Tag: 300-400

Discovery of 2-(1H-imidazo-2-yl)piperazines as a new class of potent and non-cytotoxic inhibitors of Trypanosoma brucei growth in vitro was written by Ferrigno, Federica;Biancofiore, Ilaria;Malancona, Savina;Ponzi, Simona;Paonessa, Giacomo;Graziani, Rita;Bresciani, Alberto;Gennari, Nadia;Di Marco, Annalise;Kaiser, Marcel;Summa, Vincenzo;Harper, Steven;Ontoria, Jesus M.. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2018.Formula: C18H24N2O6 This article mentions the following:

The identification of a new series of growth inhibitors of Trypanosoma brucei rhodesiense, causative agent of Human African Trypanosomiasis (HAT), is described. A selection of compounds from our inhouse compound collection was screened in vitro against the parasite leading to the identification of compounds with nanomolar inhibition of T. brucei growth. Preliminary SAR on the hit compound led to the identification of compound 34 that shows low nanomolar parasite growth inhibition (T. brucei EC₅₀ 5 nM), is not cytotoxic (HeLa CC₅₀ > 25,000 nM) and is selective over other parasites, such as Trypanosoma cruzi and Plasmodium falciparum (T. cruzi EC₅₀ 8120 nM, P. falciparum EC₅₀ 3624 nM). In the experiment, the researchers used many compounds, for example, 4-((Benzyloxy)carbonyl)-1-(tert-butoxycarbonyl)piperazine-2-carboxylic acid (cas: 149057-19-2Formula: C18H24N2O6).

4-((Benzyloxy)carbonyl)-1-(tert-butoxycarbonyl)piperazine-2-carboxylic acid (cas: 149057-19-2) belongs to piperazine derivatives. A form in which piperazine is commonly available industrially is as the hexahydrate, C4H10N2. 6H2O, which melts at 44 闁硅櫣鐓?and boils at 125闂?30 闁硅櫣鐓? Intermediate for a wide range of pharmaceuticals, polymers, dyes, corrosion inhibitors, rubber accelerators and surfactants.Formula: C18H24N2O6

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

Discovery of Substituted 1H-Pyrazolo[3,4-b]pyridine Derivatives as Potent and Selective FGFR Kinase Inhibitors was written by Zhao, Bin;Li, Yixuan;Xu, Pan;Dai, Yang;Luo, Cheng;Sun, Yiming;Ai, Jing;Geng, Meiyu;Duan, Wenhu. And the article was included in ACS Medicinal Chemistry Letters in 2016.Computed Properties of C16H22N2O4 This article mentions the following:

Fibroblast growth factor receptors (FGFRs) are important targets for cancer therapy. Herein, we describe the design, synthesis, and biol. evaluation of a novel series of 1H-pyrazolo[3,4-b]pyridine derivatives as potent and selective FGFR kinase inhibitors. On the basis of its excellent in vitro potency and favorable pharmacokinetic properties, compound I was selected for in vivo evaluation and showed significant antitumor activity in a FGFR1-driven H1581 xenograft model. These results indicated that I would be a promising candidate for further drug development. In the experiment, the researchers used many compounds, for example, 4-(4-(tert-Butoxycarbonyl)piperazin-1-yl)benzoic acid (cas: 162046-66-4Computed Properties of C16H22N2O4).

4-(4-(tert-Butoxycarbonyl)piperazin-1-yl)benzoic acid (cas: 162046-66-4) belongs to piperazine derivatives. Simple N-substituted piperazines have been found in many drug molecules. 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. Computed Properties of C16H22N2O4

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

On-DNA Palladium-Catalyzed Hydrogenation-like Reaction Suitable for DNA-Encoded Library Synthesis was written by Priego, Julian;de Pedro Beato, Eduardo;Benavides, Jesus;Gironda-Martinez, Adrian;Gonzalez, Fernando;Blas, Jesus;Martin-Ortega, Maria Dolores;Rama-Garda, Ramon;Ezquerra, Jesus;Toledo, Miguel A.;Torrado, Alicia. And the article was included in Bioconjugate Chemistry in 2021.Safety of 4-((Benzyloxy)carbonyl)-1-(tert-butoxycarbonyl)piperazine-2-carboxylic acid This article mentions the following:

Herein we describe a method to orthogonally remove on-DNA N-Cbz, N-Alloc, N-Allyl, O-Bn, and O-Allyl protecting groups in the presence of other common protecting groups to afford free amines and carboxylic acids, resp. The developed method uses NaBH₄ as the source of hydrogen in the presence of Pd(OAc)₂ under DNA aqueous conditions. In addition, under the developed conditions we were able to successfully hydrogenate triple and double bonds to totally saturated compounds Furthermore, we introduce a new alternative procedure to reduce azides and aromatic nitro compounds to primary amines. In the experiment, the researchers used many compounds, for example, 4-((Benzyloxy)carbonyl)-1-(tert-butoxycarbonyl)piperazine-2-carboxylic acid (cas: 149057-19-2Safety of 4-((Benzyloxy)carbonyl)-1-(tert-butoxycarbonyl)piperazine-2-carboxylic acid).

4-((Benzyloxy)carbonyl)-1-(tert-butoxycarbonyl)piperazine-2-carboxylic acid (cas: 149057-19-2) 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.Safety of 4-((Benzyloxy)carbonyl)-1-(tert-butoxycarbonyl)piperazine-2-carboxylic acid

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

Synthesis, biological evaluation, X-ray molecular structure and molecular docking studies of RGD mimetics containing 6-amino-2,3-dihydroisoindolin-1-one fragment as ligands of integrin 濞?sub>IIb閻?sub>3 was written by Krysko, Andrei A.;Samoylenko, Georgiy V.;Polishchuk, Pavel G.;Fonari, Marina S.;Kravtsov, Victor Ch.;Andronati, Sergei A.;Kabanova, Tatyana A.;Lipkowski, Janusz;Khristova, Tetiana M.;Kuz’min, Victor E.;Kabanov, Vladimir M.;Krysko, Olga L.;Varnek, Alexandre A.. And the article was included in Bioorganic & Medicinal Chemistry in 2013.Synthetic Route of C16H22N2O4 This article mentions the following:

Acylaminooxoisoindolealkanoic acid RGD mimetics such as tetrahydroisoquinolinecarbonylamino oxoisoindolylpropanoic acid I闂佺偨鍎洪弫鐟縧 were prepared as integrin 濞?sub>IIb閻?sub>3 ligands for inhibiting platelet aggregation for potential use as antithrombotic agents. The inhibition of platelet aggregation by the oxoisoindolealkanoic acids was determined, and for some compounds, the inhibition of fluorescein-labeled fibrinogen binding to human platelets (and thus to integrin 濞?sub>IIb閻?sub>3) was also determined; for example, I闂佺偨鍎洪弫鐟縧 inhibited platelet aggregation with an IC₅₀ value of 1.1 婵炴挾鎷?and inhibited the binding of fluorescein-labeled fibrinogen to platelets with an IC₅₀ value of 6.5 nM. Mol. docking calculations of eight of the prepared compounds bound to integrin 濞?sub>IIb閻?sub>3 were performed, indicating the key interactions present; correlations between docking scores and binding affinities were also found. Of the motifs tried, the use of an N-terminal tetrahydroisoquinolinecarbonyl group and a C-terminal 閻?alanine moiety provided the most effective platelet aggregation inhibitors. The structures for a Me aminooxoisoindolebutanoate, a tetrahydroisoquinolinedicarboxylic acid mono-tert-Bu ester, and solvates, salts, or free bases of five of the oxoisoindolealkanoic acids prepared including I闂佺偨鍎洪弫?sub>2O were determined by X-ray crystallog. In the experiment, the researchers used many compounds, for example, 4-(4-(tert-Butoxycarbonyl)piperazin-1-yl)benzoic acid (cas: 162046-66-4Synthetic Route of C16H22N2O4).

4-(4-(tert-Butoxycarbonyl)piperazin-1-yl)benzoic acid (cas: 162046-66-4) 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.Synthetic Route of C16H22N2O4

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

Development of Gleevec Analogues for Reducing Production of 閻?Amyloid Peptides through Shifting 閻?Cleavage of Amyloid Precursor Proteins was written by Sun, Weilin;Netzer, William J.;Sinha, Anjana;Gindinova, Katherina;Chang, Emily;Sinha, Subhash C.. And the article was included in Journal of Medicinal Chemistry in 2019.SDS of cas: 162046-66-4 This article mentions the following:

Imatinib mesylate, I, inhibits production of 閻?amyloid (A閻? peptides both in cells and in animal models. It reduces both the 閻?secretase and 缂?secretase cleavages of the amyloid precursor protein (APP) and mediates a synergistic effect, when combined with a 閻?secretase inhibitor, BACE IV. Toward developing more potent brain-permeable leads, we have synthesized and evaluated over 75 I-analogs. Several compounds inhibited production of A閻?peptides with improved activity in cells. These compounds affected 閻?secretase cleavage of APP similarly to I. Compound II significantly reduced production of the A閻?2 peptide, when administered (100 mg/kg, twice daily by oral gavage) to 5 mo old female mice for 5 days. A combination of compound II with BACE IV also reduced A閻?levels in cells, more than the additive effect of the two compounds These results open a new avenue for developing treatments for Alzheimer’s disease using I-analogs. In the experiment, the researchers used many compounds, for example, 4-(4-(tert-Butoxycarbonyl)piperazin-1-yl)benzoic acid (cas: 162046-66-4SDS of cas: 162046-66-4).

