Month: November 2022

Chen, Wang published the artcileSynthesis and antitumor activity of Lycogarubin C and Lycogalic acid, Computed Properties of 149108-61-2, the publication is Youji Huaxue (2014), 34(4), 797-803, database is CAplus.

Lycogarubin C and lycogalic acid were first isolated independently by Steglich and Akazawa from Lycogala epidendrum in 1994. Lycogarubin C showed a potential cytotoxic activity. Lycogalic acid is an inhibitor of Hes1 dimmer of helix-loop-helix (bHLH) transcriptional repressor factor. Lycogalic acid is also the key intermediate in the biosynthesis of indolo[2,3-a]carbazole alkaloids that exhibit broad spectrum of bioactivity. Two efficient synthetic pathways of lycogarubin C and lycogalic acid were completed in this study. The first pathway included eight steps started from the com. available indole and pyrrole to produce lycogarubin C with an overall yield of 27%. The second pathway was completed in seven steps with an overall yield of 25%. The key reactions are palladium-catalyzed Suzuki-Miyaura coupling of bis-iodo or bis-triflate derivative and indolboronic acid derivatives and Hinsberg-type synthesis of di-Me N-benzyl-3,4-dihydroxypyrrole-2,5-dicarboxylate, resp. Treatment of lycogarubin C with sodium hydroxide in ethanol under refluxing followed by acidification afforded lycogalic acid quant. Lycogarubin C and lycogalic acid showed the antiproliferative activities against four human tumor cell lines of MDA-MB-231, A549, HeLa and PC3. Further study showed that lycogarubin C inhibited the activity of DNA topoisomerase 2.

Youji Huaxue published new progress about 149108-61-2. 149108-61-2 belongs to indole-building-block, auxiliary class Indole,Boronic acid and ester,Sulfamide,Benzene,Boronic Acids,Boronic Acids,Boronic acid and ester,, name is (1-tosyl-1H-Indol-3-yl)boronic acid, and the molecular formula is C15H14BNO4S, Computed Properties of 149108-61-2.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Landstrom, Evan B. published the artcileEvanPhos: a ligand for ppm level Pd-catalyzed Suzuki-Miyaura couplings in either organic solvent or water, SDS of cas: 480438-51-5, the publication is Green Chemistry (2018), 20(15), 3436-3443, database is CAplus.

A new biaryl phosphine-containing palladium complex was constructed and its usefulness in Suzuki-Miyaura cross-couplings of functionalized substrates so as to yield biaryls was evaluated. By a combination of pre-activation using DIBAL and employment of uncommon solvent EtOAc, the novel catalyst proved effective with extended bench stability at loadings in the ppm (0.1-0.5 mol%) range with highly functionalized reaction partners. Similar reactions run in water containing nanomicelles were as fast or faster. This methodol. represented an attractive green synthetic advance in highly valued Suzuki-Miyaura couplings.

Green Chemistry published new progress about 480438-51-5. 480438-51-5 belongs to indole-building-block, auxiliary class Indole,Boronic acid and ester,Sulfamide,Benzene,Boronic Acids,Boronic Acids,Boronic acid and ester,, name is (1-(Phenylsulfonyl)-1H-indol-5-yl)boronic acid, and the molecular formula is C14H12BNO4S, SDS of cas: 480438-51-5.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Landstrom, Evan B. published the artcileEvanPhos: a ligand for ppm level Pd-catalyzed Suzuki-Miyaura couplings in either organic solvent or water, COA of Formula: C15H14BNO4S, the publication is Green Chemistry (2018), 20(15), 3436-3443, database is CAplus.

A new biaryl phosphine-containing palladium complex was constructed and its usefulness in Suzuki-Miyaura cross-couplings of functionalized substrates so as to yield biaryls was evaluated. By a combination of pre-activation using DIBAL and employment of uncommon solvent EtOAc, the novel catalyst proved effective with extended bench stability at loadings in the ppm (0.1-0.5 mol%) range with highly functionalized reaction partners. Similar reactions run in water containing nanomicelles were as fast or faster. This methodol. represented an attractive green synthetic advance in highly valued Suzuki-Miyaura couplings.

