Synthesis, structural, conformational and pharmacological study of esters derived from 3‐methyl‐2,4‐diphenyl‐3‐azabicyclo[3.3.1]nonan‐9α‐ol as potential analgesics

Abstract

A series of esters derived from 3-methyl-2,4-diphenyl-3-azabicyclo[3.3.1]nonan-9a-ol (1) was synthesized and studied by 1 H and 13 C NMR spectroscopy, and the crystal structure of 3-methyl-2,4-diphenyl-9a-(3,5-dimethylbenzoyloxy)-3-azabicyclo[3.3.1]nonane (2) was determined by x-ray diffraction. The compounds studied display in CDCl 3 a preferred flattened chair-chair conformation. This bicycle conformation is similar to that found for 2 in the crystal state. Pharmacological assays on mice were performed to evaluate drug-induced behavioral alteration, peripheral or central acute toxicity and analgesic activity.

Synthesis, structural, conformational and pharmacological study of some amides derived from 3-methyl-2,4-diphenyl-3-azabicyclo[3.3.1]nonan-9α-amine

“…The N-CH 3 13 C chemical shifts of compounds 2-5 of about 44 ppm (Table 2) agree with the values found in equatorial N-CH 3 substituted piperidines [4][5][6][7][8][9]12]. Furthermore, in the 13 C NMR spectra, the twin-chair conformation is confirmed by the C2(4) (73.86-73.89 ppm) and C6(8) (20.59-20.72 ppm) chemical shifts in agreement with previous work [4][5][6][7][8][9].…”

“…Assignment of proton resonances for compounds 2-5 was made on the basis of our previous studies for related systems [4][5][6][7][8][9]. The 1 H NMR spectra of compounds 2-5 showed great similarity in relation to the bicyclic systems.…”

“…In the 1 H NMR spectra, the W 1/2 value (8-9 Hz) for the H1(5) signals is in agreement with previously reported values for a flattened chair-chair conformation in related bicyclic systems [4][5][6][7][8][9]. For a boat disposition of one of these rings, the signal corresponding to H1(5) would be an apparent doublet with a coupling constant about 18 Hz [10].…”

“…For the assignment of the 13 C NMR chemical shifts (Table 2), substituent steric and electronic effects and our previous studies of related compounds [4][5][6][7][8][9] were taken into consideration.…”

“…As continuation of our studies on the synthesis of heterocyclic compounds with potential therapeutic activity, we report in this paper the synthesis and the structural study of a series of amides (2)(3)(4)(5) derived from 3-methyl-2,4-diphenyl-3-azabicyclo[3.3.1]nonan-9a-amine (1) by IR and NMR spectroscopy. The unambiguous assignment of all proton and carbon resonances was achieved by double resonance experiments.…”