Month: February 2023

Discovery of a Highly Potent and Selective Degrader Targeting Hematopoietic Prostaglandin D Synthase via In Silico Design was written by Yokoo, Hidetomo;Shibata, Norihito;Endo, Akinori;Ito, Takahito;Yanase, Yuta;Murakami, Yuki;Fujii, Kiyonaga;Hamamura, Kengo;Saeki, Yasushi;Naito, Mikihiko;Aritake, Kosuke;Demizu, Yosuke. And the article was included in Journal of Medicinal Chemistry in 2021.Formula: C15H21N3O4 This article mentions the following:

Targeted protein degradation by proteolysis-targeting chimera (PROTAC) is one of the exciting modalities for drug discovery and biol. discovery. It is important to select an appropriate linker, an E3 ligase ligand, and a target protein ligand in the development; however, it is necessary to synthesize a large number of PROTACs through trial and error. Herein, using a docking simulation of the ternary complex of a hematopoietic prostaglandin D synthase (H-PGDS) degrader, H-PGDS, and cereblon, we have succeeded in developing PROTAC(H-PGDS)-7 (6), which showed potent and selective degradation activity (DC₅₀ = 17.3 pM) and potent suppression of prostaglandin D₂ production in KU812 cells. Addnl., in a Duchenne muscular dystrophy model using mdx mice with cardiac hypertrophy, compound 6 showed better inhibition of inflammatory cytokines than a potent H-PGDS inhibitor TFC-007. Thus, our results demonstrated that in silico simulation would be useful for the rational development of PROTACs. In the experiment, the researchers used many compounds, for example, 1-Boc-4-(4-Nitrophenyl)piperazine (cas: 182618-86-6Formula: C15H21N3O4).

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. 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.Formula: C15H21N3O4

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

Optimization of 4-Phenylamino-3-quinolinecarbonitriles as Potent Inhibitors of Src Kinase Activity was written by Boschelli, Diane H.;Ye, Fei;Wang, Yanong D.;Dutia, Minu;Johnson, Steve L.;Wu, Biqi;Miller, Karen;Powell, Dennis W.;Yaczko, Deanna;Young, Mairead;Tischler, Mark;Arndt, Kim;Discafani, Carolyn;Etienne, Carlo;Gibbons, Jay;Grod, Janet;Lucas, Judy;Weber, Jennifer M.;Boschelli, Frank. And the article was included in Journal of Medicinal Chemistry in 2001.Computed Properties of C7H16N2 This article mentions the following:

Subsequent to the discovery of 4-[(2,4-dichlorophenyl)amino]-6,7-dimethoxy-3-quinolinecarbonitrile as an inhibitor of Src kinase activity (IC₅₀ = 30 nM), several addnl. analogs were prepared Optimization of the C-4 anilino group led to I [R = Me]. Replacement of the methoxy group at C-7 with a 3-(morpholin-4-yl)propoxy group provided I [R = morpholinopropyl], resulting in increased inhibition of both Src kinase activity and Src-mediated cell proliferation. Analogs of I [R = morpholinopropyl] with other trisubstituted anilines at C-4 were also potent Src inhibitors, and the propoxy group was preferred over ethoxy, butoxy, or pentoxy. Replacement of the morpholine group with a 4-methylpiperazine group provided I [R = 4-methylpiperazinopropyl], which had an IC₅₀ of 1.2 nM in the Src enzymic assay, an IC₅₀ of 100 nM for the inhibition of Src-dependent cell proliferation and was selective for Src over non-Src family kinases. I [R = 4-methylpiperazinopropyl], which had higher 1 and 4 h plasma levels than I [R = 4-morpholinopropyl], effectively inhibited tumor growth in xenograft models. In the experiment, the researchers used many compounds, for example, 1-Propylpiperazine (cas: 21867-64-1Computed Properties of C7H16N2).

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. 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 C7H16N2

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

Design, synthesis, and antiproliferative activity of new 1H-pyrrolo[3,2-c]pyridine derivatives against melanoma cell lines. Part 2 was written by Jung, Myung-Ho;El-Gamal, Mohammed I.;Abdel-Maksoud, Mohammed S.;Sim, Taebo;Yoo, Kyung Ho;Oh, Chang-Hyun. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2012.Synthetic Route of C14H20F3N3 This article mentions the following:

A new series of 16 diarylureas and diarylamides possessing the 1H-pyrrolo[3,2-c]pyridine scaffold was designed and synthesized. Their in vitro antiproliferative activities against A375P human melanoma cell line and NCI-9 human melanoma cell line panel were tested. All the target compounds, except three amino derivatives demonstrated superior potencies against A375P to Sorafenib. In addition, 6 compounds demonstrated higher potencies than Vemurafenib against A375P. Two compounds were 7.50 and 454.90 times, resp., more selective towards A375P melanoma cells over NIH3T3 fibroblasts. Furthermore, 7 compounds demonstrated very high potencies against the nine tested melanoma cell lines at the NCI. Of the bisamide derivatives, 4 showed 2-digit nanomolar IC₅₀ values over different cell lines of the NCI-9 melanoma cell lines and 1 of these, I, is a promising lead for a new selective anticancer agent for treatment of melanoma.. In the experiment, the researchers used many compounds, for example, 4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline (cas: 630125-91-6Synthetic Route of C14H20F3N3).

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. 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.Synthetic Route of C14H20F3N3

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

The First Structure-Activity Relationship Studies for Designer Receptors Exclusively Activated by Designer Drugs was written by Chen, Xin;Choo, Hyunah;Huang, Xi-Ping;Yang, Xiaobao;Stone, Orrin;Roth, Bryan L.;Jin, Jian. And the article was included in ACS Chemical Neuroscience in 2015.Product Details of 21867-64-1 This article mentions the following:

Over the past decade, two independent technologies have emerged and been widely adopted by the neuroscience community for remotely controlling neuronal activity: optogenetics which utilize engineered channelrhodopsin and other opsins, and chemogenetics which utilize engineered G protein-coupled receptors (Designer Receptors Exclusively Activated by Designer Drugs (DREADDs)) and other orthologous ligand-receptor pairs. Using directed mol. evolution, two types of DREADDs derived from human muscarinic acetylcholine receptors have been developed: hM3Dq which activates neuronal firing, and hM4Di which inhibits neuronal firing. Importantly, these DREADDs were not activated by the native ligand acetylcholine (ACh), but selectively activated by clozapine N-oxide (CNO), a pharmacol. inert ligand. CNO has been used extensively in rodent models to activate DREADDs, and although CNO is not subject to significant metabolic transformation in mice, a small fraction of CNO is apparently metabolized to clozapine in humans and guinea pigs, lessening the translational potential of DREADDs. To effectively translate the DREADD technol., the next generation of DREADD agonists are needed and a thorough understanding of structure-activity relationships (SARs) of DREADDs is required for developing such ligands. The authors therefore conducted the first SAR studies of hM3Dq. The authors explored multiple regions of the scaffold represented by CNO, identified interesting SAR trends, and discovered several compounds that are very potent hM3Dq agonists but do not activate the native human M3 receptor (hM3). The authors also discovered that the approved drug perlapine is a novel hM3Dq agonist with >10 000-fold selectivity for hM3Dq over hM3. In the experiment, the researchers used many compounds, for example, 1-Propylpiperazine (cas: 21867-64-1Product Details of 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. 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.Product Details of 21867-64-1

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

Design, synthesis, and antiproliferative activity of new 1H-pyrrolo[3,2-c]pyridine derivatives against melanoma cell lines was written by El-Gamal, Mohammed I.;Jung, Myung-Ho;Lee, Woong San;Sim, Taebo;Yoo, Kyung Ho;Oh, Chang-Hyun. And the article was included in European Journal of Medicinal Chemistry in 2011.Recommanded Product: 4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline This article mentions the following:

Synthesis of a new series of diarylureas and diarylamides having 1H-pyrrolo[3,2-c]pyridine scaffold is described. Their in vitro antiproliferative activity against A375P human melanoma cell line was tested and the effect of substituents on pyrrolo[3,2-c]pyridine nucleus was investigated. The newly synthesized compounds, except three N-tolyl derivatives, generally showed superior activity against A375P to Sorafenib. The most potent compounds I [R = 4-(4-ethylpiperazino)-3-trifluoromethylphenylamino, 4-morpholino-3-trifluoromethylphenyl] were further tested and showed high potency over nine melanoma cell lines at the NCI. In the experiment, the researchers used many compounds, for example, 4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline (cas: 630125-91-6Recommanded Product: 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. Industrial applications of piperazine include the manufacture of plastics, resins, pesticides and brake fluids. 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).Recommanded Product: 4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline

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

The use of solid-supported reagents for the multi-step synthesis of analytically pure α,β-unsaturated compounds in miniaturized flow reactors was written by Wiles, Charlotte;Watts, Paul;Haswell, Stephen J.. And the article was included in Lab on a Chip in 2007.Electric Literature of C7H16N2 This article mentions the following:

Micro reaction technol. offers a safe, controllable and information rich technique suitable for the long-term production of pharmaceutical agents and fine chems. To date however, few of the syntheses performed using this technol. have addressed the problems associated with product purification The incorporation of multiple supported reagents into EOF-based miniaturized flow reactors for the two-step synthesis of anal. pure compounds is reported. Using this approach, the successful synthesis of 20 α,β-unsaturated compounds in excellent yields (>99.1%) and purities (>99.9%) has been achieved, illustrating significant improvements compared to traditional batch techniques. 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. 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. 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 C7H16N2

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

Liquid-phase parallel synthesis of 4-sulfanylbenzoic acid derivatives was written by Trifilenkov, A. S.;Il’in, A. P.;Kravchenko, D. V.;Dorogov, M. V.;Tkachenko, S. E.;Ivashchenko, A. V.. And the article was included in Izvestiya Vysshikh Uchebnykh Zavedenii, Khimiya i Khimicheskaya Tekhnologiya in 2005.Category: piperazines This article mentions the following:

Combinatorial libraries of substituted 4-sulfanylbenzamides and their derivatives were synthesized on the basis of 4-fluoro-3-nitrobenzoic acid. The procedure for nucleophilic substitution of fluorine by various thiols has been developed; the resulting 4-sulfenyl-3-nitrobenzoic acids were further converted into the corresponding esters and amides. Oxidation of the sulfide fragment with hydrogen peroxide afforded the corresponding sulfones. 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. 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.Category: piperazines

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

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

Poly(N-acryloyl-N’-propylpiperazine): A New Stimuli-Responsive Polymer was written by Gan, L. H.;Gan, Y. Y.;Deen, G. Roshan. And the article was included in Macromolecules in 2000.Recommanded Product: 1-Propylpiperazine This article mentions the following:

A new water-soluble stimuli-responsive poly(N-acryloyl-N’-propylpiperazine) (PAcrNPP) was synthesized and characterized. The polymer exhibited a lower critical solution temperature (LCST) in water at 37°. The phase transition temperature was highly sensitive to pH changes. The effects of some simple salts and cationic surfactants were studied. The enthalpy of phase separation determined by microcalorimetry was 21.4 kJ mol^-1. This value corresponds to the breaking of one hydrogen bond per monomer unit. Dynamic light scattering studies indicated some aggregations of polymer chains below the LCST. No such aggregations were observed for the lower analogs, poly(N-acryloyl-N’-methylpiperazine) (PAcrNMP) and poly(N-acryloyl-N’-ethylpiperazine) (PAcrNEP) which exhibited no LCST. The crosslinked polymer gels were sensitive to both pH and temperature Their response time to swelling and deswelling was 150 min. The water sorption of the gels was non-Fickian under both acidic and neutral conditions. In the experiment, the researchers used many compounds, for example, 1-Propylpiperazine (cas: 21867-64-1Recommanded Product: 1-Propylpiperazine).

1-Propylpiperazine (cas: 21867-64-1) 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.Recommanded Product: 1-Propylpiperazine

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

Synthesis and biological evaluation of 3-(pyridine-3-yl)-2-oxazolidinone derivatives as antibacterial agents was written by Jin, Bo;Wang, Tong;Chen, Jia-yi;Liu, Xiao-qing;Zhang, Yi-xin;Zhang, Xiu-ying;Sheng, Zun-lai;Yang, Hong-Liang. And the article was included in Frontiers in Chemistry (Lausanne, Switzerland) in 2022.Reference of 119285-07-3 This article mentions the following:

In this research, a series of 3-(pyridine-3-yl)-2-oxazolidinone derivatives I [R = (pyridin-3-yl)carbonyl, Me, N-cyclohexylcarbamoyl, etc.], II (X = F, H) was designed, synthesized, and evaluated for in vitro antibacterial activity, which included bacteriostatic, morphol., kinetic studies, and mol. docking. The results demonstrated that compounds II [R = cyclohexanecarbonyl, (2E)-3-(furan-2-yl)prop-2-enoyl (III), (2E)-3-(pyridin-3-yl)prop-2-enoyl, N-(4-chlorophenyl)carbamoyl; X = F] exhibited strong antibacterial activity similar to that of linezolid toward five Gram-pos. bacteria. After observing the effect of the drug on the morphol. and growth dynamics of the bacteria, the possible modes of action were predicted by mol. docking. Furthermore, the antibiofilm activity and the potential drug resistance assay were proceeded. These compounds exhibited universal antibiofilm activity and compound III showed significant concentration-dependent inhibition of biofilm formation. Compound III also showed a stable effect on S. pneumoniae (ATCC 49619) with less drug resistance growth for 15 days, which is much longer than that of linezolid. Overall, these results can be used to guide further exploration of novel antimicrobial agents. 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. 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).Reference of 119285-07-3

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