I) wherein: X represents at any available ring position -CONH-, -SO 2 NH-, -O-, -CH 2 -, -NHCO- or -NHSO 2 -; R represents a lower C1-6 alkylene optionally substituted with one or more groups including hydroxyl, amino and N-oxides therefrom or dialkylamino and N-oxides therefrom; Y represents at any available ring position -N-aziridinyl, -N(CH 2 CH 2 W) 2 or -N(CH 2 CHMeW) 2 , where each W is independently selected from halogen or -OSO 2 Me; Z represents at any available ring position -NO 2 , -halogen, -CN, -CF 3 or -SO 2 Me; or a pharmaceutically acceptable salt or derivative thereof, before, after or simultaneously with an effective amount of Gemcitabine.
摘要翻译：本发明涉及癌症治疗的组合疗法。特别地，本发明涉及一种在温血动物如人中治疗癌症的方法，其包括向动物施用有效量的式（I）化合物，其中：X表示任何可用的环位置-CONH-，-SO 2 NH-，-O-，-CH 2 - ， - NHCO-或-NHSO 2 - ; R表示任选被一个或多个基团取代的低级C 1-6亚烷基，包括羟基，氨基和N-氧化物，或二烷基氨基和N-氧化物; Y表示任何可用的环位置-N-氮丙啶基，-N（CH 2 CH 2 CH 2）2或-N（CH

9. 发明申请

WO2011028135A1 KINASE INHIBITORS, PRODRUG FORMS THEREOF AND THEIR USE IN THERAPY 审中-公开
标题翻译：激素抑制剂，其制剂及其在治疗中的使用
公开(公告)号：WO2011028135A1
公开(公告)日：2011-03-10
申请号：PCT/NZ2010/000174
申请日：2010-09-02
申请人： AUCKLAND UNISERVICES LIMITED , SMAILL, Jeffrey Bruce , PATTERSON, Adam Vorn , LU, Guo-Liang , LEE, Ho Huat , ASHOORZADEH, Amir , ANDERSON, Robert Forbes , WILSON, William Robert , DENNY, William Alexander , HSU, Huai-Ling (Annie) , MAROZ, Andrej , JAMIESON, Stephen Michael Frazer , MOWDAY, Alexandra Marie , CARLIN, Kendall Marie
发明人： SMAILL, Jeffrey Bruce , PATTERSON, Adam Vorn , LU, Guo-Liang , LEE, Ho Huat , ASHOORZADEH, Amir , ANDERSON, Robert Forbes , WILSON, William Robert , DENNY, William Alexander , HSU, Huai-Ling (Annie) , MAROZ, Andrej , JAMIESON, Stephen Michael Frazer , MOWDAY, Alexandra Marie , CARLIN, Kendall Marie
IPC分类号： C07D471/04 , C07D403/12 , C07D403/14 , A61K31/519 , A61P35/00
CPC分类号： C07D471/04 , A61K31/519
摘要： The present invention relates to pyrido[3,4-d]pyrimidine compounds of formula (I) suitable as kinase inhibitors, kinase inhibitors in prodrug form, their use in compositions and medicaments which are suitable for the treatment of diseases related to kinase activity such as cancers.
摘要翻译：本发明涉及适合作为激酶抑制剂的式（I）的吡啶并[3,4-d]嘧啶化合物，其为前体药物形式的激酶抑制剂，其在组合物和药物中的用途，其适用于治疗与激酶活性相关的疾病作为癌症。

10. 发明申请

WO2010104406A1 PRODRUG FORMS OF KINASE INHIBITORS AND THEIR USE IN THERAPY 审中-公开
标题翻译：激素形式的激素抑制剂及其在治疗中的使用
公开(公告)号：WO2010104406A1
公开(公告)日：2010-09-16
申请号：PCT/NZ2010000040
申请日：2010-03-11
申请人： AUCKLAND UNISERVICES LTD , SMAILL JEFFREY BRUCE , PATTERSON ADAM VORN , DENNY WILLIAM ALEXANDER , WILSON WILLIAM ROBERT , LU GUO-LIANG , ANDERSON ROBERT FORBES , LEE HO HUAT , ASHOORZADEN AMIR
发明人： SMAILL JEFFREY BRUCE , PATTERSON ADAM VORN , DENNY WILLIAM ALEXANDER , WILSON WILLIAM ROBERT , LU GUO-LIANG , ANDERSON ROBERT FORBES , LEE HO HUAT , ASHOORZADEN AMIR
IPC分类号： C07D471/04 , A61K31/4178 , A61K31/4709 , A61K31/517 , A61K31/519 , A61P35/00 , C07D239/94 , C07D403/12 , C07D403/14 , C07D405/14
CPC分类号： C07D471/04 , A61K31/4178 , A61K31/4709 , A61K31/517 , A61K31/519 , C07D239/94 , C07D401/12 , C07D401/14 , C07D403/12 , C07D403/14 , C07D405/14
摘要： The invention provides novel prodrug compounds comprising a kinase inhibitor and a reductively-activated fragmenting aromatic nitroheterocycle or aromatic nitrocarbocycle trigger, where the compound carries a positive charge. In preferred embodiments, the compounds are of Formula I: where: X is any negatively charged counterion; R1 is a group of the formula -(CH2)nTr, where Tr is an aromatic nitroheterocycle or aromatic nitrocarbocycle and -(CH2)nTr acts as a reductively-activated fragmenting trigger; and n is an integer from 0 to 6; R2, R3 and R4 may each independently be selected from aliphatic or aromatic groups of a tertiary amine kinase inhibitor (R2)(R3)(R4)N, or two of R2, R3, and R4 may form an aliphatic or aromatic heterocyclic amine ring of a kinase inhibitor, or one of R2, R3 and R4 may be absent and two of R2, R3 and R4 form an aromatic heterocyclic amine ring of a kinase inhibitor. The compounds of the invention are useful in treating proliferative diseases such as cancer.
摘要翻译：本发明提供包含激酶抑制剂和还原活化的片段化芳族硝基杂环或芳族硝基碳环触发剂的新型前药化合物，其中化合物携带正电荷。在优选的实施方案中，化合物具有式I：其中：X是任何带负电的抗衡离子; R1是式 - （CH2）nTr的基团，其中Tr是芳族硝基杂环或芳族硝基碳环，和 - （CH2）nTr作为还原活化的片段触发剂; n为0〜6的整数。 R2，R3和R4可以各自独立地选自叔胺激酶抑制剂（R2）（R3）（R4）N的脂族或芳族基团，或者R2，R3和R4中的两个可以形成脂族或芳族杂环胺环的激酶抑制剂，或R 2，R 3和R 4中的一个可以不存在，R2，R3和R4中的两个形成激酶抑制剂的芳族杂环胺环。本发明的化合物可用于治疗增殖性疾病如癌症。

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