39146-45-7

Upstream product

• 51787-84-9 4-(1,4-dioxa-8-azaspiro<4.5>dec-8-yl)-4'-fluorobutyrophenone 
• 177-11-7 4,4-ethylenedioxy-piperidine 
• 3874-54-2 4-(4-fluorophenyl)-4-oxo-n-butyl chloride 

Downstream Products

• 185507-81-7 4-{4-[(4-Chloro-2-nitro-phenyl)-hydrazono]-piperidin-1-yl}-1-(4-fluoro-phenyl)-butan-1-one 
• 185507-83-9 1-(4-Fluoro-phenyl)-4-{4-[(4-methoxy-2-nitro-phenyl)-hydrazono]-piperidin-1-yl}-butan-1-one 
• 185507-80-6 1-(4-Fluoro-phenyl)-4-{4-[(2-nitro-phenyl)-hydrazono]-piperidin-1-yl}-butan-1-one 
• 185507-82-8 1-(4-Fluoro-phenyl)-4-{4-[(2-nitro-4-trifluoromethyl-phenyl)-hydrazono]-piperidin-1-yl}-butan-1-one 
• 185507-84-0 1-(4-Fluoro-phenyl)-4-{4-[(5-methoxy-2-nitro-phenyl)-hydrazono]-piperidin-1-yl}-butan-1-one 
• 1250265-69-0 1-(4-fluorophenyl)-4-[4-([2.2]paracyclophan-4-yl)-4-hydroxypiperidin-1-yl]butan-1-one 

Relevant academic research and scientific papers

Bioisosteric replacement leading to biologically active [2.2]Paracyclophanes with altered binding profiles for aminergic g-protein-coupled receptors

Exploring the chemical diversity space of GPCR ligands, we recently discovered [2.2]paracyclophanes as valuable atypical bioisosteres for secondary affinity and selectivity generating moieties. To find out if such an exchange also works for structural moieties that simulate the endogenous neurotransmitter, π1 or π2 or both systems π1 and π2 of three representative privileged structures of types 1, 2, and 3 were replaced by a [2.2]paracyclophane unit. Contributions of the respective functionalities to the binding affinities of a panel of relevant monoaminergic GPCRs were systematically examined. The study led to the paracyclophanylpiperazine 3a displaying excellent D3 affinity (Ki = 1.6 nM) and a strongly attenuated binding to D4, 5-HT1 and α1. Whereas functional experiments showed neutral D3 antagonist properties, mutagenesis studies indicated a binding mode that is similar to its lead compounds of type 3.

Spiro[1,2,4-benzotriazine-3(4H),4′-(1′-substituted)piperidines] and related compounds as ligands for sigma receptors

As analogues of some conformationally restricted spiropiperidine derivatives which are endowed with high affinity for σ1 receptor, a set of 16 spiro[1,2,4-benzotriazine-3(4H),4′-(1′-substituted)piperidines] and congeneric compounds was prepared and tested for affinity to σ1 receptor subtype. All N-arylalkyl substituted derivatives exhibited high affinity for the relevant receptor, with Ki in the low nanomolar range. Affinity for σ2 subtype (assayed only for a few representative compounds) was from one to three order of magnitude lower. Spiro[1,2,4-benzotriazine-3(4H),4′-(1′-benzyl)piperidine] (2), with a ratio Kiσ2/Kiσ1=7000 should represent the most selective σ1 ligand so far described.

Preparation and pharmacological activities of spiro[3,4-dihydro-6/7-R-1,2,4-benzotriazine-3,4'-(1'-substituted)piper idines]

A set of spiro[3,4-dihydro-1,2,4-benzotriazines-3,4'-piperidine] derivatives was prepared and subjected to a broad pharmacological screening. Many of these compounds are characterized by a 3-(4-fluorobenzoyl)propyl substituent on the piperidine nitrogen, thus resembling the p-fluorobutyrophenone antipsychotics. Modest dopamine antagonism was observed for the tested compounds, which however were mainly endowed with analgesic and antihypertensive activities. Antihypercholesterolemic activity was also seen in compound 5, which represents an interesting new lead, being completely structurally unrelated to the known agents in this field.