Day: November 21, 2022

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

Askey, Hannah E. published the artcilePhotocatalytic Hydroaminoalkylation of Styrenes with Unprotected Primary Alkylamines, Synthetic Route of 167015-84-1, the publication is Journal of the American Chemical Society (2021), 143(39), 15936-15945, database is CAplus and MEDLINE.

A solution to these problems using organophotoredox catalysis, enabling a direct, modular and sustainable preparation of α-(di)substituted γ-arylamines, including challenging electron-neutral and moderately electron-rich aryl groups was reported. A broad range of functionalities were tolerated, and the reactions was run on multigram scale in continuous flow. The method was applied to a concise, protecting-group-free synthesis of the blockbuster drug Fingolimod, as well as a phosphonate mimic of its in-vivo active form (by iterative α-C-H functionalization of ethanolamine). The reaction was sequenced with an intramol. N-arylation to provided a general and modular access to valuable (spirocyclic) 1,2,3,4-tetrahydroquinolines and 1,2,3,4-tetrahydronaphthyridines. Mechanistic and kinetic studies supportes an irreversible hydrogen atom transfer activation of the alkylamine by the azidyl radical and some contribution from a radical chain. The reaction was photon-limited and exhibits a zero-order dependence on amine, azide, and photocatalyst, with a first-order dependence on styrene.

Journal of the American Chemical Society 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, Synthetic Route of 167015-84-1.

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

Tani, Masanobu published the artcileSynthetic studies on indoles and related compounds. Part 40. Regioselective and non-reductive C(3)-debromination of indole nucleus, Category: indole-building-block, the publication is Synlett (1996), 931-932, database is CAplus.

A method of debromination of 3-bromoindoles was developed. Various 3-bromoindole-2-carboxylates were treated with H₂SO₄ and LiBr in AcOH to give the corresponding C(3)-debrominated indoles in excellent yields. The same reaction with 3-bromo-N-tosylindoles gave lower yields.

Synlett published new progress about 20538-12-9. 20538-12-9 belongs to indole-building-block, auxiliary class Indole,Ester,Ether, name is Ethyl 7-methoxy-1H-indole-2-carboxylate, and the molecular formula is C10H15ClO3S, 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

Galvan, Alicia published the artcileExploiting the Multidentate Nature of Chiral Disulfonimides in a Multicomponent Reaction for the Asymmetric Synthesis of Pyrrolo[1,2-a]indoles: A Remarkable Case of Enantioinversion, Product Details of C9H6FNO, the publication is Angewandte Chemie, International Edition (2016), 55(10), 3428-3432, database is CAplus and MEDLINE.

A new multicomponent coupling reaction for the enantioselective synthesis of pyrrolo[1,2-a]indoles under the catalysis of a chiral disulfonimide is described. The high specificity of the reaction is a consequence of the multidentate character of the Bronsted acid catalyst. Insights from DFT calculations helped explain the unexpected high enantioselectivity observed with the simplest 3,3′-unsubstituted binaphthyl catalyst as a result of transition-state stabilization by a network of cooperative noncovalent interactions. The remarkable enantioinversion resulting from the simple introduction of substituents at 3- and 3′-positions, the first reported example of this phenomenon in the context of binaphthalene-derived Bronsted acid catalysis, was instead attributed to destabilizing steric interactions.

Angewandte Chemie, International Edition published new progress about 220943-23-7. 220943-23-7 belongs to indole-building-block, auxiliary class Indole,Fluoride,Aldehyde, name is 5-Fluoro-1H-indole-2-carbaldehyde, and the molecular formula is C9H6FNO, Product Details of C9H6FNO.

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

Labre, Flavien published the artcileApplication of cooperative iron/copper catalysis to a palladium-free borylation of aryl bromides with pinacolborane, Product Details of C14H18BNO2, the publication is Organic Letters (2014), 16(9), 2366-2369, database is CAplus and MEDLINE.

