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    Cyclic triamine chelating agents
    1.
    发明授权
    Cyclic triamine chelating agents 失效
    环状三胺螯合剂

    公开(公告)号：US5476644A

    公开(公告)日：1995-12-19

    申请号：US227161

    申请日：1994-04-13

    申请人： Carl R. Illig ,  Thomas J. Caulfield ,  John L. Toner ,  Peng Guo ,  David L. Ladd

    发明人： Carl R. Illig ,  Thomas J. Caulfield ,  John L. Toner ,  Peng Guo ,  David L. Ladd

    IPC分类号： A61K49/00 ,  A61K49/06 ,  C07C227/02 ,  C07C229/16 ,  C07C229/76 ,  C07C237/06 ,  C07C237/08 ,  C07C265/12 ,  C07C327/38 ,  C07C331/28 ,  C07F5/00 ,  C07F9/00 ,  C07F11/00 ,  C07F13/00 ,  C07F15/02 ,  C07F15/04 ,  C07F15/06 ,  C09K3/00 ,  A61K51/00 ,  A61K31/28

    CPC分类号： A61K49/06 ,  C07C229/16 ,  C07C2101/14

    摘要： The present invention provides compounds of the formula ##STR1## chelated with a paramagnetic metal ion wherein Z1 and Z2 each represent the atoms necessary to complete a monocyclic or polycyclic carbocyclic or heterocyclic ring system, said Z1 and Z2 independently optionally substituted with R.sup.6 and R.sup.7, respectively;R.sup.l, R.sup.2, R.sup.3 and R.sup.4 are independently carboxyalkyl (C.sub.1 -C.sub.2), --(CH.sub.2).sub.n --C(.dbd.O)--NH--R.sup.8, or --(CH.sub.2).sub.n --C(.dbd.O)--O--R.sup.8R.sup.5 is carboxyalkyl (C.sub.1 -C.sub.2);R.sup.6 and R.sup.7 are independently hydrogen, benzyl, or benzyloxy, said benzyl or benzyloxy optionally substituted with one, two or three substituents selected from the group consisting of amino, isocyanato (--N.dbd.C.dbd.O), isothiocyanato (--N.dbd.C.dbd.S), --NH--C(.dbd.O)--X or --NH--C(.dbd.S)--X;R.sup.8 is alkyl (C.sub.1 -C.sub.20), --(CH.sub.2).sub.m --Ar, or polyhydroxyalkyl (C.sub.1 -C.sub.20);n is 1 or 2;m is 1 to 15;X is a targeting moiety; andAr is phenyl optionally substituted with one, two or three substituents selected from the group consisting of amino, acylamino, hydroxy, alkyl (C1-C5) and halogen.

    摘要翻译： 本发明提供了与顺磁金属离子螯合的式“IMAGE”化合物，其中Z 1和Z 2各自表示完成单环或多环碳环或杂环系统所必需的原子，所述Z 1和Z 2独立地任选地被R6和R7取代， 分别; R1，R2，R3和R4独立地是羧基烷基（C1-C2）， - （CH2）nC（= O）-NH-R8或 - （CH2）nC（= O）-O-R8 R5是羧基烷基 C2）; R6和R7独立地是氢，苄基或苄氧基，所述苄基或苄氧基任选地被一个，两个或三个选自氨基，异氰酸酯基（-N = C = O），异硫氰酸酯（-N = C = S），-NH-C（= O）-X或-NH-C（= S）-X; R8是烷基（C1-C20）， - （CH2）m-Ar或多羟基烷基（C1-C20）; n为1或2; m为1〜15; X是靶向部分; 并且Ar是任选地被一个，两个或三个选自氨基，酰基氨基，羟基，烷基（C 1 -C 5）和卤素的取代基取代的苯基。

