A series of potent and selective beta(1)-adrenoreceptor ligands were identified (IC(50) range, 0.04-0.25 nM; beta(1)/beta(2) selectivity range, 65-450-fold), labeled with the PET radioisotope fluorine-18 and evaluated in...
Hybrid nitrate drugs have been reported to provide NO bioactivity to ameliorate side effects or to provide ancillary therapeutic activity. Hybrid nitrate selective serotonin reuptake inhibitors (NO-SSRIs) were prepared t...
The natural product aigialomycin D (1) is a member of the resorcylic acid lactone (RAL) family possessing protein kinase inhibitory activities. This paper describes the synthesis of aigialomycin D and a series of its ana...
Classic galactosemia is a rare human disease associated with the accumulation of a toxic level of galactose-1-phosphate (gal-1P) caused by the inherited deficiency of galactose-1-phosphate uridyltransferase (GALT) activi...
(18)F-labeled imidazo[2,1-b]benzothiazole ([(18)F]8) was synthesized and evaluated as a tracer for cerebral beta-amyloid deposits (A beta) by means of positron emission tomography (PET). [(18)F]8 exhibits a high affinity...
17 beta-Hydroxysteroid dehydrogenase type 1 (17 beta-HSD1) represents a promising therapeutic target for breast cancer treatment. To reduce the undesirable estrogenic activity of potent 17 beta-HSD1 inhibitor 16 beta-(m-...
The new emerging immunosuppressive effects displayed by iminosugars have not been much investigated so far. Several new N-alkyl dideoxy iminoalditols were designed and synthesized to explore their immunosuppressive effec...
The formation of unusual seven-membered, sterically overloaded chelates [Pt(en)(L/L')](NO(3))(2) (4a/4b) from the corresponding potent hybrid antitumor agents [PtCl(en)(LH/L'H)](NO(3))(2) (3a/3b) is described, where en i...
The synthesis of 4'-ethynyl-2'-deoxy-4'-thioribonucleosides was carried out utilizing an electrophilic glycosidation in which 4-ethynyl-4-thiofuranoid glycal 16 served as a glycosyl donor. Electrophilic glycosidation bet...
The synthesis of a stereochemically diverse library of medium-sized rings accessible via a "build/couple/pair" strategy is described. Key aspects of the synthesis include S(N)Ar cycloetherification of a linear amine temp...
Cystic fibrosis (CF) is a loss-of-function disease caused by mutations in the CF transmembrane conductance regulator (CFTR) protein, a chloride ion channel that localizes to the apical plasma membrane of epithelial cells...
Inhibition of dihydroorotate dehydrogenase (DHODH) for P. falciparum potentially represents a new treatment option for malaria, since DHODH catalyzes the rate-limiting step in the pyrimidine biosynthetic pathway and P. f...