Category: 622-40-2

Ervin, Samantha M. published the artcileTargeting Regorafenib-Induced Toxicity through Inhibition of Gut Microbial β-Glucuronidases, SDS of cas: 622-40-2, the publication is ACS Chemical Biology (2019), 14(12), 2737-2744, database is CAplus and MEDLINE.

Regorafenib (Stivarga) is an oral small mol. kinase inhibitor used to treat metastatic colorectal cancer, hepatocellular carcinomas, and gastrointestinal stromal tumors. Diarrhea is one of the most frequently observed adverse reactions associated with regorafenib. This toxicity may arise from the reactivation of the inactive regorafenib-glucuronide to regorafenib by gut microbial β-glucuronidase (GUS) enzymes in the gastrointestinal tract. We sought to unravel the mol. basis of regorafenib-glucuronide processing by human intestinal GUS enzymes and to examine the potential inhibition of these enzymes. Using a panel of 31 unique gut microbial GUS enzymes derived from the 279 mapped from the human gut microbiome, we found that only four were capable of regorafenib-glucuronide processing. Using crystal structures as a guide, we pinpointed the mol. features unique to these enzymes that confer regorafenib-glucuronide processing activity. Furthermore, a pilot screen identified the FDA-approved drug raloxifene as an inhibitor of regorafenib reactivation by the GUS proteins discovered. Novel synthetic raloxifene analogs exhibited improved potency in both in vitro and ex vivo studies. Taken together, these data establish that regorafenib reactivation is exclusively catalyzed by gut microbial enzymes and that these enzymes are amenable to targeted inhibition. Our results unravel key mol. details of regorafenib reactivation in the GI tract and provide a potential pathway to improve clin. outcomes with regorafenib.

ACS Chemical Biology published new progress about 622-40-2. 622-40-2 belongs to alcohols-buliding-blocks, auxiliary class Morpholine,Alcohol, name is 2-Morpholinoethanol, and the molecular formula is C6H13NO2, SDS of cas: 622-40-2.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Xu, Shiyang published the artcileRh(I)-Catalyzed Coupling of Azides with Boronic Acids Under Neutral Conditions, Category: alcohols-buliding-blocks, the publication is Organic Letters (2022), 24(30), 5546-5551, database is CAplus and MEDLINE.

A neutral amination reaction using azides RN₃ (R = Ph, 4-nitrophenyl, 4-bromophenyl, etc.) as the nitrogen source and arylboronic acids ArB(OH)₂ (Ar = 4-cyanobutyl, cyclooctyl, Ph, etc.) with a rhodium(I) catalyst to afford alkyl-aryl and aryl-aryl secondary amines RNHAr was presented. Natural products and pharmaceutical derivatives were applied, and gram-scale reactions were performed, which demonstrated the utility. Mechanistic experiments and DFT calculations suggested that the reaction involves a metal-nitrene intermediate.

Organic Letters published new progress about 622-40-2. 622-40-2 belongs to alcohols-buliding-blocks, auxiliary class Morpholine,Alcohol, name is 2-Morpholinoethanol, and the molecular formula is C4H8Cl2S2, Category: alcohols-buliding-blocks.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Riva, Beatrice published the artcilePyrtriazoles, a Novel Class of Store-Operated Calcium Entry Modulators: Discovery, Biological Profiling, and in Vivo Proof-of-Concept Efficacy in Acute Pancreatitis, Formula: C6H13NO2, the publication is Journal of Medicinal Chemistry (2018), 61(21), 9756-9783, database is CAplus and MEDLINE.

In recent years, channels that mediate store-operated calcium entry (SOCE, i.e., the ability of cells to sense a decrease in endoplasmic reticulum luminal calcium and induce calcium entry across the plasma membrane) have been associated with a number of disorders, spanning from immune disorders to acute pancreatitis and have been suggested to be druggable targets. In the present contribution, we exploited the click chem. approach to synthesize a class of SOCE modulators where the arylamide substructure that characterizes most inhibitors so far described is substituted by a 1,4-disubstituted 1,2,3-triazole ring. Within this series, inhibitors of SOCE were identified and the best compound I proved effective in an animal model of acute pancreatitis, a disease characterized by a hyperactivation of SOCE. Strikingly, two enhancers of the process were discovered, affording invaluable research tools to further explore the (patho)physiol. role of capacitative calcium entry.

Journal of Medicinal Chemistry published new progress about 622-40-2. 622-40-2 belongs to alcohols-buliding-blocks, auxiliary class Morpholine,Alcohol, name is 2-Morpholinoethanol, and the molecular formula is C6H13NO2, Formula: C6H13NO2.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Song, Fengqin published the artcileGas chromatography-mass spectrometry profiling of volatile compounds reveals metabolic changes in a non-aflatoxigenic Aspergillus flavus induced by 5-azacytidine, SDS of cas: 622-40-2, the publication is Toxins (2020), 12(1), 57, database is CAplus and MEDLINE.

