Month: January 2023

Synthesis of piperazine derivatives. XII. Preparation of N¹-substituted N⁴-(3-phenylpropyl)piperazines was written by Zikolova, S.. And the article was included in Trudove na Nauchnoizsledovatelskiya Khimikofarmatsevtichen Institut in 1978.Application In Synthesis of 1-Propylpiperazine This article mentions the following:

N-(3-Phenylpropyl)piperazine was alkylated with alkyl halides (e.g., EtI) in refluxing solvent containing Na₂CO₃ to give 26 title compounds [I; R = C₁-C₈ alkyl, allyl, crotyl, cycloalkyl, aralkyl, (aryloxy)alkyl, XCH₂CH₂; X = Et₂N, piperidino, morpholino] in 65-98% yield, isolated as hydrochlorides and oxalates. I (R = Me) was also prepared from N-methylpiperazine and Pr(CH₂)₃Br (II) and I [R = Ph(CH₂)₃], from II and piperazine. In the experiment, the researchers used many compounds, for example, 1-Propylpiperazine (cas: 21867-64-1Application In Synthesis of 1-Propylpiperazine).

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 In Synthesis of 1-Propylpiperazine

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

Design, synthesis and biological evaluation of 3-arylisoquinoline derivatives as topoisomerase I and II dual inhibitors for the therapy of liver cancer was written by Deng, Xuemei;Luo, Tian;Zhang, Xi;Li, Yuehua;Xie, Liming;Jiang, Weifan;Liu, Linyi;Wang, Zhen. And the article was included in European Journal of Medicinal Chemistry in 2022.COA of Formula: C7H16N2 This article mentions the following:

To explore novel topoisomerase inhibitors with high activity and druggability, 3-aryl isoquinoline alkaloids based on the corydamine modification and preliminary SARs of isoquinoline alkaloids in our previous works were re-designed. Currently, the design strategy is mainly revolved around the rigidity and flexibility of the mol. side chain and the mol. size. Consequently, not only the activity and druggability of the compound could be further improved, also the mechanism behind could been discovered. In vitro pharmacol. studies, the outstanding nature with the excellent activity and the researchable depth of azepane-substituted compound has been found through the vitro cytotoxicity test (IC₅₀ = 1.93μM in HuH7 cells and 2.10μM in LM9 cells) and topoisomerase test. It was found that azepane-substituted compound had dual inhibitory effects on topoisomerase I and II, and its inhibitory activity on topoisomerase II is stronger than the pos. drug etoposide. From the perspective of mol. docking, it had been verified that azepane-substituted compound could insert between DNA base pairs, which was consistent with the results of the DNA unwinding experiment Meanwhile, azepane-substituted isoquinoline could inhibit cell proliferation, invasion and migration, and induce apoptosis by inhibiting PI3K/Akt/mTOR signaling pathway. Therefore, this study may lay a foundation for the discovery of 3-arylisoquinoline compounds with anti-liver cancer potential. 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. 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.COA of Formula: C7H16N2

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 4-(heterocyclic substituted amino)-1H-pyrazole-3-carboxamide derivatives and their potent activity against acute myeloid leukemia (AML) was written by Zhi, Yanle;Wang, Zhijie;Yao, Chao;Li, Baoquan;Heng, Hao;Cai, Jiongheng;Xiang, Li;Wang, Yue;Lu, Tao;Lu, Shuai. And the article was included in International Journal of Molecular Sciences in 2019.Recommanded Product: 1-Boc-4-(4-Nitrophenyl)piperazine This article mentions the following:

Fms-like receptor tyrosine kinase 3 (FLT3) has been emerging as an attractive target for the treatment of acute myeloid leukemia (AML). By modifying the structure of FN-1501, a potent FLT3 inhibitor, 24 novel 1H-pyrazole-3-carboxamide derivatives I [R = Ph, pyridin-4-yl, 1-(tert-butoxycarbonyl)piperidine-4-yl, piperidin-4-yl] and II [R¹ = H, (morpholin-4-yl)carbonyl, (4-methylpiperazin-1-yl)carbonyl, piperazin-1-yl, etc.; R² = H, 4-methyl-1,4-diazepan-1-yl; X = CH, N; R³ = thieno[2,3-d]pyrimidin-4-yl, 7H-pyrrolo[2,3-d]pyrimidin-4-yl, etc.] were designed and synthesized. Compound II [R¹ = piperazin-1-yl, R² = H, X = CH, R³ = 7-thia-9,11-diazatricyclo[6.4.0.0(2,6)]dodeca-1(8),2(6),9,11-tetraen-12-yl (III)] showed strong activity against FLT3 (IC⁵⁰: 0.089 nM) and CDK2/4 (IC⁵⁰: 0.719/0.770 nM), which is more efficient than FN-1501(FLT3, IC⁵⁰: 2.33 nM; CDK2/4, IC⁵⁰: 1.02/0.39 nM). Compound III also showed excellent inhibitory activity against a variety of FLT3 mutants (IC⁵⁰ >5 nM), and potent anti-proliferative effect within the nanomolar range on acute myeloid leukemia (MV4-11, IC⁵⁰: 1.22 nM). In addition, compound III significantly inhibited the proliferation of most human cell lines of NCI60 (GI⁵⁰ < 1μ M for most cell lines). Taken together, these results demonstrated the potential of III as a novel compound for further development into a kinase inhibitor applied in cancer therapeutics. In the experiment, the researchers used many compounds, for example, 1-Boc-4-(4-Nitrophenyl)piperazine (cas: 182618-86-6Recommanded Product: 1-Boc-4-(4-Nitrophenyl)piperazine).

1-Boc-4-(4-Nitrophenyl)piperazine (cas: 182618-86-6) 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.Recommanded Product: 1-Boc-4-(4-Nitrophenyl)piperazine

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

Improvement on the synthetic process of N-aryl piperazines was written by Liu, Ning;Chen, Jin-chun. And the article was included in Guangzhou Huagong in 2014.HPLC of Formula: 182618-86-6 This article mentions the following:

By using N,N-bis(2-chloroethyl) amine hydrochloride and substituted aniline as initial material, Bu alc. as the solvent, refluxing in the absence of base to convert to corresponding N-aryl piperazines in high yield. The structure was confirmed by ¹H-NMR. The product can crystallize directly from the system and the filtrate can be used several times so that the new synthetic method was applicable in the industrial scale production Compared to the reported method, the new process simplified the operation steps, reduced the difficulty of the product separation and improved the yield and purity of the product. In the experiment, the researchers used many compounds, for example, 1-Boc-4-(4-Nitrophenyl)piperazine (cas: 182618-86-6HPLC of Formula: 182618-86-6).

1-Boc-4-(4-Nitrophenyl)piperazine (cas: 182618-86-6) belongs to piperazine derivatives. Piperazine belongs to the family of medicines called anthelmintics. 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.HPLC of Formula: 182618-86-6

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

Synthesis, single crystal X-ray analysis, and DFT calculations of tert-butyl 4-(4-nitrophenyl)piperazine-1-carboxylate was written by Yang, Zhi song;Cai, Xiangzhi;Chen, Junjiang;Shi, Yuan;Huang, Pengyue;Chai, Huifang;Zhao, Chun shen. And the article was included in Molecular Crystals and Liquid Crystals in 2022.Category: piperazines This article mentions the following:

Tert-Bu 4-(4-nitrophenyl)piperazine-1-carboxylate is an organic intermediate. In this paper, the title compound was obtained by nucleophilic substitution reaction. The structure of the compound was confirmed by FT-IR, ¹H NMR, ¹³C NMR spectroscopy, and MS. The single crystal of the title compound was measured by X-ray diffraction and was subjected to crystallog. and conformational anal. The mol. structure was further calculated using d. functional theory, which was compared with the X-ray diffraction value. In addition, the mol. electrostatic potential and frontier MOs of the title compound were further investigated using DFT, revealing stability of mol. structure and mol. conformations. In the experiment, the researchers used many compounds, for example, 1-Boc-4-(4-Nitrophenyl)piperazine (cas: 182618-86-6Category: piperazines).

1-Boc-4-(4-Nitrophenyl)piperazine (cas: 182618-86-6) 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. 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.Category: piperazines

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

Piperazinyl Bicyclic Derivatives as Selective Ligands of the α2δ-1 Subunit of Voltage-Gated Calcium Channels was written by Fernandez, Ariadna;Diaz, Jose Luis;Garcia, Monica;Rodriguez-Escrich, Sergi;Lorente, Adriana;Enrech, Raquel;Dordal, Albert;Portillo-Salido, Enrique;Porras, Monica;Fernandez, Begona;Reinoso, Raquel F.;Vela, Jose Miguel;Almansa, Carmen. And the article was included in ACS Medicinal Chemistry Letters in 2021.COA of Formula: C6H14N2 This article mentions the following:

