Tag: 200-300

Synthesis, interaction with DNA and bioactivity of N-piperazinoalkylamide was written by Wang, Yu-Xia;Zhao, Jin;Sun, Xin-Qi;Wang, Chao-Jie. And the article was included in Youji Huaxue in 2006.Computed Properties of C12H25N3O2 This article mentions the following:

Nine novel N-piperazinoalkylamide derivatives were synthesized and their structures were confirmed by ¹H NMR, MS spectra and elemental anal. All the target compounds, together with the four com. drugs, naproxen, 4-biphenylacetic acid, brufen (as the acyl agents) and 5-fluorouracil, were tested in vitro for their inhibition on four kinds of human cancer cells, KB, A-549, MDA and Bel-7402. The data showed that all the synthesized compounds exhibited pos. effect on KB and Bel-7402 cells, but neg. effect on A-549 and MDA cells, while the com. medicines had the similar results unexpectedly. In addition, the inhibition rate of 4-biphenylacetic acid and naproxen on Bel-7402 cell was equivalent with 5-fluorouracil, while their inhibition on KB cell was higher than that of 5-fluorouracil. The inhibitory ability of the samples on tyrosine kinase was also measured, however no obvious effect was found. The fluorescence spectra of 13a and 4-biphenylacetic acid demonstrated that 13a did not show the interaction with DNA while 4-biphenylacetic acid exhibited the intercalary effect on DNA. In the experiment, the researchers used many compounds, for example, tert-Butyl 4-(3-aminopropyl)piperazine-1-carboxylate (cas: 373608-48-1Computed Properties of C12H25N3O2).

tert-Butyl 4-(3-aminopropyl)piperazine-1-carboxylate (cas: 373608-48-1) 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. 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.Computed Properties of C12H25N3O2

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

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

Multistep Continuous-Flow Synthesis in Medicinal Chemistry: Discovery and Preliminary Structure-Activity Relationships of CCR8 Ligands was written by Petersen, Trine P.;Mirsharghi, Sahar;Rummel, Pia C.;Thiele, Stefanie;Rosenkilde, Mette M.;Ritzen, Andreas;Ulven, Trond. And the article was included in Chemistry – A European Journal in 2013.Formula: C13H18N2O2 This article mentions the following:

A three-step continuous-flow synthesis system and its application to the assembly of a new series of chemokine receptor ligands directly from com. building blocks is reported. No scavenger columns or solvent switches are necessary to recover the desired test compounds, which were obtained in overall yields of 49-94%. The system is modular and flexible, and the individual steps of the sequence can be interchanged with similar outcome, extending the scope of the chem. Biol. evaluation confirmed activity on the chemokine CCR8 receptor and provided initial structure-activity-relationship (SAR) information for this new ligand series, with the most potent member displaying full agonist activity with single-digit nanomolar potency. To the best of the knowledge, this represents the first published example of efficient use of multistep flow synthesis combined with biol. testing and SAR studies in medicinal chem. In the experiment, the researchers used many compounds, for example, (R)-1-Cbz-2-methylpiperazine (cas: 923565-99-5Formula: C13H18N2O2).

(R)-1-Cbz-2-methylpiperazine (cas: 923565-99-5) 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.Formula: C13H18N2O2

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

Development of protein degradation inducers of oncogenic BCR-ABL protein by conjugation of ABL kinase inhibitors and IAP ligands was written by Shibata, Norihito;Miyamoto, Naoki;Nagai, Katsunori;Shimokawa, Kenichiro;Sameshima, Tomoya;Ohoka, Nobumichi;Hattori, Takayuki;Imaeda, Yasuhiro;Nara, Hiroshi;Cho, Nobuo;Naito, Mikihiko. And the article was included in Cancer Science in 2017.Electric Literature of C14H20F3N3 This article mentions the following:

Chromosomal translocation occurs in some cancer cells, which results in the expression of aberrant oncogenic fusion proteins that include BCR-ABL in chronic myelogenous leukemia (CML). Inhibitors of ABL tyrosine kinase, such as imatinib and dasatinib, exhibit remarkable therapeutic effects, although emergence of drug resistance hampers the therapy during long-term treatment. An alternative approach to treat CML is to downregulate the BCR-ABL protein. We have devised a protein knockdown system by hybrid mols. named Specific and Non-genetic inhibitor of apoptosis protein [IAP]-dependent Protein Erasers (SNIPER), which is designed to induce IAP-mediated ubiquitylation and proteasomal degradation of target proteins, and a couple of SNIPER(ABL) against BCR-ABL protein have been developed recently. In this study, we tested various combinations of ABL inhibitors and IAP ligands, and the linker was optimized for protein knockdown activity of SNIPER(ABL). The resulting SNIPER(ABL)-39, in which dasatinib is conjugated to an IAP ligand LCL161 derivative by polyethylene glycol (PEG) × 3 linker, shows a potent activity to degrade the BCR-ABL protein. Mechanistic anal. suggested that both cellular inhibitor of apoptosis protein 1 (cIAP1) and X-linked inhibitor of apoptosis protein (XIAP) play a role in the degradation of BCR-ABL protein. Consistent with the degradation of BCR-ABL protein, the SNIPER(ABL)-39 inhibited the phosphorylation of signal transducer and activator of transcription 5 (STAT5) and Crk like proto-oncogene (CrkL), and suppressed the growth of BCR-ABL-pos. CML cells. These results suggest that SNIPER(ABL)-39 could be a candidate for a degradation-based novel anti-cancer drug against BCR-ABL-pos. CML. In the experiment, the researchers used many compounds, for example, 4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline (cas: 630125-91-6Electric Literature of C14H20F3N3).

