Month: October 2022

Ospanov, Meirambek; Sulochana, Suresh P.; Paris, Jason J.; Rimoldi, John M.; Ashpole, Nicole; Walker, Larry; Ross, Samir A.; Shilabin, Abbas G.; Ibrahim, Mohamed A. published the artcile< Identification of an Orally Bioavailable, Brain-Penetrant Compound with Selectivity for the Cannabinoid Type 2 Receptor>, Application of C4H3NOS, the main research area is pyrrolobenzodiazepine preparation neuroinflammation cannabinoid receptor antineurodegenerative activity pharmacokinetic property; cannabinoid receptors CB1/CB2; central nervous system (CNS); neurodegenerative diseases; neuroinflammation; pharmacokinetics (PK); pyrrolobenzodiazepines; radioligand binding assay.

Modulation of the endocannabinoid system (ECS) is of great interest for its therapeutic relevance in several pathophysiol. processes. The CB2 subtype is largely localized to immune effectors, including microglia within the central nervous system, where it promotes anti-inflammation. Recently, a rational drug design toward precise modulation of the CB2 active site revealed the novelty of Pyrrolo[2,1-c][1,4]benzodiazepines tricyclic chemotype with a high conformational similarity in comparison to the existing leads. These compounds are structurally unique, confirming their chemotype novelty. In our continuing search for new chemotypes as selective CB2 regulatory mols., following SAR approaches, a total of 17 selected (S,E)-11-[2-(arylmethylene)hydrazono]-PBD analogs were synthesized and tested for their ability to bind to the CB1 and CB2 receptor orthosteric sites. A competitive [3H]CP-55,940 binding screen revealed five compounds that exhibited >60% displacement at 10 μM concentration Further concentration-response anal. revealed two compounds, 4k and 4q, as potent and selective CB2 ligands with sub-micromolar activities (Ki = 146 nM and 137 nM, resp.). In order to support the potential efficacy and safety of the analogs, the oral and i.v. pharmacokinetic properties of compound 4k were sought. Compound 4k was orally bioavailable, reaching maximum brain concentrations of 602 ± 162 ng/g (p.o.) with an elimination half-life of 22.9 ± 3.73 h. Whether administered via the oral or i.v. route, the elimination half-lives ranged between 9.3 and 16.7 h in the liver and kidneys. These compounds represent novel chemotypes, which can be further optimized for improved affinity and selectivity toward the CB2 receptor.

Moleculespublished new progress about Anti-neurodegenerative agents. 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, Application of C4H3NOS.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Yevtodiyenko, Aleksey; Bazhin, Arkadiy; Khodakivskyi, Pavlo; Godinat, Aurelien; Budin, Ghyslain; Maric, Tamara; Pietramaggiori, Giorgio; Scherer, Sandra S.; Kunchulia, Marina; Eppeldauer, George; Polyakov, Sergey V.; Francis, Kevin P.; Bryan, Jeffrey N.; Goun, Elena A. published the artcile< Portable bioluminescent platform for in vivo monitoring of biological processes in non-transgenic animals>, Name: (S)-2-(6-Hydroxybenzo[d]thiazol-2-yl)-4,5-dihydrothiazole-4-carboxylic acid, the main research area is bioluminescent transgenic animal biol process invivo monitoring.

Bioluminescent imaging (BLI) is one of the most powerful and widely used preclin. imaging modalities. However, the current technol. relies on the use of transgenic luciferase-expressing cells and animals and therefore can only be applied to a limited number of existing animal models of human disease. Here, we report the development of a “”portable bioluminescent”” (PBL) technol. that overcomes most of the major limitations of traditional BLI. We demonstrate that the PBL method is capable of noninvasive measuring the activity of both extracellular (e.g., dipeptidyl peptidase 4) and intracellular (e.g., cytochrome P 450) enzymes in vivo in non-luciferase-expressing mice. Moreover, we successfully utilize PBL technol. in dogs and human cadaver, paving the way for the translation of functional BLI to the noninvasive quantification of biol. processes in large animals. The PBL methodol. can be easily adapted for the noninvasive monitoring of a plethora of diseases across multiple species.

Nature Communicationspublished new progress about Animal gene, CYP3A Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 2591-17-5 belongs to class thiazole, and the molecular formula is C11H8N2O3S2, Name: (S)-2-(6-Hydroxybenzo[d]thiazol-2-yl)-4,5-dihydrothiazole-4-carboxylic acid.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Martin-Burgos, Blanca; Wang, Wanqi; William, Ivana; Tir, Selma; Mohammad, Innus; Javed, Reja; Smith, Stormi; Cui, Yilin; Arzavala, Jessica; Mora, Dalilah; Smith, Ciearra B.; van der Vinne, Vincent; Molyneux, Penny C.; Miller, Stephen C.; Weaver, David R.; Leise, Tanya L.; Harrington, Mary E. published the artcile< Methods for detecting PER2:LUCIFERASE bioluminescence rhythms in freely moving mice>, Quality Control of 2591-17-5, the main research area is circadian rhythm bioluminescence gene expression photomultiplier tube; CycLuc1; PERIOD2; bioluminescence; circadian; in vivo; luciferase; peripheral oscillators; reporter gene.

