Day: January 5, 2023

Probing the Subpockets of Factor Xa Reveals Two Binding Modes for Inhibitors Based on a 2-Carboxyindole Scaffold: A Study Combining Structure-Activity Relationship and X-ray Crystallography was written by Nazare, Marc;Will, David W.;Matter, Hans;Schreuder, Herman;Ritter, Kurt;Urmann, Matthias;Essrich, Melanie;Bauer, Armin;Wagner, Michael;Czech, Joerg;Lorenz, Martin;Laux, Volker;Wehner, Volkmar. And the article was included in Journal of Medicinal Chemistry in 2005.Quality Control of Methyl 5-fluoro-1H-indole-2-carboxylate This article mentions the following:

Structure-activity relationships within a series of highly potent 2-carboxyindole-based factor Xa inhibitors incorporating a neutral P1 ligand are described with particular emphasis on the structural requirements for addressing subpockets of the factor Xa enzyme. Interactions with the subpockets were probed by systematic substitution of the 2-carboxyindole scaffold, in combination with privileged P1 and P4 substituents. Combining the most favorable substituents at the indole nucleus led to the discovery of a remarkably potent factor Xa inhibitor displaying a K_i value of 0.07 nM. X-ray crystallog. of inhibitors bound to factor Xa revealed substituent-dependent switching of the inhibitor binding mode and provided a rationale for the SAR obtained. These results underscore the key role played by the P1 ligand not only in determining the binding affinity of the inhibitor by direct interaction but also in modifying the binding mode of the whole scaffold, resulting in a nonlinear SAR. In the experiment, the researchers used many compounds, for example, Methyl 5-fluoro-1H-indole-2-carboxylate (cas: 167631-84-7Quality Control of Methyl 5-fluoro-1H-indole-2-carboxylate).

Methyl 5-fluoro-1H-indole-2-carboxylate (cas: 167631-84-7) belongs to indole derivatives. Indole could be stereoselectively alkylated with chiral cyclopentyl sulfone reagent. Due to this activity, the indole ring system has become an important component or intermediate in the synthesis of heterocycles.Quality Control of Methyl 5-fluoro-1H-indole-2-carboxylate

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

Ultraviolet spectra of indoles in strong sulfuric acid was written by Mollan, R. C.;Harmey, M. A.;Donnelly, D. M. X.. And the article was included in Phytochemistry (Elsevier) in 1973.SDS of cas: 6639-06-1 This article mentions the following:

Measurement of the uv spectra in 12.7M H2SO4 at 30 and 70° provides a simple, quant. and specific method for the identification of variously substituted, naturally occurring plant indoles in μg quantities. In the experiment, the researchers used many compounds, for example, 3-(1H-Indol-1-yl)propanoic acid (cas: 6639-06-1SDS of cas: 6639-06-1).

3-(1H-Indol-1-yl)propanoic acid (cas: 6639-06-1) 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.SDS of cas: 6639-06-1

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

Asymmetric organocatalytic sulfenylation for the construction of a diheteroatom-bearing tetrasubstituted carbon centre was written by Tan, Qingfa;Chen, Qianping;Zhu, Zitong;Liu, Xiaohua. And the article was included in Chemical Communications (Cambridge, United Kingdom) in 2022.Synthetic Route of C14H9NO2S This article mentions the following:

Catalytic enantioselective sulfenylation to construct diheteroatom-bearing carbon centers was achieved by employing chiral guanidine organocatalysts. This protocol provided a facile route toward the synthesis of α-fluoro-α-sulfenyl-β-ketoamides, azlactone adducts and α-sulfur-substituted amino acid derivatives in high yields with good to excellent enantioselectivities. A possible working mode was proposed to elucidate the chiral control of the process. In the experiment, the researchers used many compounds, for example, 2-(Phenylthio)isoindoline-1,3-dione (cas: 14204-27-4Synthetic Route of C14H9NO2S).

2-(Phenylthio)isoindoline-1,3-dione (cas: 14204-27-4) belongs to indole derivatives. Indole could be stereoselectively alkylated with chiral cyclopentyl sulfone reagent. 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 C14H9NO2S

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

Structure-based drug design, synthesis, In vitro, and In vivo biological evaluation of indole-based biomimetic analogs targeting estrogen receptor-α inhibition was written by Hendy, Moataz S.;Ali, Aya A.;Ahmed, Lubna;Hossam, Reham;Mostafa, Alaa;Elmazar, Mohamed M.;Naguib, Bassem H.;Attia, Yasmeen M.;Ahmed, Mahmoud Salama. And the article was included in European Journal of Medicinal Chemistry in 2019.Recommanded Product: 4769-96-4 This article mentions the following:

Offering novel scaffolds targeting estrogen receptor creates huge necessity to overcome the evolving resistance developed by tumors. Structure-based drug design coupled with ring opening strategy of the steroids skeleton revealed the potential of indole-based analogs to be synthesized targeting the ligand binding domain of estrogen receptor-α. In vitro studies revealed the potential of the total sub-classes of the synthesized analogs to show anti-proliferative activity against estrogen receptor-dependent cancer cell lines at IC₅₀ ranging from 28.23 to 57.13 μM. This was further validated by evaluating the potential of the synthesized analogs to compete along with estradiol via ER-α ELISA assay to show inhibitory profile at IC₅₀ ranging from 1.76 to 204.75 nM. Two analogs (YMA-005 and YMA-006) showed significant reduction in tumor size at two dose levels with extensive degeneration and necrosis. Both YMA-005 and YMA-006 showed in-situ reduction of ER-α Immunohistochem. expression at both dose levels. Ultimately, novel analogs of indole-based biomimetic of estrone scaffolds were offered as estrogen receptor-α inhibitors. In the experiment, the researchers used many compounds, for example, 6-Nitro-1H-indole (cas: 4769-96-4Recommanded Product: 4769-96-4).

6-Nitro-1H-indole (cas: 4769-96-4) belongs to indole derivatives. Indole could be stereoselectively alkylated with chiral cyclopentyl sulfone reagent. 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.Recommanded Product: 4769-96-4

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

Study on synthesis of some substituted N-propargyl isatins by propargylation reaction of corresponding isatins using potassium carbonate as base under ultrasound- and microwave-assisted conditions was written by Tri, Nguyen Minh;Thanh, Nguyen Dinh;Ha, Luong Ngoc;Anh, Dang Thi Tuyet;Toan, Vu Ngoc;Giang, Nguyen Thi Kim. And the article was included in Chemical Papers in 2021.Related Products of 150560-58-0 This article mentions the following:

Substituted N-propargyl isatins were synthesized by S_N2 reaction of corresponding substituted isatins with propargyl bromide in the presence of anhydrous K₂CO₃ as base. Study on systematically synthesis of these compounds using heating procedures under different reaction conditions, including microwave-assisted heating conditions at power of 100 W (procedure A), conventional heating conditions in water bath at 50°C in acetonitrile (procedure B) and conventional heating conditions in water bath at 50°C in DMF (procedure C) was reported. The best procedure A was deduced based on the investigations on the reaction conditions. Almost all substituted N-propargyl isatins were new, except compounds unsubstitited, 5-methyl/5-chloro/5-chloro- N-propargylisatins. The structures of the obtained compounds were confirmed by the modern spectroscopic methods. In the experiment, the researchers used many compounds, for example, 5-Isopropylindoline-2,3-dione (cas: 150560-58-0Related Products of 150560-58-0).

5-Isopropylindoline-2,3-dione (cas: 150560-58-0) 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.Indole was synthesized in moderate yield via an o-naphthoquinone catalyzed tandem cross-coupling of substituted aniline and benzylamine under aerobic oxidation conditions.Related Products of 150560-58-0

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

Transfer of substituent effects across the indole ring was written by Kost, A. N.;Minkin, V. I.;Sagitullin, R. S.;Gorbunov, V. I.;Sadekov, I. D.. And the article was included in Zhurnal Organicheskoi Khimii in 1970.Application In Synthesis of 4-Bromo-1H-indole-2-carboxylic acid This article mentions the following:

The pK values and σ constants (Taft, Hammett, Webster, and Dewar constants) were determined for substituted indole-2-carboxylic acids (I). The transfer of the elec. charges in this ring system is weaker than in carbocyclic systems. The electron-donating groups have very little effect. The relation of structure with the pK of I is best expressed in terms of the Dewar theory. In the experiment, the researchers used many compounds, for example, 4-Bromo-1H-indole-2-carboxylic acid (cas: 16732-64-2Application In Synthesis of 4-Bromo-1H-indole-2-carboxylic acid).

4-Bromo-1H-indole-2-carboxylic acid (cas: 16732-64-2) belongs to indole derivatives. Indole exists overwhelmingly in the 1H-indole form as do other simple indoles. More than 200 indole derivatives have already been marketed as drugs or are under advanced stages of clinical trials.Application In Synthesis of 4-Bromo-1H-indole-2-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

Facile Installation of 2-Reverse Prenyl Functionality into Indoles by a Tandem N-Alkylation-Aza-Cope Rearrangement Reaction and Its Application in Synthesis was written by Chen, Xiaobei;Fan, Huaqiang;Zhang, Shilei;Yu, Chenguang;Wang, Wei. And the article was included in Chemistry – A European Journal in 2016.Reference of 827-01-0 This article mentions the following:

An unprecedented tandem N-alkylation-ionic aza-Cope (or Claisen) rearrangement-hydrolysis reaction of readily available indolyl bromides with enamines is described. Due to the complicated nature of the two processes, an operationally simple N-alkylation and subsequent microwave-irradiated ionic aza-Cope rearrangement-hydrolysis process was uncovered. The tandem reaction serves as a powerful approach to the preparation of synthetically and biol. important, but challenging, 2-reverse quaternary-centered prenylated indoles with high efficiency. Notably, unusual nonaromatic 3-methylene-2,3-dihydro-1H-indole architectures, instead of aromatic indoles, are produced. Furthermore, the aza-Cope rearrangement reaction proceeds highly regioselectively to give the quaternary-centered reverse prenyl functionality, which often produces a mixture of two regioisomers by reported methods. The synthetic value of the resulting nonaromatic 3-methylene-2,3-dihydro-1H-indole architectures was demonstrated as versatile building blocks in the efficient synthesis of structurally diverse 2-reverse prenylated indoles, such as indolines, indole-fused sultams and lactams, and the natural product bruceolline D. In the experiment, the researchers used many compounds, for example, 5-Chloroindole-3-carboxaldehyde (cas: 827-01-0Reference of 827-01-0).

5-Chloroindole-3-carboxaldehyde (cas: 827-01-0) belongs to indole derivatives. Indole exists overwhelmingly in the 1H-indole form as do other simple indoles. Due to this activity, the indole ring system has become an important component or intermediate in the synthesis of heterocycles.Reference of 827-01-0

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

Effects of chlorosubstituted indoleacetic acids on root growth, ethylene and ATP formation was written by Stenlid, Goeran;Engvild, Kjeld C.. And the article was included in Physiologia Plantarum in 1987.Recommanded Product: 2-(5-Chloro-1H-indol-3-yl)acetic acid This article mentions the following:

7-Chloroindoleacetic acid and dichloroindoleacetic acids with a Cl in the 7 position showed anti-auxinic activity and promoted root growth in wheat (Triticum aestivum c. Diamant II). In contrast, 4-, 5-, and 6-chloroindoleacetic acids acted as strong auxins inhibiting the growth of wheat roots. Flax (Linum usitatissimum cv. Conconcurrent) and cucumber (Cucumis sativus cv. Favr̈) roots showed similar, but less clear-cut responses. 7-Chloroindoleacetic acid and 4,7-dichloroindoleacetic acid alleviated root growth inhibition in wheat caused by IAA, monochloroindoleacetic acids, and benzyladenine. 2,4-D, and 4-, and 6-chloroindoleacetic acids strongly induced ethylene formation in cucumber seedlings; 4,7- and 6,7-dichloroindoleacetic acids did not, except at high concentrations The more lipid-soluble dichloroindoleacetic acids were stronger inhibitors of ATP formation in cucumber mitochondria than monochloroindoleacetic acids, while IAA itself had only a very slight effect. In the experiment, the researchers used many compounds, for example, 2-(5-Chloro-1H-indol-3-yl)acetic acid (cas: 1912-45-4Recommanded Product: 2-(5-Chloro-1H-indol-3-yl)acetic acid).