    Compositions of iodophenoxy alkanes and iodophenyl ethers in film-forming materials for visualization of the gastrointestinal tract
    3.
    发明授权
    Compositions of iodophenoxy alkanes and iodophenyl ethers in film-forming materials for visualization of the gastrointestinal tract 失效
    用于可视化胃肠道的成膜材料中碘苯氧基烷烃和碘苯基醚的组成

    公开(公告)号：US5326553A

    公开(公告)日：1994-07-05

    申请号：US12171

    申请日：1993-02-02

    申请人： Carl R. Illig ,  Eugene R. Cooper ,  John L. Toner ,  Donald A. Upson ,  Brent D. Douty ,  Thomas J. Caulfield ,  Bacon, Edward R. ,  Kimberly G. Estep ,  Kurt A. Josef ,  Shaughnessy Robinson ,  Paul P. Spara

    发明人： Carl R. Illig ,  Eugene R. Cooper ,  John L. Toner ,  Donald A. Upson ,  Brent D. Douty ,  Thomas J. Caulfield ,  Bacon, Edward R. ,  Kimberly G. Estep ,  Kurt A. Josef ,  Shaughnessy Robinson ,  Paul P. Spara

    IPC分类号： A61K49/04 ,  A61K31/075

    CPC分类号： A61K49/0433 ,  Y10S514/941 ,  Y10S514/942

    摘要： Disclosed are x-ray contrast compositions for oral or retrograde examination of the gastrointestinal tract comprising a polymeric material capable of forming a coating on the gastrointestinal tract and an x-ray producing agent of the formula ##STR1## and methods for their use in diagnostic radiology of the gastrointestinal tract whereinZ=H, halo, C.sub.1 -C.sub.20 alkyl, cycloalkyl, lower alkoxy, cyano, where the alkyl and cycloalkyl groups can be substituted with halogen or halo-lower-alkyl groups;R=C.sub.1 -C.sub.25 alkyl, cycloalkyl, or halo-lower-alkyl, optionally substituted with halo, fluoro-lower-alkyl, aryl, lower-alkoxy, hydroxy, carboxy, lower-alkoxy carbonyl or lower-alkoxycarbonyloxy, (CR.sub.1 R.sub.2).sub.p-- (CR.sub.3 .dbd.CR.sub.4).sub.m Q, or (CR.sub.1 R.sub.2).sub.p --C.tbd.C--Q;R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are independently lower-alkyl, optionally substituted with halo;x is 1-4;n is 1-5;m is 1-15;p is 1-10; andQ is H, lower-alkyl, lower-alkenyl, lower-alkynyl, lower-alkylene, aryl, or aryl-lower alkylin a pharmaceutically acceptable carrier.

    摘要翻译： 公开了用于口腔或逆行检查胃肠道的x射线造影剂组合物，其包含能够在胃肠道上形成涂层的聚合物材料和具有式“IMAGE”的X射线产生剂及其用于诊断放射学的方法 的胃肠道，其中Z = H，卤素，C 1 -C 20烷基，环烷基，低级烷氧基，氰基，其中烷基和环烷基可被卤素或卤代低级烷基取代; 任选被卤素，氟 - 低级 - 烷基，芳基，低级 - 烷氧基，羟基，羧基，低级 - 烷氧基羰基或低级 - 烷氧基羰基氧基取代的C 1 -C 25烷基，环烷基或卤代低级烷基，（CR 1 R 2）p - （CR3 = CR4）mQ，或（CR1R2）pC 3BOND CQ; R 1，R 2，R 3和R 4独立地为低级烷基，任选被卤素取代; x为1-4; n为1-5; m为1-15; p为1-10; Q为药学上可接受的载体中的H，低级烷基，低级烯基，低级炔基，低级亚烷基，芳基或芳基 - 低级烷基。

    Compositions of iodophenoxy alkylene ethers and cellulose derivatives for visualization of the gastrointestinal tract
    4.
    发明授权
    Compositions of iodophenoxy alkylene ethers and cellulose derivatives for visualization of the gastrointestinal tract 失效
    碘苯氧基亚烷基醚和纤维素衍生物用于胃肠道可视化的组合物