A new cooperative copper/iron catalysis, comprising CuI/Fe(acac)₃ mixtures modified with diamines, provides facile access to arylboronates ArBpin bromine for boron substitution in reaction of ArBr with HBpin at -10°. Use of the toxic, precious metal Pd is avoided. The mechanisms of the borylation and protodebromination side reaction, giving arenes ArH, are discussed on the basis of calculated potential energy surfaces.

Organic Letters published new progress about 642494-36-8. 642494-36-8 belongs to indole-building-block, auxiliary class Indole,Boronic acid and ester,Indole,Boronate Esters,Boronic acid and ester, name is 6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole, and the molecular formula is C14H18BNO2, Product Details of C14H18BNO2.

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

Butini, Stefania published the artcileDiscovery of a New Class of Potential Multifunctional Atypical Antipsychotic Agents Targeting Dopamine D₃ and Serotonin 5-HT_1A and 5-HT_2A Receptors: Design, Synthesis, and Effects on Behavior, COA of Formula: C12H13NO3, the publication is Journal of Medicinal Chemistry (2009), 52(1), 151-169, database is CAplus and MEDLINE.

Dopamine D₃ antagonism combined with serotonin 5-HT_1A and 5-HT_2A receptor occupancy may represent a novel paradigm for developing innovative antipsychotics. The unique pharmacol. features of 5i are a high affinity for dopamine D₃, serotonin 5-HT_1A and 5-HT_2A receptors, together with a low affinity for dopamine D₂ receptors (to minimize extrapyramidal side effects), serotonin 5-HT_2C receptors (to reduce the risk of obesity under chronic treatment), and for hERG channels (to reduce incidence of torsade des pointes). Pharmacol. and biochem. data, including specific c-fos expression in mesocorticolimbic areas, confirmed an atypical antipsychotic profile of 5i in vivo, characterized by the absence of catalepsy at antipsychotic dose.

Journal of Medicinal Chemistry published new progress about 20538-12-9. 20538-12-9 belongs to indole-building-block, auxiliary class Indole,Ester,Ether, name is Ethyl 7-methoxy-1H-indole-2-carboxylate, and the molecular formula is C12H13NO3, COA of Formula: C12H13NO3.

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

Heaner, William L. IV published the artcileIndoles via Knoevenagel-Hemetsberger reaction sequence, Related Products of indole-building-block, the publication is RSC Advances (2013), 3(32), 13232-13242, database is CAplus.

A series of substituted indoles was designed and the synthesis of the target compounds was achieved by a sequential reaction of aromatic aldehyde with Et (azido)acetate in the presence of sodium ethoxide to form a corresponding Et α-(azido)-β-(aryl)acrylate (Knoevenagel process) followed by a solvent mediated thermolysis (Hemetsberger process). The isolated yields of the Et α-azido-β-(aryl)acrylates were significantly increased when employing sacrificial electrophile Et trifluoroacetate. ¹H NMR and coupled ¹H-¹³C NMR anal. of the Et α-azido-β-arylacrylates indicate that the condensation is stereospecific-only the (Z)-isomer could be detected. Solvent mediated thermal treatment of the meta-substituted Et α-azido-β-arylacrylates resulted in the formation of both the 5-substituted indole derivatives and 7-substituted indole derivatives (the 5-regioisomer being slightly favored over the 7-regioisomer). Analogous thermal treatment of di-Et (2Z,2Z’)-3,3′-(1,3-phenylene)bis[2-(azido)acrylate] and di-Et (2Z,2Z’)-3,3′-(1,4-phenylene)bis[2-(azido)acrylate] exclusively produced pyrroloindole derivatives, di-Et 1,5-dihydropyrrolo[2,3-f]indole-2,6-dicarboxylate and di-Et 1,5-dihydropyrrolo[2,3-f]indole-2,6-dicarboxylate, resp. Results are also reported which indicate that the α-azido-β-arylacrylates can be used in the subsequent Hemetsberger indolization process without prior purification

RSC Advances published new progress about 20538-12-9. 20538-12-9 belongs to indole-building-block, auxiliary class Indole,Ester,Ether, name is Ethyl 7-methoxy-1H-indole-2-carboxylate, and the molecular formula is C12H13NO3, 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