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1. 发明申请

US20090234019A1 T Type Calcium Channel Inhibitors 有权
标题翻译： T型钙通道抑制剂
公开(公告)号：US20090234019A1
公开(公告)日：2009-09-17
申请号：US11660693
申请日：2005-08-22
申请人： Lloyd S. Gray , Timothy L. MacDonald , Doris M. Haverstick , Jaclyn R. Patterson , William F. McClamont
发明人： Lloyd S. Gray , Timothy L. MacDonald , Doris M. Haverstick , Jaclyn R. Patterson , William F. McClamont
IPC分类号： A61K31/138 , C07C211/27 , A61P35/00
CPC分类号： A61K31/14 , A61K31/085 , A61K31/12 , A61K31/137 , A61K31/138 , A61K45/06 , C07C217/58 , C07C217/60 , C07C217/62 , A61K2300/00
摘要： The present invention provides novel T type calcium channel inhibitors of formula (I), the use thereof in the treatment of a disease or condition in a mammal associated with influx of extracellular calcium via T type calcium channels, whereinR1 is C1-C4 alkyl, hydroxy, or C1-C4 alkoxy;Z is NH, NCH3, O, S, or CH2;Y is NH, O, or CH2 with the proviso that Y and Z are not the same;R2 is H, halo, NH2, C1-C4 alkyl, hydroxy, or C1-C4 alkoxy;m and n are independently selected from integers ranging from 1-5 with the proviso that m+n=an integer ranging from 2-9; andR3 is H, halo, NH2, C1-C4 alkyl, hydroxy, or C1-C4 alkoxy.
摘要翻译：本发明提供式（I）的新型T型钙通道抑制剂，其用于治疗与通过T型钙通道流入胞外钙相关的哺乳动物中的疾病或病症，其中R 1为C 1 -C 4烷基，羟基或C 1 -C 4烷氧基; Z是NH，NCH 3，O，S或CH 2; Y是NH，O或CH 2，条件是Y和Z不相同; R2是H，卤素，NH2，C1-C4烷基，羟基或C1-C4烷氧基; m和n独立地选自1-5的整数，条件是m + n = 2-9的整数; 并且R 3是H，卤素，NH 2，C 1 -C 4烷基，羟基或C 1 -C 4烷氧基。

2. 发明授权

US09212127B2 T type calcium channel inhibitors 有权
标题翻译： T型钙通道抑制剂
公开(公告)号：US09212127B2
公开(公告)日：2015-12-15
申请号：US11660693
申请日：2005-08-22
申请人： Lloyd S. Gray , Timothy L. MacDonald , Doris M. Haverstick , Jaclyn R. Patterson , William F. McCalmont
发明人： Lloyd S. Gray , Timothy L. MacDonald , Doris M. Haverstick , Jaclyn R. Patterson , William F. McCalmont
IPC分类号： C07C217/58 , C07C217/60 , C07C217/62 , A61K31/137 , A61K31/138 , A61K45/06
CPC分类号： A61K31/14 , A61K31/085 , A61K31/12 , A61K31/137 , A61K31/138 , A61K45/06 , C07C217/58 , C07C217/60 , C07C217/62 , A61K2300/00
摘要： The present invention provides novel T type calcium channel inhibitors of formula (I), the use thereof in the treatment of a disease or condition in a mammal associated with influx of extracellular calcium via T type calcium channels, wherein R1 is C1-C4 alkyl, hydroxy, or C1-C4 alkoxy; Z is NH, NCH3, O, S, or CH2; Y is NH, O, or CH2 with the proviso that Y and Z are not the same; R2 is H, halo, NH2, C1-C4 alkyl, hydroxy, or C1-C4 alkoxy; m and n are independently selected from integers ranging from 1-5 with the proviso that m+n=an integer ranging from 2-9; and R3 is H, halo, NH2, C1-C4 alkyl, hydroxy, or C1-C4 alkoxy.
摘要翻译：本发明提供式（I）的新型T型钙通道抑制剂，其用于治疗与通过T型钙通道流入胞外钙相关的哺乳动物中的疾病或病症，其中R 1为C 1 -C 4烷基，羟基或C 1 -C 4烷氧基; Z是NH，NCH 3，O，S或CH 2; Y是NH，O或CH 2，条件是Y和Z不相同; R2是H，卤素，NH2，C1-C4烷基，羟基或C1-C4烷氧基; m和n独立地选自1-5的整数，条件是m + n = 2-9的整数; 并且R 3是H，卤素，NH 2，C 1 -C 4烷基，羟基或C 1 -C 4烷氧基。

3. 发明申请

US20100222406A1 T Type Calcium Channel Blockers and the Treatment of Diseases 审中-公开
标题翻译： T型钙通道阻滞剂和疾病治疗
公开(公告)号：US20100222406A1
公开(公告)日：2010-09-02
申请号：US12687641
申请日：2010-01-14
申请人： Lloyd S. Gray , Doris M. Haverstick
发明人： Lloyd S. Gray , Doris M. Haverstick
IPC分类号： A61K31/40 , A61K31/137 , A61K31/075 , A61K31/085 , A61K31/045 , A61K31/10 , A61P35/00
CPC分类号： A61K31/045 , A61K31/075 , A61K31/085 , A61K31/10 , A61K31/137 , A61K31/40
摘要： The present invention provides a method for treating a disease or condition in a mammal associated with influx of extracellular calcium via T type calcium channels, which comprises administering to the mammal a therapeutically effective amount of a T type calcium channel inhibitor, a prodrug thereof, or a pharmaceutically acceptable salt of said inhibitor or prodrug, wherein the T type calcium channel inhibitor has a structure represented by Formula (I): Formula (I), wherein R1 is selected from the group consisting of C1-C4 alkyl, hydroxy and C1-C4 alkoxy; X is selected from the group consisting of N and CH; Z is selected from the group consisting of NH, O, S and CH2; R2 is selected from the group consisting of H, halo, NH2, C1-C4 alkyl, hydroxy and C1-C4 alkoxy; and R3 is selected from the group consisting of H, halo, NH2, C1-C4 alkyl, hydroxy and C1-C4 alkoxy. In one embodiment R1 is selected from the group consisting of C1-C4 alkyl, hydroxyl and C1-C4 alkoxy, X is N, Z is O or CH2, R2 is H, halo, NH2 or hydroxyl and R3 is H.
摘要翻译：本发明提供了一种用于治疗与通过T型钙通道流入细胞外钙的哺乳动物有关的疾病或病症的方法，其包括向哺乳动物施用治疗有效量的T型钙通道抑制剂，其前药或所述抑制剂或前药的药学上可接受的盐，其中所述T型钙通道抑制剂具有由式（I）表示的结构：式（I），其中R 1选自C 1 -C 4烷基，羟基和C 1 -C 4烷基， C4烷氧基; X选自N和CH; Z选自NH，O，S和CH 2; R 2选自H，卤素，NH 2，C 1 -C 4烷基，羟基和C 1 -C 4烷氧基; 并且R 3选自H，卤素，NH 2，C 1 -C 4烷基，羟基和C 1 -C 4烷氧基。在一个实施方案中，R 1选自C 1 -C 4烷基，羟基和C 1 -C 4烷氧基，X是N，Z是O或CH 2，R 2是H，卤素，NH 2或羟基，R 3是H.

4. 发明授权

US06413967B1 Inhibition of novel calcium entry pathway in electrically non-excitable cells acting as an anti-proliferative therapy 失效
标题翻译：抑制作为抗增殖治疗的电不可兴奋细胞中的新钙进入途径
公开(公告)号：US06413967B1
公开(公告)日：2002-07-02
申请号：US08413229
申请日：1995-03-30
申请人： Lloyd S. Gray , Doris M. Haverstick , John J. Densmore , Gabor Szabo
发明人： Lloyd S. Gray , Doris M. Haverstick , John J. Densmore , Gabor Szabo
IPC分类号： A61K31502
CPC分类号： A61K31/495
摘要： The present invention provides methods for screening for voltage gated (VG)-selective inhibitors, novel VG-selective inhibitors, compositions containing the same, methods for inhibiting calcium entry into electrically non-excitable cells with said VG-selective inhibitors, methods for preventing proliferation of electrically non-excitable cells with said VG-selective inhibitors as well as methods of treating autoimmune diseases, preventing graft rejections, preventing apoptosis and treating cancer with the same.
摘要翻译：本发明提供了筛选电压门控（VG）选择性抑制剂，新型VG选择性抑制剂，含有其的组合物的方法，用所述VG-选择性抑制剂抑制钙进入电不可兴奋细胞的方法，用于预防增殖的方法具有所述VG选择性抑制剂的电不可兴奋细胞以及治疗自身免疫性疾病，预防移植排斥，预防凋亡和用其治疗癌症的方法。

5. 发明申请

US20120264804A1 T TYPE CALCIUM CHANNEL BLOCKERS AND THE TREATMENT OF DISEASES 审中-公开
标题翻译： T型钙通道阻塞剂和治疗疾病
公开(公告)号：US20120264804A1
公开(公告)日：2012-10-18
申请号：US13267609
申请日：2011-10-06
申请人： Lloyd S. Gray , Doris M. Haverstick
发明人： Lloyd S. Gray , Doris M. Haverstick
IPC分类号： A61K31/40 , A61P35/00
CPC分类号： A61K31/045 , A61K31/075 , A61K31/085 , A61K31/10 , A61K31/137 , A61K31/40 , A61K45/06 , A61K2300/00
摘要： The present invention provides a method for treating a disease or condition in a mammal associated with influx of extracellular calcium via T type calcium channels, which comprises administering to the mammal a therapeutically effective amount of a T type calcium channel inhibitor, a prodrug thereof, or a pharmaceutically acceptable salt of said inhibitor or prodrug, wherein the T type calcium channel inhibitor blocks a splice variant of an α1H isoform of T type calcium channels.
摘要翻译：本发明提供了一种用于治疗与通过T型钙通道流入细胞外钙的哺乳动物有关的疾病或病症的方法，其包括向哺乳动物施用治疗有效量的T型钙通道抑制剂，其前药或所述抑制剂或前药的药学上可接受的盐，其中所述T型钙通道抑制剂阻断T型钙通道的α1H同种型的剪接变体。

6. 发明申请

US20080194669A1 T Type Calcium Channel Blockers and the Treatment of Diseases 审中-公开
标题翻译： T型钙通道阻滞剂和疾病治疗
公开(公告)号：US20080194669A1
公开(公告)日：2008-08-14
申请号：US11660401
申请日：2005-08-22
申请人： Lloyd S. Gray , Doris M. Haverstick
发明人： Lloyd S. Gray , Doris M. Haverstick
IPC分类号： A61K31/40 , C12N5/06 , A61P35/00
CPC分类号： A61K31/455 , A61K31/553
摘要： The present invention provides a method for treating a disease or condition in a mammal associated with influx of extracellular calcium via T type calcium channels, which comprises administering to the mammal a therapeutically effective amount of a T type calcium channel inhibitor, a prodrug thereof, or a pharmaceutically acceptable salt of said inhibitor or prodrug, wherein the T type calcium channel inhibitor has a structure represented by Formula (I): Formula (I), wherein R1 is selected from the group consisting of C1-C4 alkyl, hydroxy and C1-C4 alkoxy; X is selected from the group consisting of N and CH; Z is selected from the group consisting of NH, O, S and CH2; R2 is selected from the group consisting of H, halo, NH2, C1-C4 alkyl, hydroxy and C1-C4 alkoxy; and R3 is selected from the group consisting of H, halo, NH2, C1-C4 alkyl, hydroxy and C1-C4 alkoxy. In one embodiment R1 is selected from the group consisting of C1-C4 alkyl, hydroxyl and C1-C4 alkoxy, X is N, Z is O or CH2, R2 is H, halo, NH2 or hydroxyl and R3 is H.
摘要翻译：本发明提供了一种用于治疗与通过T型钙通道流入细胞外钙的哺乳动物有关的疾病或病症的方法，其包括向哺乳动物施用治疗有效量的T型钙通道抑制剂，其前药或所述抑制剂或前药的药学上可接受的盐，其中所述T型钙通道抑制剂具有由式（I）表示的结构：式（I），其中R 1选自C C 1 -C 4烷基，羟基和C 1 -C 4烷氧基; C 1 -C 4烷基，C 1 -C 4烷基， X选自N和CH; Z选自NH，O，S和CH 2 2; R 2选自H，卤素，NH 2，C 1 -C 4烷基，C 1 -C 4烷基，，羟基和C 1 -C 4烷氧基; 且R 3选自H，卤素，NH 2，C 1 -C 4烷基，烷基，羟基和C 1 -C 4烷氧基。在一个实施方案中，R 1选自C 1 -C 4 - 烷基，羟基和C 1〜 -C≡4烷氧基，X是N，Z是O或CH 2，R 2是H，卤素，NH 2 或羟基，R 3是H.

7. 发明申请

US20080160009A1 Inhibiting Cav3 Isoforms and the 25B Splice Varients for the Diagnosis and Treatment of Cancer 审中-公开
标题翻译：抑制Cav3同种型和25B接头变量用于诊断和治疗癌症
公开(公告)号：US20080160009A1
公开(公告)日：2008-07-03
申请号：US10589216
申请日：2005-02-11
申请人： Lloyd S. Gray , Timothy L. MacDonald
发明人： Lloyd S. Gray , Timothy L. MacDonald
IPC分类号： A61K39/00 , C07K16/00 , G01N33/53 , A61K31/135
CPC分类号： A61K31/4422
摘要： The invention provides a pharmaceutical composition comprising an antibody that specifically binds to a Cav3 isoform or its δ25 splice variants thereof. The present invention also relates to compositions and methods for inhibiting cancer cell proliferation, preventing, treating and/or controlling cancer and/or related disorders in a patient by administering to the patient a therapeutically effective amount of the T type calcium channel selective inhibitor. A preferred T type calcium channel selective inhibitor is mibefradil.
摘要翻译：本发明提供了一种药物组合物，其包含特异性结合Cav3同种型或其delta25剪接变体的抗体。本发明还涉及通过向患者施用治疗有效量的T型钙通道选择性抑制剂来抑制癌细胞增殖，预防，治疗和/或控制患者的癌症和/或相关病症的组合物和方法。优选的T型钙通道选择性抑制剂是mibefradil。

8. 发明授权

US06946475B1 Anticancer calcium channel blockers 有权
标题翻译：抗癌钙通道阻滞剂
公开(公告)号：US06946475B1
公开(公告)日：2005-09-20
申请号：US09544968
申请日：2000-04-07
申请人： Lloyd S. Gray , Timothy L. Macdonald , Doris Haverstick , Tiffany N. Heady
发明人： Lloyd S. Gray , Timothy L. Macdonald , Doris Haverstick , Tiffany N. Heady
IPC分类号： A61K31/40 , A61K31/445 , C07D207/08 , C07D207/46 , C07D211/20 , C07D211/22 , C07D295/02 , C07D295/03
CPC分类号： C07D207/08 , C07D211/22 , C07D295/03
摘要： The present invention is directed to compounds useful as cancer cell inhibitors, compositions containing such compounds and methods for inhibiting proliferation of electrically non-excitable cells.
摘要翻译：本发明涉及可用作癌细胞抑制剂的化合物，含有这些化合物的组合物和抑制电不可兴奋细胞增殖的方法。

9. 发明申请

US20120088807A1 INTERLACED METHOD FOR TREATING CANCER OR A PRECANCEROUS CONDITION 审中-公开
标题翻译：用于治疗癌症或预防性病症的相互联系的方法
公开(公告)号：US20120088807A1
公开(公告)日：2012-04-12
申请号：US13375846
申请日：2010-06-04
申请人： Andrew J. Krouse , Lloyd S. Gray , Timothy MacDonald , Joel Linden
发明人： Andrew J. Krouse , Lloyd S. Gray , Timothy MacDonald , Joel Linden
IPC分类号： A61K31/4188 , A61P35/00
CPC分类号： A61K31/70 , A61K31/4184 , A61K31/66 , A61K33/24 , A61K38/14 , A61K2300/00
摘要： The present invention provides a method for treating a disease or condition in a mammal which comprises the steps of; administering a therapeutically effective amount of a T type calcium channel inhibitor to effectively slow or stop progression of eukaryotic cells through the S, G2 and M phases of the cell cycle to increase the proportion of the eukaryotic cells in the G1 phase, stopping administration of the T type calcium channel inhibitor for a period of time, and administering a dosage selected from the group consisting of a dosage of at least one chemotherapeutic agent, a dosage of radiation, and combinations thereof, to kill the proportion of eukaryotic cells progressing past the G1 phase of the cell cycle after the stopping of the administration of the T type calcium channel inhibitor.
摘要翻译：本发明提供一种治疗哺乳动物疾病或病症的方法，其包括以下步骤：施用治疗有效量的T型钙通道抑制剂以有效地减缓或停止通过细胞周期的S，G2和M期进行真核细胞的进展，以增加G1期中真核细胞的比例，停止施用 T型钙通道抑制剂持续一段时间，并施用选自剂量的至少一种化学治疗剂，剂量的辐射剂及其组合的剂量，以杀死通过G1进行的真核细胞的比例在停止施用T型钙通道抑制剂后，细胞周期的相位。

10. 发明授权

US09427429B2 Cancer diagnosis and imaging 有权
标题翻译：癌症诊断和成像
公开(公告)号：US09427429B2
公开(公告)日：2016-08-30
申请号：US13581390
申请日：2011-02-28
申请人： Lloyd S. Gray
发明人： Lloyd S. Gray
IPC分类号： A61K31/4184 , A61K31/675 , A61K31/4015 , A61K51/04 , A61K33/24 , A61K45/06
CPC分类号： A61K31/4184 , A61K31/4015 , A61K31/675 , A61K33/24 , A61K45/06 , A61K51/0491 , A61K2300/00
摘要： The present invention provides a method for imaging a disease or condition in a mammal which includes the steps of; administering a therapeutically effective amount of a cell cycle inhibitor to effectively stop proliferation of eukaryotic cells at a cell cycle checkpoint between the G1 and S phase, stopping administration of the cell cycle inhibitor for a period of time, administering a marker to the mammal and imaging the mammal.
摘要翻译：本发明提供一种用于对哺乳动物的疾病或病症进行成像的方法，其包括以下步骤：施用治疗有效量的细胞周期抑制剂以有效地停止在G1期和S期之间的细胞周期检查点的真核细胞的增殖，停止给予细胞周期抑制剂一段时间，向哺乳动物施用标记物和成像哺乳动物。

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