公开(公告)号：US20090082314A1

公开(公告)日：2009-03-26

申请号：US12163853

申请日：2008-06-27

申请人： John Francis Gilmer ,  Juan Francisco Marquez ,  Dermot Kelleher

发明人： John Francis Gilmer ,  Juan Francisco Marquez ,  Dermot Kelleher

IPC分类号： A61K31/655 ,  C09B56/00 ,  C09B29/00 ,  A61K31/573 ,  A61P35/00 ,  A61P29/00 ,  C07K16/00

CPC分类号： C07C245/08 ,  C07J41/005 ,  C07J71/0031 ,  C09B29/0007

摘要： Provided herein are compounds, compositions and methods for decreasing NFκB DNA-binding activity in a patient comprising administering of a therapeutically effective amount of a compound or composition of the application to the patient to reduce, alleviate or treat various gastrointestinal diseases, such as inflammatory bowel disease (IBD).

摘要翻译： 本文提供用于降低患者中NFkappaB DNA结合活性的化合物，组合物和方法，包括向患者施用治疗有效量的该应用的化合物或组合物以减少，缓解或治疗各种胃肠疾病，例如炎性肠 疾病（IBD）。

公开(公告)号：US20120094963A1

公开(公告)日：2012-04-19

申请号：US13141663

申请日：2009-12-21

申请人： John Francis Gilmer ,  Juan Francisco Marquez Ruiz ,  Dermot Kelleher

发明人： John Francis Gilmer ,  Juan Francisco Marquez Ruiz ,  Dermot Kelleher

IPC分类号： A61K31/655 ,  C07D261/08 ,  A61P1/00 ,  A61P29/00 ,  C07D237/04 ,  A61P35/00

CPC分类号： C07C311/51 ,  C07D231/12

摘要： Provided herein are compounds of formula (I) as well as compounds of formula (I) which are prodrugs in which the (R7)a-phenyl-S(O)2NH group represents a sulphonamide-bond compound, compositions and methods for preventing or treating gastrointestinal diseases such as inflammatory bowel disease and colorectal cancer, wherein the method comprises delivering an effective amount of a COX-2 or a similar sulphonamide inhibitor as a prodrug or a derivative thereof to the colon, wherein the COX-2 or similar inhibitor is released in vivo.

摘要翻译： 本文提供式（I）化合物以及式（I）化合物，其是其中（R7）a-苯基-S（O）2 NH基团代表磺酰胺键化合物的前药，其组合物和方法用于预防或 治疗诸如炎症性肠病和结肠直肠癌的胃肠疾病，其中所述方法包括将有效量的COX-2或类似的磺酰胺抑制剂作为其前药或衍生物递送至结肠，其中COX-2或类似抑制剂为 体内释放

公开(公告)号：US08486974B2

公开(公告)日：2013-07-16

申请号：US12808693

申请日：2008-12-19

申请人： John Francis Gilmer ,  Louise Clune-Moriarty ,  Maeve Lally

发明人： John Francis Gilmer ,  Louise Clune-Moriarty ,  Maeve Lally

IPC分类号： A61K31/4406 ,  C07D405/12

CPC分类号： C07D493/04

摘要： Aspirin is one of the most widely used drugs in the treatment of inflammation, pain and fever. It has more recently found application in the prevention of heart attacks and stroke and is being studied as a cancer chemopreventative agent. Despite its value aspirin continues to be underutilized because it causes gastric bleeding. The technology under development potentially removes this problem. It is designed to reduce contact between the drug and the intestinal lining. An isosorbide aspirinate prodrug compound is thus provided. The compound has the general structure as shown in general formula (I) wherein Y is a C1-C8 alkyl ester, a C1-C8 alkoxy ester, a C3-C10 cycloalkyl ester, an arylester, a C1-C8 alkylaryl ester or —C(O)ORring, wherein Rring is a 5-membered aromatic or nonaromatic 5-member ring having at least one heteroatom substituted for a carbon of the ring system, which can be unsubstituted or substituted with at least one nitric oxide releasing group.

摘要翻译： 阿司匹林是治疗炎症，疼痛和发烧最广泛使用的药物之一。 最近发现应用于预防心脏病发作和中风，并正在研究中作为癌症化学预防剂。 尽管阿司匹林的价值仍然不足，因为它导致胃出血。 正在开发的技术可能会消除这个问题。 它旨在减少药物和肠内膜之间的接触。 因此提供了异山梨醇阿司匹林前药化合物。 该化合物具有通式（I）所示的一般结构，其中Y为C1-C8烷基酯，C1-C8烷氧基酯，C3-C10环烷基酯，芳基酯，C1-C8烷基芳基酯或-C （O）ORring，其中Rring是具有至少一个取代环系的碳的杂原子的5元芳族或非芳族5元环，其可以是未取代的或被至少一个一氧化氮释放基团取代。

