Tag: 300-400

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

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

Development, synthesis and biological investigation of a novel class of potent PC-PLC inhibitors was written by Pilkington, Lisa I.;Sparrow, Kevin;Rees, Shaun W. P.;Paulin, Emily K.;van Rensburg, Michelle;Xu, Chris Sun;Langley, Ries J.;Leung, Ivanhoe K. H.;Reynisson, Johannes;Leung, Euphemia;Barker, David. And the article was included in European Journal of Medicinal Chemistry in 2020.SDS of cas: 182618-86-6 This article mentions the following:

Phospholipases are enzymes that are involved in the hydrolysis of acyl and phosphate esters of phospholipids, generating secondary messengers that have implications in various cellular processes including proliferation, differentiation and motility. As such inhibitors of phospholipases have been widely studied for their use as anti-cancer therapeutics. Phosphatidylcholine-specific phospholipase C (PC-PLC) is implicated in the progression of a number of cancer cell lines including aggressing triple-neg. breast cancers. Most current studies on PC-PLC have utilized D609 as the standard inhibitor however it is known to have multiple failings, including poor stability in aqueous media. 2-Morpholinobenzoic acids were recently identified using vHTS as a potential class of lead compounds, with improvements over D609. In this work 129 analogs in this class were prepared and their PC-PLC inhibitory activity was assessed. It was found that the majority of these novel compounds had improved activity when compared to D609 with the most potent inhibitors completely inhibiting enzyme activity. It was determined that the best compound/s contained a morpholino and 2-substituted N-benzyl moieties with these findings explained using mol. modeling. The compounds reported here will allow for improved study of PC-PLC activity. In the experiment, the researchers used many compounds, for example, 1-Boc-4-(4-Nitrophenyl)piperazine (cas: 182618-86-6SDS of cas: 182618-86-6).

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. 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.SDS of cas: 182618-86-6

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

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

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

Photoswitchable Inhibitor of the Calcium Channel TRPV6 was written by Cunha, Micael R.;Bhardwaj, Rajesh;Lindinger, Sonja;Butorac, Carmen;Romanin, Christoph;Hediger, Matthias A.;Reymond, Jean-Louis. And the article was included in ACS Medicinal Chemistry Letters in 2019.Reference of 182618-86-6 This article mentions the following:

Herein the authors report the first photoswitchable inhibitor of Transient Receptor Potential Vanilloid 6 (TRPV6), a selective calcium channel involved in a number of diseases and in cancer progression. By surveying analogs of a previously reported TRPV6 inhibitor appended with a phenyl-diazo group, the authors identified a compound switching between a weak TRPV6 inhibitor in its dark, E-diazo stereoisomer (Z/E = 3:97, IC₅₀ >> 10 μM) and a potent inhibitor as the Z-diazo stereoisomer accessible reversibly by UV irradiation at λ = 365 nm (Z/E = 3:1, IC₅₀ = 1.7±0.4 μM), thereby allowing precise spatiotemporal control of inhibition. This new tool compound should be useful to deepen the understanding of TRPV6. 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. 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. Reference of 182618-86-6

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