22/11/2022 - Page 4 of 6 - Indole Building Blocks

Hart, Harold et al. published their research in Tetrahedron Letters in 1977 | CAS: 15540-90-6

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

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).

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

Blanck, Sebastian et al. published their research in Dalton Transactions in 2012 | CAS: 82104-06-1

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

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).

Morales-Rios, Martha S. et al. published their research in Natural Product Communications in 2012 | CAS: 885272-25-3

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

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).

Crosignani, Stefano et al. published their research in Journal of Medicinal Chemistry in 2017 | 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

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).

Greenwood, Simon O. R. et al. published their research in Bioorganic & Medicinal Chemistry Letters in 2020 | CAS: 82104-06-1

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

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).

Tosso, Perrer N. et al. published their research in Journal of Medicinal Chemistry in 2014 | CAS: 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

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).

Damgaard, Maria et al. published their research in ACS Chemical Neuroscience in 2015 | CAS: 15540-90-6

4,7-Dimethylindoline-2,3-dione (cas: 15540-90-6) belongs to indole derivatives. Indole exists overwhelmingly in the 1H-indole form as do other simple indoles. 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.Electric Literature of C10H9NO2

Identification of the First Highly Subtype-Selective Inhibitor of Human GABA Transporter GAT3 was written by Damgaard, Maria;Al-Khawaja, Anas;Vogensen, Stine B.;Jurik, Andreas;Sijm, Maarten;Lie, Maria E. K.;Baek, Mathias I.;Rosenthal, Emil;Jensen, Anders A.;Ecker, Gerhard F.;Froelund, Bente;Wellendorph, Petrine;Clausen, Rasmus P.. And the article was included in ACS Chemical Neuroscience in 2015.Electric Literature of C10H9NO2 The following contents are mentioned in the article:

Screening a library of small-mol. compounds using a cell line expressing human GABA transporter 3 (hGAT3) in a [³H]GABA uptake assay identified isatin derivatives as a new class of hGAT3 inhibitors. A subsequent structure-activity relationship (SAR) study led to the identification of hGAT3-selective inhibitors (i.e., compounds 20 and 34) that were superior to the reference hGAT3 inhibitor, (S)-SNAP-5114, in terms of potency (low micromolar IC₅₀ values) and selectivity (>30-fold selective for hGAT3 over hGAT1/hGAT2/hBGT1). Further pharmacol. characterization of compound 20 (5-(thiophen-2-yl)indoline-2,3-dione) revealed a noncompetitive mode of inhibition at hGAT3. This suggests that this compound class, which has no structural resemblance to GABA, has a binding site different from the substrate, GABA. This was supported by a mol. modeling study that suggested a unique binding site that matched the observed selectivity, inhibition kinetics, and SAR of the compound series. These compounds are the most potent GAT3 inhibitors reported to date that provide selectivity for GAT3 over other GABA transporter subtypes. This study involved multiple reactions and reactants, such as 4,7-Dimethylindoline-2,3-dione (cas: 15540-90-6Electric Literature of C10H9NO2).

Nicolaou, K. C. et al. published their research in Journal of the American Chemical Society in 2009 | CAS: 1132910-79-2

tert-Butyl (2-(5-(trifluoromethyl)-1H-indol-3-yl)ethyl)carbamate (cas: 1132910-79-2) 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.Category: indole-building-block

New Synthetic Technologies for the Construction of Heterocycles and Tryptamines was written by Nicolaou, K. C.;Krasovskiy, Arkady;Majumder, Utpal;Trepanier, Vincent E.;Chen, David Y.-K.. And the article was included in Journal of the American Chemical Society in 2009.Category: indole-building-block The following contents are mentioned in the article:

New synthetic methods for the construction of novel heterocycles and tryptamines are described. Thus, N-Boc anilines are sequentially converted to (3-(2-aminophenyl)pyrrolidin-3-ol) derivatives, substituted 2-oxo-1,2-dihydrospirobenzo[d][1,3]oxazine-4,3′-pyrrolidines, and 2-(4,5-dihydro-1H-pyrrol-3-yl)aniline derivatives through a route involving t-BuLi induced ortho-metalation/LaCl₃·2LiCl metal exchange, reaction with N-Boc pyrrolidin-3-one, and subsequent decarboxylative fragmentation. Labile intermediates 2-(4,5-dihydro-1H-pyrrol-3-yl)anilines are effectively converted to tryptamines under controlled protic acid conditions. In addition to providing expedient access to the 2-oxo-1,2-dihydrospirobenzo[d][1,3]oxazine-4,3′-pyrrolidines, the method is applicable to the synthesis of the corresponding 2-oxo-1,2-dihydrospirobenzo[d][1,3]oxazine-4,3′-piperidine series of spirocycles and their precursors 3-(2-aminophenyl)piperidin-3-ol derivatives by using N-Boc-protected piperidin-3-one. Applications of the developed synthetic technologies to the synthesis of regioisomeric spirocycles, tryptamines, Corey’s aspidophytine tryptamine, and efavirenz are also described. This study involved multiple reactions and reactants, such as tert-Butyl (2-(5-(trifluoromethyl)-1H-indol-3-yl)ethyl)carbamate (cas: 1132910-79-2Category: indole-building-block).

Inoue, Satoru et al. published their research in Pesticide Science in 1985 | CAS: 100831-25-2

7-Bromo-1-methylindolin-2-one (cas: 100831-25-2) 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. Due to this activity, the indole ring system has become an important component or intermediate in the synthesis of heterocycles.Synthetic Route of C9H8BrNO

New melanin biosynthesis inhibitors and their structural similarities was written by Inoue, Satoru;Uematsu, Tamon;Kato, Toshiro;Ueda, Kenzo. And the article was included in Pesticide Science in 1985.Synthetic Route of C9H8BrNO The following contents are mentioned in the article:

Relationships between their activities as rice blast (Pyricularia oryzae) control agents and their abilities to inhibit mycelial melanization on a nutrient agar were described for 103 substituted benzothiazol-2(3H)-ones, benzoxazol-2(3H)-ones, indolin-2-ones, quinolin-2(1H)-ones, 1,2,3,4-tetrahydroquinolin-2-ones, benzo-1,4-thiazin-3(2H)-ones and benz-1,4-oxazin-3(2H)-ones, and some corresponding thiones. Several compounds had a high protective activity and an antimelanization activity against P. oryzae. There was good correlation between these activities. Structural similarities of the compounds were identified as: (1) having a benzo-bicyclic ring system; (b) containing a N atom in one ring at a position alpha to the benzene ring system; and (c) substitution, at the ring N atom, at the peri position in the aromatic ring relative to the N atom, and at the position alpha to the N atom in the ring system, with a double bond, such as in carbonyl and thiocarbonyl groups. The findings are discussed in relation to the structures of previously identified melanin biosynthesis inhibitors. This study involved multiple reactions and reactants, such as 7-Bromo-1-methylindolin-2-one (cas: 100831-25-2Synthetic Route of C9H8BrNO).

Hyatt, Janice L. et al. published their research in Journal of Medicinal Chemistry in 2007 | CAS: 15540-90-6

4,7-Dimethylindoline-2,3-dione (cas: 15540-90-6) belongs to indole derivatives. Indole produced by Proteus, Pseudomonas, Escherichia and other species was shown to be a growth promoting factor in Arabidopsis thaliana. In addition to indole, the strain-release chemistry worked for numerous substrates including amines, alcohols, thiols, carboxylic acids, imidazoles, and pyrazoles.Formula: C10H9NO2

Selective Inhibition of Carboxylesterases by Isatins, Indole-2,3-diones was written by Hyatt, Janice L.;Moak, Teri;Hatfield, M. Jason;Tsurkan, Lyudmila;Edwards, Carol C.;Wierdl, Monika;Danks, Mary K.;Wadkins, Randy M.;Potter, Philip M.. And the article was included in Journal of Medicinal Chemistry in 2007.Formula: C10H9NO2 The following contents are mentioned in the article:

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 K_i 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. This study involved multiple reactions and reactants, such as 4,7-Dimethylindoline-2,3-dione (cas: 15540-90-6Formula: C10H9NO2).