Month: January 2023

Discovery of a novel dual fungal CYP51/human 5-lipoxygenase inhibitor: implications for anti-fungal therapy was written by Hoobler, Eric K.;Rai, Ganesha;Warrilow, Andrew G. S.;Perry, Steven C.;Smyrniotis, Christopher J.;Jadhav, Ajit;Simeonov, Anton;Parker, Josie E.;Kelly, Diane E.;Maloney, David J.;Kelly, S. L.;Holman, Theodore R.. And the article was included in PLoS One in 2013.Application In Synthesis of tert-Butyl 4-(5-aminopyridin-2-yl)piperazine-1-carboxylate This article mentions the following:

We report the discovery of a novel dual inhibitor targeting fungal sterol 14α-demethylase (CYP51 or Erg11) and human 5-lipoxygenase (5-LOX) with improved potency against 5-LOX due to its reduction of the iron center by its phenylenediamine core. A series of potent 5-LOX inhibitors containing a phenylenediamine core, were synthesized that exhibit nanomolar potency and >30-fold selectivity against the LOX paralogs, platelet-type 12-human lipoxygenase, reticulocyte 15-human lipoxygenase type-1 and epithelial 15-human lipoxygenase type-2 and >100-fold selectivity against ovine cyclooxygenase-1 and human cyclooxygnease-2. The phenylenediamine core was then translated into the structure of ketoconazole, a highly effective anti-fungal medication for seborrheic dermatitis, to generate a novel compound, ketaminazole. Ketaminazole was found to be a potent dual inhibitor against human 5-LOX (IC₅₀ = 700 nM) and CYP51 (IC₅₀ = 43 nM) in vitro. It was tested in whole blood and found to down-regulate LTB4 synthesis, displaying 45% inhibition at 10 μM. In addition, ketaminazole selectively inhibited yeast CYP51 relative to human CYP51 by 17-fold, which is greater selectivity than that of ketoconazole and could confer a therapeutic advantage. This novel dual anti-fungal/anti-inflammatory inhibitor could potentially have therapeutic uses against fungal infections that have an anti-inflammatory component. In the experiment, the researchers used many compounds, for example, tert-Butyl 4-(5-aminopyridin-2-yl)piperazine-1-carboxylate (cas: 119285-07-3Application In Synthesis 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. 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.Application In Synthesis of tert-Butyl 4-(5-aminopyridin-2-yl)piperazine-1-carboxylate

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

Development, synthesis and biological investigation of a novel class of potent PC-PLC inhibitors was written by Pilkington, Lisa I.;Sparrow, Kevin;Rees, Shaun W. P.;Paulin, Emily K.;van Rensburg, Michelle;Xu, Chris Sun;Langley, Ries J.;Leung, Ivanhoe K. H.;Reynisson, Johannes;Leung, Euphemia;Barker, David. And the article was included in European Journal of Medicinal Chemistry in 2020.SDS of cas: 182618-86-6 This article mentions the following:

Phospholipases are enzymes that are involved in the hydrolysis of acyl and phosphate esters of phospholipids, generating secondary messengers that have implications in various cellular processes including proliferation, differentiation and motility. As such inhibitors of phospholipases have been widely studied for their use as anti-cancer therapeutics. Phosphatidylcholine-specific phospholipase C (PC-PLC) is implicated in the progression of a number of cancer cell lines including aggressing triple-neg. breast cancers. Most current studies on PC-PLC have utilized D609 as the standard inhibitor however it is known to have multiple failings, including poor stability in aqueous media. 2-Morpholinobenzoic acids were recently identified using vHTS as a potential class of lead compounds, with improvements over D609. In this work 129 analogs in this class were prepared and their PC-PLC inhibitory activity was assessed. It was found that the majority of these novel compounds had improved activity when compared to D609 with the most potent inhibitors completely inhibiting enzyme activity. It was determined that the best compound/s contained a morpholino and 2-substituted N-benzyl moieties with these findings explained using mol. modeling. The compounds reported here will allow for improved study of PC-PLC activity. In the experiment, the researchers used many compounds, for example, 1-Boc-4-(4-Nitrophenyl)piperazine (cas: 182618-86-6SDS of cas: 182618-86-6).

1-Boc-4-(4-Nitrophenyl)piperazine (cas: 182618-86-6) belongs to piperazine derivatives. Piperazine is a fairly basic compound and is an amine solvent. 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.SDS of cas: 182618-86-6

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

Synthesis and antimuscarinic activity of some 1-cycloalkyl-1-hydroxy-1-phenyl-3-(4-substituted piperazinyl)-2-propanones and related compounds was written by Kaiser, Carl;Audia, Vicki H.;Carter, J. Paul;McPherson, Daniel W.;Waid, Philip P.;Lowe, Valerie C.;Noronha-Blob, Lalita. And the article was included in Journal of Medicinal Chemistry in 1993.COA of Formula: C7H16N2 This article mentions the following:

A new class of substituted 1-phenyl-3-piperazinyl-2-propanones I (R = cyclobutyl, cyclohexyl, iso-Bu, cyclopropyl, Ph, cyclopentyl, R¹ = H, Me, CH₂CCH, CH₂Ph, CH₂CN, CH₂C₆H₄NO₂-4, etc.) and PhCR(OH)COCH₂R² [II, R = cyclopropyl, cyclobutyl, cyclopentyl, Ph, R² = 4-hydroxy-1-piperidinyl, 4-(1-pyrrolidinyl)piperidinyl, NH(CH₂)₂NMe₂) with antimuscarinic activity were prepared Thus, PhCR(OH)COMe were brominated to give PhCR(OH)COCH₂Br which were aminated to give I and II. As part of a structure-activity relationship study of this class, various structural modifications, particularly one involving substitution of position 1 and the terminal piperazine nitrogen, were investigated. The objective of this study was to derive new antimuscarinic agents with potential utility in treating urinary incontinence associated with bladder muscle instability. These compounds were examined for M₁, M₂, and M₃ muscarinic receptor selectivity in isolated tissue assay and for in vivo effects on urinary bladder contraction, mydriasis, and salivation in guinea pigs. Potency and selectivity in these assays were influenced most notably by the nature of the substituent group on the terminal nitrogen of the piperazine moiety. Benzyl substitution was particularly advantageous in producing compounds with functional M₃ receptor (smooth muscle) and bladder selectivity; it provided several candidates for clin. study. In vivo, I (R = cyclobutyl, R¹ = CH₂Ph) demonstrated 11- and 37-fold separations in its effect on bladder function vs. mydriatic and salivation responses, resp. The corresponding 2-chlorobenzyl derivative was more than 178-fold selective for M₃ vs. M₁ and M₂ muscarinic receptors. I (R = Ph, R¹ = CH₂Ph) was 18-fold selective for M₃ vs. M₁ and 242-fold selective for M₃ vs. M₂ receptors. It was also selective in guinea pigs, where it displayed 20- and 41-fold separations between bladder function and effect on mydriasis and salivation, resp. In general, the results of this study are consistent with the proposition that the described piperazinylpropanones interact with muscarinic receptors in a hydrogen-bonded form that presents a conformation similar to that apparently adopted by classical antimuscarinic agents. In the experiment, the researchers used many compounds, for example, 1-Propylpiperazine (cas: 21867-64-1COA of Formula: C7H16N2).

1-Propylpiperazine (cas: 21867-64-1) belongs to piperazine derivatives. Piperazine belongs to the family of medicines called anthelmintics. 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. COA of Formula: C7H16N2

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

Synthesis and investigation of novel benzimidazole derivatives as antifungal agents was written by Chandrika, Nishad Thamban;Shrestha, Sanjib K.;Ngo, Huy X.;Garneau-Tsodikova, Sylvie. And the article was included in Bioorganic & Medicinal Chemistry in 2016.SDS of cas: 21867-64-1 This article mentions the following:

The rise and emergence of resistance to antifungal drugs by diverse pathogenic fungal strains have resulted in an increase in demand for new antifungal agents. Various heterocyclic scaffolds with different mechanisms of action against fungi have been investigated in the past. Herein, we report the synthesis and antifungal activities of 18 alkylated mono-, bis-, and trisbenzimidazole derivatives, their toxicities against mammalian cells, as well as their ability to induce reactive oxygen species (ROS) in yeast cells. Many of our bisbenzimidazole compounds exhibited moderate to excellent antifungal activities against all tested fungal strains, with MIC values ranging from 15.6 to 0.975 μg/mL. The fungal activity profiles of our bisbenzimidazoles were found to be dependent on alkyl chain length. Our most potent compounds were found to display equal or superior antifungal activity when compared to the currently used agents amphotericin B, fluconazole, itraconazole, posaconazole, and voriconazole against many of the strains tested. In the experiment, the researchers used many compounds, for example, 1-Propylpiperazine (cas: 21867-64-1SDS of cas: 21867-64-1).

1-Propylpiperazine (cas: 21867-64-1) 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.SDS of cas: 21867-64-1

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

Evaluation of functionalized silica’s for the adsorptive recovery of homogeneous catalysts through interaction with the metal centre was written by Djekic, T.;van der Ham, A. G. J.;de Haan, A. B.. And the article was included in Journal of Chromatography A in 2007.Application of 21867-64-1 This article mentions the following:

The goal of this paper is the evaluation of functionalized silicas for the recovery of homogeneous catalysts by adsorption via its metal center. As model catalysts, we selected bis(triphenylphosphine)cobalt(II)dichloride (CoCl₂(PPh₃)₂), bis(triphenylphosphine)palladium(II)dichloride (PdCl₂(PPh₃)₂) and tris(triphenylphosphine)rhodium(I)dichloride (RhCl(PPh₃)₃). Twelve functionalized groups selected from four classes containing one or more N-, O-, P- or S-atoms were evaluated. A preliminary selection of the adsorbents was done by investigating the adsorption of the metal salts for the cobalt and the palladium complex. The results could be explained by the Hard and Soft Acid Base (HSAB) theory. For the most suitable functionalized adsorbents, these experiments were extended by introducing the ligand in the system which promoted the competition of the functionalized groups on adsorbent and the ligands present in solution These experiments demonstrated that different complex species are adsorbed. 2-(2Pyridyl)ethyl-functionalized silica is selected as a promising adsorbent for adsorption of the CoCl₂(PPh₃)₂ from acetonitrile, while 3-(mercapto)propyl-functionalized silica is selected as a promising adsorbent for adsorption of the PdCl₂(PPh₃)₂ and RhCl(PPh₃)₃ from DMF. The presence of a ligand, an increase of the temperature and the presence of a solvent with the donor properties can decrease the adsorption equilibrium and need to be taken into account. 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 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.Application of 21867-64-1

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

Novel and High Affinity 2-[(Diphenylmethyl)sulfinyl]acetamide (Modafinil) Analogues as Atypical Dopamine Transporter Inhibitors was written by Cao, Jianjing;Slack, Rachel D.;Bakare, Oluyomi M.;Burzynski, Caitlin;Rais, Rana;Slusher, Barbara S.;Kopajtic, Theresa;Bonifazi, Alessandro;Ellenberger, Michael P.;Yano, Hideaki;He, Yi;Bi, Guo-Hua;Xi, Zheng-Xiong;Loland, Claus J.;Newman, Amy Hauck. And the article was included in Journal of Medicinal Chemistry in 2016.Safety of 1-Propylpiperazine This article mentions the following:

The development of pharmacotherapeutic treatments of psychostimulant abuse has remained a challenge, despite significant efforts made toward relevant mechanistic targets, such as the dopamine transporter (DAT). The atypical DAT inhibitors have received attention due to their promising pharmacol. profiles in animal models of cocaine and methamphetamine abuse. Herein the authors report a series of modafinil analogs that have an atypical DAT inhibitor profile. The authors extended SAR by chem. manipulating the oxidation states of the sulfoxide and the amide functional groups, halogenating the Ph rings, and/or functionalizing the terminal nitrogen with substituted piperazines, resulting in several novel leads such as 1-(4-(2-((bis(4-fluorophenyl)methyl)sulfinyl)ethyl)piperazin-1-yl)-3-phenylpropan-2-ol (compound 11b), which demonstrated high DAT affinity (K_i = 2.5 nM) and selectivity without producing concomitant locomotor stimulation in mice, as compared to cocaine. These results are consistent with an atypical DAT inhibitor profile and suggest that 11b may be a potential lead for development as a psychostimulant abuse medication. In the experiment, the researchers used many compounds, for example, 1-Propylpiperazine (cas: 21867-64-1Safety of 1-Propylpiperazine).

1-Propylpiperazine (cas: 21867-64-1) belongs to piperazine derivatives. Industrial applications of piperazine include the manufacture of plastics, resins, pesticides and brake fluids. 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.Safety of 1-Propylpiperazine

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

Organocatalytic synthesis of novel purine and pyrimidine acyclic nucleosides was written by Palazzolo, Martin A.;Perez-Sanchez, Maria;Iribarren, Adolfo M.;Lewkowicz, Elizabeth S.;Dominguez de Maria, Pablo. And the article was included in Tetrahedron Letters in 2012.Electric Literature of C7H16N2 This article mentions the following:

Organocatalysis is assessed for the first time in the synthesis of purine and pyrimidine acyclic nucleosides providing high yields and straightforward work-up procedures. Nucleobases containing aldehydes are catalytically ligated (C-C bond formation) to acetone or to phosphonate-containing ketones by means of pyrrolidine or silica-immobilized piperazine as amine-based organocatalysts. In the experiment, the researchers used many compounds, for example, 1-Propylpiperazine (cas: 21867-64-1Electric Literature of C7H16N2).

1-Propylpiperazine (cas: 21867-64-1) belongs to piperazine derivatives. Piperazine belongs to the family of medicines called anthelmintics. 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.Electric Literature of C7H16N2

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

Silica-functionalized N-propylpiperazine for immobilization of palladium nanoparticles as efficient heterogeneous catalyst for cyanation reactions was written by Niknam, Khodabakhsh;Deris, Abdollah;Panahi, Farhad. And the article was included in Cuihua Xuebao in 2013.Recommanded Product: 21867-64-1 This article mentions the following:

An efficient heterogeneous Pd catalytic system has been developed, based on immobilization of Pd nanoparticles (PNPs) on a silica-bonded N-propylpiperazine (SBNPP) substrate. The SBNPP substrate effectively stabilizes the PNPs and improves their stability against aggregation. The catalytic activity of this catalyst was investigated in the cyanation of aryl halides with K₄[Fe(CN)₆] as the cyanide source. The catalyst could be recycled several times without appreciable loss of catalytic activity. In the experiment, the researchers used many compounds, for example, 1-Propylpiperazine (cas: 21867-64-1Recommanded Product: 21867-64-1).

1-Propylpiperazine (cas: 21867-64-1) belongs to piperazine derivatives. Industrial applications of piperazine include the manufacture of plastics, resins, pesticides and brake fluids. 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.Recommanded Product: 21867-64-1