    公开(公告)号：US5466435A

    公开(公告)日：1995-11-14

    申请号：US222787

    申请日：1994-04-04

    申请人： Edward J. Baker ,  Edward R Bacon ,  Carl R. Illig ,  Thomas J. Caulfield ,  Brent D. Douty ,  Kurt A. Josef ,  John L. Toner ,  Robert W. Lee

    发明人： Edward J. Baker ,  Edward R Bacon ,  Carl R. Illig ,  Thomas J. Caulfield ,  Brent D. Douty ,  Kurt A. Josef ,  John L. Toner ,  Robert W. Lee

    IPC分类号： A61K49/04 ,  C07C43/225 ,  C07C43/23 ,  C07C69/92 ,  C07C255/54

    CPC分类号： A61K49/0404 ,  A61K49/04 ,  A61K49/0409 ,  A61K49/0461 ,  C07C43/225

    摘要： Disclosed are contrast agents of the formula ##STR1## wherein Z is H, halo, C.sub.1 -C.sub.20 alkyl, cycloalkyl, lower alkoxy, alkoxycarbonyl, cyano, where the alkyl and cycloalkyl groups can be substituted with halogen or halo-lower-alkyl groups;R is C.sub.1 -C.sub.25 alkyl, cycloalkyl, ##STR2## or halo-lower-alkyl; each of which may be optionally substituted with halo, fluoro-lower-alkyl, aryl, lower-alkoxy, hydroxy, carboxy, lower-alkoxy carbonyl or lower-alkoxy-carbonyloxy;(CR.sub.1 R.sub.2).sub.p --(CR.sub.3 .dbd.CR.sub.4).sub.m Q, or (CR.sub.1 R.sub.2).sub.p --C.tbd.C--Q;R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are independently H or lower-alkyl, optionally substituted with halo;x is 1-4;n is 1-4;m is 1-15;p is 1-20; andQ is H, lower-alkyl, lower-alkenyl, lower-alkynyl, lower-alkylene, aryl, or aryl-lower alkyl;in an aqueous, pharmaceutically acceptable carrier comprising a cellulose derivative.

    摘要翻译： 公开了式IMA的造影剂，其中Z是H，卤素，C 1 -C 20烷基，环烷基，低级烷氧基，烷氧基羰基，氰基，其中烷基和环烷基可以被卤素或卤代低级烷基取代; R为C1-C25烷基，环烷基，低级或低级烷基; 其中每一个可以任选被卤素，氟 - 低级 - 烷基，芳基，低级 - 烷氧基，羟基，羧基，低级 - 烷氧基羰基或低级 - 烷氧基 - 羰氧基取代; （CR 1 R 2）p - （CR 3 = CR 4）m Q或（CR 1 R 2）p -C 3OND C-Q; R 1，R 2，R 3和R 4独立地为H或低级烷基，任选被卤素取代; x为1-4; n为1-4; m为1-15; p是1-20; Q为H，低级烷基，低级烯基，低级炔基，低级亚烷基，芳基或芳基 - 低级烷基; 在包含纤维素衍生物的水性药学上可接受的载体中。

    Compositions of iodoaniline derivatives in film-forming materials for visualization of the gastrointestinal tract
    6.
    发明授权
    Compositions of iodoaniline derivatives in film-forming materials for visualization of the gastrointestinal tract 失效
    用于胃肠道可视化的成膜材料中的碘苯胺衍生物的组合物

