Day: October 20, 2022

Jiang, Yuqi; Xu, Jie; Yue, Kairui; Huang, Chao; Qin, Mengting; Chi, Dongyu; Yu, Qixin; Zhu, Yue; Hou, Xiaohan; Xu, Tongqiang; Li, Min; Chou, C. James; Li, Xiaoyang published the artcile< Potent Hydrazide-Based HDAC Inhibitors with a Superior Pharmacokinetic Profile for Efficient Treatment of Acute Myeloid Leukemia In Vivo>, HPLC of Formula: 399-76-8, the main research area is hydrazide HDAC inhibitor pharmacokinetic myeloid leukemia.

As “”Michael acceptors”” may induce promiscuous responses in mammalian cells by reacting with various proteins, we modified the cinnamamide of our previous hydrazide-based HDAC inhibitors (HDACIs) to deactivate the Michael reaction. Representative compound 11h is 2-5 times more potent than lead compound 17 in both HDAC inhibitory activity (IC50 = 0.43-3.01 nM) and cell-based antitumor assay (IC50 = 19.23-61.04 nM). The breakthrough in the pharmacokinetic profile of 11h (oral bioavailability: 112%) makes it a lead-in-class oral active agent, validated in the in vivo anti-AML study (4 mg/kg p.o., TGI = 78.9%). Accumulated AcHH3 and AcHH4 levels in tumor tissue directly correlate with the in vivo efficacy, as panobinostat with lower AcHH3 and AcHH4 levels than 11h displays limited activity. To the best of our knowledge, this work contributes the first report of in vivo antitumor activity of hydrazide-based HDACIs. The outstanding pharmacokinetic/pharmacodynamic and antitumor activity of 11h could potentially extend the clin. application of current HDACIs.

Journal of Medicinal Chemistry published new progress about Acetylated histone H3 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 399-76-8 belongs to class indole-building-block, and the molecular formula is C9H6FNO2, HPLC of Formula: 399-76-8.

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

Wang, Qinghui; Arnst, Kinsie E.; Wang, Yuxi; Kumar, Gyanendra; Ma, Dejian; White, Stephen W.; Miller, Duane D.; Li, Weimin; Li, Wei published the artcile< Structure-Guided Design, Synthesis, and Biological Evaluation of (2-(1H-Indol-3-yl)-1H-imidazol-4-yl)(3,4,5-trimethoxyphenyl) Methanone (ABI-231) Analogues Targeting the Colchicine Binding Site in Tubulin>, Application of C10H9NO, the main research area is ABI 231 analog design synthesis anticancer.

ABI-231 is a potent, orally bioavailable tubulin inhibitor that interacts with the colchicine binding site and is currently undergoing clin. trials for prostate cancer. Guided by the crystal structure of ABI-231 in complex with tubulin, we performed structure-activity relationship studies around the 3-indole moiety that led to the discovery of several potent ABI-231 analogs, most notably 10ab (I) and 10bb. The crystal structures of 10ab and 10bb in complex with tubulin confirmed their improved mol. interactions to the colchicine site. In vitro, biol. studies showed that new ABI-231 analogs disrupt tubulin polymerization, promote microtubule fragmentation, and inhibit cancer cell migration. In vivo, analog 10bb not only significantly inhibits primary tumor growth and decreases tumor metastasis in melanoma xenograft models but also shows a significant ability to overcome paclitaxel resistance in a taxane-resistant PC-3/TxR model. In addition, pharmacol. screening suggested that 10bb has a low risk of potential off-target function.

Journal of Medicinal Chemistry published new progress about Antiproliferative agents. 4771-48-6 belongs to class indole-building-block, and the molecular formula is C10H9NO, Application of C10H9NO.

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

Zhang, Xiaoxiang; Yu, Wenhua; Nie, Yiyu; Zhang, Yingying; Gu, Xiaoting; Wei, Wanxing; Zhang, Zhuan; Liang, Taoyuan published the artcile< Copper-iodine co-catalyzed C-H aminoalkenylation of indoles via temperature-controlled selectivity switch: facile synthesis of 2-azolyl-3-alkenylindoles>, Electric Literature of 93247-78-0, the main research area is azolyl alkenylindole preparation green chem regioselective chemoselective; indole azole phenol aminoalkenylation copper iodine.

An efficient copper-iodine co-catalyzed 2,3-difunctionalization of indoles with azoles and phenols via temperature-controlled selectivity switch has been developed for the green synthesis of 2-azolyl-3-alkenylindoles. The strategy involves the simultaneous establishment of C-C and C-N bonds in one single operation and provides straightforward access to a wide range of functionalized indoles with high regio-selectivity and good functional group compatibility. The utility of the new protocol was demonstrated by the concise synthesis of the analog of a potent anticancer agent. This work paves the way for further innovative direct difunctionalization of carbon-carbon double bonds.

Organic Chemistry Frontiers published new progress about Alkenylation. 93247-78-0 belongs to class indole-building-block, and the molecular formula is C10H9NO2, Electric Literature of 93247-78-0.

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

Makra, Zsofia; Benyei, Attila; Puskas, Laszlo G.; Kanizsai, Ivan published the artcile< One-Pot Access towards 4,5-Disubstituted 2-Amino-1H-imidazoles Starting from Mannich Substrates and their Transformation Utilities>, SDS of cas: 399-76-8, the main research area is Mannich substrate one pot oxidative annulation ring cleavage sequence; amino imidazole preparation.

An efficient protocol for the preparation of 4,5-functionalized 2-amino-1H-imidazoles, e.g., I, as fragment-like structures was developed in isolated yields up to 95%. The demonstrated one-pot manner includes an intramol. oxidative annulation and ring cleavage sequence starting from Mannich precursors. The suggested one-pot sequential synthetic methodol. is easy to apply in automatic and robotic chem. laboratories for which a rapidly increasing demand is foreseen because of the ongoing revolution in the field of continuous manufacturing of pharmaceutical drug substances and products. Further transformation utilities such as Groebke-Blackburn-Bienayme 3CR and the formation of marine alkaloid analogs were also represented.

European Journal of Organic Chemistry published new progress about Aldehydes Role: RCT (Reactant), RACT (Reactant or Reagent). 399-76-8 belongs to class indole-building-block, and the molecular formula is C9H6FNO2, SDS of cas: 399-76-8.

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

Lin, Cai; Ferreira de Almeida Fiuza, Ludmila; Cardoso Santos, Camila; Ferreira Nunes, Daniela; Cruz Moreira, Otacilio; Bouton, Jakob; Karalic, Izet; Maes, Louis; Caljon, Guy; Hulpia, Fabian; de Nazare C. Soeiro, Maria; Van Calenbergh, Serge published the artcile< 6-Methyl-7-Aryl-7-Deazapurine Nucleosides as Anti-Trypanosoma cruzi Agents: Structure-Activity Relationship and in vivo Efficacy>, Formula: C7H5N3O2, the main research area is purine nucleoside preparation human parasiticide parasitemia prodrug; 7-deazapurine nucleosides; Trypanosoma cruzi; in vivo efficacy; structure-activity relationships.

Chagas disease is a tropical infectious disease resulting in progressive organ-damage and currently lacks efficient treatment and vaccine options. By modifying the pyrimidine part of a previously identified 7-aryl-7-deazapurine nucleoside, we found that substitution of a 6-Me for a 6-amino group allows retaining T. cruzi amastigote growth inhibitory activity but confers improved selectivity towards mammalian cells. The 7-(4-chlorophenyl) analog I, which was stable in microsomes, was evaluated in an acute mouse model. Oral administration of 25 mg/kg b.i.d. suppressed peak parasitemia and protected mice from infection-related mortality, gave similar reductions as the reference drug of blood parasite loads determined by qPCR, but as benznidazole failed to induce sterile cure in the short time period of drug exposure (5 days).