4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline (cas: 630125-91-6) 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. Electric Literature of C14H20F3N3

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

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

Discovery of a Nanomolar Multikinase Inhibitor (KST016366): A New Benzothiazole Derivative with Remarkable Broad-Spectrum Antiproliferative Activity was written by El-Damasy, Ashraf Kareem;Cho, Nam-Chul;Nam, Ghilsoo;Pae, Ae Nim;Keum, Gyochang. And the article was included in ChemMedChem in 2016.Application of 630125-91-6 This article mentions the following:

Herein we report the discovery of compound 6 [KST016366; 4-((2-(3-(4-((4-ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)ureido)benzo[d]thiazol-6-yl)oxy)picolinamide] as a new potent multikinase inhibitor through minor structural modification of our previously reported RAF kinase inhibitor A. In vitro anticancer evaluation of 6 showed substantial broad-spectrum antiproliferative activity against 60 human cancer cell lines. In particular, it showed GI₅₀ values of 51.4 and 19 nM against leukemia K-562 and colon carcinoma KM12 cell lines, resp. Kinase screening of compound 6 revealed its nanomolar-level inhibitory activity of certain oncogenic kinases implicated in both tumorigenesis and angiogenesis. Interestingly, 6 displays IC₅₀ values of 0.82, 3.81, and 53 nM toward Tie2, TrkA, and ABL-1 (wild-type and T315I mutant) kinases, resp. Moreover, 6 is orally bioavailable with a favorable in vivo pharmacokinetic profile. Compound 6 may serve as a promising candidate for further development of potent anticancer chemotherapeutics. In the experiment, the researchers used many compounds, for example, 4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline (cas: 630125-91-6Application of 630125-91-6).

4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline (cas: 630125-91-6) 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 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.Application of 630125-91-6

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

Synthesis and evaluation of novel amonafide-polyamine conjugates as anticancer agents was written by Wang, Yuxia;Zhang, Jianying;Li, Meng;Li, Ming;Xie, Songqiang;Wang, Chaojie. And the article was included in Chemical Biology & Drug Design in 2017.Related Products of 373608-48-1 This article mentions the following:

Hydrochloride salts of aminoacetamido and ureido-substituted analogs of amonafide I [R = Bu, cyclohexyl, Me₂NCH₂CH₂, H₂N(CH₂)₃, H₂N(CH₂)₄, 3-(4-Boc-1-piperazinyl)propyl, H₂N(CH₂)_nNH(CH₂)_m, H₂N(CH₂)_mNH(CH₂)_nNH(CH₂)_m; m, n = 1, 2; X = bond, CH₂] were prepared as potential antitumor agents; their antitumor activity against various human cancer cell lines, the toxicities of selected compounds, and the in vivo antitumor activity and inhibition of cell migration and metastasis of I•5 HCl [R = H₂N(CH₂)₂NH(CH₂)₂NH(CH₂)₂; X = CH₂] (II) alone in concert with aspirin were determined Amonafide analogs with urea linkers were not active. Aspirin elevated the potency of II against tumor cells, wound healing, and the protein expression of cyclic D1 and MMP9; in vivo trials on three H22 tumor transplant models demonstrated that the combination of II and aspirin inhibited tumor growth and metastasis and extended lifespan while showing reduced side effects compared to amonafide. In the experiment, the researchers used many compounds, for example, tert-Butyl 4-(3-aminopropyl)piperazine-1-carboxylate (cas: 373608-48-1Related Products of 373608-48-1).

tert-Butyl 4-(3-aminopropyl)piperazine-1-carboxylate (cas: 373608-48-1) belongs to piperazine derivatives. A form in which piperazine is commonly available industrially is as the hexahydrate, C4H10N2. 6H2O, which melts at 44 °C and boils at 125–130 °C. 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.Related Products of 373608-48-1

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

Design and synthesis of pyridine-substituted itraconazole analogues with improved antifungal activities, water solubility and bioavailability was written by Liu, Yu;Liu, Zining;Cao, Xufeng;Liu, Xin;He, Huili;Yang, Yushe. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2011.Category: piperazines This article mentions the following:

To improve antifungal activities, water solubility and bioavailability, a series of novel analogs of itraconazole-containing pyridine rings were designed and synthesized. Their antifungal activities were evaluated in vitro against six clin. important fungi by measuring the minimal inhibitory concentrations (MICs). Most of the compounds showed more potent antifungal activities than that of itraconazole. In particular, I [X = CH, X¹ = N, R = CH₂CHMe₂, CHMe₂; X = N, X¹ = CH, R = CHMe₂, CH₂CMe₂CH₂OH, II] exhibited much higher solubility and bioavailability than that of itraconazole. The bioavailability of II (42.2%) was five times higher than that of itraconazole (8%) and was neg. for genetic toxicol. in the Ames test. In the experiment, the researchers used many compounds, for example, tert-Butyl 4-(5-aminopyridin-2-yl)piperazine-1-carboxylate (cas: 119285-07-3Category: piperazines).

tert-Butyl 4-(5-aminopyridin-2-yl)piperazine-1-carboxylate (cas: 119285-07-3) belongs to piperazine derivatives. Piperazine is a fairly basic compound and is an amine solvent. 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.Category: piperazines

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