Month: February 2023

Discovery of 2-substituted 1H-benzo[d]imidazole-4-carboxamide derivatives as novel poly(ADP-ribose)polymerase-1 inhibitors with in vivo anti-tumor activity was written by Zhou, Jie;Ji, Ming;Zhu, Zhixiang;Cao, Ran;Chen, Xiaoguang;Xu, Bailing. And the article was included in European Journal of Medicinal Chemistry in 2017.Electric Literature of C8H18N2 This article mentions the following:

Novel 1H-benzo[d]imidazole-4-carboxamide derivatives bearing five-membered or six-membered N-heterocyclic moieties at the 2-position were designed and synthesized as PARP-1 inhibitors. Structure-activity relationships were conducted and led to a number of potent PARP-1 inhibitors having IC₅₀ values in the single or double digit nanomolar level. Some potent PARP-1 inhibitors also had similar inhibitory activities against PARP-2. Among all the synthesized compounds, compound I and II (R = cyclohexyl) displayed strong potentiation effects on temozolomide (TMZ) in MX-1 cells (PF₅₀ = 7.10, PF₅₀ = 4.17). In vivo tumor growth inhibition was investigated using compound I in combination with TMZ, and it was demonstrated that compound I could strongly potentiate the cytotoxicity of TMZ in MX-1 xenograft tumor model. Two co-crystal structures of compounds II (R = H) and III complexed with PARP-1 were achieved and demonstrated a unique binding mode of these benzo-imidazole derivatives In the experiment, the researchers used many compounds, for example, 1-Isobutylpiperazine (cas: 5308-28-1Electric Literature of C8H18N2).

1-Isobutylpiperazine (cas: 5308-28-1) belongs to piperazine derivatives. Piperazine was first introduced as an anthelmintic in 1953. Piperazine compounds mediate their anthelmintic action by generally paralyzing parasites, allowing the host body to easily remove or expel the invading organism. Piperazine and its salts did not induce point mutations in a bacterial test. A series of mutagenicity studies in cells, both in vitro and in vivo, has been completed and showed no evidence of mutagenic effect.Electric Literature of C8H18N2

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Assessment of a specific sample cleanup for the multiresidue determination of veterinary drugs and pesticides in salmon using liquid chromatography/tandem mass spectrometry was written by Castilla-Fernandez, Delia;Moreno-Gonzalez, David;Bouza, Marcos;Saez-Gomez, Andrea;Ballesteros, Evaristo;Garcia-Reyes, Juan F.;Molina-Diaz, Antonio. And the article was included in Food Control in 2021.Recommanded Product: 98105-99-8 This article mentions the following:

A novel sample treatment approach based on a modified QuEChERS method was evaluated for the simultaneous determination of veterinary drug and pesticide residues in salmon in this work. To improve the QuEChERS performance, Enhanced Matrix Removal-Lipid dSPE cleanup sorbent was evaluated for the first time for the simultaneous anal. of these organic contaminants in salmon samples. Due to this sorbent can effectively remove coextd. families of lipids. To cover a wide range of polarities, 65 pesticides and 41 veterinary drugs with log Kow ranging from -1.4 to 5.5 were selected. Extracts after cleanup were analyzed by ultra-high-performance liquid chromatog.-tandem mass spectrometry for analyte confirmation and quantitation. Outstanding results were obtained for both extraction efficiency and matrix removal. A negligible matrix effect was obtained for 57% of the studied compounds, whereas the rest presented a soft matrix effect. The recovery for spiked samples was in agreement with the current European Union recommendations for most compounds The rest of the parameters were also satisfactory, reaching quantification limits lower than 3.7μg kg-1 in all cases. The precision was better than 20% in all cases. Finally, the method performance was successfully demonstrated with 20 salmon samples, five of which contained pesticide or veterinary drug residues. In the experiment, the researchers used many compounds, for example, 6-Fluoro-1-(4-fluorophenyl)-4-oxo-7-(piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid (cas: 98105-99-8Recommanded Product: 98105-99-8).