Green Chemistry published new progress about 149108-61-2. 149108-61-2 belongs to indole-building-block, auxiliary class Indole,Boronic acid and ester,Sulfamide,Benzene,Boronic Acids,Boronic Acids,Boronic acid and ester,, name is (1-tosyl-1H-Indol-3-yl)boronic acid, and the molecular formula is C15H14BNO4S, COA of Formula: C15H14BNO4S.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Pieniazek, Anna published the artcileIndoxyl Sulfate Generates Free Radicals, Decreases Antioxidant Defense, and Leads to Damage to Mononuclear Blood Cells, Category: indole-building-block, the publication is Chemical Research in Toxicology (2018), 31(9), 869-875, database is CAplus and MEDLINE.

Indoxyl sulfate (IS) is a uremic toxin that has been associated with inflammation, oxidative stress as well as with the progression of chronic kidney disease (CKD). Indoxyl sulfate is a protein metabolite that is concentrated in the serum of CKD patients. IS is a well-known uremic toxin but there are very few reports on the effect of IS on cells including mononuclear cells (MNCs). We hypothesized that a high concentration of IS in CKD patients may induce changes in redox balance in the in vitro cells exposed. In the present study, we investigated the effect of indoxyl sulfate on free radical production, antioxidant capacity and protein damage in the mononuclear blood cells. As already determined, the concentrations (0.2 or 1 mM) of IS used in this study do not affect the survival rate of MNCs. For both the concentrations of indoxyl sulfate, there was an increase in superoxide and nitric oxide, and a release of other reactive oxygen species (ROS) inside the cells, as measured using fluorescent probes. However, an increase in other ROS as indicated by H2DCF-DA was found only for 1 mM of IS. Moreover, a decrease in the non-enzymic antioxidant capacity (NAC) and an increase in the superoxide dismutase activity after incubation of the cells with indoxyl sulfate were observed Furthermore, we found an increase in the levels of carbonyl compounds and peroxides in the cells treated with both the concentrations of IS. The obtained results show that indoxyl sulfate induces oxidative stress and a decrease in antioxidant defense in cells leading to lipids and proteins damage.

Chemical Research in Toxicology published new progress about 2642-37-7. 2642-37-7 belongs to indole-building-block, auxiliary class Indole,Salt,Sulfonate,Inhibitor,Inhibitor, name is Potassium 1H-indol-3-yl sulfate, and the molecular formula is C8H6KNO4S, Category: indole-building-block.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

McBriar, Mark D. published the artcileBicyclo[3.1.0]hexyl urea melanin concentrating hormone (MCH) receptor-1 antagonists: Impacting hERG liability via aryl modifications, Formula: C14H18BNO3, the publication is Bioorganic & Medicinal Chemistry Letters (2006), 16(16), 4262-4265, database is CAplus and MEDLINE.

Herein, we report the discovery of an effective strategy to modulate liabilities related to affinity of previously disclosed bicyclohexane MCHR-1 antagonists for the hERG channel. This paper describes one of several strategies incorporated to limit hERG binding via modifications of a terminal aryl group in an otherwise promising bicyclohexyl urea series.

Bioorganic & Medicinal Chemistry Letters published new progress about 837392-64-0. 837392-64-0 belongs to indole-building-block, auxiliary class Indoline,Boronic acid and ester,Amide,Boronate Esters, name is 5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)indolin-2-one, and the molecular formula is C14H18BNO3, Formula: C14H18BNO3.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Wu, Xiaoyun published the artcileMolecular mechanism study of EGFR allosteric inhibitors using molecular dynamics simulations and free energy calculations, Recommanded Product: 2-(5-Fluoro-2-hydroxyphenyl)-2-(1-oxoisoindolin-2-yl)-N-(thiazol-2-yl)acetamide, the publication is Journal of Biomolecular Structure and Dynamics (2022), 40(13), 5848-5857, database is CAplus and MEDLINE.

The epidermal growth factor receptor (EGFR) kinase inhibitors Gefitinib, Erlotinib, Afatinib and Osimertinib have been approved for the treatments of non-small cell lung cancer patients harboring sensitive EGFR mutations, but resistance arises rapidly. To date all approved EGFR inhibitors are ATP-competitive inhibitors, highlighting the need for therapeutic agents with alternative mechanisms of action. Allosteric kinase inhibitors offer a promising new therapeutic strategy to ATP-competitive inhibitors. The mutant-selective allosteric EGFR inhibitors EAI045 exhibited higher potency for EGFRL858R&T790M compared to WT, which was also effective in EGFR-mutant models including those harboring the C797S mutation. However, it was not effective as a single-agent inhibitor, and require the co-administration of the anti-EGFR antibody Cetuximab. Further efforts produced a more potent analog JBJ-04-125-02, which can inhibit cell proliferation as a single-agent inhibitor. In the present study, mol. dynamics simulations and free energy calculations were performed and revealed the detailed inhibitory mechanism of JBJ-04-125-02 as more potent EGFR inhibitor. Moreover, the energy difference between HOMO and LUMO calculated by DFT implied the higher interaction of JBJ-04-125-02 than EAI045 in the active site of the EGFR. The identified key features obtained from the mol. modeling enabled us to design novel EGFR allosteric inhibitors.

Journal of Biomolecular Structure and Dynamics published new progress about 1942114-09-1. 1942114-09-1 belongs to indole-building-block, auxiliary class Indoline,Thiazole,Fluoride,Amine,Benzene,Amide,Alcohol,Protein Tyrosine Kinase/RTK, name is 2-(5-Fluoro-2-hydroxyphenyl)-2-(1-oxoisoindolin-2-yl)-N-(thiazol-2-yl)acetamide, and the molecular formula is C9H8F2O2, Recommanded Product: 2-(5-Fluoro-2-hydroxyphenyl)-2-(1-oxoisoindolin-2-yl)-N-(thiazol-2-yl)acetamide.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Hao, Lu published the artcileDevelopment of Kilogram-Scale Synthesis of EGFR Inhibitor EAI045, COA of Formula: C19H14FN3O3S, the publication is Organic Process Research & Development (2019), 23(3), 397-402, database is CAplus.

Herein, we report a synthetic route for an EGFR inhibitor, 2-(5-fluoro-2-hydroxyphenyl)-2-(1-oxoisoindolin-2-yl) acetic acid (EAI045), using a three-step approach. This short and efficient route is the first report of a scalable process for EAI045, which employs a convergent three-component coupling strategy as the key step, producing EAI045 in good yield on kilogram scale.

Organic Process Research & Development published new progress about 1942114-09-1. 1942114-09-1 belongs to indole-building-block, auxiliary class Indoline,Thiazole,Fluoride,Amine,Benzene,Amide,Alcohol,Protein Tyrosine Kinase/RTK, name is 2-(5-Fluoro-2-hydroxyphenyl)-2-(1-oxoisoindolin-2-yl)-N-(thiazol-2-yl)acetamide, and the molecular formula is C19H14FN3O3S, COA of Formula: C19H14FN3O3S.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Dolle, Roland E. published the artcileA statistical-based approach to assessing the fidelity of combinatorial libraries encoded with electrophoric molecular tags. Development and application of tag decode-assisted single bead LC/MS analysis, Formula: C15H20N2O2, the publication is Journal of Combinatorial Chemistry (2000), 2(6), 716-731, database is CAplus and MEDLINE.

A statistical sampling protocol is described to assess the fidelity of libraries encoded with mol. tags. The methodol., termed library QA, is based on the combined application of tag decode anal. and single bead LC/MS. The phys. existence of library compounds eluted from beads is established by comparing the mol. weight predicted by tag decode with empirical measurement. The goal of sampling is to provide information on overall library fidelity and an indication of the performance of individual library synthons. The minimal sampling size n for library QA is 10× the largest synthon set. Data are reported as proportion (p) ± lower and upper boundary (lb-ub) computed at the 95% confidence level (α = 0.05). As a practical demonstration, library QA was performed on a 25 200-member library of statine-containing peptide amides (size = 40 × 63 × 10). Sampling was conducted three times at n âˆ?630 beads per run for a total of 1902 beads. The overall proportions found for the three runs were consistent with one another: p = 84.4%, lb-ub = 81.5-87.2%; p = 83.1%, lb-ub = 80.2-85.95; and p = 84.5%, lb-ub = 81.8-87.3%, suggesting the true value of p is close to 84% compound confirmation. The performance p_i of individual synthons was also computed. Corroboration of QA data with biol. screening results obtained from assaying the library against cathepsin D and plasmepsin II is discussed.