ChemMedChem published new progress about Biological uptake. 101083-92-5 belongs to class indole-building-block, and the molecular formula is C7H5N3O2, Formula: C7H5N3O2.

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

Bhat, Prasanna V.; Dere, Ravindra T.; Ravikumar, S.; Hindupur, Rama Mohan; Pati, Hari N. published the artcile< Efficient and Scalable Process for Synthesis of 5-Nitro-7-azaindole>, Formula: C7H5N3O2, the main research area is nitroazaindole preparation scalable process; nitrotrimethylsilanylethynylpyridinylamine preparation cycloisomerization; nitropyridinamine iodination Sonogashira reaction.

A simple and straightforward methodol. for the synthesis of 5-nitro-7-azaindole I has been developed using metal-free cycloisomerization of 5-nitro-3-trimethylsilanylethynyl-pyridin-2-ylamine. Large-scale applicability of this newly developed method was successfully demonstrated on multikilogram scale to obtain I in consistent yield and purity.

Organic Process Research & Development published new progress about Cycloisomerization. 101083-92-5 belongs to class indole-building-block, and the molecular formula is C7H5N3O2, Formula: C7H5N3O2.

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

Butkevich, Alexey N.; Bossi, Mariano L.; Lukinavicius, Grazvydas; Hell, Stefan W. published the artcile< Triarylmethane Fluorophores Resistant to Oxidative Photobluing>, Recommanded Product: 5-Fluoroindole-2-carboxylic acid, the main research area is triarylmethane fluorophore oxidative photobluing STED nanoscopy.

Spectral stability of small-mol. fluorescent probes is required for correct interpretation and reproducibility of multicolor fluorescence imaging data, in particular under high (de)excitation light intensities of super-resolution imaging or in single-mol. applications. The authors propose a synthetic approach to a series of spectrally stable rhodamine fluorophores based on sequential Ru- and Cu-catalyzed transformations, evaluate their stability against photobleaching and photoconversion in the context of other fluorophores using chemometric anal., and demonstrate chem. reactivity of fluorophore photoproducts. The substitution patterns providing the photoconversion-resistant triarylmethane fluorophores have been identified, and the applicability of nonbluing labels in live-cell STED nanoscopy is demonstrated.

Journal of the American Chemical Society published new progress about Fluorescence. 399-76-8 belongs to class indole-building-block, and the molecular formula is C9H6FNO2, Recommanded Product: 5-Fluoroindole-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

Woldegiorgis, Alemayehu Gashaw; Han, Zhao; Lin, Xufeng published the artcile< Asymmetric [3 + 3] Annulation to Construct Trifluoromethylated Pyrazolo[3,4-b]pyridin-6-ones via Chiral Phosphoric Acid and MgSO4 Synergistic Catalysis>, Reference of 20870-77-3, the main research area is trifluoromethyl pyrazolopyridinone preparation enantioselective diastereoselective; aminopyrazole trifluoroethylidene oxindole Friedel Crafts alkylation transamidation phosphoric acid.

A novel asym. Friedel-Crafts alkylation/transamidation tandem reaction for the enantio- and diastereoselective synthesis of pyrazolo[3,4-b]pyridin-6-ones I (R = H, Me, Cl; R1 = H, OMe, Br, Cl, F; R2 = H, Me, Br, F; R3 = H, Br; R4 = Boc, Cbz; R5 = H, Et, i-Pr; R6 = Ph, 3-bromophenyl, 1H-benzo[d]imidazol-2-yl, etc.; R7 = Me, Et, i-Pr, Ph) bearing a -CF3 unit via synergistic chiral phosphoric acid and MgSO4 catalysis was developed. This [3 + 3] annulation protocol allows the formation of trifluoromethylated pyrazolo[3,4-b]pyridin-6-ones I with two adjacent tertiary stereocenters in moderate to high yields (up to 90%), enantioselectivities (up to 97% ee), and diastereoselectivities (up to >20:1 dr).

Organic Letters published new progress about Diastereoselective synthesis. 20870-77-3 belongs to class indole-building-block, and the molecular formula is C8H6ClNO, Reference of 20870-77-3.

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

Ruel, Rejean; Thibeault, Carl; L’Heureux, Alexandre; Martel, Alain; Cai, Zhen-Wei; Wei, Donna; Qian, Ligang; Barrish, Joel C.; Mathur, Arvind; D’Arienzo, Celia; Hunt, John T.; Kamath, Amrita; Marathe, Punit; Zhang, Yueping; Derbin, George; Wautlet, Barri; Mortillo, Steven; Jeyaseelan, Robert Sr.; Henley, Benjamin; Tejwani, Ravindra; Bhide, Rajeev S.; Trainor, George L.; Fargnoli, Joseph; Lombardo, Louis J. published the artcile< Discovery and preclinical studies of 5-isopropyl-6-(5-methyl-1,3,4-oxadiazol-2-yl)-N-(2-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-4-amine (BMS-645737), an in vivo active potent VEGFR-2 inhibitor>, Name: 5-Nitro-1H-pyrrolo[2,3-b]pyridine, the main research area is BMS 645737 preparation structure VEGFR inhibitor antitumor.

The authors report herein a series of substituted N-(1H-pyrrolo[2,3-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-4-amines as inhibitors of vascular endothelial growth factor receptor-2 tyrosine kinase. Through structure-activity relationship studies, biochem. potency, pharmacokinetics, and kinase selectivity were optimized to afford BMS-645737 (I), a compound with good preclin. in vivo activity against human tumor xenograft models.

Bioorganic & Medicinal Chemistry Letters published new progress about Antitumor agents. 101083-92-5 belongs to class indole-building-block, and the molecular formula is C7H5N3O2, Name: 5-Nitro-1H-pyrrolo[2,3-b]pyridine.

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

Hu, Yuanyuan; Ruan, Wenchen; Gao, Anhui; Zhou, Yubo; Gao, Lixin; Xu, Meng; Gao, Jianrong; Ye, Qing; Li, Jia; Pang, Tao published the artcile< Synthesis and biological evaluation of novel 4,5-bisindolyl-1,2,4-triazol-3-ones as glycogen synthase kinase-3β inhibitors and neuroprotective agents>, Name: 5-Fluoro-1H-indole-3-carboxylic acid, the main research area is bisindolyltriazolone preparation glycogen synthase kinase inhibitor SAR neuroprotective agent.

A series of novel 4,5-bisindolyl-1,2,4-triazol-3-ones, compounds I [R1 = H, 6-F, 5-Cl, 6-Br, etc.; R2 = H, Me] were designed, prepared and evaluated for their glycogen synthase kinase (GSK)-3β inhibitory activities. Compounds exhibited favorable inhibitory potency towards GSK-3β kinase at the mol. level and in cells indicated by significantly reducing GSK-3β substrate Tau phosphorylation at Ser396 in primary neurons showing the inhibition of cellular GSK-3β. In an in vitro model of neuronal injury, compounds I [R1 = 5-F, 5-Cl, 5-Br; R2 = Me] prevented glutamate-induced neuronal death which was closely associated with cerebral ischemic stroke. Preliminary structure-activity relationship was examined and showed that different substituents on the indole ring had significant influences on the GSK-3β inhibitory potency. These findings may provide new insights into the development of novel GSK-3β inhibitors as neuroprotective agents.

Pharmazie published new progress about Blood-brain barrier. 23077-43-2 belongs to class indole-building-block, and the molecular formula is C9H6FNO2, Name: 5-Fluoro-1H-indole-3-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