Tag: 200-300

Virtual Screening Approach and Investigation of Structure-Activity Relationships To Discover Novel Bacterial Topoisomerase Inhibitors Targeting Gram-Positive and Gram-Negative Pathogens was written by Magaro, Gabriele;Prati, Federica;Garofalo, Barbara;Corso, Gaia;Furlotti, Guido;Apicella, Claudia;Mangano, Giorgina;D’Atanasio, Noemi;Robinson, Daniel;Di Giorgio, Francesco Paolo;Ombrato, Rosella. And the article was included in Journal of Medicinal Chemistry in 2019.Recommanded Product: tert-Butyl 4-(3-aminopropyl)piperazine-1-carboxylate This article mentions the following:

Bacterial resistance is increasing rapidly, requiring urgent identification of new antibacterial drugs that are effective against multidrug-resistant pathogens. Novel bacterial topoisomerase inhibitors (NBTIs) provide a new strategy for investigating the well-validated DNA gyrase and topoisomerase IV targets while preventing cross-resistance issues. On this basis, starting from a virtual screening campaign and subsequent structure-based hit optimization guided by X-ray studies, a novel class of piperazine-like NBTIs with outstanding enzymic activity against Staphylococcus aureus and Escherichia coli DNA gyrase and topoisomerase IV was identified. Notably, compounds (±)-33, (±)-35, and (±)-36 with potent and balanced multitarget enzymic profiles exhibited excellent efficacy against selected Gram-pos. and Gram-neg. pathogens, as well as clin. relevant resistant strains. Overall, the new NBTI chemotype described herein, owing to the broad-spectrum antibacterial activity and favorable in vitro safety profile, might serve as a basis for the development of novel treatments against serious infections. In the experiment, the researchers used many compounds, for example, tert-Butyl 4-(3-aminopropyl)piperazine-1-carboxylate (cas: 373608-48-1Recommanded Product: 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. 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.Recommanded Product: tert-Butyl 4-(3-aminopropyl)piperazine-1-carboxylate

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

Small Molecules Targeting the Flavivirus E Protein with Broad-Spectrum Activity and Antiviral Efficacy in Vivo was written by Li, Pi-Chun;Jang, Jaebong;Hsia, Chih-Yun;Groomes, Patrice V.;Lian, Wenlong;de Wispelaere, Melissanne;Pitts, Jared D.;Wang, Jinhua;Kwiatkowski, Nicholas;Gray, Nathanael S.;Yang, Priscilla L.. And the article was included in ACS Infectious Diseases in 2019.Computed Properties of C14H20F3N3 This article mentions the following:

Vaccines and antivirals to combat dengue, Zika, and other flavivirus pathogens present a major, unmet medical need. Vaccine development has been severely challenged by the antigenic diversity of these viruses and the propensity of non-neutralizing, cross-reactive antibodies to facilitate cellular infection and increase disease severity. As an alternative, direct-acting antivirals targeting the flavivirus envelope protein, E, have the potential to act via an analogous mode of action without the risk of antibody-dependent enhancement of infection and disease. We previously discovered that structurally diverse small mol. inhibitors of the dengue virus E protein exhibit varying levels of antiviral activity against other flaviviruses in cell culture. Here, we demonstrate that the broad-spectrum activity of several cyanohydrazones against dengue, Zika, and Japanese encephalitis viruses is due to specific inhibition of E-mediated membrane fusion during viral entry and provide proof of concept for pharmacol. inhibition of E as an antiviral strategy in vivo. In the experiment, the researchers used many compounds, for example, 4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline (cas: 630125-91-6Computed Properties of C14H20F3N3).

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. 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 C14H20F3N3

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

Identification of 2-aminooxazole amides as acyl-CoA: Diacylglycerol acyltransferase 1 (DGAT1) inhibitors through scaffold hopping strategy was written by Kim, Hyunjin M.;Smith, Michelle D.;Kim, Jae-Hun;Caplen, Mary Ann;Chan, Tin Yau;McKittrick, Brian A.;Cook, John A.;van Heek, Margaret;Lachowicz, Jean. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2013.Safety of tert-Butyl 4-(5-aminopyridin-2-yl)piperazine-1-carboxylate This article mentions the following:

A scaffold hopping strategy was successfully applied in discovering 2-aminooxazole amides as potent DGAT1 inhibitors for the treatment of dyslipidemia. Further optimization in potency and PK properties resulted in a lead series with oral in vivo efficacy in a mouse postprandial triglyceridemia (PPTG) assay. In the experiment, the researchers used many compounds, for example, tert-Butyl 4-(5-aminopyridin-2-yl)piperazine-1-carboxylate (cas: 119285-07-3Safety 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. 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. 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 tert-Butyl 4-(5-aminopyridin-2-yl)piperazine-1-carboxylate

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

Synthesis of substituted 4-oxo-7-sulfamoyl-2,3,4,5-tetrahydrobenzo[b][1,4]thiazepines was written by Kravchenko, D. V.;Ivanovskii, S. A.;Korsakov, M. K.;Dorogov, M. V.;Tkachenko, S. E.;AsHchenko, A. V.. And the article was included in Izvestiya Vysshikh Uchebnykh Zavedenii, Khimiya i Khimicheskaya Tekhnologiya in 2005.COA of Formula: C13H21N3 This article mentions the following:

A combinatorial library of substituted 4-oxo-7-sulfamoyl-2,3,4,5-tetrahydrobenzo[b][1,4]thiazepines was synthesized via chlorosulfonylation of tetrahydrobenzothiazepinones followed by reaction with a range of primary and secondary amines. Physicochem. parameters of some of the products, such as lipophilicity, number of rotating bonds and number of hydrogen bond donors and acceptors have been calculated In the experiment, the researchers used many compounds, for example, 4-(4-Ethylpiperazin-1-ylmethyl)phenylamine (cas: 611225-86-6COA of Formula: C13H21N3).

4-(4-Ethylpiperazin-1-ylmethyl)phenylamine (cas: 611225-86-6) belongs to piperazine derivatives. Industrial applications of piperazine include the manufacture of plastics, resins, pesticides and brake fluids. 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: C13H21N3

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

N,N’-Bisoxalamides Enhance the Catalytic Activity in Cu-Catalyzed Coupling of (Hetero)Aryl Bromides with Anilines and Secondary Amines was written by Bhunia, Subhajit;Kumar, S. Vijay;Ma, Dawei. And the article was included in Journal of Organic Chemistry in 2017.Application of 780705-64-8 This article mentions the following:

N,N’-Bis(furan-2-ylmethyl)oxalamide (BFMO), an inexpensive and conveniently available bidentate ligand, is very effective for promoting Cu-catalyzed N-arylation of anilines and cyclic secondary amines. The method enables coupling of a broad range of (hetero)aryl bromides with various (hetero)aryl amines and cyclic secondary amines at 0.5-5 mol % catalyst loadings at relatively low temperatures For coupling with more sterically hindered acyclic secondary amines, using N,N’-bis(2,4,6-trimethoxyphenyl)oxalamide (BTMPO) as a ligand gives the better results. Addnl., high selectivity is achieved in CuI/BFMO-catalyzed direct monoarylation of piperazine with (hetero)aryl bromides to afford pharmaceutically important building blocks. In the experiment, the researchers used many compounds, for example, tert-Butyl 4-(pyrimidin-2-yl)piperazine-1-carboxylate (cas: 780705-64-8Application of 780705-64-8).

tert-Butyl 4-(pyrimidin-2-yl)piperazine-1-carboxylate (cas: 780705-64-8) 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 formed as a co-product in the ammoniation of 1,2-dichloroethane or ethanolamine. These are the only routes to the chemical used commercially.Application of 780705-64-8

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

Discovery of N-(3-Fluorophenyl)-1-[(4-([(3S)-3-methyl-1-piperazinyl]methyl)phenyl)acetyl]-4-piperidinamine (GSK962040), the First Small Molecule Motilin Receptor Agonist Clinical Candidate was written by Westaway, Susan M.;Brown, Samantha L.;Fell, Stephen C. M.;Johnson, Christopher N.;MacPherson, David T.;Mitchell, Darren J.;Myatt, James W.;Stanway, Steven J.;Seal, Jon T.;Stemp, Geoffrey;Thompson, Mervyn;Lawless, Kirk;McKay, Fiona;Muir, Alison I.;Barford, Jonathan M.;Cluff, Chermaine;Mahmood, Sadhia R.;Matthews, Kim L.;Mohamed, Shiyam;Smith, Beverley;Stevens, Alexander J.;Bolton, Victoria J.;Jarvie, Emma M.;Sanger, Gareth J.. And the article was included in Journal of Medicinal Chemistry in 2009.Category: piperazines This article mentions the following:

N-(3-Fluorophenyl)-1-[(4-([(3S)-3-methyl-1-piperazinyl]methyl)phenyl)acetyl]-4-piperidinamine 12 (GSK962040) is a novel small mol. motilin receptor agonist. It possesses excellent activity at the recombinant human motilin receptor and also at the native rabbit motilin receptor where its agonist activity results in potentiation of the amplitude of neuronal-mediated contractions of isolated gastric antrum tissue. Compound 12 also possesses highly promising pharmacokinetic profiles in both rat and dog, and these results, in combination with further profiling in human native tissue and an in vivo model of gastrointestinal transit in the rabbit, have led to its selection as a candidate for further development. In the experiment, the researchers used many compounds, for example, (R)-1-Cbz-2-methylpiperazine (cas: 923565-99-5Category: piperazines).

(R)-1-Cbz-2-methylpiperazine (cas: 923565-99-5) 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 formed as a co-product in the ammoniation of 1,2-dichloroethane or ethanolamine. These are the only routes to the chemical used commercially.Category: piperazines

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

Optimization of a Series of RIPK2 PROTACs was written by Miah, Afjal H.;Smith, Ian E. D.;Rackham, Mark;Mares, Alina;Thawani, Aditya R.;Nagilla, Rakesh;Haile, Pamela A.;Votta, Bartholomew J.;Gordon, Laurie J.;Watt, Gillian;Denyer, Jane;Fisher, Don T.;Dace, Phoebe;Giffen, Paul;Goncalves, Andrea;Churcher, Ian;Scott-Stevens, Paul;Harling, John D.. And the article was included in Journal of Medicinal Chemistry in 2021.Computed Properties of C13H18N2O2 This article mentions the following:

Receptor-interacting serine/threonine protein kinase 2 (RIPK2) is an important kinase of the innate immune system. Herein, we describe the optimization of a series of RIPK2 PROTACs which recruit members of the inhibitor of apoptosis (IAP) family of E3 ligases. Our PROTAC optimization strategy focused on reducing the lipophilicity of the early lead which resulted in the identification of analogs with improved solubility and increased human and rat microsomal stability. We identified a range of IAP binders that were successfully incorporated into potent RIPK2 PROTACs with attractive pharmacokinetic profiles. Compound 20 possessed the best overall profile with good solubility, potent degradation of RIPK2, and associated inhibition of TNFα release. A proof-of-concept study utilizing a slow release matrix demonstrated the feasibility of a long-acting parenteral formulation with >1 mo duration. This represents an attractive alternative dosing paradigm to oral delivery, especially for chronic diseases where compliance can be challenging. In the experiment, the researchers used many compounds, for example, (R)-1-Cbz-3-methylpiperazine (cas: 623586-00-5Computed Properties of C13H18N2O2).

(R)-1-Cbz-3-methylpiperazine (cas: 623586-00-5) 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).Computed Properties of C13H18N2O2

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

Discovery of Type II Inhibitors of TGFβ-Activated Kinase 1 (TAK1) and Mitogen-Activated Protein Kinase Kinase Kinase Kinase 2 (MAP4K2) was written by Tan, Li;Nomanbhoy, Tyzoon;Gurbani, Deepak;Patricelli, Matthew;Hunter, John;Geng, Jiefei;Herhaus, Lina;Zhang, Jianming;Pauls, Eduardo;Ham, Youngjin;Choi, Hwan Geun;Xie, Ting;Deng, Xianming;Buhrlage, Sara J.;Sim, Taebo;Cohen, Philip;Sapkota, Gopal;Westover, Kenneth D.;Gray, Nathanael S.. And the article was included in Journal of Medicinal Chemistry in 2015.Application In Synthesis of 4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline This article mentions the following:

The authors developed a pharmacophore model for type II inhibitors that was used to guide the construction of a library of kinase inhibitors. Kinome-wide selectivity profiling of the library resulted in the identification of a series of 4-substituted 1H-pyrrolo[2,3-b]pyridines that exhibited potent inhibitory activity against two mitogen-activated protein kinases (MAPKs), TAK1 (MAP3K7) and MAP4K2, as well as pharmacol. well interrogated kinases such as p38α (MAPK14) and ABL. Further investigation of the structure-activity relationship (SAR) resulted in the identification effect two potent dual TAK1 and MAP4K2 inhibitors such as I as well as two MAP4K2 selective inhibitors such as II. Some of these inhibitors possess good pharmacokinetic properties that will enable their use in pharmacol. studies in vivo. A 2.4 Å cocrystal structure of TAK1 in complex with 1 confirms that the activation loop of TAK1 assumes the DFG-out conformation characteristic of type II inhibitors. In the experiment, the researchers used many compounds, for example, 4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline (cas: 630125-91-6Application In Synthesis of 4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline).

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. 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 In Synthesis of 4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline

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

Bis-heteroaryl pyrazoles: identification of orally bioavailable inhibitors of activin receptor-like kinase-2 (R206H) was written by Sekimata, Katsuhiko;Sato, Tomohiro;Sakai, Naoki;Watanabe, Hisami;Mishima-Tsumagari, Chiemi;Taguri, Tomonori;Matsumoto, Takehisa;Fujii, Yoshifumi;Handa, Noriko;Honma, Teruki;Tanaka, Akiko;Shirouzu, Mikako;Yokoyama, Shigeyuki;Miyazono, Kohei;Hashizume, Yoshinobu;Koyama, Hiroo. And the article was included in Chemical & Pharmaceutical Bulletin in 2019.Reference of 119285-07-3 This article mentions the following:

Mutant activin receptor-like kinase-2 (ALK2) was reported to be closely associated with the pathogenesis of fibrodysplasia ossificans progressiva (FOP) and diffuse intrinsic pontine glioma (DIPG), and therefore presents an attractive target for therapeutic intervention. Through in silico virtual screenings and structure-activity relationship studies assisted by X-ray crystallog. analyses, a novel series of bis-heteroaryl pyrazole was identified as potent inhibitors of ALK2 (R206H). Derived from in silico hit compound RK-59638 (6a), compound 18p was identified as a potent inhibitor of ALK2 (R206H) with good aqueous solubility, liver microsomal stability, and oral bioavailability. In the experiment, the researchers used many compounds, for example, tert-Butyl 4-(5-aminopyridin-2-yl)piperazine-1-carboxylate (cas: 119285-07-3Reference 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 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 119285-07-3

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

Structure-activity relationship (SAR) investigations of substituted imidazole analogs as TRPV1 antagonists was written by Gore, Vijay K.;Ma, Vu V.;Tamir, Rami;Gavva, Narender R.;Treanor, James J. S.;Norman, Mark H.. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2007.Electric Literature of C13H18N2O2 This article mentions the following:

A novel series of 4,5-biarylimidazoles as TRPV1 antagonists were designed based on the previously reported 4,6-disubstituted benzimidazole series. The analogs were evaluated for their ability to block capsaicin- or acid-induced calcium influx in TRPV1-expressing CHO cells. These studies led to the identification of a highly potent and orally bioavailable TRPV1 antagonist, imidazole 33. In the experiment, the researchers used many compounds, for example, (R)-1-Cbz-3-methylpiperazine (cas: 623586-00-5Electric Literature of C13H18N2O2).

(R)-1-Cbz-3-methylpiperazine (cas: 623586-00-5) belongs to piperazine derivatives. Simple N-substituted piperazines have been found in many drug molecules. 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 C13H18N2O2

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