622-40-2 Archives - Alcohols-buliding-blocks

Peng, Jingjing’s team published research in European Journal of Medicinal Chemistry in 158 | CAS: 622-40-2

European 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, Application of 2-Morpholinoethanol.

Peng, Jingjing published the artcileDesign, synthesis, and biological evaluation of 2-(phenoxyaryl)-3-urea derivatives as novel P2Y₁ receptor antagonists, Application of 2-Morpholinoethanol, the publication is European Journal of Medicinal Chemistry (2018), 302-310, database is CAplus and MEDLINE.

A novel series of 2-(phenoxyaryl)-3-urea derivatives I [R¹ = H, Me; R² = n-Bu, 4-F₃COC₆H₄, 5-methoxycarbonyl-2-thienyl, etc.; X = CH, N] were designed, synthesized and biol. evaluated for their anti-thrombotic activity and antiplatelet aggregation study. Most of compounds exhibited good inhibition against P2Y₁ receptor among them, compounds I [R¹ = H, Me; R² = 2-methylcyclohexyl, 2-adamantyl, 4-F₃COC₆H₄; X = N] demonstrated good P2Y₁ receptor antagonistic potency in vitro (IC₅₀ = 0.62 μM, 0.82 μM, and 0.21 μM, resp.). Four compounds I [R¹ = H, Me; R² = 4-methylcyclohexyl, 4-F₃COC₆H₄, 5-ethoxycarbonyl-2-thienyl, 5-benzyloxycarbonyl-2-thienyl, etc.; X = N] showed good antiplatelet activity. The possible binding modes of compounds with P2Y₁ receptor were also explored by mol. docking simulation. The docking studies demonstrated that compound I [R¹ = Me; R² = 4-F₃COC₆H₄; X = N] interacted well with Phe119 through hydrophobic interaction and modestly improved the P2Y₁ receptor antagonistic activity.

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

Xue, Si-tu’s team published research in European Journal of Medicinal Chemistry in 200 | CAS: 622-40-2

Xue, Si-tu published the artcileSubstituted benzothiophene and benzofuran derivatives as a novel class of bone morphogenetic protein-2 upregulators: Synthesis, anti-osteoporosis efficacies in ovariectomized rats and a zebrafish model and ADME properties, Computed Properties of 622-40-2, the publication is European Journal of Medicinal Chemistry (2020), 112465, database is CAplus and MEDLINE.

This study optimized the structure of the anti-osteoporosis compound I [R¹ = H; R² = OMe; R⁵ = OEt; X = O] by balancing its lipophilicity and improving its stability. Substituted benzothiophenes/benzofurans derivatives I [R¹ = H; R² = OMe; R¹R² = OCH₂O; R⁵ = Cl, OH, OEt; X = O, S] and II [R¹ = H; R² = OMe; R¹R² = OCH₂O; R³ = n-Pr, P(O)(OH)₂, CH₂N(CH₃)₂, etc.; X = O, S; Y = O, NH, NMe] which were not reported in the literature were designed and synthesized. The ovariectomized rat model of osteoporosis was selected to evaluate the therapeutic effects, compound II [R¹ = H; R² = OMe; R³ = CH₂N(CH₃)₂, etc.; X = O; Y = NH] showed better therapeutic efficacy than that of compound I [R¹ = H; R² = OMe; R⁵ = OEt; X = O]. The anti-osteoporosis activity and BMP-2 (bone morphogenetic protein-2) protein upregulation after treatment with compound II [R¹ = H; R² = OMe; R³ = CH₂N(CH₃)₂, etc.; X = O; Y = NH] in a zebrafish osteoporosis model was verified. Compound II [R¹ = H; R² = OMe; R³ = CH₂N(CH₃)₂, etc.; X = O; Y = NH] improved the ADME properties, therapeutic efficacy and pharmacokinetics of the drug than that of compound I [R¹ = H; R² = OMe; R⁵ = OEt; X = O]. Overall, the anti-osteoporosis effects of the compounds I and II of this type, preliminarily determined the target patient population, verified the mechanism of action, clarified the level of toxicity and provided preliminary ADME data was evaluated. These compounds I and II could both correct bone loss that was already occurring in patients and had broad clin. applicability.

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

Jiao, Yang’s team published research in Angewandte Chemie, International Edition in 59 | CAS: 622-40-2

Angewandte Chemie, International Edition 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.

