Tetracyclic indole derivatives as imaging agents in vivo and having affinity for peripheral benzodiazepine receptors (PBR)

摘要

A compound of formula I: ** Formula ** or a salt or solvate thereof, wherein said compound is labeled with an imaging moiety, and wherein: X1 and X2 are independently selected from hydrogen, halogen, alkoxy C1-6, C1-6 alkyl; R1 and R2 are independently selected from C1-6 alkyl, C1-6 aminoalkyl, (C1-6 alkoxy) alkyl, C1-6 alkoxy, C1-6 hydroxyalkyl, a group of polyethylene glycol (PEG), C3-10 cycloalkyl, C3- cycloethers 10, and C3-10 cycloamines; R3 is the group -A-R5, where: A is the optional group - (CH2) z-R6-, where z = 0-6, R6 is a 5- or 6-membered heterocycle having 1- 3 hetero atoms selected from N, S, and O, and wherein R5 is a substituent selected from hydrogen, C1-6 alkyl, C1-6 alkoxy, C1-6 alkenyl, C1-6 alkynyl, C1-6 alkanoyl, C1-6 haloalkyl , C1-6 haloalkenyl, C1-6 haloalkynyl, C1-6 haloalkoxy, C1-6 haloalkylthiol, C1-6 haloalkylsulfinyl, C1-6 haloalkylsulfonyl, (C1-6 haloalkyl ketone), sulfinyl, (C1-6 haloalkyl alkyl) ) sulfonyl, a polyethylene glycol (PEG) group, hydroxyC 1-6 alkyl, a C2-10 alkyl containing nitrogen and hydroxy; R4 is hydrogen, C1-6alkyl, C1-6alkanoyl, C1-6cycloalkyl, fluoroC1-6alkyl, hydroxy, or halogen: Y1 is S, SO, SO2, or CH2; n is 0 to 10; and wherein said imaging residue is selected from: (i) a radioactive metal ion; (ii) a paramagnetic metal ion; (iii) a radioactive gamma-ray emitting halogen; (iv) a radioactive non-metal positron emitter; (v) a hyperpolarized NMR active nucleus; (vi) a suitable indicator for in vivo optical imaging; and (vii) a β-emitter suitable for intravascular detection