Month: January 2023

Photoswitchable Inhibitor of the Calcium Channel TRPV6 was written by Cunha, Micael R.;Bhardwaj, Rajesh;Lindinger, Sonja;Butorac, Carmen;Romanin, Christoph;Hediger, Matthias A.;Reymond, Jean-Louis. And the article was included in ACS Medicinal Chemistry Letters in 2019.Reference of 182618-86-6 This article mentions the following:

Herein the authors report the first photoswitchable inhibitor of Transient Receptor Potential Vanilloid 6 (TRPV6), a selective calcium channel involved in a number of diseases and in cancer progression. By surveying analogs of a previously reported TRPV6 inhibitor appended with a phenyl-diazo group, the authors identified a compound switching between a weak TRPV6 inhibitor in its dark, E-diazo stereoisomer (Z/E = 3:97, IC₅₀ >> 10 μM) and a potent inhibitor as the Z-diazo stereoisomer accessible reversibly by UV irradiation at λ = 365 nm (Z/E = 3:1, IC₅₀ = 1.7±0.4 μM), thereby allowing precise spatiotemporal control of inhibition. This new tool compound should be useful to deepen the understanding of TRPV6. In the experiment, the researchers used many compounds, for example, 1-Boc-4-(4-Nitrophenyl)piperazine (cas: 182618-86-6Reference of 182618-86-6).

1-Boc-4-(4-Nitrophenyl)piperazine (cas: 182618-86-6) belongs to piperazine derivatives. Piperazine causes primary dermal irritation and skin burns at high concentrations. Piperazine also causes eye irritation in humans. 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. Reference of 182618-86-6

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

Synthesis and biological properties of heterylalkylamides of 4-substituted piperazin-1-ylacetic acids was written by Vartanyan, S. O.;Avakyan, A. S.;Sargsyan, A. B.;Arutyunyan, S. A.;Gukasyan, T. G.;Tsatinyan, A. S.;Noravyan, O. S.;Markaryan, I. A.. And the article was included in Hayastani Kimiakan Handes in 2010.Related Products of 21867-64-1 This article mentions the following:

Reaction of chloroacetyl chloride with 1,4-benzodioxan-2-yl or isochroman-1-yl-containing aliphatic amines gave the corresponding N-substituted chloroacetamides. Subsequent treatment of the latter with monosubstituted piperazines afforded the corresponding substituted piperazineacetamides. The biol. properties of these compounds have been investigated. In the experiment, the researchers used many compounds, for example, 1-Propylpiperazine (cas: 21867-64-1Related Products of 21867-64-1).

1-Propylpiperazine (cas: 21867-64-1) 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. 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. Related Products of 21867-64-1

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

Discovery of a First-in-Class Gut-Restricted RET Kinase Inhibitor as a Clinical Candidate for the Treatment of IBS was written by Schenck Eidam, Hilary;Russell, John;Raha, Kaushik;De Martino, Michael;Qin, Donghui;Guan, Huiping Amy;Zhang, Zhiliu;Zhen, Gong;Yu, Haiyu;Wu, Chengde;Pan, Yan;Joberty, Gerard;Zinn, Nico;Laquerre, Sylvie;Robinson, Sharon;White, Angela;Giddings, Amanda;Mohammadi, Ehsan;Greenwood-Van Meerveld, Beverly;Oliff, Allen;Kumar, Sanjay;Cheung, Mui. And the article was included in ACS Medicinal Chemistry Letters in 2018.SDS of cas: 630125-91-6 This article mentions the following:

Abdominal pain and abnormal bowel habits represent major symptoms for irritable bowel syndrome (IBS) patients that are not adequately managed. Although the etiol. of IBS is not completely understood, many of the functions of the gastrointestinal (GI) tract are regulated by the enteric nervous system (ENS). Inflammation or stress-induced expression of growth factors or cytokines may lead to hyperinnervation of visceral afferent neurons in GI tract and contribute to the pathophysiol. of IBS. Rearranged during transfection (RET) is a neuronal growth factor receptor tyrosine kinase critical for the development of the ENS as exemplified by Hirschsprung patients who carry RET loss-of-function mutations and lack normal colonic innervation leading to colonic obstruction. Similarly, RET signaling in the adult ENS maintains neuronal function by contributing to synaptic formation, signal transmission, and neuronal plasticity. Inhibition of RET in the ENS represents a novel therapeutic strategy for the normalization of neuronal function and the symptoms of IBS patients. Herein, we describe our screening effort and subsequent structure-activity relationships (SARs) in optimizing potency, selectivity, and mutagenicity of the series, which led to the discovery of a first-in-class, gut-restricted RET kinase inhibitor, 2-(4-(4-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)-N-(5-(1,1,1-trifluoro-2-methylpropan-2-yl)isoxazol-3-yl)acetamide (15, GSK3179106), as a clin. candidate for the treatment of IBS. GSK3179106 is a potent, selective, and gut-restricted pyridone hinge binder small mol. RET kinase inhibitor with a RET IC₅₀ of 0.3 nM and is efficacious in vivo. In the experiment, the researchers used many compounds, for example, 4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline (cas: 630125-91-6SDS of cas: 630125-91-6).

4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline (cas: 630125-91-6) belongs to piperazine derivatives. Piperazine is a fairly basic compound and is an amine solvent. Although many piperazine derivatives occur naturally, piperazine itself can be synthesized by reacting alcoholic ammonia with 1,2-dichloroethane, by the action of sodium and ethylene glycol on ethylene diamine hydrochloride, or by reduction of pyrazine with sodium in ethanol.SDS of cas: 630125-91-6

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

Design and synthesis of novel antifungal triazole derivatives with good activity and water solubility was written by Cao, Xu-Feng;Chu, Wen-Jing;Cao, Yong-Bing;Yang, Yu-She. And the article was included in Chinese Chemical Letters in 2013.Product Details of 119285-07-3 This article mentions the following:

To find novel antifungal agents with good activity and aqueous solubility, a series of SYN-2869 analogs containing a pyridine ring were synthesized and were evaluated for their in vitro antifungal activity and water-solubility Some of the compounds showed potent activity against pathogenic fungi. In particular, an analog having an iso-Bu substitution on the triazolone exhibited significant broad spectrum antifungal activity. In addition, the water solubility of this compound was sufficiently improved over SYN-2869. In the experiment, the researchers used many compounds, for example, tert-Butyl 4-(5-aminopyridin-2-yl)piperazine-1-carboxylate (cas: 119285-07-3Product Details of 119285-07-3).

tert-Butyl 4-(5-aminopyridin-2-yl)piperazine-1-carboxylate (cas: 119285-07-3) belongs to piperazine derivatives. Industrial applications of piperazine include the manufacture of plastics, resins, pesticides and brake fluids. Piperazine is formed as a co-product in the ammoniation of 1,2-dichloroethane or ethanolamine. These are the only routes to the chemical used commercially.Product Details of 119285-07-3

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

Glutathione. X. Human erythrocyte membrane diffusion coefficients for diazene derivatives of the DIP [diazenedicarboxylic acid bis(N’-methylpiperazide)] series via intracellular thiol oxidation was written by Kosower, Nechama S.;Kosower, Edward M.;Saltoun, Gilda;Lev, Lilly. And the article was included in Biochemical and Biophysical Research Communications in 1975.Application of 21867-64-1 This article mentions the following:

The thiol-oxidizing agent, DIP and its homologs with different N’-alkyl groups can be used to obtain membrane diffusion coefficients for human erythrocytes at 1°. From the initial rates of intracellular glutathione oxidation and the 2-octanol partition coefficients for the specific DIP homolog, diffusion coefficients of ∼1 × 10-8 cm2/sec were observed The method (irreversible loss of permeant through well-defined intracellular reaction) may be used to evaluate membrane properties and possibly for the study of substituent effects on drug entry into cells. In the experiment, the researchers used many compounds, for example, 1-Propylpiperazine (cas: 21867-64-1Application of 21867-64-1).

1-Propylpiperazine (cas: 21867-64-1) belongs to piperazine derivatives. Piperazine is a fairly basic compound and is an amine solvent. Intermediate for a wide range of pharmaceuticals, polymers, dyes, corrosion inhibitors, rubber accelerators and surfactants.Application of 21867-64-1

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

Discovery of Orally Active Carboxylic Acid Derivatives of 2-Phenyl-5-trifluoromethyloxazole-4-carboxamide as Potent Diacylglycerol Acyltransferase-1 Inhibitors for the Potential Treatment of Obesity and Diabetes was written by Qian, Yimin;Wertheimer, Stanley J.;Ahmad, Mushtaq;Cheung, Adrian Wai-Hing;Firooznia, Fariborz;Hamilton, Matthew M.;Hayden, Stuart;Li, Shiming;Marcopulos, Nicholas;McDermott, Lee;Tan, Jenny;Yun, Weiya;Guo, Liang;Pamidimukkala, Anjula;Chen, Yingsi;Huang, Kuo-Sen;Ramsey, Gwendolyn B.;Whittard, Toni;Conde-Knape, Karin;Taub, Rebecca;Rondinone, Cristina M.;Tilley, Jefferson;Bolin, David. And the article was included in Journal of Medicinal Chemistry in 2011.Product Details of 119285-07-3 This article mentions the following:

Diacylglycerol acyltransferase-1 (DGAT-1) is the enzyme that catalyzes the final and committed step of triglyceride formation, namely, the acylation of diacylglycerol with acyl CoA. DGAT-1 deficient mice demonstrate resistance to weight gain on high fat diet, improved insulin sensitivity, and reduced liver triglyceride content. Inhibition of DGAT-1 thus represents a potential novel approach for the treatment of obesity, dyslipidemia, and metabolic syndrome. In this communication, we report the identification of the lead structure 6 and our lead optimization efforts culminating in the discovery of potent, selective, and orally efficacious carboxylic acid derivatives of 2-phenyl-5-trifluoromethyloxazole-4-carboxamides. In particular, compound 29 (I) (DGAT-1 enzyme assay, IC₅₀ = 57 nM; CHO-K1 cell triglyceride formation assay, EC₅₀ = 0.5 μM) demonstrated dose dependent inhibition of weight gain in diet induced obese (DIO) rats (0.3, 1, and 3 mg/kg, PO, qd) during a 21-day efficacy study. Furthermore, compound 29 demonstrated improved glucose tolerance determined by an oral glucose tolerance test (OGTT). In the experiment, the researchers used many compounds, for example, tert-Butyl 4-(5-aminopyridin-2-yl)piperazine-1-carboxylate (cas: 119285-07-3Product Details of 119285-07-3).

tert-Butyl 4-(5-aminopyridin-2-yl)piperazine-1-carboxylate (cas: 119285-07-3) belongs to piperazine derivatives. Simple N-substituted piperazines have been found in many drug molecules. 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.Product Details of 119285-07-3

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

Convergent Synthesis of Polynitrile and/or Polyamine Dendrimers through Hydroaminomethylation and Michael Addition was written by Beigi, Maryam;Ricken, Stefan;Mueller, Kai Sven;Koc, Fikret;Eilbracht, Peter. And the article was included in European Journal of Organic Chemistry in 2011.Application In Synthesis of tert-Butyl 4-(3-aminopropyl)piperazine-1-carboxylate This article mentions the following:

A new convergent approach is presented to prepare polynitrile/polyamine dendrimers. Highly versatile dendrons obtained by Voegtle’s method (Michael-type addition with acrylonitrile) are combined with suitable cores by allylation/hydroaminomethylation or alkylation/acylation. In the experiment, the researchers used many compounds, for example, tert-Butyl 4-(3-aminopropyl)piperazine-1-carboxylate (cas: 373608-48-1Application In Synthesis of tert-Butyl 4-(3-aminopropyl)piperazine-1-carboxylate).

tert-Butyl 4-(3-aminopropyl)piperazine-1-carboxylate (cas: 373608-48-1) belongs to piperazine derivatives. Industrial applications of piperazine include the manufacture of plastics, resins, pesticides and brake fluids. 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).Application In Synthesis of tert-Butyl 4-(3-aminopropyl)piperazine-1-carboxylate

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

Aryl Amination Using Soluble Weak Base Enabled by a Water-Assisted Mechanism was written by Lau, Sii Hong;Yu, Peng;Chen, Liye;Madsen-Duggan, Christina B.;Williams, Michael J.;Carrow, Brad P.. And the article was included in Journal of the American Chemical Society in 2020.Electric Literature of C15H21N3O4 This article mentions the following:

The amination of aryl halides has become one of the most commonly practiced C-N bond-forming reactions in pharmaceutical and laboratory syntheses. The widespread use of strong or poorly soluble inorganic bases for amine activation nevertheless complicates the compatibility of this important reaction class with sensitive substrates as well as applications in flow and automated synthesis, to name a few. We report a palladium-catalyzed C-N coupling using Et₃N as a weak, soluble base, which allows a broad substrate scope that includes bromo- and chloro(hetero)arenes, primary anilines, secondary amines, and amide type nucleophiles together with tolerance for a range of base-sensitive functional groups. Mechanistic data have established a unique pathway for these reactions in which water serves multiple beneficial roles. In particular, ionization of a neutral catalytic intermediate via halide displacement by H₂O generates, after proton loss, a coordinatively unsaturated Pd-OH species that can bind amine substrate triggering intramol. N-H heterolysis. This water-assisted pathway operates efficiently with even weak terminal bases, such as Et₃N. The use of a simple, com. available ligand, PAd₃, is key to this water-assisted mechanism by promoting coordinative unsaturation in catalytic intermediates responsible for the heterolytic activation of strong element-hydrogen bonds, which enables broad compatibility of carbon-heteroatom cross-coupling reactions with sensitive substrates and functionality. In the experiment, the researchers used many compounds, for example, 1-Boc-4-(4-Nitrophenyl)piperazine (cas: 182618-86-6Electric Literature of C15H21N3O4).

