Month: November 2022

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

Bartolowits, Matthew D. published the artcileDiscovery of inhibitors for proliferating cell nuclear antigen using a computational-based linked-multiple-fragment screen, Computed Properties of 167015-84-1, the publication is ACS Omega (2019), 4(12), 15181-15196, database is CAplus and MEDLINE.

Proliferating cell nuclear antigen (PCNA) is a central factor in DNA replication and repair pathways that plays an essential role in genome stability. The functional roles of PCNA are mediated through an extensive list of protein-protein interactions, each of which transmits specific information in protein assemblies. The flexibility at the PCNA-protein interaction interfaces offers opportunities for the discovery of functionally selective inhibitors of DNA repair pathways. Current fragment-based drug design methodologies can be limited by the flexibility of protein interfaces. These factors motivated an approach to defining compounds that could leverage previously identified subpockets on PCNA that are suitable for fragment-binding sites. Methodologies for screening multiple connected fragment-binding events in distinct subpockets are deployed to improve the selection of fragment combinations. A flexible backbone based on N-alkyl-glycine amides offers a scaffold to combinatorically link multiple fragments for in silico screening libraries that explore the diversity of subpockets at protein interfaces. This approach was applied to discover new potential inhibitors of DNA replication and repair that target PCNA in a multiprotein recognition site. The screens of the libraries were designed to computationally filter ligands based upon the fragments and positions to <1%, which were synthesized and tested for direct binding to PCNA. Mol. dynamics simulations also revealed distinct features of these novel mols. that block key PCNA-protein interactions. Furthermore, a Bayesian classifier predicted 15 of the 16 new inhibitors to be modulators of protein-protein interactions, demonstrating the method’s utility as an effective screening filter. The cellular activities of example ligands with similar affinity for PCNA demonstrate unique properties for novel selective synergy with therapeutic DNA-damaging agents in drug-resistant contexts.

ACS Omega 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, Computed Properties 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

Zhang, Jian published the artcileCooperative N-heterocyclic Carbene and Iridium Catalysis Enables Stereoselective and Regiodivergent [3 + 2] and [3 + 3] Annulation Reactions, Recommanded Product: 5-Fluoro-1H-indole-2-carbaldehyde, the publication is ACS Catalysis (2021), 11(7), 3810-3821, database is CAplus.

A cooperative N-heterocyclic carbene (NHC)/iridium catalysis has been developed to achieve highly stereoselective and regiodivergent [3 + 2] and [3 + 3] annulation reactions of 2-indolyl allyl carbonates I (R = H, Me; R¹ = H, OMe, Me, F, Cl; R¹ = H, OMe, Cl) with enals R³CH=CHCHO (R¹ = Ph, hexyl, 4-chlorophenyl, furan-2-yl, etc.). The use of the NHC catalyst has introduced switchable homoenolate and enolate intermediates from the common enal precursor via a simple adjustment of reaction conditions in a predictable manner. This protocol furnishes two types of biol. important products, pyrrolo[1,2-a]indoles II and pyridine[1,2-a]indoles III, with high diastereo- and enantioselectivities (up to >20:1 dr and >99% ee). Notably, all four stereoisomers of these products with two vicinal stereocenters could be afforded through permutations of the enantiomers of the two chiral catalysts. Mechanistic investigations and further computational d. functional theory calculations give an explanation of the origin of the regioselectivity. In addition, the NHC-enolate intermediate generated from formylcyclopropanes IV (R⁴ = Ph, tert-Bu, naphthalen-2-yl, etc.) was also compatible in this cooperative catalytic system and thus the arsenal of optically pure pyrrolo[1,2-a]indole products V was enriched.

ACS Catalysis 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 C18H12FN, Recommanded Product: 5-Fluoro-1H-indole-2-carbaldehyde.

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

Zhang, Huairong published the artcileIdentification of differentially expressed kinase and screening potential anticancer drugs in papillary thyroid carcinoma, Name: SU6656, the publication is Disease Markers (2016), 2832980/1-2832980/9, database is CAplus and MEDLINE.

We aim to identify protein kinases involved in the pathophysiol. of papillary thyroid carcinoma (PTC) in order to provide potential therapeutic targets for kinase inhibitors and unfold possible mol. mechanisms. The gene expression profile of GSE27155 was analyzed to identify differentially expressed genes and mapped onto human protein kinases database. Correlation of kinases with PTC was addressed by systematic literature search, GO and KEGG pathway anal. The functional enrichment anal. indicated that “mitogen-activated protein kinases pathway” expression was extremely enriched, followed by “neurotrophin signaling pathway,” “focal adhesion,” and “GnRH signaling pathway.”. MAPK, SRC, PDGFRa, ErbB, and EGFR were significantly regulated to correct these pathways. Kinases investigated by the literature on carcinoma were considered to be potential novel mol. therapeutic target in PTC and application of corresponding kinase inhibitors could be possible therapeutic tool. SRC,MAPK, and EGFR were the most important differentially expressed kinases in PTC. Combined inhibitors may have high efficacy in PTC treatment by targeting these kinases.

Disease Markers 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 C20H21ClN4O4, Name: SU6656.

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

Tamm, Christoffer published the artcileDifferential effects on cell motility, embryonic stem cell self-renewal and senescence by diverse Src kinase family inhibitors, HPLC of Formula: 330161-87-0, the publication is Experimental Cell Research (2012), 318(4), 336-349, database is CAplus and MEDLINE.

The Src family of non-receptor tyrosine kinases (SFKs) has been shown to play an intricate role in embryonic stem (ES) cell maintenance. In the present study we have focused on the underlying mol. mechanisms responsible for the vastly different effects induced by various commonly used SFK inhibitors. We show that several diverse cell types, including fibroblasts completely lacking SFKs, cannot undergo mitosis in response to SU6656 and that this is caused by an unselective inhibition of Aurora kinases. In contrast, PP2 and PD173952 block motility immediately upon exposure and forces cells to grow in dense colonies. The subsequent halt in proliferation of fibroblast and epithelial cells in the center of the colonies approx. 24 h post-treatment appears to be caused by cell-to-cell contact inhibition rather than a direct effect of SFK kinase inhibition. Interestingly, in addition to generating more homogenous and dense ES cell cultures, without any diverse effect on proliferation, PP2 and PD173652 also promote ES cell self-renewal by reducing the small amount of spontaneous differentiation typically observed under standard ES cell culture conditions. These effects could not be mirrored by the use of Gleevec, a potent inhibitor of c-Abl and PDGFR kinases that are also inhibited by PP2.

Experimental Cell Research 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 C7H7IN2O, HPLC of Formula: 330161-87-0.

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