Indole Building Blocks

Kim, Jae-Uk et al. published their research in Journal of the Korean Chemical Society in 2009 | CAS: 36499-49-7

3-(4-(Diethylamino)-2-methylphenyl)-3-(1,2-dimethyl-1H-indol-3-yl)isobenzofuran-1(3H)-one (cas: 36499-49-7) belongs to indole derivatives. Indole produced by Proteus, Pseudomonas, Escherichia and other species was shown to be a growth promoting factor in Arabidopsis thaliana. Due to this activity, the indole ring system has become an important component or intermediate in the synthesis of heterocycles.Synthetic Route of C29H30N2O2

A thermodynamic study on thermochromism of 3-(1,2-dimethyl-3-indolyl)-3-[4-(diethylamino)-2-methylphenyl]phthalide was written by Kim, Jae-Uk;Ji, Myoung-Jin;Kim, Jong-Gyu. And the article was included in Journal of the Korean Chemical Society in 2009.Synthetic Route of C29H30N2O2 This article mentions the following:

The thermochromism of 3-(1,2-dimethyl-3-indolyl)-3-[4-(diethylamino)-2-methylphenyl]phthalide (DIDMP) is studied by UV-VIS absorption spectroscopy. The DIDMP shows a closed form under solvent and changes to an open form in the presence of acid and the absorption spectra shows the increased intensity as function of the temperature increase. From the absorption spectra, the equilibrium constant between a closed and an open form is obtained and the corresponding enthalpy change was also obtained as function of various solvents. In the experiment, the researchers used many compounds, for example, 3-(4-(Diethylamino)-2-methylphenyl)-3-(1,2-dimethyl-1H-indol-3-yl)isobenzofuran-1(3H)-one (cas: 36499-49-7Synthetic Route of C29H30N2O2).

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

Manzella, Christopher R. et al. published their research in Cellular Physiology & Biochemistry in 2020 | CAS: 172922-91-7

5,11-Dihydroindolo[3,2-b]carbazole-6-carbaldehyde (cas: 172922-91-7) 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.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 C19H12N2O

Serotonin modulates AhR activation by interfering with CYP1A1-mediated clearance of AhR ligands was written by Manzella, Christopher R.;Ackerman, Max;Singhal, Megha;Ticho, Alexander L.;Ceh, Justin;Alrefai, Waddah A.;Saksena, Seema;Dudeja, Pradeep K.;Gill, Ravinder K.. And the article was included in Cellular Physiology & Biochemistry in 2020.Synthetic Route of C19H12N2O This article mentions the following:

Background/Aims: Serotonin (5-hydroxytryptamine, 5-HT) is a neurotransmitter and hormone with important physiol. functions in many organs, including the intestine. We have previously shown that 5-HT activates the aryl hydrocarbon receptor (AhR) in intestinal epithelial cells (IECs) via a serotonin transporter (SERT)-dependent mechanism. AhR is a nuclear receptor that binds a variety of mols. including tryptophan (TRP) metabolites to regulate physiol. processes in the intestine including xenobiotic detoxification and immune modulation. We hypothesized that 5-HT activates AhR indirectly by interfering with metabolic clearance of AhR ligands by cytochrome P 450 1A1 (CYP1A1). Methods: Inhibition of CYP1A1 activity by 5-HT was assessed in the human intestinal epithelial cell line Caco-2 and recombinant CYP1A1 microsomes using both luciferase and LC-MS/MS. Degradation of 5-HT by recombinant CYP1A1 was measured by LC-MS/MS. For in vitro studies, CYP1A1 and CYP1B1 mRNA expression levels were measured by RT-PCR and CYP1A1 activity was measured by ethoxyresorufin-O-deethylase (EROD) assays. For in vivo studies, AhR ligands were administered to SERT KO mice and WT littermates and intestinal mucosa CYP1A1 mRNA was measured. Results: We show that 5-HT inhibits metabolism of both the pro-luciferin CYP1A1 substrate Luc-CEE as well as the high affinity AhR ligand 6-formylindolo[3,2-b] carbazole (FICZ). Recombinant CYP1A1 assays revealed that 5-HT is metabolized by CYP1A1 in an NADPH dependent manner. Treatment with 5-HT in TRP-free medium, which is devoid of trace AhR ligands, showed that 5-HT requires the presence of AhR ligands to activate AhR. Cotreatment with 5-HT and FICZ confirmed that 5-HT potentiates induction of AhR target genes by AhR ligands. However, this was only true for ligands which are CYP1A1 substrates such as FICZ. Administration of 尾-naphthoflavone by gavage or indole-3-carbinol via diet to SERT KO mice revealed that lack of SERT impairs intestinal AhR activation. Conclusion: Our studies provide novel evidence of crosstalk between serotonergic and AhR signaling where 5-HT can influence the ability of AhR ligands to activate the receptor in the intestine. In the experiment, the researchers used many compounds, for example, 5,11-Dihydroindolo[3,2-b]carbazole-6-carbaldehyde (cas: 172922-91-7Synthetic Route of C19H12N2O).

Reddy, Gangireddy Sujeevan et al. published their research in Bioorganic Chemistry in 2021 | CAS: 10102-94-0

5-Bromo-1-methyl-1H-indole-3-carbaldehyde (cas: 10102-94-0) 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. In addition to indole, the strain-release chemistry worked for numerous substrates including amines, alcohols, thiols, carboxylic acids, imidazoles, and pyrazoles.Category: indole-building-block

Amberlyst-15 catalysed synthesis of novel indole derivatives under ultrasound irradiation: Their evaluation as serotonin 5-HT_2C receptor agonists was written by Reddy, Gangireddy Sujeevan;Kamaraj, Rajamanikkam;Hossain, Kazi Amirul;Kumar, Jetta Sandeep;Thirupataiah, B.;Medishetti, Raghavender;Sushma Sri, N.;Misra, Parimal;Pal, Manojit. And the article was included in Bioorganic Chemistry in 2021.Category: indole-building-block This article mentions the following:

A series of indole based novel Schiff bases I [R¹ = H, Me, prop-2-yn-1-yl, etc; R² = H, Br] was designed as potential agonists of 5-HT_2C receptor that was supported by docking studies in-silico. These compounds I were synthesized via Amberlyst-15 catalyzed condensation of an appropriate pyrazole based primary amine with the corresponding indole-3-aldehydes under ultrasound irradiation at ambient temperature A number of target Schiff bases I were obtained in good yields (77-87%) under mild conditions within 1 h. Notably, the methodol. afforded the corresponding pyrazolo[4,3-d]pyrimidin-7(4H)-one derivatives II [R³ = Et, n-Bu, benzyl; R⁴ = H, Br] when the primary amine was replaced by a secondary amine. Several Schiff bases I showed agonist activity when tested against human 5-HT_2C using luciferase assay in HEK293T cells in-vitro. The SAR (Structure-Activity-Relationship) studies suggested that the imine moiety was more favorable over its cyclic form i.e. the corresponding pyrazolopyrimidinone ring. The Schiff bases I [R¹ = Me, R² = H] (EC₅₀ 1.8 nM) and I [R¹ = Bn, R² = H] (EC₅₀ 5.7 nM) were identified as the most active compounds and were comparable with Lorcaserin (EC₅₀ 8.5 nM). Also like Lorcaserin, none of these compounds I were found to be PAM of 5-HT_2C. With 鈭?4 and 鈭?50 fold selectivity towards 5-HT_2C over 5-HT_2A and 5-HT_2B resp. the compound I [R¹ = Bn, R² = H] that reduced locomotor activity in zebrafish (Danio rerio) larvae model emerged as a promising hit mol. for further study. In the experiment, the researchers used many compounds, for example, 5-Bromo-1-methyl-1H-indole-3-carbaldehyde (cas: 10102-94-0Category: indole-building-block).

Shannon, H. E. et al. published their research in Life Sciences in 1984 | CAS: 93835-05-3

tert-Butyl 9H-pyrido[3,4-b]indole-3-carboxylate (cas: 93835-05-3) 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. 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.Formula: C16H16N2O2

尾-Carboline-3-carboxylate-tert-butyl ester: a selective BZ₁ benzodiazepine receptor antagonist was written by Shannon, H. E.;Guzman, F.;Cook, J. M.. And the article was included in Life Sciences in 1984.Formula: C16H16N2O2 This article mentions the following:

The effectiveness of 尾-carboline-3-carboxylate-tert-Bu聽ester (尾CCtB) [93835-05-3] in antagonizing the anticonvulsant, ataxic, and antipunishment effects of diazepam were evaluated. The mice, 尾CCtB at doses of 3 and 10 mg/kg produced a dose-related antagonism of the anticonvulsant effects of diazepam against pentylenetetrazole (80 mg/kg). A dose of 30 mg/kg of BCCtB did not produce a further shift in the diazepam dose-effect curve, apparently because 尾CCtB failed to block the muscle-relaxant effects of diazepam. Further, 尾CCtB (30 mg/kg) failed to antagonize the ataxic effects of diazepam in an inverted screen test. Rats responded under a multiple schedule where in one component every twentieth response (FR20) resulted in water presentation (unpunished component) and in another component every twentieth response (FR20) resulted in both shock and water presentation (punished component). Diazepam orally (0.1 to 10 mg/kg) first increased and then decreased rates in the punished component but only decreased rates in the unpunished component. 尾CCtB had no effect on response rates when administered alone, but antagonized the rate-increasing effects of diazepam in the punished component. 尾CCtB did not alter the rate-decreasing effects of diazepam in either component. Thus, 尾CCtB selectively antagonized the effects of diazepam on punished behavior as well as the anticonvulsant effects of diazepam, but 尾CCtB failed to antagonize the rate-decreasing and ataxic effects of diazepam. These results are consistent with the interpretation that 尾CCtB is a selective BZ₁ benzodiazepine receptor antagonist. In the experiment, the researchers used many compounds, for example, tert-Butyl 9H-pyrido[3,4-b]indole-3-carboxylate (cas: 93835-05-3Formula: C16H16N2O2).

Boekelheide, V. et al. published their research in Journal of the American Chemical Society in 1950 | CAS: 5094-12-2

2-Methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (cas: 5094-12-2) 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.Computed Properties of C12H14N2

Curariform activity and chemical structure. VI. Syntheses in the 尾- and 纬-carboline series was written by Boekelheide, V.;Ainsworth, C.. And the article was included in Journal of the American Chemical Society in 1950.Computed Properties of C12H14N2 This article mentions the following:

On the basis of the probable carboline structure of several of the calabash curare alkaloids, some 1,2,3,4-tetrahydro-尾- and 纬-carbolines were prepared and tested for curariform activity. The Fischer indole synthesis was used to prepare 2-methyl-1,2,3,4-tetrahydro-纬-carboline (I). PhNHNH₂.HCl and 1-methyl-4-piperidone in a modification of the method of Cook and Reed (C.A. 39, 4610.9), yielded 54% I, white plates, m. 169-70掳 (C. and R. report 170-1掳); picrate, yellow, prisms from alc., m. 130-1掳; methiodide (II) (Ia, R = H, R’ = Me, X = I) from I with MeI in ether, colorless plates from H₂O, m. 215-16掳; benzyl chloride (III) (61% yield from I with PhCH₂Cl in dioxane), colorless prisms from Me₂CO, m. 155-9掳. The 8-Br derivatives of I, II, and III were prepared by substituting p-BrC₆H₄NHNH₂ for PhNHNH₂ in the synthesis used for I, and preparing the salts in the same way as for II and III; 8-bromo-2-methyl-1,2,3,4-tetrahydro- 纬-carboline (IV), (yield, 52%), coarse prisms from MeOH-H₂O, m. 185-6掳; methiodide (V) (Ia, R = Br, R’ = Me, X = I), colorless prisms from MeOH, m. 241-3掳; benzyl chloride (VI), colorless needles from MeNO₂, m. 170-2掳. 尾-Carboline, prepared by the method of Speitel and Schlittler (C.A. 43, 6627c), was reduced with Na and BuOH by the procedure of Ashley and Robinson (C.A. 22, 2949) to the 1,2,3,4-tetrahydro compound (VII), m. 207-8掳 (C.A. 25, 300). Reductive methylation of VII was carried out by passing dry N and HCHO vapor into a cooled solution of VII for 30 min., addition of Raney nickel catalyst, and shaking the mixture under 3 atm. H for 3 hrs., giving 70% 3-methyl-1,2,3,4-tetrahydro-尾-carboline (VIII), colorless needles from alc., m. 217-18掳; picrate, bright yellow needles from alc., m. 197-8掳; methiodide (IX) (62% from VIII in C₆H₆ refluxed with MeI for 30 min.), white needles from absolute alc., m. 265掳; benzyl chloride (X), prepared similarly, very hygroscopic white needles from alc.-ether, m. 165掳. Analysis of X, even after drying at 100掳, showed the presence of solvent of crystallization Attempts to prepare 2-ethyl-1,2,3,4-tetrahydro-尾-carboline by the cyclization of 伪-ethyltryptamine (picrate, scarlet prisms, m. 223-4掳) with HCHO were unsuccessful. Preliminary testing with frogs showed that all the quaternary salts had curariform activity. III and X were the most active, with activity about one-fifth that of d-tubocurarine chloride. The Br derivatives were less active than the Br-free compounds In the experiment, the researchers used many compounds, for example, 2-Methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (cas: 5094-12-2Computed Properties of C12H14N2).

Zheng, Min et al. published their research in Organic Letters in 2016 | CAS: 1841512-58-0

1,3-Dioxoisoindolin-2-yl 4-phenylbutanoate (cas: 1841512-58-0) belongs to indole derivatives. Indole produced by Proteus, Pseudomonas, Escherichia and other species was shown to be a growth promoting factor in Arabidopsis thaliana. Due to this activity, the indole ring system has become an important component or intermediate in the synthesis of heterocycles.SDS of cas: 1841512-58-0

Ester Formation via Nickel-Catalyzed Reductive Coupling of Alkyl Halides with Chloroformates was written by Zheng, Min;Xue, Weichao;Xue, Teng;Gong, Hegui. And the article was included in Organic Letters in 2016.SDS of cas: 1841512-58-0 This article mentions the following:

The synthesis of alkyl esters from readily available alkyl halides and chloroformates was achieved for the first time using a mild Ni-catalyzed reductive coupling protocol. Unactivated primary and secondary alkyl iodides as well as glycosyl, benzyl, and aminomethyl halides were successfully employed to yield products in moderate to excellent yields with high functional group tolerance. In the experiment, the researchers used many compounds, for example, 1,3-Dioxoisoindolin-2-yl 4-phenylbutanoate (cas: 1841512-58-0SDS of cas: 1841512-58-0).

Herbig, Marcus et al. published their research in Zeitschrift fuer Anorganische und Allgemeine Chemie in 2019 | CAS: 480-91-1

Isoindolin-1-one (cas: 480-91-1) 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. More than 200 indole derivatives have already been marketed as drugs or are under advanced stages of clinical trials.Electric Literature of C8H7NO

Lactamomethylsilanes – Synthesis, Structures, and Reactivity towards CO₂ and Phenyl isocyanate was written by Herbig, Marcus;Boehme, Uwe;Kroke, Edwin. And the article was included in Zeitschrift fuer Anorganische und Allgemeine Chemie in 2019.Electric Literature of C8H7NO This article mentions the following:

Lactamomethylsilanes of 纬-butyrolactam, 未-valerolactam, 蔚-caprolactam, and 1-isoindolinone (phthalimidine) with up to three Me moieties were synthesized according to the chem. formula Me_xSiLac_(4-x) (x = 0, 1, 2, and 3). Using the lactams as starting materials four synthetic routes were tested: salt elimination, transsilylation, transamination, and metalation of the lactames followed by reaction with methylchlorosilanes. All products were analyzed by NMR (¹H, ¹³C and ²⁹Si) and RAMAN spectroscopy. Selected solid products were crystallized and the mol. structure was determined by single-crystal x-ray diffraction. The reactivity of the lactamomethylsilanes towards Ph isocyanate and CO₂ was studied. In the experiment, the researchers used many compounds, for example, Isoindolin-1-one (cas: 480-91-1Electric Literature of C8H7NO).

Baud, Matthias G. J. et al. published their research in Journal of Medicinal Chemistry in 2012 | CAS: 3130-75-4

4-(1,3-Dioxoisoindolin-2-yl)butanoic acid (cas: 3130-75-4) 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. 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 C12H11NO4

Defining the Mechanism of Action and Enzymatic Selectivity of Psammaplin A against Its Epigenetic Targets was written by Baud, Matthias G. J.;Leiser, Thomas;Haus, Patricia;Samlal, Sharon;Wong, Ai Ching;Wood, Robert J.;Petrucci, Vanessa;Gunaratnam, Mekala;Hughes, Siobhan M.;Buluwela, Lakjaya;Turlais, Fabrice;Neidle, Stephen;Meyer-Almes, Franz-Josef;White, Andrew J. P.;Fuchter, Matthew J.. And the article was included in Journal of Medicinal Chemistry in 2012.Electric Literature of C12H11NO4 This article mentions the following:

Psammaplin A (11c) is a marine metabolite previously reported to be a potent inhibitor of two classes of epigenetic enzymes: histone deacetylases and DNA methyltransferases. The design and synthesis of a focused library based on the psammaplin A core has been carried out to probe the mol. features of this mol. responsible for its activity. By direct in vitro assay of the free thiol generated upon reduction of the dimeric psammaplin scaffold, we have unambiguously demonstrated that 11c functions as a natural prodrug, with the reduced form being highly potent against HDAC1 in vitro (IC₅₀ 0.9 nM). Furthermore, we have shown it to have high isoform selectivity, being 360-fold selective for HDAC1 over HDAC6 and more than 1000-fold less potent against HDAC7 and HDAC8. SAR around our focused library revealed a number of features, most notably the oxime functionality to be important to this selectivity. Many of the compounds show significant cytotoxicity in A549, MCF7, and W138 cells, with the SAR of cytotoxicity correlating to HDAC inhibition. Furthermore, compound treatment causes upregulation of histone acetylation but little effect on tubulin acetylation. Finally, we have found no evidence for 11c functioning as a DNMT inhibitor. In the experiment, the researchers used many compounds, for example, 4-(1,3-Dioxoisoindolin-2-yl)butanoic acid (cas: 3130-75-4Electric Literature of C12H11NO4).

Mizrahi, Dana M. et al. published their research in Phosphorus, Sulfur and Silicon and the Related Elements in 2001 | CAS: 3130-75-4

4-(1,3-Dioxoisoindolin-2-yl)butanoic acid (cas: 3130-75-4) belongs to indole derivatives. Indole could be stereoselectively alkylated with chiral cyclopentyl sulfone reagent. More than 200 indole derivatives have already been marketed as drugs or are under advanced stages of clinical trials.Quality Control of 4-(1,3-Dioxoisoindolin-2-yl)butanoic acid

伪-Amino acid derived bisphosphonates. Synthesis and anti-resorptive activity was written by Mizrahi, Dana M.;Waner, Trevor;Segall, Yoffi. And the article was included in Phosphorus, Sulfur and Silicon and the Related Elements in 2001.Quality Control of 4-(1,3-Dioxoisoindolin-2-yl)butanoic acid This article mentions the following:

Eleven new bisphosphonates were prepared from naturally-occurring L-amino acids. The synthesis required special attention to amino and side-chain protections. The novel compounds were tested in TPTX (thyroparathyroidectomized) rats against arotinoid-induced hypercalcemia and were compared to alendronate. Leucine and phenylalanine bisphosphonates showed modest antiresorptive activity, as compared to alendronate. Limited SAR conclusions were drawn. In the experiment, the researchers used many compounds, for example, 4-(1,3-Dioxoisoindolin-2-yl)butanoic acid (cas: 3130-75-4Quality Control of 4-(1,3-Dioxoisoindolin-2-yl)butanoic acid).

Borghs, Jannik C. et al. published their research in Organic Letters | CAS: 2343-22-8

5-Fluoroindoline (cas: 2343-22-8) 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.Name: 5-Fluoroindoline

Manganese-Catalyzed Regioselective Dehydrogenative C- versus N-Alkylation Enabled by a Solvent Switch: Experiment and Computation was written by Borghs, Jannik C.;Zubar, Viktoriia;Azofra, Luis Miguel;Sklyaruk, Jan;Rueping, Magnus. And the article was included in Organic Letters.Name: 5-Fluoroindoline This article mentions the following:

In the presence of an air-stable manganese(I) bis(diphenylphosphinoethyl)amine complex, indolines underwent regioselective alkylation and dehydrogenation reactions with alkyl and benzylic alcs. mediated by CsOH in either toluene or toluene/2,2,2-trifluoroethanol to yield 3-alkylindoles and 1-alkylindoles, resp. The mechanism was studied exptl. and by calculation of the transition states and their free energies for the alkylation; the reaction takes place through combined acceptorless dehydrogenation and hydrogen autotransfer reactions. In the experiment, the researchers used many compounds, for example, 5-Fluoroindoline (cas: 2343-22-8Name: 5-Fluoroindoline).