- Synthesis and Anticonvulsant Studies of Thiazolidinone and Azetidinone Derivatives from Indole Moiety
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2-Amino-5-(3'-indolomethylene)-1, 3, 4 - oxadiazole (3) undergoes facile condensation with various aromatic aldehydes to gave 2-substitiuted arylidenylamino-5-(3'- indolomethylene) - 1, 3, 4 - oxadiazole (4-8). Cyclocondensation of (4-8) with thioglycolic acid and triethylamine yielded 3-[5'-(3- indolomethylene)- 1', 3', 4'- oxadiazol-2'-yl]- 2- (substituted aryl)-4- thiazolidinones (9-13) and 1-[5'-(3- indolomethylene) -1', 3', 4'- oxadiazol - 2'- yl ] -4-(substituted aryl) -2- azetidinones (14-18). The structures of these compounds were established on the basis of analytical and spectral data. The newly synthesised compounds were evaluated for their anticonvulsant activity and acute toxicity.
- Saini, Sachin
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Read Online
- Discovery, synthesis and biological characterization of a series of: N -(1-(1,1-dioxidotetrahydrothiophen-3-yl)-3-methyl-1 H -pyrazol-5-yl)acetamide ethers as novel GIRK1/2 potassium channel activators
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The present study describes the discovery and characterization of a series of N-(1-(1,1-dioxidotetrahydrothiophen-3-yl)-3-methyl-1H-pyrazol-5-yl)acetamide ethers as G protein-gated inwardly-rectifying potassium (GIRK) channel activators. From our previous lead optimization efforts, we have identified a new ether-based scaffold and paired this with a novel sulfone-based head group to identify a potent and selective GIRK1/2 activator. In addition, we evaluated the compounds in tier 1 DMPK assays and have identified compounds that display nanomolar potency as GIRK1/2 activators with improved metabolic stability over the prototypical urea-based compounds. This journal is
- Alnouti, Yazen,Aretz, Christopher D.,Chhonker, Yashpal S.,Dhuria, Nikilesh V.,Du, Yu,Gautam, Nagsen,Hopkins, Corey R.,Kumar, Sushil,Lesiak, Lauren,Sharma, Swagat,Weaver, C. David
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supporting information
p. 1366 - 1373
(2021/09/28)
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- Fe-catalyzed Fukuyama-type indole synthesis triggered by hydrogen atom transfer
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Fe, Co, and Mn hydride-initiated radical olefin additions have enjoyed great success in modern synthesis, yet the extension of other hydrogen radicalophiles instead of olefins remains largely elusive. Herein, we report an efficient Fe-catalyzed intramolec
- Huang, Hanmin,Yu, Min,Zhang, Tianze
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p. 10501 - 10505
(2021/08/20)
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- SUBSTITUTED TETRAHYDROPYRANOINDOLES, DERIVATIVES THEREOF, AND THEIR METHODS OF SYNTHESIS AND USE
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Disclosed herein are tetrahydropyranoindole compounds and derivatives thereof, as well as their methods of synthesis and use. The disclosed compounds may be synthesized by methods that utilize a cooperative hydrogen bond donor/Br?nsted acid system. The disclosed compounds may be useful for treating a disease, disorder, or a symptom thereof in a subject in need thereof, such as pain, swelling, and joint stiffness. The disclosed compounds also may be useful for treating cell proliferative diseases and disorders such as cancer.
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Paragraph 0146; 0147; 0175; 0176
(2021/01/25)
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- A new CDK2 inhibitor with 3-hydrazonoindolin-2-one scaffold endowed with anti-breast cancer activity: Design, synthesis, biological evaluation, and in silico insights
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Background: Cyclin-dependent kinases (CDKs) regulate mammalian cell cycle progression and RNA transcription. Based on the structural analysis of previously reported CDK2 inhibitors, a new compound with 3-hydrazonoindolin-2-one scaffold (HI 5) was well designed, synthesized, and biologically evaluated as a promising anti-breast cancer hit compound. Methods: The potential anti-cancerous effect of HI 5 was evaluated using cytotoxicity assay, flow cytometric analysis of apoptosis and cell cycle distribution, ELISA immunoassay, in vitro CDK2/cyclin A2 activity, and molecular operating environment (MOE) virtual docking studies. Results: The results revealed that HI 5 exhibits pronounced CDK2 inhibitory activity and cytotoxicity in human breast cancer MCF-7 cell line. The cytotoxicity of HI 5 was found to be intrinsically mediated apoptosis, which in turn, is associated with low Bcl-2 expression and high activation of caspase 3 and p53. Besides, HI 5 blocked the proliferation of the MCF-7 cell line and arrested the cell cycle at the G2/M phase. The docking studies did not confirm which one of geometric isomers (syn and anti) is responsible for binding affinity and intrinsic activity of HI 5. However, the molecular dynamic studies have confirmed that the syn-isomer has more favorable binding interaction and thus is responsible for CDK2 inhibitory activity. Discussion: These findings displayed a substantial basis of synthesizing further derivatives based on the 3-hydrazonoindolin-2-one scaffold for favorable targeting of breast cancer.
- Al-Sanea, Mohammad M.,Obaidullah, Ahmad J.,Shaker, Mohamed E.,Chilingaryan, Garri,Alanazi, Mohammed M.,Alsaif, Nawaf A.,Alkahtani, Hamad M.,Alsubaie, Sultan A.,Abdelgawad, Mohamed A.
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- Diversity-oriented synthesis and antifungal activities of novel pimprinine derivative bearing a 1,3,4-oxadiazole-5-thioether moiety
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Abstract: Based on the strategy of diversity-oriented synthesis and the structures of natural product pimprinine and streptochlorin, two series of novel pimprinine derivatives containing 1,3,4-oxadiazole-5-thioether moieties were efficiently synthesized under the optimized reaction conditions. Biological assays conducted at Syngenta showed the designed derivatives displayed an altered pattern of biological activity, of which 5h was identified as the most promising compound with strong activity against Pythium dissimile and also a broad antifungal spectrum in primary screening. Further structural optimization of pimprinine and streptochlorin derivatives is well under way, aiming to discover synthetic analogues with improved antifungal activity. Graphic abstract: Two series of novel pimprinine derivatives containing 1,3,4-oxadiazole-5-thioether moieties wereefficiently synthesized through diversity-oriented synthesis strategy under the optimizedconditions. Biological assays showed the designed derivatives exhibited potential activity.[Figure not available: see fulltext.].
- Song, Zi-Long,Zhu, Yun,Liu, Jing-Rui,Guo, Shu-Ke,Gu, Yu-Cheng,Han, Xinya,Dong, Hong-Qiang,Sun, Qi,Zhang, Wei-Hua,Zhang, Ming-Zhi
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p. 205 - 221
(2020/02/18)
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- Remarkably Efficient Iridium Catalysts for Directed C(sp2)-H and C(sp3)-H Borylation of Diverse Classes of Substrates
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Here we describe the discovery of a new class of C-H borylation catalysts and their use for regioselective C-H borylation of aromatic, heteroaromatic, and aliphatic systems. The new catalysts have Ir-C(thienyl) or Ir-C(furyl) anionic ligands instead of the diamine-type neutral chelating ligands used in the standard C-H borylation conditions. It is reported that the employment of these newly discovered catalysts show excellent reactivity and ortho-selectivity for diverse classes of aromatic substrates with high isolated yields. Moreover, the catalysts proved to be efficient for a wide number of aliphatic substrates for selective C(sp3)-H bond borylations. Heterocyclic molecules are selectively borylated using the inherently elevated reactivity of the C-H bonds. A number of late-stage C-H functionalization have been described using the same catalysts. Furthermore, we show that one of the catalysts could be used even in open air for the C(sp2)-H and C(sp3)-H borylations enabling the method more general. Preliminary mechanistic studies suggest that the active catalytic intermediate is the Ir(bis)boryl complex, and the attached ligand acts as bidentate ligand. Collectively, this study underlines the discovery of new class of C-H borylation catalysts that should find wide application in the context of C-H functionalization chemistry.
- Chattopadhyay, Buddhadeb,Hassan, Mirja Md Mahamudul,Hoque, Md Emdadul
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supporting information
p. 5022 - 5037
(2021/05/04)
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- Enantioselective Desymmetrization of 2-Aryl-1,3-propanediols by Direct O-Alkylation with a Rationally Designed Chiral Hemiboronic Acid Catalyst That Mitigates Substrate Conformational Poisoning
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Enantioselective desymmetrization by direct monofunctionalization of prochiral diols is a powerful strategy to prepare valuable synthetic intermediates in high optical purity. Boron acids can activate diols toward nucleophilic additions; however, the design of stable chiral catalysts remains a challenge and highlights the need to identify new chemotypes for this purpose. Herein, the discovery and optimization of a bench-stable chiral 9-hydroxy-9,10-boroxarophenanthrene catalyst is described and applied in the highly enantioselective desymmetrization of 2-aryl-1,3-diols using benzylic electrophiles under operationally simple, ambient conditions. Nucleophilic activation and discrimination of the enantiotopic hydroxy groups on the diol substrate occurs via a defined chairlike six-membered anionic complex with the hemiboronic heterocycle. The optimal binaphthyl-based catalyst 1g features a large aryloxytrityl group to effectively shield one of the two prochiral hydroxy groups on the diol complex, whereas a strategically placed "methyl blocker"on the boroxarophenanthrene unit mitigates the deleterious effect of a competing conformation of the complexed diol that compromised the overall efficiency of the desymmetrization process. This methodology affords monoalkylated products in enantiomeric ratios equal or over 95:5 for a wide range of 1,3-propanediols with various 2-aryl/heteroaryl groups.
- Estrada, Carl D.,Ang, Hwee Ting,Vetter, Kim-Marie,Ponich, Ashley A.,Hall, Dennis G.
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supporting information
(2021/04/07)
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- Investigation of indole functionalized pyrazoles and oxadiazoles as anti-inflammatory agents: Synthesis, in-vivo, in-vitro and in-silico analysis
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There are several potential side and adverse effects are found to be associated with the anti-inflammatory drugs in clinical practice. The long-term use of these clinical agents highly unsafe. It encouraged the development of novel heterocyclic compounds with potential anti-inflammatory activity and low to no toxicity. In present investigation, a total of 12 indole functionalized pyrazole and oxadiazole derivatives were designed, synthesized and evaluated for the in-vivo anti-inflammatory and analgesic potential. These compounds displayed comparable anti-inflammatory and analgesic potential to the reference drugs. Finally, molecular docking analysis was performed considering different anti-inflammatory targets to determine the mechanistic target of the designed molecules. Detailed analysis suggested that the molecules inhibit COX-2, preferably over other anti-inflammatory targets. The results suggested that two compounds (15c and 15f) were found promising candidates for the development of novel anti-inflammatory agents.
- Kalra, Sourav,Kumar, Bhupinder,Kumar, Devendra,Kumar, Ravi Ranjan,Pathania, Shelly,Singh, Pankaj Kumar
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- Synthesis, Pharmacological Evaluation and Molecular Docking Studies of N-[2-(1H-indol-3-yl)Acetyl]Arylsulfonohydrazides
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Synthesis of heterocyclic compounds encompassing multiple functionalities and their biological screening is the most adapted strategy in the world for pharmacological evaluation of future drug candidates. The undertaken research was initiated by esterification 2-(1H-indol-3-yl)acetic acid (1) with catalytic amount of sulfuric acid in ethanol to ethyl 2-(1H-indol-3-yl)acetate (2), which was then reacted with hydrazine hydrate in methanol to achieve 2-(1H-indol-3-yl)acetohydrazide (3). The corresponding hydrazide 3 was reacted with a variety of arylsulfonyl chlorides (4a-j) in sodium carbonate solution (pH 9-10) to afford N-[2-(1H-indol-3-yl)acetyl]arylsulfonohydrazides (5a-j). The structural characterization of synthesized compounds was done by 1H-NMR, 13C-NMR, IR and EI-MS spectral data. Moreover, these derivatives were evaluated for anti-bacterial potentials along with their % age hemolytic and enzyme inhibitory activities. It was found that compounds 5a, 5b, 5d and 5h revealed good anti-bacterial against all the bacterial strains used in this study, while 5d, 5g and 5h exhibited good enzyme inhibition potentials against BChE which were close to the reference standard eserine. These compounds also revealed low values of % hemolytic activity. Results of computational docking were also found in agreement with the enzyme inhibition data.
- Abbasi, M. A.,Ahmad, I.,Ashraf, M.,Aziz-ur-Rehman,Fatima, Hina,Khan, F. A.,Lodhi, M. A.,Qurat-ul-Ain,Rubab, K.,Shah, S. A. A.,Shahid, M.,Siddiqui, S. Z.
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p. 665 - 678
(2021/10/30)
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- INDOLEACETIC ACID DERIVATIVE AND PREPARATION METHOD AND PHARMACEUTICAL USE THEREOF
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The present invention relates to an indoleacetic acid derivative and a preparation method and pharmaceutical use thereof. In particular, the present invention relates to a compound shown in general formula (I), a preparation method thereof, a pharmaceutical composition comprising the same, and a use thereof as a cough suppressant in treating a disease such as a cough. The definition of each substituent in the general formula (I) is the same as the definition in the specification.
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Paragraph 0084; 0085; 0086
(2020/04/10)
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- Directed Evolution of a Cytochrome P450 Carbene Transferase for Selective Functionalization of Cyclic Compounds
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Transfers of carbene moieties to heterocycles or cyclic alkenes to obtain C(sp2)-H alkylation or cyclopropane products are valuable transformations for synthesis of pharmacophores and chemical building blocks. Through their readily tunable active-site geometries, hemoprotein "carbene transferases" could provide an alternative to traditional transition metal catalysts by enabling heterocycle functionalizations with high chemo-, regio-, and stereocontrol. However, carbene transferases accepting heterocyclic substrates are scarce; the few enzymes capable of heterocycle or cyclic internal alkene functionalization described to date are characterized by low turnovers or depend on artificially introduced, costly iridium-porphyrin cofactors. We addressed this challenge by evolving a cytochrome P450 for highly efficient carbene transfer to indoles, pyrroles, and cyclic alkenes. We first developed a spectrophotometric high-throughput screening assay based on 1-methylindole C3-alkylation that enabled rapid analysis of thousands of P450 variants and comprehensive directed evolution via random and targeted mutagenesis. This effort yielded a P450 variant with 11 amino acid substitutions and a large deletion of the non-catalytic P450 reductase domain, which chemoselectively C3-alkylates indoles with up to 470 turnovers per minute and 18000 total turnovers. We subsequently used this optimized alkylation variant for parallel evolution toward more challenging heterocycle carbene functionalizations, including C2/C3 regioselective pyrrole alkylation, enantioselective indole alkylation with ethyl 2-diazopropanoate, and cyclic internal alkene cyclopropanation. The resulting set of efficient biocatalysts showcases the tunability of hemoproteins for highly selective functionalization of cyclic targets and the power of directed evolution to enhance the scope of new-to-nature enzyme catalysts.
- Brandenberg, Oliver F.,Chen, Kai,Arnold, Frances H.
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supporting information
p. 8989 - 8995
(2019/06/13)
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- Fe-catalyzed esterification of amides via C-N bond activation
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An efficient Fe-catalyzed esterification of primary, secondary, and tertiary amides with various alcohols for the preparation of esters was performed. The esterification process was accomplished with FeCl3$6H2O, which is a stable, inexpensive, environmentally friendly catalyst with high functional group tolerance.
