Month: November 2022

Structure-Activity Relationship (SAR) Optimization of 6-(Indol-2-yl)pyridine-3-sulfonamides: Identification of Potent, Selective, and Orally Bioavailable Small Molecules Targeting Hepatitis C (HCV) NS4B was written by Zhang, Nanjing;Zhang, Xiaoyan;Zhu, Jin;Turpoff, Anthony;Chen, Guangming;Morrill, Christie;Huang, Song;Lennox, William;Kakarla, Ramesh;Liu, Ronggang;Li, Chunshi;Ren, Hongyu;Almstead, Neil;Venkatraman, Srikanth;Njoroge, F. George;Gu, Zhengxian;Clausen, Valerie;Graci, Jason;Jung, Stephen P.;Zheng, Yingcong;Colacino, Joseph M.;Lahser, Fred;Sheedy, Josephine;Mollin, Anna;Weetall, Marla;Nomeir, Amin;Karp, Gary M.. And the article was included in Journal of Medicinal Chemistry in 2014.Computed Properties of C9H8FN The following contents are mentioned in the article:

Nonracemic (aminosulfonyl)pyridinyl indolecarbonitriles such as I were prepared as inhibitors of the hepatitis C viral protein NS4B for use as antihepatitis C agents. The substitution patterns on the indole rings were modified to limit oxidative metabolism of the indolecarbonitriles and to avoid potential liver damage and cytochrome P₄₅₀ inhibition; the compounds were also optimized to improve their oral bioavailabilities. I was potent against the HCV 1b replicon, with an EC₅₀ value of 2 nM and a selectivity of >5000 with respect to cellular glyceraldehyde-3-phosphate dehydrogenase. I had a favorable pharmacokinetic profile with oral bioavailabilities of 62%, 78%, and 18% in rats, dogs, and monkeys, resp., and favorable tissue distribution properties (liver to plasma exposure ratio in rats of 25). This study involved multiple reactions and reactants, such as 5-Fluoro-6-methyl-1H-indole (cas: 1000343-16-7Computed Properties of C9H8FN).

5-Fluoro-6-methyl-1H-indole (cas: 1000343-16-7) belongs to indole derivatives. Indole could be stereoselectively alkylated with chiral cyclopentyl sulfone reagent. Indole plays a fundamental role for QS in E. coli, being one of the signal molecules responsible for the transcription of a variety of genes (gabT, and tnaB ASTD). Computed Properties of C9H8FN

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

Visible-Light-Mediated Aerobic Tandem Dehydrogenative Povarov/Aromatization Reaction: Synthesis of Isocryptolepines was written by Schendera, Eva;Unkel, Lisa-Natascha;Huyen Quyen, Phung Phan;Salkewitz, Gwen;Hoffmann, Frank;Villinger, Alexander;Brasholz, Malte. And the article was included in Chemistry – A European Journal in 2020.HPLC of Formula: 1215205-77-8 The following contents are mentioned in the article:

A metal-free, photoinduced aerobic tandem amine dehydrogenation/Povarov cyclization/aromatization reaction between N-aryl glycine esters and indoles leads to tetracyclic 11H-indolo[3,2-c]quinolines under mild conditions and with high yields. The reaction can be performed by using mol. iodine along with visible light, or by combining an organic photoredox catalyst with a halide anion. Mechanistic studies reveal that product formation occurs through a combination of radical-mediated oxidation steps with an iminium ion or N-haloiminium ion [4+2]-cycloaddition, and the N-heterocyclic products constitute new analogs of the antiplasmodial natural alkaloid isocryptolepine. Thus, e.g., reaction of N-(p-anisidinyl)glycine Et ester with N-Boc-indole in presence of I₂ and O₂ under blue light afforded indoloquinoline I (70%) in mixture with its deprotected derivative (22%). This study involved multiple reactions and reactants, such as tert-Butyl 7-methoxy-1H-indole-1-carboxylate (cas: 1215205-77-8HPLC of Formula: 1215205-77-8).

tert-Butyl 7-methoxy-1H-indole-1-carboxylate (cas: 1215205-77-8) belongs to indole derivatives. The indole subunit is an almost ubiquitous component of biologically active natural products, and its study has been the focus of research for decades. More than 200 indole derivatives have already been marketed as drugs or are under advanced stages of clinical trials.HPLC of Formula: 1215205-77-8

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

Autoxidation/Aldol Tandem Reaction of 2-Oxindoles with Ketones: A Green Approach for the Synthesis of 3-Hydroxy-2-Oxindoles was written by Zhang, Qing-Bao;Jia, Wen-Liang;Ban, Yong-Liang;Zheng, Yong;Liu, Qiang;Wu, Li-Zhu. And the article was included in Chemistry – A European Journal in 2016.SDS of cas: 100831-25-2 The following contents are mentioned in the article:

In the presence of tetrabutylammonium fluoride (i.e., catalyst, quaternary ammonium halide) and mol. sieves (MS) 4Å in DMF, an efficient autoxidation reaction (tandem reaction, domino reaction) of 2-oxindoles with ketones under air at room temperature has been developed. This approach may provide a green, practical, and metal-free protocol (i.e., green chem. method) for a wide range of biol. important 3-hydroxy-3-(2-oxo-alkyl)-2-oxindoles. The synthesis of the target compounds was achieved by a reaction of 1,3-dihydro-1-methyl-2H-indol-2-one derivs, and ketones, such as 1-phenylethanone (acetophenone), 1-(2-naphthalenyl)ethanone, 1-(1H-pyrrol-2-yl)ethanone (pyrrole-ketone), 1-(2-furanyl)ethanone (furan-ketone), 1-(2-thienyl)ethanone, 1-(4-pyridinyl)ethanone (pyridine-ketone). The title compounds thus formed included 1,3-dihydro-3-hydroxy-1-methyl-3-(2-oxo-2-phenylethyl)-2H-indol-2-one derivatives This study involved multiple reactions and reactants, such as 7-Bromo-1-methylindolin-2-one (cas: 100831-25-2SDS of cas: 100831-25-2).

7-Bromo-1-methylindolin-2-one (cas: 100831-25-2) belongs to indole derivatives. In addition to tryptophan, indigo, and indoleacetic acid, numerous compounds obtainable from plant or animal sources contain the indole molecular structure. It is used in perfumery and in making tryptophan, an essential amino acid, and indoleacetic acid (heteroauxin), a hormone that promotes the development of roots in plant cuttings.SDS of cas: 100831-25-2

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

1,2,3,4-Tetrahydro-β-carboline-3-carboxylic acid and 1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid in wines was written by Herraiz, Tomas;Huang, Zhixian;Ough, Cornelius S.. And the article was included in Journal of Agricultural and Food Chemistry in 1993.Safety of 1-Isobutyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic acid The following contents are mentioned in the article:

1,2,3,4-Tetrahydro-β-carboline-3-carboxylic acids were analyzed in 16 table wines, 34 old and new dessert and aperitif wines, 8 sparkling wines, 18 distillates, and 5 grape juices. The concentrations found ranged from 0 to 17.8 mg/L for 1-methyl-1,2,3,4-tetrahydro-β-carboline-3-COOH (MTCA) and from 0 to 0.65 mg/L for 1,2,3,4-tetrahydro-β-carboline-3-COOH (THCA). Higher concentrations were generally found in fortified wines than in table wines and very low or no concentration at all in distillates and grape juices. No correlation was detected between the two tetrahydro-β-carboline-3-COOHs and the concentration of tryptophan or acetaldehyde in the wines. However, a good correlation in the formation of tetrahydro-β-carboline-3-COOH was found when tryptophan or tryptophan and acetaldehyde were added to a sherry and a white wine, resp. This may be due to the blocking effects of sulfur dioxide that would be variable from wine to wine. This study involved multiple reactions and reactants, such as 1-Isobutyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic acid (cas: 146436-31-9Safety of 1-Isobutyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic acid).

1-Isobutyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic acid (cas: 146436-31-9) belongs to indole derivatives. Indole produced by Proteus, Pseudomonas, Escherichia and other species was shown to be a growth promoting factor in Arabidopsis thaliana. Indole plays a fundamental role for QS in E. coli, being one of the signal molecules responsible for the transcription of a variety of genes (gabT, and tnaB ASTD). Safety of 1-Isobutyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic acid

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

Decamethylanthracene and its 9,10-‘Dewar’ isomer was written by Hart, Harold;Ruge, Bernd. And the article was included in Tetrahedron Letters in 1977.COA of Formula: C10H9NO2 The following contents are mentioned in the article:

Decamethylanthracene (I) was prepared from 4,7-dimethylisatin by sequential addition of Br (Br, boiling EtOH), bromination (Br/AlBr₃ in fuming H₂SO₄, 24 h), treatment with H₂O₂/OH^–, diazotization, cycloaddition of hexamethyl-2,4-cyclohexadienone (ClCH₂CH₂Cl containing propylene oxide, 70-80°), reduction (LiAlH₄), reflux in mesitylene, cycloaddition of N-butyltetramethylpyrrole (room temperature, BuLi/C₆H₁₃, 1 h), and oxidation with m-ClC₆H₄C(O)OOH in CHCl₃/aqueous Na₂CO₃. Treatment of I in CH₂Cl₂ with one drop of CF₃CO₂H gave tautomer II. Irradiation of I in C₆H₆ or Et₂O gave th 9,10-‘Dewar’ isomer III. This study involved multiple reactions and reactants, such as 4,7-Dimethylindoline-2,3-dione (cas: 15540-90-6COA of Formula: C10H9NO2).

4,7-Dimethylindoline-2,3-dione (cas: 15540-90-6) belongs to indole derivatives. Indole, also called Benzopyrrole, a heterocyclic organic compound occurring in some flower oils, such as jasmine and orange blossom, in coal tar, and in fecal matter. In addition to indole, the strain-release chemistry worked for numerous substrates including amines, alcohols, thiols, carboxylic acids, imidazoles, and pyrazoles.COA of Formula: C10H9NO2

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

Bioactive cyclometalated phthalimides: design, synthesis and kinase inhibition was written by Blanck, Sebastian;Geisselbrecht, Yann;Kraeling, Katja;Middel, Stephen;Mietke, Thomas;Harms, Klaus;Essen, Lars-Oliver;Meggers, Eric. And the article was included in Dalton Transactions in 2012.Synthetic Route of C15H10BrNO2 The following contents are mentioned in the article:

The regioselective cyclometalation of 4-(pyridin-2-yl)phthalimide was exploited for the economical design of organometallic protein kinase inhibitors. 4-(Pyridin-2-yl)phthalimide can be prepared from inexpensive 4-bromophthalimide in just three steps including one Pd-catalyzed Stille cross-coupling. The versatility of this new ligand was demonstrated with the synthesis of ruthenium(II) half-sandwich as well as octahedral ruthenium(II) and iridium(III) complexes. The regioselectivity of the C-H activation in the course of the cyclometalation can be influenced by the reaction conditions and the steric demand of the introduced metal complex fragment. The biol. activity of this new class of metalated phthalimides was evaluated by profiling two representative members against a large panel of human protein kinases. A cocrystal structure of one metallo-phthalimide with the protein kinase Pim1 confirmed an ATP-competitive binding with the intended hydrogen bonding between the phthalimide moiety and the hinge region of the ATP-binding site. This study involved multiple reactions and reactants, such as 2-Benzyl-5-bromoisoindoline-1,3-dione (cas: 82104-06-1Synthetic Route of C15H10BrNO2).

2-Benzyl-5-bromoisoindoline-1,3-dione (cas: 82104-06-1) belongs to indole derivatives. Indole produced by Proteus, Pseudomonas, Escherichia and other species was shown to be a growth promoting factor in Arabidopsis thaliana.Indole was synthesized in moderate yield via an o-naphthoquinone catalyzed tandem cross-coupling of substituted aniline and benzylamine under aerobic oxidation conditions.Synthetic Route of C15H10BrNO2

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

Preparation of O-methyl substituted 2-oxofuro- and 2-oxopyrrolidinoindolines by reductive lactonization of oxindolylacetic acids was written by Morales-Rios, Martha S.;Rivera-Becerril, Ernesto;Lopez-Camacho, Perla Y.;Perez-Rojas, Nadia A.;Suarez-Castillo, Oscar R.. And the article was included in Natural Product Communications in 2012.Synthetic Route of C11H11NO4 The following contents are mentioned in the article:

A practical procedure for the preparation of O-methyl-substituted 3a,8-dialkyl-2-oxofuroindoline derivatives was described. A reductive lactonization of the corresponding (oxindolyl)acetic acids provides a route for the formation of this class of compounds Further transformation of 2-oxofuroindolines into 2-oxopyrrolidinoindolines and then to pyrrolidinoindolines demonstrates their versatility as key intermediates in natural products synthesis. The results of single-crystal X-ray crystallog. analyses are given for five of the studied compounds The title compounds thus formed included a 3,3a,8,8a-tetrahydro-2H-furo[2,3-b]indol-2-one (furanone) derivative (I) and (3aR,8aS)-rel-1,2,3,3a,8,8a-hexahydro-5-methoxy-1-methyl-3a,8-bis(phenylmethyl)pyrrolo[2,3-b]indole (II) and related compounds, such as 5-methoxydebromoflustramine B. The synthesis of the target compounds was achieved using 2,3-dihydro-5-methoxy-1H-indole-3-acetic acid derivatives as key intermediates. This study involved multiple reactions and reactants, such as 2-(5-Methoxy-2-oxoindolin-3-yl)acetic acid (cas: 885272-25-3Synthetic Route of C11H11NO4).

2-(5-Methoxy-2-oxoindolin-3-yl)acetic acid (cas: 885272-25-3) belongs to indole derivatives. The indole subunit is an almost ubiquitous component of biologically active natural products, and its study has been the focus of research for decades. They are capable of binding to a variety of receptors with high affinity and thus have applications in a wide range of therapeutic areas.Synthetic Route of C11H11NO4

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

Discovery of a Novel and Selective Indoleamine 2,3-Dioxygenase (IDO-1) Inhibitor 3-(5-Fluoro-1H-indol-3-yl)pyrrolidine-2,5-dione (EOS200271/PF-06840003) and Its Characterization as a Potential Clinical Candidate was written by Crosignani, Stefano;Bingham, Patrick;Bottemanne, Pauline;Cannelle, Helene;Cauwenberghs, Sandra;Cordonnier, Marie;Dalvie, Deepak;Deroose, Frederik;Feng, Jun Li;Gomes, Bruno;Greasley, Samantha;Kaiser, Stephen E.;Kraus, Manfred;Negrerie, Michel;Maegley, Karen;Miller, Nichol;Murray, Brion W.;Schneider, Manfred;Soloweij, James;Stewart, Albert E.;Tumang, Joseph;Torti, Vince R.;Van Den Eynde, Benoit;Wythes, Martin. And the article was included in Journal of Medicinal Chemistry in 2017.SDS of cas: 1000343-16-7 The following contents are mentioned in the article:

Tumors use tryptophan-catabolizing enzymes such as indoleamine 2,3-dioxygenase (IDO-1) to induce an immunosuppressive environment. IDO-1 is induced in response to inflammatory stimuli and promotes immune tolerance through effector T-cell anergy and enhanced Treg function. As such, IDO-1 is a nexus for the induction of a key immunosuppressive mechanism and represents an important immunotherapeutic target in oncol. Starting from HTS hit I, IDO-1 inhibitor II has been developed. The structure-activity relationship around II is described and rationalized using the x-ray crystal structure of II bound to human IDO-1, which shows that II, differently from most of the IDO-1 inhibitors described so far, does not bind to the heme iron atom and has a novel binding mode. Clin. candidate II shows good potency in an IDO-1 human whole blood assay and also shows a very favorable ADME profile leading to favorable predicted human pharmacokinetic properties, including a predicted half-life of 16-19 h. This study involved multiple reactions and reactants, such as 5-Fluoro-6-methyl-1H-indole (cas: 1000343-16-7SDS of cas: 1000343-16-7).

5-Fluoro-6-methyl-1H-indole (cas: 1000343-16-7) belongs to indole derivatives. The indole subunit is an almost ubiquitous component of biologically active natural products, and its study has been the focus of research for decades. Indole plays a fundamental role for QS in E. coli, being one of the signal molecules responsible for the transcription of a variety of genes (gabT, and tnaB ASTD). SDS of cas: 1000343-16-7

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

Potent non-hydroxamate inhibitors of histone deacetylase-8: Role and scope of an isoindolin-2-yl linker with an α-amino amide as the zinc-binding unit was written by Greenwood, Simon O. R.;Chan, A. W. Edith;Hansen, D. Flemming;Marson, Charles M.. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2020.Safety of 2-Benzyl-5-bromoisoindoline-1,3-dione The following contents are mentioned in the article:

A series of potent inhibitors of histone deacetylase-8 (HDAC8) is described that contains an α-amino amide zinc-binding unit and a substituted isoindolinyl capping group. The presence of a 2,4-dichlorophenyl unit located in the acetate-release cavity was shown to confer a gain of approx. 4.3 kJ mol^-1 in binding energy compared to a Ph group, and the isoindoline linker has approx. 5.8 kJ mol^-1 greater binding energy than the corresponding tetrahydroisoquinoline ring system. In a series of 5-substituted isoindolin-2-yl inhibitors, a 5-acetylamino derivative was found to be more potent than the 5-unsubstituted lead HDAC8 inhibitor (increase in binding energy of 2.0 kJ mol^-1, ascribed to addnl. binding interactions within the N_ε-acetyl-L-lysine binding tunnel in HDAC8, including hydrogen bonding to Asp101. Tolerance of a 5-substituent (capping group) on the isoindoline ring has been demonstrated, and which in some cases confers improved enzyme inhibition, the HDAC8 substrate-binding region providing a platform for addnl. interactions. This study involved multiple reactions and reactants, such as 2-Benzyl-5-bromoisoindoline-1,3-dione (cas: 82104-06-1Safety of 2-Benzyl-5-bromoisoindoline-1,3-dione).

2-Benzyl-5-bromoisoindoline-1,3-dione (cas: 82104-06-1) belongs to indole derivatives. The indole subunit is an almost ubiquitous component of biologically active natural products, and its study has been the focus of research for decades. It is used in perfumery and in making tryptophan, an essential amino acid, and indoleacetic acid (heteroauxin), a hormone that promotes the development of roots in plant cuttings.Safety of 2-Benzyl-5-bromoisoindoline-1,3-dione

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

Synthesis and Structure-Activity Relationship Studies of Small Molecule Disruptors of EWS-FLI1 Interactions in Ewing’s Sarcoma was written by Tosso, Perrer N.;Kong, Yali;Scher, Lauren;Cummins, Ryan;Schneider, Jeffrey;Rahim, Said;Holman, K. Travis;Toretsky, Jeffrey;Wang, Kan;Uren, Aykut;Brown, Milton L.. And the article was included in Journal of Medicinal Chemistry in 2014.Application of 15540-90-6 The following contents are mentioned in the article:

EWS-FLI1 is an oncogenic fusion protein implicated in the development of Ewing’s sarcoma family tumors (ESFT). Using the previously reported lead compound I, the authors designed and synthesized a focused library of analogs. The functional inhibition of the analogs was measured by an EWS-FLI1/NR0B1 reporter luciferase assay and a paired cell screening approach measuring effects on growth inhibition for human cells containing EWS-FLI1 (TC32 and TC71) and control PANC1 cell lines devoid of the oncoprotein. The data revealed that substitution of electron donating groups at the para-position on the Ph ring was the most favorable for inhibition of EWS-FLI1 by analogs of I. Compound II was the most active inhibitor with GI₅₀ = 0.26±0.1 μM. Further, a correlation of growth inhibition (EWS-FLI1 expressing TC32 cells) and the luciferase reporter activity was established (R² = 0.84). Finally, the authors designed and synthesized a biotinylated analog and determined the binding affinity for recombinant EWS-FLI1 (K_d = 4.8±2.6 μM). This study involved multiple reactions and reactants, such as 4,7-Dimethylindoline-2,3-dione (cas: 15540-90-6Application of 15540-90-6).

4,7-Dimethylindoline-2,3-dione (cas: 15540-90-6) belongs to indole derivatives. Indole, first isolated in 1866, and it is commonly synthesized from phenylhydrazine and pyruvic acid, although several other procedures have been discovered. More than 200 indole derivatives have already been marketed as drugs or are under advanced stages of clinical trials.Application of 15540-90-6

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