Ronald J. Post

The synthesis of a conformationally restricted analog of the anti-migraine drug sumatriptan

The synthesis of 5-N-Methylaminosulfonylmethyl-3-(N-methylpyrrolidin-2-ylmethyl)indole (1), a conformationally restricted analog of the anti-migraine drug, sumatriptan, is described. To incorporate our novel stereogenic replacement for the aminoethyl sidechain in sumatriptan, a convergent synthesis of the 3,5-disubstituted indole (1) was employed which utilized an intramolecular Heck reaction as the cornerstone reaction.

Synthesis and reactivity of pyrrolo[3,2-e]indole: Removal of a N-BOM group from an unactivated indole

A practical synthesis of pyrrolo[3,2-e]indole (1) is described. Different hydrogenation conditions of the indol-4-ylacetonitrile (3) afforded either 1-BOM-pyrrolo[3,2-e]indole (4, 42% from 5-nitroindole) or 1-hydroxymethylpyrrolo[3,2-e]indole (5, 46% from 5-nitroindole). Removal of the benzyl group was found to be problematic, but could be accomplished in moderate yield. Treatment of the resulting 1-hydroxymethylpyrrolo[3,2-e]indole (5) with NaOH in THF afforded 1 (94% from 5). Limited studies on the chemistry of 1 are also presented.

The synthesis of conformationally/rotationally restricted analogs of the neurotransmitter serotonin

The syntheses of two novel conformationally/rotationally restricted analogs of the neurotransmitter serotonin which are modeled after the 5-HT2 receptor selective agonist CP-132,484 [a dihydropyrano[3,2-e]indole] are described.

Ethoxymethylenemalonates and Malononitriles (EMM reagents) as formic acid equivalents: Synthesis of fused-imidazoles under neutral or mildly acidic con

Abstract The use of ethoxymethylenemalonates and malononitriles (EMM reagents) for the efficient synthesis of fused imidazoles and related compounds is describe

A Simple Synthesis of 5-Amino-3-(2-dimethylaminoethyl) indole [5-Amino-N,N-dimethyltryptamine]

Abstract A short (three step) synthesis of 5-amino-3-(2-dimethylaminoethyl)indole [5-amino-N, N-dimethyltryptamine, 4] from commercially available starting materials is presented. Reaction of 5-nitroindole with oxalyl chloride followed by dimethylamine afforded N,N-dimethyl 5-nitroindole-3-glyoxamide (1), which was reduced by diborane to 5-nitro-3-(2-dimethylaminoethyl)indole (3). Catalytic reduction of (3) afforded the title compound in 19% overall yield from 5-nitroindole.

5-cyano-1-[3-(N-methylpyrrolidin-2R-ylmethyl)indol-5-yl] benzimidazole (CP-161,242): A potent, centrally active 5-HT1D receptor agonist and benzodiazepine partial agonist

Abstract The discovery of CP-161,242 (5-cyano-1-[3-(N-methylpyrrolidin-2R-ylmethyl)indol-5-yl]benzimidazole), a potent, selective, orally active central serotonin (5-HT1D) agonist [IC50 (binding) = 1.3 nM, EC50 (inhibition of adenylate cyclase) = 42 pM] and benzodiazepine ligand [IC50 (binding) = 3.3 nM], is presented.

THE DISCOVERY OF A NOVEL AND POTENT BENZODIAZEPINE RECEPTOR PHARMACOPHORE

Abstract 1-(Indol-5-yl)pyrido[2,3-b]imidazoles and 1-(indol-5-yl)benzimidazoles (1) have been found to be unique, novel templates for potent benzodiazepine receptor affinity. The “molecular switch” for this activity lies in the imidazole N3 atom: replacement of this nitrogen for carbon [i.e., as in 5-(indol-1-yl)indoles (2)] affords compounds devoid of affinity for the benzodiazepine receptor (Figure 1).