公开(公告)号：US20140024681A1

公开(公告)日：2014-01-23

申请号：US13980533

申请日：2012-01-20

申请人： John Francis Gilmer ,  Mark Ledwidge ,  Pat O'lynn ,  Shona Harmon ,  Mark Radomski ,  Carlos Medina Martin

发明人： John Francis Gilmer ,  Mark Ledwidge ,  Pat O'lynn ,  Shona Harmon ,  Mark Radomski ,  Carlos Medina Martin

IPC分类号： C07D493/04

CPC分类号： C07D493/04

摘要： A compound having the structural formula (I) and pharmaceutically acceptable salt and/or hydrates thereof, (I) wherein Y is an arylester or an C1-C8 alkylaryl ester, selected from the group consisting of: benzene, toluene, xylene, benzoic acid, benzoate, nicotinate, isonicotinate and halobenzene, which can be unsubstituted or substituted with at least one nitric oxide releasing group; and/or at least one of hydroxide, —Cl, —Br, a C1-C8 alkyl, benzyl, a C1-C8 alkoxy, benzyloxy, —NHC(O)R, —NH2, —NO2—ONO2, —(CH2)nONO2, —OC(O)[(CH2)n]cyclicONO2, —OCOArONO2, —OCOAr(CH2)nONO2 or a C1-C5 haloalkyl ester, wherein R is a C1-C8 alkyl or a C1-C8 alkoxy group, n=1-8 and m=3-10, to produce a super-aspirin effect.

摘要翻译： 具有结构式（I）的化合物及其药学上可接受的盐和/或其水合物，（I）其中Y是芳基酯或C1-C8烷基芳基酯，选自：苯，甲苯，二甲苯，苯甲酸 苯甲酸盐，烟酸盐，异烟酸盐和卤代苯，其可以是未取代的或被至少一个一氧化氮释放基团取代; 和/或氢氧化物，-Cl，-Br，C1-C8烷基，苄基，C1-C8烷氧基，苄氧基，-NHC（O）R，-NH2，-NO2-ONO2， - （CH2） NONO 2，-OC（O）[（CH 2）n]环氧基，-OCOOOR 2，-OCOAr（CH 2）nONO 2或C 1 -C 5卤代烷基酯，其中R是C 1 -C 8烷基或C 1 -C 8烷氧基，n = 1-8和m = 3-10，以产生超阿司匹林效应。

公开(公告)号：US20110046182A1

公开(公告)日：2011-02-24

申请号：US12808693

申请日：2008-12-19

申请人： John Francis Gilmer ,  Louise Clune-Moriarty ,  Maeve Lally

发明人： John Francis Gilmer ,  Louise Clune-Moriarty ,  Maeve Lally

IPC分类号： A61K31/443 ,  C07D493/04 ,  C07D261/02 ,  C07D285/06 ,  C07D405/12 ,  A61K31/34 ,  A61K31/422 ,  A61K31/433 ,  A61P25/28 ,  A61P9/00 ,  A61P35/00 ,  A61P29/00

CPC分类号： C07D493/04

摘要： Aspirin is one of the most widely used drugs in the treatment of inflammation, pain and fever. It has more recently found application in the prevention of heart attacks and stroke and is being studied as a cancer chemopreventative agent. Despite its value aspirin continues to be underutilized because it causes gastric bleeding. The technology under development potentially removes this problem. It is designed to reduce contact between the drug and the intestinal lining. An isosorbide aspirinate prodrug compound is thus provided. The compound has the general structure as shown in general formula (I) wherein Y is a C1-C8 alkyl ester, a C1-C8 alkoxy ester, a C3-C10 cycloalkyl ester, an arylester, a C1-C8 alkylaryl ester or —C(O)ORring, wherein Rring is a 5-membered aromatic or nonaromatic 5-member ring having at least one heteroatom substituted for a carbon of the ring system, which can be unsubstituted or substituted with at least one nitric oxide releasing group.

摘要翻译： 阿司匹林是治疗炎症，疼痛和发烧最广泛使用的药物之一。 最近发现应用于预防心脏病发作和中风，并正在研究中作为癌症化学预防剂。 尽管阿司匹林的价值仍然不足，因为它导致胃出血。 正在开发的技术可能会消除这个问题。 它旨在减少药物和肠内膜之间的接触。 因此提供了异山梨醇阿司匹林前药化合物。 该化合物具有通式（I）所示的一般结构，其中Y为C1-C8烷基酯，C1-C8烷氧基酯，C3-C10环烷基酯，芳基酯，C1-C8烷基芳基酯或-C （O）ORring，其中Rring是具有至少一个取代环系的碳的杂原子的5元芳族或非芳族5元环，其可以是未取代的或被至少一个一氧化氮释放基团取代。