Samuel George Gibson

Discovery and SAR of org 24598-a selective glycine uptake inhibitor.

The discovery of Org 24598, one of the first potent and selective inhibitors of the glycine transporter is discussed. In vitro structure-activity relationships (SARs) data for interaction of a ligand with this system is discussed.

Synthesis of 1-amino-1,2,3,14b-tetrahydro-4H-pyrido[1,2-d]-dibenzo[b,f][1,4]oxazepine and related compounds

The synthesis is described of the epimeric 1-amino-1,2,3,14b-tetrahydro-4H-pyrido [1,2-d]dibenzo [b,f][1,4]oxazepines 2 and their N-substituted analogues. The cis-amines 33, 36 and 38 were prepared from the ketone 31 by reduction of the corresponding oxime whereas the trans isomers 12, 50 and 51 were prepared from the 1-ethoxycarbonyl derivative 44 by Curtius degradation. Attempts to convert the trans alcohol 7 into the epimeric azido compound by an SN2 replacement reaction with sodium azide resulted in rearrangement to give the novel ring system, 14-azido-11-methoxy-1,2,14,14a-tetrahydro-4H-pyrrolo [1,2-d] dibenzo [b,g][1,4] oxazocine 24 instead of the titled compounds.

18-Norandrosta-8,11,13-trienes. Part III. 1-Amino-derivatives

The syntheses of 1α-amino-17,17-dimethyl-18-nor-5α-androsta-8,11,13-triene (9e) and its N-methyl derivatives are described. Bromination–dehydrobromination of 1α-benzolyoxy-17,17-dimethyl-18-nor-5α-androst-13-ene (6b) gave 1α-benzoyloxy-17,17-dimethyl-18-nor-5α-androsta-7,13-diene (7), which on subsequent bromination–dehydrobromination and saponification gave 17,17-dimethyl-18-nor-5α-androsta-8,11,13-trien-1α-ol (9a). This was converted into the 1α-amino-derivatives via the ketone (8a). Reduction of 17,17-dimethyl-18-nor-5α-androsta-8,11,13-trien-1-one (8a) with sodium in alcohol gave a mixture of the 1α- and 1β-alcohols (9a) and (10), whereas reduction with lithium aluminium hydride gave the 1α-epimer (9a) stereospecifically. Both methods of reduction when applied to the corresponding 1-oxime (8b) gave entirely the 1α-amine (9e), a result which is explained in terms of steric interaction between positions 1 and 11. The corresponding 1β-amines could not be prepared.