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US 8,778,305 B2Granted
PSMA-binding agents and uses thereof
AssigneeThe Johns Hopkins University
InventorsMartin Pomper, Ronnie Charles Mease, Ying Chen
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Abstract
Prostate-specific membrane antigen (PSMA) binding compounds having radioisotope substituents are described, as well as chemical precursors thereof. Compounds include pyridine containing compounds, compounds having phenylhydrazine structures, and acylated lysine compounds. The compounds allow ready incorporation of radionuclides for single photon emission computed tomography (SPECT) and positron emission tomography (PET) for imaging, for example, prostate cancer cells and angiogenesis.
Claims18
A compound having the structure
- Wherein Z is tetrazole or CO2Q;
- each Q is independently selected from hydrogen or a protecting group;
- and wherein
- (A) m is 0, 1, 2, 3, 4, 5, or 6;
- R is a pyridine ring selected from the group consisting of
- wherein X is fluorine, iodine, a radioisotope of fluorine, a radioisotope of iodine, chlorine, bromine, a radioisotope of bromine, a radioisotope of astatine, NO2, NH2, N+(R2)3, Sn(R2)3, Si(R2)3, Hg(R2), B(OH)2, —NHNH2, —NHN═CHR3, —NHNH—CH2R3;
- n is 1, 2, 3, 4, or 5;
- Y is O, S, N(R′), C(O), NR′C(O), C(O)N(R′), OC(O), C(O)O, NR′C(O)NR′, NR′C(S)NR′, NR′S(O)2, S(CH2)p, NR′(CH2)p, O(CH2)p, OC(O)CHR8NHC(O), NHC(O)CHR8NHC(O), or a covalent bond;
- wherein p is 1, 2, or 3, R′ is H or C1-C6 alkyl, and R8 is hydrogen, alkyl, aryl or heteroaryl, each of which may be substituted;
- R2 is C1-C6 alkyl;
- and
- R3 is alkyl, alkenyl, alkynyl, aryl, or heteroaryl each of which is substituted by fluorine, iodine, a radioisotope of fluorine, a radioisotope of iodine, chlorine, bromine, a radioisotope of bromine, or a radioisotope of astatine, NO2, NH2, N+(R2)3, Sn(R2)3, Si(R2)3, Hg(R2), or B(OH)2.
9 more elements
Dependencies are inferred from the claim text.