Aspergillus flavus is one of the most opportunistic pathogens invading many important oilseed crops and foodstuffs with such toxic secondary metabolites as aflatoxin (AF) and Cyclopiazonic acid. We previously used the DNA methylation inhibitor 5-azacytidine to treat with an AF-producing A. flavus A133 strain, and isolated a mutant (NT) of A. flavus, which displayed impaired abilities of AF biosynthesis and fungal development. In this study, gas chromatog.-mass spectrometry (GC-MS) anal. was used to reveal the metabolic changes between these two strains. A total of 1181 volatiles were identified in these two strains, among which 490 volatiles were found in these two strains in vitro and 332 volatiles were found in vivo. The NT mutant was found to produce decreasing volatile compounds, among which most of the fatty acid-derived volatiles were significantly downregulated in the NT mutant compared to the A133 strain, which are important precursors for AF biosynthesis. Two antioxidants and most of the amino acids derived volatiles were found significantly upregulated in the NT mutant. Overall, our results reveal the difference of metabolic profiles in two different A. flavus isolates, which may provide valuable information for controlling infections of this fungal pathogen.

Toxins published new progress about 622-40-2. 622-40-2 belongs to alcohols-buliding-blocks, auxiliary class Morpholine,Alcohol, name is 2-Morpholinoethanol, and the molecular formula is C8H7NaO4S, SDS of cas: 622-40-2.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Bell, Mark published the artcileDiscovery of super soft-drug modulators of sphingosine-1-phosphate receptor 1, Related Products of alcohols-buliding-blocks, the publication is Bioorganic & Medicinal Chemistry Letters (2018), 28(19), 3255-3259, database is CAplus and MEDLINE.

The oral S1PR1 agonist ponesimod demonstrated substantial efficacy in a phase II clin. trial of psoriasis. Unfortunately, systemic side effects were observed, which included lymphopenia and transient bradycardia. We sought to develop a topical soft-drug S1PR1 agonist with an improved therapeutic index. By modifying ponesimod, we discovered an ester series of S1PR agonists. To increase metabolic instability in plasma we synthesized esters described as specific substrates for paraoxonase and butyrylcholinesterases, esterases present in human plasma.

Bioorganic & Medicinal Chemistry Letters published new progress about 622-40-2. 622-40-2 belongs to alcohols-buliding-blocks, auxiliary class Morpholine,Alcohol, name is 2-Morpholinoethanol, and the molecular formula is C6H13NO2, Related Products of alcohols-buliding-blocks.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Zhu, Mei published the artcileNovel HIV-1 Protease Inhibitors with Morpholine as the P2 Ligand to Enhance Activity against DRV-Resistant Variants, Application of 2-Morpholinoethanol, the publication is ACS Medicinal Chemistry Letters (2020), 11(6), 1196-1204, database is CAplus and MEDLINE.

Flexible heterocyclic moieties as the P2 ligands of HIV-1 protease inhibitors may be adapted to the minimally distorted active site of mutations easily and enhance activity against DRV-resistant HIV-1 variants. Herein, the design, synthesis, and biol. evaluation of a new series of inhibitors containing morpholine derivatives as the P2 ligands were described, among which, carbamate inhibitor I and carbamido inhibitor II exhibited almost 4- and 2-fold superior activity with enzyme Ki of 0.092 nM and 0.21 nM, as well as antiviral IC50 values of 0.41 nM and 0.95 nM, resp., compared to DRV. Besides, they exhibited excellent activity with inhibition of 94% and 91%, resp. Furthermore, they also showed appreciable antiviral activity against DRV-resistant HIV-1 variants.

ACS Medicinal Chemistry Letters published new progress about 622-40-2. 622-40-2 belongs to alcohols-buliding-blocks, auxiliary class Morpholine,Alcohol, name is 2-Morpholinoethanol, and the molecular formula is C8H6BrF3S, Application of 2-Morpholinoethanol.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Chen, Xingmei published the artcileMachine learning-based prediction of toxicity of organic compounds towards fathead minnow, Quality Control of 622-40-2, the publication is RSC Advances (2020), 10(59), 36174-36180, database is CAplus and MEDLINE.

