24/11/2022 - Indole Building Blocks

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).

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

Zhang, Ji-Quan et al. published their research in Catalysis Communications in 2020 | CAS: 100831-25-2

7-Bromo-1-methylindolin-2-one (cas: 100831-25-2) belongs to indole derivatives. Indole is an important structural motif of various drugs, therapeutic leads besides its prevalence in numerous natural products, agrochemicals, perfumery, and dyes. More than 200 indole derivatives have already been marketed as drugs or are under advanced stages of clinical trials.Safety of 7-Bromo-1-methylindolin-2-one

The synthesis of symmetrical 3,3-Disubstituted oxindoles by phosphine-catalyzed 纬/纬-addition of oxindoles with allenoates was written by Zhang, Ji-Quan;Li, Shu-Min;Wu, Chun-Feng;Wang, Xing-Lan;Wu, Ting-Ting;Du, Yao;Yang, Yuan-Yong;Fan, Ling-Ling;Dong, Yong-Xi;Wang, Jian-Ta;Tang, Lei. And the article was included in Catalysis Communications in 2020.Safety of 7-Bromo-1-methylindolin-2-one The following contents are mentioned in the article:

A phosphine-catalyzed 纬/纬-addition of oxindoles I (R¹ = H, 5,7-F₂, 6-OMe, 5-Cl, etc.; R² = Me, Boc, Bn, Ph; R³ = H, R⁴ = H, Ph) and II (R² = acetyl, Boc; R³ = H) with allenoates as Et buta-2,3-dienoate, Me buta-2,3-dienoate, benzyl buta-2,3-dienoate has been developed that enables the efficient synthesis of highly functionalized sym. 3,3-disubstituted oxindoles I (R³ = (2E)-4-ethoxy-4-oxobut-2-en-1-yl, (2E)-4-methoxy-4-oxobut-2-en-1-yl, (2E)-4-benzyloxy-4-oxobut-2-en-1-yl; R⁴ = (2E)-4-ethoxy-4-oxobut-2-en-1-yl, (2E)-4-methoxy-4-oxobut-2-en-1-yl, (2E)-4-benzyloxy-4-oxobut-2-en-1-yl, Ph), II (R³ = (2E)-4-ethoxy-4-oxobut-2-en-1-yl). This protocol features mild reaction conditions and wide functional group tolerance and affords corresponding addition products in good to excellent yields. Besides, have also been investigated the biol. utility of the typical 3,3-disubstituted oxindoles against nine phytopathogenic fungi, and I (R¹ = H, R² = Me, R³ = R⁴ = (2E)-4-ethoxy-4-oxobut-2-en-1-yl; R¹ = 5-Br, R² = Me, R³ = R⁴ = (2E)-4-ethoxy-4-oxobut-2-en-1-yl) and exhibited promising antifungal activities. This study involved multiple reactions and reactants, such as 7-Bromo-1-methylindolin-2-one (cas: 100831-25-2Safety of 7-Bromo-1-methylindolin-2-one).

Guise, G. Bruce et al. published their research in Journal of the Chemical Society in 1982 | 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. 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). Application of 15540-90-6

Conformational behavior of medium-sized rings. Part 10. Dithiosalicylides and trithiosalicylides was written by Guise, G. Bruce;Ollis, W. David;Peacock, Judith A.;Stephanatou, Julia Stephanidou;Stoddart, J. Fraser. And the article was included in Journal of the Chemical Society in 1982.Application of 15540-90-6 The following contents are mentioned in the article:

The trithiosalicylides I [R = Me, R¹-R³ = H (II); R = R² = R³ = H, R¹ = Me; R = R¹ = R³ = H, R² = Me (III); R-R² = H, R³ = Me] were prepared and shown to exist in solution as ring inverting enantiomeric helical conformations with trans thio ester linkages. The free energies of activation for these conformational changes are 鈭?0 kcal/mol higher than for the same process in analogous trisalicylides. The crystal structures and solid state conformations of II and III were determined by x-ray anal. The dithiosalicylides IV [R = Me, R¹-R³ = H; R = R¹ = R³ = H, R² = Me; R = H, Me, CHMe₂ (V), R¹ = R² = H, R³ = Me] were also prepared and their conformations studied. The temp dependent ¹H NMR spectrum of V is interpreted in terms of ring inversion between enantiomeric boat conformations. The 螖G^{猝?/sup> value of 24.6 kcal/mol for this conformation change, as compared with that of 17-7 kcal/mol for di-o-thymotide, suggests that cis thio ester linkages are subject to more resonance stabilization than cis ester linkages. 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 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). Application of 15540-90-6

Li, Wei’s team published research in Journal of Virology in 95 | CAS: 330161-87-0

Journal of Virology published new progress about 330161-87-0. 330161-87-0 belongs to indole-building-block, auxiliary class Protein Tyrosine Kinase/RTK,Src, name is SU6656, and the molecular formula is C19H21N3O3S, Computed Properties of 330161-87-0.

Li, Wei published the artcileHIV-1 uses dynamic podosomes for entry into macrophages, Computed Properties of 330161-87-0, the publication is Journal of Virology (2021), 95(10), e02480, database is CAplus and MEDLINE.

Macrophages are one of the major targets of human immunodeficiency virus 1 (HIV-1) and play crucial roles in viral dissemination and persistence during AIDS progression. Here, we reveal the dynamic podosome-mediated entry of HIV-1 into macrophages. Inhibition of podosomes prevented HIV-1 entry into macrophages, while stimulation of podosome formation promoted viral entry. Single-virus tracking revealed the temporal and spatial mechanism of the dynamic podosome-mediated viral entry process. The core and ring structures of podosomes played complex roles in viral entry. The HIV coreceptor CCR5 was recruited to form specific clusters at the podosome ring, where it participated in viral entry. The podosome facilitated HIV-1 entry with a rotation mode triggered by dynamic actin. Our discovery of this novel HIV-1 entry route into macrophages, mediated by podosomes critical for cell migration and tissue infiltration, provides a new view of HIV infection and pathogenesis, which may assist in the development of new antiviral strategies.

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

Yang, Cai-Guang’s team published research in Journal of Organic Chemistry in 67 | CAS: 149108-61-2

Journal of Organic Chemistry 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 C40H35N7O8, Formula: C15H14BNO4S.

Yang, Cai-Guang published the artcilePreparing Functional Bis(indole) Pyrazine by Stepwise Cross-coupling Reactions: An Efficient Method to Construct the Skeleton of Dragmacidin D, Formula: C15H14BNO4S, the publication is Journal of Organic Chemistry (2002), 67(26), 9392-9396, database is CAplus and MEDLINE.

A direct approach for selective construction of properly substituted bis(indole) pyrazine I, the skeleton of a marine alkaloid dragmacidin D, has been developed. The key steps involved the regioselective introduction of two indole units, using the palladium(0)-catalyzed Suzuki and the Stille cross-coupling reactions sequentially.

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

Li, Youxin’s team published research in Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences in 879 | CAS: 330161-87-0

Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences published new progress about 330161-87-0. 330161-87-0 belongs to indole-building-block, auxiliary class Protein Tyrosine Kinase/RTK,Src, name is SU6656, and the molecular formula is C19H21N3O3S, Application of SU6656.

Li, Youxin published the artcileCharacterization of tyrosine kinase and screening enzyme inhibitor by capillary electrophoresis with laser-induced fluoresce detector, Application of SU6656, the publication is Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences (2011), 879(1), 107-112, database is CAplus and MEDLINE.

An effective, rapid and reliable capillary electrophoresis-laser induced fluorescence (CE-LIF) procedure was built to study the characterization of tyrosine kinase (TK), which was a target for drug screening. In this procedure, CE separated the sample of the TK reaction and LIF selectively detected the fluorescence-labeled polypeptide substrate and product. The precise TK activity was quantitated by introducing the transformation ratio of the substrate (T%) to avoid the deviation resulting from the detection sensitivity and the injection amounts in different runs and different capillaries. By measuring the T%, the effects of various reaction conditions were optimized. Meanwhile, the progression of the enzyme reaction was monitored. The K_m and V_max were calculated for TK under the optimized exptl. conditions. In addition, the inhibition effectiveness of two model inhibitors, staurosporine and SU6656 were evaluated. The results indicated that the screening platform based on electrophoresis was suitable for TK anal. and laid a foundation for the high-throughput screening (HTS) of TK 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

Cho, Er-Chieh’s team published research in Journal of Enzyme Inhibition and Medicinal Chemistry in 36 | CAS: 57663-18-0

Journal of Enzyme Inhibition and Medicinal Chemistry published new progress about 57663-18-0. 57663-18-0 belongs to indole-building-block, auxiliary class Indole,Ester, name is Methyl 2-methyl-1H-indole-5-carboxylate, and the molecular formula is C11H11NO2, Safety of Methyl 2-methyl-1H-indole-5-carboxylate.

Cho, Er-Chieh published the artcileRing size changes in the development of class I HDAC inhibitors, Safety of Methyl 2-methyl-1H-indole-5-carboxylate, the publication is Journal of Enzyme Inhibition and Medicinal Chemistry (2021), 36(1), 1386-1400, database is CAplus and MEDLINE.

Five pathways involving different ring structures led to generation of fourteen thienylbenzamides which display the structure-activity relationships of class I HDAC inhibitors. All the synthesized compounds inhibit HDAC1 and HDAC2 selectively over other isoforms and many inhibit DLD1 and HCT116 cells more effectively than a parent compound Compounds and inhibit HCT116 cells by activation of the apoptosis pathway.

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

Fossey, Stacey L.’s team published research in BMC Cancer in 9 | CAS: 330161-87-0

BMC Cancer published new progress about 330161-87-0. 330161-87-0 belongs to indole-building-block, auxiliary class Protein Tyrosine Kinase/RTK,Src, name is SU6656, and the molecular formula is C19H21N3O3S, Related Products of indole-building-block.

Fossey, Stacey L. published the artcileCharacterization of STAT3 activation and expression in canine and human osteosarcoma, Related Products of indole-building-block, the publication is BMC Cancer (2009), No pp. given, database is CAplus and MEDLINE.

Dysregulation of signal transducer and activator of transcription 3 (STAT3) has been implicated as a key participant in tumor cell survival, proliferation, and metastasis and is often correlated with a more malignant tumor phenotype. STAT3 phosphorylation has been demonstrated in a subset of human osteosarcoma (OSA) tissues and cell lines. OSA in the canine population is known to exhibit a similar clin. behavior and mol. biol. when compared to its human counterpart, and is often used as a model for preclin. testing of novel therapeutics. The purpose of this study was to investigate the potential role of STAT3 in canine and human OSA, and to evaluate the biol. activity of a novel small mol. STAT3 inhibitor. To examine STAT3 and Src expression in OSA, we performed Western blotting and RT-PCR. OSA cells were treated with either STAT3 siRNA or small mol. Src (SU6656) or STAT3 (LLL3) inhibitors and cell proliferation (CyQUANT), caspase 3/7 activity (ELISA), apoptosis (Western blotting for PARP cleavage) and/or viability (Wst-1) were determined Addnl., STAT3 DNA binding after treatment was determined using EMSA. Expression of STAT3 targets after treatment was demonstrated with Western blotting, RT-PCR, or gel zymog. Our data demonstrate that constitutive activation of STAT3 is present in a subset of canine OSA tumors and human and canine cell lines, but not normal canine osteoblasts. In both canine and human OSA cell lines, downregulation of STAT3 activity through inhibition of upstream Src family kinases using SU6656, inhibition of STAT3 DNA binding and transcriptional activities using LLL3, or modulation of STAT3 expression using siRNA, all resulted in decreased cell proliferation and viability, ultimately inducing caspase-3/7 mediated apoptosis in treated cells. Furthermore, inhibition of either Src or STAT3 activity downregulated the expression of survivin, VEGF, and MMP2, all known transcriptional targets of STAT3. These data suggest that STAT3 activation contributes to the survival and proliferation of human and canine OSA cells, thereby providing a potentially promising target for therapeutic intervention. Future investigational trials of LLL3 in dogs with spontaneous OSA will help to more accurately define the role of STAT3 in the clin. setting.

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

Mu, Xin-Peng’s team published research in Angewandte Chemie, International Edition in 60 | CAS: 167015-84-1

Angewandte Chemie, International Edition 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 C15H20N2O2, Application of tert-Butyl 3-(2-aminoethyl)-1H-indole-1-carboxylate.

Mu, Xin-Peng published the artcileStereoselective Synthesis of Cyclohepta[b]indoles by Visible-Light-Induced [2+2]-Cycloaddition/retro-Mannich-type Reactions, Application of tert-Butyl 3-(2-aminoethyl)-1H-indole-1-carboxylate, the publication is Angewandte Chemie, International Edition (2021), 60(20), 11211-11216, database is CAplus and MEDLINE.

A novel method for the concise synthesis of cyclohepta[b]indoles in high yields was developed. The method involves a visible-light-induced, photocatalyzed [2+2]-cycloaddition/ retro-Mannich-type reaction of enaminones such as I to yield cycloheptaindoles such as II. Exptl. and computational studies suggested that the reaction is a photoredox process initiated by single-electron oxidation of enaminones, which undergo subsequent cyclobutane formation and rapid fragmentation of the intermediate radical cations to form cyclohepta[b]indoles.

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

White, James D.’s team published research in Heterocycles in 88 | CAS: 167015-84-1

Heterocycles 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 C6H10O7, HPLC of Formula: 167015-84-1.

White, James D. published the artcileSynthesis of the ABCD ring system of Vinca alkaloids using tandem intramolecular [2 + 2]-photocycloaddition-retro-Mannich fragmentation, HPLC of Formula: 167015-84-1, the publication is Heterocycles (2014), 88(2), 899-910, database is CAplus.

Irradiation of 3-alkylindole (E)- and (Z)-I gave spiropyrroline II via [2+2]-photocycloaddition and subsequent in situ retro-Mannich fragmentation of a fused cyclobutane. N-Alkylation of II followed by treatment of the resulting pyrrolinium salt with sodium hydride and lithium diisopropylamide generated a dienolate dianion which underwent cyclization to afford tetracyclic products, e.g., III. The configuration of III was proven by a series of NMR experiments which established that ring C in the major stereoisomer resides in a boat conformation. The prepared tetracycles contain structural features including the ABCD ring system and substituents found in certain alkaloids of the Vinca family.

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