Tag: M.W=150-200

Cho, Er-Chieh published the artcileRing size changes in the development of class I HDAC inhibitors, Application of Methyl 2-methyl-1H-indole-5-carboxylate, the main research area is thienylbenzamide anticancer SAR HDAC inhibitor docking; HDAC; Thienylbenzamides; colon cancer; ring transformation.

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.

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

Nimbarte, Vijaykumar D. published the artcileSynthesis and in Vitro Evaluation of Novel 5-Nitroindole Derivatives as c-Myc G-Quadruplex Binders with Anticancer Activity, Quality Control of 5654-92-2, the main research area is human cervical cancer anticancer cMyc; G-quadruplex binders; c-Myc; nitroindoles; oncogene promoters, reactive oxygen species, structure-activity relationships.

Lead-optimization strategies for compounds targeting c-Myc G-quadruplex (G4) DNA are being pursued to develop anticancer drugs. Here, we investigate the structure-activity- relationship (SAR) of a newly synthesized series of mols. based on the pyrrolidine-substituted 5-nitro indole scaffold to target G4 DNA. Our synthesized series allows modulation of flexible elements with a structurally preserved scaffold. Biol. and biophys. analyses illustrate that substituted 5-nitroindole scaffolds bind to the c-Myc promoter G-quadruplex. These compounds downregulate c-Myc expression and induce cell-cycle arrest in the sub-G1/G1 phase in cancer cells. They further increase the concentration of intracellular reactive oxygen species. NMR spectra show that three of the newly synthesized compounds interact with the terminal G-quartets (5′- and 3-ends) in a 2 : 1 stoichiometry.

ChemMedChem published new progress about Antitumor agents. 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.

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. 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.

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.

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

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.

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.

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

Saczewski, Franciszek published the artcile1-[(Imidazolin-2-yl)amino]indoline and 1-[(imidazolin-2-yl)amino]1,2,3,4-tetrahydroquinoline derivatives: new insights into their circulatory activities, Category: indole-building-block, the main research area is imidazolinylamino indoline hydrochloride preparation mol modeling imidazoline adrenoceptor antihypertensive; quinoline imidazolinylamino hydrochloride preparation mol modeling imidazoline adrenoceptor antihypertensive.

N-[(Imidazolinyl)amino]indoline-hydrochlorides I·HCl [R = H, 2-CH3, 7-CH3, 4-Cl] and N-[(imidazolinyl)amino]tetrahydroquinoline-hydrochlorides II·HCl [R = H, 8-CH3] were synthesized and tested in vitro for their affinities to α1 and α2-adrenoceptors as well as imidazoline I1 and I2 receptors. The compounds most potent at either α1 or α2-adrenoceptors were administered i.v. to normotensive Wistar rats to determine their effects on mean arterial blood pressure and heart rate. Upon i.v. administration at dose of 0.1 mg/kg to normotensive male Wistar rats, the initial transient pressor effect was followed by long-lasting hypotension and bradycardia. The results revealed that the synthesized compounds I and II were found to possess circulatory profile characteristic of the centrally acting clonidine-like hypotensive imidazolines.

Acta Poloniae Pharmaceutica published new progress about Adrenoceptor antagonists. 41910-64-9 belongs to class indole-building-block, name is 4-Chloroindoline, and the molecular formula is C8H8ClN, Category: indole-building-block.

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

See, Cheng Shang published the artcileDiscovery of the cancer cell selective dual acting anti-cancer agent (Z)-2-(1H-indol-3-yl)-3-(isoquinolin-5-yl)acrylonitrile (A131), Application of N,N-Dimethyl-1-(1H-pyrrolo[2,3-b]pyridin-3-yl)methanamine, the main research area is indolyl isoquinolinyl acrylonitrile analogs preparation cancer mitosis autophagy; Antimitotic; Antiproliferative; Antitumor; Tumor-selective.

Selective targeting of cancer cells over normal cells is a key objective of targeted therapy. However few approaches achieve true mechanistic selectivity resulting in debilitating side effects and dose limitation. In this work we describe the discovery of A131 (4a), a new agent with an unprecedented dual mechanism of action targeting both mitosis and autophagy. Compound 4a was first identified in a phenotypic screen in which HeLa cells treated with 4a manifested mitotic arrest along with formation of multiple vesicles. Further investigations showed that 4a causes an increase in mitotic marker pH3 and autophagy marker LC3. Importantly 4a induces cell death in cancer cells while sparing normal cells which regrow after 4a is removed. Dual activities against pH3 and LC3 markers are required for cancer cell selectivity. An extensive SAR investigation confirmed 4a as the optimal dual inhibitor with potency against a panel of 30 cancer cell lines (average antiproliferative GI50 1.5μM). In a mouse model of paclitaxel-resistant colon cancer, 4a showed 74% tumor growth inhibition when administered at a dose of 20mg/kg IP twice a day.

European Journal of Medicinal Chemistry published new progress about Antiproliferative agents. 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, Application of N,N-Dimethyl-1-(1H-pyrrolo[2,3-b]pyridin-3-yl)methanamine.

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

Dong, Yanan published the artcileReductive cyanation of organic chlorides using CO2 and NH3 via Triphos-Ni(I) species, Application In Synthesis of 41910-64-9, the main research area is nitrile preparation; chloride organic reductive cyanation.

The reductive cyanation of organic chlorides RCl (R = C6H5, naphthalen-1-yl, cyclohexyl, etc.) using CO2/NH3 as the electrophilic CN source has been described. The use of tridentate phosphine ligand Triphos allows for the nickel-catalyzed cyanation of a broad array of aryl and aliphatic chlorides to produce the desired nitrile products RCN in good yields, and with excellent functional group tolerance. Cheap and bench-stable urea was also shown as suitable CN source, suggesting promising application potential. Mechanistic studies imply that Triphos-Ni(I) species are responsible for the reductive C-C coupling approach involving isocyanate intermediates. This method expands the application potential of reductive cyanation in the synthesis of functionalized nitrile compounds under cyanide-free conditions, which is valuable for safe synthesis of (isotope-labeled) drugs.

Nature Communications published new progress about Antiproliferative agents. 41910-64-9 belongs to class indole-building-block, name is 4-Chloroindoline, and the molecular formula is C8H8ClN, Application In Synthesis of 41910-64-9.

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

Lillich, Felix F. published the artcileStructure-Based Design of Dual Partial Peroxisome Proliferator-Activated Receptor γ Agonists/Soluble Epoxide Hydrolase Inhibitors, Safety of Methyl 2-methyl-1H-indole-5-carboxylate, the main research area is antitumor structure activity relationship epoxide hydrolase inhibitor.

A dual partial PPARγ agonist/sEH inhibitor using a structure-guided approach was designed. Exhaustive structure-activity relationship studies lead to the successful optimization of the designed lead. Crystal structures of one representative compound with both targets revealed potential points for optimization. The optimized compounds exhibited favorable metabolic stability, toxicity, selectivity, and desirable activity in adipocytes and macrophages.

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

Zhao, He published the artcileIndoline and piperazine containing derivatives as a novel class of mixed D2/D4 receptor antagonists. Part 1: Identification and structure-activity relationships, SDS of cas: 41910-64-9, the main research area is dopamine receptor antagonist indoline piperazine derivative preparation SAR.

Optimization of the lead compound 2-[-4-(4-chlorobenzyl)piperazin-1-yl]-1-(2,3-dihydroindol-1-yl)ethanone by systematic structure-activity relation (SAR) studies leads to two potent compounds 2-[-4-(4-chlorobenzyl)piperazin-1-yl]-1-(2-methyl-2,3-dihydroindol-1-yl)ethanone and 2-[-4-(4-chlorobenzyl)piperazin-1-yl]-1-(2-methy-2,3-dihydroindol-1-yl)ethanone. Synthesis and structure-activity relationship as mixed D2/D4 receptor antagonists are reported.

Bioorganic & Medicinal Chemistry Letters published new progress about Dopamine D2 antagonists. 41910-64-9 belongs to class indole-building-block, name is 4-Chloroindoline, and the molecular formula is C8H8ClN, SDS of cas: 41910-64-9.

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

Kulagowski, Janusz J. published the artcile3-[[4-(4-Chlorophenyl)piperazin-1-yl]methyl]-1H-pyrrolo[2,3-b]pyridine: An Antagonist with High Affinity and Selectivity for the Human Dopamine D4 Receptor, Category: indole-building-block, the main research area is dopamine D4 receptor chlorophenylpiperazinylmethyl pyrrolopyridine.

A topol. similarity search of the Merck sample collection using known dopamine agonists and antagonists as probe structures identified indole I as having modest binding selectivity for cloned human dopamine D4 receptors over D2 and D3 subtypes. Optimization of the amino side chain and introduction of a nitrogen atom into the indole nucleus resulted in L-745,870 (II), having high D4 affinity (Ki 0.43 nM) with 2200 and >5000-fold selectivity over D2 and D3 receptors, resp. Also identified in the course of this work was the piperidinol III which demonstrated the opposite selectivity, being 100-fold binding selective for the D2 receptor.

Journal of Medicinal Chemistry published new progress about Dopamine D4 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, Category: indole-building-block.

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