Biliary excretion of a stretched bilirubin in UGT1A1-deficient (Gunn) and Mrp2-deficient (TR-) rats.

The metabolism and biliary excretion of a stretched bilirubin analog with a p-xylyl group replacing the central CH2 hinge were investigated in normal rats, Gunn rats deficient in bilirubin conjugation, and TR- rats deficient in bilirubin glucuronide hepatobiliary transport. Unlike bilirubin, the analog was excreted rapidly in bile unchanged in all three rat strains after intravenous administration. In TR- rats biliary excretion of the analog was diminished, but still substantial, demonstrating that the ATP-binding cassette transporter Mrp2 is not required for its hepatic efflux.

Analogs of 3-hydroxy-1H-1-benzazepine-2,5-dione: structure-activity relationship at N-methyl-D-aspartate receptor glycine sites.

A series of aromatic and azepine ring-modified analogs of 3-hydroxy-1H-1-benzazepine-2,5-dione (HBAD) were synthesized and evaluated as antagonists at NMDA receptor glycine sites. Aromatic ring-modified HBADs were generally prepared via a Schmidt reaction with substituted 2-methoxynaphthalene-1,4-diones followed by demethylation. Electrophilic aromatic substitution of benzazepine 3-methyl ethers gave 7-substituted analogs.

On the structure of bilirubin in solution. 13C[1H] heteronuclear Overhauser effect NMR analyses in aqueous buffer and organic solvents.

Select hydrogen-carbon distances have been determined from 13C[1H] heteronuclear Overhauser effects observed in a 99% carbon-13 enriched 13CO2H bilirubin analog, [8(3), 12(3)-13C2]-mesobilirubin XIII alpha. Analysis of the data confirms that the propionic acid carbonyl lies within hydrogen bonding distance to the dipyrrinone lactam and pyrrole N-H groups in chloroform and indicates, surprisingly, that those distances are only slightly longer in dimethyl sulfoxide solvent or when the carboxyl group is ionized in pH 7.4 aqueous buffered solutions of the pigment.