Selective κ-Opioid Agonists: Synthesis and Structure-Activity Relationships of Piperidines Incorporating an Oxo-Containing Acyl Group was written by Giardina, Giuseppe;Clarke, Geoffrey D.;Dondio, Giulio;Petrone, Giuseppe;Sbacchi, Massimo;Vecchietti, Vittorio. And the article was included in Journal of Medicinal Chemistry in 1994.Formula: C4H7NO This article mentions the following:
The (S)-(-)-enantiomers of a novel class of 2-(aminomethyl)piperidine derivatives were prepared and and the structure-activity relationships (SARs) studied using κ-opioid binding affinity and antinociceptive potency as the indexes of biol. activity. Compounds incorporating the 1-tetralon-6-ylacetyl residue I (R = Me, Et; R1 = alkyl, cycloalkyl; RR1N = pyrrolidino) demonstrated an in vivo antinociceptive activity greater than predicted on the basis of their κ-binding affinities. In particular, (2S)-2-[(dimethylamino)methyl]-1-[(5,6,7,8-tetrahydro-5-oxo-2-naphthyl)acetyl]piperidine (I, R = R1 = Me) was found to have a potency similar to spiradoline in animal models of antinociception after s.c. administration, with ED50s of 0.47 and 0.73 μmol/kg in the mouse and in the rat abdominal constriction tests, resp. Further in vivo studies in mice and/or rats revealed that compound I (R = R1 = Me), compared to other selective κ-agonists, has a reduced propensity to cause a number of κ-related side effects, including locomotor impairment/sedation and diuresis, at antinociceptive doses. For example, it has an ED50 of 26.5 μmol/kg s.c. in the rat rotarod model, exhibiting a ratio of locomotor impairment/sedation vs analgesia of I (R = R1 = Et). Possible reasons for this differential activity and its clin. consequence are discussed. In the experiment, the researchers used many compounds, for example, N-Cyclopropylformamide (cas: 58644-54-5Formula: C4H7NO).
N-Cyclopropylformamide (cas: 58644-54-5) belongs to amides. Amides are pervasive in nature and technology. Proteins and important plastics like Nylons, Aramid, Twaron, and Kevlar are polymers whose units are connected by amide groups (polyamides); these linkages are easily formed, confer structural rigidity, and resist hydrolysis. Amides are stable compounds. The lower-melting members (such as acetamide) can be readily purified by fractional distillation. Most amides are solids which have low solubilities in water.Formula: C4H7NO
Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics