Month: November 2022

Kraynack, Erica A. published the artcileAn improved procedure for the regiospecific synthesis of electron deficient 4- and 6-substituted isatins, Related Products of indole-building-block, the main research area is isatin electron deficient regiospecific preparation; nitrochlorobenzene substitution malonate; chloroisatin regiospecific preparation; benzoylisatin regiospecific preparation.

The regiospecific synthesis of C-4 and C-6 substituted isatins I (R = H, Cl; R1 = H, Cl; R2 = H, Cl, Bz, 4-MeC6H4CO, 4-ClC6H4CO, 4-MeOC6H4CO) in four steps from halonitrobenzenes II (X = Cl, F) was investigated for a variety of substrates. The procedure makes use of readily available, easily handled materials and in most cases purification of neither intermediates nor final products is required. Yields of isatins I are between 26 and 75%. Improved yields of known isatins are reported as well as the syntheses of previously unreported isatins. This method, taken together with known procedures, provides for the synthesis of the full complement of isatin regioisomers.

Tetrahedron Letters published new progress about Regiochemistry. 71293-59-9 belongs to class indole-building-block, name is 5,6-Dichloroindolin-2-one, and the molecular formula is C8H5Cl2NO, Related Products of indole-building-block.

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

McKew, John C. published the artcileInhibition of Cytosolic Phospholipase A2α: Hit to Lead Optimization, Quality Control of 69622-40-8, the main research area is indole derivative preparation structure phospholipase A2 inhibitor.

Compound (I) was previously reported to be a potent inhibitor of cPLA2α in both artificial monomeric substrate and cell-based assays. However, I was inactive in whole blood assays previously used to characterize cyclooxygenase and lipoxygenase inhibitors. The IC50 of I increased dramatically with cell number or lipid/detergent concentration In an attempt to insert an electrophilic ketone between the indole and benzoic acid moieties, the authors discovered that increasing the distance between the two moieties gave a compound with activity in the GLU (7-hydroxycoumarinyl-γ-linolenate) micelle assay, which contains lipid and detergent. Extensive structure-activity relationship work around this lead identified a potent pharmacophore for cPLA2α inhibition. The IC50s between the GLU micelle and rat whole blood assays correlated highly. No correlation was found for other parameters, including lipophilicity or acidity of the required acid functionality. Three compounds emerged as potent, selective inhibitors of cPLA2α and represent well-validated starting points for further optimization.

Journal of Medicinal Chemistry published new progress about Pharmacophores. 69622-40-8 belongs to class indole-building-block, name is 2-(tert-Butyl)-5-chloro-1H-indole, and the molecular formula is C12H14ClN, Quality Control of 69622-40-8.

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Traxler, Peter M. published the artcile4-(Phenylamino)pyrrolopyrimidines: Potent and Selective, ATP Site Directed Inhibitors of the EGF-Receptor Protein Tyrosine Kinase, Related Products of indole-building-block, the main research area is phenylamino pyrrolopyrimidine EGFRPTK inhibitor preparation SAR.

Using a pharmacophore model for ATP-competitive inhibitors interacting with the active site of the EGF-R protein tyrosine kinase (PTK), 4-(phenylamino)-7H-pyrrolo[2,3-d]pyrimidines have been identified as a novel class of potent EGF-R protein tyrosine kinase inhibitors. In an interactive process, this class of compounds was then optimized. The most potent compounds of this series inhibited the EGF-R PTK with IC50 values in the low nanomolar range. High selectivity toward a panel of nonreceptor tyrosine kinases (c-Src, v-Abl) and serine/threonine kinases (PKC α, PKA) was observed Kinetic anal. revealed competitive type kinetics relative to ATP. In cells, EGF-stimulated cellular tyrosine phosphorylation was inhibited by 4 compounds at IC50 values between 0.1 and 0.4 μM, whereas PDGF-induced tyrosine phosphorylation was not affected by concentrations up to 10 μM. In addition, these compounds were able to selectively inhibit c-fos mRNA expression in EGF-dependent cell lines with IC50 values between 0.1 and 2 μM, but did not affect c-fos mRNA induction in response to PDGF or PMA (IC50 >100 μM). Proliferation of the EGF-dependent MK cell line was inhibited with similar IC50 values. From SAR studies, a binding mode for 4-(phenylamino)-7H-pyrrolo[2,3-d]pyrimidines as well as for the structurally related 4-(phenylamino)quinazolines at the ATP-binding site of the EGF-R tyrosine kinase is proposed. 4-(Phenylamino)-7H-pyrrolo[2,3-d]pyrimidines therefore represent a new class of highly potent tyrosine kinase inhibitors which preferentially inhibit the EGF-mediated signal transduction pathway and have the potential for further evaluation as anticancer agents.

Journal of Medicinal Chemistry published new progress about Pharmacophores. 173458-87-2 belongs to class indole-building-block, name is 4-CHloro-6,7,8,9-Tetrahydro-5H-Pyrimido[4,5-B]Indole, and the molecular formula is C10H10ClN3, Related Products of indole-building-block.

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Sall, Daniel J. published the artcileUse of Conformationally Restricted Benzamidines as Arginine Surrogates in the Design of Platelet GPIIb-IIIa Receptor Antagonists, Quality Control of 104291-81-8, the main research area is bicyclic amidine preparation platelet receptor antagonist; glycoprotein platelet receptor antagonist bicyclic amidine.

The use of 5,6-bicyclic amidines, e.g., I, as arginine surrogates in the design of a novel class of potent platelet glycoprotein IIb-IIIa receptor antagonists is described. The addnl. conformational restriction offered by the bicyclic nucleus results in 20-400-fold increases in potency compared to the freely flexible, acyclic benzamidine counterpart. The design, synthesis, structure-activity relationships (SAR), and in vitro activity of this novel class of GPIIb-IIIa antagonists are presented.

Journal of Medicinal Chemistry published new progress about Blood platelet. 104291-81-8 belongs to class indole-building-block, name is Ethyl 6-cyano-1H-indole-2-carboxylate, and the molecular formula is C12H10N2O2, Quality Control of 104291-81-8.

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Ono, Shin’ichiro published the artcilePreparation and pharmacological evaluation of novel glycoprotein (Gp) IIb/IIIa antagonists. 2. Condensed heterocyclic derivatives, Application of Ethyl 6-cyano-1H-indole-2-carboxylate, the main research area is benzofuran preparation structure integrin antagonist antithrombotic; platelet aggregation inhibitor integrin receptor antagonist; prodrug amidinobenzofuran integrin antagonist antithrombotic.

A novel series of platelet receptor glycoprotein (Gp) IIb/IIIa antagonists with condensed heterocycles as their basic core was synthesized. In an in vitro assay, trans-4-(5-amidinobenzofuran-2-carboxamido)cyclohexyloxyacetic acid (I) and trans-3-[4-(5-amidinobenzofuran-2-carboxamido)cyclohexyl]propionic acid (II) produced marked inhibitions with IC50 values of 0.018 and 0.006 μM, resp., in a human platelet adenosine-5′-diphospate (ADP)-induced aggregation assay; they also exhibited a wide spectrum of inhibition toward major aggregation agonists (ADP, collagen, thrombin, PMA (tumor promoter) and arachidonic acid). These compounds were >2-3 orders of magnitude more effective in inhibiting platelet aggregation than human umbilical vein endothelial cell (HUVEC) binding. The oral administration of 10 mg/kg of either I and II to guinea pig, resulted in a 60% inhibition of ex vivo platelet aggregation after 5 h. Oral administration of Et trans-4-(5-amidinobenzofuran-2-carboxamido)cyclohexyloxyacetate (III) (10 mg/kg) resulted in 80% inhibition of platelet aggregation in dogs for 6 h after oral administration with a return to baseline by 24 h. Et trans-3-[4-(5-amidinobenzofuran-2-carboxamido)cyclohexyl]propionate (AR0598) produced 80% inhibition for 5 h after oral administration. Prodrug III showed a good profile in dogs with a long duration of action. III (AR0510) was selected as suitable clin. candidate for development as an orally active antithrombotic agent.

Chemical & Pharmaceutical Bulletin published new progress about Anticoagulants. 104291-81-8 belongs to class indole-building-block, name is Ethyl 6-cyano-1H-indole-2-carboxylate, and the molecular formula is C12H10N2O2, Application of Ethyl 6-cyano-1H-indole-2-carboxylate.

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Huang, Wenrong published the artcileDesign, synthesis and structure-activity relationships of benzoxazinone-based factor Xa inhibitors, Related Products of indole-building-block, the main research area is benzoxazinone derivative preparation structure Activity relationship factor Xa inhibitor.

A series of benzoxazinone derivatives was designed and synthesized as factor Xa inhibitors. We demonstrated that the naphthyl moiety in two aniline-based compounds can be replaced with benzene-fused heterobicycles and biaryls to give factor Xa inhibitors with improved trypsin selectivity. The P4 modifications lead to monoamidines which are moderately active. The prepared benzoxazinones are potent against factor Xa, retain the improved trypsin selectivity of the corresponding aniline-based compounds, and show strong antithrombotic effect dose responsively.

Bioorganic & Medicinal Chemistry Letters published new progress about Anticoagulants. 104291-81-8 belongs to class indole-building-block, name is Ethyl 6-cyano-1H-indole-2-carboxylate, and the molecular formula is C12H10N2O2, Related Products of indole-building-block.

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Kumar, A. Sanjeeva published the artcileIndium/Fe(III)- mediated regioselective β-cross-coupling aldol type addition reaction of activated alkenes with isatins/isatinimines in aqueous media, HPLC of Formula: 1677-47-0, the main research area is hydroxy oxindole regioselective preparation; alkene isatin indium iron catalyst coupling aldol addition; amino oxindole regioselective preparation; isatinimine alkene indium iron catalyst Mannich coupling.

A highly efficient and regioselective synthesis of 3-amino/hydroxy-substituted oxindole derivatives, e.g., I and II, via β-cross coupling aldol type addition reaction of activated alkenes with isatins and Mannich-type coupling of isatinimines in presence of indium/Fe (III) was described. This synthetic protocol explores a broad substrate scope and smoothly proceeds under base-free conditions and resulting products were obtained in a short reaction time with moderate to high yields.

RSC Advances published new progress about Aldol addition. 1677-47-0 belongs to class indole-building-block, name is 4,5-Dichloroisatin, and the molecular formula is C8H3Cl2NO2, HPLC of Formula: 1677-47-0.

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Hyatt, Janice L. published the artcileSelective Inhibition of Carboxylesterases by Isatins, Indole-2,3-diones, Application In Synthesis of 1677-47-0, the main research area is isatin inhibitor carboxylesterase structure activity relationship drug metabolism.

Carboxylesterases (CE) are ubiquitous enzymes thought to be responsible for the metabolism and detoxification of xenobiotics. Numerous clin. used drugs including Demerol, lidocaine, capecitabine, and CPT-11 are hydrolyzed by these enzymes. Hence, the identification and application of selective CE inhibitors may prove useful in modulating the metabolism of esterified drugs in vivo. Having recently identified benzil (diphenylethane-1,2-dione) as a potent selective inhibitor of CEs, we sought to evaluate the inhibitory activity of related 1,2-diones toward these enzymes. Biochem. assays and kinetic studies demonstrated that isatins (indole-2,3-diones), containing hydrophobic groups attached at a variety of positions within these mols., could act as potent, specific CE inhibitors. Interestingly, the inhibitory potency of the isatin compounds was related to their hydrophobicity, such that compounds with clogP values of <1.25 were ineffective at enzyme inhibition. Conversely, analogs demonstrating clogP values >5 routinely yielded Ki values in the nM range. Furthermore, excellent 3D QSAR correlates were obtained for 2 human CEs, hCE1 and hiCE. While the isatin analogs were generally less effective at CE inhibition than the benzils, the former may represent valid lead compounds for the development of inhibitors for use in modulating drug metabolism in vivo.

Journal of Medicinal Chemistry published new progress about Drug metabolism. 1677-47-0 belongs to class indole-building-block, name is 4,5-Dichloroisatin, and the molecular formula is C8H3Cl2NO2, Application In Synthesis of 1677-47-0.

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Chen, Weidong published the artcileCatalytic Aerobic Dehydrogenation of N-Heterocycles by N-Hydoxyphthalimide, Application In Synthesis of 13523-93-8, the main research area is indole preparation; indoline dehydrogenation hydoxyphthalimide catalyst; quinoline preparation; tetrahydroquinolinine aerobic dehydrogenation hydoxyphthalimide catalyst copper.

Catalytic methods for the aerobic dehydrogenation of N-heterocycles were reported. In most cases, indoles were accessed efficiently from indolines using catalytic N-hydroxyphthalimide (NHPI) as the sole additive under air. For more challenging substrates and to expand the scope to other heterocycles, a catalyst system of NHPI and copper was developed.

Advanced Synthesis & Catalysis published new progress about Dehydrogenation. 13523-93-8 belongs to class indole-building-block, name is 4-(Benzyloxy)-1-methyl-1H-indole, and the molecular formula is C16H15NO, Application In Synthesis of 13523-93-8.

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Li, Laiqiang published the artcileSite-Selective Electrochemical C-H Cyanation of Indoles, COA of Formula: C16H15NO, the main research area is carbonitrile indole green regioselective preparation; indole trimethylsilyl cyanide electrochem cyanation tris bromophenyl amine catalyst.

An electrochem. approach for the site-selective C-H cyanation of indoles to form indole-carbonitriles I [R1 = CN, Ph; R2 = Me, CN, C(O)OMe, etc.; R3 = H, 4-Me, 5-F, 6-Cl, etc.; R4 = Me, Bn, i-Pr, etc.] employing readily available TMSCN as cyano source has been developed. The electrosynthesis relied on the tris(4-bromophenyl)amine as a redox catalyst, which achieved better yield and regioselectivity. A variety of C2- and C3-cyanated indoles were obtained in satisfactory yields. The reactions were conducted in a simple undivided cell at room temperature and obviated the need for transition-metal reagent and chem. oxidant.

Organic Letters published new progress about Cyanation (C-H). 13523-93-8 belongs to class indole-building-block, name is 4-(Benzyloxy)-1-methyl-1H-indole, and the molecular formula is C16H15NO, COA of Formula: C16H15NO.

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles