857650-85-2

Upstream product

• 50541-93-0 4-amino-1-benzylpiperidine 
• 86-84-0 1-Naphthyl isocyanate 
• 879-18-5 naphthalene-1-carbonic acid chloride 

Downstream Products

• 857729-74-9 N-(piperidin-4-yl)-1-naphthamide 

Relevant academic research and scientific papers

Synthesis and in vitro binding studies of substituted piperidine naphthamides. Part I: Influence of the substitution on the basic nitrogen and the position of the amide on the affinity for D2L, D4.2, and 5-HT2A receptors

A series of 1- and 2-naphthamides has been prepared and tested for in vitro binding to D2L, D4.2, and 5-HT2A receptors. Different compounds display selectivity for D4.2 and 5-HT2A receptors versus Ds

Synthesis and in vitro binding studies of substituted piperidine naphthamides. Part II: Influence of the substitution on the benzyl moiety on the affinity for D2L, D4.2, and 5-HT2A receptors

In continuation of our work on N-(piperidin-4-yl)-naphthamides, the effect of substituted benzyl groups on D2L, D4.2, and 5-HT2A receptor affinity was evaluated. In the 1-naphthamide series most compounds were highly selective for D4.2 over D2L and 5-HT2A receptors. Halogen and methyl substitution in position 3 or 4 of the benzyl group increased D4.2 affinity. In the 2-naphthamide series a similar high D4.2 over D2L selectivity was retained while 5-HT2A affinity was increased. 3-Methoxy, 3-methyl, and 4-methyl substituents were favorable for D4.2 affinity while halogens reduced affinity. 2-Naphthamides with a 3-bromo- or a 3-methyl group were mixed D4.2/5-HT2A ligands similar to their unsubstituted parent compound. All compounds from both series with significant affinity for D4.2 and 5-HT2A receptors were antagonists.

5-HTX MODULATORS

This invention relates to compounds which bind to serotonin receptors inside or outside the central nervous system, in particular compounds which bind to the 5-HT2 or 5-HT7 receptors, their preparation and use, compositions containing them, and methods of treatment using them.

MODULATORS OF PERIPHERAL 5-HT RECEPTORS

Novel modulators of 5-HT4 receptors have been developed which have a selectivity for peripheral receptors rather than those of the central nervous systems. Theses include novel derivatives of known modulators as well as entirely novel entities. Surprisingly, the derivatised compounds of the known modulators maintain a high binding affinity to 5-HT4 receptors, despite the presence of an acidic moiety at the end of an optional chain. The entirely novel entities also exhibit good binding affinity to 5-HT4 receptors. All of the compounds of the invention have a common motif which includes a basic nitrogen moiety and an acidic moiety. The compounds of the invention, due at least in part to their high ionisation potential at physiological pH, have the unique properties of selectively for peripheral 5HT4 receptors over those of the CNS, good binding affinity, and selectively of 5HT4 receptors over other serotonin receptors.

Synthesis and structure-activity relationships of N-(1-benzylpiperidin-4-yl)arylacetamide analogues as potent σ1receptor ligands

A series of N-(1-benzylpiperidin-4-yl)arylacetamides were synthesized and evaluated for their binding properties for σ1 and σ2 receptors. In agreement with previously reported σ1/σ2 receptor binding data for N-(1-benzylpiperidin-4-yl)phenylacetamide, all of the N-(1-benzylpiperidin-4-yl)arylacetamide compounds reported below displayed higher affinity for σ1 vs σ1 receptors. Replacement of the phenyl ring of the phenylacetamide moiety with a thiophene, naphthyl, or indole aromatic ring had no significant effect on the σ1 receptor affinity. Replacement of the phenyl ring with an imidazole or pyridyl aromatic ring resulted in a >60-fold loss in affinity for σ1 receptors and no significant binding affinity for σ2 receptors. Substitution on the aromatic ring of the benzyl group showed a similar or slightly decreased affinity for σ1 receptors. Substitution on the aromatic rings of both the phenylacetamide moiety and the benzyl group with a halogen resulted in a similar affinity for σ1 receptors and a significantly increased affinity for σ2 receptors. Comparative molecular field analysis revealed that electrostatic properties of the substituents in the phenylacetamide aromatic ring strongly influenced binding to σ1 receptors. Compounds 1, 10, 18, 22, 37, and 40 showed the highest selectivity for σ1 receptors with Ki (σ2) to Ki (σ1) ratios of 100, >92, >122, 77, 74, and 80, respectively. In agreement with previously reported results, the phenylacetamide analogues had no binding affinity for dopamine receptors (D2/D3).