186.25 | - Indole Building Blocks

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).

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

Beugelmans, Rene et al. published their research in Tetrahedron, Supplement in 1981 | 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. 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.Quality Control of 2-Methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

Nucleophilic substitution of aromatic radicals. A new synthesis of the indole skeleton was written by Beugelmans, Rene;Roussi, Georges. And the article was included in Tetrahedron, Supplement in 1981.Quality Control of 2-Methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole This article mentions the following:

Photochem. nucleophilic substitution reactions of 2-IC₆H₄NH₂ with aliphatic ketone enolates, aldehyde enolates, and cyclic and heterocyclic enolates, gave indole derivatives (20-85%). E.g., 2-IC₆H₄NH₂ with MeC(OK):CH₂ (irradiation, liquid NH₃, 16 min) gave 83% I. Ketone enolates gave 2-substituted indoles whereas aldehyde enolates gave 3-substituted products; cyclic enolates gave tricyclic indoles. The reaction occurs by an S_RN1 process. In the experiment, the researchers used many compounds, for example, 2-Methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (cas: 5094-12-2Quality Control of 2-Methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole).

Schwarthoff, Sigrid et al. published their research in Bioorganic & Medicinal Chemistry in 2021 | 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. 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: 5094-12-2

Evaluation of 纬-carboline-phenothiazine conjugates as simultaneous NMDA receptor blockers and cholinesterase inhibitors was written by Schwarthoff, Sigrid;Tischer, Nicolas;Sager, Henrike;Schaetz, Bianca;Rohrbach, Marius M.;Raztsou, Ihar;Robaa, Dina;Gaube, Friedemann;Arndt, Hans-Dieter;Winckler, Thomas. And the article was included in Bioorganic & Medicinal Chemistry in 2021.Recommanded Product: 5094-12-2 This article mentions the following:

Alzheimer’s disease (AD) is the most common form of dementia. It is associated with the impairment of memory and other cognitive functions that are mainly caused by progressive defects in cholinergic and glutamatergic signaling in the central nervous system. Inhibitors of acetylcholinesterase (AChE) and ionotropic glutamate receptors of the N-methyl-D-aspartate (NMDA) receptor family are currently approved as AD therapeutics. We previously showed using a cell-based assay of NMDA receptor-mediated glutamate-induced excitotoxicity that bis-纬-carbolinium conjugates are useful NMDA receptor blockers. However, these compounds also act as subnanomolar AChE inhibitors, which may cause serious anticholinergic side effects when applied in vivo. Here, we evaluated new structures containing 纬-carbolines linked to phenothiazine via a propionyl spacer. These compounds were superior to the previously characterized bis-纬-carbolinium conjugates because they blocked NMDA receptors without requiring a quaternary pyridine N-atom and inhibited AChE with moderate IC50 values of 0.54-5.3渭M. In addition, these new compounds displayed considerable selectivity for the inhibition of butyrylcholinesterase (BChE; IC₅₀ = 0.008-0.041渭M), which may be favorable for AD treatment. Inhibitory activities towards the NMDA receptors and AChE were in the same micromolar range, which may be beneficial for equal dosing against multiple targets in AD patients. In the experiment, the researchers used many compounds, for example, 2-Methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (cas: 5094-12-2Recommanded Product: 5094-12-2).

Lizarzaburu, Mike E. et al. published their research in Tetrahedron Letters in 2004 | 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. Indole is an important structural motif of various drugs, therapeutic leads besides its prevalence in numerous natural products, agrochemicals, perfumery, and dyes. 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: 5094-12-2

1,2,3,4-Tetrahydro-纬-carbolinium salts. Novel reactions with thiols, mediated by polymer-supported reagents was written by Lizarzaburu, Mike E.;Shuttleworth, Stephen J.. And the article was included in Tetrahedron Letters in 2004.Recommanded Product: 5094-12-2 This article mentions the following:

A series of dialkyl-[2-(3-alkylsulfanylmethyl-1H-indol-2-yl)-ethyl]amines was produced using a novel route involving nucleophilic ring opening of 2,2-dialkyl-1,2,3,4-tetrahydro-纬-carbolinium salts with thiols. The insertion reaction was mediated by a strong, polymer-supported base, and the purification of the target compounds was facilitated using resin-bound sulfonic acid. In the experiment, the researchers used many compounds, for example, 2-Methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (cas: 5094-12-2Recommanded Product: 5094-12-2).

Schwarthoff, Sigrid et al. published their research in Bioorganic & Medicinal Chemistry in 2021 | CAS: 5094-12-2

Evaluation of γ-carboline-phenothiazine conjugates as simultaneous NMDA receptor blockers and cholinesterase inhibitors was written by Schwarthoff, Sigrid;Tischer, Nicolas;Sager, Henrike;Schaetz, Bianca;Rohrbach, Marius M.;Raztsou, Ihar;Robaa, Dina;Gaube, Friedemann;Arndt, Hans-Dieter;Winckler, Thomas. And the article was included in Bioorganic & Medicinal Chemistry in 2021.Recommanded Product: 5094-12-2 This article mentions the following:

Alzheimer’s disease (AD) is the most common form of dementia. It is associated with the impairment of memory and other cognitive functions that are mainly caused by progressive defects in cholinergic and glutamatergic signaling in the central nervous system. Inhibitors of acetylcholinesterase (AChE) and ionotropic glutamate receptors of the N-methyl-D-aspartate (NMDA) receptor family are currently approved as AD therapeutics. We previously showed using a cell-based assay of NMDA receptor-mediated glutamate-induced excitotoxicity that bis-γ-carbolinium conjugates are useful NMDA receptor blockers. However, these compounds also act as subnanomolar AChE inhibitors, which may cause serious anticholinergic side effects when applied in vivo. Here, we evaluated new structures containing γ-carbolines linked to phenothiazine via a propionyl spacer. These compounds were superior to the previously characterized bis-γ-carbolinium conjugates because they blocked NMDA receptors without requiring a quaternary pyridine N-atom and inhibited AChE with moderate IC50 values of 0.54-5.3μM. In addition, these new compounds displayed considerable selectivity for the inhibition of butyrylcholinesterase (BChE; IC₅₀ = 0.008-0.041μM), which may be favorable for AD treatment. Inhibitory activities towards the NMDA receptors and AChE were in the same micromolar range, which may be beneficial for equal dosing against multiple targets in AD patients. In the experiment, the researchers used many compounds, for example, 2-Methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (cas: 5094-12-2Recommanded Product: 5094-12-2).

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

Lizarzaburu, Mike E. et al. published their research in Tetrahedron Letters in 2004 | CAS: 5094-12-2

1,2,3,4-Tetrahydro-γ-carbolinium salts. Novel reactions with thiols, mediated by polymer-supported reagents was written by Lizarzaburu, Mike E.;Shuttleworth, Stephen J.. And the article was included in Tetrahedron Letters in 2004.Recommanded Product: 5094-12-2 This article mentions the following:

A series of dialkyl-[2-(3-alkylsulfanylmethyl-1H-indol-2-yl)-ethyl]amines was produced using a novel route involving nucleophilic ring opening of 2,2-dialkyl-1,2,3,4-tetrahydro-γ-carbolinium salts with thiols. The insertion reaction was mediated by a strong, polymer-supported base, and the purification of the target compounds was facilitated using resin-bound sulfonic acid. In the experiment, the researchers used many compounds, for example, 2-Methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (cas: 5094-12-2Recommanded Product: 5094-12-2).