公开(公告)号：WO2011120053A1

公开(公告)日：2011-09-29

申请号：PCT/US2011/030225

申请日：2011-03-28

申请人： MERSANA THERAPEUTICS, INC. ,  YURKOVETSKIY, Aleksandr ,  YIN, Mao ,  LOWINGER, Timothy, B. ,  CABRAL, Carolina, B. ,  STEVENSON, Cheri, A. ,  HAMMOND, Charles, E.

发明人： YURKOVETSKIY, Aleksandr ,  YIN, Mao ,  LOWINGER, Timothy, B. ,  CABRAL, Carolina, B. ,  STEVENSON, Cheri, A. ,  HAMMOND, Charles, E.

IPC分类号： C08L59/00 ,  C07D401/00 ,  A61K31/785 ,  A61K47/48

CPC分类号： C08L59/00 ,  A61K47/59 ,  A61K48/0041 ,  C12N15/111 ,  C12N2310/11 ,  C12N2310/12 ,  C12N2310/14 ,  C12N2320/32

摘要： A polynucleotide delivery vehicle comprising a modified polymer is provided herein, the modified polymer having the following formula (I) in which W 1, W 2, W 3, W 4 , W 5 , W 6 , Z 1 , Z 2 , Z 3 , Z 4 , Z 5 , Z 9 , R 1 , R 2 , R 3 , R 4 , R 5 , n 1 , n 2 , n 3 , n 4 , n 5 , and n 6 are defined herein. Also disclosed are methods of delivering a polynucleotide to the cytoplasm of a selected tissue type or cell type and methods of reducing expression of a gene in a cell or a subject in need thereof with the modified polymer.

摘要翻译： 本文提供了包含改性聚合物的多核苷酸递送载体，具有下式（I）的改性聚合物，其中W1，W2，W3，W4，W5，W6，Z1，Z2，Z3，Z4，Z5，Z9，R1， R2，R3，R4，R5，n1，n2，n3，n4，n5和n6定义如下。 还公开了将多核苷酸递送至所选组织类型或细胞类型的细胞质的方法以及在有需要的细胞或受试者中用改性聚合物降低基因表达的方法。

公开(公告)号：WO2009073445A3

公开(公告)日：2010-01-28

申请号：PCT/US2008084539

申请日：2008-11-24

申请人： MERSANA THERAPEUTICS INC ,  AKULLIAN LAURA C ,  PETTER RUSSELL C ,  KANE JOHN J ,  HAMMOND CHARLES E ,  YIN MAO ,  YURKOVETSKIY ALEKSANDR ,  STEVENSON CHERI A

发明人： AKULLIAN LAURA C ,  PETTER RUSSELL C ,  KANE JOHN J ,  HAMMOND CHARLES E ,  YIN MAO ,  YURKOVETSKIY ALEKSANDR ,  STEVENSON CHERI A

IPC分类号： A61K47/48 ,  A61P35/00 ,  C07D303/22

CPC分类号： C07D303/40 ,  A61K47/59 ,  C07D303/18 ,  C07D303/22 ,  C07D303/36 ,  C07D405/14 ,  C07D487/08

摘要： Fumagillin analog polymer conjugates, methods of making fumagillin analog polymer conjugates, compositions comprising a polymer conjugate of a fumagillin analog, and methods for treating cancer, or treating angiogenic diseases comprising administering to a subject in need thereof an effective amount of a polymer conjugate of a fumagillin analog, are described. Also described are novel fumagillin analogs, methods of making fumagillin analogs, compositions comprising at least one fumagillin analog, and methods for treating cancer, or treating angiogenic diseases comprising administering to a subject in need thereof an effective amount of a fumagillin analog.

摘要翻译： 烟曲霉素类似物聚合物共轭物，制备烟曲霉素类似物聚合物共轭物的方法，包含烟曲霉素类似物的聚合物缀合物的组合物，以及用于治疗癌症的方法或治疗血管发生疾病的方法，包括向有需要的受试者施用有效量的 烟曲霉素类似物。 还描述了新的烟曲霉素类似物，制备烟曲霉素类似物的方法，包含至少一种烟曲霉素类似物的组合物，以及用于治疗癌症的方法或治疗血管发生疾病，包括向有需要的受试者施用有效量的烟曲霉素类似物。

公开(公告)号：WO2006099058A3

公开(公告)日：2007-05-18

申请号：PCT/US2006008441

申请日：2006-03-09

申请人： NITROMED INC ,  GARVEY DAVID S ,  CAI XIONG ,  LIN CHIA-EN ,  RANATUNGE RAMINI R ,  STEVENSON CHERI A ,  WEY SHIOW-JYI

发明人： GARVEY DAVID S ,  CAI XIONG ,  LIN CHIA-EN ,  RANATUNGE RAMINI R ,  STEVENSON CHERI A ,  WEY SHIOW-JYI

IPC分类号： A61K31/41 ,  C07D257/04

CPC分类号： C07D257/04 ,  C07C291/02 ,  C07D213/82

摘要： The invention describes compositions and kits comprising at least one organic nitric oxide enhancing salt of an angiotensin p antagonist, and, optionally, at least one nitric oxide enhancing compound and/or at least one therapeutic agent. The invention also provides methods for (a) treating cardiovascular diseases; (b) treating renovascular diseases; (c) treating diabetes; (d) treating diseases resulting from oxidative stress; (e) treating endothelial dysfunctions; (f) treating diseases caused by endothelial dysfunctions; (g) treating cirrhosis; (h) treating pre-eclampsia; (j) treating osteoporosis; (k) treating nephropathy; (1) treating peripheral vascular diseases; (m) treating portal hypertension; (n) treating ophthalmic disorders; (o) treating metabolic syndrome; and (p) treating hyperlipidemia. The organic nitric oxide enhancing compounds that form salts with the angiotensin II antagonists are organic nitrates, organic nitrites, nitrosothiols, thionitrites, thionitrates, NONOates, heterocyclic nitric oxide donors and/or nitroxides. The heterocyclic nitric oxide donors are furoxans, sydnonimines, oxatriazole-5-ones and/or oxatriazole-5-imines.

摘要翻译： 本发明描述了包含血管紧张素p拮抗剂的至少一种有机一氧化氮增强盐和任选的至少一种一氧化氮增强化合物和/或至少一种治疗剂的组合物和试剂盒。 本发明还提供了（a）治疗心血管疾病的方法; （b）治疗血管性疾病; （c）治疗糖尿病; （d）治疗由氧化应激引起的疾病; （e）治疗内皮功能障碍; （f）治疗由内皮功能障碍引起的疾病; （g）治疗肝硬化; （h）治疗先兆子痫; （j）治疗骨质疏松症; （k）治疗肾病; （1）治疗外周血管疾病; （m）治疗门静脉高压; （n）治疗眼科疾病; （o）治疗代谢综合征; 和（p）治疗高脂血症。 与血管紧张素II拮抗剂形成盐的有机一氧化氮增强化合物是有机硝酸盐，有机亚硝酸盐，亚硝基硫醇，硫堇啶，硫堇酸盐，非硝酸盐，杂环一氧化氮供体和/或氮氧化物。 杂环一氧化氮供体是呋喃糖，苏氨酸，氧杂三唑-5-酮和/或氧杂三唑-5-亚胺。

公开(公告)号：WO2005023183A3

公开(公告)日：2005-10-13

申请号：PCT/US2004026911

申请日：2004-08-20

申请人： NITROMED INC ,  GARVEY DAVID S ,  LETTS L GORDON ,  WORCEL MANUEL ,  EARL RICHARD A ,  EZAWA MAIKO ,  FANG XINQIN ,  KHANAPURE SUBHASH P ,  LIN CHIA-EN ,  RANATUNGE RAMANI R ,  STEVENSON CHERI A

发明人： GARVEY DAVID S ,  LETTS L GORDON ,  WORCEL MANUEL ,  EARL RICHARD A ,  EZAWA MAIKO ,  FANG XINQIN ,  KHANAPURE SUBHASH P ,  LIN CHIA-EN ,  RANATUNGE RAMANI R ,  STEVENSON CHERI A

IPC分类号： A61K20060101 ,  A61K31/4523 ,  A61K31/517 ,  A61K31/5415 ,  A61K31/549 ,  C07D211/00 ,  C07D285/22 ,  C07D295/00 ,  C07D307/00 ,  C07D417/12 ,  C07D417/14

CPC分类号： C07D403/10 ,  C07C205/40 ,  C07D233/68 ,  C07D235/18 ,  C07D257/04 ,  C07D307/52 ,  C07D401/12 ,  C07D401/14 ,  C07D405/06 ,  C07D405/12 ,  C07D405/14 ,  C07D409/04 ,  C07D409/06 ,  C07D409/14 ,  C07D413/10 ,  C07D471/04 ,  C07D487/04 ,  C07D495/04 ,  C07D498/04

摘要： The invention describes novel nitrosated and/or nitrosylated diuretic compounds or pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated and/or nitrosylated diuretic compound, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent. The invention also provides novel compositions and kits comprising at least one diuretic compound of the invention, that is optionally nitrosated and/or nitrosylated, and, optionally, at least one nitric oxide donor compound and/or at least one therapeutic agent. The invention also provides methods for (a) treating conditions resulting from excessive water and/or electrolyte retention; (b) treating cardiovascular diseases; (c) treating renovascular diseases; (d) treating diabetes; (e) treating diseases resulting from oxidative stress; (f) treating endothelial dysfunctions; (g) treating diseases caused by endothelial dysfunctions; (h) treating cirrhosis; (j) treating pre-eclampsia; (k) treating osteoporosis; and (1) treating nephropathy.

摘要翻译： 本发明描述了新的亚硝化和/或亚硝化化利尿化合物或其药学上可接受的盐，以及包含至少一种亚硝化和/或亚硝化化利尿化合物以及任选地至少一种一氧化氮供体和/或至少一种治疗剂 。 本发明还提供了包含至少一种本发明的任选亚硝化和/或亚硝基化的利尿化合物和任选的至少一种一氧化氮供体化合物和/或至少一种治疗剂的新组合物和试剂盒。 本发明还提供了用于（a）处理由过量的水和/或电解质保留引起的状况的方法; （b）治疗心血管疾病; （c）治疗肾血管性疾病; （d）治疗糖尿病; （e）治疗由氧化应激引起的疾病; （f）治疗内皮功能障碍; （g）治疗由内皮功能障碍引起的疾病; （h）治疗肝硬化; （j）治疗先兆子痫; （k）治疗骨质疏松症; 和（1）治疗肾病。

公开(公告)号：WO2006091716A3

公开(公告)日：2007-07-12

申请号：PCT/US2006006375

申请日：2006-02-24

申请人： NITROMED INC ,  GARVEY DAVID S ,  LETTS GORDON L ,  EARL RICHARD A ,  EZAWA MAIKO ,  FANG XINQIN ,  GASTON RICKY D ,  KHANAPURE SUBHASH P ,  LIN CHIA-EN ,  RANATUNGE RAMANI R ,  STEVENSON CHERI A ,  WEY SHIOW-JYI

发明人： GARVEY DAVID S ,  LETTS GORDON L ,  EARL RICHARD A ,  EZAWA MAIKO ,  FANG XINQIN ,  GASTON RICKY D ,  KHANAPURE SUBHASH P ,  LIN CHIA-EN ,  RANATUNGE RAMANI R ,  STEVENSON CHERI A ,  WEY SHIOW-JYI

IPC分类号： A61K31/549 ,  C07D417/02

CPC分类号： C07D285/30 ,  C07D285/28 ,  C07D285/32 ,  C07D417/04 ,  C07D417/06 ,  C07D513/10

摘要： The invention describes novel compositions and kits comprising at least one nitric oxide enhancing diuretic compound, or pharmaceutically acceptable salts thereof, and, optionally, at least one nitric oxide enhancing compound and/or at least one therapeutic agent. The invention also provides methods for (a) treating conditions resulting from excessive water and/or electrolyte retention; (b) treating cardiovascular diseases; (c) treating renovascular diseases; (d) treating diabetes; (e) treating diseases resulting from oxidative stress; (f) treating endothelial dysfunctions; (g) treating diseases caused by endothelial dysfunctions; (h) treating cirrhosis; (j) treating pre-eclampsia; (k) treating osteoporosis; (1) treating nephropathy; (m) treating peripheral vascular diseases; (n) treating portal hypertension; (o) treating central nervous system disorders; (p) treating metabolic syndrome; (q) treating sexual dysfunctions; and (r) hyperlipidemia. The nitric oxide enhancing diuretic compounds comprise at least one nitric oxide enhancing group linked to the diuretic compound through one or more sites such as carbon, oxygen and/or nitrogen via a bond or moiety that cannot be hydrolyzed.

摘要翻译： 本发明描述了包含至少一种一氧化氮增强利尿剂或其药学上可接受的盐，和任选的至少一种一氧化氮增强化合物和/或至少一种治疗剂的新型组合物和试剂盒。 本发明还提供了（a）处理由过量水和/或电解质滞留导致的条件的方法; （二）治疗心血管疾病; （c）治疗血管性疾病; （d）治疗糖尿病; （e）治疗由氧化应激引起的疾病; （f）治疗内皮功能障碍; （g）治疗由内皮功能障碍引起的疾病; （h）治疗肝硬化; （j）治疗先兆子痫; （k）治疗骨质疏松症; （1）治疗肾病; （m）治疗外周血管疾病; （n）治疗门静脉高压; （o）治疗中枢神经系统疾病; （p）治疗代谢综合征; （q）治疗性功能障碍; 和（r）高脂血症。 一氧化氮增强利尿化合物包含通过一个或多个位点如碳，氧和/或氮通过不能水解的键或部分与利尿剂化合物连接的至少一个一氧化氮增强基团。

公开(公告)号：WO2005030135A3

公开(公告)日：2005-06-16

申请号：PCT/US2004031372

申请日：2004-09-27

申请人： NITROMED INC ,  GARVEY DAVID S ,  EARL RICHARD A ,  EZAWA MAIKO ,  FANG XINQIN ,  GASTON RICKY D ,  KHANAPURE SUBHASH P ,  LIN CHIA-EN ,  RANATUNGE RAMANI R ,  STEVENSON CHERI A ,  WEY SHIOW-JYI

发明人： GARVEY DAVID S ,  EARL RICHARD A ,  EZAWA MAIKO ,  FANG XINQIN ,  GASTON RICKY D ,  KHANAPURE SUBHASH P ,  LIN CHIA-EN ,  RANATUNGE RAMANI R ,  STEVENSON CHERI A ,  WEY SHIOW-JYI

IPC分类号： A61K20060101 ,  C07C229/24 ,  C07C237/12 ,  C07C271/22 ,  C07D295/185 ,  C07K5/06

CPC分类号： C07C271/22 ,  C07C229/24 ,  C07C237/12 ,  C07D295/185

摘要： The invention describes novel nitrosated glutamic acid compounds and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated glutamic acid compound, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one nitrosated glutamic acid compound, and, and, optionally, at least one nitric oxide donor compound and/or at least one therapeutic agent. The invention also provides methods for (a) treating cardiovascular diseases; (b) treating renovascular diseases; (c) treating diabetes; (d) treating diseases resulting from oxidative stress; (e) treating endothelial dysfunctions; (f) treating diseases caused by endothelial dysfunctions; (g) treating cirrhosis; (h) treating pre-eclampsia; (j) treating osteoporosis; (k) treating nephropathy; (1) treating diseases resulting from elevated levels of gamma-glutamyl transpeptidase and (m) the targeted delivery of compounds and nitric oxide to organs, cells or tissues containing the enzyme gamma-glutamyl transpeptidase.

摘要翻译： 本发明描述了新的亚硝酸化谷氨酸化合物及其药学上可接受的盐，以及包含至少一种亚硝酸化谷氨酸化合物和任选的至少一种一氧化氮供体和/或至少一种治疗剂的新型组合物。 本发明还提供了包含至少一种亚硝酸化谷氨酸化合物和任选的至少一种一氧化氮供体化合物和/或至少一种治疗剂的新型试剂盒。 本发明还提供了（a）治疗心血管疾病的方法; （b）治疗血管性疾病; （c）治疗糖尿病; （d）治疗由氧化应激引起的疾病; （e）治疗内皮功能障碍; （f）治疗由内皮功能障碍引起的疾病; （g）治疗肝硬化; （h）治疗先兆子痫; （j）治疗骨质疏松症; （k）治疗肾病; （1）治疗由γ-谷氨酰转肽酶水平升高引起的疾病和（m）将化合物和一氧化氮靶向递送至含有γ-谷氨酰转肽酶的器官，细胞或组织。

公开(公告)号：WO2004098538A2

公开(公告)日：2004-11-18

申请号：PCT/US2004/007943

申请日：2004-03-15

申请人： NITROMED, INC. ,  EARL, Richard, A. ,  GARVEY, David, S. ,  GASTON, Ricky, D. ,  LIN, Chia-En ,  RANATUNGE, Ramani, R. ,  RICHARDSON, Stewart, K. ,  STEVENSON, Cheri, A.

发明人： EARL, Richard, A. ,  GARVEY, David, S. ,  GASTON, Ricky, D. ,  LIN, Chia-En ,  RANATUNGE, Ramani, R. ,  RICHARDSON, Stewart, K. ,  STEVENSON, Cheri, A.

IPC分类号： A61K

CPC分类号： C07J17/00 ,  C07J1/00 ,  C07J31/006 ,  C07J41/0044 ,  C07J43/00 ,  C07J43/003

摘要： The invention describes novel nitrosated and/or nitrosylated compounds of the invention, and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated and/or nitrosylated compound of the invention, and, optionally, at least one nitric oxide donor compound and/or at least one therapeutic agent. The invention also provides novel compositions comprising at least one compound of the invention, that is optionally nitrosated and/or nitrosylated, and at least one nitric oxide donor compound and/or at least one therapeutic agent. The compounds and compositions of the invention can also be bound to a matrix. The invention also provides methods for treating cardiovascular diseases, for inhibiting platelet aggregation and platelet adhesion caused by the exposure of blood to a medical device, for treating pathological conditions resulting from abnormal cell proliferation; transplantation rejections, autoimmune, inflammatory, proliferative, hyperproliferative or vascular diseases; for reducing scar tissue or for inhibiting wound contraction, particularly the prophylactic and/or therapeutic treatment of restenosis by administering at least one compound of the invention that is optionally nitrosated and/or nitrosylated, in combination with nitric oxide donors that are capable of releasing nitric oxide or indirectly delivering or transferring nitric oxide to targeted sites under physiological conditions. The compounds of the invention are preferably estradiol compounds, troglitazone compounds, tranilast compounds, retinoic acid compounds, resveratol compounds, myophenolic acid compounds, acid compounds, anthracenone compounds and trapidil compounds.

摘要翻译： 本发明描述了本发明的新型亚硝化和/或亚硝基化化合物及其药学上可接受的盐，以及包含至少一种本发明的亚硝基化和/或亚硝化化合物和任选的至少一种一氧化氮供体化合物和/ 或至少一种治疗剂。 本发明还提供了包含至少一种本发明的化合物，其任选被亚硝化和/或亚硝基化的新化合物，以及至少一种一氧化氮供体化合物和/或至少一种治疗剂。 本发明的化合物和组合物也可以结合到基质上。 本发明还提供治疗心血管疾病的方法，用于抑制由血液暴露于医疗器械引起的血小板聚集和血小板粘附，用于治疗由异常细胞增殖引起的病理状况; 移植排斥，自身免疫，炎症，增殖，过度增生或血管疾病; 用于减少瘢痕组织或抑制伤口收缩，特别是预防和/或治疗再狭窄的方法，通过给予至少一种任选地亚硝化和/或亚硝基化的本发明化合物与能释放硝酸的一氧化氮供体组合 在生理条件下氧化或间接地将一氧化氮递送或转移到靶位点。 本发明的化合物优选是雌二醇化合物，曲格列酮化合物，曲尼司特化合物，视黄酸化合物，白藜芦醇化合物，肌醇酸化合物，酸化合物，蒽酮化合物和捕获剂化合物。

公开(公告)号：WO2004004648A2

公开(公告)日：2004-01-15

申请号：PCT/US0321026

申请日：2003-07-03

申请人： NITROMED INC ,  EARL RICHARD A ,  EZAWA MAIKO ,  FANG XINQIN ,  GARVEY DAVID S ,  GASTON RICKY D ,  KHANAPURE SUBHASH P ,  LETTS GORDON L ,  LIN CHIA-EN ,  RANATUNGE RAMANI R ,  RICHARDSON STEWART K ,  SCHROEDER JOSEPH D ,  STEVENSON CHERI A ,  WEY SHIOW-JYI