Jiao, Yang published the artcileA cofactor-substrate-based supramolecular fluorescent probe for the ultrafast detection of nitroreductase under hypoxic Conditions, Quality Control of 622-40-2, the publication is Angewandte Chemie, International Edition (2020), 59(15), 6021-6027, database is CAplus and MEDLINE.

Identifying the location and expression levels of enzymes under hypoxic conditions in cancer cells is vital in early-stage cancer diagnosis and monitoring. By encapsulating a fluorescent substrate, L-NO₂, within the NADH mimic-containing metal-organic capsule Zn-MPB, we developed a cofactor-substrate-based supramol. luminescent probe for ultrafast detection of hypoxia-related enzymes in solution in vitro and in vivo. The host-guest structure fuses the coenzyme and substrate into one supramol. probe to avoid control by NADH, switching the catalytic process of nitroreductase from a double-substrate mechanism to a single-substrate one. This probe promotes enzyme efficiency by altering the substrate catalytic process and enhances the electron transfer efficiency through an intra-mol. pathway with increased activity. The enzyme content and fluorescence intensity showed a linear relationship and equilibrium was obtained in seconds, showing potential for early tumor diagnosis, biomimetic catalysis, and prodrug activation.

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

Rajesh, Sarigama’s team published research in Journal of Colloid and Interface Science in 589 | CAS: 622-40-2

Journal of Colloid and Interface Science 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, Recommanded Product: 2-Morpholinoethanol.

Rajesh, Sarigama published the artcileSynthetic ionizable aminolipids induce a pH dependent inverse hexagonal to bicontinuous cubic lyotropic liquid crystalline phase transition in monoolein nanoparticles, Recommanded Product: 2-Morpholinoethanol, the publication is Journal of Colloid and Interface Science (2021), 85-95, database is CAplus and MEDLINE.

A prospective class of materials for drug delivery is lyotropic liquid crystalline (LLC) nanoparticles, such as cubosomes and hexosomes. Efforts are being made to generate a pH dependent system, which exhibits slow release hexosomes (H2) at physiol. pH and relatively fast release cubosomes (Q2) at acidic disease sites such as in various cancers and bacterial infection (pH ∼ 5.5-6.5). Herein, we report the synthesis of nine ionizable aminolipids, which were doped into monoolein (MO) lipid nanoparticles. Using high throughput formulation and synchrotron small angle X-ray scattering (SAXS), the effects of aminolipid structure and concentration on the mesophase of MO nanoparticles at various pHs were determined As the pH changed from neutral to acidic, mesophases, could be formed in an order L2 (inverse micelles) → H2 → Q2. Specifically, systems with heterocyclic oleates exhibited the H2 to Q2 transition at pH 5.5-6.5. Furthermore, the phase transition pH could be fine-tuned by incorporating two aminolipids into the nanoparticles. Nanoparticles with a pH dependent phase transition as described in this study may be useful as drug delivery carriers for the treatment of cancers and certain bacterial infection.

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

Liu, Gang’s team published research in European Journal of Medicinal Chemistry in 178 | CAS: 622-40-2

Liu, Gang published the artcileStructure-activity relationship studies on Bax activator SMBA1 for the treatment of ER-positive and triple-negative breast cancer, Safety of 2-Morpholinoethanol, the publication is European Journal of Medicinal Chemistry (2019), 589-605, database is CAplus and MEDLINE.

In an effort to develop novel Bax activators for breast cancer treatment, a series of diverse analogs have been designed and synthesized based on lead compound SMBA1 through several strategies, including introducing various alkylamino side chains to have a deeper access to S184 pocket, replacing carbon atoms with nitrogen, and reducing the nitro group of 9H-fluorene scaffold. Compounds 14 (CYD-2-11, I) and 49 (CYD-4-61, II) have been identified to exhibit significantly improved antiproliferative activity compared to SMBA1, with IC₅₀ values of 3.22 μM and 0.07 μM against triple-neg. breast cancer MDA-MB-231 and 3.81 μM and 0.06 μM against ER-pos. breast cancer MCF-7 cell lines, resp. Mechanism of action studies of II indicated that it can activate Bax protein to induce cytochrome c release and regulate apoptotic biomarkers, leading to cancer cell apoptosis. Further in vivo efficacy studies of I and II in nude mice bearing MDA-MB-231 tumor xenografts demonstrated that these drug candidates can significantly suppress tumor growth, indicating their therapeutic potential for the treatment of breast cancer.

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

Li, Yingxiu’s team published research in European Journal of Medicinal Chemistry in 181 | CAS: 622-40-2

Li, Yingxiu published the artcileDiscovery of 4-piperazinyl-2-aminopyrimidine derivatives as dual inhibitors of JAK2 and FLT3, Application of 2-Morpholinoethanol, the publication is European Journal of Medicinal Chemistry (2019), 111590, database is CAplus and MEDLINE.

Hybridization strategy is an effective strategy to obtain multi-target inhibitors in drug design. In this study, we assembled the pharmacophores of momelotinib and tandutinib to get a series of 4-piperazinyl-2-aminopyrimidine derivatives All compounds were tested for the inhibition of JAK2 and FLT3 enzymes, of which, compounds with potent enzyme activities were assayed for antiproliferative activities against three cancer cell lines (HEL, MV4-11, and HL60). The structure-activity relationship studies were conducted through variations in two regions, the “A” Ph ring and “B” Ph ring. Compound 14j showed the most balanced in vitro inhibitory activity against JAK2 and FLT3 (JAK2 IC₅₀ = 27 nM, FLT3 IC₅₀ = 30 nM), and it also showed potent inhibition against the above tested cell lines. In the cellular context, 14j strongly induced apoptosis by arresting cell cycle in the G₁/S phase, and was selected as a promising JAK2/FLT3 dual inhibitor.

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

Kuang, Yuting’s team published research in Journal of Medicinal Chemistry in 65 | CAS: 622-40-2

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, Computed Properties of 622-40-2.

Kuang, Yuting published the artcileInduction of Genes Implicated in Stress Response and Autophagy by a Novel Quinolin-8-yl-nicotinamide QN523 in Pancreatic Cancer, Computed Properties of 622-40-2, the publication is Journal of Medicinal Chemistry (2022), 65(8), 6133-6156, database is CAplus and MEDLINE.

Using a cytotoxicity-based phenotypic screen of a highly diverse library of 20,000 small-mol. compounds, we identified a quinolin-8-yl-nicotinamide, QN519, as a promising lead. QN519 represents a novel scaffold with drug-like properties, showing potent in vitro cytotoxicity in a panel of 12 cancer cell lines. Subsequently, lead optimization campaign generated compounds with IC₅₀ values < 1μM. An optimized compound, QN523, shows significant in vivo efficacy in a pancreatic cancer xenograft model. QN523 treatment significantly increased the expression of HSPA5, DDIT3, TRIB3, and ATF3 genes, suggesting activation of the stress response pathway. We also observed a significant increase in the expression of WIPI1, HERPUD1, GABARAPL1, and MAP1LC3B, implicating autophagy as a major mechanism of action. Due to the lack of effective treatments for pancreatic cancer, discovery of novel agents such as the QN series of compounds with unique mechanism of action has the potential to fulfill a clear unmet medical need.

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

Yu, Qian’s team published research in European Journal of Medicinal Chemistry in 152 | CAS: 622-40-2

Yu, Qian published the artcileSynthesis, cytotoxicity and structure-activity relationship of indolizinoquinolinedione derivatives as DNA topoisomerase IB catalytic inhibitors, Category: alcohols-buliding-blocks, the publication is European Journal of Medicinal Chemistry (2018), 195-207, database is CAplus and MEDLINE.

A series of indolizinoquinolinedione derivatives I [X₁ = N; X₂ = X₃ = X₄ = CH; n = 2, 3; R¹ = H, F, Cl; R² = NMe₂, pyrrolidinyl, piperidinyl, morpholinyl, 4-methylpiperazinyl] and II [R3 = NMe₂, pyrrolidinyl, piperidinyl, morpholinyl] was synthesized. TOP1-mediated relaxation, nicking and unwinding assays revealed that three fluorinated derivatives I [X₁ = N; X₂ = X₃ = X₄ = CH; n = 2, 3; R¹ = F; R² = pyrrolidinyl, piperidinyl] and one N,N-trans derivative I [X₁ = X₂ = X₃ = CH; X₄ = N; n = 2; R² = morpholinyl] act as TOP1 catalytic inhibitors with higher TOP1 inhibition (++++) than camptothecin (+++) and without TOP1-mediated unwinding effect. MTT assay against five human cancer cell lines indicated that the highest cytotoxicity was II [R³ = piperidinyl] for CCRF-CEM cells, I [X₁ = N; X₂ = X₃ = X₄ = CH; n = 3; R¹ = F; R² = NMe2] for A549 and DU-145 cells, I [X₁ = N; X₂ = X₃ = X₄ = CH; n = 2; R¹ = F; R² = pyrrolidinyl] for HCT116 cells, and I [X₁ = N; X₂ = X₃ = X₄ = CH; n = 3; R¹ = F; R² = 4-methylpiperazinyl] for Huh7 cells with GI₅₀ values at nanomolar range. The drug-resistant cell assay indicated that compound I [X₁ = N; X₂ = X₃ = X₄ = CH; n = 2; R¹ = F; R² = pyrrolidinyl] may mainly act to TOP1 in cells and was less of Pgp substrates. Flow cytometric anal. showed that compounds I [X₁ = N; X₂ = X₃ = X₄ = CH; n = 2, 3; R¹ = F; R² = pyrrolidinyl, piperidinyl] could obviously induce apoptosis of HCT116 cells. Moreover, the structure-activity relationship (SAR) of indolizinoquinolinedione derivatives was analyzed.

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

Luo, Shanshan’s team published research in European Journal of Medicinal Chemistry in 200 | CAS: 622-40-2

Luo, Shanshan published the artcileDesign and synthesis of novel SCM-198 analogs as cardioprotective agents: Structure-activity relationship studies and biological evaluations, Recommanded Product: 2-Morpholinoethanol, the publication is European Journal of Medicinal Chemistry (2020), 112469, database is CAplus and MEDLINE.

SCM-198 (Leonurine) has attracted great attention due to its cardioprotective effects in myocardial infarction (MI). However, no systematic modifications and structure-activity relationship (SAR) studies could be traced so far. In this study, 35 analogs of SCM-198 were designed, synthesized and their cardioprotective effects were evaluated. The cell viability assay on cardiomyocyte cell line H9c2 challenged with H₂O₂ showed that several analogs exhibited more potent cytoprotective effects than SCM-198 at 1μM and 10μM concentrations LDH release level in cells treated with 1μM 14o was comparable with cells treated with 10μM SCM-198. Results of Bcl-2 expression and caspase-3 activation accordingly indicated higher protective activity of 14o than SCM-198. Moreover, in a mouse model of MI, the mice pretreated with 14o had much lower infarct size compared with that of SCM-198. The mechanism study suggested that 14o improved cardiac morphol. and reduced apoptosis of cardiomyocytes in the border zone of infarction, as proved by H&E and TUNEL staining.

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

Lin, Wen-Hsing’s team published research in Journal of Medicinal Chemistry in 62 | CAS: 622-40-2

Lin, Wen-Hsing published the artcileIdentification of a Multitargeted Tyrosine Kinase Inhibitor for the Treatment of Gastrointestinal Stromal Tumors and Acute Myeloid Leukemia, Application In Synthesis of 622-40-2, the publication is Journal of Medicinal Chemistry (2019), 62(24), 11135-11150, database is CAplus and MEDLINE.

Gastrointestinal stromal tumors (GISTs) are prototypes of stem cell factor receptor (c-KIT)-driven cancer. Two receptor tyrosine kinases, c-KIT and fms-tyrosine kinase (FLT3), are frequently mutated in AML patients, and these mutations are associated with poor prognosis. In this study, the authors discovered a multitargeted tyrosine kinase inhibitor, (6-(4-ethylpiperazin-1-yl)-2-methylpyrimidin-4-yl)(5-pyridin-4-ylthiazol-2-yl)amine Hydrochloride [2581827-29-2] (15a), with potent inhibition against single or double mutations of c-KIT developed in GISTs. Moreover, crystal structure anal. revealed the unique binding mode of (15a) with c-KIT and may elucidate its high potency in inhibiting c-KIT kinase activity. (15A) inhibited cell proliferation and induced apoptosis by targeting c-KIT in c-KIT-mutant GIST cell lines. The antitumor effects of (15a) were also demonstrated in GIST430 and GIST patient-derived xenograft (PDX) models. Further studies demonstrated that (15a) inhibited the proliferation of c-KIT- and FLT3-driven AML cells in vitro and in vivo. The results of this study suggest that (15a) may be a potential anticancer drug for the treatment of GISTs and AML.

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