409127-86-2

Upstream product

• 501-94-0 p-hydroxyphenethyl alcohol 
• 5472-49-1 1-(3-chloropropyl)piperidine hydrochloride 
• 110-89-4 piperidine 
• 214614-63-8 2-[(4-bromopropoxy)phenyl]ethyl alcohol 
• 913851-39-5 4-(3-chloropropoxy)phenylacetonitrile 
• 1239461-49-4 methyl 2-(4-(3-(piperidin-1-yl)propoxy)phenyl)acetate 
• 14191-95-8 4-cyanomethylphenol 

Downstream Products

• 409127-88-4 toluene-4-sulfonic acid 2-(4-(3-piperidinopropoxy)phenyl)ethyl ester 

Relevant academic research and scientific papers

Compound for treating schizophrenia and application of compound

The invention provides an H3 receptor compound and an application thereof. In vitro experiments of the compound show that the compound has high affinity to H3, suggesting that negative symptoms and cognitive disorders can be improved. Compared with risper

Novel and highly potent histamine H3 receptor ligands. Part 3: An alcohol function to improve the pharmacokinetic profile

Synthesis and biological evaluation of potent histamine H3 receptor antagonists incorporating a hydroxyl function are described. Compounds in this series exhibited nanomolar binding affinities for human receptor, illustrating a new possible component for the H3 pharmacophore. As demonstrated with compound BP1.4160 (cyclohexanol 19), the introduction of an alcohol function counter-intuitively allowed to reach high in vivo efficiency and favorable pharmacokinetic profile with reduced half-life.

Development of a new class of nonimidazole histamine H3 receptor ligands with combined inhibitory histamine N-methyltransferase activity

In search of novel ways to enhance histaminergic neurotransmission in the central nervous system, a new class of nonimidazole histamine H3 receptor ligands were developed that simultaneously possess strong inhibitory activity on the main histamine metabolizing enzyme, histamine N-methyltransferase (HMT). The novel compounds contain an aminoquinoline moiety, which is an important structural feature for HMT inhibitory activity, connected by different spacers to a piperidino group (for H3 receptor antagonism). Variation of the spacer structure provides two different series of compounds. One series, having only an alkylene spacer between the basic centers, led to highly potent HMT inhibitors with moderate to high affinity at human histamine H3 receptors. The second series possesses a p-phenoxypropyl spacer, which may be extended by another alkylene chain. This latter series also showed strong inhibitory activity on HMT, and in most cases, the H3 receptor affinity even surpassed that of the first series. One of the most potent compounds with this dual mode of action is 4-(4-(3-piperidinopropoxy)phenylamino)quinoline (34) (hH3, Ki = 0.09 nM; HMT, IC50 = 51 nM). This class of compounds showed high antagonist potency and good H3 receptor selectivity in functional assays in guinea pig on H1, H2, and H3 receptors. Because of low or missing in vivo activity of two selected compounds, the proof of concept of these valuable pharmacological tools for the supposed superior overall enhancing effect on histaminergic neurotransmission failed to appear hitherto.