2-(5-Chloro-1H-indol-3-yl)acetic acid (cas: 1912-45-4) 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.Indole was synthesized in moderate yield via an o-naphthoquinone catalyzed tandem cross-coupling of substituted aniline and benzylamine under aerobic oxidation conditions.Recommanded Product: 2-(5-Chloro-1H-indol-3-yl)acetic 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

Syntheses of 1H-Indoles, Quinolines, and 6-Membered Aromatic N-Heterocycle-Fused Scaffolds via Palladium(II)-Catalyzed Aerobic Dehydrogenation under Alkoxide-Free Conditions was written by Yoo, Hyung-Seok;Yang, Yo-Sep;Kim, Soo Lim;Son, Seung Hwan;Jang, Yoon Hu;Shin, Jeong-Won;Kim, Nam-Jung. And the article was included in Chemistry – An Asian Journal in 2021.Quality Control of 6-Nitro-1H-indole This article mentions the following:

Aromatic N-heterocycle-fused scaffolds such as indoles and quinolines I (R₁ = H, 5-Me, 6-NH₂, etc.; R₂ = H, 2-Me, 2-C₆H₅, etc.; X = C, N) are important core structures found in various bioactive natural products and synthetic compounds Recently, various dehydrogenation methods with the help of alkoxides, known to significantly promote dihydro- or tetrahydro-heterocycles to be oxidized, were developed for the heterocycle synthesis. However, these approaches are sometimes unsuitable due to resulting undesired side reactions such as reductive dehalogenation. Herein, expedient syntheses of 1H-indoles, quinolines, and 6-membered N-heterocycle-fused scaffolds from their hydrogenated forms through palladium(II)-catalyzed aerobic dehydrogenation under alkoxide-free conditions are reported. A total of 48 compounds were successfully synthesized with a wide range of functional groups including halogens (up to 99% yield). These methodologies provide facile routes for various privileged structures possessing aromatic N-heterocycles without the help of alkoxides, in highly efficient manners. In the experiment, the researchers used many compounds, for example, 6-Nitro-1H-indole (cas: 4769-96-4Quality Control of 6-Nitro-1H-indole).

6-Nitro-1H-indole (cas: 4769-96-4) belongs to indole derivatives. Indole exists overwhelmingly in the 1H-indole form as do other simple indoles.Indole was synthesized in moderate yield via an o-naphthoquinone catalyzed tandem cross-coupling of substituted aniline and benzylamine under aerobic oxidation conditions.Quality Control of 6-Nitro-1H-indole

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

Facile Synthesis of Carbazoles via a Tandem Iodocyclization with 1,2-Alkyl Migration and Aromatization was written by Wang, Jia;Zhu, Hai-Tao;Qiu, Yi-Feng;Niu, Yuan;Chen, Si;Li, Ying-Xiu;Liu, Xue-Yuan;Liang, Yong-Min. And the article was included in Organic Letters in 2015.Recommanded Product: 827-01-0 This article mentions the following:

A strategy for the synthesis of iodocarbazoles through a tandem iodocyclization with migration and aromatization is presented. E.g., reaction of 1-(1-methyl-1H-indol-3-yl)-4-phenylbut-3-yn-1-ol (I) with 2.0 equiv of ICl at room temperature gave 89% iodocarbazole derivative (II). This sequential cascade process is concisely conducted at room temperature and in a short time. Moreover, the obtained halides can be further applied to palladium-catalyzed coupling reactions, which act as the important intermediates for building other valuable compounds In the experiment, the researchers used many compounds, for example, 5-Chloroindole-3-carboxaldehyde (cas: 827-01-0Recommanded Product: 827-01-0).

5-Chloroindole-3-carboxaldehyde (cas: 827-01-0) belongs to indole derivatives. Indole could be stereoselectively alkylated with chiral cyclopentyl sulfone reagent. They are capable of binding to a variety of receptors with high affinity and thus have applications in a wide range of therapeutic areas.Recommanded Product: 827-01-0

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