Contrast agents for myocardial perfusion imaging

Abstract

The present disclosure is directed, in part, to compounds and methods for imaging myocardial perfusion, comprising administering to a patient a contrast agent which comprises a compound that binds MC-1, and an imaging moiety, and scanning the patient using diagnostic imaging.

1 - 25 . (canceled) 
     
     
         26 . A contrast agent comprising an imaging moiety and a compound selected from deguelin, pyridaben, pyridimifen, tebufenpyrad, a deguelin analog, a pyridaben analog, a pyridimifen analog, and a tebufenpyradanalog. 
     
     
         27 . The contrast agent of  claim 26  wherein the imaging moiety is a radioisotope for nuclear medicine imaging, a paramagnetic species for use in MRI imaging, an echogenic entity for use in ultrasound imaging, a fluorescent entity for use in fluorescence imaging, or a light-active entity for use in optical imaging. 
     
     
         28 . The contrast agent of  claim 27  wherein the paramagnetic species for use in MRI imaging is Gd 3+ , Fe 3+ , In 3+ , or Mn 2+ . 
     
     
         29 . The contrast agent of  claim 27  wherein the echogenic entity for use in ultrasound imaging is a fluorocarbon encapsulated surfactant microsphere. 
     
     
         30 . The contrast agent of  claim 27  wherein the radioisotope for nuclear medicine imaging is  11 C,  13 N,  18 F,  123 I,  125 I,  99m Tc,  95 Tc,  111 In,  62 Cu,  64 Cu,  67 Ga, or  68 Ga. 
     
     
         31 . The contrast agent of  claim 26  wherein the imaging moiety is  18 F. 
     
     
         32 . The contrast agent of  claim 26  wherein the imaging moiety is  99m Tc. 
     
     
         33 . The contrast agent of  claim 26 , having the structure of formula (IV) 
       
         
           
           
               
               
           
         
       
       wherein:
 J is selected from N(R 27 ), S, O, C(═O), C(═O)O, NHCH 2 CH 2 O, a bond, and C(═O)N(R 27 ), with each group being drawn with its left end attached to G and its right end attached to the carbon substituted with R 21  and R 22 ; 
 when present, K is selected from hydrogen, alkoxyalkyl, alkyloxy, aryl, C 1 -C 6  alkyl optionally substituted with an imaging moiety, heteroaryl, and an imaging moiety; 
 L is selected from hydrogen, alkoxyalkyl, alkyloxy, aryl, C 1 -C 6  alkyl optionally substituted with an imaging moiety, heteroaryl, and an imaging moiety; 
 M is selected from hydrogen, alkoxyalkyl, alkyloxy, aryl, C 1 -C 6  alkyl optionally substituted with an imaging moiety, heteroaryl, and an imaging moiety; or 
 L and M, together with the atom to which they are attached, form a three- or four-membered carbocyclic ring; 
 Q is halo or haloalkyl; 
 n is 0, 1, 2, or 3; 
 R 21 , R 22 , R 23 , R 24 , R 25 , R 26 , R 27 , R 28 , R 35 , R 36 , R 37 , R 38 , and R 39  are independently selected from hydrogen, C 1 -C 6  alkyl optionally substituted with an imaging moiety, and an imaging moiety; and 
 Y is selected from a bond, carbon, and oxygen, provided that when Y is a bond, K and L are absent and M is selected from aryl and heteroaryl; and provided that when Y is oxygen, K and L are absent and M is selected from hydrogen, alkoxyalkyl, aryl, C 1 -C 6  alkyl optionally substituted with an imaging moiety, and heteroaryl; 
 provided that at least one imaging moiety is present in formula (IV). 
 
     
     
         34 . The contrast agent of  claim 26  wherein the contrast agent is selected from 
       
         
           
           
               
               
           
         
       
     
     
         35 . The contrast agent of  claim 26 , having the structure of formula (V) 
       
         
           
           
               
               
           
         
       
       wherein
 J is selected from N(R 27 ), S, O, C(═O), C(═O)O, NHCH 2 CH 2 O, a bond, and C(═O)N(R 27 ); 
 K is selected from hydrogen, alkoxyalkyl, alkyloxy, aryl, C1-C6 alkyl optionally substituted with an imaging moiety, heteroaryl, and an imaging moiety; 
 when present, L is selected from hydrogen, alkoxyalkyl, alkyloxy, aryl, C 1 -C 6  alkyl optionally substituted with an imaging moiety, heteroaryl, and an imaging moiety; 
 when present, M is selected from hydrogen, alkoxyalkyl, alkyloxy, aryl, C 1 -C 6  alkyl optionally substituted with an imaging moiety, heteroaryl, and an imaging moiety; or 
 L and M, together with the atom to which they are attached, form a three- or four-membered carbocyclic ring; 
 T and U are independently selected from hydrogen, alkoxy, alkoxyalkyl, C 1 -C 6  alkyl optionally substituted with an imaging moiety, halo, and an imaging moiety; or 
 T and U, together with the carbon atoms to which they are attached, form a five- to six-membered aromatic or non-aromatic ring containing zero to two heteroatoms selected from oxygen, nitrogen, and sulfur; wherein said ring is optionally substituted with one, two, or three substituents independently selected from C 1 -C 6  alkyl optionally substituted with an imaging moiety and an imaging moiety; 
 n is 0, 1, 2, or 3; and 
 R 21 , R 22 , R 23 , R 24 , R 25 , R 26 , R 27 , and R 34  are independently selected from hydrogen, C 1 -C 6  alkyl optionally substituted with an imaging moiety, and an imaging moiety; 
 Y is selected from a bond, carbon, and oxygen, provided that when Y is a bond, K and L are absent and M is selected from aryl and heteroaryl; and provided that when Y is oxygen, K and L are absent and M is selected from hydrogen, alkoxyalkyl, aryl, C 1 -C 6  alkyl optionally substituted with an imaging moiety, and heteroaryl; 
 provided at least one imaging moiety is present in formula (V). 
 
     
     
         36 . The contrast agent of  claim 35  wherein J is O. 
     
     
         37 . The contrast agent of  claim 35  of formula (VI) 
       
         
           
           
               
               
           
         
       
       wherein
 R 23 , R 24 , R 25 , R 26 , and R 34  are independently selected from hydrogen, C 1 -C 6  alkyl optionally substituted with an imaging moiety, and an imaging moiety; 
 provided that at least one imaging moiety is present in formula (VI). 
 
     
     
         38 . A method of imaging myocardial perfusion comprising administering to a patient a contrast agent of  claim 26 , and scanning the patient using diagnostic imaging. 
     
     
         39 . The method of  claim 38 , wherein the imaging moiety is a radioisotope for nuclear medicine imaging, a paramagnetic species for use in MRI imaging, an echogenic entity for use in ultrasound imaging, a fluorescent entity for use in fluorescence imaging, or a light-active entity for use in optical imaging. 
     
     
         40 . The method of  claim 38 , wherein the imaging moiety is  18 F. 
     
     
         41 . The method of  claim 38 , wherein the contrast agent has the structure of formula (IV) according to  claim 33 . 
     
     
         42 . The method of  claim 38 , wherein the contrast agent has the structure of formula (V) according to  claim 35 . 
     
     
         43 . The method of  claim 38 , wherein the contrast agent has the structure of formula (VI) according to  claim 37 .