Month: January 2023

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

Synthesis and evaluation of conformationally restricted N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamines at σ receptors. 2. Piperazines, bicyclic amines, bridged bicyclic amines, and miscellaneous compounds was written by de Costa, Brian R.;He, Xiaoshu;Linders, Joannes T. M.;Dominguez, Celia;Gu, Zi Qiang;Williams, Wanda;Bowen, Wayne. And the article was included in Journal of Medicinal Chemistry in 1993.Computed Properties of C7H16N2 This article mentions the following:

As a continuation of an earlier study (J. Med. Chem. 1992, 35, 4334-4343) the σ-receptor ligand was conformationally restricted in 2-(1-pyrrolidinyl)-N-[2-(3,4-dichlorophenyl)ethyl]-N-methylethylamine (I) by incorporating it into homologous piperazines and homopiperazines, diazabicyclononanes and decanes, bridgehead bicyclooctanes and nonanes as well as other miscellaneous compounds σ-Receptor binding affinities were obtained using [³H](+)-pentazocine in guinea pig brain membranes. Probably the N lone pair orientation found in the piperazines affords the strongest binding interaction. Other N lone pair orientations or compounds representing unlikely staggered conformations of I [as in 4-[2-(3,4-dichlorophenyl)ethyl]-1,4-diazabicyclo[3.2.2]nonane] show very weak σ interaction. Comparison of the binding data of different N-substituted homologs of I with those of the 1-[2-(3,4-dichlorophenyl)ethyl]-4-alkylpiperazines suggests that the 2 N atoms of I are working in opposition to one another in terms of their sensitivity to steric bulk. The high binding affinity of 1,4-diazabicyclo[4.3.0]nonanes suggests that these may approx. the Me and pyrrolidine ring conformations found in I when it is bound to the σ receptor. Binding data suggest that the conformation of I favors strong binding interaction at σ-receptors. σ-Receptor K_i‘s was 0.55 nM for 1-[2-(3,4-dichlorophenyl)ethyl]-4-n-butylpiperazine. Overall comparison of the results indicate that I is subject to considerable conformational freedom and suggests that the σ receptor is not subject to rigid stereochem. restraints with I. These results corroborate an earlier study where I was restrained using simple monocyclic heterocycles. 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. 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.Computed Properties of C7H16N2

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

Structural Evolution and Photoluminescence Properties of Two-dimensional Lead Halide Perovskites was written by Ma, Yue-Yu;Pan, Hong-Mei;Li, Dong-Yang;Wu, Shuang;Jing, Zhihong. And the article was included in Zeitschrift fuer Anorganische und Allgemeine Chemie in 2022.Computed Properties of C7H16N2 This article mentions the following:

Herein, by using different size of organic mols. as cation templates, we prepared four new two-dimensional (2D) lead halide perovskites, [PrPipz]PbBr₄ (1), [DMEDA]PbBr₄ (2), [TMEDA]₀.₅[DMA]PbCl₄ (3) and [TMA]₄Pb₃Cl₁₀ (4). Under the distinct structural directing effects of organic cations, compounds 1-4 present four different types of 2D inorganic layers. Remarkably, compounds 1, 3 and 4 exhibit broadband blue emissions, while compound 2 exhibits broadband yellow emission upon the excitation of UV light at room temperature This work paves a way to modulate the crystal structure and photoluminescent property of low-dimensional halide perovskite via structural modulation strategy from the mol. level. 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. 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.Computed Properties of C7H16N2

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

Synthesis of substituted 2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b]diazepine-7-sulfamides was written by Filimonov, S. I.;Kravchenko, D. V.;Khakhina, M. Yu.;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.Product Details of 21867-64-1 This article mentions the following:

Liquid-phase parallel synthesis of a combinatorial library of 320 2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-sulfonamides I (R¹, R² = H, Me; R³R⁴N = primary or secondary aliphatic, cycloaliphatic, aromatic or heterocyclic amine) was carried out by chlorosulfonylation of the corresponding benzodiazepines followed by reaction with primary and secondary amines. The pharmacol. important parameters of some of these compounds (mol. weight, lipophilicity and number of hydrogen bond donor and acceptors) have been calculated 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. 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.Product Details of 21867-64-1

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

Strategies toward Discovery of Potent and Orally Bioavailable Proteolysis Targeting Chimera Degraders of Androgen Receptor for the Treatment of Prostate Cancer was written by Han, Xin;Zhao, Lijie;Xiang, Weiguo;Qin, Chong;Miao, Bukeyan;McEachern, Donna;Wang, Yu;Metwally, Hoda;Wang, Lu;Matvekas, Aleksas;Wen, Bo;Sun, Duxin;Wang, Shaomeng. And the article was included in Journal of Medicinal Chemistry in 2021.Synthetic Route of C16H22N2O4 This article mentions the following:

Proteolysis targeting chimera (PROTAC) small-mol. degraders have emerged as a promising new type of therapeutic agents, but the design of PROTAC degraders with excellent oral pharmacokinetics is a major challenge. In this study, we present our strategies toward the discovery of highly potent PROTAC degraders of androgen receptor (AR) with excellent oral pharmacokinetics. Employing thalidomide to recruit cereblon/cullin 4A E3 ligase and through the rigidification of the linker, we discovered highly potent AR degraders with good oral pharmacokinetic properties in mice with ARD-2128 (I) being the best compound ARD-2128 achieves 67% oral bioavailability in mice, effectively reduces AR protein and suppresses AR-regulated genes in tumor tissues with oral administration, leading to the effective inhibition of tumor growth in mice without signs of toxicity. This study supports the development of an orally active PROTAC AR degrader for the treatment of prostate cancer and provides insights and guidance into the design of orally active PROTAC degraders. 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. A form in which piperazine is commonly available industrially is as the hexahydrate, C4H10N2. 6H2O, which melts at 44 °C and boils at 125â€?30 °C. Intermediate for a wide range of pharmaceuticals, polymers, dyes, corrosion inhibitors, rubber accelerators and surfactants.Synthetic Route of C16H22N2O4

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