Indole Building Blocks

Zheng, Qi published the artcileVinylation of the indole 3-position via palladium-catalyzed cross-coupling, Quality Control of 149108-61-2, the publication is Heterocycles (1994), 37(3), 1761-72, database is CAplus.

The palladium-catalyzed cross-coupling between 3-indoleboronic acids and vinyl triflates is an excellent method for the regioselective introduction of vinyl groups into the indole 3-position. The regioselectivity of the enolization of N-substituted 3-piperidones, as dictated by the nitrogen substituent, is far greater than previously reported. N-tosyl-3-indoleboronic acids can be easily synthesized using the mercuration-boronation method.

Heterocycles 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 C10H14O, Quality Control 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

Kim, Soo Lim published the artcileSynthesis and biological evaluation of anilide derivatives as epidermal growth factor receptor L858R / T790M and L858R / T790M / C797S inhibitors, Name: 2-(5-Fluoro-2-hydroxyphenyl)-2-(1-oxoisoindolin-2-yl)-N-(thiazol-2-yl)acetamide, the publication is Bulletin of the Korean Chemical Society (2022), 43(8), 1032-1036, database is CAplus.

Development of a mutant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor is important for the treatment of various cancers. Third-generation EGFR tyrosine kinase inhibitors (TKIs) have been clin. used by targeting T790M specifically but are recently known to induce T790M/C797S mutation after the treatment. Therefore, there is an unmet need to develop novel kinase inhibitors targeting the mutant EGFRs. Here, we designed and synthesized 16 analogs by hybridizing EAI045 (1) and 3′,4′,5′-trihydroxyflavone (2) and identified 9a, 9b, and 20b as EGFR L858R/T790M/C797S mutant inhibitors. In addition, we found that 10a and 10b can inhibit both L858R/T790M and L858R/T790M/C797S. Mol. docking study on a plausible binding mode of the compounds is also provided.

Bulletin of the Korean Chemical Society 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, Name: 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

Tian, Fei published the artcileCatalytic asymmetric dipolar cycloadditions of indolyl delocalized metal-allyl species for the enantioselective synthesis of cyclopenta [b]indoles and pyrrolo[1,2-a]indoles, Application of 5-Fluoro-1H-indole-2-carbaldehyde, the publication is Science China: Chemistry (2021), 64(1), 34-40, database is CAplus.

Herein, a novel indolyl substituted metal-allyl zwitterionic intermediates through the decarboxylation of conveniently available vinyl indoloxazolidones, which could be regarded as two types of dipolar species through the anionic delocalization was disclosed. The palladium-π-allyl species tended to served as an all-carbon 1,3-dipole in the asym. [3+2] cycloaddition with electron-deficient alkenes, which furnished polysubstituted cyclopenta[b]indoles I [R¹ = H, 7-F, 7-Cl, etc.; R² = Ph, 1-naphthyl, 2-furanyl, etc.; R³ = CN, CO₂Me] with high regio- and stereoselectivities. Meanwhile, the iridium-π-allyl species was recognized as an aza-1,3-dipole in asym. [3+2] cycloaddition with in situ generated C1 ammonium enolates, afforded pyrrolo[1,2-a]indoles II [R¹ = H, 7-F, 7-Cl, etc.; R⁴ = CH:CHCH₃, Ph, 3-thienyl, etc.] with high diastereo- and enantioselectivities. In addition, the dipolar cycloadditions could be easily scaled-up and several synthetic transformations of the cycloadducts were demonstrated for the rapid synthesis of diverse chiral polycyclic indoles.

Science China: Chemistry 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 C9H8BrF3, Application of 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

Chen, Huayan published the artcileDiscovery of 3-Substituted 1H-Indole-2-carboxylic Acid Derivatives as a Novel Class of CysLT₁ Selective Antagonists, Name: Ethyl 7-methoxy-1H-indole-2-carboxylate, the publication is ACS Medicinal Chemistry Letters (2016), 7(3), 335-339, database is CAplus and MEDLINE.

The indole I was identified as a novel and highly potent and selective CysLT₁ antagonist with IC₅₀ values of 0.0059±0.0011 and 15±4 μM for CysLT₁ and CysLT₂, resp.

ACS Medicinal Chemistry Letters 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, Name: Ethyl 7-methoxy-1H-indole-2-carboxylate.

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

Jiang, Biao published the artcileSynthesis of indolylpyrimidines via cross-coupling of indolylboronic acid with chloropyrimidines: facile synthesis of meridianin D, Application In Synthesis of 149108-61-2, the publication is Heterocycles (2000), 53(7), 1489-1498, database is CAplus.

Palladium catalyzed cross-coupling reaction of 3-indolylboronic acid with 2,4-dichloropyrimidines proceeded regioselectively to yield indolyl- or bis(indolyl)pyrimidines in high yield, depending on the projection of 3-indolylboronic acid. The marine indole alkaloid meridianin D and an analog were synthesized via the palladium catalyzed cross-coupling reaction as a key step.

Heterocycles 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, Application In Synthesis 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

Xiong, W.-N. published the artcileSynthesis of Novel Analogues of Marine Indole Alkaloids: Mono(indolyl)-4-trifluoromethylpyridines and Bis(indolyl)-4-trifluoromethylpyridines as Potential Anticancer Agents, Related Products of indole-building-block, the publication is Bioorganic & Medicinal Chemistry (2001), 9(7), 1773-1780, database is CAplus and MEDLINE.

Mono(indolyl)-4-trifluoromethylpyridines and bis(indolyl)-4-trifluoromethylpyridines were synthesized using Suzuki cross-coupling reaction between 2-chloro-4-trifluoromethylpyridine 9,2,6-dichloro-4-trifluoromethylpyridine or 2,6-dichloro-3-cyano-4-trifluoromethylpyridine 23 and N-tosyl-3-indolylboronic acid. They were evaluated for cytotoxic activity against P388 and A-549 cells with IC₅₀ values. 4-Trifluoromethyl-2,6-bis[3′-(N-tosyl-6′-methoxylindolyl)]pyridine (I) was identified as the most potent in this series. The synthesis and anticancer activities of the mono(indolyl)-4-trfluoromethylpyridines and bis(indolyl)-4-trifluoromethylpyridines are reported.

Bioorganic & Medicinal 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 C7H10BNO4S, 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

Jiang, B. published the artcileA highly stereoselective synthesis of indolyl N-substituted glycines, Recommanded Product: (1-tosyl-1H-Indol-3-yl)boronic acid, the publication is Tetrahedron Letters (2001), 42(13), 2545-2547, database is CAplus.

Optically active N-substituted α-indolylglycines were synthesized with high diastereoselectivity by Mannich reaction of an indolylboronic acid with glyoxylic acid using (R)-α-methylbenzylamine as the chiral auxiliary. The absolute configuration of one of the products was determined by a single-crystal x-ray anal.

Tetrahedron Letters 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, Recommanded Product: (1-tosyl-1H-Indol-3-yl)boronic acid.

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

Jiang, B. published the artcileSynthesis and cytotoxicity evaluation of novel indolylpyrimidines and indolylpyrazines as potential antitumor agents, Computed Properties of 149108-61-2, the publication is Bioorganic & Medicinal Chemistry (2001), 9(5), 1149-1154, database is CAplus and MEDLINE.

Novel indolylpyrimidines and indolylpyrazines have been synthesized as potential antitumor agents. They were screened in a panel of 60 human tumor cell lines in vitro. Several compounds exhibited efficiently cytotoxic activities with GI₅₀ values in the low micromolar range against a variety of human cancer cell lines. 2,4-Bis(3′-indolyl)pyrimidine displayed selective cytotoxic activity against IGROV1 tumor cell line with the GI₅₀ value below 0.01 μM.

Bioorganic & Medicinal 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, 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

Wan, Shanhe published the artcileInsight into binding mechanisms of EGFR allosteric inhibitors using molecular dynamics simulations and free energy calculations, Quality Control of 1942114-09-1, the publication is Journal of Biomolecular Structure and Dynamics (2019), 37(16), 4384-4394, database is CAplus and MEDLINE.

Lung cancer is the leading cause of cancer death, and epidermal growth factor receptor (EGFR) kinase domain mutations are a common cause of non-small-cell lung cancer (NSCLC), a major subtype of lung cancers. Patients harboring most of these mutations respond well to the EGFR inhibitors Gefitinib and Erlotinib initially, but soon develop resistance to them due to the emergence of the gatekeeper mutation T790M. The new-generation inhibitors such as AZD9291, HM61713, CO-1686 and WZ4002 can overcome T790M through covalent binding to Cys 797, but ultimately lose their efficacy upon the emergence of the C797S mutation that abolishes the covalent bonding. Allosteric inhibitors EAI001 and EAI045 are a new type of EGFR inhibitors that bind to EGFR away from the ATP-binding site and not relying on Cys 797. In this study, mol. dynamics simulations and free energy calculations were carried out on EAI001 and EAI045 in complex with EGFR, revealing the detailed inhibitory mechanism of EAI001 and EAI045 as EGFR allosteric inhibitor, which was expected to provide a basis for rational drug design of the 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 C15H14Cl2S2, Quality Control of 1942114-09-1.

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

Dufour, Marine published the artcileMechanism-Based Inhibition of Quinone Reductase 2 (NQO2): Selectivity for NQO2 over NQO1 and Structural Basis for Flavoprotein Inhibition, Recommanded Product: 5-Methoxy-1,2-dimethyl-3-[(4-nitrophenoxy)methyl]indole-4,7-dione, the publication is ChemBioChem (2011), 12(8), 1203-1208, database is CAplus and MEDLINE.

A role for the flavoprotein NRH:quinone oxidoreductase 2 (NQO2, QR2) in human diseases such as malaria, leukemia and neurodegeneration has been proposed. In order to explore the potential of NQO2 as a therapeutic target, we have developed potent and selective mechanism-based inhibitors centered on the indolequinone pharmacophore. The compounds show remarkable selectivity for NQO2 over the closely related flavoprotein NQO1, with small structural changes defining selectivity. Biochem. studies confirmed the mechanism-based inhibition, whereas x-ray crystallog. and mass spectrometry revealed the nature of the inhibitor interaction with the protein. These indolequinones represent the first mechanism-based inhibitors of NQO2, and their novel mode of action involving alkylation of the flavin cofactor, provides significant advantages over existing competitive inhibitors in terms of potency and irreversibility, and will open new opportunities to define the role of NQO2 in disease.

ChemBioChem published new progress about 192820-78-3. 192820-78-3 belongs to indole-building-block, auxiliary class Fused/Partially Saturated Cycles,Dihydroindoles, name is 5-Methoxy-1,2-dimethyl-3-[(4-nitrophenoxy)methyl]indole-4,7-dione, and the molecular formula is C18H16N2O6, Recommanded Product: 5-Methoxy-1,2-dimethyl-3-[(4-nitrophenoxy)methyl]indole-4,7-dione.

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