- Chen, Xiuling,Hu, Siying,Chen, Rongxing,Wang, Jian,Wu, Minghu,Guo, Haibin,Sun, Shaofa
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p. 4571 - 4576
(2018/02/09)
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- A catalytic N-deacylative alkylation approach to hexahydropyrrolo[2,3-b]indole alkaloids
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A versatile unprecedented strategy to diversely functionalized hexahydropyrrolo[2,3-b]indole alkaloids is described in high chemical yields. The synthesis features a key Pd(0)-catalyzed deacylative alkylation of N-acyl 3-substituted indoles using only 1 mol% of Pd(PPh3)4. The scope of this methodology is further defined in the asymmetric synthesis of pyrroloindolines using a diastereoselective approach.
- Kumar, Nivesh,Maity, Arindam,Gavit, Vipin R.,Bisai, Alakesh
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supporting information
p. 9083 - 9086
(2018/08/21)
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- Myoglobin-Catalyzed C?H Functionalization of Unprotected Indoles
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Functionalized indoles are recurrent motifs in bioactive natural products and pharmaceuticals. While transition metal-catalyzed carbene transfer has provided an attractive route to afford C3-functionalized indoles, these protocols are viable only in the presence of N-protected indoles, owing to competition from the more facile N?H insertion reaction. Herein, a biocatalytic strategy for enabling the direct C?H functionalization of unprotected indoles is reported. Engineered variants of myoglobin provide efficient biocatalysts for this reaction, which has no precedents in the biological world, enabling the transformation of a broad range of indoles in the presence of ethyl α-diazoacetate to give the corresponding C3-functionalized derivatives in high conversion yields and excellent chemoselectivity. This strategy could be exploited to develop a concise chemoenzymatic route to afford the nonsteroidal anti-inflammatory drug indomethacin.
- Vargas, David A.,Tinoco, Antonio,Tyagi, Vikas,Fasan, Rudi
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supporting information
p. 9911 - 9915
(2018/07/31)
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- A Cooperative Hydrogen Bond Donor–Br?nsted Acid System for the Enantioselective Synthesis of Tetrahydropyrans
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Carbocations stabilized by adjacent oxygen atoms are useful reactive intermediates involved in fundamental chemical transformations. These oxocarbenium ions typically lack sufficient electron density to engage established chiral Br?nsted or Lewis acid catalysts, presenting a major challenge to their widespread application in asymmetric catalysis. Leading methods for selectivity operate primarily through electrostatic pairing between the oxocarbenium ion and a chiral counterion. A general approach to new enantioselective transformations of oxocarbenium ions requires novel strategies that address the weak binding capabilities of these intermediates. We demonstrate herein a novel cooperative catalysis system for selective reactions with oxocarbenium ions. This new strategy has been applied to a highly selective and rapid oxa-Pictet–Spengler reaction and highlights a powerful combination of an achiral hydrogen bond donor with a chiral Br?nsted acid.
- Maskeri, Mark A.,O'Connor, Matthew J.,Jaworski, Ashley A.,Davies, Anna V.,Scheidt, Karl A.
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supporting information
p. 17225 - 17229
(2018/12/05)
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- Development and Application of a Recyclable High-Load Magnetic Co/C Hybrid ROMP-Derived Benzenesulfonyl Chloride Reagent and Utility of Corresponding Analogues
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The development and application of high-load, recyclable magnetic Co/C hybrid ROMP-derived benzenesulfonyl chloride and analogues is reported. The regeneration and utility of these reagents in the methylation/alkylation of various carboxylic acids is demonstrated via efficient retrieval of the magnetic reagent with a neodymium magnet. Additional reactions employing the analogue sulfonic acid and in situ generated magnetic benzenesulfonyl azide are also reported.
- Faisal, Saqib,Zang, Qin,Maity, Pradip K.,Brandhofer, Agnes,Kearney, Patrick C.,Reiser, Oliver,Grass, Robert N.,Stoianova, Diana,Hanson, Paul R.
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supporting information
p. 2274 - 2277
(2017/05/12)
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- Tert-Butyl Iodide Mediated Reductive Fischer Indolization of Conjugated Hydrazones
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A novel reductive Fischer indolization of readily available N-aryl conjugated hydrazones with tert-butyl iodide has been developed. In this reaction, tert-butyl iodide is used as anhydrous HI source, and the generated HI acts as a Br?nsted acid and a reducing agent. This operationally simple method allows access to various indole derivatives. Furthermore, the procedure can be applied to the synthesis of biologically active compounds.
- Ito, Yuta,Ueda, Masafumi,Takeda, Norihiko,Miyata, Okiko
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supporting information
p. 2616 - 2619
(2016/02/26)
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- Tryptophan and thiosemicarbazide derivatives: Design, synthesis, and biological evaluation as potential β-D-galactosidase and β-D-glucosidase inhibitors
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Glycosidases, including β-D-galactosidase and β-D-glucosidase, are involved in a range of metabolic disorders, such as cancer, viral or bacterial infections, and diabetes. Previously, we scanned the pharmacophoric space of these enzymes and had a self-consistent and predictive quantitative structure-activity relationship that was used to identify several β-D-galactosidase and β-D-glucosidase inhibitors via in silico search of structural databases. Guided by the preceding modeling efforts, synthesis of a series of tryptophan and thiosemicarbazide derivatives as β-D-galactosidase and β-D-glucosidase inhibitors that match the generated pharmacophores followed by in vitro bioassay was carried out. Synthesized compounds 3c (37 % inhibition at 100 μM) and 4d (49 % inhibition at 100 μM) exhibited the best inhibitory bioactivities against β-D-galactosidase and β-D-glucosidase, respectively. They can serve as a promising lead compounds for the development of potential glycosidase inhibitors.
