November 2022 - Page 42 of 81 - Indole Building Blocks

Nakamura, Hideshi’s team published research in Tetrahedron Letters in 41 | CAS: 149108-61-2

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, Safety of (1-tosyl-1H-Indol-3-yl)boronic acid.

Nakamura, Hideshi published the artcileConvergent and short-step syntheses of dl-Cypridina luciferin and its analogs based on Pd-mediated cross couplings, Safety of (1-tosyl-1H-Indol-3-yl)boronic acid, the publication is Tetrahedron Letters (2000), 41(13), 2185-2188, database is CAplus.

(±)-Cypridina luciferin and its analogs I (X = NH, O, S) were synthesized from 2-aminopyrazine by an eight-step method that included two regio-selective Pd-mediated cross couplings, and their chemi- and bioluminescent activities were compared. Analogs having a 3-benzofuranyl or a 3-benzothienyl group in the place of a 3-indolyl group showed luciferase affinities similar to Cypridina luciferase but with a lower luminescent efficiency, suggesting that the NH group is unimportant for mol. recognition whereas the indolyl group is crucial for efficient luminescence.

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, Dengyou’s team published research in Bioorganic & Medicinal Chemistry in 20 | CAS: 837392-64-0

Bioorganic & Medicinal Chemistry published new progress about 837392-64-0. 837392-64-0 belongs to indole-building-block, auxiliary class Indoline,Boronic acid and ester,Amide,Boronate Esters, name is 5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)indolin-2-one, and the molecular formula is C12H23N3S, Category: indole-building-block.

Zhang, Dengyou published the artcileDiscovery of novel 2-aminopyridine-3-carboxamides as c-Met kinase inhibitors, Category: indole-building-block, the publication is Bioorganic & Medicinal Chemistry (2012), 20(17), 5169-5180, database is CAplus and MEDLINE.

A series of 2-aminopyridine-3-carboxamide derivatives against c-Met were designed and synthesized by employing bioisosteric replacement of heterocyclic moieties with the amide bond. The structure-activity relationship (SAR) at various positions of the scaffold was explored. In this study, a promising compound (S)-24o (I) with a c-Met IC₅₀ of 0.022 μM was identified. The compound exhibited dose-dependent inhibition of the phosphorylation of c-Met as well as downstream signaling in EBC-1 cells. Furthermore, the interactive binding model of (S)-24o with c-Met was elucidated by virtue of a mol. modeling study.

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

Patel, Harun M.’s team published research in Journal of Biomolecular Structure and Dynamics in 39 | CAS: 1942114-09-1

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 C19H14FN3O3S, Computed Properties of 1942114-09-1.

Patel, Harun M. published the artcileIn silico search of triple mutant T790M/C797S allosteric inhibitors to conquer acquired resistance problem in non-small cell lung cancer (NSCLC): a combined approach of structure-based virtual screening and molecular dynamics simulation, Computed Properties of 1942114-09-1, the publication is Journal of Biomolecular Structure and Dynamics (2021), 39(4), 1491-1505, database is CAplus and MEDLINE.

Third generation EGFR inhibitor osimertinib was approved as the first-line treatment for EGFR T790M mutation-pos. Non-Small Cell Lung Cancer (NSCLC) patients in 2017. However, EGFR tertiary Cys797 to Ser797 (C797S) point mutation emanate rapidly after treatment of osimertinib, which is undruggable mutation to the all existing drugs. Recently, EAI045 fourth-generation allosteric EGFR inhibitor has been reported, which binds away from the ATP-binding site and not rely on Cys 797 binding. Here, we are reporting compound ZINC20531199 by virtual based screening studies as allosteric inhibitor to overcome the EGFR T790M/C797S Tyrosine Kinase (TK) mutation problem. Mol. Dynamics simulation for 10 ns further suggested that docked compound ZINC20531199 was stable into the allosteric pocket of the C797S EGFR tyrosine kinase. In silico pharmacokinetic predictions of the virtually screened compounds are within the defined range described for human use. Results indicate that the virtual screened compounds could be potential leads for the further development of new allosteric EGFR T790M/C797S inhibitors to overcome the problem of drug resistance.

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

Wesche, Frank’s team published research in Journal of Medicinal Chemistry in 61 | CAS: 167015-84-1

Journal of Medicinal Chemistry 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 C18H28N2O7, Recommanded Product: tert-Butyl 3-(2-aminoethyl)-1H-indole-1-carboxylate.

Wesche, Frank published the artcileCombined approach of backbone amide linking and on-resin N-methylation for the synthesis of bioactive and metabolically stable peptides, Recommanded Product: tert-Butyl 3-(2-aminoethyl)-1H-indole-1-carboxylate, the publication is Journal of Medicinal Chemistry (2018), 61(9), 3930-3938, database is CAplus and MEDLINE.

Rhabdopeptides are a large class of nonribosomal peptides from the bacteria Xenorhabdus and Photorhabdus with low micromolar activity against different protozoa, which are the causative agents of several tropical diseases. The development of a facile and flexible synthesis combining backbone amide linking with on-resin peralkylation for the synthesis of permethylated rhabdopeptides is described. This strategy allows the fast generation of permethylated naturally occurring and artificial rhabdopeptides for a structure-activity study. Furthermore, in vitro experiments revealed their superior properties regarding their stability and passive membrane diffusion.

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

Jang, Ye Jin’s team published research in Antiviral Research in 107 | CAS: 220943-23-7

Antiviral Research 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, Application In Synthesis of 220943-23-7.

Jang, Ye Jin published the artcileSynthesis and anti-influenza virus activity of 4-oxo- or thioxo-4,5-dihydrofuro[3,4-c]pyridin-3(1H)-ones, Application In Synthesis of 220943-23-7, the publication is Antiviral Research (2014), 66-75, database is CAplus and MEDLINE.

A series of dihydrofuropyridinones I (X = O, S; R¹ = H, Me; R² = Me, Ph; R³ = 5-fluoro-3-indolyl, 2-thienyl, 3-furyl, 3-benzothienyl, etc.) has been synthesized under conventional thermal and microwave irradiation conditions. To investigate the structure-activity relationships, two dozens of the hit analogs were synthesized. One of the hit compounds, I (X = S; R¹ = H; R² = Me; R³ = 5-fluoro-3-indolyl), had half-maximal effective concentrations of 17.4-21.1 μM against influenza A/H1N1, A/H3N2 and B viruses without any cellular toxicity at 900 μM. Among the products, I (X = S; R¹ = H; R² = Me; R³ = 2-benzothienyl, 3-thienyl, 2-thienyl, 5-Me-2-thienyl) and I (X = S; R¹ = R² = Me; R³ = 3-Me-2-thienyl) had anti-influenza viral activity comparable or superior to that of the initial hit. Based on a mode-of-action study, these compounds did not affect virus entry or RNA replication. Instead, they suppressed viral neuraminidase activity. This study is the first to demonstrate that dihydrofuropyridinones could serve as lead compounds for the discovery of alternative influenza virus inhibitors.

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

Abdelbaset, Mahmoud S.’s team published research in Bioorganic & Medicinal Chemistry in 27 | CAS: 1942114-09-1

Bioorganic & Medicinal Chemistry 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.

Abdelbaset, Mahmoud S. published the artcileDiscovery of novel thienoquinoline-2-carboxamide chalcone derivatives as antiproliferative EGFR tyrosine kinase inhibitors, Name: 2-(5-Fluoro-2-hydroxyphenyl)-2-(1-oxoisoindolin-2-yl)-N-(thiazol-2-yl)acetamide, the publication is Bioorganic & Medicinal Chemistry (2019), 27(6), 1076-1086, database is CAplus and MEDLINE.

Novel thienoquinoline carboxamide-chalcone derivatives were prepared via the cyclization of acylated chalcones and 2-mercaptoquinoline-3-carbaldehyde in DMF with K₂CO₃. Thienoquinolines 9a-f, h exhibited promising antiproliferative effect against all the tested cell lines and gave a significant activity as EGFR inhibitors, with IC₅₀ values ranging from 0.5 and 3.2 μM, and compounds 9e and 9f being the most active of the series. They also showed better activity than Erlotinib against melanoma cancer cell line A375. Moreover, compound 9f influenced pre G1 apoptosis and cell cycle arrest at G2/M phase. The binding mode of the best EGFR inhibitor 9e in the EGFR active site revealed that the thienoquinoline ring occupied the ATP-binding site while the chalcone moiety is located in the allosteric site and is responsible for the enhanced activity of these compounds

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

Swaminathan, S.’s team published research in Indian Journal of Chemistry in 1964 | CAS: 1009-27-4

Indian Journal of Chemistry published new progress in CAplus about 1009-27-4, 1009-27-4 belongs to class indole-building-block, name is 2-Ethoxy-1H-indole, and the molecular formula is C10H11NO, Recommanded Product: 2-Ethoxy-1H-indole.

Swaminathan, S. published the artcileSynthesis of ethyl 1-acetyl-2-(3-indolylmethyl)carbazate. An analog of Nα-acetyltryptophan ethyl ester, Recommanded Product: 2-Ethoxy-1H-indole, the main research area is .

Indole-3-carboxaldehyde (5 g.) in 100 ml. EtOH was added to a solution of 2.69 g. NH2NHAc in 10 ml. H2O containing 1 drop HOAc, and the mixture refluxed 2 hrs. to yield 4.5 g. 3-indolealdehyde acetohydrazone (I), m. 253-5° (EtOH). I (1 g.) in 150 ml. EtOH was hydrogenated 2.5 hrs. at 50 psi over Pd-BaCO3 to yield 0.75 g. 1-acetyl-2-(3-indolylmethyl)hydrazine (II), m. 147.5-8.5° (EtOAc-petr. ether). Et3N (1 g.) in 10 ml. C6H6 was added to a solution of 1 g. II in 100 ml. C6H6, followed by dropwise addition during 30 min. of a solution of 0.6 g. ClCO2Et in 29 ml. C6H6, and the mixture stirred 3 hrs., kept overnight, and worked up to yield 1.1 g. Et 1-acetyl-2-(3-indolylmethyl)carbazate (III), m. 91-2° (C6H6). III was of interest as a potential tryptophan antagonist. A mixture of 0.5 g. II in 20 ml. 40% alc. NaOH was refluxed 6 hrs., EtOH removed in vacuo, and the residue diluted with H2O to yield 0.275 g. 3-indolealdazine (IV), m.p. and mixed m.p. 310-12°. IV (0.5 g.) was also obtained by refluxing 1 g. I with 40 ml. 20% alc. NaOH. A mixture of 1.5 g. indole-3-aldehyde, 0.5 g. 98-100% N2H4.H2O, 10 ml. EtOH, and a drop HOAc was refluxed 1 hr. and cooled to yield 1.2 g. IV, m. 310-12° (Me2CO).

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

Florvall, Lennart’s team published research in Journal of Medicinal Chemistry in 1986 | CAS: 41910-64-9

Journal of Medicinal Chemistry published new progress about monoamine oxidase inhibitor aminoethylindole; neuron selective aminoethylindole. 41910-64-9 belongs to class indole-building-block, name is 4-Chloroindoline, and the molecular formula is C8H8ClN, Product Details of C8H8ClN.

Florvall, Lennart published the artcileSelective monoamine oxidase inhibitors. 3. Cyclic compounds related to 4-aminophenethylamine. Preparation and neuron-selective action of some 5-(2-aminoethyl)-2,3-dihydroindoles, Product Details of C8H8ClN, the main research area is monoamine oxidase inhibitor aminoethylindole; neuron selective aminoethylindole.

Nine (aminoethyl)dihydroindoles I (R = Me, Et; R1, R3 = H, Me; R2 = H, Cl, Me; R4 = H, Et) were prepared and tested as monoamine oxidase (MAO) inhibitors in vitro and in vivo. I are selective MAO-A inhibitors in vitro, the most active compounds, 5-[1-(2-aminopropyl)]-2,3-dihydro-4-methylindole acetate (II), 5-[1-(2-aminopropyl)]-4-chloro-2,3-dihydroindole acetate, 5-[1-(2-aminopropyl)]-2,3-dihydro-1-ethyl-4-methylindole tartrate (III), 5-[1-(2-aminopropyl)]-2,3-dihydro-1-ethyl-6-methylindole tartrate, and 5-[1-(2-aminobutyl)]-4-chloro-2,3-dihydroindole acetate being equipotent with amiflamine. II, III, 5-[1-(2-aminopropyl)]-2,3-dihydroindole acetate (IV), and 5-[1-(2-amino-2-methylpropyl)]-2,3-dihydroindole acetate were very potent inhibitors of MAO in serotonergic and/or noradrenergic nerve terminals in the rat brain in vivo, inhibiting MAO within these neurons at doses 1/10 of those required to inhibit MAO in other neurons or cells. IV was also a potent and selective inhibitor of MAO within dopaminergic nerve terminals in vivo.

Lavrenov, Sergei N.’s team published research in Synthesis in 2002-02-28 | CAS: 136818-66-1

Synthesis published new progress about methyl nitro indole carboxylate nitration; indoline carboxylic acid methyl ester nitro preparation. 136818-66-1 belongs to class indole-building-block, name is Methyl 6-nitro-1H-indole-2-carboxylate, and the molecular formula is C10H8N2O4, COA of Formula: C10H8N2O4.

Lavrenov, Sergei N. published the artcileSynthesis of methyl 5- and 6-nitroindole-2-carboxylates by nitration of indoline-2-carboxylic acid, COA of Formula: C10H8N2O4, the main research area is methyl nitro indole carboxylate nitration; indoline carboxylic acid methyl ester nitro preparation.

Indoline-2-carboxylic acid was transformed into 6-nitroindoline-2-carboxylic acid, the Me ester of which was easily dehydrogenated by DDQ to Me 6-nitroindole-2-carboxylate (total yield: 67%). Me 5-nitroindole-2-carboxylate was obtained by the nitration of Me 1-acetylindoline-2-carboxylate acid followed by dehydrogenation with MnO2 in toluene in 40% total yield.

Benghiat, Eric’s team published research in Journal of Heterocyclic Chemistry in 1983-04-30 | CAS: 5654-92-2

Journal of Heterocyclic Chemistry published new progress about indolylmethylthiodeoxyadenosine; adenosine indolylmethylthiodeoxy. 5654-92-2 belongs to class indole-building-block, name is N,N-Dimethyl-1-(1H-pyrrolo[2,3-b]pyridin-3-yl)methanamine, and the molecular formula is C10H13N3, Synthetic Route of 5654-92-2.

Benghiat, Eric published the artcileSynthesis of S-3-indolemethyl derivatives of 5′-deoxy-5′-thioadenosine, Synthetic Route of 5654-92-2, the main research area is indolylmethylthiodeoxyadenosine; adenosine indolylmethylthiodeoxy.

The title compounds (I; R = H, Me) were prepared by reaction of the appropriate 3-indolemethyl thioacetate with 5′-deoxy-5′-chloroadenosine in basic media. 5′-Deoxy-5′-(3-indolemethylthio)adenosines unsubstituted at the indolic nitrogen, cannot be prepared via this route due to facile conversion of the precursor 3-indolemethylthiol derivative to the corresponding 3,3′-diindolemethyl sulfide.