- Rhodium-Catalyzed C?H Functionalization of Indoles with Diazo Compounds: Synthesis of Structurally Diverse 2,3-Fused Indoles
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A Rhodium-catalyzed C2-H functionalization of indoles with diazo compounds, followed by intramolecular nucleophilic addition to C=O or C=C bonds, is reported for divergent synthesis of 2,3-fused indoles. Besides acceptor/acceptor diazo compounds, donor/acceptor diazo compounds are broadly tolerated, giving various 2,3-fused indoles with perfect diastereocontrol. Notably, a selective C?H dialkylation reaction at C2 and C7 position of indoles has also been developed by simply changing the reaction conditions. This environmentally benign transformation proceeds under mild conditions and gives dinitrogen as the only by-product. (Figure presented.).
- Gao, Mengying,Yang, Yaxi,Chen, Hua,Zhou, Bing
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Read Online
- Indole based oxadiazole derivatives, preparation method therof
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The present invention provides an indole-based oxadiazole derivative, an optical isomer thereof, or a pharmaceutically acceptable salt thereof. The indole-based oxadiazole derivative, the optical isomer thereof, or the pharmaceutically acceptable salt thereof according to the present invention has little cytotoxicity and effectively inhibits urease activity, thereby exhibiting an excellent effect in the prevention or treatment of diseases related to urease activity or diseases caused by Helicobacter pylori.
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Paragraph 0084-0086
(2021/01/29)
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- Synthesis of CF3-Containing Spirocyclic Indolines via a Red-Light-Mediated Trifluoromethylation/Dearomatization Cascade
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A red-light-mediated nPr-DMQA+-catalyzed cascade intramolecular trifluoromethylation and dearomatization of indole derivatives with Umemoto's reagent has been developed. This protocol provides a facile and efficient approach for the construction of functionalized and potentially biologically important CF3-containing 3,3-spirocyclic indolines with moderate to high yields and excellent diastereoselectivities under mild conditions. The success of multiple gram-scale (1 and 10 g) experiments further highlights the robustness and practicality of this protocol and the merit of the employment of red light. Mechanistic studies support the formation of a crucial CF3 radical species and a dearomatized benzyl carbocation intermediate.
- Gianetti, Thomas L.,Mei, Liangyong,Moutet, Jules,Stull, Savannah M.
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supporting information
p. 10640 - 10653
(2021/07/31)
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- METHODS AND MATERIALS FOR INCREASING OR MAINTAINING NICOTINAMIDE MONONUCLEOTIDE ADENYLYL TRANSFERASE-2 (NMNAT2) POLYPEPTIDE LEVELS
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This document provides methods and materials for increasing or maintaining NMNAT2 polypeptide levels within cells. For example, compounds (e.g., organic compounds) having the ability to increase or maintain NMNAT2 polypeptide levels within cells, formulations containing compounds having the ability to increase or maintain NMNAT2 polypeptide levels within cells, methods for making compounds having the ability to increase or maintain NMNAT2 polypeptide levels within cells, methods for making formulations containing compounds having the ability to increase or maintain NMNAT2 polypeptide levels within cells, methods for increasing or maintain NMNAT2 polypeptide levels within cells, and methods for treating mammals (e.g., humans) having a condition responsive to an increase in NMNAT2 polypeptide levels are provided (or for preventing said condition).
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Page/Page column 182; 183
(2020/09/08)
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- Convergent synthesis, free radical scavenging, Lineweaver-Burk plot exploration, hemolysis and in silico study of novel indole-phenyltriazole hybrid bearing acetamides as potent urease inhibitors
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In the current paper, through a convergent multi-step approach, a library of novel indole-phenyltriazole hybrids containing an amide moiety (9a-k) was synthesized. The structural verification of all synthesized molecules was accomplished by CHN and spectral analyses data. These synthesized bi-heterocyclic derivatives (9a-k) were evaluated for their anti-ulcer potential by inhibitory action against Jack bean urease enzyme and subsequently their structure-activity relationship was perceived. Moreover, these compounds were inspected for cytotoxic profile by hemolytic activity and it was professed that nearly all the synthesized compounds showed low cytotoxicity. In addition, free radical scavenging activity and kinetic analysis were also carried out for these compounds to understand their mode of inhibition. So, it was summated that these derivatives might lead to further research gateways for obtaining better and safe anti-ulcer agents.
- Abbasi, Muhammad A.,Ali Shah, Syed A.,Hassan, Mubashir,Khan, Wajiha,Nazir, Majid,Raza, Hussain,Rehman, Aziz-ur,Seo, Sung Y.,Shahid, Muhammad,Siddiqui, Sabahat Z.
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- Bi-heterocyclic benzamides as alkaline phosphatase inhibitors: Mechanistic comprehensions through kinetics and computational approaches
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Novel bi-heterocyclic benzamides were synthesized by sequentially converting 4-(1H-indol-3-yl)butanoic acid (1) into ethyl 4-(1H-indol-3-yl)butanoate (2), 4-(1H-indol-3-yl)butanohydrazide (3), and a nucleophilic 5-[3-(1H-indol-3-yl)propyl]-1,3,4-oxadiazole-2-thiol (4). In a parallel series of reactions, various electrophiles were synthesized by reacting substituted anilines (5a–k) with 4-(chloromethyl)benzoylchloride (6) to afford 4-(chloromethyl)-N-(substituted-phenyl)benzamides (7a–k). Finally, the nucleophilic substitution reaction of 4 was carried out with newly synthesized electrophiles, 7a–k, to acquire the targeted bi-heterocyclic benzamides, 8a–k. The structural confirmation of all the synthesized compounds was done by IR, 1H NMR, 13C NMR, EI-MS, and CHN analysis data. The inhibitory effects of these bi-heterocyclic benzamides (8a–k) were evaluated against alkaline phosphatase, and all these molecules were identified as potent inhibitors relative to the standard used. The kinetics mechanism was ascribed by evaluating the Lineweaver–Burk plots, which revealed that compound 8b inhibited alkaline phosphatase non-competitively to form an enzyme–inhibitor complex. The inhibition constant Ki calculated from Dixon plots for this compound was 1.15 μM. The computational study was in full agreement with the experimental records and these ligands exhibited good binding energy values. These molecules also exhibited mild cytotoxicity toward red blood cell membranes when analyzed through hemolysis. So, these molecules might be deliberated as nontoxic medicinal scaffolds to render normal calcification of bones and teeth.
- Abbasi, Muhammad A.,Nazir, Majid,ur-Rehman, Aziz,Siddiqui, Sabahat Z.,Hassan, Mubashir,Raza, Hussain,Shah, Syed A. A.,Shahid, Muhammad,Seo, Sung-Yum
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- Novel indole based hybrid oxadiazole scaffolds with: N -(substituted-phenyl)butanamides: Synthesis, lineweaver-burk plot evaluation and binding analysis of potent urease inhibitors
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In the study presented herein, 4-(1H-indol-3-yl)butanoic acid (1) was sequentially transformed in the first phase into ethyl 4-(1H-indol-3-yl)butanoate (2), 4-(1H-indol-3-yl)butanohydrazide (3) and 5-[3-(1H-indol-3-yl)propyl]-1,3,4-oxadiazole-2-thiol (4)
- Nazir, Majid,Abbasi, Muhammad Athar,Aziz-Ur-Rehman,Siddiqui, Sabahat Zahra,Raza, Hussain,Hassan, Mubashir,Ali Shah, Syed Adnan,Shahid, Muhammad,Seo, Sung-Yum
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p. 25920 - 25931
(2018/08/03)
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- New indole based hybrid oxadiazole scaffolds with N-substituted acetamides: As potent anti-diabetic agents
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Current study is based on the sequential conversion of indolyl butanoic acid (1) into ethyl indolyl butanoate (2), indolyl butanohydrazide (3), and 1,3,4-oxadiazole-2-thiol analogs (4) by adopting chemical transformations. In a parallel series of reaction
- Nazir, Majid,Abbasi, Muhammad Athar,Aziz-ur-Rehman,Siddiqui, Sabahat Zahra,Khan, Khalid Mohammed,Kanwal,Salar, Uzma,Shahid, Muhammad,Ashraf, Muhammad,Arif Lodhi, Muhammad,Ali Khan, Farman
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p. 253 - 263
(2018/09/05)
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- Catalytic Enantioselective Synthesis of Tetrahydocarbazoles and Exocyclic Pictet-Spengler-Type Reactions
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A synthetic strategy for the synthesis of chiral tetrahydrocarbazoles (THCAs) has been developed. The strategy relies on two types of 6-exo-trig cyclization of 3-substituted indole substrates. Enantioselective domino Friedel-Crafts-type reactions leading to THCAs can be catalyzed by chiral phosphoric acid derivatives (with up to >99% ee), and the first examples of exocyclic Pictet-Spengler reactions to form THCAs are reported.
- Hansen, Casper L.,Ohm, Ragnhild G.,Olsen, Lasse B.,Ascic, Erhad,Tanner, David,Nielsen, Thomas E.
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supporting information
p. 5990 - 5993
(2016/12/09)
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- SUBSTITUTED HETEROARYL COMPOUNDS AND METHODS OF USE THEREOF
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Provided herein are novel heteroaryl compounds, pharmaceutically acceptable salts and pharmaceutical formulations thereof for selectively inhibiting serotonin reuptake and/or acting as 5-HT1A receptor agonists. Also provided herein are pharmaceutical compositions comprising the heteroaryl compounds and methods of using the pharmaceutical compositions in treating central nervous system (CNS) dysfunction in a mammal, especially a human being.
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- SUBSTITUTED PIPERAZINE COMPOUNDS AND METHODS AND USE THEREOF
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Provided herein are novel piperazine compounds acting as selective serotonin reuptake inhibitors and/or the 5-HT1A receptor agonists. The invention also relates to the methods of preparing the compound and pharmaceutical composition, and the use of treating central nervous system dysfunction in mammals especially in humans.
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Paragraph 00225; 00314
(2015/11/27)
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- Synthesis and biological screening of 5-(alkyl(1H-indol-3-yl))-2- (substituted)-1,3,4-oxadiazoles as antiproliferative and anti-inflammatory agents
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A series of 5-(alkyl(1H-indol-3-yl))-2-(substituted)-1,3,4-oxadiazoles were efficiently synthesized by oxidative cyclisation of N0 -benzylidene-(1H-indol- 3-yl)alkane hydrazides using di(acetoxy)iodobenzene. N0 -Benzylidene-(1H-indol- 3-yl)alkane hydrazid
- Rapolu, Sreevani,Alla, Manjula,Bommena, Vittal Rao,Murthy, Ramalinga,Jain, Nishant,Bommareddy, Venkata Ramya,Bommineni, Madhava Reddy
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- Indolyl-3-acetaldoxime dehydratase from the phytopathogenic fungus Sclerotinia sclerotiorum: Purification, characterization, and substrate specificity
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The purification and characterization of indolyl-3-acetaldoxime dehydratase produced by the plant fungal pathogen Sclerotinia sclerotiorum is described. The substrate specificity indicates that it is an indolyl-3-acetaldoxime dehydratase (IAD, EC 4.99.1.6), which catalyzes transformation of indolyl-3-acetaldoxime to indolyl-3-acetonitrile. The enzyme showed Michaelis-Menten kinetics and had an apparent molecular mass of 44 kDa. The amino acid sequence of IAD, determined using LC-ESI-MS/MS, identified it as the protein SS1G-01653 from S. sclerotiorum. IADSs was highly homologous (84% amino acid identity) to the hypothetical protein BC1G-14775 from Botryotinia fuckeliana B05.10. In addition, similarity to the phenylacetaldoxime dehydratases from Gibberella zeae (33% amino acid identity) and Bacillus sp. (20% amino acid identity) was noted. The specific activity of IADSs increased about 17-fold upon addition of Na2S2O4 under anaerobic conditions, but in the absence of Na2S2O 4 no significant change was observed, whether aerobic or anaerobic conditions were used. As with other aldoxime dehydratases isolated from microbes, the role of IADSs in fungal plant pathogens is not clear, but given its substrate specificity, it appears unlikely that IADSs is a general xenobiotic detoxifying enzyme.
- Pedras, M. Soledade C.,Minic, Zoran,Thongbam, Premila D.,Bhaskar, Vangala,Montaut, Sabine
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experimental part
p. 1952 - 1962
(2011/06/26)
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- New N-(pyridin-4-yl)-(indol-3-yl)acetamides and propanamides as antiallergic agents
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A series of new N-(pyridin-4-yl)-(indol-3-yl)alkylamides 44-84 has been prepared in the search of novel antiallergic compounds. Synthesis of the desired ethyl (2-methyindol-3-yl)acetates 1-4 was achieved by indolization under Fischer conditions; Japp-Klingemann method followed by 2- decarboxylation afforded the ethyl (indol-3-yl)alkanoates 17-25. Amidification was successfully carried out by condensation of the corresponding acids or their N-aryl(methyl) derivatives with 4-aminopyridine promoted by 2-chloro-1-methylpyridinium iodide. Efforts to improve the antiallergic potency of the title series by variation of the indole substituents (R1, R2, R) and the length of the alkanoic chain (n = 1, 2, 3) led to the selection of N-(pyridin-4-yl)-[1-(4-fluorobenzyl)indol-3- yl]acetamide 45, out of 41 compounds. This amide was 406-fold more potent than astemizole in the ovalbumin-induced histamine release assay, using guinea pig peritoneal mast cells, with an IC50 = 0.016 μM. Its inhibitory activity in IL-4 production test from Th-2 cells was identical to that of the reference histamine antagonist (IC50 = 8.0 μM) and twice higher in IL-5 assay: IC50 = 1.5 and 3.3 μM, respectively. In vivo antiallergic activity evaluation confirmed efficiency of 45 in sensitized guinea pig late phase eosinophilia inhibition, after parenteral and oral administration at 5 and 30 mg/kg, respectively. Its efficiency in inhibition of microvascular permeability was assessed in two rhinitis models; ovalbumin and capsaicin- induced rhinorrhea could be prevented after topical application of submicromolar concentrations of 45 (IC50 = 0.25 and 0.30 μM); and it also exerted significant inhibitory effect in the first test after iv and oral administration, with ID50 = 0.005 and 0.46 mg/kg.
- Menciu, Cecilia,Duflos, Muriel,Fouchard, Fabienne,Le Baut, Guillaume,Emig, Peter,Achterrath, Ute,Szelenyi, Istvan,Nickel, Bernd,Schmidt, Jürgen,Kutscher, Bernhard,Günther, Eckhardt
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p. 638 - 648
(2007/10/03)
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- AN EFFECTIVE DEHYDROGENATIONS OF INDOLINES TO INDOLES WITH COBALT(II) SCHIFF'S BASE COMPLEXES
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Facile dehydrogenations of indolines to indoles were performed with the catalytic amount of bis(salicylidene)ethylenediaminatocobalt(II) and bis(3-methoxysalicylidene)ethylenediaminatocobalt(II) under mild conditions in 55-92percent yields.
- Inada, Akira,Nakamura, Yushin,Morita, Yutaka
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p. 1287 - 1290
(2007/10/02)
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