223514-16-7

Usage

Uses

Used in Pharmaceutical Industry:
Piperazine, 1-(6-fluoro-2-pyridinyl)(9CI) is used as a key intermediate compound for the synthesis of dihydroceramide desaturase inhibitors. These inhibitors play a crucial role in treating various diseases by targeting and modulating the activity of dihydroceramide desaturase, an enzyme involved in cellular processes and disease progression.

Upstream product

• 1016167-46-6 4-(6-fluoropyridin-2-yl)piperazine-1-carboxylic acid t-butyl ester 
• 1513-65-1 2,6-difluoro pyridine 
• 223514-14-5 1-acetyl-4-(6-fluoropyridin-2-yl)piperazine 

Downstream Products

• 1016167-59-1 C₁₇H₁₈FN₅ 
• 1443744-70-4 C₂₈H₂₉FN₆O₅S 
• 1443745-34-3 C₂₃H₂₁FN₆O₃S 
• 1351411-09-0 1-cyclohexyl-N-(4-(4-(6-fluoropyridin-2-yl)piperazin-1-yl)butyl)methane-sulfonamide 
• 1351410-22-4 N-(3-(4-(6-fluoropyridin-2-yl)piperazin-1-yl)propyl)-4-phenylthiazol-2-amine 
• 1351410-82-6 N-(2-(4-(6-fluoropyridin-2-yl)piperazin-1-yl)ethyl)cyclohexanecarboxamide 
• 1351410-69-9 N-(3-(4-(6-fluoropyridin-2-yl)piperazin-1-yl)propyl)cyclohexanecarboxamide 
• 1351410-60-0 N-(4-(4-(6-fluoropyridin-2-yl)piperazin-1-yl)butyl)cyclohexanecarboxamide 
• 223512-05-8 N-(4-((4-(6-Fluoropyridin-2-yl)piperazin-1-yl)methyl)phenylmethyl)acetamide Hydrochloride 

Relevant academic research and scientific papers

Development of an 18F-Labeled Irreversible Inhibitor of Transglutaminase 2 as Radiometric Tool for Quantitative Expression Profiling in Cells and Tissues

The transamidase activity of transglutaminase 2 (TGase 2) is considered to be important for several pathophysiological processes including fibrotic and neoplastic tissue growth, whereas in healthy cells this enzymatic function is predominantly latent. Methods that enable the highly sensitive detection of TGase 2, such as application of radiolabeled activity-based probes, will support the exploration of the enzyme's function in various diseases. In this context, the radiosynthesis and detailed in vitro radiopharmacological evaluation of an 18F-labeled N?-acryloyllysine piperazide are reported. Robust and facile detection of the radiotracer-TGase 2 complex by autoradiography of thin layer plates and polyacrylamide gels after chromatographic and electrophoretic separation owing to irreversible covalent bond formation was demonstrated for the isolated protein, cell lysates, and living cells. By use of this radiotracer, quantitative data on the expression profile of activatable TGase 2 in mouse organs and selected tumors were obtained for the first time by autoradiography of tissue sections.

N?-Acryloyllysine Piperazides as Irreversible Inhibitors of Transglutaminase 2: Synthesis, Structure-Activity Relationships, and Pharmacokinetic Profiling

Transglutaminase 2 (TGase 2)-catalyzed transamidation represents an important post-translational mechanism for protein modification with implications in physiological and pathophysiological conditions, including fibrotic and neoplastic processes. Consequently, this enzyme is considered a promising target for the diagnosis of and therapy for these diseases. In this study, we report on the synthesis and kinetic characterization of N?-acryloyllysine piperazides as irreversible inhibitors of TGase 2. Systematic structural modifications on 54 new compounds were performed with a major focus on fluorine-bearing substituents due to the potential of such compounds to serve as radiotracer candidates for positron emission tomography. The determined inhibitory activities ranged from 100 to 10?000 M-1 s-1, which resulted in comprehensive structure-activity relationships. Structure-activity correlations using various substituent parameters accompanied by covalent docking studies provide an advanced understanding of the molecular recognition for this inhibitor class within the active site of TGase 2. Selectivity profiling of selected compounds for other transglutaminases demonstrated an excellent selectivity toward transglutaminase 2. Furthermore, an initial pharmacokinetic profiling of selected inhibitors was performed, including the assessment of potential membrane permeability and liver microsomal stability.

HETEROCYCLIC COMPOUNDS AS IMAGING PROBES OF TAU PATHOLOGY

Pyridazinone compounds of Formula I: (I) wherein: R' is alkyl or Ar, optionally substituted with at least one alkyl, halo? gen, hydroxyl, alkoxy, haloalkoxy, acid, ester, amino, nitro, amide, or alkoxyhalo; 2 R is independently alkyi, alkynyl, ester, amino, amide, acid, aryl, heteroaryl, aminoalkyl, -C(=0)alkyl, -C(=0)aryl, -C(=0)heteroaryl, -C(=0)heterocycloalkyl, - C(=0)heterocycloalkylAr, -C(=0)(CH2)nhalo, -C(=0)(CH2)nheterocyclyl, or -SC^Ar, optionally substituted with at least one alkyi, alkylhalo, halogen, nitro, aryl, heteroaryl, or heteroaryl(CH2)nhalo; R 3 and R4 are independently hydrogen, alkyi, alkenyl, alkynyl, aryl, heteroaryl; Ar is an aryl, heteroaryl, cycloalkyl, heterocycloalkyl group; n is an integer from 0-10; or a radiolabeled derivative thereof. The compounds are useful as imaging probes of Tau pathology in Alzheimer's disease are described. Compositions and methods of making such compounds are also described.

Synthesis, radiofluorination, and in vitro evaluation of pyrazolo[1,5-a]pyridine-based dopamine D4 receptor ligands: Discovery of an inverse agonist radioligand for PET

A series of fluoro-substituted analogs structurally derived from the aminomethyl-substituted pyrazolo[1,5-a]pyridine lead compounds 9 (FAUC 113) and 10 (FAUC 213) were synthesized and evaluated as high-affinity D4 receptor (D4R) ligands (3a-3h, Ki = 1.3-28 nM). The para-fluoroethoxy-substituted derivatives 3f and 3h revealed an outstanding D4 subtype selectivity of more than 3 orders of magnitude over both congeners D2 and D3 combined with inverse agonism at D4R. The corresponding 18F-labeled radioligands revealed high serum stability in vitro and log P values of 2-3. In vitro rat brain autoradiography showed specific binding of [18F]3h in distinct brain regions, including the gyrus dentate of the hippocampus, that were inhibited by both eticlopride (65-80%) and the selective D4R antagonist 10 (78-93%). The observed binding pattern was mainly consistent with the known D4R distribution in the rat brain. Thus, [18F]3h (FAUC F41) represents a potential radioligand for studying the D4R in vivo by positron emission tomography (PET).

Piperazine compounds and medicinal use thereof

The present invention relates to a piperazine compound of the formula wherein R1and R2are each hydrogen, halogen, lower alkyl, lower alkoxy, amino, substituted amino, nitro, hydroxy or cyano, R3, R4and R5are each hydrogen, halogen, lower alkyl, lower alkoxy, nitro, amino, substituted amino or hydroxy, R6and R7are each hydrogen, lower alkyl, lower alkyl substituted by halogen, aralkyl, acyl or lower acyl substituted by halogen, R8and R9are each hydrogen or lower alkyl, Y is lower alkylene and the like, and ring A is phenyl, pyrimidyl, thiazolyl, pyridyl, pyrazyl or imidazolyl, a pharmaceutically acceptable salt thereof and pharmaceutical agents containing these compounds. The compound of the present invention has superior TNF-α production inhibitory effect and/or IL-10 production promoting effect, and, since it is free of or shows only strikingly reduced expression of an effect on the central nervous system, the compound is useful as a highly safe and superior TNF-α production inhibitor an/or IL-10 production promoter and is useful as an agent for the prophylaxis or treatment of various diseases caused by abnormal TNF-α production, diseases curable with IL-10, such as chronic inflammatory diseases, acute inflammatory diseases, inflammatory diseases due to infection, autoimmune diseases, allergic diseases, and TNF-α mediated diseases.