6-Fluoro-1-(4-fluorophenyl)-4-oxo-7-(piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid (cas: 98105-99-8) belongs to piperazine derivatives. Piperazine causes primary dermal irritation and skin burns at high concentrations. Piperazine also causes eye irritation in humans. Two common salts in the form of which piperazine is usually prepared for pharmaceutical or veterinary purposes are the citrate, 3C4H10N2.2C6H8O7 (i.e. containing 3 molecules of piperazine to 2 molecules of citric acid), and the adipate, C4H10N2.C6H10O4 (containing 1 molecule each of piperazine and adipic acid).Recommanded Product: 98105-99-8

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Studies on Development of Sufficiently Chemoselective N-Acylation Reagents: N-Acyl-N-(2,3,4,5,6-pentafluorophenyl)methanesulfonamides was written by Kondo, K.;Sekimoto, E.;Nakao, J.;Murakami, Y.. And the article was included in Tetrahedron in 2000.Safety of Benzyl 3-methylpiperazine-1-carboxylate This article mentions the following:

A variety of storable N-acyl-N-(2,3,4,5,6-pentafluorophenyl)methanesulfonamides, prepared from N-2,3,4,5,6-pentafluorophenylmethanesulfonamide, have been developed after systematic research on the structure-reactivity relationship and were found to serve as N-acylation reagents exhibiting sufficiently good chemoselectivity. In the experiment, the researchers used many compounds, for example, Benzyl 3-methylpiperazine-1-carboxylate (cas: 84477-85-0Safety of Benzyl 3-methylpiperazine-1-carboxylate).

Benzyl 3-methylpiperazine-1-carboxylate (cas: 84477-85-0) belongs to piperazine derivatives. Simple N-substituted piperazines have been found in many drug molecules. Piperazine is an anthelminthic especially useful in the treatment of partial intestinal obstruction caused by Ascaris worms, which is a condition primarily seen in children. Piperazine hydrate and piperazine citrate are the main anthelminthic piperazines.Safety of Benzyl 3-methylpiperazine-1-carboxylate

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Reusable Co-nanoparticles for general and selective N-alkylation of amines and ammonia with alcohols was written by Ma, Zhuang;Zhou, Bei;Li, Xinmin;Kadam, Ravishankar G.;Gawande, Manoj B.;Petr, Martin;Zboril, Radek;Beller, Matthias;Jagadeesh, Rajenahally V.. And the article was included in Chemical Science in 2022.Name: 4,4-Difluorobenzhydrylpiperazine This article mentions the following:

A general cobalt-catalyzed N-alkylation of amines with alcs. by borrowing hydrogen methodol. to afford alkylated amines I [R = Pr-n, cyclohexyl, Ph, etc.; R¹ = Ph, 4-MeC₆H₄, 4-FC₆H₄, etc.] was reported. The optimal catalyst for this transformation was prepared by pyrolysis of a specific templated material, which was generated in situ by mixing cobalt salts, nitrogen ligands and colloidal silica and subsequent removal of silica. Applying this novel Co-nanoparticle-based material, >100 primary, secondary and tertiary amines including N-methylamines and selected drug mols. were conveniently prepared starting from inexpensive and easily accessible alcs. and amines or ammonia. In the experiment, the researchers used many compounds, for example, 4,4-Difluorobenzhydrylpiperazine (cas: 27469-60-9Name: 4,4-Difluorobenzhydrylpiperazine).

4,4-Difluorobenzhydrylpiperazine (cas: 27469-60-9) belongs to piperazine derivatives. Piperazine was first introduced as an anthelmintic in 1953. Piperazine compounds mediate their anthelmintic action by generally paralyzing parasites, allowing the host body to easily remove or expel the invading organism. Intermediate for a wide range of pharmaceuticals, polymers, dyes, corrosion inhibitors, rubber accelerators and surfactants.Name: 4,4-Difluorobenzhydrylpiperazine

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Synthesis and biological screening of 1-N-[4-[bis((4-fluorophenyl)methyl]-1-piperazinyl]-4-arylidene-2-(4-methoxyphenyl)-5-oxoimidazolines was written by Savaliya, M. D.;Dobaria, J. G.;Bhuva, V. V.;Purohit, D. M.. And the article was included in Organic Chemistry: An Indian Journal in 2010.Quality Control of 4,4-Difluorobenzhydrylpiperazine This article mentions the following:

Several piperazine imidazolone derivatives were designed for a study of their antimicrobial activity, the synthesis of the target compounds was achieved by a reaction of 4-[bis(4-fluorophenyl)methyl]-1-piperazinamine with 2-(4-methoxyphenyl)-4-(arylmethylene)-5-oxazolone derivatives and the products thus obtained were confirmed by IR, ¹H-NMR, MS, and elemental anal. The title compounds thus obtained [i.e., 3-[4-bis(4-fluorophenyl)methyl]-3,5-dihydro-2-(4-methoxyphenyl)-5-(arylmethylene)-4H-imidazol-4-one derivatives] were evaluated against Bacillus subtilis, Bacillus cereus, Escherichia coli, Enterobacter aerogenes, and Aspergillus niger and it was discovered that these compounds displayed moderate antimicrobial activity in comparison with ampicillin, chloramphenicol, norfloxacin, and griseofulvin at a concentration of 50 μg/mL. In the experiment, the researchers used many compounds, for example, 4,4-Difluorobenzhydrylpiperazine (cas: 27469-60-9Quality Control of 4,4-Difluorobenzhydrylpiperazine).

4,4-Difluorobenzhydrylpiperazine (cas: 27469-60-9) belongs to piperazine derivatives. The piperazine scaffold is often found in biologically active compounds in different therapeutic areas. These therapeutic areas include antifungals, antidepressants, antivirals, and serotonin receptor (5-HT) antagonists/agonists. Outside the body, piperazine has a remarkable power to dissolve uric acid and producing a soluble urate, but in clinical experience it has not proved equally successful. Quality Control of 4,4-Difluorobenzhydrylpiperazine

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Efficacy of donepezil for the treatment of oxaliplatin-induced peripheral neuropathy: DONEPEZOX, a protocol of a proof of concept, randomised, triple-blinded and multicentre trial was written by Kerckhove, Nicolas;Tougeron, David;Lepage, Come;Pezet, Denis;Le Malicot, Karine;Pelkowski, Manon;Pereira, Bruno;Balayssac, David. And the article was included in BMC Cancer in 2022.Formula: C43H58N4O12 This article mentions the following:

The use of oxaliplatin in digestive tract cancers could induce severe peripheral neuropathy (OIPN) decreasing the quality of life of patients and survivors. There is currently, no univocal treatment for these peripheral neuropathies. Donepezil, a reversible inhibitor of cholinesterase, used to treat Alzheimer’s disease and dementia, is reported to have a good safety profile in humans, and preclin. data have provided initial evidence of its effectiveness in diminishing neuropathic symptoms and related comorbidities in OIPN animal models. The DONEPEZOX trial will be a proof-of-concept, randomised, triple-blinded, and multicentre study. It will be the first clin. trial evaluating the efficacy and safety of donepezil for the management of OIPN. Adult cancer survivors with OIPN that report sensory neuropathy according to QLQ-CIPN20 sensory score (equivalence of a grade ≥ 2), at least 6 mo after the end of an oxaliplatin-based chemotherapy will be included. Eighty patients will be randomly assigned to receive either donepezil or placebo over 16 wk of treatment. The primary endpoint will be the rate of responders (neuropathic grade decreases according to the QLQ-CIPN20 sensory score) in the donepezil arm. The severity of OIPN will be assessed by the QLQ-CIPN20 sensory scale before and after 16 wk of treatment. The comparison vs. the placebo arm will be a secondary objective. The other secondary endpoints will be tolerance to donepezil, the severity and features of OIPN in each arm before and after treatment, related-comorbidities and quality of life. Fleming’s one-stage design will be used for sample size estimation This design yields a type I error rate of 0.0417 and power of 91% for a responder rate of at least 30% in donepezil arm. A total of 80 randomized patients is planned. This study will allow, in the case of pos. results, to initiate a phase 3 randomized and placebo-controlled (primary endpoint) clin. study to assess the therapeutic interest of donepezil to treat OIPN. In the experiment, the researchers used many compounds, for example, 8-(n-(4-methyl-1-piperazinyl)formidoyl)-rifomycins (cas: 13292-46-1Formula: C43H58N4O12).

8-(n-(4-methyl-1-piperazinyl)formidoyl)-rifomycins (cas: 13292-46-1) belongs to piperazine derivatives. Simple N-substituted piperazines have been found in many drug molecules. Piperazines are very broad chemical group, covering a wide range of drugs from antidepressants to antihistamines. The connecting property of all these chemicals is the presence of a piperazine functional group.Formula: C43H58N4O12

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Profiling of LINS01 compounds at human dopamine D₂ and D₃ receptors was written by Correa, Michelle F.;Reiner, David;Fernandes, Gustavo A. B.;Varela, Marina T.;Aranha, Cecilia M. S. Q.;Stark, Holger;Fernandes, Joao Paulo S.. And the article was included in Journal of Chemical Sciences (Berlin, Germany) in 2020.Application In Synthesis of 3-(trans-4-(2-(4-(2,3-Dichlorophenyl)piperazin-1-yl)ethyl)cyclohexyl)-1,1-dimethylurea This article mentions the following:

Abstract: Histamine and dopamine neuronal pathways display interesting overlapping in the CNS, especially in the limbic areas, making them very attractive to designing drugs with synergistic and/or additive effects. The roles of these systems to treat schizophrenia, drug addiction, Parkinson’s and Alzheimer’s diseases, among others are widely known. The LINS01 compounds were previously reported as histamine H₃ receptor (H₃R) antagonists and some of them are under evaluation in rodent memory models. Considering their pharmacol. potential and similarities to literature dopamine D₂ receptor (D₂R) and dopamine D₃ receptor (D₃R) ligands, this work aimed to evaluate these compounds as ligands these receptors by using [³H]spiperone displacement assays. A set of 11 compounds containing the dihydrobenzofuranyl-piperazine core with substituents at 5-position of dihydrobenzofuran ring and at the piperazine nitrogen was examined With the LINS01 compounds showing moderate binding affinity, new lead structures for optimization with regards to combined H₃R and D₂R/D₃R-ligands are provided. Graphic abstract: Histamine and dopamine neuronal pathways display interesting overlapping in the CNS, and thus LINS01 compounds previously reported as histamine H₃ receptor antagonists were evaluated as dopamine D₂R and D₃R ligands. In the experiment, the researchers used many compounds, for example, 3-(trans-4-(2-(4-(2,3-Dichlorophenyl)piperazin-1-yl)ethyl)cyclohexyl)-1,1-dimethylurea (cas: 839712-12-8Application In Synthesis of 3-(trans-4-(2-(4-(2,3-Dichlorophenyl)piperazin-1-yl)ethyl)cyclohexyl)-1,1-dimethylurea).

3-(trans-4-(2-(4-(2,3-Dichlorophenyl)piperazin-1-yl)ethyl)cyclohexyl)-1,1-dimethylurea (cas: 839712-12-8) belongs to piperazine derivatives. Piperazine was first introduced as an anthelmintic in 1953. Piperazine compounds mediate their anthelmintic action by generally paralyzing parasites, allowing the host body to easily remove or expel the invading organism. Piperazine and its salts did not induce point mutations in a bacterial test. A series of mutagenicity studies in cells, both in vitro and in vivo, has been completed and showed no evidence of mutagenic effect.Application In Synthesis of 3-(trans-4-(2-(4-(2,3-Dichlorophenyl)piperazin-1-yl)ethyl)cyclohexyl)-1,1-dimethylurea

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Desirability-Based Methods of Multiobjective Optimization and Ranking for Global QSAR Studies. Filtering Safe and Potent Drug Candidates from Combinatorial Libraries was written by Cruz-Monteagudo, Maykel;Borges, Fernanda;Cordeiro, M. Natalia D. S.;Cagide Fajin, J. Luis;Morell, Carlos;Molina Ruiz, Reinaldo;Canizares-Carmenate, Yudith;Dominguez, Elena Rosa. And the article was included in Journal of Combinatorial Chemistry in 2008.SDS of cas: 112811-57-1 This article mentions the following:

Up to now, very few applications of multiobjective optimization (MOOP) techniques to quant. structure-activity relationship (QSAR) studies have been reported in the literature. However, none of them report the optimization of objectives related directly to the final pharmaceutical profile of a drug. In this paper, a MOOP method based on Derringer’s desirability function that allows conducting global QSAR studies, simultaneously considering the potency, bioavailability, and safety of a set of drug candidates, is introduced. The results of the desirability-based MOOP (the levels of the predictor variables concurrently producing the best possible compromise between the properties determining an optimal drug candidate) are used for the implementation of a ranking method that is also based on the application of desirability functions. This method allows ranking drug candidates with unknown pharmaceutical properties from combinatorial libraries according to the degree of similarity with the previously determined optimal candidate. Application of this method will make it possible to filter the most promising drug candidates of a library (the best-ranked candidates), which should have the best pharmaceutical profile (the best compromise between potency, safety and bioavailability). In addition, a validation method of the ranking process, as well as a quant. measure of the quality of a ranking, the ranking quality index (Ψ), is proposed. The usefulness of the desirability-based methods of MOOP and ranking is demonstrated by its application to a library of 95 fluoroquinolones, reporting their gram-neg. antibacterial activity and mammalian cell cytotoxicity. Finally, the combined use of the desirability-based methods of MOOP and ranking proposed here seems to be a valuable tool for rational drug discovery and development. In the experiment, the researchers used many compounds, for example, 1-Cyclopropyl-6-fluoro-8-methoxy-4-oxo-7-(piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid (cas: 112811-57-1SDS of cas: 112811-57-1).

1-Cyclopropyl-6-fluoro-8-methoxy-4-oxo-7-(piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid (cas: 112811-57-1) belongs to piperazine derivatives. Piperazine was first introduced as an anthelmintic in 1953. Piperazine compounds mediate their anthelmintic action by generally paralyzing parasites, allowing the host body to easily remove or expel the invading organism. Intermediate for a wide range of pharmaceuticals, polymers, dyes, corrosion inhibitors, rubber accelerators and surfactants.SDS of cas: 112811-57-1

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

A simple method of hiPSCs differentiation into insulin-producing cells is improved with vitamin C and RepSox was written by Horikawa, Ayumi;Mizuno, Keiko;Tsuda, Kyoko;Yamamoto, Takayoshi;Michiue, Tatsuo. And the article was included in PLoS One in 2021.Synthetic Route of C25H22N6 This article mentions the following:

Human induced pluripotent stem cells (hiPSCs) are considered a promising source of pancreatic β-cells for the treatment of diabetes. However, this approach is limited by issues such as low efficiency and high cost. Here, we have developed a new protocol to induce insulin-producing cells. To reduce costs, we decreased the number of reagents and replaced protein reagents with chem. compounds In this method, we increased induction efficiency with ascorbic acid (vitamin C) and an ALK5 inhibitor, RepSox. In 2D culture, the majority of cells were immature β-cells with low glucose-stimulated insulin secretion. Transferring to 3D culture immediately after endocrine progenitor cell differentiation, however, improved glucose-stimulated insulin secretion. This simplified method will contribute to realizing transplantation therapy of β-cells using iPSCs. In the experiment, the researchers used many compounds, for example, 4-(6-(4-(Piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline (cas: 1062368-24-4Synthetic Route of C25H22N6).

4-(6-(4-(Piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline (cas: 1062368-24-4) belongs to piperazine derivatives. Piperazine belongs to the family of medicines called anthelmintics. Piperazine and its salts did not induce point mutations in a bacterial test. A series of mutagenicity studies in cells, both in vitro and in vivo, has been completed and showed no evidence of mutagenic effect.Synthetic Route of C25H22N6

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

American College of Rheumatology White Paper on Antimalarial Cardiac Toxicity was written by Desmarais, Julianna;Rosenbaum, James T.;Costenbader, Karen H.;Ginzler, Ellen M.;Fett, Nicole;Goodman, Susan;O′Dell, James;Pineau, Christian A.;Schmajuk, Gabriela;Werth, Victoria P.;Link, Mark S.;Kovacs, Richard. And the article was included in Arthritis & Rheumatology in 2021.Recommanded Product: 2-(2-(4-((4-Chlorophenyl)(phenyl)methyl)piperazin-1-yl)ethoxy)ethanol This article mentions the following:

Hydroxychloroquine (HCQ) and chloroquine (CQ) are well-established medications used in treating systemic lupus erythematosus and rheumatoid arthritis, as well as skin conditions such as cutaneous lupus erythematosus. In rare cases, arrhythmias and conduction system abnormalities, as well as cardiomyopathy, have been reported in association with HCQ/CQ use. Recently, however, the corrected QT interval (QTc)-prolonging potential of these medications, and risk of torsade de pointes (TdP) in particular, have been highlighted in the setting of their exptl. use for COVID-19 infection. This report was undertaken to summarize the current understanding of HCQ/CQ cardiac toxicity, describe QTc prolongation and TdP risks, and discuss areas of priority for future research. A working group of experts across rheumatol., cardiol., and dermatol. performed a nonsystematic literature review and offered a consensus-based expert opinion. Current data clearly indicate that HCQ and CQ are invaluable medications in the management of rheumatic and dermatol. diseases, but they are associated with QTc prolongation by directly affecting cardiac repolarization. Prescribing clinicians should be cognizant of this small effect, especially in patients taking addnl. medications that prolong the QTc interval. Long-term use of HCQ/CQ may lead to a cardiomyopathy associated with arrhythmias and heart failure. Risk and benefit assessment should be considered prior to initiation of any medication, and both initial and ongoing risk-benefit assessments are important with regard to prescription of HCQ/CQ. While cardiac toxicity related to HCQ/CQ treatment of rheumatic diseases is rarely reported, it can be fatal. Awareness of the potential adverse cardiac effects of HCQ and CQ can increase the safe use of these medications. There is a clear need for addnl. research to allow better understanding of the cardiovascular risk and safety profile of these therapies used in the management of rheumatic and cutaneous diseases. In the experiment, the researchers used many compounds, for example, 2-(2-(4-((4-Chlorophenyl)(phenyl)methyl)piperazin-1-yl)ethoxy)ethanol (cas: 68-88-2Recommanded Product: 2-(2-(4-((4-Chlorophenyl)(phenyl)methyl)piperazin-1-yl)ethoxy)ethanol).

2-(2-(4-((4-Chlorophenyl)(phenyl)methyl)piperazin-1-yl)ethoxy)ethanol (cas: 68-88-2) belongs to piperazine derivatives. Piperazine belongs to the family of medicines called anthelmintics. Two common salts in the form of which piperazine is usually prepared for pharmaceutical or veterinary purposes are the citrate, 3C4H10N2.2C6H8O7 (i.e. containing 3 molecules of piperazine to 2 molecules of citric acid), and the adipate, C4H10N2.C6H10O4 (containing 1 molecule each of piperazine and adipic acid).Recommanded Product: 2-(2-(4-((4-Chlorophenyl)(phenyl)methyl)piperazin-1-yl)ethoxy)ethanol

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics