公开(公告)号：EP0831806A1

公开(公告)日：1998-04-01

申请号：EP96924270.0

申请日：1996-06-07

Applicant: WASHINGTON UNIVERSITY

Inventor： PIWNICA-WORMS, David, R. ,  SHARMA, Vijay

IPC: A61K41 ,  A61K31 ,  A61K38 ,  A61K45 ,  A61P33 ,  A61P35 ,  A61P43 ,  C07D273 ,  C07F5 ,  C07F15

CPC classification number: C07D273/00 ,  A61K31/555 ,  Y02A50/411

Abstract: The invention relates to multidentate metal complexes having formula (I) wherein M is Fe, In, Ga or Al; the dashed lines represent independently a sigle or a double bond; the hatched lines represent coordination to the metal cation (M); A and B are oxygen, or in the case where Ar is 2-pyridyl or 2-pyrrolyl, a shared pair of electrons on the nitrogen; Ar is optionally substituted phenyl, optionally substituted naphthyl, optionally substituted 2-pyridyl or optionally substituted 2-pyrrolyl, with the proviso that at least one of the substituents comprises a boron atom; X is alternatively (i) (CHR )p[NR (CHR )q]r, wherein p and q are independently 1, 2, 3, 4, 5 or 6; r is 0, 1 or 2; and R , R and R are independently hydrogen, lower alkyl or phenyl, or two adjacent R or R groups represent a double bond or a fused benzene ring where p or q, respectively, is greater than 2; with the proviso that where r is 1 or 2, then there are 1 or two additional sites of coordination to the metal; or (ii) optionally substituted phenyl, wherein the phenyl, when substituted, has lower alkyl substituents, optionally with: proviso (A), wherein at least one of the substituents of Ar comprises boron, or with proviso (B), wherein at least one of substituents of Ar comprises a linkage to a pharmaceutically active substituent.

公开(公告)号：EP2673257B1

公开(公告)日：2018-07-18

申请号：EP12744282.0

申请日：2012-02-10

Applicant: Washington University

Inventor： SHARMA, Vijay ,  SIVAPACKIAM, Jothilingam ,  PIWNICA-WORMS, David

IPC: C07C211/49 ,  C07F5/00 ,  C05D9/00

CPC classification number: A61K51/0478 ,  C05D9/02 ,  C07B59/001 ,  C07B59/002 ,  C07C251/24 ,  C07F5/003

Abstract: Tracers that can be used for PET or SPECT imaging of the distribution of Pgp are disclosed. The tracers are metalloprobes that can comprise a radioactive metal ion such as 67Ga or 68Ga. Methods of synthesizing the tracers, and methods of imaging heart and other tissues are also disclosed. The tracers can be used to obtain high signal-to-background ratios for imaging tissues in vivo such as heart or tumor tissue. In various embodiments, disclosed tracers can exhibit, a) enhanced first pass extraction into heart tissue compared to presently available probes, b) linearity with true blood flow, c) enhanced detection of myocardial viability compared to presently available probes, d) reduced liver retention compared to presently available probes, and e) more efficient clearance from non-cardiac and adjoining tissues compared to presently available probes.

公开(公告)号：EP2673257A2

公开(公告)日：2013-12-18

申请号：EP12744282.0

申请日：2012-02-10

Applicant: Washington University

Inventor： SHARMA, Vijay ,  SIVAPACKIAM, Jothilingam ,  PIWNICA-WORMS, David

IPC: C07C211/49 ,  C07F5/00 ,  C05D9/00

CPC classification number: A61K51/0478 ,  C05D9/02 ,  C07B59/001 ,  C07B59/002 ,  C07C251/24 ,  C07F5/003

Abstract: Tracers that can be used for PET or SPECT imaging of the distribution of Pgp are disclosed. The tracers are metalloprobes that can comprise a radioactive metal ion such as 67Ga or 68Ga. Methods of synthesizing the tracers, and methods of imaging heart and other tissues are also disclosed. The tracers can be used to obtain high signal-to-background ratios for imaging tissues in vivo such as heart or tumor tissue. In various embodiments, disclosed tracers can exhibit, a) enhanced first pass extraction into heart tissue compared to presently available probes, b) linearity with true blood flow, c) enhanced detection of myocardial viability compared to presently available probes, d) reduced liver retention compared to presently available probes, and e) more efficient clearance from non cardiac and adjoining tissues compared to presently available probes.