发明人： EARL RICHARD A ,  EZAWA MAIKO ,  FANG XINQIN ,  GARVEY DAVID S ,  GASTON RICKY D ,  KHANAPURE SUBHASH P ,  LETTS GORDON L ,  LIN CHIA-EN ,  RANATUNGE RAMANI R ,  RICHARDSON STEWART K ,  SCHROEDER JOSEPH D ,  STEVENSON CHERI A ,  WEY SHIOW-JYI

IPC分类号： C07D295/08 ,  A61K31/21 ,  A61K31/405 ,  A61K31/445 ,  A61K45/00 ,  A61P1/00 ,  A61P1/04 ,  A61P1/10 ,  A61P1/14 ,  A61P3/04 ,  A61P17/02 ,  A61P25/28 ,  A61P27/02 ,  A61P29/00 ,  A61P35/00 ,  A61P35/02 ,  A61P43/00 ,  C07C203/04 ,  C07C205/40 ,  C07C205/56 ,  C07C219/10 ,  C07C229/42 ,  C07C235/08 ,  C07C235/12 ,  C07C235/34 ,  C07C235/42 ,  C07C237/08 ,  C07C243/28 ,  C07C271/16 ,  C07C271/64 ,  C07C291/02 ,  C07C311/17 ,  C07C317/18 ,  C07C317/32 ,  C07C317/46 ,  C07C323/12 ,  C07C327/28 ,  C07D209/18 ,  C07D209/28 ,  C07D211/22 ,  C07D211/56 ,  C07D493/04 ,  C07F9/40 ,  A61K

CPC分类号： C07D493/04 ,  C07C291/02 ,  C07C311/17 ,  C07C317/18 ,  C07C323/12 ,  C07C327/28 ,  C07D209/18 ,  C07D211/22 ,  C07D211/56

摘要： The invention describes novel nitrosated nonsteroidal antiinflammatory drugs (NSAIDs) and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated NSAID, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or at least one therapeutic agent. The invention also provides novel compositions comprising at least one nitrosated NSAID, and at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one nitrosated NSAID, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent. The invention also provides methods for treating inflammation, pain and fever; for treating gastrointestinal disorders; for facilitating wound healing; for treating and/or preventing gastrointestinal, renal and/or respiratory toxicities resulting from the use of nonsteroidal antiinflammatory compounds; for treating inflammatory disease states and/or disorders; and for treating and/or preventing ophthalmic diseases and/or disorders.

摘要翻译： 本发明描述了新的亚硝化非甾族抗炎药（NSAID）及其药学上可接受的盐，以及包含至少一种亚硝化NSAID和任选地至少一种捐赠，转移或释放一氧化氮的化合物的新组合物，刺激一氧化氮 ，提高内源性内皮细胞衍生的松弛因子的水平或者是一氧化氮合酶的底物，和/或至少一种治疗剂。 本发明还提供了新组合物，其包含至少一种亚硝基化的NSAID和至少一种提供，转移或释放一氧化氮，提高内源性内皮水平的内皮衍生的松弛因子，刺激内源性合成一氧化氮或者是一氧化氮的底物 合酶和/或至少一种治疗剂。 本发明还提供了新颖的试剂盒，其包含至少一种亚硝化的NSAID和任选的至少一种一氧化氮供体和/或至少一种治疗剂。 本发明还提供治疗炎症，疼痛和发热的方法; 用于治疗胃肠疾病; 用于促进伤口愈合; 用于治疗和/或预防由使用非甾体抗炎化合物引起的胃肠，肾和/或呼吸毒性; 用于治疗炎性疾病状态和/或病症; 并用于治疗和/或预防眼科疾病和/或病症。

公开(公告)号：WO2004002409A2

公开(公告)日：2004-01-08

申请号：PCT/US2003/019850

申请日：2003-06-25

申请人： NITROMED, INC. ,  BANDARAGE, Upul, K. ,  EARL, Richard, A. ,  EZAWA, Maiko ,  FANG, Xinqin ,  GARVEY, David, S. ,  KHANAPURE, Subhash, P. ,  RANATUNGE, Ramani, R. ,  RICHARDSON, Stewart, K. ,  SCHROEDER, Joseph, D. ,  STEVENSON, Cheri, A. ,  WEY, Shiow-Jyi

发明人： BANDARAGE, Upul, K. ,  EARL, Richard, A. ,  EZAWA, Maiko ,  FANG, Xinqin ,  GARVEY, David, S. ,  KHANAPURE, Subhash, P. ,  RANATUNGE, Ramani, R. ,  RICHARDSON, Stewart, K. ,  SCHROEDER, Joseph, D. ,  STEVENSON, Cheri, A. ,  WEY, Shiow-Jyi

IPC分类号： A61K

CPC分类号： C07D231/12 ,  C07D261/08 ,  C07D401/04

摘要： The invention describes novel cyclooxygenase 2 (COX-2) selective inhibitors and novel compositions comprising at least one cyclooxygenase 2 (COX-2) selective inhibitor, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one COX-2 selective inhibitor, optionally nitrosated and/or nitrosylated, and, optionally, at least one nitric oxide donor, and/or, optionally, at least one therapeutic agent. The novel cyclooxygenase 2 selective inhibitors of the invention can be optionally nitrosated and/or nitrosylated. The invention also provides methods for treating inflammation, pain and fever; for treating and/or improving the gastrointestinal properties of COX-2 selective inhibitors; for facilitating wound healing; for treating and/or preventing renal and/or respiratory toxicity; for treating and/or preventing other disorders resulting from elevated levels of cyclooxygenase-2; and for improving the cardiovascular profile of COX-2 selective inhibitors.

摘要翻译： 本发明描述了新颖的环加氧酶2（COX-2）选择性抑制剂和包含至少一种环氧合酶2（COX-2）选择性抑制剂和任选地至少一种化合物的新型组合物， 或释放一氧化氮，刺激一氧化氮的内源性合成，提高内源性内皮细胞衍生的松弛因子水平或是一氧化氮合酶的底物，和/或至少一种治疗剂。 本发明还提供了包含至少一种选择性抑制剂（任选亚硝化和/或亚硝基化）和任选地至少一种一氧化氮供体和/或任选地至少一种治疗剂的新型试剂盒。 本发明的新型环加氧酶2选择性抑制剂可以任选地亚硝化和/或亚硝基化。 本发明还提供治疗炎症，疼痛和发热的方法; 用于治疗和/或改善COX-2选择性抑制剂的胃肠道特性; 用于促进伤口愈合; 用于治疗和/或预防肾和/或呼吸毒性; 用于治疗和/或预防由环氧合酶-2水平升高引起的其他疾病; 并用于改善COX-2选择性抑制剂的心血管特征。

公开(公告)号：WO2010138719A1

公开(公告)日：2010-12-02

申请号：PCT/US2010/036413

申请日：2010-05-27

申请人： MERSANA THERAPEUTICS, INC. ,  YURKOVETSKIY, Aleksandr ,  YIN, Mao ,  LIU, Gui ,  AKULLIAN, Laura, C. ,  KANE, John, J. ,  STEVENSON, Cheri, A. ,  HAMMOND, Charles, E. ,  PETTER, Russell, C. ,  VAN DUZER, John, H. ,  LOWINGER, Timothy, B.

发明人： YURKOVETSKIY, Aleksandr ,  YIN, Mao ,  LIU, Gui ,  AKULLIAN, Laura, C. ,  KANE, John, J. ,  STEVENSON, Cheri, A. ,  HAMMOND, Charles, E. ,  PETTER, Russell, C. ,  VAN DUZER, John, H. ,  LOWINGER, Timothy, B.

IPC分类号： A61K31/74

CPC分类号： C07D519/04 ,  A61K47/59 ,  C07D491/22 ,  G01N2500/00 ,  Y10T436/145555

摘要： Polyal-Drug conjugates comprising a variable rate-releasing linker are described along with methods of making such conjugates. Uses for such Polyal-Drug conjugates is also described.

摘要翻译： 描述包含可变速率释放连接体的多价 - 药物共轭物以及制备这种缀合物的方法。 也描述了这种多种药物共轭物的用途。