Month: October 2022

Zhen, Shijie; Yi, Xiaoqing; Zhao, Zujin; Lou, Xiaoding; Xia, Fan; Tang, Ben Zhong published the artcile< Drug delivery micelles with efficient near-infrared photosensitizer for combined image-guided photodynamic therapy and chemotherapy of drug-resistant cancer>, Recommanded Product: 4-(4-Methyl-1-piperazinyl)phenylboronic Acid, the main research area is near IR photosensitizer guided photodynamic antitumor reduction release micelle; Chemotherapy; Drug delivery; Near-infrared fluorophore; Photodynamic therapy; Photosensitizer.

The combination of photodynamic therapy (PDT) and chemotherapy (CT) offers a promising approach for the tumor eradication for overcoming multidrug resistance (MDR), which is a major obstacle to effective cancer treatment. However, for PDT, simultaneously achieving near-IR (NIR) emission and efficient reactive oxygen species (ROS) generation with low dark toxicity is urgently needed but remains challenging. Herein, a series of novel fluorophores with strong NIR emission, hybridized local and charge transfer characteristics, good two-photon absorption, high photostability, low dark cytotoxicity and excellent ROS generation ability are developed. By encapsulating the NIR fluorophore (DEB-BDTO) as a photosensitizer along with a drug resistance inhibitor tariquidar (TQR) within a polymeric prodrug (PMP), a reduction-sensitive drug co-delivery system (DEB/TQR@PMP micelles) is constructed. The DEB/TQR@PMP micelles exhibit a prominent synergistic lethal effect of PDT and CT on SKOV-3 cells and SKOV-3/MDR cells, and can apparently enhance the inhibition of tumor growth compared with sole PDT or CT in the tumor-bearing mouse model. Both in vitro and in vivo experiments prove that the new NIR fluorophores are excellent photosensitizers and can furnish an efficient combination therapy of image-guided PDT and CT within drug delivery micelles, which is particularly useful for eradicating multidrug resistance cancer.

Biomaterials published new progress about Antitumor agents. 229009-40-9 belongs to class piperazines, and the molecular formula is C11H17BN2O2, Recommanded Product: 4-(4-Methyl-1-piperazinyl)phenylboronic Acid.

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

Holmes, Jane L.; Almeida, Lynsie; Barlaam, Bernard; Croft, Rosemary A.; Dishington, Allan P.; Gingipalli, Laksmaiah; Hassall, Lorraine A.; Hawkins, Janet L.; Ioannidis, Stephanos; Johannes, Jeffrey W.; McGuire, Thomas M.; Moore, Jane E.; Patel, Anil; Pike, Kurt G.; Pontz, Timothy; Wu, Xiaoyun; Wang, Tao; Zhang, Hai-Jun; Zheng, Xiaolan published the artcile< Synthesis of Novel Hydroxymethyl-Substituted Fused Heterocycles>, Safety of 4-(4-Methyl-1-piperazinyl)phenylboronic Acid, the main research area is fused heterocycle preparation.

Examples of hydroxymethylated analogs of heteroaryl cores such as quinazolin-4-ones, isoquinolin-1(2H)-ones, pyrido[3,4-d]pyrimidin-4(3H)-ones, chromen-4-ones and pyrrolo[2,1-f][1,2,4]triazin-4(3H)-ones were sparse or non-existent in the scientific literature. Synthesis of such compounds by using standard procedures from readily available raw materials was demonstrated.

Synthesis published new progress about Aryl aldehydes Role: RCT (Reactant), RACT (Reactant or Reagent). 229009-40-9 belongs to class piperazines, and the molecular formula is C11H17BN2O2, Safety of 4-(4-Methyl-1-piperazinyl)phenylboronic Acid.

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

Jain, Rama; Mathur, Michelle; Lan, Jiong; Costales, Abran; Atallah, Gordana; Ramurthy, Savithri; Subramanian, Sharadha; Setti, Lina; Feucht, Paul; Warne, Bob; Doyle, Laura; Basham, Stephen; Jefferson, Anne B.; Lindvall, Mika; Appleton, Brent A.; Shafer, Cynthia M. published the artcile< Discovery of Potent and Selective RSK Inhibitors as Biological Probes>, Recommanded Product: 4-(4-Methyl-1-piperazinyl)phenylboronic Acid, the main research area is difluorophenol pyridine RSK inhibitor preparation antitumor.

While the p90 ribosomal S6 kinase (RSK) family has been implicated in multiple tumor cell functions, the full understanding of this kinase family has been restricted by the lack of highly selective inhibitors. A bis-phenol pyrazole was identified from high-throughput screening as an inhibitor of the N-terminal kinase of RSK2. Structure-based drug design using crystallog., conformational anal., and scaffold morphing resulted in highly optimized difluorophenol pyridine inhibitors of the RSK kinase family as demonstrated cellularly by the inhibition of YB1 phosphorylation. These compounds provide for the first time in vitro tools with an improved selectivity and potency profile to examine the importance of RSK signaling in cancer cells and to fully evaluate RSK as a therapeutic target.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 229009-40-9 belongs to class piperazines, and the molecular formula is C11H17BN2O2, Recommanded Product: 4-(4-Methyl-1-piperazinyl)phenylboronic Acid.

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

Moreno-Cinos, Carlos; Sassetti, Elisa; Salado, Irene G.; Witt, Gesa; Benramdane, Siham; Reinhardt, Laura; Cruz, Cristina D.; Joossens, Jurgen; Van der Veken, Pieter; Brotz-Oesterhelt, Heike; Tammela, Paivi; Winterhalter, Mathias; Gribbon, Philip; Windshugel, Bjorn; Augustyns, Koen published the artcile< α-Amino diphenyl phosphonates as novel inhibitors of Escherichia coli ClpP protease>, Quality Control of 197638-83-8, the main research area is aminodiphenylphosphonate Escherichia ClpP protease inhibitor.

Increased Gram-neg. bacteria resistance to antibiotics is becoming a global problem, and new classes of antibiotics with novel mechanisms of action are required. The caseinolytic protease subunit P (ClpP) is a serine protease conserved among bacteria that is considered as an interesting drug target. ClpP function is involved in protein turnover and homeostasis, stress response, and virulence among other processes. The focus of this study was to identify new inhibitors of Escherichia coli ClpP and to understand their mode of action. A focused library of serine protease inhibitors based on diaryl phosphonate warheads was tested for ClpP inhibition, and a chem. exploration around the hit compounds was conducted. Altogether, 14 new potent inhibitors of E. coli ClpP were identified. Compounds 85 and 92 emerged as most interesting compounds from this study due to their potency and, resp., to its moderate but consistent antibacterial properties as well as the favorable cytotoxicity profile.

Journal of Medicinal Chemistry published new progress about Antibiotic resistance (overcoming). 197638-83-8 belongs to class piperazines, and the molecular formula is C16H22N2O3, Quality Control of 197638-83-8.

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

Jiang, Cheng-Shi; Fu, Yan; Zhang, Li; Gong, Jing-Xu; Wang, Zhen-Zhong; Xiao, Wei; Zhang, Hai-Yan; Guo, Yue-Wei published the artcile< Synthesis and biological evaluation of novel marine-derived indole-based 1,2,4-oxadiazoles derivatives as multifunctional neuroprotective agents>, SDS of cas: 229009-40-9, the main research area is indole oxadiazole preparation SAR neurotoxicity neuroprotective activity Alzheimer; 1,2,4-Oxadiazole derivatives; Amyloid-β-peptide; Neuroprotective activity; Oxygen–glucose deprivation; Phidianidines.

Phidianidines I [R = H, Br], isolated from the marine opisthobranch mollusk Phidiana militaris, present the first example of natural products possessing an 1,2,4-oxadiazole ring system and show various bioactivities. However, the structure-activity relationship study related to I has not been reported yet. As our ongoing effect toward marine-derived potential neuroprotective agents, a series of phidianidine-based derivatives II [R = ph, 4-Me-C6H4, 4-Et-C6H4, etc.] have been synthesized and evaluated for neuroprotective effects against amyloid-β25-35 (Aβ25-35)-, hydrogenperoxide (H2O2)-, and oxygen-glucose deprivation (OGD)-induced neurotoxicity in SH-SY5Y cells. The bioassay results indicated that some of analogs, especially II [R = 4-OEt-C6H4] and II [R = 4-OPr-C6H4], exhibited good in vitro neuroprotective effects in the above three screening models. The preliminary SAR study indicated that substituent groups introduced to the benzene ring play a crucial role in their bioactivity. In particular, the linear alkoxy group at 4-position favors the neuroprotective activity, while a bulky group could lead the activity decrease or loss. These findings could provide an alternative strategy for the development of novel indole-based 1,2,4-oxadiazole derivatives for the treatment of Alzheimer’s disease.

Bioorganic & Medicinal Chemistry Letters published new progress about Alzheimer disease. 229009-40-9 belongs to class piperazines, and the molecular formula is C11H17BN2O2, SDS of cas: 229009-40-9.

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

Rabal, Obdulia; Sanchez-Arias, Juan A.; Cuadrado-Tejedor, Mar; de Miguel, Irene; Perez-Gonzalez, Marta; Garcia-Barroso, Carolina; Ugarte, Ana; Estella-Hermoso de Mendoza, Ander; Saez, Elena; Espelosin, Maria; Ursua, Susana; Haizhong, Tan; Wei, Wu; Musheng, Xu; Garcia-Osta, Ana; Oyarzabal, Julen published the artcile< Design, Synthesis, and Biological Evaluation of First-in-Class Dual Acting Histone Deacetylases (HDACs) and Phosphodiesterase 5 (PDE5) Inhibitors for the Treatment of Alzheimer's Disease>, Electric Literature of 374930-88-8, the main research area is histone deacetylase HDAC phosphodiesterase PDE5 inhibitor antialzheimer Alzheimer.

Simultaneous inhibition of phosphodiesterase 5 (PDE5) and histone deacetylases (HDAC) has recently been validated as a potentially novel therapeutic approach for Alzheimer’s Disease (AD). To further extend this concept, the authors designed and synthesized the first chem. series of dual acting PDE5 and HDAC inhibitors, and the authors validated this systems therapeutics approach. Following the implementation of structure- and knowledge-based approaches, initial hits were designed and were shown to validate the hypothesis of dual in vitro inhibition. Then, an optimization strategy was pursued to obtain a proper tool compound for in vivo testing in AD models. Initial hits were translated into mols. with adequate cellular functional responses (histone acetylation and cAMP/cGMP response element-binding (CREB) phosphorylation in the nanomolar range), an acceptable therapeutic window (>1 log unit) and the ability to cross the blood-brain barrier, leading to the identification of 7 as a candidate for in vivo proof-of-concept testing.

Journal of Medicinal Chemistry published new progress about Alzheimer disease. 374930-88-8 belongs to class piperazines, and the molecular formula is C13H19BrN4O2, Electric Literature of 374930-88-8.

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

He, Longwei; Yang, Yunzhen; Lin, Weiying published the artcile< Rational Design of a Rigid Fluorophore-Molecular Rotor-Based Probe for High Signal-to-Background Ratio Detection of Sulfur Dioxide in Viscous System>, Quality Control of 197638-83-8, the main research area is rigid fluorophore mol rotor probe sulfur dioxide viscous.

Many viscous microenvironments exist in living systems. For instance, at the cellular level, the viscosity of subcellular organelles (mitochondria, lysosomes, endoplasmic reticulum, nucleus, etc.) is much greater than that of cytoplasm; at the organismal level, compared with normal states of health, blood, or lymphatic fluid viscosity will increase to some extent in diabetes, hypertension, inflammation, tumors, and so on. However, due to the design shortcoming, there is a lack of efficient tools for detecting biomols. in viscous living systems. Herein, we propose a rational design strategy for constructing ratiometric fluorescent probes with superior response signal-to-background (S/B) ratio in viscous systems based on rigid-fluorophore-mol. rotor platform, and a practical sulfur dioxide (SO2) probe (RFC-MRC) based on conmarin-cyanine dyad was prepared as a proof-of-concept. The probe performs a significant enhancement (71.5-fold) of ratiometric response signal stimulated by SO2 in viscous aqueous media. The cationic probe can selectively in mitochondria and was successfully utilized to sense SO2 in living HeLa cells through ratiometric fluorescence imaging. What’s more, in the fluorescence imaging experiments of monitoring SO2 in apoptotic cells using probe RFC-MRC, a more obvious superior of S/B ratio was observed in the early apoptotic cells than in the lately apoptotic cells.

Analytical Chemistry (Washington, DC, United States) published new progress about Fluorescent indicators. 197638-83-8 belongs to class piperazines, and the molecular formula is C16H22N2O3, Quality Control of 197638-83-8.

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

Li, Zhe; Gever, Joel R.; Rao, Satish; Widjaja, Kartika; Prusiner, Stanley B.; Silber, B. Michael published the artcile< Discovery and Preliminary Structure-Activity Relationship of Arylpiperazines as Novel, Brain-Penetrant Antiprion Compounds>, HPLC of Formula: 197638-83-8, the main research area is arylpiperazine antiprion neurodegenerative disease creutzfeldt jakob preparation; Creutzfeldt-Jakob disease; Neurodegenerative diseases; SAR; arylpiperazine; piperazine; prion disease.

Creutzfeldt-Jakob disease and kuru in humans, BSE in cattle, and scrapie in sheep are fatal neurodegenerative disorders. Such illnesses are caused by the conversion and accumulation of a misfolded pathogenic isoform (termed PrPSc) of a normally benign, host cellular protein, denoted PrPC. The authors employed high-throughput screening enzyme-linked immunosorbent assays to evaluate compounds for their ability to reduce the level of PrPSc in Rocky Mountain Laboratory prion-infected mouse neuroblastoma cells (ScN2a-cl3). Arylpiperazines were among the active compounds identified, but the initial hits suffered from low potency and poor drug-likeness. The best of those hits, such as 1-(4-(4-Benzylpiperazine-1-yl)phenyl)ethanone, 1-(4-(4-(3-pyridinylmethyl)-1-piperazinyl)phenyl)ethanone, 1-(4-(4-(2-thienylmethyl)-1-piperazinyl)phenyl)ethanone, and 1-(4-(4-[(5-methyl-2-furanyl)methyl]-1-piperazinyl)phenyl)ethanone, displayed moderate antiprion activity with EC50 values in the micromolar range. Key analogs were designed and synthesized on the basis of the structure-activity relationship, with analogs 2-(4-(4-(Pyridin-3-ylmethyl)piperazin-1-yl)phenyl)benzo[d]oxazole, 2-(4-(4-(Pyridin-3-ylmethyl)piperazin-1-yl)phenyl)benzo[d]thiazole, 2-(4-(4-((6-Fluoropyridin-3-yl)methyl)piperazin-1-yl)phenyl)benzo[d]oxazole, and 2-(4-(4-((6-methoxypyridin-3-yl)methyl)piperazin-1-yl)phenyl)benzo[d]oxazole found to have submicromolar potency. Analogs 2-(4-(4-(Pyridin-3-ylmethyl)piperazin-1-yl)phenyl)benzo[d]oxazole and 2-(4-(4-(Pyridin-3-ylmethyl)piperazin-1-yl)phenyl)benzo[d]thiazole were able to penetrate the blood-brain barrier and achieved excellent drug concentrations in the brains of mice after oral dosing. These compounds represent good starting points for further lead optimization in the authors’ pursuit of potential drug candidates for the treatment of prion diseases.

ACS Medicinal Chemistry Letters published new progress about Creutzfeldt-Jakob disease. 197638-83-8 belongs to class piperazines, and the molecular formula is C16H22N2O3, HPLC of Formula: 197638-83-8.

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

Du, Lifei; Wang, Xiaoyu; Cui, Guonan; Xu, Bailing published the artcile< Design, synthesis and biological evaluation of novel thiazole-based derivatives as human Pin1 inhibitors>, Recommanded Product: tert-Butyl piperazine-1-carboxylate hydrochloride, the main research area is thiazole based derivative human Pin1 inhibitors; PPIase; Pin1; Pin1 inhibitor; Thiazole derivatives.

Pin1 is a peptidyl prolyl cis-trans isomerase (PPIase) and inhibiting Pin1 is a potential way for discovering anti-tumor agents. With an aim to find potent Pin1 inhibitors with a novel scaffold, a series of thiazole derivatives with an alicyclic heterocycles on the 2-position were designed, synthesized and tested against human Pin1. Compound 9p bearing a 2-oxa-6-azaspiro [3,3] heptane moiety on the thiazole scaffold was identified as the most potent Pin1 inhibitor of this series with an IC50 value of 0.95μM. The structure-activity relationship (SAR) and mol. modeling study indicated that introducing an alicyclic ring with an H-bond acceptor would be a viable way to improve the binding affinity.

Bioorganic & Medicinal Chemistry published new progress about Antitumor agents. 76535-74-5 belongs to class piperazines, and the molecular formula is C9H19ClN2O2, Recommanded Product: tert-Butyl piperazine-1-carboxylate hydrochloride.

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

Yamamoto, Eiji; Ukigai, Satoshi; Ito, Hajime published the artcile< Boryl substitution of functionalized aryl-, heteroaryl- and alkenyl halides with silylborane and an alkoxy base: expanded scope and mechanistic studies>, Formula: C13H19BrN4O2, the main research area is arylbromide dimethylphenylsilyl boronic acid pinacol ester borylation; boronic acid pinacol ester aryl preparation; aryl iodide aryl boronate Suzuki coupling biaryl preparation; alkenyl halide dimethylphenylsilyl boronic acid pinacol ester borylation; alkenylboronate preparation.

A transition-metal-free method was developed for the boryl substitution of functionalized aryl-, heteroaryl- and alkenyl halides with a silylborane in the presence of an alkali-metal alkoxide. The base-mediated boryl substitution of organohalides with a silylborane was recently reported to provide the corresponding borylated products in good to high yields, and exhibit good functional group compatibility and high tolerance to steric hindrance. The scope of this transformation was extended significantly to include a wide variety of functionalized aryl-, heteroaryl- and alkenyl halides. In particular, the boryl substitution of (E)- and (Z)-alkenyl halides proceeded smoothly to afford the corresponding alkenyl boronates in good to high yields with retention of the configuration using modified reaction conditions. The results of the mechanistic studies suggest that this boryl substitution proceeds via a carbanion-mediated mechanism.

Chemical Science published new progress about Aryl halides Role: RCT (Reactant), RACT (Reactant or Reagent). 374930-88-8 belongs to class piperazines, and the molecular formula is C13H19BrN4O2, Formula: C13H19BrN4O2.

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