Journal of Combinatorial Chemistry published new progress about 167015-84-1. 167015-84-1 belongs to indole-building-block, auxiliary class Indols, name is tert-Butyl 3-(2-aminoethyl)-1H-indole-1-carboxylate, and the molecular formula is C15H20N2O2, Formula: C15H20N2O2.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Gindi, Natalie published the artcileFyn and argonaute 2 participate in maternal-mRNA degradation during mouse oocyte maturation, Related Products of indole-building-block, the publication is Cell Cycle (2022), 21(8), 792-804, database is CAplus and MEDLINE.

Fertilization triggers physiol. degradation of maternal-mRNAs, which are then replaced by embryonic transcripts. Ample evidence suggests that Argonaut 2 (AGO2) is a possible post-fertilization regulator of maternal-mRNAs degradation; but its role in degradation of maternal-mRNAs during oocyte maturation remains obscure. Fyn, a member of the Src family kinases (SFKs), and an essential factor in oocyte maturation, was reported to inhibit AGO2 activity in oligodendrocytes. Our aim was to examine the role of Fyn and AGO2 in degradation of maternal-mRNAs during oocyte maturation by either suppressing their activity with SU6656 – an SFKs inhibitor; or by microinjecting DN-Fyn RNA for suppression of Fyn and BCl-137 for suppression of AGO2. Batches of fifteen mouse oocytes or embryos were analyzed by qPCR to measure the expression level of nine maternal-mRNAs that were selected for their known role in oocyte growth, maturation and early embryogenesis. We found that Fyn/SFKs are involved in maintaining the stability of at least four pre-transcribed mRNAs in oocytes at the germinal vesicle (GV) stage, whereas AGO2 had no role at this stage. During in-vivo oocyte maturation, eight maternal-mRNAs were significantly degraded. Inhibition of AGO2 prevented the degreadation of at least five maternal-mRNAs, whereas inhibition of Fyn/SFK prevented degradation of at least five Fyn maternal-mRNAs and two SFKs maternal-mRNAs; pointing at their role in promoting the physiol. degradation which occurs during in-vivo oocyte maturation. Our findings imply the involvement of Fyn/SFKs in stabilization of maternal-mRNA at the GV stage and the involvement of Fyn, SFKs and AGO2 in degradation of maternal mRNAs during oocyte maturation.

Cell Cycle published new progress about 330161-87-0. 330161-87-0 belongs to indole-building-block, auxiliary class Protein Tyrosine Kinase/RTK,Src, name is SU6656, and the molecular formula is C19H21N3O3S, Related Products of indole-building-block.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Mashkani, Baratali published the artcileColony stimulating factor-1 receptor as a target for small molecule inhibitors, Related Products of indole-building-block, the publication is Bioorganic & Medicinal Chemistry (2010), 18(5), 1789-1797, database is CAplus and MEDLINE.

Imatinib, dasatinib, sunitinib, CEP-701, and PKC-412, ATP-competitive small mol. inhibitors of type III receptor tyrosine kinases c-KIT and/or FLT3, were evaluated for binding to the closely related receptor, FMS, by docking into models of inactive and active conformations of the FMS kinase domain. To confirm the docking predictions, the drugs were tested for their activity and selectivity in inhibiting cell proliferation and FMS phosphorylation upon stimulation by the FMS ligand, CSF-1. All five drugs inhibited FMS activity. Imatinib, dasatinib and CEP-701 represent three different types of interactions determining drug potency and selectivity.

Bioorganic & Medicinal Chemistry published new progress about 330161-87-0. 330161-87-0 belongs to indole-building-block, auxiliary class Protein Tyrosine Kinase/RTK,Src, name is SU6656, and the molecular formula is C19H21N3O3S, Related Products of indole-building-block.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles