RADIOLABELED DERIVATIVES OF POTENT CHYMASE INHIBITORS
Methods of imaging tissue of a mammal which expresses chymase include administering to the mammal an effective amount of a radiolabeled chymase inhibitor. Radiopharmaceuticals that may be used in diagnostic imaging and therapeutic treatment of disease characterized by expression of chymase have the structure of Formula I:
1 . A compound of Formula I, its stereoisomer or pharmaceutically acceptable salt:
wherein:
R 1 is hydroxyl or an alkyl having 1 to 6 carbon atoms;
W is a sulfur atom or N—R 2 group;
R 2 is hydrogen or an alkyl group having 1 to 6 carbon atoms;
X is hydrogen, or a radioactive or non-radioactive halogen;
Y is a radioactive or non-radioactive halogen;
Z is a radioactive or non-radioactive halogen; and
one of X, Y, and Z is a radioactive halogen.
2 . The compound of claim 1 , wherein said radioactive halogen is 18 F, 123 I, 125 I, 131 I, or 76 Br.
3 . The compound of claim 1 , wherein W is a sulfur atom, R 1 is hydroxyl group or an alkyl group having 1 to 6 carbon atoms, and one of X, Y and Z is a radioactive halogen.
4 . The compound of claim 1 , wherein W is a sulfur atom, R 1 is hydroxyl group, X is a radioactive halogen, and Y and Z are independently a non-radioactive halogen.
5 . The compound of claim 1 , wherein W is a sulfur atom, R 1 is hydroxyl group, X is 18 F, and Y and Z are independently a non-radioactive halogen.
6 . The compound of claim 1 , wherein W is a sulfur atom, and R 1 is methyl group.
7 . The compound of claim 1 , wherein W is a sulfur atom, R 1 is methyl group, Z is 123 I, X is hydrogen, and Y are independently a non-radioactive halogen.
8 . The compound of claim 1 , wherein W is a sulfur atom, R 1 is methyl group, Y is 123 I, X is hydrogen, and Z is a non-radioactive halogen.
9 . The compound of claim 1 , wherein W is a N—R 2 group, R 2 is an alkyl group having 1 to 6 carbon atoms, and R 1 is an alkyl group having 1 to 6 carbon atoms.
10 . The compound of claim 1 , wherein W is an N-methyl group, R 1 is methyl group, X is 18 F, and Y and Z are independently a non-radioactive halogen.
11 . The compound of claim 1 which is:
12 . The compound of claim 1 which is:
13 . The compound of claim 1 which is:
14 . The compound of claim 1 which is:
15 . A method of imaging tissue of a mammal which expresses chymase comprising administering to said mammal an effective amount of a compound of Formula I, its stereoisomer or pharmaceutically acceptable salt:
wherein:
R 1 is hydroxyl or an alkyl having 1 to 6 carbon atoms;
W is a sulfur atom or N—R 2 group;
R 2 is hydrogen or an alkyl group having 1 to 6 carbon atoms;
X is hydrogen, or a radioactive or non-radioactive halogen;
Y is a radioactive or non-radioactive halogen;
Z is a radioactive or non-radioactive halogen; and
one of X, Y, and Z is a radioactive halogen.
16 . The method of claim 15 , wherein said radioactive halogen is 18 F, 123 I, 125 I, 131 I, or 76 Br.
17 . The method of claim 15 , wherein W is a sulfur atom or N-methyl group, and R 1 is hydroxyl or methyl group.
18 . The method of claim 15 , wherein the compound is:
19 . The method of claim 15 , wherein said mammal suffers from hypertension, diabetes, left ventricular dysfunction, heart failure, or atherosclerosis.
20 . The method of claim 19 further comprising administering to said mammal an effective amount of angiotensin-converting enzyme inhibitor.
21 . A method of imaging tissue of a mammal which expresses chymase comprising administering to said mammal an effective amount of a radiolabeled chymase inhibitor.
22 . The method of claim 21 , wherein said mammal suffers from a disease of hypertension, diabetes, left ventricular dysfunction, heart failure, or atherosclerosis.
23 . The method of claim 22 further comprising administering to said mammal an effective amount of a radiolabeled angiotensin-converting enzyme inhibitor.