公开(公告)号：WO1991007911A1

公开(公告)日：1991-06-13

申请号：PCT/US1990005967

申请日：1990-10-17

Applicant: CONCAT LTD.

Inventor： CONCAT LTD. ,  WINCHELL, Harry, S. ,  KLEIN, Joseph, Y. ,  SIMHON, Elliot, D. ,  CYJON, Rosa, L. ,  KLEIN, Ofer ,  ZAKLAD, Haim

IPC: A61B05/05

CPC classification number: G01R33/5601 ,  A61K49/06 ,  C07F9/6524

Abstract: Polyphosphonate ligands containing three or more phosphonate groups, combined with paramagnetic metal cations and administered in the form of pharmacologically acceptable salts, are useful as MRI contrast enhancement agents, which tend to localize in bone tissue without being conjugated to bone-specific biomolecules. Triazacyclononanes and tetraazacyclododecanes, with dihydroxyphosphorylmethyl or dihydroxyphosphorylethyl groups, optionally substituted at the methyl or ethyl bridges with alkyl, aryl, hydroxyl or amino groups, are particularly preferred.

Abstract translation: 含有三个或更多个膦酸酯基团的多膦酸酯配体与顺磁性金属阳离子组合并以药理学上可接受的盐的形式施用可用作MRI对比度增强剂，其倾向于定位在骨组织中而不与骨特异性生物分子缀合。 三氮杂环壬烷和四氮杂环十二烷与任选在甲基或乙基桥上被烷基，芳基，羟基或氨基取代的二羟基磷酰基甲基或二羟基磷酰基乙基是特别优选的。

公开(公告)号：EP0513000B1

公开(公告)日：1996-07-31

申请号：EP90917189.4

申请日：1990-10-17

Applicant: CONCAT LTD.

Inventor： WINCHELL, Harry, S. ,  KLEIN, Joseph, Y. ,  SIMHON, Elliot, D. ,  CYJON, Rosa, L. ,  KLEIN, Ofer ,  ZAKLAD, Haim

IPC: A61K49/00

CPC classification number: G01R33/5601 ,  A61K49/06 ,  C07F9/6524

Abstract: Polyphosphonate ligands containing three or more phosphonate groups, combined with paramagnetic metal cations and administered in the form of pharmacologically acceptable salts, are useful as MRI contrast enhancement agents, which tend to localize in bone tissue without being conjugated to bone-specific biomolecules. Triazacyclononanes and tetraazacyclododecanes, with dihydroxyphosphorylmethyl or dihydroxyphosphorylethyl groups, optionally substituted at the methyl or ethyl bridges with alkyl, aryl, hydroxyl or amino groups, are particularly preferred.

公开(公告)号：EP0841951A2

公开(公告)日：1998-05-20

申请号：EP96926054.0

申请日：1996-06-24

Applicant: CONCAT LTD.

Inventor： WINCHELL, Harry, S. ,  KLEIN, Joseph, Y. ,  SIMHON, Elliot, D. ,  CYJON, Rosa, L. ,  KLEIN, Ofer ,  ZAKLAD, Haim

IPC: G01R33 ,  A61B5 ,  A61K31 ,  A61K47 ,  A61K49 ,  A61K51 ,  A61P3 ,  A61P7 ,  A61P17 ,  A61P19 ,  A61P29 ,  A61P31 ,  A61P35 ,  A61P37 ,  A61P39 ,  C07C215 ,  C07D255 ,  C07D257 ,  C07D403 ,  C07D405 ,  C07D487 ,  C07F9 ,  C09K3

CPC classification number: C07D405/14 ,  A61K31/13 ,  A61K31/131 ,  A61K31/135 ,  A61K31/136 ,  A61K31/137 ,  A61K31/395 ,  A61K31/4025 ,  A61K31/415 ,  A61K31/44 ,  A61K31/675 ,  A61K47/54 ,  A61K47/547 ,  A61K49/0002 ,  A61K49/04 ,  A61K49/06 ,  A61K51/0478 ,  A61K51/0482 ,  C07D255/02 ,  C07D255/04 ,  C07D257/00 ,  C07D403/14 ,  C07D487/08 ,  C07D487/10 ,  C07F9/6515 ,  C07F9/6524 ,  C07F9/6561 ,  Y10S514/836

Abstract: This invention involves synthesis and use of a class of compounds having formula (I), wherein, p and q are each independently integers of from 2 to 3; r is an integer of from 0 to 4; R?2, R3 and R4¿ are each independently selected from the group consisting of H, alkyl, alkenyl, aryl, arylalkyl, alkoxy, alkylthio, alkenoxy, alkenylthio, aryloxy, arylthio, alkyl interrupted by one or more oxa, alkenyl interrupted by one or more oxa, alkyl interrupted by thia, alkenyl interrupted by thia, aryloxyalkyl, alkoxyaryl, aminoalkyl, aminoalkenyl, aminoaryl, aminoarylalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyaryl, hydroxyarylalkyl, halogen substituted versions thereof; R1 is a member selected from the group consisting of R?2, R3, R4¿, and radicals of formula (V), and wherein, optionally, any two of R?1, R2, R3, and R4¿ are combined to form a ring structure; and dimers thereof, said dimers being formed by the covalent attachment of two complexing agents of formula (I) through a linking group having from 1 to 6 carbon atoms; and physiological salts thereof with the proviso that the molecular weight of said complexing agent does not exceed 2000, with chelation affinity and selectivity for first transition series elements. Administration of the free or conjugated compound, or physiological salts of the free or conjugated compound, results in decrease in the in vivo bioavailability of first transition series elements and/or removal from the body of first transition series elements and elements with similar chemical properties. Theses characteristics make such compounds useful in the management of diseases associated with a bodily excess of first transition series elements and elements with similar chemical properties. This invention demonstrates that such compounds inhibit mammalian, bacterial, and fungal cell replication and are therefore useful in the treatment of neoplasia, infection, inflammation, immune response, and in termination of pregnancy. Since these compounds are capable of decreasing the in vivo availability of tissue iron they are useful in management of free radical mediated tissue damage, and oxidation mediated tissue damage. When combined with radioisotopic or paramagnetic cations of first transition series elements, or elements with chemical properties similar to those of first transition series elements, prior to their administration, the resulting complexes are useful as diagnostic agents in nuclear medicine and magnetic resonance imaging (MRI).

公开(公告)号：EP1261349A1

公开(公告)日：2002-12-04

申请号：EP01909263.4

申请日：2001-02-14

Applicant: CONCAT, LTD.

Inventor： WINCHELL, Harry, S. ,  KLEIN, Joseph, Y. ,  SIMHON, Elliot, D. ,  CYJON, Rosa, L. ,  KLEIN, Ofer ,  ZAKLAD, Haim

IPC: A61K31/675 ,  A61K31/33 ,  A61K7/16 ,  A61K7/00

CPC classification number: A61Q11/00 ,  A61K8/41 ,  A61K8/494 ,  A61K31/395 ,  A61K31/675 ,  A61K2800/51 ,  A61K2800/522 ,  A61K2800/782 ,  A61Q15/00 ,  Y10S514/836 ,  Y10S514/90 ,  Y10S514/902

Abstract: This invention involves the use of a class of compounds with chelation affinity and selectivity for first transition series elements. Application or administration of the free or conjugated compound, or physiological salts of the free or conjugated compound, results in decrease of the bioavailability and/or chemical action of first transition series elements. These characteristics make such compounds useful in cosmetics and personal care products to decrease odor arising from microbial growth on body surfaces and in body cavities, decrease microbial growth on teeth, plaque, and gums that cause tooth decay and gum disease, inhibition of oxidative damage to the skin, inhibition of enzymatic action of metalloenzymes dependent on first transition series elements, and inhibition of reperfusion injury.

公开(公告)号：EP0513000A1

公开(公告)日：1992-11-19

申请号：EP90917189.0

申请日：1990-10-17

Applicant: CONCAT LTD.

Inventor： WINCHELL, Harry, S. ,  KLEIN, Joseph, Y. ,  SIMHON, Elliot, D. ,  CYJON, Rosa, L. ,  KLEIN, Ofer ,  ZAKLAD, Haim

IPC: A61K49 ,  C07F9 ,  G01R33

CPC classification number: G01R33/5601 ,  A61K49/06 ,  C07F9/6524

Abstract: Des ligands de polyphosphonate contenant trois groupes phosphonate ou plus, combinés à des cations d'un métal et administrés sous forme de sels pharmacologiquement acceptables, sont utiles en tant qu'agents améliorant le contratse en IRM, lesquels tendent à se localiser dans les tissus osseux sans être conjugués à des biomolécules spécifiques aux os. Les triazacyclononanes et les tétraazacyclododécanes présentant des groupes dihydroxyphosphorylméthyle ou dihydroxyphosphoryléthyle, facultativement remplacés au niveau des ponts méthyle ou éthyle par des groupes alkyle, aryle, hydroxyle ou amino sont particulièrement préférés.

Abstract translation: 含有三个或更多个膦酸基团，结合金属阳离子和在药理学上可接受的盐的形式给药的聚膦酸酯配体，可用作用于改善contratse MRI，其倾向于在骨组织中局部化剂 而不与骨特异性生物分子结合。 具有dihydroxyphosphorylméthyle或dihydroxyphosphoryléthyle基团，任选在烷基，芳基，羟基或氨基的甲基或乙基取代的桥接的triazacyclononanes和tétraazacyclododécanes是特别优选的。