4-(4-(tert-Butoxycarbonyl)piperazin-1-yl)benzoic acid (cas: 162046-66-4) belongs to piperazine derivatives. A form in which piperazine is commonly available industrially is as the hexahydrate, C4H10N2. 6H2O, which melts at 44 闁硅櫣鐓?and boils at 125闂?30 闁硅櫣鐓? 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: 162046-66-4

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

Discovery of the selective and efficacious inhibitors of FLT3 mutations was written by Zhi, Yanle;Li, Baoquan;Yao, Chao;Li, Hongmei;Chen, Puzhou;Bao, Jiyin;Qin, Tianren;Wang, Yue;Lu, Tao;Lu, Shuai. And the article was included in European Journal of Medicinal Chemistry in 2018.Reference of 182618-86-6 This article mentions the following:

Fms-like tyrosine kinase 3 (FLT3) is among the most frequently mutated protein in acute myeloid leukemia (AML), which has been confirmed as an important drug target for AML chemotherapy. Starting from the lead compound LT-106-175, a series of 1-H-pyrazole-3-carboxamide derivatives were synthesized to improve the FLT3 inhibitory potency and selectivity. Among them, compound 50 (4-((2-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)amino)-N-(4-(piperazin-1-yl)phenyl)-1H-pyrazole-3-carboxamide) was identified as a highly potent and selective FLT3 inhibitor (IC₅₀ = 0.213 nM), which showed equal activities against various mutants of FLT3 including FLT3 (ITD)-D835V and FLT3 (ITD)-F691L that is resistant to quizartinib. Compound 50 also exhibited efficacy against the human AML cell line MV4-11 (IC₅₀ = 16.1 nM) harboring FLT3-ITD mutants. Inversely, compound 50 displayed no cytotoxicity to FLT3-independent cells, and the biochem. analyses showed that its effects were related to the inhibition of FLT3 signal pathways. Addnl., compound 50 induced apoptosis in MV4-11 cell as demonstrated by flow cytometry. Moreover, compound 50 showed enhanced metabolic stability. Altogether, it was concluded that compound 50 could be a promising FLT3 inhibitor for further developing therapeutic remedy of AML. 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. Simple N-substituted piperazines have been found in many drug molecules. 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.Reference of 182618-86-6

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

Improved synthesis of 4-[4-(5-oxo-1,5-dihydro-[1,2,4 triazoyl-4-yl) phenyl]piperazine-1-carboxylic t-butyl ester was written by Sheng, Chunquan;Zhang, Wannian;Xu, Hui;Che, Xiaoying;Zhang, Min;Yao, Jianzhong;Miao, Zhenyuan. And the article was included in Zhongguo Yaowu Huaxue Zazhi in 2006.Computed Properties of C15H21N3O4 This article mentions the following:

To improve the synthetic process of 4-[4-(5-oxo-1,5-dihydro-[1,2,4] triazoyl-4-yl) phenyl] piperazine-1-carboxylic t-Bu ester, which was used as the key intermediate of triazole antifungal agents, the product was synthesized from 1-(4-nitrophenyl) piperazine by Boc protection, reduction of nitro group, acylation, hydrazinolysis and cyclization. The new synthetic process had several advantages such as facile reaction condition, convenient operation and purification without chromatog. The overall yield was improved from 39.10% to 71.94%. In the experiment, the researchers used many compounds, for example, 1-Boc-4-(4-Nitrophenyl)piperazine (cas: 182618-86-6Computed Properties of C15H21N3O4).

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. Computed Properties of C15H21N3O4

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

Discovery of benzo[d]oxazole derivatives as the potent type-I FLT3-ITD inhibitors was written by Bao, Jiyin;Liu, Haichun;Zhi, Yanle;Yang, Wenqianzi;Zhang, Jiawei;Lu, Tao;Wang, Yue;Lu, Shuai. And the article was included in Bioorganic Chemistry in 2020.Safety of 1-Boc-4-(4-Nitrophenyl)piperazine This article mentions the following:

A series of compounds I [R¹ = H, Me, F, MeO; R² = diethylamino, piperidinyl, piperazin-1-yl, etc.; R³ = Ph, pyridin-3-yl, pyridin-4-yl, etc.] were designed and synthesized based on benzo[d]oxazole-2-amine scaffold to discover new potent Fms-like tyrosine kinase 3 inhibitors. During the medicinal chem. works, flexible mol. docking was used to provide design rationale and study the binding modes of the target compounds Through the mixed SAR exploration based on the enzymic and cellular activities, compound I [R¹ = MeO; R² = piperazin-1-yl; R³ = 3-carbamoylphenyl] was identified with potent FLT3-ITD inhibitory (IC₅₀: 0.41 nM) and anti-proliferative (IC₅₀: 0.037娓璏 against MV4-11 cells) activities. And the binding mode of I [R¹ = MeO; R² = piperazin-1-yl; R³ = 3-carbamoylphenyl] with ”DFG-in” FLT3 was simulated by a 20-ns mol. dynamics run, providing some insights into further medicinal chem. efforts toward novel FLT3 inhibitors in AML therapy. In the experiment, the researchers used many compounds, for example, 1-Boc-4-(4-Nitrophenyl)piperazine (cas: 182618-86-6Safety of 1-Boc-4-(4-Nitrophenyl)piperazine).

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. 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.Safety of 1-Boc-4-(4-Nitrophenyl)piperazine

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

Discovery of ARD-2585 as an Exceptionally Potent and Orally Active PROTAC Degrader of Androgen Receptor for the Treatment of Advanced Prostate Cancer was written by Xiang, Weiguo;Zhao, Lijie;Han, Xin;Qin, Chong;Miao, Bukeyan;McEachern, Donna;Wang, Yu;Metwally, Hoda;Kirchhoff, Paul D.;Wang, Lu;Matvekas, Aleksas;He, Miao;Wen, Bo;Sun, Duxin;Wang, Shaomeng. And the article was included in Journal of Medicinal Chemistry in 2021.Application of 162046-66-4 This article mentions the following:

We report herein the discovery of exceptionally potent and orally bioavailable PROTAC AR degraders with ARD-2585 being the most promising compound ARD-2585 achieves DC₅₀ values of 閳?.1 nM in the VCaP cell line with AR gene amplification and in the LNCaP cell line carrying an AR mutation. It potently inhibits cell growth with IC₅₀ values of 1.5 and 16.2 nM in the VCaP and LNCaP cell lines, resp., and achieves excellent pharmacokinetics and 51% of oral bioavailability in mice. It is more efficacious than enzalutamide in inhibition of VCaP tumor growth and does not cause any sign of toxicity in mice. ARD-2585 is a promising AR degrader for extensive investigations for the treatment of advanced prostate cancer. In the experiment, the researchers used many compounds, for example, 4-(4-(tert-Butoxycarbonyl)piperazin-1-yl)benzoic acid (cas: 162046-66-4Application of 162046-66-4).

4-(4-(tert-Butoxycarbonyl)piperazin-1-yl)benzoic acid (cas: 162046-66-4) belongs to piperazine derivatives. Industrial applications of piperazine include the manufacture of plastics, resins, pesticides and brake fluids. 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.Application of 162046-66-4

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

New 1-aryl-3-substituted propanol derivatives as antimalarial agents was written by Perez-Silanes, Silvia;Berrade, Luis;Garcia-Sanchez, Rory N.;Mendoza, Adela;Galiano, Silvia;Perez-Solorzano, Berta Martin;Nogal-Ruiz, Juan J.;Martinez-Fernandez, Antonio R.;Aldana, Ignacio;Monge, Antonio. And the article was included in Molecules in 2009.Application In Synthesis of 1-Boc-4-(4-Nitrophenyl)piperazine This article mentions the following:

This paper describes the synthesis and in vitro antimalarial activity against a P. falciparum 3D7 strain of some new 1-aryl-3-substituted propanol derivatives Twelve of the tested compounds showed an IC₅₀ lower than 1 娓璏. These compounds were also tested for cytotoxicity in murine J774 macrophages. The most active compounds were evaluated for in vivo activity against P. berghei in a 4-day suppressive test. Compound 12 inhibited more than 50% of parasite growth at a dose of 50 mg/kg/day. In addition, an FBIT test was performed to measure the ability to inhibit ferriprotoporphyrin biocrystn. This data indicates that 1-aryl-3-substituted propanol derivatives hold promise as a new therapeutic option for the treatment of malaria. In the experiment, the researchers used many compounds, for example, 1-Boc-4-(4-Nitrophenyl)piperazine (cas: 182618-86-6Application In Synthesis of 1-Boc-4-(4-Nitrophenyl)piperazine).

1-Boc-4-(4-Nitrophenyl)piperazine (cas: 182618-86-6) 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.Application In Synthesis of 1-Boc-4-(4-Nitrophenyl)piperazine

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