- Abu Khalaf, Reema,Abdula, Ahmed Mutanabbi,Mubarak, Mohammad S.,Taha, Mutasem O.
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p. 2529 - 2550
(2015/06/22)
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- Synthesis of 3-hydroxyindanones via potassium salt of amino acid catalyzed regioselective intramolecular aldolization of ortho-diacylbenzenes
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First organocatalytic intramolecular aldolization of ortho-diacylbenzenes to construct highly functionalized 3-hydroxyindanones is described. In this transformation a high trans-selectivity is achieved by the use of metal salt of amino acid. This method allows an easy access to the strained spirocyclic 3-hydroxyindanones related to a number of natural product frameworks. Synthesis of a new class of indole skeleton substituted by 3-hydroxyindanones added an extra essence to this new protocol.
- Chanda, Tanmoy,Chowdhury, Sushobhan,Anand, Namrata,Koley, Suvajit,Gupta, Ashutosh,Singh, Maya Shankar
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supporting information
p. 981 - 985
(2015/03/04)
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- Catalytic functionalization of indoles by copper-mediated carbene transfer
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The complex [TpBr3Cu(NCMe)] (TpBr3=hydrotris(3,4,5- tribromo)pyrazolylborate) efficiently catalyzes the C-H functionalization of indole derivatives at C3 by carbene transfer from different diazoesters in a high-yield transformation involving low catalyst loadings and short reaction times. This system has shown that the previously proposed dichotomy of carbene addition (to the double bond) vs carbene insertion (to the C-H bond) corresponds to two consecutive reaction steps: the cyclopropane intermediates, observed in the reaction mixtures, are the precursors of the final C-H functionalization derivatives in a ring-opening process involving acid catalysis. Those in situ generated cyclopropanes undergo nucleophilic ring opening with Me 2CuLi to afford both C2 and C3 functionalized indoles.
- Delgado-Rebollo, Manuela,Prieto, Auxiliadora,Perez, Pedro J.
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p. 2047 - 2052
(2014/08/05)
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- Amide-Functionalized Naphthyridines on a RhII-RhII Platform: Effect of Steric Crowding, Hemilability, and Hydrogen-Bonding Interactions on the Structural Diversity and Catalytic Activity of Dirhodium(II) Complexes
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Ferrocene-amide-functionalized 1,8-naphthyridine (NP) based ligands {[(5,7-dimethyl-1,8-naphthyridin-2-yl)amino]carbonyl}ferrocene (L1H) and {[(3-phenyl-1,8-naphthyridin-2-yl)amino]carbonyl}ferrocene (L2H) have been synthesized. Room-temperature treatment of both the ligands with Rh2(CH3COO)4 produced [Rh2(CH3COO)3(L1)] (1) and [Rh2(CH3COO)3(L2)] (2) as neutral complexes in which the ligands were deprotonated and bound in a tridentate fashion. The steric effect of the ortho-methyl group in L1H and the inertness of the bridging carboxylate groups prevented the incorporation of the second ligand on the {RhII-RhII} unit. The use of the more labile Rh2(CF3COO)4 salt with L1H produced a cis bis-adduct [Rh2(CF3COO)4(L1H)2] (3), whereas L2H resulted in a trans bis-adduct [Rh2(CF3COO)3(L2)(L2H)] (4). Ligand L1H exhibits chelate binding in 3 and L2H forms a bridge-chelate mode in 4. Hydrogen-bonding interactions between the amide hydrogen and carboxylate oxygen atoms play an important role in the formation of these complexes. In the absence of this hydrogen-bonding interaction, both ligands bind axially as evident from the X-ray structure of [Rh2(CH3COO)2(CH3CN)4(L2H)2](BF4)2 (6). However, the axial ligands reorganize at reflux into a bridge-chelate coordination mode and produce [Rh2(CH3COO)2(CH3CN)2(L1H)](BF4)2 (5) and [Rh2(CH3COO)2(L2H)2](BF4)2 (7). Judicious selection of the dirhodium(II) precursors, choice of ligand, and adaptation of the correct reaction conditions affords 7, which features hemilabile amide side arms that occupy sites trans to the Rh-Rh bond. Consequently, this compound exhibits higher catalytic activity for carbene insertion to the C-H bond of substituted indoles by using appropriate diazo compounds, whereas other compounds are far less reactive. Thus, this work demonstrates the utility of steric crowding, hemilability, and hydrogen-bonding functionalities to govern the structure and catalytic efficacyof dirhodium(II,II) compounds.
- Sarkar, Mithun,Daw, Prosenjit,Ghatak, Tapas,Bera, Jitendra K.
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supporting information
p. 16537 - 16549
(2016/02/12)
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- New CRTh2 antagonists.
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The present invention relates to compounds of formula (I), to the process for preparing such compounds and to their use in the treatment of a pathological condition or disease susceptible to amelioration by CRTh2 antagonist activity.
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Paragraph 0247
(2013/03/26)
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- NEW CRTh2 ANTAGONISTS
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The present invention relates to compounds of formula (I), to the process for preparing such compounds and to their use in the treatment of a pathological condition or disease susceptible to amelioration by CRTh2 antagonist activity.
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Page/Page column 95-96
(2013/03/26)
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- Synthesis and screening of some novel substituted indoles contained 1,3,4-oxadiazole and 1,2,4-triazole moiety
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A series of novel 3-[5-(1H-indol-3-yl-methyl)-2-oxo-[1,3,4]oxadiazol-3-yl] propionitrile (5), 3-[4-amino-3-(1H-indol-3-yl-methyl)-5-oxo-4,5-dihydro-[1,2,4] triazol-1-yl]propionitrile (6), 3-[5-(1H-indol-3-yl-methyl)-2-thioxo-[1,3,4] oxadiazol-3-yl]propionitrile (7) and 3-[4-amino-3-(1H-indol-3-yl-methyl)-5- thioxo-4,5-dihydro-[1,2,4]triazol-1-yl]propionitrile (8) were synthesized in good yields from the intermediate (1H-indol-3-yl)-acetic acid N′-(2-cyanoethyl)hydrazide (4). The chemical structures of the newly synthesized compounds were elucidated by their IR, 1H NMR and MS. Further, all the compounds were screened for their antimicrobial activity against Gram-positive, Gram-negative bacteria and also tested their ability toward anti-inflammatory activity.
- Gadegoni, Hemalatha,Manda, Sarangapani
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p. 127 - 130
(2013/06/26)
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- Dual Bronsted acid/nucleophilic activation of carbonylimidazole derivatives
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Carbonylimidazole derivatives have been found to be highly active acylation reagents for esterification and amidation in the presence of pyridinium salts. These reactions are thought to involve both Bronsted acid and nucleophilic catalysis. This mode of activation has been applied to the synthesis of difficult to access oxazolidinones, as well as esters and amides. Finally, the use of pyridinium salts has been shown to accelerate the esterification of carboxylic acids with imidazole carbamates.
- Heller, Stephen T.,Fu, Tingting,Sarpong, Richmond
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supporting information; experimental part
p. 1970 - 1973
(2012/06/01)
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- A series of 2-arylamino-5-(indolyl)-1,3,4-thiadiazoles as potent cytotoxic agents
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A series of 2-arylamino-5-(indolyl)-1,3,4-thiadiazoles 6a-v were prepared and studied for their anticancer activity against selected human cancer cell lines. The reaction of indolylhydrazides 3a-h with a variety of aryl isothiocyanates 4 afforded the key intermediate thiosemicarbazides 5a-v, which upon treatment with acetyl chloride produced the 2-arylamino-5-(indolyl)-1,3,4- thiadiazoles 6a-v in good yields. Most of the synthesized compounds showed selective cytotoxicity towards human breast cancer cell line (MDA-MB-231). Of the synthesized 2-arylamino-5-(indolyl)-1,3,4-thiadiazoles, compound 6f is the most potent towards tested cancer cell lines (IC50 = 0.15-1.18 μM).
- Kumar, Dalip,Kumar, N. Maruthi,Noel, Brett,Shah, Kavita
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p. 432 - 438
(2012/11/07)
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- Synthesis and biological evaluation of novel 4-indolyl-5-phenyl(indolyl)-1, 2-dihydropyrazol-3-ones as glycogen synthase kinase-3β (GSK-3β) inhibitors
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Nineteen novel 4-indolyl-5-phenyl(indolyl)-1,2-dihydropyrazol-3-ones were synthesized and evaluated for their GSK-3β inhibitory activity. Half of the tested compounds showed moderate GSK-3β inhibitory activity. Preliminary structure-activity relationships were discussed, which showed that the presence of 3,4,5-trimethoxy group on the benezene ring enhanced potency while the existence of an electron-withdrawing group at the 4-position of the benezene ring deceased activity. Compounds 11c and 14, the most potent compounds with IC50 values of 9.28 and 8.98 μM, respectively, would be promising candidates for further development of novel GSK-3β inhibitors.
- Yin, Hong,Shangguan, Yingying,Sui, Fengying,Yang, Xinji,Song, Guojie
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p. 780 - 788,9
(2020/09/15)
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- A total synthesis of (±)-α-cyclopiazonic acid using a cationic cascade as a key step
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The indole alkaloid α-cyclopiazonic acid 1 has been synthesised by a route, which features at its core an acid-catalysed cationic cascade cyclisation terminated by a sulfonamide group.
- Griffiths-Jones, Charlotte M.,Knight, David W.
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experimental part
p. 8515 - 8528
(2011/11/29)
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- Efficient indole N-detosylation using thioglycolate
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The dilithium salt of thioglycolic acid in DMF can be used for the very efficient and convenient removal of N-p-toluenesulfonyl (tosyl) groups from a range of indoles at ambient temperature.
- Haskins, Charlotte M.,Knight, David W.
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p. 599 - 601
(2007/10/03)
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- 1,2-disubstituted-6-oxo-3-phenyl-piperidine-3-carboxamides and combinatorial libraries thereof
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The invention relates to combinatorial libraries containing two or more novel piperidine-3-carboxamide derivative compounds, methods of preparing the piperidine-3-carboxamide derivative compounds and piperidine-3-carboxamide derivative compounds bound to a resin
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- Synthesis of newer indolyl/phenothiazinyl substituted 2-oxo/thiobarbituric acid derivatives as potent anticonvulsant agents
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2-Amino-5-(heteroarylmethylene)-1,3,4-oxadiazoles/thiadiazoles 7-10 were synthesized by cyclisation of 1-(heteroarylacetyl)semicarbazides/thiosemicarbazides 3-6. 5-(2′-Heteroarylmethylene-5′-aminomethylene-1′, 3′, 4′-oxadiazol-2′-yl/thiadiazol-2′-yl)-2-oxo/thiobarbituric acids 11-18 were synthesized by condensation of compounds 7-10 at the 5th position of 2-oxo/thiobarbituric acids. The newly synthesized compounds showed anticonvulsant activity ranging from 50-90% (seizures protection). Compound 18 (5-(2′-phenothiazinylmethylene-5′- aminomethylene-1′3′,4′-thiadiazol-2′-yl)-2- thiobarbituric acid) showed maximum activity being more potent than the reference drug phenytoin sodium (CAS 630-93-3).
- Archana,Rani, Preeti,Bajaj, Kiran,Srivastava, Virendra Kishore,Chandra, Ramesh,Kumar, Ashok
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p. 301 - 306
(2007/10/03)
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- InBr3/Cu(OTf)2-catalyzed C-alkylation of pyrroles and indoles with α-diazocarbonyl compounds
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Pyrroles and indoles react smoothly with α-diazocarbonyl compounds in the presence of 10 mol% of InBr3 under mild conditions to afford the corresponding 2- and 3-alkyl pyrrole and 3-alkyl indole derivatives, respectively, in good yields with high selectivity.
- Yadav,Reddy,Satheesh
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p. 8331 - 8334
(2007/10/03)
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- Synthesis of some newer indolyl-thiadiazolyl-pyrazolines and indolyl-oxadiazolyl-pyrazolines as potential anti-inflammatory agents
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Some new 1-acetyl-5-substitutedaryl-3-[5′-(3″ -indolylmethyl)-2′-amino-1′,3′,4′,-thiadiazol- 2′N-yl]-2-pyrazolines 6a-6e and 1-acetyl-5-substitutedaryl-3-[5′-(3″-indolylmethyl)-2′- amino-1′,3′,4′-oxadiazol-2′N-yl]-2-pyrazolines 6′a-6′e have been synthesized by 5-(3′-indolymethyl)-1,3,4-thiadiazolyl)-2-aminosubstitutedchalkones 5a-5e and 5-(3′-indolylmethyl)-1,3,4-oxadiazolyl-2-aminosubstitutedchalkones 5′a-5′e, respectively. All these compounds of the present series have been screened for their anti-inflammatory activity. Compounds 6c and 6′c are found to be most active compound of this series, which show 47.6% and 49.0% inflammation inhibitory activity at a dose of 50 mg/kg p.o., while standard drug phenylbutazone exhibit 45.6% anti-inflammatory activity at same dose. The structure of these compounds has been illustrated by IR and 1H NMR spectra.
- Sharma, Shalabh,Srivastava, Virendra Kishor,Kumar, Ashok
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p. 2647 - 2654
(2007/10/03)
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- Synthesis and pharmacological evaluation of (indol-3-yl)alkylamides as potent analgesic agents
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A series of (indol-3-yl)alkylamides was synthesized and evaluated for analgesic activity. Two N-(pyridin-4-yl)acetamides, compounds 24 and 25, bearing benzyl or 4-fluorobenzyl moieties in 1-position of indole ring exhibited promising analgesic properties (ED50 = 8.1 and 11 mg/kg p.o., respectively), being as potent as the reference drugs flupirtine (CAS 56995-20-1), ibuprofen (CAS 15687-27-1) and diclofenac (CAS 15307-86-5). The two test compounds were tested for their anti-inflammatory activity by carrageenin-induced edema in rat paw test. 4-Fluorobenzyl derivative 25 whose ID50 was 0.085 ± 0.021 mmol/kg was selected as a lead compound for further pharmacomodulation.
- Fouchard,Marchand,Le Baut,Emig,Nickel
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p. 814 - 824
(2007/10/03)
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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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- SELECTIVITY IN THE REACTIONS OF ELECTRON-RICH PENTATOMIC HETEROAROMATIC COMPOUNDS WITH CARBON-CENTRED FREE RADICALS
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The relative reactives of pyrrole, N-methylpyrrole, furan and thiophene with electrophilic carbon-centred free radicals .CH2CN, .CH2CO2Et and .CH(CO2Et)2 have been determined.The results have indicated a relatively low intermolecular selectivity, with a reactivity order N-methylpyrrole > pyrrole ca. furan > thiophene.The intramolecular selectivities (relative reactivity of the α and β positions) of these reactions, as well as that of indole with .CH2CN and .CH2CO2Et have also been determined.The α/β ratio is very high (> 50) with N-methylpyrrole, pyrrole, furan and thiophene, but becomes lower (between 6 and 12) with indole.These results can be rationalized by suggesting that in the homolytic substitutions of electrophilic carbon radicals with electron-rich pentatomic heteroaromatics, the SOMO of the radical probably interacts with both the HOMO and the LUMO of the substrate, and not only with the HOMO as expected.
- Baciocchi, Enrico,Manna, Livia,Muraglia, Ester
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p. 249 - 252
(2007/10/02)
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- Hexitol derivatives having vasodilative activity
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Disclosed is a hexitol derivative represented by the formula (I): STR1 wherein Q represents a formula selected from the group consisting of STR2 wherein a represents NH, O or S; each of b, c and d independently represents CH or N; each of R1, R2, R3 and R4 independently represents hydrogen, lower alkyl, trifluoromethyl, aryl, lower alkanoyloxy, amino, lower alkylamino, lower alkanoylamino, lower alkanoyl, aroyl, halogen, nitro, (CH2)m OR 7, (CH2)m SR7, (CH2)m CO2 R7 where R7 represents hydrogen or lower alkyl and m represents an integer of 0 to 3; each of R5 and R6 independently represents hydrogen or lower alkyl; U represents >N-- or STR3 W represents a single bond, --O-- or --S--; X represents STR4 wherein each of Y1 and Y2 independently represents hydrogen, lower alkyl, hydroxyl, lower alkanoyloxy, nitrile or phenyl; or Y1 and Y2 are combined together to form oxygen; each of Y3 and Y4 independently represents hydrogen or lower alkyl; and l is an integer of 0 to 6, and where l is an integer of 2 to 6, each STR5 may be the same or different; Z represents hydrogen or nitro; and, n is 2 or 3 or a pharmaceutically acceptable salt thereof. The compounds show prominent coronary vasodilative activities, and are useful in treating angina pectoris and myocardial infarction.
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- A ONE-STEP CONVERSION OF CERTAIN INDOLE AND PYRROLE GLYOXYLIC ACID ESTERS TO THE CORRESPONDING ACETATES
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In this study, a catalytic hydrogen transfer type of hydrogenolysis was developed for the one step conversion of ethyl indole-3-, pyrrole-2- and pyrrole-3-glyoxalates to the corresponding acetates.The structural requirements for this hydrogenolysis were also investigated.
- Demopoulos, Vassilis J.
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p. 2585 - 2594
(2007/10/02)
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- Synthesis of 1-(β-D-Ribofuranosyl)indol-3-acetic Acid
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By condensation of ethyl indolin-3-acetate (4) and 2,3,5-tri-O-benzoylribofuranosyl-1-acetate (5), ethyl 1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)indolin-3-acetate (6) was obtanied in good yield.The indoline nucleoside 6 was aromatized to ethyl 1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)indol-3-acetate (7) with DDQ.The treatment of the indole nucleoside with barium hydroxide and methanol gave the methyl ester 8, which was further treated in water to give the desired 1-(β-D-ribofuranosyl)indol-3-acetic acid (9).
- Chu, Chung K.,Suh, Jungjin,Cutler, Horace G.
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p. 1777 - 1779
(2007/10/02)
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- QUANTIFICATION OF INDOL-3-YL ACETIC ACID IN PEA AND MAIZE SEEDLINGS BY GAS CHROMATOGRAPHY-MASS SPECTROMETRY
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A procedure is described for the identification and quantification of IAA in plant tissues by GC/MS analysis of the N-heptafluorobutyryl ethyl ester of IAA using IAA as an internal standard.The detection limit is ca. 3 pmol IAA/tissue sample.By using this method, IAA levels of 30-90 pmol/g fr. wt were obtained for dark-grown Pisum sativum epicotyls and 71-199 pmol/g fr. wt for dark-grown Zea mays seedlings.When either methanol or ethanol was used as extraction solvent, some esterification of IAA during sample preparation was observed.No evidence for the natural occurence of methyl or ethyl esters of IAA in Pisum sativum seedlings was found.Key Word Index-Pisum sativum; Zea mays; Leguminosae; Gramineae; hormone; indol-2-yl acetic acid; GC/MS; deuterium label.
- Allen, James R. F.,Rivier, Laurent,Pilet, Paul-Emile
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p. 525 - 530
(2007/10/02)
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- SYNTHESIS AND PROPERTIES OF AZOLES AND THEIR DERIVATIVES. 32. SYNTHESIS AND SOME TRANSFORMATIONS OF HYDROCHLORIDES OF IMIDO ESTERS OF INDOLECARBOXYLIC ACIDS
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The Pinner reaction with the nitriles of indole-3-carboxylic and 3-indolylacetic acids was studied.The hydrochlorides of the imide esters of these acids, which were converted to the free bases, amides, and esters, were synthesized.Imidazolines, benzimidazoles, and benzoxazoles that contain indole substituents were obtained by condensation of the hydrochlorides of the imido esters of the indolecarboxylic acids with ethylenediamine, o-phenylenediamine, and o-aminophenol.
- Kelarev, V. I.,Shvekhgeimer, G. A.
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p. 501 - 506
(2007/10/02)
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