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