144734-22-5

Upstream product

• 50-00-0 formaldehyd 
• 56346-57-7 (4-fluorophenyl)-piperidin-4-ylmethanone 
• 462-06-6 fluorobenzene 
• 41776-24-3 1-methylpiperidine-4-carboxylic acid chloride 
• 92822-02-1 4-(4-fluorobenzyl)piperidine 
• 459-57-4 4-fluorobenzaldehyde 
• 77216-41-2 p-toluenesulphonyl-hydrazone of N-methylpiperid-4-one 
• 25519-77-1 1-(4-(4-fluorobenzoyl)piperidin-1-yl)ethanone 

Downstream Products

• 720674-19-1 4-fluorophenyl-1-methylpiperidin-4-yl-methanol 

Relevant academic research and scientific papers

Harnessing the Role of HDAC6 in Idiopathic Pulmonary Fibrosis: Design, Synthesis, Structural Analysis, and Biological Evaluation of Potent Inhibitors

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by a progressive-fibrosing phenotype. IPF has been associated with aberrant HDAC activities confirmed by our immunohistochemistry studies on HDAC6 overexpression in IPF lung tissues. We herein developed a series of novelhHDAC6 inhibitors, having low inhibitory potency overhHDAC1 andhHDAC8, as potential pharmacological tools for IPF treatment. Their inhibitory potency was combined with lowin vitroandin vivotoxicity. Structural analysis of 6h and structure-activity relationship studies contributed to the optimization of the binding mode of the new molecules. The best-performing analogues were tested for their efficacy in inhibiting fibrotic sphere formation and cell viability, proving their capability in reverting the IPF phenotype. The efficacy of analogue 6h was also determined in a validated human lung model of TGF-β1-dependent fibrogenesis. The results highlighted in this manuscript may pave the way for the identification of first-in-class molecules for the treatment of IPF.

Iron-catalyzed oxyfunctionalization of aliphatic amines at remote benzylic C-H sites

We report the development of an iron-catalyzed method for the selective oxyfunctionalization of benzylic C(sp3)-H bonds in aliphatic amine substrates. This transformation is selective for benzylic C-H bonds that are remote (i.e., at least three carbons) from the amine functional group. High site selectivity is achieved by in situ protonation of the amine with trifluoroacetic acid, which deactivates more traditionally reactive C-H sites that are α to nitrogen. The scope and synthetic utility of this method are demonstrated via the synthesis and derivatization of a variety of amine-containing, biologically active molecules.

Structure-activity relationships of diphenylpiperazine N-type calcium channel inhibitors

A novel series of compounds derived from the previously reported N-type calcium channel blocker NP118809 (1-(4-benzhydrylpiperazin-1-yl)-3,3-diphenylpropan-1-one) is described. Extensive SAR studies resulted in compounds with IC50 values in the range of 10-150 nM and selectivity over the L-type channels up to nearly 1200-fold. Orally administered compounds 5 and 21 exhibited both anti-allodynic and anti-hyperalgesic activity in the spinal nerve ligation model of neuropathic pain.

Urea derivatives as calcium channel blockers

Urea derivatives which comprise piperidine or piperazine rings and further substitution are effective in ameliorating conditions characterized by unwanted calcium ion channel activity.

Ketanserin Analogues: Structure-Affinity Relationships for 5-HT2 and 5-HT1C Serotonin Receptor Binding

Ketanserin is the prototypic 5-HT2 serotonin antagonist; although it has been an important tool for the study of serotonin pharmacology, it has had relatively little impact on drug design because remarkably little is known about its structure-affinity relationships.Furthermore, ketanserin also binds at 5-HT1C receptors and even less is known about the influence of its structural features on 5-HT1C receptor affinity.The present study reveals that the fluoro and carbonyl groups of the 4-fluorobenzoyl portion of ketanserin make small contributions to 5-HT2 binding and that the intact benzoylpiperidine moiety is an important feature.Ring opening of the piperidine ring reduces affinity.Although the quinazoline-2,4-dione moiety also contributes to binding, it appears to play a smaller role and can be structurally simplified with retention of 5-HT2 affinity.N-(4-Phenylbutyl)-4-(4-fluorobenzoyl)piperidine (39), for example, binds with nearly tha same affinity (Ki=5.3 nM) as ketanserin (Ki=3.5 nM).All of the compounds examined bind at 5-HT1C sites with lower affinity than ketanserin, and some of the simplified analogues bind with nearly 10 times the 5-HT2 versus 5-HT1C selectivity of ketanserin; however, none displays > 120 fold selectivity.Several of the compounds, such as the amide 32 and the urea 33 represent examples of new structural classes of 5-HT2 ligands.