The synthesis and pharmacol. activities of a new series of piperazinyl quinazolin-4-(3H)-one derivatives I [R¹ = H, 5-Br, 6-(4-pyridinyl), 8-Br, etc.; R² = 2-methoxyethyl, benzyl, 2-furylmethyl, etc.; R³ = H, Me, Pr, n-Bu, etc.; R⁴ = piperazin-1-yl, (3R,5S)-3,5-dimethylpiperazin-1-yl, (S)-3-methylpiperazin-1-yl, etc.] acting toward the α2δ-1 subunit of voltage-gated calcium channels (Cavα2δ-1) were reported. Different positions of a micromolar HTS hit were explored, and best activities were obtained for compounds I containing a small alkyl group in position 3 of the quinazolin-4-(3H)-one scaffold and a 3-methyl-piperazin-1-yl- or 3,5-dimethyl-piperazin-1-yl-Bu group in position 2. The activity was shown to reside in the R enantiomer of the chain in position 2, and several eutomers reached single digit nanomolar affinities. Final modification of the central scaffold to reduce lipophilicity provided the pyrido[4,3-d]pyrimidin-4(3H)-one II, which showed high selectivity for Cavα2δ-1 vs. Cavα2δ-2, probably linked to its improved analgesic efficacy-safety ratio in mice over pregabalin. In the experiment, the researchers used many compounds, for example, (S)-2-Ethylpiperazine (cas: 207284-20-6COA of Formula: C6H14N2).

(S)-2-Ethylpiperazine (cas: 207284-20-6) 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. COA of Formula: C6H14N2

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

Synthesis of New 5-(1,4-Benzodioxan-2-yl)thieno[2,3-d]pyrimidine Derivatives was written by Vardanyan, S. O.;Aghekyan, A. A.;Avagyan, A. S.;Sargsyan, A. B.;Panosyan, H. A.;Harutyunyan, S. A.;Gasparyan, H. V.. And the article was included in Russian Journal of Organic Chemistry in 2022.Name: 1-Propylpiperazine This article mentions the following:

Cyclization of previously synthesized Et 2-amino-4-(1,4-benzodioxan-2-yl)thiophene-3-carboxylate with formamide gave 5-(1,4-benzodioxan-2-yl)thieno[2,3-d]pyrimidin-4(3H)-one which was treated with phosphoryl chloride in pyridine to obtain the corresponding 4-chloro derivative The latter reacted with various primary and secondary amines to produce a series of new thieno[2,3-d]pyrimidines containing a pharmacophoric fragment at the 4-position. The reaction of 5-(1,4-benzodioxan-2-yl)-4-chlorothieno[2,3-d]pyrimidine with hydrazine hydrate afforded the corresponding 4-hydrazinyl derivative which was cyclized with formic acid to thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine derivative Antihypoxic properties of the synthesized compounds were studied. In the experiment, the researchers used many compounds, for example, 1-Propylpiperazine (cas: 21867-64-1Name: 1-Propylpiperazine).

1-Propylpiperazine (cas: 21867-64-1) 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.Name: 1-Propylpiperazine

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

Benzophenone-Based Farnesyltransferase Inhibitors with High Activity against Trypanosoma cruzi was written by Esteva, Monica I.;Kettler, Katja;Maidana, Cristina;Fichera, Laura;Ruiz, Andres M.;Bontempi, Esteban J.;Andersson, Bjoern;Dahse, Hans-Martin;Haebel, Peter;Ortmann, Regina;Klebe, Gerhard;Schlitzer, Martin. And the article was included in Journal of Medicinal Chemistry in 2005.Category: piperazines This article mentions the following:

Less toxic drugs are needed to combat the human parasite Trypanosoma cruzi (Chagas’s disease). One novel target for antitrypanosomal drug design is farnesyltransferase. Several farnesyltransferase inhibitors based on the benzophenone scaffold were assayed in vitro and in vivo with the parasite. The common structural feature of all inhibitors is an amino function which can be protonated. Best in vitro activity (LC₅₀ values 1 and 10 nM, resp.) was recorded for the R-phenylalanine derivative 4a and for the N-propylpiperazinyl derivative 2f. These inhibitors showed no cytotoxicity to cells. When tested in vivo, the survival rates of infected animals receiving the inhibitors at 7 mg/kg body weight/day were 80 and 60% at day 115 postinfection, resp. In the experiment, the researchers used many compounds, for example, 1-Propylpiperazine (cas: 21867-64-1Category: piperazines).

1-Propylpiperazine (cas: 21867-64-1) belongs to piperazine derivatives. Piperazine causes primary dermal irritation and skin burns at high concentrations. Piperazine also causes eye irritation in humans. 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.Category: piperazines

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