    公开(公告)号：US5330740A

    公开(公告)日：1994-07-19

    申请号：US24714

    申请日：1993-03-01

    申请人： Carl R. Illig ,  Thomas J. Caulfield

    发明人： Carl R. Illig ,  Thomas J. Caulfield

    IPC分类号： A61K9/107 ,  A61K49/04 ,  C08K5/315 ,  C08L101/00 ,  C08L101/06 ,  G01N21/00

    CPC分类号： A61K49/0404 ,  A61K49/0409 ,  A61K49/0461

    摘要： Disclosed are x-ray contrast compositions for oral or retrograde examination of the gastrointestinal tract comprising a polymeric material capable of forming a coating on the gastrointestinal tract and an x-ray producing agent of the formula ##STR1## and methods for their use in diagnostic radiology of the gastrointestinal tract whereinZ=H, halo, C.sub.1 -C.sub.20 alkyl, cycloalkyl, lower alkoxy, cyano, where the alkyl and cycloalkyl groups can be substituted with halogen or halo-lower-alkyl groups;R.sub.1 and R.sub.2 are independently H, C.sub.1 -C.sub.25 alkyl, cycloalkyl acetyl, or halo-lower-alkyl, wherein said C.sub.1 -C.sub.25 alkyl, cycloalkyl, acetyl and halo-lower-alkyl are optionally substituted with, fiuoro-lower-alkyl, aryl, lower-alkoxy, hydroxy, carboxy, lower-alkoxy carbonyl or lower-alkoxy-carbonyloxy;n is 1-5;y is 1-4; andx is 1 or 2in a pharmaceutically acceptable carrier.

    摘要翻译： 公开了用于口腔或逆行检查胃肠道的x射线造影剂组合物，其包含能够在胃肠道上形成涂层的聚合物材料和具有式“IMAGE”的X射线产生剂及其用于诊断放射学的方法 的胃肠道，其中Z = H，卤素，C 1 -C 20烷基，环烷基，低级烷氧基，氰基，其中烷基和环烷基可被卤素或卤代低级烷基取代; R 1和R 2独立地为H，C 1 -C 25烷基，环烷基乙酰基或卤代低级烷基，其中所述C 1 -C 25烷基，环烷基，乙酰基和卤代低级烷基任选被氟低级烷基，芳基 ，低级烷氧基，羟基，羧基，低级烷氧基羰基或低级烷氧基 - 羰基氧基; n为1-5; y为1-4; 并且x在药学上可接受的载体中为1或2。

    Compositions of iodophenoxy alkylene ethers in film-forming materials for visualization of the gastrointestinal tract
    7.
    发明授权
    Compositions of iodophenoxy alkylene ethers in film-forming materials for visualization of the gastrointestinal tract 失效
    用于可视化胃肠道的成膜材料中碘苯氧基亚烷基醚的组成

    公开(公告)号：US5310538A

    公开(公告)日：1994-05-10

    申请号：US29484

    申请日：1993-03-11

    申请人： Edward R. Bacon ,  Carl R. Illig ,  Thomas J. Caulfield ,  Brent D. Douty ,  Kurt A. Josef

    发明人： Edward R. Bacon ,  Carl R. Illig ,  Thomas J. Caulfield ,  Brent D. Douty ,  Kurt A. Josef

    IPC分类号： A61K47/36 ,  A61K47/38 ,  A61K49/04 ,  C08K5/13 ,  A61K31/275 ,  A61K31/19 ,  A61K31/075

    CPC分类号： A61K49/0433 ,  Y10S514/941 ,  Y10S514/942

    摘要： R=C.sub.1 -C.sub.25 alkyl, cycloalkyl, ##STR2## or halo-lower-alkyl, each of which may be optionally substituted with halo, fluoro-lower-alkyl, aryl, lower-alkoxy, hydroxy, carboxy, lower-alkoxy carbonyl or lower-alkoxy-carbonyloxy, (CR.sub.1 R.sub.2).sub.p --(CR.sub.3 =CR.sub.4).sub.m Q ,or (CR.sub.1 R.sub.2).sub.p --C.tbd.C--Q;R.sub.1, R.sub.2 and R.sub.3 and R.sub.4 are independently H, or lower-alkyl, optionally substituted with halo;x is 1-4;n is 1-4;m is 1-15;p is 1-20; andQ is H, lower-alkyl, lower-alkenyl, lower-alkynyl, lower-alkylene, aryl, or aryl-lower alkylThese compounds are combined in a polymer for use as an X-ray contrast agent.

    摘要翻译： 其中Z = H，卤素，C 1 -C 20烷基，环烷基，低级烷氧基，烷氧基羰基，氰基，其中烷基和环烷基可被卤素或卤代低级烷基取代; R = C 1 -C 25烷基，环烷基，或卤代低级烷基，其各自可以任选被卤素，氟 - 低级 - 烷基，芳基，低级 - 烷氧基，羟基，羧基，低级 - 烷氧基羰基或 低级烷氧基 - 羰基氧基，（CR1R2）p-（CR3 = CR4）mQ或（CR1R2）pC 3BOND CQ; R 1，R 2和R 3和R 4独立地为H或低级烷基，任选被卤素取代; x为1-4; n为1-4; m为1-15; p是1-20; 并且Q是H，低级烷基，低级烯基，低级炔基，低级亚烷基，芳基或芳基 - 低级烷基。这些化合物在用作X射线造影剂的聚合物中组合。

    Compositions of iodoaniline derivatives and cellulose derivatives for visualization of the gastrointestinal tract
    8.
    发明授权
    Compositions of iodoaniline derivatives and cellulose derivatives for visualization of the gastrointestinal tract 失效
    用于可视化胃肠道的碘苯胺衍生物和纤维素衍生物的组合物

    公开(公告)号：US5422114A

    公开(公告)日：1995-06-06

    申请号：US201731

    申请日：1994-02-25

    申请人： Carl R. Illig ,  Thomas J. Caulfield ,  Robert W. Lee ,  Edward J. Baker

    发明人： Carl R. Illig ,  Thomas J. Caulfield ,  Robert W. Lee ,  Edward J. Baker

    IPC分类号： A61K9/107 ,  A61K49/04 ,  C08K5/315 ,  C08L101/00 ,  C08L101/06 ,  G01N21/00

    CPC分类号： A61K49/0404 ,  A61K49/0409 ,  A61K49/0461

    摘要： Disclosed are x-ray contrast compositions for oral or retrograde examination of the gastrointestinal tract comprising an x-ray producing agent of the formula or a pharmaceutically acceptable salt thereof ##STR1## and methods for their use in diagnostic radiology of the gastrointestinal tract, whereinZ is H, halo, C.sub.1 -C.sub.20 alkyl, cycloalkyl, lower alkoxy, cyano, where the alkyl and cycloalkyl groups can be substituted with halogen or halo-lower-alkyl groups;R.sub.1 and R.sub.2 are independently H, C.sub.1 -C.sub.25 alkyl, cycloalkyl, acetyl or halo-lower-alkyl, wherein said C.sub.1 -C.sub.25 alkyl, cycloalkyl and halo lower-alkyl are optionally substituted with fluoro-lower-alkyl, aryl, lower-alkoxy, hydroxy, carboxy, lower-alkoxy carbonyl or lower-alkoxy-carbonyloxy and said acetyl is optionally substituted with fluoro-lower-alkyl, aryl, lower-alkoxy, hydroxy, lower-alkoxy carbonyl or lower-alkoxy-carbonyloxy;n is 1-4;y is 1-4; andx is 1 or 2in a pharmaceutically acceptable carrier comprising a cellulose derivative.

    摘要翻译： 公开了用于胃肠道口服或逆行检查的x射线造影剂组合物，其包含下式的x射线产生剂或其药学上可接受的盐及其用于胃肠道诊断放射学的方法，其中Z 是H，卤素，C 1 -C 20烷基，环烷基，低级烷氧基，氰基，其中烷基和环烷基可被卤素或卤代低级烷基取代; R 1和R 2独立地为H，C 1 -C 25烷基，环烷基，乙酰基或卤代低级烷基，其中所述C 1 -C 25烷基，环烷基和卤代低级烷基任选被氟 - 低级 - 烷基，芳基，低级 - 烷氧基 ，羟基，羧基，低级烷氧基羰基或低级烷氧基 - 羰氧基，所述乙酰基任选被氟 - 低级 - 烷基，芳基，低级 - 烷氧基，羟基，低级 - 烷氧基羰基或低级 - 烷氧基 - 羰氧基取代; n为1-4; y为1-4; 并且在包含纤维素衍生物的药学上可接受的载体中x为1或2。

    Compositions of iodophenoxy alkylene ethers for visualization of the gastrointestinal tract
    9.
    发明授权
    Compositions of iodophenoxy alkylene ethers for visualization of the gastrointestinal tract 失效
    用于可视化胃肠道的碘苯氧基亚烷基醚的组合物

    公开(公告)号：US5348727A

    公开(公告)日：1994-09-20

    申请号：US29485

    申请日：1993-03-11

    申请人： Edward R. Bacon ,  Carl R. Illig ,  Thomas J. Caulfield ,  Brent D. Douty ,  Kurt A. Josef

    发明人： Edward R. Bacon ,  Carl R. Illig ,  Thomas J. Caulfield ,  Brent D. Douty ,  Kurt A. Josef

    IPC分类号： A61K49/04 ,  C07C43/225 ,  C07C43/23 ,  C07C69/92 ,  C07C255/54 ,  A61B5/055 ,  A61K31/075 ,  C07C41/00

    CPC分类号： A61K49/0404 ,  A61K49/04 ,  A61K49/0409 ,  A61K49/0461 ,  C07C43/225

    摘要： A compound of the formula: ##STR1## wherein Z.dbd.H, halo, C.sub.1 -C.sub.20 alkyl, cycloalkyl, lower alkoxy, alkoxycarbonyl, cyano, wherein thealkyl and cycloalkyl groups can be substituted with halogen or halo-lower-alkyl groups;R.dbd.C.sub.1 -C.sub.25 alkyl, cycloalkyl, ##STR2## or halo-lower-alkyl; each of which may be optionally substituted with halo, fluoro-lower-alkyl, aryl, lower-alkoxy, hydroxy, carboxy, lower-alkoxy carbonyl or lower-alkoxy-carbonyloxy, (CR.sub.1 R.sub.2).sub.p -(CR.sub.3 .dbd.CR.sub.4).sub.m Q, or (CR.sub.1 R.sub.2).sub.p --C.tbd.C-Q;R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are independently H, or lower-alkyl, optionally substituted with halo;x is 1-4;n is [1-5]1-4;m is 1-15;p is 1-20; andQ is H, lower-alkyl, lower-alkenyl, lower-alkynyl, lower-alkylene, aryl, these compounds are useful as X-ray contrast agents or aryl-lower alkyl.

    摘要翻译： 其中Z = H，卤素，C 1 -C 20烷基，环烷基，低级烷氧基，烷氧基羰基，氰基，其中烷基和环烷基可以被卤素或卤代低级烷基取代; R = C 1 -C 25烷基，环烷基，或低级烷基; 羟基，羧基，低级烷氧基羰基或低级烷氧基 - 羰基氧基（CR 1 R 2）p - （CR 3 = CR 4）m Q或任选被卤素，氟 - 低级 - 烷基，芳基， （CR1R2）pC 3BOND CQ; R 1，R 2，R 3和R 4独立地为H或被卤素取代的低级烷基; x为1-4; n是[1-5] 1-4; m为1-15; p是1-20; Q为H，低级烷基，低级烯基，低级炔基，低级亚烷基，芳基，这些化合物可用作X射线造影剂或芳基 - 低级烷基。