1-Boc-4-(4-Nitrophenyl)piperazine (cas: 182618-86-6) belongs to piperazine derivatives. Industrial applications of piperazine include the manufacture of plastics, resins, pesticides and brake fluids. 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).Electric Literature of C15H21N3O4

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

Facile synthesis of C1-substituted β-carbolines as CDK4 inhibitors for the treatment of cancer was written by Li, Deping;Liu, Wenwu;Huang, Yaoguan;Liu, Mingyue;Tian, Caizhi;Lu, Hongyuan;Jia, Hui;Xu, Zihua;Ding, Huaiwei;Zhao, Qingchun. And the article was included in Bioorganic Chemistry in 2022.Quality Control of tert-Butyl 4-(5-aminopyridin-2-yl)piperazine-1-carboxylate This article mentions the following:

Cyclin-dependent kinase 4 (CDK4), which is involved in dynamic regulation of cell cycle, has gained particularly attention for its role in controlling tumor growth. Increasing evidence showed that β-carboline derivatives have the potential to inhibit CDK4. Herein, on the basis of previous work, authors designed and synthesized a series of novel β-carbolines and evaluated their antitumor activity. Among them, compounds I and II, with the most potent anti-proliferative activity and CDK4 enzymic inhibition activity, were selected for further pharmacol. research in vitro and in vivo. The results in vitro showed that I and II exhibited potent anti-HCT116 activity including inhibition of colony formation, inhibition of invasion and migration, inducing of apoptosis, and arresting of G1 phase in cell cycle. In vivo, I showed significant tumor growth inhibition in HCT116 tumor xenograft model without causing significant weight loss and toxicity consistent with the acute toxicity test. In addition, silico study showed I and II not only have good biol. actions, but also acceptable predicted ADME and physicochem. properties. Taken together, compounds I and II could be selected for further modification and preclin. evaluation. In the experiment, the researchers used many compounds, for example, tert-Butyl 4-(5-aminopyridin-2-yl)piperazine-1-carboxylate (cas: 119285-07-3Quality Control of tert-Butyl 4-(5-aminopyridin-2-yl)piperazine-1-carboxylate).

tert-Butyl 4-(5-aminopyridin-2-yl)piperazine-1-carboxylate (cas: 119285-07-3) 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. 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.Quality Control of tert-Butyl 4-(5-aminopyridin-2-yl)piperazine-1-carboxylate

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

Combinatorial synthesis of 3-substituted 5-aminoisoxazole-4-carboxamides was written by Alyab’ev, S. B.;Kravchenko, D. V.;Dorogov, M. V.;Ivashchenko, A. V.. And the article was included in Izvestiya Vysshikh Uchebnykh Zavedenii, Khimiya i Khimicheskaya Tekhnologiya in 2007.Reference of 611225-86-6 This article mentions the following:

The combinatorial library of novel 3-substituted 5-aminoisoxazole-4-carboxamides I (R¹ = Ph, 2-FC₆H₄, 4-F₃CC₆H₄, 4-ClC₆H₄, etc.; R² = 1-imidazolyl, 4-EtC₆H₄NH, 2-Me-3-ClC₆H₃NH, etc.; R³ = 1-pyrrolidinyl, 1-piperidinyl, 4-morpholinyl, azepan-1-yl) was prepared using a parallel synthesis approach. The target compounds were obtained by alk. hydrolysis of the esters I (R² = OMe) followed by treatment with POCl₃ and amination with secondary amines in the presence of Et₃N in dioxane. The esters I (R² = OMe) were in turn prepared from the corresponding Me 3-aryl-5-hydroxy-4-isoxazolecarboxylates by chlorination with POCl₃ followed by amination with secondary cyclic amines R³H. In the experiment, the researchers used many compounds, for example, 4-(4-Ethylpiperazin-1-ylmethyl)phenylamine (cas: 611225-86-6Reference of 611225-86-6).

4-(4-Ethylpiperazin-1-ylmethyl)phenylamine (cas: 611225-86-6) 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.Reference of 611225-86-6

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