- Synthesis and pharmacological evaluation of 6a,7-dihydro-6H,13H-pyrazino[1,2-a;4,5-a′]diindole analogs as melatonin receptor ligands
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The synthesis of two melatonin-derived analogs of the novel 6a,7-dihydro-6H,13H-pyrazino[1,2-a;4,5-a′]diindole ring system is described. The non-methoxy and methoxy analogs, 4a and 4b were prepared in seven steps starting from indoline-2-carboxylic acid 5a and 5-methoxyindoline-2-carboxylic acid 5b, respectively. While 4a exhibited micromolar affinities for both melatonin receptors, the methoxy analog 4b displayed moderate affinity for MT2 receptors (Ki=0.41 μM) being 4.4-fold higher than for the MT1 subtype.
- Attia, Mohamed I.,Julius, Justin,Witt-Enderby, Paula A.,Zlotos, Darius P.
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Read Online
- Design and synthesis of two cytotoxic analogs of the novel pyrrolo[1′,2′:1,2][1,4]diazepin [7,6-b]indol-5(6h)-one nucleus
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The design and synthesis of the two cytotoxic derivatives 15 and 16 of the novel pyrrolo[1′,2′:1,2][1,4]diazepin[7,6-b]indol-5(6H)-one nucleus is described. Readily available methyl 2-indolecarboxylates 5 and 6 are nitrosated with NaNO2 in AcOH to give the analogs 7 and 8, which are then oxidized with KMnO4 in aq. NaOH to provide the 3-NO2 acids 9 and 10. These, in turn, are subjected to amidation with (2S)-pyrrolidine-2-carboxaldehyde diethyl thioacetal in the presence of EDCI and HOBt and then to a 7-exo-trig cyclization reaction to give the target molecules 15 and 16. The new analogs were evaluated in the human leukemic K 562 cell line and were shown to have micromolar potency.
- Tsotinis, Andrew,Vlachou, Margarita,Kiakos, Konstantinos,Hartley, John A.,Thurston, David E.
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Read Online
- Spectroscopic (FT-IR, FT-Raman, UV, 1H and 13C NMR) profiling and computational studies on methyl 5-methoxy-1H-indole-2-carboxylate: A potential precursor to biologically active molecules
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Methyl 5-methoxy-1H-indole-2-carboxylate (MMIC) was prepared via esterification of commercially available 5-methoxyindole-2-carboxylic acid. The title molecule MMIC was characterised using FT-IR and FT-Raman in the ranges of 4000–500 and 4000–50?cm?1, respectively. The fundamental modes of the vibrations were assigned and the UV–visible spectrum of the MMIC molecule was recorded in the range of 200–400?nm to explore its electronic nature. The HOMO-LUMO energy distribution was calculated and the bonding and anti-bonding structures of the title molecule were studied and analysed using the natural bond orbital (NBO) approach. The reactivity of the MMIC molecule was also investigated and both the positive and negative centres of the molecule were identified using chemical descriptors and molecular electrostatic potential (MEP) analysis. The chemical shifts of the 1H and 13C NMR spectra were noted and the magnetic field environment of the MMIC molecule are discussed. The non-linear optical (NLO) properties of the title molecule were studied based on its calculated values of polarisability and hyperpolarisability. All computations were obtained by DFT methods using the 6-311++G (d,p) basis set.
- Almutairi, Maha S.,Xavier,Sathish,Ghabbour, Hazem A.,Sebastian,Periandy,Al-Wabli, Reem I.,Attia, Mohamed I.
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- Iodine/Manganese Catalyzed Sulfenylation of Indole via Dehydrogenative Oxidative Coupling in Anisole
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This protocol describes an iodine/manganese catalytic system for dehydrogenative oxidative coupling reaction of indoles with thiols in anisole. Particularly, the dual roles of anisole have been first demonstrated as a solvent and as a promoter via the formation of an oxonium ion intermediate to accelerate the generation of products. A series of sulfenylindoles are readily constructed under aerobic mild reaction conditions. In addition, the achievement for preparing anticancer and anti-AIDS drugs testifies the practicability of this approach. The mechanism studies disclose probable alternative pathways and a single-electron transfer process are involved in this transformation. (Figure presented.).
- Li, Weihe,Wang, Hao,Liu, Shengping,Feng, Hua,Benassi, Enrico,Qian, Bo
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supporting information
p. 2666 - 2671
(2020/05/25)
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- Novel indole hydrazide derivatives: Synthesis and their antiproliferative activities through inducing apoptosis and DNA damage
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A series of novel indole hydrazide derivatives was synthesized and evaluated for their anticancer activities. Compound 12 exhibited the highest antiproliferative activity against the MCF-7 cell line, with an IC50 value of 3.01 μM. Treatment of MCF-7 cells with compound 12 led to cell cycle arrest at the G0/G1 phase and also displayed a significant annexin V binding pattern, indicating that compound 12 is effective in apoptotic cell death. The Western blot analysis showed that compound 12 increased the expression of proapoptotic Bax and decreased the levels of the antiapoptotic Bcl-2 protein. It was also observed that MCF-7 cells treated with compound 12 showed reduced levels of procaspase-3 and -9 proteins. Moreover, compound 12 treatment induced a significant DNA damage in MCF-7 cells by increasing H2AX and ATM phosphorylation.
- Kilic-Kurt, Zühal,Acar, Cemre,Ergul, Mustafa,Bakar-Ates, Filiz,Altuntas, Tunca G.
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- Antiproliferative activity and possible mechanism of action of certain 5-methoxyindole tethered C-5 functionalized isatins
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Background: Cancer is one of the most dreaded human diseases, that has become an ever-increasing health problem and is a prime cause of death globally. The potential antiproliferative activity of certain indole–isatin molecular hybrids 5a-w was evaluated in vitro against three human cancer cell lines. Methods: Standard protocols were adopted to examine the antiproliferative potential and mechanisms of compounds 5a-w. Western blot analysis was carried out on compound 5o. Results: Compounds 5a-w demonstrated in vitro antiproliferative activity in the range of 22.6–97.8%, with compounds 5o and 5w being the most active antiproliferative compounds with IC50 values of 1.69 and 1.91 μM, which is fivefold and fourfold more potent than sunitinib (IC50=8.11 μM), respectively. Compound 5o was selected for in-depth pharmacological testing to understand its possible mechanism of antiproliferative activity. It caused a lengthening of the G1 phase and a reduction in the S and G2/M phases of the cell cycle and had an IC50 value of 10.4 μM with the resistant NCI-H69AR cancer cell line. Moreover, compound 5o significantly decreased the amount of phosphorylated Rb protein in a dose-dependent fashion, which was confirmed via Western blot analysis. Conclusion: The current investigation highlighted the potential antiproliferative activity of compounds 5a-w as well as the antiproliferative profile of compound 5o. These compounds can be harnessed as new lead antiproliferatives in the preclinical studies of cancer chemotherapy.
- Almutairi, Maha S.,Hassan, Eman S.,Keeton, Adam B.,Piazza, Gary A.,Abdelhameed, Ali S.,Attia, Mohamed I.
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p. 3069 - 3078
(2019/09/10)
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- Palladium(0)-Catalyzed Intermolecular Asymmetric Cascade Dearomatization Reaction of Indoles with Propargyl Carbonate
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An intermolecular asymmetric cascade dearomatization reaction of indole derivatives with propargyl carbonate was developed. The challenges associated with both the chemoselectivity between the carbon and nitrogen nucleophile and the enantioselective control during the formation of an all-carbon quaternary stereogenic center were well addressed by a Pd catalytic system derived from the Feringa ligand. A series of enantioenriched multiply substituted fused indolenines were provided in good yields (71–86 %) with excellent enantioselectivity (91–96 % ee) and chemoselectivity (3/4>19:1 in most cases).
- Ding, Lu,Gao, Run-Duo,You, Shu-Li
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supporting information
p. 4330 - 4334
(2019/02/25)
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- Synthesis, spectroscopic identification and molecular docking of certain N-(2-[2-(1H-Indol-2-ylcarbonyl) hydrazinyl](oxo)acetyl phenyl)acetamides and N-[2-(2-[2-(Acetylamino)phenyl](oxo)acetyl hydrazinyl)-2-oxoethyl]-1H-indole-2-carboxamides: New antimicrobial agents
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N-(2-[2-(1H-Indol-2-ylcarbonyl)hydrazinyl](oxo)acetyl phenyl)acetamides (5a–h) and N-[2-(2-[2-(acetylamino)phenyl](oxo)acetyl hydrazinyl)-2-oxoethyl]-1H-indole-2-carboxamides (5i–l) were synthesized and characterized with different analytical tools. N-Acetylisatines 4a–d were subjected to ring opening at their C2 carbons with the aid of different indole-bearing hydrazides 3a,b and 7 to afford the respective glyoxylamides 5a–l. The antimicrobial activity of the target compounds 5a–l was assessed with the aid of Diameter of the Inhibition Zone (DIZ) and Minimum Inhibitory Concentration (MIC) assays against a panel of Gram-positive and Gram-negative bacteria and certain fungal strains. The antimicrobial screening revealed that Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans are the most sensitive microorganisms towards the synthesized compounds 5a–l. In addition, compounds 5c and 5h emerged as the most active congeners towards Staphylococcus aureus and Candida albicans, respectively. Molecular docking studies revealed the possible binding mode of compounds 5c and 5h to their target proteins.
- Almutairi, Maha S.,Zakaria, Azza S.,Al-Wabli, Reem I.,Hubert Joe,Abdelhameed, Ali S.,Attia, Mohamed I.
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- Synthesis, spectroscopic investigations, DFT studies, molecular docking and antimicrobial potential of certain new indole-isatin molecular hybrids: Experimental and theoretical approaches
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Indole-isatin molecular hybrids 5a-i have been synthesized and characterized by different spectroscopic methods to be evaluated as new antimicrobial agents against a panel of Gram positive bacteria, Gram negative bacteria, and moulds. Compound 5h was selected as a representative example of the prepared compounds 5a-i to perform computational investigations. Its vibrational properties have been studied using FT-IR and FT-Raman with the aid of density functional theory approach. The natural bond orbital analysis as well as HOMO and LUMO molecular orbitals investigations of compound 5h were carried out to explore its possible intermolecular delocalization or hyperconjugation and its possible interactions with the target protein. Molecular docking of compound 5h predicted its binding mode with the fungal target protein.
- Almutairi, Maha S.,Zakaria, Azza S.,Ignasius, P. Primsa,Al-Wabli, Reem I.,Joe, Isaac Hubert,Attia, Mohamed I.
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p. 333 - 345
(2017/10/18)
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- PYRROLOBENZODIAZEPINE PRODRUGS AND ANTIBODY CONJUGATES THEREOF
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The invention relates generally to pyrrolobenzodiazepine monomer and dimer prodrugs having a glutathione-activated disulfide prodrug moiety, a DT-diaphorase-activated quinone prodrug moiety or a reactive oxygen species-activated aryl boronic acid or aryl boronic ester prodrug moiety. The invention further relates to pyrrolobenzodiazepine prodrug dimer-antibody conjugates.
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Page/Page column 180; 181; 184
(2018/03/06)
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- Design, synthesis, in vitro antiproliferative activity and apoptosis-inducing studies of 1-(3′,4′,5′-trimethoxyphenyl)-3-(2′-alkoxycarbonylindolyl)-2-propen-1-one derivatives obtained by a molecular hybridisation approach
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Inhibition of microtubule function using tubulin targeting agents has received growing attention in the last several decades. The indole scaffold has been recognized as an important scaffold in the design of novel compounds acting as antimitotic agents. Indole-based chalcones, in which one of the aryl rings was replaced by an indole, have been explored in the last few years for their anticancer potential in different cancer cell lines. Eighteen novel (3′,4′,5′-trimethoxyphenyl)-indolyl-propenone derivatives with general structure 9 were synthesized and evaluated for their antiproliferative activity against a panel of four different human cancer cell lines. The highest IC50 values were obtained against the human promyelocytic leukemia HL-60 cell line. This series of chalcone derivatives was characterized by the presence of a 2-alkoxycarbonyl indole ring as the second aryl system attached at the carbonyl of the 3-position of the 1-(3′,4′,5′-trimethoxyphenyl)-2-propen-1-one framework. The structure–activity relationship (SAR) of the indole-based chalcone derivatives was investigated by varying the position of the methoxy group, by the introduction of different substituents (hydrogen, methyl, ethyl or benzyl) at the N-1 position and by the activity differences between methoxycarbonyl and ethoxycarbonyl moieties at the 2-position of the indole nucleus. The antiproliferative activity data of the novel synthesized compounds revealed that generally N-substituted indole analogues exhibited considerably reduced potency as compared with their parent N-unsubstituted counterparts, demonstrating that the presence of a hydrogen on the indole nitrogen plays a decisive role in increasing antiproliferative activity. The results also revealed that the position of the methoxy group on the indole ring is a critical determinant of biological activity. Among the synthesized derivatives, compound 9e, containing the 2-methoxycarbonyl-6-methoxy-N-1H-indole moiety exhibited the highest antiproliferative activity, with IC50 values of 0.37, 0.16 and 0.17 μM against HeLa, HT29 and MCF-7 cancer cell lines, respectively, and with considerably lower activity against HL-60 cells (IC50: 18 μM). This derivative also displayed cytotoxic properties (IC50 values ~1 μM) in the human myeloid leukemia U-937 cell line overexpressing human Bcl-2 (U-937/Bcl-2) via cell cycle progression arrest at the G2-M phase and induction of apoptosis. The results obtained also demonstrated that the antiproliferative activity of this molecule is related to inhibition of tubulin polymerisation. The presence of a methoxy group at the C5- or C6-position of the indole nucleus, as well as the absence of substituents at the N-1-indole position, contributed to the optimal activity of the indole-propenone-3′,4′,5′-trimethoxyphenyl scaffold.
- Preti, Delia,Romagnoli, Romeo,Rondanin, Riccardo,Cacciari, Barbara,Hamel, Ernest,Balzarini, Jan,Liekens, Sandra,Schols, Dominique,Estévez-Sarmiento, Francisco,Quintana, José,Estévez, Francisco
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p. 1225 - 1238
(2018/09/04)
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- Synthesis, spectroscopic characterization and antimicrobial potential of certain new isatin-indole molecular hybrids
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Molecular hybridization has a wide application in medicinal chemistry to obtain new biologically active compounds. New isatin-indole molecular hybrids 5a-n have been synthesized and characterized by various spectroscopic tools. The in vitro antimicrobial potential of the prepared compounds 5a-n was assessed using diameter of the inhibition zone (DIZ) and minimum inhibitory concentration (MIC) assays against a panel of Gram-negative bacteria, Gram-positive bacteria and fungi. Most of the synthesized compounds 5a-n showed weak activities against Gram-negative bacteria while compounds 5b and 5c exhibited good activities against Gram-positive bacteria. On the other hand, compound 5j emerged as the most active compound towards Candida albicans (C. albicans), with an MIC value of 3.9 μg/mL, and compound 5g as the most active congener towards Asperagillus Niger (A. Niger), with an MIC value of 15.6 μg/mL. Moreover, compound 5h manifested the best anti-P. notatum effect, with an MIC value of 7.8 μg/mL, making it equipotent with compound 5g.
- Al-Wabli, Reem I.,Zakaria, Azza S.,Attia, Mohamed I.
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- Flexible synthesis of isomeric pyranoindolones and evaluation of cytotoxicity towards HeLa cells
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A hybrid pharmacophore approach for the synthesis of isomeric pyranoindolones was achieved by employing gold(III) chloride-catalyzed cycloisomerization of alkyne-tethered indole carboxylic acids in good to excellent yield. All the synthesized compounds were evaluated for their tumor cell growth inhibitory activity against human cervix adenocarcinoma (HeLa) which revealed that three compounds exhibited activity comparable with the standard cis-platin (IC50 = 0.08 μM). Molecular docking of all the compounds in Vaccinia H1-Related (VHR) Phosphatase receptor also supported that compound 7d as the most active with a free energy of binding as ?8.27 kcal/mol. [Figure not available: see fulltext.]
- Jeyaveeran,Praveen, Chandrasekar,Arun,Prince,Perumal
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p. 787 - 802
(2016/05/19)
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- Structure-based design and biological evaluation of novel 2-(indol-2-yl) thiazole derivatives as xanthine oxidase inhibitors
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Inhibition of xanthine oxidase (XO) has obviously been a central concept for controlling hyperuricemia, which causes serious and painful inflammatory arthritis disease such as gout. We discovered a series of novel 2-(indol-2-yl)thiazole derivatives as XO inhibitors at the level of nanomolar activity. Structure-guided design using molecular modeling program (Accelrys Software program) provided an excellent basis for optimization of 2-(indol-2-yl)thiazole compounds. Structure-activity relationship indicated that hydrophobic alkoxy group (isopropoxy, cyclopentoxy) at 5-position and hydrogen binding acceptor (NO2, CN) at 7-position of indole ring appear as critical functional groups. Among the compounds, 2-(7-nitro-5-isopropoxy-indol-2-yl)-4-methylthiazole-5-carboxylic acid (9m) exhibits the most potent XO inhibitory activity (IC50value: 5.1 nM) and the excellent uric acid lowering activity in potassium oxonate induced hyperuricemic rat model.
- Song, Jeong Uk,Jang, Jae Wan,Kim, Tae Hun,Park, Heuisul,Park, Wan Su,Jung, Sang-Hun,Kim, Geun Tae
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p. 950 - 954
(2016/05/24)
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- Synthesis and biological evaluation of indolyl-pyridinyl-propenones having either methuosis or microtubule disruption activity
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Methuosis is a form of nonapoptotic cell death characterized by an accumulation of macropinosome-derived vacuoles with eventual loss of membrane integrity. Small molecules inducing methuosis could offer significant advantages compared to more traditional anticancer drug therapies that typically rely on apoptosis. Herein we further define the effects of chemical substitutions at the 2-and 5-indolyl positions on our lead compound 3-(5-methoxy-2-methyl-1H-indol-3-yl)-1-(4-pyridinyl)-2-propene-1-one (MOMIPP). We have identified a number of compounds that induce methuosis at similar potencies, including an interesting analogue having a hydroxypropyl substituent at the 2-position. In addition, we have discovered that certain substitutions on the 2-indolyl position redirect the mode of cytotoxicity from methuosis to microtubule disruption. This switch in activity is associated with an increase in potency as large as 2 orders of magnitude. These compounds appear to represent a new class of potent microtubule-active anticancer agents.
- Trabbic, Christopher J.,Overmeyer, Jean H.,Alexander, Evan M.,Crissman, Emily J.,Kvale, Heather M.,Smith, Marcie A.,Erhardt, Paul W.,Maltese, William A.
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p. 2489 - 2512
(2015/03/30)
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- Enantioselective Borylative Dearomatization of Indoles through Copper(I) Catalysis
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The enantioselective borylative dearomatization of a heteroaromatic compound has been achieved using a copper(I) catalyst and a diboron reagent. This reaction involves the regio- and enantioselective addition of active borylcopper(I) species to indole-2-carboxylates, followed by the diastereoselective protonation of the resulting copper(I) enolate to give the corresponding chiral indolines, which bear consecutive stereogenic centers.
- Kubota, Koji,Hayama, Keiichi,Iwamoto, Hiroaki,Ito, Hajime
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supporting information
p. 8809 - 8813
(2015/11/27)
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- Optimization of chemical functionalities of indole-2-carboxamides to improve allosteric parameters for the cannabinoid receptor 1 (CB1)
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5-Chloro-3-ethyl-N-(4-(piperidin-1-yl)phenethyl)-1H-indole-2-carboxamide (1; ORG27569) is a prototypical allosteric modulator for the cannabinoid type 1 receptor (CB1). Here, we reveal key structural requirements of indole-2-carboxamides for allosteric modulation of CB1: a critical chain length at the C3-position, an electron withdrawing group at the C5-position, the length of the linker between the amide bond and the phenyl ring B, and the amino substituent on the phenyl ring B these significantly impact the binding affinity (KB) and the binding cooperativity (α). A potent CB1 allosteric modulator 5-chloro-N-(4-(dimethylamino)phenethyl)-3-propyl-1H-indole- 2-carboxamide (12d) was identified. It exhibited a KB of 259.3 nM with a strikingly high binding α of 24.5. We also identified 5-chloro-N-(4-(dimethylamino)phenethyl)-3-hexyl-1H-indole-2-carboxamide (12f) with a KB of 89.1 nM, which is among the lowest KB values obtained for any allosteric modulator of CB1 these positive allosteric modulators of orthosteric agonist binding nonetheless antagonized the agonist-induced G-protein coupling to the CB1 receptor, yet induced β-arrestin mediated ERK1/2 phosphorylation.
- Khurana, Leepakshi,Ali, Hamed I.,Olszewska, Teresa,Ahn, Kwang H.,Damaraju, Aparna,Kendall, Debra A.,Lu, Dai
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p. 3040 - 3052
(2014/05/06)
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- INDOLE DERIVATIVES
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The present invention relates to the indole derivatives of formula (I), wherein R1-R6 and X are defined in the claims and optical antipodes or racemates and/or salts thereof which are selective antagonists of bradykinin B1 to process for producing these compounds, pharmacological compositions containing them and to their use in therapy or prevention of painful and inflammatory conditions.
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Paragraph 0187
(2013/08/28)
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- Extending the versatility of the Hemetsberger-Knittel indole synthesis through microwave and flow chemistry
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Microwave, flow and combination methodologies have been applied to the synthesis of a number of substituted indoles. Based on the Hemetsberger-Knittel (HK) process, modifications allow formation of products rapidly and in high yield. Adapting the methodology allows formation of 2-unsubstituted indoles and derivatives, and a route to analogs of the antitumor agent PLX-4032 is demonstrated. The utility of the HK substrates is further demonstrated through bioconjugation and subsequent ring closure and via Huisgen type [3+2] cycloaddition chemistry, allowing formation of peptide adducts which can be subsequently labeled with fluorine tags.
- Ranasinghe, Nadeesha,Jones, Graham B.
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p. 1740 - 1742
(2013/04/10)
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- INDOLE DERIVATIVES
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The present invention relates to the indole derivatives of formula (I), wherein R1- R6 and X are defined in the claims and optical antipodes or racemates and/or salts thereof which are selective antagonists of bradykinin B1 to process for producing these compounds, pharmacological compositions containing them and to their use in therapy or prevention of painful and inflammatory conditions.
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Page/Page column 57
(2012/05/20)
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- Synthesis of carbazoles by gold(I)-catalyzed carbocyclization of 2-(enynyl)indoles
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A new synthetic protocol for carbazoles through gold(I)-catalyzed intramolecular hydroarylation of (Z)-2-(enynyl)indoles was achieved in good yields. The requisite (Z)-2-(enynyl)indoles were synthesized stereoselectively by trimethylgallium-promoted, Z-selective Wittig olefination of N-alkylindole-2-carboxaldehydes with propargyl ylides. Substrates possessing both alkyl as well as aromatic groups are well tolerated under these reaction conditions. Georg Thieme Verlag Stuttgart.
- Praveen, Chandrasekaran,Perumal, Paramasivan Thirumalai
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scheme or table
p. 521 - 524
(2011/04/17)
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- Gold(III) chloride catalyzed regioselective synthesis of pyrano[3,4-b]indol-1(9H)-ones and evaluation of anticancer potential towards human cervix adenocarcinoma
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A highly regioselective synthesis of pyrano[3,4-b]indol-1(9H)-ones via gold(III) chloride catalyzed cycloisomerization of 3-ethynyl-indole-2-carboxylic acid was achieved in good to excellent yields. These compounds were screened for their in vitro cytotoxicity against human cervical (HeLa) cell lines. Out of ten compounds, three compounds (7d, 7e and 7j) showed comparable proliferation inhibitory activity against the standard drug cisplatin. Compound 7d was found to be the most efficacious with IC50 value of 0.22 μM.
- Praveen, Chandrasekaran,Ayyanar, Asairajan,Perumal, Paramasivan Thirumalai
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supporting information; experimental part
p. 4170 - 4173
(2011/08/06)
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- Continuous flow thermolysis of azidoacrylates for the synthesis of heterocycles and pharmaceutical intermediates
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An efficient, safe and scalable procedure for the continuous flow thermolysis of azidoacrylates to yield indoles has been developed and was applied to the synthesis of related heterocycles. The scalability of the process was demonstrated in the continuous flow synthesis of a precursor to the DAAO inhibitor 4H-furo[3,2-b]pyrrole-5-carboxylic acid.
- O'Brien, Alexander G.,Levesque, Francois,Seeberger, Peter H.
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supporting information; experimental part
p. 2688 - 2690
(2011/04/25)
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- [Fe(F20TPP)Cl] catalyzed intramolecular C-N bond formation for alkaloid synthesis using aryl azides as nitrogen source
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The syntheses of alkaloids including indoles, indolines, tetrahydroquinolines, dihydroquinazolinones and quinazolinones have been accomplished in moderate to excellent yields via [Fe(F20TPP)Cl] catalyzed intramolecular C-N bond formation using aryl azides as nitrogen source.
- Liu, Yungen,Wei, Jinhu,Che, Chi-Ming
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supporting information; experimental part
p. 6926 - 6928
(2010/11/16)
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- Synthesis and pharmacological evaluation of 1,2,3,4-tetrahydropyrazino[1,2-a]indole and 2-[(phenylmethylamino)methyl]-1H-indole analogues as novel melatoninergic ligands
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Two novel series of melatonin-derived compounds have been synthesized and pharmacologically evaluated at the MT1 and MT2 subtypes of melatonin receptors. Compounds 12b-c are non-selective high-affinity MT1 and MT2/su
- Markl, Christian,Attia, Mohamed I.,Julius, Justin,Sethi, Shalini,Witt-Enderby, Paula A.,Zlotos, Darius P.
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scheme or table
p. 4583 - 4594
(2009/12/04)
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- Examination of the mechanism of Rh2(II)-catalyzed carbazole formation using intramolecular competition experiments
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(Chemical Equation Presented) The use of a rhodium(II) carboxylate catalyst enables the mild and stereoselective formation of carbazoles from biaryl azides. Intramolecular competition experiments of triaryl azides suggested the source of the selectivity. A primary intramolecular kinetic isotope effect was not observed, and correlation of the product ratios with Hammett σ+ values produced a plot with two intersecting lines with opposite ρ values. These data suggest that electronic donation by the biaryl π-system accelerates the formation of rhodium nitrenoid and that C-N bond formation occurs through a 4π-electron-5-atom electrocyclization.
- Stokes, Benjamin J.,Richert, Kathleen J.,Driver, Tom G.
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supporting information; experimental part
p. 6442 - 6451
(2009/12/24)
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- INDOLE DERIVATIVES AND DRUGS CONTAINING THE SAME
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An indole derivative represented by the following general formula (1) : wherein at least one of R1, R2, R3, and R4 represents an alkoxy group containing 1 to 20 carbon atoms, and other groups of the R1, R2, R3, and R4 represent hydrogen, an alkyl group containing 1 to 6 carbon atoms, acetyl group, or hydroxyl group; and either one of X and Y represents -(CH2)nOH wherein n is an integer of 0 to 30, and the other one of the X and Y represents hydrogen atom; or a salt thereof; and a drug and an agent for promoting differentiation of a stem cell containing such indole derivative or its salt as an effective component. The indole derivative (1) of the present invention has action of inducing differentiation of neural stem cell specifically into a neuron, and this indole derivative is useful as a prophylactic or therapeutic drug for brain dysfunction or neuropathy caused by loss or degeneration of the neuron.
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(2010/02/11)
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- Effects of indole fatty alcohols on the differentiation of neural stem cell derived neurospheres
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In a search for inducers of neuronal differentiation to treat neurodegenerative diseases such as Alzheimer's disease, a series of indole fatty alcohols (IFAs) were prepared, 13c (n = 18) was able to promote the differentiation of neural stem cell derived neurospheres into neurons at a concentration of 10 nM. Analysis of the expression of the Notch pathway genes in neurospheres treated during the differentiation phase with 13c (n = 18) revealed a significant decrease in the transcription of the Notch 4 receptor.
- Coowar, Djalil,Bouissac, Julien,Hanbali, Mazen,Paschaki, Marie,Mohier, Eliane,Luu, Bang
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p. 6270 - 6282
(2007/10/03)
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- Solid-phase synthesis of indolecarboxylates using palladium-catalyzed reactions
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Polymer-supported, palladium-catalyzed cyclization reactions effectively synthesized indolecarboxylates. Palladium-catalyzed carbon - carbon bond-forming reactions of immobilized enaminoesters followed by transesterification yielded indole 2- or 3-carboxylates with various functional groups on the benzene ring. Indolecarboxylates were efficiently cyclized via an intramolecular palladium-catalyzed amination reaction of immobilized N-substituted dehydrohalophenylalanines, and immobilized N-acetyl-dehydroalanines were efficiently converted into indolecarboxylates via tandem Heck-amination reactions.
- Yamazaki, Kazuo,Nakamura, Yosuke,Kondo, Yoshinori
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p. 6011 - 6019
(2007/10/03)
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- RCM in indoles. A new entry to the mitosene skeleton
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The RCM metathesis reaction catalyzed by Grubbs' ruthenium catalyst is used with a series of 1,2-disubstituted indoles leading with excellent yields to tricyclic compounds. When applied to 1-allyl-2-vinylindoles this methodology allows a new entry to the mitosene skeleton.
- González-Pérez, Patxi,Pérez-Serrano, Leticia,Casarrubios, Luis,Domínguez, Gema,Pérez-Castells, Javier
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p. 4765 - 4767
(2007/10/03)
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- Process development of 5-methoxy-1H-indole-2-carboxylic acid from ethyl 2-methylmalonate
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Development is described of a new process for the preparation from malonates of 5-methoxy-1H-indole-2-carboxylic acid esters, useful intermediates in the synthesis of pharmaceutical compounds. The process uses readily available starting materials, produces little waste, can be operated safely on at least 1 molar scale, and gives high yields. The main areas of optimization included the azo coupling of a diazonium salt with malonate derivatives, the Japp-Klingemann rearrangement, and the Fischer indole synthesis.
- Bessard, Yves
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p. 214 - 220
(2013/09/08)
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- Synthesis of indolylalkoxyiminoalkylcarboxylates as leukotriene biosynthesis inhibitors
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A series of substituted indolylalkoxyiminoalkylcarboxylates were found to be potent leukotriene biosynthesis inhibitors. The structure-activity relationships were investigated. Representative potent inhibitors identified were the quinolyl 3a (A-86885) and pyridyl 3b (A-86886) congeners with in vitro IC50s of 21 and 9 nM and in vivo leukotriene inhibition in the rat with oral ED50s of 0.9 and 1.7 mg/kg, respectively.
- Kolasa, Teodozyj,Bhatia, Pramila,Brooks, Clint D. W.,Hulkower, Keren I.,Bouska, Jennifer B.,Harris, Richard R.,Bell, Randy L.
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p. 507 - 514
(2007/10/03)
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- 9-substituted 6H-pyrido[4,3-b]carbazoles
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Compounds comprising the series of 9-substituted 5-hydroxymethyl-11-methyl-6H-pyrido[4,3-b]carbazole N-alkyl or aryl carbamates of general structure: STR1 where R=H, lower alkoxy, OH, aryloxy R1 =H or lower alkyl R2 =lower alkyl or aryl.
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