Predicting the acute toxicity of a large dataset of diverse chems. against fathead minnows (Pimephales promelas) is challenging. In this paper, 963 organic compounds with acute toxicity towards fathead minnows were split into a training set (482 compounds) and a test set (481 compounds) with an approx. ratio of 1 : 1. Only six mol. descriptors were used to establish the quant. structure-activity/toxicity relationship (QSAR/QSTR) model for 96 h pLC₅₀ through a support vector machine (SVM) along with genetic algorithm. The optimal SVM model (R² = 0.756) was verified using both internal (leave-one-out cross-validation) and external validations. The validation results (q_int² = 0.699 and q_ext² = 0.744) were satisfactory in predicting acute toxicity in fathead minnows compared with other models reported in the literature, although our SVM model has only six mol. descriptors and a large data set for the test set consisting of 481 compounds

RSC Advances published new progress about 622-40-2. 622-40-2 belongs to alcohols-buliding-blocks, auxiliary class Morpholine,Alcohol, name is 2-Morpholinoethanol, and the molecular formula is C6H13NO2, Quality Control of 622-40-2.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Berecz, Gabor published the artcileTowards Tianeptine Analogues: Synthesis of New Ring Systems Containing a Dibenzo[c,f[1,2]thiazepine S,S -Dioxide Core, Quality Control of 622-40-2, the publication is Synthesis (2022), 54(17), 3874-3882, database is CAplus.

In the course of the synthesis of fused-ring analogs of the antidepressant drug tianeptine, representatives of three new heterocyclic ring systems, indolo[1,7- bc][1,2]benzothiazepines (and their 4,5-dihydro analogs), 5,6-dihydroquino[1,8- bc][1,2]benzothiazepine, and [1,2]benzothiazepino[4,3,2- jk]carbazoles, as well as their intermediates, was prepared The tetracyclic and pentacyclic ring systems containing either an oxo or a hydroxy functional group are suitable for introducing various side chains, including potential pharmacophores. For this latter transformation, examples are demonstrated by conversion of the hydroxy group into a chloro moiety and subsequent reaction with amines or with primary alcs. bearing a tertiary amino side chain. Two fused-ring derivatives exhibiting the side-chain characteristics of tianeptine was also synthesized. Altogether 40 compounds were described in the present manuscript, eight of them are also characterized by single-crystal X-ray diffraction.

Synthesis published new progress about 622-40-2. 622-40-2 belongs to alcohols-buliding-blocks, auxiliary class Morpholine,Alcohol, name is 2-Morpholinoethanol, and the molecular formula is C6H13NO2, Quality Control of 622-40-2.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Tota, Arianna published the artcileN-N Bond Formation Using an Iodonitrene as an Umpolung of Ammonia: Straightforward and Chemoselective Synthesis of Hydrazinium Salts, Related Products of alcohols-buliding-blocks, the publication is Advanced Synthesis & Catalysis (2021), 363(1), 194-199, database is CAplus.

The formation of hydrazinium salts by N-N bond formation has typically involved the use of hazardous and difficult to handle reagents. Here, mild and operationally simple conditions for the synthesis of hydrazinium salts are reported. Electrophilic nitrogen transfer to the nitrogen atom of tertiary amines is achieved using iodosylbenzene as oxidant and ammonium carbamate as the N-source. The resulting process is highly chemoselective and tolerant to other functional groups. A wide scope is reported, including examples with bioactive mols. Insights on the structure of hydrazinium salts were provided by X-ray anal.

Advanced Synthesis & Catalysis published new progress about 622-40-2. 622-40-2 belongs to alcohols-buliding-blocks, auxiliary class Morpholine,Alcohol, name is 2-Morpholinoethanol, and the molecular formula is C5H6BNO2, Related Products of alcohols-buliding-blocks.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Lemke, Carina published the artcileChromenones as Multineurotargeting Inhibitors of Human Enzymes, Synthetic Route of 622-40-2, the publication is ACS Omega (2019), 4(26), 22161-22168, database is CAplus and MEDLINE.

The complex nature of multifactorial diseases, such as Morbus Alzheimer, has produced a strong need to design multitarget-directed ligands to address the involved complementary pathways. A purposive structural modification of a tetratarget small-mol. contilisant and generated a combinatorial library of substituted chromen-4-ones I (R = pyrrolidin-1-yl, piperidin-1-yl, morpholin-4-yl, etc.; n = 2, 3, 4, 5) is reported. The compounds comprise a basic moiety which is linker-connected to the 6-position of the heterocyclic chromenone core. The syntheses were accomplished by Mitsunobu- or Williamson-type ether formations. The resulting library members were evaluated at a panel of seven human enzymes, all of which being involved in the pathophysiol. of neurodegeneration. A concomitant inhibition of human acetylcholinesterase and human monoamine oxidase B, with IC50 values of 5.58 and 7.20 μM, resp., was achieved with the dual-target 6-(4-(piperidin-1-yl)butoxy)-4H-chromen-4-one.

ACS Omega published new progress about 622-40-2. 622-40-2 belongs to alcohols-buliding-blocks, auxiliary class Morpholine,Alcohol, name is 2-Morpholinoethanol, and the molecular formula is C6H13NO2, Synthetic Route of 622-40-2.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts