5654-92-2 | - Page 2 of 2 - Indole Building Blocks

Chou, Pi-Tai’s team published research in Journal of Physical Chemistry A in 2000-10-05 | CAS: 5654-92-2

Journal of Physical Chemistry A published new progress about Density functional theory. 5654-92-2 belongs to class indole-building-block, name is N,N-Dimethyl-1-(1H-pyrrolo[2,3-b]pyridin-3-yl)methanamine, and the molecular formula is C10H13N3, Category: indole-building-block.

Chou, Pi-Tai published the artcileExcited-State Double Proton Transfer in 3-Formyl-7-azaindole: Role of the nπ* State in Proton-Transfer Dynamics, Category: indole-building-block, the main research area is excited state double proton transfer dynamics formylazaindole hydrogen bonding.

3-Formyl-7-azaindole (3FAI) and its derivatives have been synthesized to study the role of the nπ* state in the excited-state double proton transfer (ESDPT) reaction. In 3FAI monomer as well as its associated hydrogen-bonded complexes the lowest excited singlet state has been concluded to be in the 1nπ* configuration. The association constants incorporating the hydrogen bonding formation were determined to be 1.9 × 104 (313 K), 2.2 × 104 (298 K) and 1.8 × 105 M-1 (298 K) for 3FAI dimer, 3FAI/azacyclohexanone and 3FAI/acetic acid, resp., in cyclohexane. In alcs., the rate of solvent (e.g., methanol) diffusional migration, forming a “”correct”” precursor for ESDPT, is concluded to be much slower than the rate of Sππ* → Snπ* internal conversion which has been deduced to be 4.37 × 1012 s-1. ESDPT is prohibited in the Snπ* state of which the relaxation dynamics are dominated by the rate of Snπ* → Tππ* intersystem crossing. In contrast, for 3FAI dimer or 3FAI/acetic acid complex possessing intact dual hydrogen bonds the intrinsic ESDPT is competitive with the rate of Sππ* → Snπ* internal conversion, resulting in a prominent imine-like tautomer emission. The results provide the first model among 7-azaindole analogs in which the fast rate of Sππ* → Snπ* internal conversion serves as an internal clock to examine the mechanism of guest mols. (including the bulk alcs.) assisted ESDPT.

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

Fuller, Janis J.’s team published research in Journal of Biological Chemistry in 2016-09-16 | CAS: 5654-92-2

Journal of Biological Chemistry published new progress about Chromobacterium violaceum. 5654-92-2 belongs to class indole-building-block, name is N,N-Dimethyl-1-(1H-pyrrolo[2,3-b]pyridin-3-yl)methanamine, and the molecular formula is C10H13N3, Recommanded Product: N,N-Dimethyl-1-(1H-pyrrolo[2,3-b]pyridin-3-yl)methanamine.

Fuller, Janis J. published the artcileBiosynthesis of violacein, structure and function of L-tryptophan oxidase VioA from Chromobacterium violaceum, Recommanded Product: N,N-Dimethyl-1-(1H-pyrrolo[2,3-b]pyridin-3-yl)methanamine, the main research area is tryptophan oxidase Chromobacterium structure function inhibitor substrate analog preparation; crystal structure tryptophan oxidase Chromobacterium; SAXS tryptophan oxidase Chromobacterium; L-tryptophan oxidase; crystal structure; enzyme mechanism; enzyme-inhibitor complex; flavoprotein; redox chemistry; site-directed mutagenesis; substrate specificity; violacein.

Violacein is a natural purple pigment of Chromobacterium violaceum with potential medical applications as antimicrobial, antiviral, and anticancer drugs. The initial step of violacein biosynthesis is the oxidative conversion of L-tryptophan into the corresponding α-imine catalyzed by the flavoenzyme, L-tryptophan oxidase (VioA). A substrate-related (3-(1H-indol-3-yl)-2-methylpropanoic acid) and a product-related (2-(1H-indol-3-ylmethyl)prop-2-enoic acid) competitive VioA inhibitor was synthesized for subsequent kinetic and x-ray crystallog. investigations. Structures of the binary VioA·FADH2 and of the ternary VioA·FADH2·2-(1H-indol-3-ylmethyl)prop-2-enoic acid complex were resolved. VioA formed a “”loosely associated”” homodimer as indicated by SAXS experiments VioA belongs to the glutathione reductase family 2 of FAD-dependent oxidoreductases according to the structurally conserved cofactor binding domain. The substrate-binding domain of VioA was mainly responsible for the specific recognition of L-tryptophan. Other canonical amino acids were efficiently discriminated with a minor conversion of L-phenylalanine. Furthermore, 7-aza-tryptophan, 1-methyl-tryptophan, 5-methyl-tryptophan, and 5-fluoro-tryptophan were efficient substrates of VioA. The ternary product-related VioA structure indicated involvement of protein domain movement during enzyme catalysis. Extensive structure-based mutagenesis in combination with enzyme kinetics (using L-tryptophan and substrate analogs) identified Arg-64, Lys-269, and Tyr-309 as key catalytic residues of VioA. An increased enzyme activity of protein variant H163A in the presence of l-phenylalanine indicated a functional role of His-163 in substrate binding. The combined structural and mutational analyses led to a detailed understanding of VioA substrate recognition. Related strategies for the in vivo synthesis of novel violacein derivatives were discussed.

Benghiat, Eric’s team published research in Synthesis in 1982-12-31 | CAS: 5654-92-2

Synthesis published new progress about Amino acids Role: SPN (Synthetic Preparation), PREP (Preparation). 5654-92-2 belongs to class indole-building-block, name is N,N-Dimethyl-1-(1H-pyrrolo[2,3-b]pyridin-3-yl)methanamine, and the molecular formula is C10H13N3, Safety of N,N-Dimethyl-1-(1H-pyrrolo[2,3-b]pyridin-3-yl)methanamine.

Benghiat, Eric published the artcilePreparation of S-(3-indolylmethyl) derivatives of mercapto amino acids, Safety of N,N-Dimethyl-1-(1H-pyrrolo[2,3-b]pyridin-3-yl)methanamine, the main research area is indolylmethyl mercapto amino acid; cysteine indolylmethyl; homocysteine indolylmethyl.

Title compounds I (X = CH, R = H, Me; R1 = H, Me; X = N, R = R1 = H; n = 1, 2) were prepared by treating indoles II (X = CH, R = H, Me; X = N, R = R1 = H; R2 = NMe2; X = CH, R = Me, R1 = H, Me, R2 = N+Me3 I-) with DL-HS(CH2)nCH(NH2)CO2H in aqueous NaOH. I (n = 2) were also prepared by treating the appropriate II with thialactone DL-III. I (X = CH, R = R1 = H, n = 2) was also prepared by treating II (X, R, R1 = same, R2 = N+Me3 I-) with DL-[HO2CCH(NH2)CH2CH2S].

Huang, Y.’s team published research in Bioorganic & Medicinal Chemistry Letters in 2001-06-04 | CAS: 5654-92-2

Bioorganic & Medicinal Chemistry Letters published new progress about Dopamine D4 receptors Role: BSU (Biological Study, Unclassified), BIOL (Biological Study) (antagonists). 5654-92-2 belongs to class indole-building-block, name is N,N-Dimethyl-1-(1H-pyrrolo[2,3-b]pyridin-3-yl)methanamine, and the molecular formula is C10H13N3, Computed Properties of 5654-92-2.

Huang, Y. published the artcileSynthesis of potent and selective dopamine D4 antagonists as candidate radioligands, Computed Properties of 5654-92-2, the main research area is pyridinylpyrrolyl arylpiperazine preparation dopamine serotonin antagonist; substitution azagramine arylpiperazine.

A series of dopamine D4 antagonists, pyridinylpyrrolyl arylpiperazines I (R = F, MeO, R1 = H; R = H, R1 = F, MeO, MeS, CF3, CH:CH2, Et, Pr, Ph), was synthesized and evaluated as potential candidates for development as positron emission tomog. (PET) radioligands. Thus, azagramine II was reacted with the corresponding arylpiperazine in xylene under reflux to give I in 45 to 82% yield. All new compounds display high affinity and selectivity for the D4 receptors and compounds I (R = H, R1 = MeO; R = MeO, R1 = H; R = H, R1 = MeS) were identified as candidates for radioligand development. The activity against serotonin receptors was also examined

Pierce, Larry T.’s team published research in Tetrahedron in 2011 | CAS: 5654-92-2

Tetrahedron published new progress about Heterocyclization. 5654-92-2 belongs to class indole-building-block, name is N,N-Dimethyl-1-(1H-pyrrolo[2,3-b]pyridin-3-yl)methanamine, and the molecular formula is C10H13N3, Recommanded Product: N,N-Dimethyl-1-(1H-pyrrolo[2,3-b]pyridin-3-yl)methanamine.

Pierce, Larry T. published the artcileSynthesis of novel 3,4-diaryl-5-aminopyrazoles as potential kinase inhibitors, Recommanded Product: N,N-Dimethyl-1-(1H-pyrrolo[2,3-b]pyridin-3-yl)methanamine, the main research area is aryl aminopyrazole preparation potential kinase inhibitor.

Synthesis of a diverse series of novel 3,4-diaryl-5-aminopyrazoles as candidates in the development of new protein kinase inhibitors is reported for the first time. In the course of a wider study into bisindolylmaleimide (BIM) derivatives, we examined a novel 5-aminopyrazole heterocyclic moiety as a structural analog of the highly potent VEGF-R2/3 inhibitor pyrrole-2-one, I. The versatile nature of this pharmacophore allows considerable scope for derivatization and hence exploration of structure activity relationships. Consequently, a variety of structural modifications were used in order to diversify the aminopyrazole ring substituents. Bicyclic derivatives of the parent aminopyrazoles, II (X=CH, X=N), were also synthesized as a means of probing the kinase active site, leading to formation of complex planar pyrimidine moieties. This work provides the framework for new explorations into kinase inhibition and critical investigations into selectivity of inhibitory activity.

Larsen, Matthew A.’s team published research in Journal of the American Chemical Society in 2014-03-19 | CAS: 5654-92-2

Journal of the American Chemical Society published new progress about Borylation (regioselective). 5654-92-2 belongs to class indole-building-block, name is N,N-Dimethyl-1-(1H-pyrrolo[2,3-b]pyridin-3-yl)methanamine, and the molecular formula is C10H13N3, Product Details of C10H13N3.

Larsen, Matthew A. published the artcileIridium-Catalyzed C-H Borylation of Heteroarenes: Scope, Regioselectivity, Application to Late-Stage Functionalization, and Mechanism, Product Details of C10H13N3, the main research area is iridium catalyzed carbon hydrogen borylation heteroarene regioselectivity functionalization mechanism; tetramethylphenanthroline iridium catalyzed heteroarene borylation regioselectivity computational study.

A study on the iridium-catalyzed C-H borylation of heteroarenes is reported. Several heteroarenes containing multiple heteroatoms were amenable to C-H borylation catalyzed by the combination of an iridium(I) precursor and tetramethylphenanthroline. The investigations of the scope of the reaction led to the development of powerful rules for predicting the regioselectivity of borylation, foremost of which is that borylation occurs distal to nitrogen atoms. One-pot functionalizations are reported of the heteroaryl boronate esters formed in situ, demonstrating the usefulness of the reported methodol. for the synthesis of complex heteroaryl structures. Application of this methodol. to the synthesis and late-stage functionalization of biol. active compounds is also demonstrated. Mechanistic studies show that basic heteroarenes can bind to the catalyst and alter the resting state from the olefin-bound complex observed during arene borylation to a species containing a bound heteroarene, leading to catalyst deactivation. Studies on the origins of the observed regioselectivity show that borylation occurs distal to N-H bonds due to rapid N-H borylation, creating an unfavorable steric environment for borylation adjacent to these bonds. Computational studies and mechanistic studies show that the lack of observable borylation of C-H bonds adjacent to basic nitrogen is not the result of coordination to a bulky Lewis acid prior to C-H activation, but the combination of a higher-energy pathway for the borylation of these bonds relative to other C-H bonds and the instability of the products formed from borylation adjacent to basic nitrogen.

Shultz, Michael D.’s team published research in Journal of Medicinal Chemistry in 2011-07-14 | CAS: 5654-92-2

Journal of Medicinal Chemistry published new progress about Aldehydes Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 5654-92-2 belongs to class indole-building-block, name is N,N-Dimethyl-1-(1H-pyrrolo[2,3-b]pyridin-3-yl)methanamine, and the molecular formula is C10H13N3, Quality Control of 5654-92-2.

Shultz, Michael D. published the artcileOptimization of the in vitro cardiac safety of hydroxamate-based Histone deacetylase inhibitors, Quality Control of 5654-92-2, the main research area is hydroxamate derivative preparation SAR HDAC inhibotor anticancer.

Histone deacetylase (HDAC) inhibitors have shown promise in treating various forms of cancer. However, many HDAC inhibitors from diverse structural classes have been associated with QT prolongation in humans. Inhibition of the human ether a-go-go related gene (hERG) channel has been associated with QT prolongation and fatal arrhythmias. To determine if the observed cardiac effects of HDAC inhibitors in humans is due to hERG blockade, a highly potent HDAC inhibitor devoid of hERG activity was required. Starting with dacinostat (LAQ824), a highly potent HDAC inhibitor, we explored the SAR to determine the pharmacophores required for HDAC and hERG inhibition. We disclose here the results of these efforts where a high degree of pharmacophore homol. between these two targets was discovered. This similarity prevented traditional strategies for mitigating hERG binding/modulation from being successful and novel approaches for reducing hERG inhibition were required. Using a hERG homol. model, two compounds, I and II, were discovered to be highly efficacious with weak affinity for the hERG and other ion channels.