Tag: M.W=150-200

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

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

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

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

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

Xu, Hai-Feng; Pan, You-Lu; Li, Gang-Jian; Hu, Xu-Yang; Chen, Jian-Zhong published the artcile< Copper(II)-Catalyzed Direct C-H (Hetero)arylation at the C3 Position of Indoles Assisted by a Removable N,N-Bidentate Auxiliary Moiety>, Recommanded Product: 5-Fluoroindole-2-carboxylic acid, the main research area is arylated indole regioselective preparation; indole arylboronic ester arylation copper catalyst.

The regioselective arylation of inert C3-H bonds in indoles reacting with arylboronates via effective copper-mediated catalysis with the aid of a facile and removable 2-pyridinylisopropyl (PIP) group without ligand participation was reported. This newly established method features high compatibility with diverse functional groups between coupling partners, including both indole substrates and arylboron reagents, consequentially leading to operational simplicity and providing access to generate the desired arylated products I [R = H, 4-Me, 5-MeO, 6-Br, etc.; R1 = Me, Bn; Ar = Ph, 2-thienyl, 3-pyridyl, etc.] in good to excellent yields of up to 97%. Synthetically, the PIP-derived amide moiety could subsequently be readily removed under mild reaction conditions to produce useful indolecarboxylic acids for further transformation.

Journal of Organic Chemistry published new progress about Amides, secondary Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 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

Chen, Weiliang; Xia, Yong; Lin, Lili; Yuan, Xiao; Guo, Songsong; Liu, Xiaohua; Feng, Xiaoming published the artcile< Asymmetric Synthesis of Furo[3,4-b]indoles by Catalytic [3+2] Cycloaddition of Indoles with Epoxides>, Application In Synthesis of 4771-48-6, the main research area is indole furan furoindole preparation; N,N′-dioxide-metal complex; asymmetric synthesis; epoxides; indoles.

A highly efficient N,N’-dioxide-nickel(II) catalyst system for the catalytic [3+2] cycloaddition of indoles with epoxides through C-C cleavage of oxiranes (i.e., epoxides) was accomplished under mild conditions. It provided a promising approach for chiral furo[3,4-b]indoles in up to 98% yield with up to 91% enantiomeric excess (ee) and >95:5 diastereomeric ratio (d.r.). Under optimized conditions the synthesis of the target compounds was achieved using (1R,1’R,2S,2’S)-1,1′-(1,3-propanediyl)bis[N-[2,4,6-tris(1-methylethyl)phenyl]-2-pyrrolidinecarboxamide] 1,1′-dioxide, perchloric acid nickel(2+) salt hexahydrate (nickel perchlorate hexahydrate) and 1,1,1-trifluoro-N-[(trifluoromethyl)sulfonyl]methanesulfonamide lithium salt (lithium triflimide) as ligand-catalyst combination. Starting materials included 3-(4-methylphenyl)-2,2-oxiranedicarboxylic acid di-Me ester and 1,3-dimethyl-1H-indole derivatives The title compounds thus formed included 1,3a,4,8b-tetrahydro-4,8b-dimethyl-1-(4-methylphenyl)-3H-furo[3,4-b]indole-3,3-dicarboxylic acid 3,3-di-Me ester and related substances.

Chemistry – A European Journal published new progress about [3+2] Cycloaddition reaction. 4771-48-6 belongs to class indole-building-block, and the molecular formula is C10H9NO, Application In Synthesis of 4771-48-6.

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

Wang, Qing-Dong; Zhou, Bin; Yang, Jin-Ming; Fang, Dong; Ren, Jiangmeng; Zeng, Bu-Bing published the artcile< Iron-Catalyzed C3-Formylation of Indoles with Formaldehyde and Aqueous Ammonia under Air>, Related Products of 4771-48-6, the main research area is formylindole preparation green chem regioselective; indole formaldehyde formylation iron catalyst.

An efficient iron-catalyzed C3-selective formylation of free (N-H) or N-substituted indoles such as 2-phenyl-1H-indole, 6-fluoro-1H-indole, 1-methyl-1H-indole, etc. was developed by employing formaldehyde and aqueous ammonia, with air as the oxidant. This new method gave 3-formylindoles such as 2-phenyl-1H-indole-3-carbaldehyde, 6-fluoro-1H-indole-3-carbaldehyde, 1-methyl-1H-indole-3-carbaldehyde, etc. in moderate to excellent yields with fairly short reaction times. Moreover, this procedure for catalytic formylation of indoles can be applied to gram-scale syntheses.

Synlett published new progress about Formylation, regioselective. 4771-48-6 belongs to class indole-building-block, and the molecular formula is C10H9NO, Related Products of 4771-48-6.

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