Synthesis and characterization of nonsteroidal-linked M(CO)(3)+ (M = 99mTc, Re) compounds based on the androgen receptor targeting molecule flutamide.
Androgen receptors are overexpressed in most primary and metastatic prostate cancers. A series of single photon emission computed tomography imaging agents (SPECT) utilizing the organometallic radioactive imaging species, fac-99mTc(OH(2))(3)(CO)(3)+, were prepared on the basis of the structure of Flutamide, a potent nonsteroidal antiandrogen prostate cancer drug. Novel bifunctional chelate-linked Flutamide analogues were prepared using a newly developed universal alkylating reagent, 2-bromo-N-[4-nitro-3-(trifluoromethyl)phenyl]-acetamide, 1. From compound 1, several ligands (i.e., cysteine 2, histidine 5, imidazole 3) were conjugated to the flutamide derivative to yield targeting ligands capable of either tridentate or monodentate coordination in a "2 + 1" complex. fac-Re(CO)(3)+ complexes were prepared and characterized with the functionalized conjugates to yield fac-Re(CO)(3)(2-amino-3-(1-(2-(4-nitro-3-(trifluoromethyl)phenylamino)-2-oxoethyl)-1H-imidazol-4-yl) propanoate), 4, fac-Re (CO)(3)(2-(S-cysteinyl)-N-[4-nitro-3-(trifluoromethyl) phenyl]-acetamide), 6, and fac-Re(CO)(3)(picolinate)(2-(1H-imidazol-1-yl)-N-[4-nitro-3-(trifluoromethyl)phenyl]-acetamide), 7. The corresponding radioactive 99mTc analogues were prepared and stability studies of the radioactive compounds were also conducted.
He
Haiyang
H
Department of Chemistry, Washington State University, P.O. Box 644630, Pullman, Washington 99164, and University Research Office, University of Idaho, Moscow, Idaho 83844, USA.
Morely
Jennifer E
JE
Silva-Lopez
Elsa
E
Bottenus
Brienne
B
Montajano
Maribel
M
Fugate
Glenn A
GA
Twamley
Brendan
B
Benny
Paul D
PD
D004355:Drug Stability; D005485:Flutamide / Q000031:analogs & derivatives / Q000138:chemical synthesis*; D006801:Humans; D008297:Male; D015609:Organotechnetium Compounds / Q000138:chemical synthesis*; D011471:Prostatic Neoplasms / Q000188:drug therapy; D019275:Radiopharmaceuticals / Q000138:chemical synthesis; D011944:Receptors, Androgen; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
C410798:AR protein, human; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D011944:Receptors, Androgen; D005485:Flutamide