5463-76-3

Usage

Uses

Used in Pharmaceutical Industry:
4-(1-piperidyl)butanoic acid is used as a GABA analog for its potential calming and sedative effects on the central nervous system. It is being investigated for its therapeutic potential in the treatment of various neurological and psychiatric disorders, such as anxiety, depression, and epilepsy.
Used in Research and Development:
In the field of GABA-related pharmacology and neurochemistry, 4-(1-piperidyl)butanoic acid serves as a valuable research tool. It aids scientists in understanding the mechanisms of action and potential therapeutic applications of GABA analogs, contributing to the advancement of treatments for neurological and psychiatric conditions.

InChI:InChI=1/C9H17NO2/c11-9(12)5-4-8-10-6-2-1-3-7-10/h1-8H2,(H,11,12)

Upstream product

• 116885-98-4 (piperidinyl-1)-4 butanoate d'ethyle 
• 110-89-4 piperidine 
• 2969-81-5 Ethyl 4-bromobutyrate 
• 5638-60-8 1,4-oxazepane 

Downstream Products

• 4672-11-1 4-piperidin-1-yl-butan-1-ol 
• 1314962-50-9 4-acetamidophenyl 4-(piperidin-1-yl)butanoate 
• 1314962-42-9 4-acetamidophenyl 4-(piperidin-1-yl)butanoate hydrochloride 

Relevant academic research and scientific papers

One-Component Multifunctional Sequence-Defined Ionizable Amphiphilic Janus Dendrimer Delivery Systems for mRNA

Efficient viral or nonviral delivery of nucleic acids is the key step of genetic nanomedicine. Both viral and synthetic vectors have been successfully employed for genetic delivery with recent examples being DNA, adenoviral, and mRNA-based Covid-19 vaccines. Viral vectors can be target specific and very efficient but can also mediate severe immune response, cell toxicity, and mutations. Four-component lipid nanoparticles (LNPs) containing ionizable lipids, phospholipids, cholesterol for mechanical properties, and PEG-conjugated lipid for stability represent the current leading nonviral vectors for mRNA. However, the segregation of the neutral ionizable lipid as droplets in the core of the LNP, the "PEG dilemma", and the stability at only very low temperatures limit their efficiency. Here, we report the development of a one-component multifunctional ionizable amphiphilic Janus dendrimer (IAJD) delivery system for mRNA that exhibits high activity at a low concentration of ionizable amines organized in a sequence-defined arrangement. Six libraries containing 54 sequence-defined IAJDs were synthesized by an accelerated modular-orthogonal methodology and coassembled with mRNA into dendrimersome nanoparticles (DNPs) by a simple injection method rather than by the complex microfluidic technology often used for LNPs. Forty four (81%) showed activity in vitro and 31 (57%) in vivo. Some, exhibiting organ specificity, are stable at 5 °C and demonstrated higher transfection efficiency than positive control experiments in vitro and in vivo. Aside from practical applications, this proof of concept will help elucidate the mechanisms of packaging and release of mRNA from DNPs as a function of ionizable amine concentration, their sequence, and constitutional isomerism of IAJDs.

Targeted Delivery of mRNA with One-Component Ionizable Amphiphilic Janus Dendrimers

Targeted and efficient delivery of nucleic acids with viral and synthetic vectors is the key step of genetic nanomedicine. The four-component lipid nanoparticle synthetic delivery systems consisting of ionizable lipids, phospholipids, cholesterol, and a PEG-conjugated lipid, assembled by microfluidic or T-tube technology, have been extraordinarily successful for delivery of mRNA to provide Covid-19 vaccines. Recently, we reported a one-component multifunctional sequence-defined ionizable amphiphilic Janus dendrimer (IAJD) synthetic delivery system for mRNA relying on amphiphilic Janus dendrimers and glycodendrimers developed in our laboratory. Amphiphilic Janus dendrimers consist of functional hydrophilic dendrons conjugated to hydrophobic dendrons. Co-assembly of IAJDs with mRNA into dendrimersome nanoparticles (DNPs) occurs by simple injection in acetate buffer, rather than by microfluidic devices, and provides a very efficient system for delivery of mRNA to lung. Here we report the replacement of most of the hydrophilic fragment of the dendron from IAJDs, maintaining only its ionizable amine, while changing its interconnecting group to the hydrophobic dendron from amide to ester. The resulting IAJDs demonstrated that protonated ionizable amines play dual roles of hydrophilic fragment and binding ligand for mRNA, changing delivery from lung to spleen and/or liver. Replacing the interconnecting ester with the amide switched the delivery back to lung. Delivery predominantly to liver is favored by pairs of odd and even alkyl groups in the hydrophobic dendron. This simple structural change transformed the targeted delivery of mRNA mediated with IAJDs, from lung to liver and spleen, and expands the utility of DNPs from therapeutics to vaccines.

MODIFIED DRUGS FOR USE IN LIPOSOMAL NANOPARTICLES

Drag derivatives are provided herein which are suitable for loading into liposomal nanoparticle carriers. In some preferred aspects, the derivatives comprise a poorly water-soluble drag derivatized with a weak-base moiety that facilitates active loading of the drag through a LN transmembrane pH or ion gradient into the aqueous interior of the LN. The weak-base moiety can optionally comprise a lipophilic domain that facilitates active loading of the drag to the inner monolayer of the liposomal membrane. Advantageously, LN formulations of the drag derivatives exhibit improved solubility, reduced toxicity, enhanced efficacy, and/or other benefits relative to the corresponding free drags.

Synthesis and evaluation of N-alkyl-S-[3-(piperidin-1-yl)propyl] isothioureas: High affinity and human/rat species-selective histamine H 3 receptor antagonists

S-Alkyl-N-alkylisothiourea compounds containing various cyclic amines were synthesized in the search for novel nonimidazole histamine H3 receptor (H3R) antagonists. Among them, four N-alkyl S-[3-(piperidin-1-yl)propyl]isothioureas 18, 19, 22, and 23 were found to exhibit potent and selective H3R antagonistic activities against in vitro human H3R, but were inactive against in vitro human H 4R. Furthermore, three alkyl homologs 18-20 showed inactivity for histamine release in in vivo rat brain microdialysis, suggesting differences in antagonist affinities between species. In addition, in silico docking studies of N-[4-(4-chlorophenyl)butyl]-S-[3-piperidin-1-yl)propyl]isothiourea 19 and a shorter homolog 17 with human/rat H3Rs revealed that structural differences between the antagonist-docking cavities of rat and human H 3Rs were likely caused by the Ala122/Val122 mutation.

N-[5-(5-fluoropyridin-3-yl)-1H-pyrazol-3-yl]-4-piperidin-1-ylbutyramide (SEN78702, WYE-308775): A medicinal chemistry effort toward an α7 nicotinic acetylcholine receptor agonist preclinical candidate

α7 nicotinic acetylcholine receptors (α7 nAChR) represent promising therapeutic candidates for the treatment of cognitive impairment associated with Alzheimer's disease (AD) and schizophrenia. A medicinal chemistry effort around previously reported compound 1 (SEN15924, WAY-361789) led to the identification of 12 (SEN78702, WYE-308775) a potent and selective full agonist of the α7 nAChR that demonstrated improved plasma stability, brain levels, and efficacy in behavioral cognition models.

Process for preparing acid salts of γ-(piperidyl)butyric acid

At least one of a Rh catalyst, a Pd catalyst or a Ru catalyst is used as a catalyst in preparing the salt of γ-(piperidyl)-butyric acid (2) by hydrogenating the salt of γ-(pyridyl)butyric acid (1) [preferably the salt of γ-(pyridyl)butyric acid (1) obtained in the undermentioned steps (a) and (b) and containing not more than 3% by weight of salt of bis(pyridylethyl)acetic acid (3)] in a solvent in the presence of a catalyst: (a) reacting the vinylpyridine (4) with the diester of malonic acid (5) in the presence of a base to give the 2-(pyridylethyl)malonic acid diester (6), and (b) hydrolyzing and decarboxylating the 2-(pyridylethyl)malonic acid diester (6) obtained in the step (a) in an acidic aqueous solution to give the salt of γ-(pyridyl)butyric acid (1).

Aqueous basicity and proton affinity of zwitterionic ω-(N-methylpiperidine)-alkanocarboxylates and ω-(N-piperidine)-alkanocarboxylic acids

The pK a values of 5 ω-(N-methylpiperidine)-alkanocarboxylates (N-methylpiperidine betaines) and 5 ω-(N-piperidine)-alkanocarboxylic acid were determined by potentiometric titration of their hydrohalides with KOH. Semiempirical geometry optimizations were performed for gaseous betaines. Four conformers were characterized and their PA values estimated. The PA values fulfilled the linear correlation with the aqueous pKa values estimated in ref. 1. A linear correlation between the calculated heat of formation (ΔHt) and the sum of the N...O1 and N...O2 distances, for the conformers containing the same number of CH2 groups, indicates that they are stabilized by the intramolecular electrostatic interactions between the positively charged nitrogen atom and oxygen atoms of the carboxylate group.