Month: December 2022

Lin, Shu-Yu published the artcilePhenyl Benzenesulfonylhydrazides Exhibit Selective Indoleamine 2,3-Dioxygenase Inhibition with Potent in Vivo Pharmacodynamic Activity and Antitumor Efficacy, Product Details of C9H8ClNO3S, the publication is Journal of Medicinal Chemistry (2016), 59(1), 419-430, database is CAplus and MEDLINE.

Tryptophan metabolism has been recognized as an important mechanism in immune tolerance. Indoleamine 2,3-dioxygenase plays a key role in local tryptophan metabolism via the kynurenine pathway and has emerged as a therapeutic target for cancer immunotherapy. The prior study identified Ph benzenesulfonyl hydrazide as a potent in vitro (though not in vivo) inhibitor of indoleamine 2,3-dioxygenase. Further lead optimization to improve in vitro potencies and pharmacokinetic profiles resulted in N’-(4-bromophenyl)-2-oxo-2,3-dihydro-1H-indole-5-sulfonyl hydrazide (I), which demonstrated 59% oral bioavailability and 73% of tumor growth delay without apparent body weight loss in the murine CT26 syngeneic model, after oral administration of 400 mg/kg. Accordingly, I is proposed as a potential drug lead worthy of advanced preclin. evaluation.

Journal of Medicinal Chemistry published new progress about 166883-20-1. 166883-20-1 belongs to indole-building-block, auxiliary class Indoline,Chloride,Sulfonyl chlorides,Amide, name is 1-Methyl-2-oxoindoline-5-sulfonyl chloride, and the molecular formula is C9H8ClNO3S, Product Details of C9H8ClNO3S.

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

Okubo, Ayaka published the artcileNAD(P)H dehydrogenase, quinone 1 (NQO1), protects melanin-producing cells from cytotoxicity of rhododendrol, Safety of 5-Methoxy-1,2-dimethyl-3-[(4-nitrophenoxy)methyl]indole-4,7-dione, the publication is Pigment Cell & Melanoma Research (2016), 29(3), 309-316, database is CAplus and MEDLINE.

Summary : Rhododendrol (RD) is a potent tyrosinase inhibitor that is metabolized to RD-quinone by tyrosinase, which may underlie the cytotoxicity of RD and leukoderma of the skin that may result. We have examined how forced expression of the NAD(P)H quinone dehydrogenase, quinone 1 (NQO1), a major quinone-reducing enzyme in cytosol, affects the survival of RD-treated cells. We found that treatment of the mouse melanoma cell line B16BL6 or normal human melanocytes with carnosic acid, a transcriptional inducer of the NQO1 gene, notably suppressed the cell killing effect of RD. This effect was mostly abolished by ES936, a highly specific NQO1 inhibitor. Moreover, conditional overexpression of the human NQO1 transgene in B16BL6 led to an expression-dependent increase of cell survival after RD treatment. Our results suggest that NQO1 attenuates the cytotoxicity of RD and/or its metabolites.

Pigment Cell & Melanoma Research 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, Safety of 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

Zhao, Peng published the artcileCrystal structure of EGFR T790M/C797S/V948R in complex with EAI045, Recommanded Product: 2-(5-Fluoro-2-hydroxyphenyl)-2-(1-oxoisoindolin-2-yl)-N-(thiazol-2-yl)acetamide, the publication is Biochemical and Biophysical Research Communications (2018), 502(3), 332-337, database is CAplus and MEDLINE.

Lung cancer is the leading cause of cancer deaths. Epidermal growth factor receptor (EGFR) kinase domain mutations are a common cause of non-small cell lung cancers (NSCLCs), a major subtype of lung cancers. Patients harboring most of these mutations respond well to the anti-EGFR tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib initially, but soon develop resistance to them in about half of the cases due to the emergence of the gatekeeper mutation T790M. The third-generation TKIs such as AZD9291, HM61713, CO-1686 and WZ4002 can overcome T790M through covalent binding to the EGFR kinase through Cys 797, but ultimately lose their efficacy upon emergence of the C797S mutation that abolishes the covalent bonding. Therefore to develop new TKIs to overcome EGFR drug-resistant mutants harboring T790M/C797S is urgently demanded. EAI001 and EAI045 are a new type of EGFR TKIs that bind to EGFR reversibly and not relying on Cys 797. EAI045 in combination with cetuximab is effective in mouse models of lung cancer driven by EGFR L858R/T790M and L858R/T790M/C797S. Here we report the crystal structure of EGFR T790M/C797S/V948R in complex with EAI045, and compare it to EGFR T790M/V948R in complex with EAI001. The complex structure reveals why EAI045 binds tighter to EGFR than does EAI001, and why EAI001 and EAI045 prefer binding to EGFR T790M. The knowledge may facilitate future drug development studies targeting this very important cancer target.

Biochemical and Biophysical Research Communications 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 C14H22O2, 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

Zheng, Qi published the artcilePalladium-catalyzed cross-coupling reaction between 3-indoleboronic acids and tetrahydropyridine triflates, Application In Synthesis of 149108-61-2, the publication is Tetrahedron Letters (1993), 34(14), 2235-8, database is CAplus.

The palladium catalyzed cross-coupling reactions between 3-indoleboronic acids and vinyl triflates is a good method to introduce vinyl groups into the indole 3-position, e.g. I. The regioselectivity of the enolization of N-substituted-3-piperidones is far greater than previously reported. N-tosyl-3-indole boronic acids can be easily synthesized via mercuration-boronation method.

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 C8H5F3O3, 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

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