93499-05-9

Usage

Chemical class

Piperidineamines

Common use

Pharmaceutical industry as a therapeutic agent

Salt form

Dihydrochloride salt

Crystalline form

Yes, more stable than free base compound

Structural components

Methoxybenzyl group and piperidin-4-amine group

Pharmacological properties

Influenced by methoxybenzyl and piperidin-4-amine groups

Biological activity

Potential due to structural components

Importance

Significant in medicinal chemistry and drug development

Upstream product

• 73874-95-0 (piperidin-4-yl)carbamic acid tert-butyl ester 
• 24424-99-5 di-tert-butyl dicarbonate 
• 50541-93-0 4-amino-1-benzylpiperidine 
• 73889-19-7 tert-butyl (1-benzylpiperidin-4-yl)carbamate 
• 123-11-5 4-methoxy-benzaldehyde 
• 2746-25-0 p-Methoxybenzyl bromide 
• 824-94-2 p-methoxybenzyl chloride 

Relevant academic research and scientific papers

Design and development of novel thiazole-sulfonamide derivatives as a protective agent against diabetic cataract in Wistar rats via inhibition of aldose reductase

In recent years, ALR2 (aldose reductase) inhibitors have attracted attention for their effective ability to reduce the progression of diabetes-associated cataracts. Therefore, in the present article, we intended to develop novel thiazole-sulfonamide hybrids as a potent inhibitor of ALR2. These molecules significantly inhibited the ALR2 level in the rat lenses homogenate, where the most potent compound 7b showed activity comparable to sorbinil as standard. In Wistar rats, compound 7b improved the insulin level and body weight of the experimental animal together with a reduction in the glucose output. Compound 7b showed a significant reduction in the expression of ALR2 in rat lenses in western blot analysis.

Discovery and Biological Evaluation of N-Methyl-pyrrolo[2,3- b]pyridine-5-carboxamide Derivatives as JAK1-Selective Inhibitors

Janus kinase 1 (JAK1) plays a key role in most cytokine-mediated inflammatory and autoimmune responses through JAK/STAT signaling; thus, JAK1 inhibition is a promising therapeutic strategy for several diseases. Analysis of the binding modes of current JAK inhibitors to JAK isoforms allowed the design of N-alkyl-substituted 1-H-pyrrolo[2,3-b] pyridine carboxamide as a JAK1-selective scaffold, and the synthesis of various methyl amide derivatives provided 4-((cis-1-(4-chlorobenzyl)-2-methylpiperidin-4-yl)amino)-N-methyl-1H-pyrrolo[2,3-b]pyridine-5-carboxamide (31g) as a potent JAK1-selective inhibitor. In particular, the (S,S)-enantiomer of 31g (38a) exhibited excellent potency for JAK1 and selectivity over JAK2, JAK3, and TYK2. On investigating the effect of 31g on hepatic fibrosis, it was found that it reduces the proliferation and fibrogenic gene expression of TGF-β-induced hepatic stellate cells (HSCs). Specifically, 31g significantly inhibited TGF-β-induced migration of HSCs at 0.25 μM in wound-healing assays.

Substituted 2-thioxothiazolidin-4-one derivatives showed protective effects against diabetic cataract via inhibition of aldose reductase

In an effort to develop a new class of potent aldose reductase inhibitors against diabetic cataracts, a series of novel 2-thioxothiazolidine-4-one derivatives was synthesized in excellent yields via a facile synthetic route. These compounds were tested against aldehyde (ALR1) and aldose reductase (ALR2) enzymes, where they showed considerable inhibitory activity. Among the tested derivatives, compound 6e showed selective and excellent inhibition of ALR2 over ALR1. The experimental diabetes was induced by the intraperitoneal administration of streptozotocin in male Wistar rats. Compound 6e showed positive modulation of body weight, blood glucose, and blood insulin levels in diabetic rats. Compound 6e also showed ALR2 inhibition as evidenced by Western blot analysis in lens homogenates of Wistar rats having cataract. The docking study of 6e was also performed inside the active site of ALR2 to enumerate the key contacts for inhibitory activity.

2-PHENYLIMIDAZO[4,5-B]PYRIDIN-7-AMINE DERIVATES USEFUL AS INHIBITORS OF MAMMALIAN TYROSINE KINASE ROR1 ACTIVITY

Compound of formula (I′) or (I′′) or a pharmaceutically acceptable salt thereof. The compound is an inhibitor of mammalian kinase enzyme activity, including ROR1 tyrosine kinase activity and may be used in the treatment of disorders associated with such activity.

Rational Design and Multibiological Profiling of Novel Donepezil-Trolox Hybrids against Alzheimer's Disease, with Cholinergic, Antioxidant, Neuroprotective, and Cognition Enhancing Properties

A novel series of donepezil-trolox hybrids were designed, synthesized, and evaluated as multifunctional ligands against Alzheimer's disease (AD). Biological assays showed that these derivatives possessed moderate to good inhibitory activities against acetylcholinesterase (AChE) and monoamine oxidase B (MAO-B) as well as remarkable antioxidant effects. The optimal compound 6d exhibited balanced functions with good inhibition against hAChE (IC50 = 0.54 μM) and hMAO-B (IC50 = 4.3 μM), significant antioxidant activity (41.33 μM IC50 by DPPH method, 1.72 and 1.79 trolox equivalent by ABTS and ORAC methods), excellent copper chelation, and Aβ1-42 aggregation inhibition effect. Furthermore, cellular tests indicated that 6d has very low toxicity and is capable of combating oxidative toxin (H2O2, rotenone, and oligomycin-A) induced neurotoxicity. Most importantly, oral administration of 6d demonstrated notable improvements on cognition and spatial memory against scopolamine-induced acute memory deficit as well as d-galactose (d-gal) and AlCl3 induced chronic oxidative stress in a mouse model without acute toxicity and hepatotoxicity. In summary, both in vitro and in vivo results suggested that 6d is a valuable candidate for the development of a safe and effective anti-Alzheimer's drug.

NOVEL LIPOIC ACID-4-AMINO PIPERIDINE CONJUGATED COMPOUNDS AND USES OF THE SAME

The present invention relates to a novel lipoic acid/4-amino benzyl piperidine conjugated compound in which a lipoic acid as an antioxidant is conjugated with a 4-amino benzyl piperidine derivative, and to a pharmaceutical composition and functional health food composition containing the same for preventing or treating Alzheimer′s disease and degenerative diseases. The lipoic acid/4-amino benzyl piperidine conjugated compound according to the present invention exhibits activity to inhibit cholinesterase (ChE) of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), and thus is an effective material in the prevention or treatment of Alzheimer′s disease and degenerative diseases. The pharmaceutical composition of the present invention contains, as an active ingredient, the lipoic acid/4-amino benzyl piperidine conjugated compound that inhibits activity of cholinesterase (ChE), and thus can be used to prevent and treat Alzheimer′s disease and degenerative diseases and can be utilized as a functional health food for alleviating Alzheimer′s disease and degenerative diseases or improving learning ability and memory power.

Synthesis and studies on anticonvulsant and antibacterial activities of 1-Alkyl-4-(4H-1,2,4-triazol-4-yl)piperidine derivatives

Two series of 1-Alkyl-4-(4H-1,2,4-triazol-4-yl)piperidines and 1-Alkyl-4-(2H-1,2,4-triazol-3-one-4-yl) piperidines were synthesized and their anticonvulsant and antibacterial activities were evaluated. Pharmacological tests showed that three of the synthesized compounds (6c, 6k, 7m) displayed 100% protection at a dose of 100 mg/kg. 4-(1-Octylpiperidin-4-yl)-2,4-dihydro-3H-1,2,4-triazol-3-one (6c) was the most active compound in this study, with an ED50 of 65.4 mg/kg and a TD50 value of 241.2 mg/kg, resulting in a PI of 3.6. Four of the synthesized compounds showed potent inhibitory activity against gram positive bacteria staphylococcus aureus (RN4220, KCTC 209 and KCTC 503), especially against the strains of multidrug-resistant clinical isolates (MRSA3167/3506 and QRSA3505/3519). Among which compound 1-tetradeyl-4-(4H-1,2,4-triazol-4-yl)piperidine (7f) showed the most potent levels of activity (MIC = 2 ug/mL) against the gram-positive strains.

Development of cholinesterase inhibitors using 1-benzyl piperidin-4-yl (α)-lipoic amide molecules

A series of hybrid molecules between (α)-lipoic acid (ALA) and 4-amino-1-benzyl piperidines were synthesized and their in vitro cholinesterase (acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)) inhibitory activities were evaluated. Even thoug