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

Discovery of (E)-N-(4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)-3-((3-(2-(pyridin-2-yl)vinyl)-1H-indazol-6-yl)thio)propanamide (CHMFL-ABL-121) as a highly potent ABL kinase inhibitor capable of overcoming a variety of ABL mutants including T315I for chronic myeloid leukemia was written by Liu, Xuesong;Wang, Beilei;Chen, Cheng;Jiang, Zongru;Hu, Chen;Wu, Hong;Zhang, Yicong;Liu, Xiaochuan;Wang, Wenliang;Wang, Junjie;Hu, Zhenquan;Wang, Aoli;Huang, Tao;Liu, Qingwang;Wang, Wei;Wang, Li;Wang, Wenchao;Ren, Tao;Li, Lili;Xia, Ruixiang;Ge, Jian;Liu, Qingsong;Liu, Jing. And the article was included in European Journal of Medicinal Chemistry in 2018.Product Details of 630125-91-6 This article mentions the following:

There is still a great demand in the clinic for the drugs which can overcome a variety of imatinib resistant ABL mutants. Starting from a type I inhibitor axitinib, which has been reported to overcome ABL-T315I mutant induced resistance, through a structure guided drug design approach and binding mode switch strategy, the authors have discovered a novel type II ABL inhibitor I (CHMFL-ABL-121), which significantly improved the inhibitory activity against ABL wt and a broad spectrum of mutants including the most prevalent imatinib-resistant gatekeeper mutant T315I. I exhibited IC₅₀ values of 2 nM and 0.2 nM against purified inactive ABL wt and T315I kinase protein resp. and inhibited the proliferation of the established CML cell lines with GI₅₀ at single digit nM. In cellular context, I strongly affected BCR-ABL mediated signaling pathways and induced apoptosis as well as arrested cell cycle at G0/G1 phase. In the in vivo study, 50 mg/kg/day dosage of I displayed TGI of 52% in the TEL-ABLT315I-BaF3 cell inoculated allograft mouse model without obvious toxicity. In the experiment, the researchers used many compounds, for example, 4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline (cas: 630125-91-6Product Details of 630125-91-6).

4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline (cas: 630125-91-6) belongs to piperazine derivatives. Industrial applications of piperazine include the manufacture of plastics, resins, pesticides and brake fluids. 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.Product Details of 630125-91-6

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

1-Amino-4-benzylphthalazines as Orally Bioavailable Smoothened Antagonists with Antitumor Activity was written by Miller-Moslin, Karen;Peukert, Stefan;Jain, Rishi K.;McEwan, Michael A.;Karki, Rajesh;Llamas, Luis;Yusuff, Naeem;He, Feng;Li, Yanhong;Sun, Yingchuan;Dai, Miao;Perez, Lawrence;Michael, Walter;Sheng, Tao;Lei, Huangshu;Zhang, Rui;Williams, Juliet;Bourret, Aaron;Ramamurthy, Arun;Yuan, Jing;Guo, Ribo;Matsumoto, Melissa;Vattay, Anthony;Maniara, Wieslawa;Amaral, Adam;Dorsch, Marion;Kelleher, Joseph F. III. And the article was included in Journal of Medicinal Chemistry in 2009.COA of Formula: C10H12N4 This article mentions the following:

Abnormal activation of the Hedgehog (Hh) signaling pathway has been linked to several types of human cancers, and the development of small-mol. inhibitors of this pathway represents a promising route toward novel anticancer therapeutics. A cell-based screen performed in our laboratories identified a new class of Hh pathway inhibitors, 1-amino-4-benzylphthalazines, e.g. I, that act via antagonism of the Smoothened receptor. A variety of analogs were synthesized and their structure-activity relationships determined This optimization resulted in the discovery of high affinity Smoothened antagonists, one of which was further profiled in vivo. This compound displayed a good pharmacokinetic profile and also afforded tumor regression in a genetic mouse model of medulloblastoma. In the experiment, the researchers used many compounds, for example, 6-(Piperazin-1-yl)nicotinonitrile (cas: 149554-29-0COA of Formula: C10H12N4).

6-(Piperazin-1-yl)nicotinonitrile (cas: 149554-29-0) belongs to piperazine derivatives. Piperazine is a fairly basic compound and is an amine solvent. 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).COA of Formula: C10H12N4

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