Circadian rhythms are driven by daily oscillations of gene expression. An important tool for studying cellular and tissue circadian rhythms is the use of a gene reporter, such as bioluminescence from the reporter gene luciferase controlled by a rhythmically expressed gene of interest. Here we describe methods that allow measurement of circadian bioluminescence from a freely moving mouse housed in a standard cage. Using a LumiCycle In Vivo (Actimetrics), we determined conditions that allow detection of circadian rhythms of bioluminescence from the PER2 reporter, PER2::LUC, in freely behaving mice. The LumiCycle In Vivo applies a background subtraction that corrects for effects of room temperature on photomultiplier tube (PMT) output. We tested delivery of d-luciferin via a s.c. minipump and in the drinking water. We demonstrate spikes in bioluminescence associated with drinking bouts. Further, we demonstrate that a synthetic luciferase substrate, CycLuc1, can support circadian rhythms of bioluminescence, even when delivered at a lower concentration than d-luciferin, and can support longer-term studies. A small difference in phase of the PER2::LUC bioluminescence rhythms, with females phase leading males, can be detected with this technique. We share our anal. scripts and suggestions for further improvements in this method. This approach will be straightforward to apply to mice with tissue-specific reporters, allowing insights into responses of specific peripheral clocks to perturbations such as environmental or pharmacol. manipulations.

Journal of Biological Rhythmspublished new progress about Biological oscillations. 2591-17-5 belongs to class thiazole, and the molecular formula is C11H8N2O3S2, Quality Control of 2591-17-5.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Liu, Jingjing; Tian, Zhenwei; Liu, Tianzhou; Wen, Dacheng; Ma, Zhiming; Liu, Yuanda; Zhu, Jiaming published the artcile< CHSY1 is upregulated and acts as tumor promotor in gastric cancer through regulating cell proliferation, apoptosis, and migration>, HPLC of Formula: 2591-17-5, the main research area is prognosis CHSY1 XIAP cell proliferation migration metastatic gastric cancer; CHSY1; Gastric cancer; cell apoptosis; cell migration; cell proliferation.

Gastric cancer is one of the most frequently diagnosed malignant tumors, with rapid progression and poor prognosis. The role of chondroitin sulfate synthase 1 (CHSY1) in the development and progression of gastric cancer was explored and clarified in this study. The immunohistochem. anal. of clin. tissue samples as well as data mining of public database showed that CHSY1 was significantly upregulated in gastric cancer and associated with more advanced tumor stage and poorer prognosis. In vitro loss-of-function experiments demonstrated the inhibited cell proliferation, colony formation, cell migration, as well as the promoted cell apoptosis by CHSY1 knockdown. Moreover, recovery of CHSY1 expression could attenuate the regulatory effects induced by CHSY1 knockdown. Correspondingly, gastric cancer cells with CHSY1 knockdown showed reduced tumorigenicity and slower tumor growth in vivo. In conclusion, this study identified CHSY1 as a tumor promotor in gastric cancer, which may be utilized as a novel indicator of patients′ prognosis and therapeutic target for developing more effective drug for GC treatment.

Cell Cyclepublished new progress about Apoptosis. 2591-17-5 belongs to class thiazole, and the molecular formula is C11H8N2O3S2, HPLC of Formula: 2591-17-5.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Dessi, Alessio; Calamante, Massimo; Mordini, Alessandro; Zani, Lorenzo; Taddei, Maurizio; Reginato, Gianna published the artcile< Microwave-activated synthesis of thiazolo[5,4-d]thiazoles by a condensation/oxidation sequence>, Formula: C4H3NOS, the main research area is thiazolothiazole microwave preparation condensation oxidation.

A microwave-assisted preparation of sym. thiazolo[5,4-d]thiazoles from the corresponding aldehydes is presented. The two-step reaction sequence comprises the condensation of aldehydes with dithiooxamide followed by oxidation/aromatization with 1,4-benzoquinone derivatives The new procedure provides the desired products in good yields and in most cases allows reduction of the excess of aldehyde employed in the process compared to previous methodologies. For the first time, application of the reaction both on aromatic and aliphatic aldehydes is demonstrated.

RSC Advancespublished new progress about Aliphatic aldehydes Role: RCT (Reactant), RACT (Reactant or Reagent). 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, Formula: C4H3NOS.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Mishra, Deepak; Fatima, Atiya; Rout, Chittaranjan; Singh, Ram published the artcile< An efficient one-pot synthesis of 2-aminothiazole derivatives>, COA of Formula: C9H7N3O2S, the main research area is aminothiazole preparation; haloketone thioamide cyclization.

A highly efficient, rapid and catalyst free protocol has been developed for the synthesis of 2-aminothiazoles I (R = Br, NO2, OCH3, etc.; R1 = Cl, CN, OCH3, etc.) in THF. Reaction was carried out at room temperature and the products were obtained in high yields without further purification

Chemica Sinicapublished new progress about Cyclization. 57493-24-0 belongs to class thiazole, and the molecular formula is C9H7N3O2S, COA of Formula: C9H7N3O2S.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica