Category: 101083-92-5

Forster, Michael; Liang, Xiaojun Julia; Schroeder, Martin; Gerstenecker, Stefan; Chaikuad, Apirat; Knapp, Stefan; Laufer, Stefan; Gehringer, Matthias published the artcile< Discovery of a novel class of covalent dual inhibitors targeting the protein kinases BMX and BTK>, Application In Synthesis of 101083-92-5, the main research area is phenyl pyrrolopyridine prepare kinase inhibitor mol docking SAR; Bruton’s tyrosine kinase; Janus kinase 3; bone marrow tyrosine kinase on chromosome X; chemical probes; covalent inhibitors; tyrosine kinases.

Here a novel class of dual BMX/BTK inhibitors, which were designed from irreversible inhibitors of Janus kinase (JAK) 3 targeting a cysteine located within the solvent-exposed front region of the ATP binding pocket was presented. Structure-guided design exploiting the differences in the gatekeeper residues enabled the achievement of high selectivity over JAK3 and certain other kinases harboring a sterically demanding residue at this position. The most active compounds inhibited BMX and BTK with apparent IC50 values in the single digit nanomolar range or below showing moderate selectivity within the TEC family and potent cellular target engagement. These compounds represent an important first step towards selective chem. probes for the protein kinase BMX.

International Journal of Molecular Sciences published new progress about Acid chlorides Role: RCT (Reactant), RACT (Reactant or Reagent). 101083-92-5 belongs to class indole-building-block, and the molecular formula is C7H5N3O2, Application In Synthesis of 101083-92-5.

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

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

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

Sellmer, Andreas; Pilsl, Bernadette; Beyer, Mandy; Pongratz, Herwig; Wirth, Lukas; Elz, Sigurd; Dove, Stefan; Henninger, Sven Julian; Spiekermann, Karsten; Polzer, Harald; Klaeger, Susan; Kuster, Bernhard; Boehmer, Frank D.; Fiebig, Heinz-Herbert; Kraemer, Oliver H.; Mahboobi, Siavosh published the artcile< A series of novel aryl-methanone derivatives as inhibitors of FMS-like tyrosine kinase 3 (FLT3) in FLT3-ITD-positive acute myeloid leukemia>, Reference of 101083-92-5, the main research area is aryl methanone preparation FLT3 tyrosine kinase inhibitor antitumor human; Acute myeloid leukemia; FLT3; FLT3 D835Y; FLT3-ITD; Tyrosine kinase inhibitor.

Mutants of the FLT3 receptor tyrosine kinase (RTK) with duplications in the juxtamembrane domain (FLT3-ITD) act as drivers of acute myeloid leukemia (AML). Potent tyrosine kinase inhibitors (TKi) of FLT3-ITD entered clin. trials and showed a promising, but transient success due to the occurrence of secondary drug-resistant AML clones. A further caveat of drugs targeting FLT3-ITD is the co-targeting of other RTKs which are required for normal hematopoiesis. This is observed quite frequently. Therefore, novel drugs are necessary to treat AML effectively and safely. Recently bis(1H-indol-2-yl)methanones were found to inhibit FLT3 and PDGFR kinases. In order to optimize these agents novel derivatives of these methanones with various substituents were synthesized. Methanone I and its carbamate derivative II inhibit FLT3-ITD at least as potently as the TKi AC220 (quizartinib). Models indicate corresponding interactions of I and quizartinib with FLT3. The activity of I is accompanied by a high selectivity for FLT3-ITD.

European Journal of Medicinal Chemistry published new progress about Acute myeloid leukemia. 101083-92-5 belongs to class indole-building-block, and the molecular formula is C7H5N3O2, Reference of 101083-92-5.

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

Schnute, Mark E.; Wennerstal, Mattias; Alley, Jennifer; Bengtsson, Martin; Blinn, James R.; Bolten, Charles W.; Braden, Timothy; Bonn, Tomas; Carlsson, Bo; Caspers, Nicole; Chen, Ming; Choi, Chulho; Collis, Leon P.; Crouse, Kimberly; Farnegardh, Mathias; Fennell, Kimberly F.; Fish, Susan; Flick, Andrew C.; Goos-Nilsson, Annika; Gullberg, Hjalmar; Harris, Peter K.; Heasley, Steven E.; Hegen, Martin; Hromockyj, Alexander E.; Hu, Xiao; Husman, Bolette; Janosik, Tomasz; Jones, Peter; Kaila, Neelu; Kallin, Elisabet; Kauppi, Bjorn; Kiefer, James R.; Knafels, John; Koehler, Konrad; Kruger, Lars; Kurumbail, Ravi G.; Kyne, Robert E.; Li, Wei; Lofstedt, Joakim; Long, Scott A.; Menard, Carol A.; Mente, Scot; Messing, Dean; Meyers, Marvin J.; Napierata, Lee; Noteberg, Daniel; Nuhant, Philippe; Pelc, Matthew J.; Prinsen, Michael J.; Rhonnstad, Patrik; Backstrom-Rydin, Eva; Sandberg, Johnny; Sandstrom, Maria; Shah, Falgun; Sjoberg, Maria; Sundell, Aron; Taylor, Alexandria P.; Thorarensen, Atli; Trujillo, John I.; Trzupek, John D.; Unwalla, Ray; Vajdos, Felix F.; Weinberg, Robin A.; Wood, David C.; Xing, Li; Zamaratski, Edouard; Zapf, Christoph W.; Zhao, Yajuan; Wilhelmsson, Anna; Berstein, Gabriel published the artcile< Discovery of 3-Cyano-N-(3-(1-isobutyrylpiperidin-4-yl)-1-methyl-4-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)benzamide: A Potent, Selective, and Orally Bioavailable Retinoic Acid Receptor-Related Orphan Receptor C2 Inverse Agonist>, Recommanded Product: 5-Nitro-1H-pyrrolo[2,3-b]pyridine, the main research area is cyanophenylamido isobutyrylpiperidinyl trifluoromethyl pyrrolopyridine preparation retinoic acid receptor; retinoic acid receptor related orphan receptor C2 inverse agonist; cyanobenzamide isobutyrylpiperidinyl pyrrolopyridinyl trifluoromethyl preparation retinoic acid receptor.

The nuclear hormone receptor retinoic acid receptor-related orphan C2 (RORC2, also known as RORγt) is a promising target for the treatment of autoimmune diseases. A small mol., inverse agonist of the receptor is anticipated to reduce production of IL-17, a key proinflammatory cytokine. Through a high-throughput screening approach, authors identified a mol. displaying promising binding affinity for RORC2, inhibition of IL-17 production in Th17 cells, and selectivity against the related RORA and RORB receptor isoforms. Lead optimization to improve the potency and metabolic stability of this hit focused on two key design strategies, namely, iterative optimization driven by increasing lipophilic efficiency and structure-guided conformational restriction to achieve optimal ground state energetics and maximize receptor residence time. This approach successfully identified 3-cyano-N-(3-(1-isobutyrylpiperidin-4-yl)-1-methyl-4-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)benzamide as a potent and selective RORC2 inverse agonist, demonstrating good metabolic stability, oral bioavailability, and the ability to reduce IL-17 levels and skin inflammation in a preclin. in vivo animal model upon oral administration.

Journal of Medicinal Chemistry published new progress about Autoimmune disease. 101083-92-5 belongs to class indole-building-block, and the molecular formula is C7H5N3O2, Recommanded Product: 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

Ermoli, Antonella; Bargiotti, Alberto; Brasca, Maria Gabriella; Ciavolella, Antonella; Colombo, Nicoletta; Fachin, Gabriele; Isacchi, Antonella; Menichincheri, Maria; Molinari, Antonio; Montagnoli, Alessia; Pillan, Antonio; Rainoldi, Sonia; Sirtori, Federico Riccardi; Sola, Francesco; Thieffine, Sandrine; Tibolla, Marcellino; Valsasina, Barbara; Volpi, Daniele; Santocanale, Corrado; Vanotti, Ermes published the artcile< Cell Division Cycle 7 Kinase Inhibitors: 1H-Pyrrolo[2,3-b]pyridines, Synthesis and Structure-Activity Relationships>, Product Details of C7H5N3O2, the main research area is cell division cycle 7 kinase inhibitor pyrrolopyridine preparation SAR.

Cdc7 kinase has recently emerged as an attractive target for cancer therapy and low-mol.-weight inhibitors of Cdc7 kinase have been found to be effective in the inhibition of tumor growth in animal models. In this paper, we describe synthesis and structure-activity relationships of new 1H-pyrrolo[2,3-b]pyridine derivatives identified as inhibitors of Cdc7 kinase. Progress from (Z)-2-phenyl-5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethylene)-3,5-dihydro-4H-imidazol-4-one to [(Z)-2-(benzylamino)-5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethylene)-1,3-thiazol-4(5H)-one] (I), a potent ATP mimetic inhibitor of Cdc7 kinase with IC50 value of 7 nM, is also reported.

Journal of Medicinal Chemistry published new progress about Molecular modeling. 101083-92-5 belongs to class indole-building-block, and the molecular formula is C7H5N3O2, Product Details of 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

Wang, Lei; Taniguchi, Yosuke; Okamura, Hidenori; Sasaki, Shigeki published the artcile< Modification of the aminopyridine unit of 2'-deoxyaminopyridinyl-pseudocytidine allowing triplex formation at CG interruptions in homopurine sequences>, HPLC of Formula: 101083-92-5, the main research area is aminopyridine derive sequence synthesis CG inversion site.

The antigene strategy based on site-specific recognition of duplex DNA by triplex DNA formation has been exploited in a wide range of biol. activities. However, specific triplex formation is mostly restricted to homo-purine strands within the target duplex DNA, due to the destabilizing effect of CG and TA inversion sites where there is an absence of natural nucleotides that can recognize the CG and TA base pairs. Hence, the design of artificial nucleosides, which can selectively recognize these inversion sites with high affinity, should be of great significance. Recently, we determined that 2-amino-3-methylpyridinyl pseudo-dC (3MeAP-VdC) possessed significant affinity and selectivity toward a CG inversion site and showed effective inhibition of gene expression. We now describe the design and synthesis of new modified aminopyridine derivatives by focusing on small chem. modification of the aminopyridine unit to tune and enhance the selectivity and affinity toward CG inversion sites. Remarkably, we have newly found that 2-amino-4-methoxypyridinyl pseudo-dC (4OMeAP-VdC) could selectively recognize the CG base pair in all four adjacent base pairs and form a stable triplex structure against the promoter sequence of the human gene including multiple CG inversion sites.

Nucleic Acids Research published new progress about Aminopyridines Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 101083-92-5 belongs to class indole-building-block, and the molecular formula is C7H5N3O2, HPLC of Formula: 101083-92-5.

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

Pearson, Stuart E.; Nandan, Santosh published the artcile< A practical, efficient synthesis of 5-amino-7-azaindole>, Application of C7H5N3O2, the main research area is azaindole reduction Raney nickel; azaindoline preparation nitration; nitro azaindole preparation reduction; nitropyridine amino iodination; iodo amino pyridine preparation Sonogashira reaction acetylene silane; silylacetylaminopyridine preparation heteroannulation; amino azaindole preparation.

A much improved, workable synthesis of 5-amino-7-azaindole is described in 66% overall yield starting from 2-amino-5-nitropyridine. The key stage involves a microwave promoted heteroannulation reaction of a pyridine alkyne.

Synthesis published new progress about Heterocyclization. 101083-92-5 belongs to class indole-building-block, and the molecular formula is C7H5N3O2, Application of 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

Forster, Michael; Liang, Xiaojun Julia; Schroeder, Martin; Gerstenecker, Stefan; Chaikuad, Apirat; Knapp, Stefan; Laufer, Stefan; Gehringer, Matthias published the artcile< Discovery of a novel class of covalent dual inhibitors targeting the protein kinases BMX and BTK>, Formula: C7H5N3O2, the main research area is phenyl pyrrolopyridine prepare kinase inhibitor mol docking SAR; Bruton’s tyrosine kinase; Janus kinase 3; bone marrow tyrosine kinase on chromosome X; chemical probes; covalent inhibitors; tyrosine kinases.

Here a novel class of dual BMX/BTK inhibitors, which were designed from irreversible inhibitors of Janus kinase (JAK) 3 targeting a cysteine located within the solvent-exposed front region of the ATP binding pocket was presented. Structure-guided design exploiting the differences in the gatekeeper residues enabled the achievement of high selectivity over JAK3 and certain other kinases harboring a sterically demanding residue at this position. The most active compounds inhibited BMX and BTK with apparent IC50 values in the single digit nanomolar range or below showing moderate selectivity within the TEC family and potent cellular target engagement. These compounds represent an important first step towards selective chem. probes for the protein kinase BMX.

International Journal of Molecular Sciencespublished new progress about Acid chlorides Role: RCT (Reactant), RACT (Reactant or Reagent). 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