Vera Seidl

Intramolecular transaminations of enaminones: a synthesis of fused, polycyclic, N-aryl pyridones

Abstract 2-Arylamino-3-pyridinecarbonyl chlorides acylated the β-carbon atoms of enamines, and the resulting enaminones cyclized to give a series of fused polycyclic N-aryl pyridones. The series included 10-(3-chlorophenyl)-6,8,9,10-tetrahydrobenzo[b][1,8]naphthyridin-5(7H)-one (Sch 40120 ), an antipsoriatic agent.

Synthesis and structure–activity relationships of oxime neurokinin antagonists: discovery of potent arylamides

The structural modification of the benzylic ether region of oxime 1 has resulted in the identification of several novel aryl amides as selective or dual NK(1)/NK(2) antagonists.

Synthesis, structure, and reductive rearrangement of a novel tricyclic isoxazolidine

Abstract N-Oxidation of 2-methyl-3β-phenyl-2,3α,3aβ,6aβ-tetrahydrothieno [2,3-d] isoxazole-4,4-dioxide (1) gave a nitrone (2) which underwent an intramolecular 1,3-dipolar cycloaddition yielding a tricyclic isoxazolidine (4). A single-crystal X-ray analysis unequivocally established the structure of 4 as 9β-phenyl-2-oxa-6-thia-1-azatricyclo[3.3.1.03,7]nonan-4α-o1-6,6-dioxide. LiA1H4 and LiA1D4, reduced 4 exhaustively and rearranged it profoundly to isotopomers 5 and 6, respectively ; a novel Grob fragmentation may have mediated the rearrangement. Inter alia, measurements of 13C-13C coupling constants and of m z ratios of fragment ions yielded the complete structures of 5 and 6. They are 5β-phenyl-8-thia-6-azabicyclo[3. 3. 1]octan-2α-o1 and its 3α-deuterio analog, respectively.

Transfer hydrogenolysis: an improved synthesis of (R)-(-)-α-Methyl Histamine

Abstract Ammonium formate in the presence of palladium on carbon in methanol reacted with (S)-(+)4-(2-Amino-3-chloropropyl)-imidazole to give optically pure (R)-(−)-α-methyl histamine at atmospheric pressure.

In vitro metabolism of 10-(3-chlorophenyl)-6,8,9,10-tetrahydrobenzo[b][1,8]naphthyridin-5(7H)-one, a topical antipsoriatic agent. Use of precision-cut rat, dog, monkey and human liver slices, and chemical synthesis of metabolites

The metabolism of SCH 40120, which is the clinically effective antipsoriatic drug 10‐(3‐chlorophenyl)‐6,8,9,10‐tetrahydrobenzol[b][1,8]naphthyridin‐5(7H)‐one, was determined in vitro. Rat, dog, cynomolgus monkey, and human liver slices hydroxylated the aliphatic, cyclohexenyl ring of the drug and conjugated the resulting carbinol. The identified metabolites comprised the corresponding 6‐, 7‐, and 9‐carbinols, the glucuronide of the 6‐carbinol, and the 6‐ketone derived from the parent drug.

Base-induced condensation of phenols joined by amides to ketones : a synthesis of hydroxylated isoquinolinones and derivatives

Potassium carbonate in methanol saponified the acetate ester groups of certain meta-acetoxylated α-benzamido ketones and cyclized the resulting phenols in situ to give a series of hydroxylated isoquinolinones and derivatives