- A Bu4N[Fe(CO)3(NO)]-Catalyzed Hemetsberger–Knittel Indole Synthesis
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The nucleophilic Fe complex Bu4N[Fe(CO)3(NO)] (TBA[Fe]) catalyzes the direct intramolecular amination of aryl vinyl azides to give the corresponding indole derivatives in good to excellent yields.
- Baykal, Aslihan,Plietker, Bernd
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supporting information
(2020/02/20)
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- Cu-Catalyzed Oxidation of C2 and C3 Alkyl-Substituted Indole via Acyl Nitroso Reagents
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The selective oxidation of C2-alkyl-substituted indoles to 3-oxindole and the selective C-H oxygenation or amination of C2,C3-dialkyl-substituted indoles at C2 are reported under mild conditions. The position of the alkyl substitution on the indole directs the reaction to different pathways under similar conditions.
- Zhang, Jun,Torabi Kohlbouni, Saeedeh,Borhan, Babak
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supporting information
p. 14 - 17
(2019/01/08)
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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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- Tripodal S-Ligand Complexes of Copper(I) as Catalysts for Alkene Aziridination, Sulfide Sulfimidation, and C-H Amination
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Copper(I) complexes of tris(thioimidazolyl)borates (R′TmR), including [Cu(TmPh)(PR″3)] (R″ = Ph, Cu1; Cy, Cu2) and [Cu(R′TmPh)(PR″3)]+ (R′ = N-methylimidazole; R″ = Ph, Cy) were prepared an
- Lam, Tsz Lung,Tso, Ken Chi-Hang,Cao, Bei,Yang, Chen,Chen, Daqing,Chang, Xiao-Yong,Huang, Jie-Sheng,Che, Chi-Ming
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p. 4253 - 4257
(2017/04/26)
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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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- BENZOIMIDAZOLE DERIVATIVES AS PAD4 INHIBITORS
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Compounds of formula (I): wherein X, Y, R1 and R3-R11 are as herein defined, and salts thereof are PAD4 inhibitors and may be useful in the treatment of various disorders, for example rheumatoid arthritis, vasculitis, systemic lupus erythematosus, ulcerative colitis, cancer, cystic fibrosis, asthma, cutaneous lupus erythematosis, and psoriasis.
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Page/Page column 198
(2016/12/07)
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- A porous metal-organic cage constructed from dirhodium paddle-wheels: Synthesis, structure and catalysis
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Self-assembly of dirhodium(ii) tetraacetate (Rh2(OAc)4) with a dicarboxylic acid 3,3′-(1,3-phenylenebis(ethyne-2,1-diyl))dibenzoic acid (H2pbeddb) gives rise to a metal-organic cage (MOC) containing Rh-Rh bonds with the formula of [Rh4(pbeddb)4(H2O)2(DMAC)2] (MOC-Rh-1). Single-crystal X-ray diffraction analysis reveals that MOC-Rh-1 shows a lantern-type cage structure, in which a pair of Rh2(CO2)4 paddlewheels is linked by four diacid ligands. The dimensions of the inner cavity of MOC-Rh-1 are 9.5 × 14.8 ?2 (atom-to-atom distances across opposite metal and phenyl groups of pbeddb2-). In the solid phase, the cages are aligned by π-π stacking to form one-dimensional channels (9.5 × 11.1 ?2) through cage windows. Therefore, the crystalline samples of MOC-Rh-1 are porous with the inner and outer cavities of the cages accessible under the heterogeneous condition. MOC-Rh-1 has been fully characterized by EA, TGA, PXRD, IR, UV-vis and XPS measurements. The catalytic tests disclose that activated MOC-Rh-1 is effective in the intramolecular C-H amination of vinyl, dienyl and biaryl azides, leading to the formation of indoles, pyrroles and carbazoles, respectively, and the porous catalyst can be recycled easily and used for at least nine runs without significant loss of activity. In the nine runs, the conversions were in the range of 93-99%, whereas in the tenth run, the conversion was reduced to 78%.
- Chen, Lianfen,Yang, Tao,Cui, Hao,Cai, Tao,Zhang, Li,Su, Cheng-Yong
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supporting information
p. 20201 - 20209
(2015/10/19)
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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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- Iodine-mediated one-pot synthesis of indoles and 3-dimethylaminoindoles via annulation of enaminones
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The synthesis of 2-carbonylindoles was achieved via a iodine-mediated cyclization of the corresponding enaminone precursors, which were formed by reaction of the ?-arylaminomethylene carbonyl derivatives with N,N'-dimethylformamide dimethyl acetal (DMFDMA). An alternative and more efficient procedure consisted of a similar cyclization of the enaminones, but under solvent-free and grinding reaction conditions. In another iodine-promoted procedure, 2-carbonyl-3-dimethylaminoindoles were synthesized via a one-pot cascade reaction between the α-arylaminomethylene carbonyl derivative and DMFDMA.ARKAT-USA, Inc.
- Jerezano, Alberto V.,Labarrios, Ehecatl M.,Jimenez, Fabiola E.,Del Cruz, Maria Carmen,Pazos, Diana C.,Gutierrez, Rsuini U.,Delgado, Francisco,Tamariz, Joaquin
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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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- Iron(II) triflate as a catalyst for the synthesis of indoles by intramolecular C-H amination
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A practical iron-catalyzed intramolecular C-H amination reaction and its application in the synthesis of indole derivatives are presented. As a catalyst, commercially available iron(II) triflate is used.
- Bonnamour, Julien,Bolm, Carsten
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supporting information; experimental part
p. 2012 - 2014
(2011/06/28)
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- Design and synthesis of benzoxazole containing indole analogs as peroxisome proliferator-activated receptor-γ/δ dual agonists
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A series of benzoxazole or benzothiazole containing indole analogs, 6-alkoxyindole-2-carboxylic acids and 5-alkoxy-3-indolylacetic acids, were synthesized as novel candidates of PPARγ/δ dual agonists and their ligand activities for PPAR subtypes (α, γ, an
- Gim, Hyo Jin,Cheon, Ye-Jin,Ryu, Jae-Ha,Jeon, Raok
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p. 3057 - 3061
(2011/06/26)
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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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- Rapid and easy access to indoles via microwave-assisted Hemetsberger-Knittel synthesis
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Hemetsberger-Knittel indole synthesis can be carried out under microwave activation. The optimum reaction conditions were found by using different solvents and by varying irradiation times and temperature. After 10 min of microwave irradiation, high conversion into the corresponding indole products was achieved without formation of any side products.
- Lehmann, Frank,Holm, Melanie,Laufer, Stefan
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experimental part
p. 1708 - 1709
(2009/09/05)
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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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- Intramolecular C-H amination reactions: Exploitation of the Rh 2(II)-catalyzed decomposition of azidoacrylates
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Rhodium(II) perfluorobutyrate-mediated decomposition of vinyl azides provides a new, mild entry into Rh2(II) nitrenoid chemistry. This methodology allows rapid access to a variety of complex, functionalized N-heterocycles in two steps from commercially available starting materials. Copyright
- Stokes, Benjamin J.,Dong, Huijun,Leslie, Brooke E.,Pumphrey, Ashley L.,Driver, Tom G.
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p. 7500 - 7501
(2008/02/09)
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- General and easy access to 11-substituted 4-hydroxy-2,3,4,5-tetrahydro[1,4] diazepino[1,2-a]indol-1-one derivatives
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An efficient route to prepare the 4-hydroxy-2,3,4,5-tetrahydro[1,4] diazepino[1,2-a]indol-1-one scaffold is described. The key reactions of the synthesis are an iodolactonisation followed by a lactone-to-lactam rearrangement. Various 11-substituted deriva
- Putey, Aurélien,Fournet, Guy,Joseph, Beno?t
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p. 2755 - 2758
(2008/02/11)
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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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Page/Page column 8
(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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- Stille and suzuki cross coupling reactions of o-nitrophenyl triflates: A versatile route to a variety of heterocycles
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The cross coupling reactions of selected o-nitrophenyl triflates with arylstannane and arylboron substrates are reported. The resultant 2-nitrobiphenyls provide ready access to a variety of substituted heterocycles.
- Holzapfel, Cedric W.,Dwyer, Catherine
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p. 1513 - 1518
(2007/10/03)
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- Substituted indoles as anti-AIDS pharmaceuticals
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Substituted indoles of formula (I) STR1 are useful anti-AIDS pharmaceuticals.
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- Anti-aids piperazines
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The present invention includes diaromatic substituted heterocyclic compounds (III) STR1 which are useful in treating individuals infected with the HIV virus. The invention includes certain previously generically disclosed anti-AIDS piperazinyl compounds (V) and a method of treating HIV infected individuals with the indoles of formula (V) and the anti-AIDS amines (X).
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- Entry into 6-methoxy-D(+)-tryptophans. Stereospecific synthesis of 1-benzenesulfonyl-6-methoxy-D(+)-tryptophan ethyl ester
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A strategy for the synthesis of optically active ring-A methoxylated indole alkaloids which employs the Moody azide/Schollkopf chiral auxiliary protocol has resulted in the successful preparation of 1-benzenesulfonyl-6-methoxy-D(+)-tryptophan ethyl ester 16. This amino ester is required for the synthesis of Alstonia bisindole alkaloids including macralstonine 2 via an enantiospecific Pictet-Spengler reaction
- Allen,Hamaker,La Loggia,Cook
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p. 2077 - 2102
(2007/10/02)
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