M.W=200-250 | - Page 10 of 14 - Indole Building Blocks

Sall, Daniel J.’s team published research in Journal of Medicinal Chemistry in 1997-08-29 | CAS: 104291-81-8

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.

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.

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.’s team published research in Journal of Medicinal Chemistry in 1996-06-07 | CAS: 173458-87-2

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.

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.

McKew, John C.’s team published research in Journal of Medicinal Chemistry in 2006-01-12 | CAS: 69622-40-8

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.

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.

Kraynack, Erica A.’s team published research in Tetrahedron Letters in 1998-10-15 | CAS: 71293-59-9

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.

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.

Onyeibor, Onyeka’s team published research in Journal of Medicinal Chemistry in 2005-04-07 | CAS: 1677-47-0

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

Onyeibor, Onyeka published the artcileSynthesis of Some Cryptolepine Analogues, Assessment of Their Antimalarial and Cytotoxic Activities, and Consideration of Their Antimalarial Mode of Action, Safety of 4,5-Dichloroisatin, the main research area is cryptolepine analog preparation; antiplasmodial cytotoxic antimalarial cryptolepine analog preparation; beta hematin formation inhibition cryptolepine preparation.

A series of analogs of cryptolepine were synthesized and evaluated for their in vitro antiplasmodial and cytotoxic properties. The IC50 values of several compounds against Plasmodium falciparum (strain K1) were <0.1 μM, 5-10-fold lower than that of cryptolepine but their cytotoxicities were only 2-4 times greater than that of cryptolepine. Compounds with a halogen in the quinoline ring and a halogen or a nitro group in the indole ring have enhanced antiplasmodial activity. In mice infected with P. berghei, the 7-bromo-2-chloro and 2-bromo-7-nitro derivatives of cryptolepine suppressed parasitemia by >90% at doses of 25 mg kg-1 day-1 with no apparent toxicity to the mice. 2,7-Dibromocryptolepine was evaluated at several dose levels, and a dose-dependent suppression of parasitemia was seen (ED90 = 21.6 mg kg-1 day-1). The antimalarial mode of action of cryptolepine suppressed parasitemia by >90% at doses of 25 mg kg-1 day-1 with no apparent toxicity to the mice. appears to be similar to that of chloroquine and involves the inhibition of hemozoin formation. A number of analogs were assessed for their effects on the inhibition of β-hematin (hemozoin) formation, and the results were compared with their antiplasmodial activities having taken account of their predicted accumulation into the acidic parasite food vacuole. No correlation was seen (r2 = 0.0781) suggesting that the potent antimalarial activity of compounds such as 2,7-dibromocryptolepine involves other mechanisms in addition to the inhibition of hemozoin formation.

Smith, Keith’s team published research in Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry in 1999-08-21 | CAS: 69622-40-8

Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry published new progress about Carbonylation. 69622-40-8 belongs to class indole-building-block, name is 2-(tert-Butyl)-5-chloro-1H-indole, and the molecular formula is C12H14ClN, Related Products of indole-building-block.

Smith, Keith published the artcileCarbonylation of various organolithium reagents. A novel approach to heterocycles via intramolecular trapping of aromatic acyllithiums, Related Products of indole-building-block, the main research area is pivaloylaniline pivaloylaminopyridine carbonylation; pivaloyltoluidine carbonylation; cyclization carbonylation pivaloylaniline pivaloylaminopyridine; indole preparation cyclization carbonylation pivaloylaniline pivaloylaminopyridine.

Doubly lithiated N-pivaloylanilines react smoothly with carbon monoxide at 0 °C to give 3-tert-butyl-3-hydroxy-2,3-dihydro-2-indolones in good yields. Similarly, carbonylation of doubly lithiated 4-pivaloylamino- and 2-pivaloylaminopyridines at 0 °C affords the corresponding 5-aza- and 7-aza-3-tert-butyl-3-hydroxy-2,3-dihydro-2-indolones, resp., in good yields. However, carbonylation of doubly lithiated N-pivaloyl-o-toluidines takes a different course due to direct intramol. cyclization of the dilithio reagents to afford 2-tert-butylindoles without uptake of carbon monoxide.

Lu, Dong-Liang’s team published research in Organic Letters in 2019-08-02 | CAS: 69622-40-8

Organic Letters published new progress about Atropisomers. 69622-40-8 belongs to class indole-building-block, name is 2-(tert-Butyl)-5-chloro-1H-indole, and the molecular formula is C12H14ClN, Application of 2-(tert-Butyl)-5-chloro-1H-indole.

Lu, Dong-Liang published the artcileAtroposelective Construction of Arylindoles by Chiral Phosphoric Acid-Catalyzed Cross-Coupling of Indoles and Quinones, Application of 2-(tert-Butyl)-5-chloro-1H-indole, the main research area is arylindole atroposelective synthesis phosphoric acid catalyzed coupling indole quinone.

Structurally novel atropisomeric arylindole frameworks have been successfully constructed through chiral phosphoric acid-catalyzed asym. cross-coupling of indoles and quinone derivatives in a precise regioselective manner. This approach features high convergence and functional group tolerance to efficiently deliver diverse heteroaryl atropisomers with excellent enantiocontrol. The dominant formation of axial chirality but not central chirality, as the major unmet challenge for this type of reactions, was conquered by the rational and accurate modulation of the electronic and steric effects on both coupling partners. Preliminary investigation demonstrated the practicality of such axially chiral arylindoles as chiral ligands in asym. catalysis.

Kemnitzer, William’s team published research in Journal of Medicinal Chemistry in 2008-02-14 | CAS: 13523-93-8

Journal of Medicinal Chemistry published new progress about Antitumor agents. 13523-93-8 belongs to class indole-building-block, name is 4-(Benzyloxy)-1-methyl-1H-indole, and the molecular formula is C16H15NO, Application of 4-(Benzyloxy)-1-methyl-1H-indole.

Kemnitzer, William published the artcileDiscovery of 4-aryl-4H-chromenes as a new series of apoptosis inducers using a cell- and caspase-based high throughput screening assay. Structure-activity relationships of N-alkyl substituted pyrrole fused at the 7,8-positions, Application of 4-(Benzyloxy)-1-methyl-1H-indole, the main research area is aryl chromene preparation structure antitumor neoplasm.

In the continuing effort to discover and develop apoptosis inducing 4-aryl-4H-chromenes as novel anticancer agents, the authors explored the structure-activity relationship (SAR) of alkyl substituted pyrrole fused at the 7,8-positions. A Me group substituted at the nitrogen in the 7-position of the pyrrole ring led to a series of potent apoptosis inducers with potency in the low nanomolar range. These compounds were also found to be low nanomolar or subnanomolar inhibitors of cell growth, and they inhibited tubulin polymerization, indicating that methylation of the 7-position nitrogen does not change the mechanism of action of these chromenes. Compound 2 d was identified as a highly potent apoptosis inducer with an EC50 value of 2 nM and a highly potent inhibitor of cell growth with a GI50 value of 0.3 nM in T47D cells.

Chen, Jiong J.’s team published research in Journal of Medicinal Chemistry in 2000-06-15 | CAS: 71293-59-9

Journal of Medicinal Chemistry published new progress about Antiviral agents. 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.

Chen, Jiong J. published the artcileSynthesis and Antiviral Evaluation of Trisubstituted Indole N-Nucleosides as Analogues of 2,5,6-Trichloro-1-(β-D-ribofuranosyl)benzimidazole (TCRB), Related Products of indole-building-block, the main research area is ribofuranosyl chloroindole analog stereochem preparation antiviral cytomegalovirus inhibition; indole nucleoside preparation cytotoxicity virucide structure activity.

2,5,6-Trichloro-1-(β-D-ribofuranosyl)benzimidazole (TCRB) and 2-bromo-5,6-dichloro-1-(β-D-ribofuranosyl)benzimidazole (BDCRB) are nucleosides that exhibit strong and selective activity against human cytomegalovirus (HCMV). Selected polyhalogenated indole nucleosides have now been synthesized as 3-deaza analogs of the benzimidazole nucleosides using the sodium salt glycosylation method. 2-Benzylthio-1-[2-deoxy-3,5-bis-O-(4-methylbenzoyl)-β-D-erythro-pentofuranosyl]-5,6-dichloroindole was prepared stereoselectively via the coupling of a 2-deoxyribofuranosyl α-chloride derivative with the sodium salt of 2-benzylthio-5,6-dichloroindole. This compound was then elaborated into the targeted 2-benzylthio-1-(β-D-ribofuranosyl)-5,6-dichloroindole in five steps. 2,5,6-Trichloro-(1-β-D-ribofuranosyl)indole was prepared using the same synthetic route with 2,5,6-trichloroindole as the starting material. The authors were subsequently able to prepare 2,5,6-trichloro-1-(β-D-ribofuranosyl)indole in three steps using a modification of the sodium salt glycosylation method. 2-Bromo-5,6-dichloro-1-(β-D-ribofuranosyl)indole was also prepared using the same procedures. Target compounds were tested for activity against HCMV, herpes simplex virus type 1 (HSV-1), and human herpes virus six (HHV-6) and for cytotoxicity. All of the compounds were less active against HCMV than TCRB and weakly active or inactive against HSV-1 and HHV-6.

Zheng, Xudong’s team published research in Tetrahedron in 2019-11-29 | CAS: 1677-47-0

Tetrahedron published new progress about Antibacterial agents. 1677-47-0 belongs to class indole-building-block, name is 4,5-Dichloroisatin, and the molecular formula is C8H3Cl2NO2, Related Products of indole-building-block.

Zheng, Xudong published the artcileSynthesis of substituted tryptanthrin via aryl halides and amines as antitumor and anti-MRSA agents, Related Products of indole-building-block, the main research area is tryptanthrin derivative synthesis aryl halide amine antitumor anti MRSA.

The natural alkaloid, tryptanthrin (indolo[2,1-b]quinazoline-6,12-dione, I), and its analogs are found to exhibit potent antitumor and anti-MRSA activities. An efficient and convenient method has been developed for the synthesis of tryptanthrin D-ring derivatives through the reaction of substituted tryptanthrins and secondary amines in moderate to good yields. Some of the new compounds exhibited antitumor activities against the human tumor cell lines A549, HCT116 and MDA-MB-231, with mean IC50 values at low micromolar levels. In addition, some of the compounds showed excellent anti-MRSA activities and were more effective than vancomycin, with MIC values of 0.31-1.25 μg/mL for Mu50,RN4220, and Newman strains.