45813-02-3

Usage

Uses

Used in Pharmaceutical and Agrochemical Industries:
1-Methyl-4-prop-2-ynyl-piperazine is used as a building block in the synthesis of various pharmaceuticals and agrochemicals due to its versatile chemical structure and reactivity.
Used in Central Nervous System Disorders Treatment:
1-Methyl-4-prop-2-ynyl-piperazine is used as a potential treatment for central nervous system disorders, leveraging its neuroprotective properties to support the health and function of the nervous system.
Used in Medicinal Chemistry Research:
1-Methyl-4-prop-2-ynyl-piperazine is used as a precursor in the synthesis of other biologically active compounds, making it an important chemical in the field of medicinal chemistry for the development of new therapeutic agents.

InChI:InChI=1/C8H14N2/c1-3-4-10-7-5-9(2)6-8-10/h1H,4-8H2,2H3

Upstream product

• 109-01-3 1-methyl-piperazine 
• 107-14-2 chloroacetonitrile 
• 624-65-7 2-propynyl chloride 
• 106-96-7 propargyl bromide 
• 50422-36-1 1-(2-bromo-allyl)-4-methyl-piperazine 

Downstream Products

• 872513-36-5 (2,4-difluoro-phenyl)-(3-{2-methoxy-5-[3-(4-methyl-piperazin-1-yl)-prop-1-ynyl]-phenyl}-1H-pyrazolo-[3,4-d]pyrimidin-6-yl)-amine 
• 214487-27-1 4-(4-methyl-piperazin-1-yl)-but-2-ynoic acid 
• 1453297-31-8 5-[(4-methylpiperazin-1-yl)methyl]-2-tosylisoindoline 
• 1215011-29-2 2,6-dichloro-4-[3-(4-methyl-piperazin-1-yl)-propyl]-N-(1,3,5-trimethyl-1H-pyrazol-4-yl)-benzenesulfonamide 
• 1215011-34-9 4-[3-(4-methylpiperazin-1-yl)-prop-1-ynyl]-N-(1,3,5-trimethyl-1H-pyrazol-4-yl)benzenesulfonamide 

Relevant academic research and scientific papers

Discovery of fast-acting dual-stage antimalarial agents by profiling pyridylvinylquinoline chemical space via copper catalyzed azide-alkyne cycloadditions

To identity fast-acting, multistage antimalarial agents, a series of pyridylvinylquinoline-triazole analogues have been synthesized via CuAAC. Most of the compounds display significant inhibitory effect on the drug-resistant malarial Dd2 strain at low submicromolar concentrations. Among the tested analogues, compound 60 is the most potent molecule with an EC50 value of 0.04 ± 0.01 μM. Our current study indicates that compound 60 is a fast-acting antimalarial compound and it demonstrates stage specific action at the trophozoite phase in the P. falciparum asexual life cycle. In addition, compound 60 is active against both early and late stage P. falciparum gametocytes. From a mechanistic perspective, compound 60 shows good activity as an inhibitor of β-hematin formation. Collectively, our findings suggest that fast-acting agent 60 targets dual life stages of the malarial parasites and warrant further investigation of pyridylvinylquinoline hybrids as new antimalarials.

A click chemistry approach to pleuromutilin derivatives, evaluation of anti-MRSA activity and elucidation of binding mode by surface plasmon resonance and molecular docking

Novel series of pleuromutilin analogs containing substituted 1,2,3-triazole moieties were designed, synthesised and assessed for their in vitro antibacterial activity against Methicillin-resistant Staphylococcus aureus (MRSA). Initially, the in vitro antibacterial activities of these derivatives against 4 strains of S. aureus (MRSA ATCC 43300, ATCC 29213, AD3, and 144) were tested by the broth dilution method. Most of the synthesised pleuromutilin analogs displayed potent activities. Among them, compounds 50, 62, and 64 (MIC = 0.5～1 μg/mL) showed the most effective antibacterial activity and their anti-MRSA activity were further studied by the time-killing kinetics approach. Binding mode investigations by surface plasmon resonance (SPR) with 50S ribosome revealed that the selected compounds all showed obvious affinity for 50S ribosome (KD = 2.32 × 10?8～5.10 × 10?5 M). Subsequently, the binding of compounds 50 and 64 to the 50S ribosome was further investigated by molecular modelling. Compound 50 had a superior docking mode with 50S ribosome, and the binding free energy of compound 50 was calculated to be ?12.0 kcal/mol.

1,5,7-TRISUBSTITUTED ISOQUINOLINE DERIVATIVES, PREPARATION THEREOF, AND USE THEREOF IN MEDICINES

The present disclosure relates to 1,5,7-trisubstituted isoquinoline derivatives, their preparation and pharmaceutical use. In particular, the present disclosure discloses a compound of formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate or prodrug thereof, and a preparation method and use thereof. The definitions of the groups in the formula can be found in the specification and claims.

Dioxane quinazoline and dioxane quinazoline type compound, and preparation method and application thereof

The invention relates to a dioxane quinazoline and dioxane quinazoline type compound having a formula (I) as described in the specification or a pharmaceutically acceptable salt thereof. The inventionalso provides preparation of the compound having the formula (I) and the pharmaceutically acceptable salt and application of the compound and the pharmaceutically acceptable salt as a medicine. The medicine is used as a tyrosine kinase (such as VEGFR-2, c-MET and RET) inhibitor for treating diseases relevant to tyrosine kinases.

Design, synthesis and biological activities of novel pleuromutilin derivatives with a substituted triazole moiety as potent antibacterial agents

A series of novel pleuromutilin derivatives possessing 1,2,3-triazole moieties were synthesized via click reactions under mild conditions. The in vitro antibacterial activities of these derivatives against 4 strains of S. aureus (MRSA ATCC 43300, ATCC 29213, AD 3, and 144) and 1 strain of E. coli (ATCC 25922) were tested by the broth dilution method. The majority of the synthesized derivatives displayed potent antibacterial activities against MRSA (MIC = 0.125–2 μg/mL). It was also found that most compounds had no significant inhibitory effect on the proliferation of RAW264.7 cells at the concentration of 8 μg/mL. Among these derivatives, compound 32 (～1.71 log10 CFU/g) containing dimethylamine group side chain displayed more effective than tiamulin (～0.77 log10 CFU/g) at the dose of 20 mg/kg in reducing MRSA load in thigh infected mice. Additionally, compound 32 (the survival rate was 50%) also displayed superior in vivo efficacy to that of tiamulin (the survival rate was 20%) in the mouse systemic model. Structure-activity relationship (SAR) studies resulted in compound 32 with the most potent in vitro and in vivo antibacterial activity among the series. Moreover, compound 32 was evaluated in CYP450 inhibition assay and showed moderate in vitro inhibition of CYP3A4 (IC50 = 6.148 μM).

Design, synthesis and biological evaluation of novel pleuromutilin derivatives containing piperazine and 1,2,3-triazole linker

A series of novel pleuromutilin derivatives containing piperazine ring, 1, 2, 3-triazoles and secondary amines on the side chain of C14 were synthesized under mild conditions via click reaction. The in vitro antibacterial activities of the synthesized derivatives against four strains of Staphylococcus aureus (MRSA ATCC 43300, ATCC 29213, 144 and AD3) and one strain of Escherichia coli (ATCC 25922) were evaluated by the broth dilution method. Among these derivatives, 22–[2-(4-((4-nitrophenyl piperazine)methyl)-1,2,3-triazol-1-yl)-1-(piperazine-1-yl) ethyl-1-one] deoxy pleuromutilin (compound 59) showed the most prominent in vitro antibacterial effect against MRSA (MIC = 1 μg/mL). Furthermore, compound 59 displayed more rapid bactericidal kinetic than tiamulin time-kill studies and possessed a longer PAE than tiamulin against MRSA in vitro. In addition, in vivo antibacterial activities of compound 59 against MRSA were further evaluated employing thigh infection model. And compound 59 (-8.89 log10 CFU/mL) displayed superior activities than tiamulin. Compound 59 was further evaluated in CYP450 inhibition assay and the results showed that it exhibited low to moderate inhibitory effects on CYP1A2, CYP2E1, CYP2D6 and CYP3A4 enzymes. The PK properties of compound 59 were then measured. The half-life (t1/2), clearance rate (Cl) and the area under the plasma concentration time curve (AUC0→∞) of compound 59 were 0.74 h, 0.29 L/h/kg and 46.28 μg·h/mL, respectively.

Pleuromutilin derivative with 2-aminothiophenol and 1,2,3-triazole side chain, preparation and application

The invention belongs to the field of medicinal chemistry, and particularly relates to a pleuromutilin derivative with 2-aminothiophenol and a 1,2,3-triazole side chain, preparation and application. The pleuromutilin derivative with 2-aminothiophenol and the 1,2,3-triazole side chain is a compound of a formula 2 or a pharmaceutically acceptable salt of the compound, and a solvent compound, an enantiomer, a diastereomer and a tautomer of the compound of the formula 2 or the pharmaceutically acceptable salt of the compound or a mixture of the compound of the formula 2 or the pharmaceutically acceptable salt of the compound in any ratio, and includes a racemic mixture, and the compound has good inhibition to methicillin-resistant staphylococcus aureus activity, and is especially suitable forbeing used as a novel antibacterial drug for prevention and treatment of infectious diseases caused by human or animals or methicillin-resistant staphylococcus aureus or multi-drug resistant bacteria.(Please see the specification for the formula).

Pleuromutilin derivative containing piperazine and 1, 2, 3-triazole secondary amine side chains, and preparation and applications thereof

The invention belongs to the field of pharmaceutical chemistry, and especially relates to a pleuromutilin derivative containing piperazine and 1, 2, 3-triazole secondary amine side chains, and preparation and applications thereof. The pleuromutilin derivative containing piperazine and 1, 2, 3-triazole secondary amine side chains is a compound represented by formula 2 or a pharmaceutically acceptable salt of the compound, or a solvate, an enantiomer, a diastereomer, a tautomer of the compound represented by formula 2 or the pharmaceutically acceptable salt of the compound, or a mixture of the above substances at a random ratio comprising a racemic mixture. The compound possesses excellent in vitro antibacterial activity, the cost is lower than that of valnemulin and retapamulin, so that thecompound is especially suitable to be taken as a novel antibacterial drug in prevention and treatment of human or animal bacterial infectious diseases, especially infectious diseases caused by medicine resistant Staphylococcus aureus.

Balancing Physicochemical Properties of Phenylthiazole Compounds with Antibacterial Potency by Modifying the Lipophilic Side Chain

Bacterial resistance to antibiotics is presently one of the most pressing healthcare challenges and necessitates the discovery of new antibacterials with unique chemical scaffolds. However, the determination of the optimal balance between structural requirements for pharmacological action and pharmacokinetic properties of novel antibacterial compounds is a significant challenge in drug development. The incorporation of lipophilic moieties within a compound's core structure can enhance biological activity but have a deleterious effect on drug-like properties. In this Article, the lipophilicity of alkynylphenylthiazoles, previously identified as novel antibacterial agents, was reduced by introducing cyclic amines to the lipophilic side chain. In this regard, substitution with methylpiperidine (compounds 14-16) and thiomorpholine (compound 19) substituents significantly enhanced the aqueous solubility profile of the new compounds more than 150-fold compared to the first-generation lead compound 1b. Consequently, the pharmacokinetic profile of compound 15 was significantly enhanced with a notable improvement in both half-life and the time the compound's plasma concentration remained above its minimum inhibitory concentration (MIC) against methicillin-resistant Staphylococcus aureus (MRSA). In addition, compounds 14-16 and 19 were found to exert a bactericidal mode of action against MRSA and were not susceptible to resistance formation after 14 serial passages. Moreover, these compounds (at 2× MIC) were superior to the antibiotic vancomycin in the disruption of the mature MRSA biofilm. The modifications to the alkynylphenylthiazoles reported herein successfully improved the pharmacokinetic profile of this new series while maintaining the compounds' biological activity against MRSA.

Design and synthesis of novel triazolo-lapatinib hybrids as inhibitors of breast cancer cells

A series of triazolo-lapatinib hybrids were synthesized via copper (II)-oxide nanoparticle (Cu2O-NP)-catalyzed azide-alkyne cycloaddition. The ability of these compounds to reduce the viability of breast cancer SKBR3 and SUM159 cells and stem cell-like KG-1a leukemia cells was subsequently evaluated. Compared with lapatinib, compounds 6c–f were more potent than lapatinib against the three cell lines. Next, the toxicity of compounds 6c–f was assessed in zebrafish. Compound 6d had comparable toxicity with lapatinib at 200 μM (mortality rate = 10 vs. 10%), and compound 6e had lower toxicity than lapatinib at 200 μM (mortality rate = 0 vs. 10%). Thus, compound 6e is a promising lead compound worthy of further investigation. [Figure not available: see fulltext.].