- Fluorescence Decay of Tryptophan Conformers in Aqueous Solution
-
The fluorescence decay parameters of aqueous solutions of tryptophan and several tryptophan and indole derivatives are reported.The fluorescence decays of tryptophan, tryptophan ethyl ester, and 5-methyl- and 6-methyltryptophan are all described by double exponential kinetics.The relative proportions of the two components vary with emission wavelength.The fluorescence of all other derivatives obeys single exponential decay kinetics.In the case of tryptophan the two components, τ1 = 3.1 ns and τ2 = 0.51 ns, had fluorescence maxima at 350 and 335 nm, respectively.The origin of this behavior is discussed in terms of several models bur is most consistent with the assignment of the emission to different rotamers or conformers of the alanyl side chain of tryptophan.
- Szabo, A. G.,Rayner, D. M.
-
-
Read Online
- Anhydrous Hydrogen Iodide-Mediated Reductive Indolization of in Situ-Generated Cyclopropyl Hydrazones
-
Fischer-type indolization of N-aryl-C-cyclopropyl hydrazones generated in situ followed by chemoselective reduction using tert-butyl iodide as an anhydrous HI generator was developed. This protocol provides indoles bearing carboxylic acid derivative units. A series of control experiments indicated the HI-mediated formation and reduction of spirocyclopropyl indolenines. Anhydrous HI functions as a Br?nsted acid as well as a reducing agent, facilitating the successful conversion of unstable reaction intermediates and iodinated mixtures in equilibrium.
- Yasui, Motohiro,Fujioka, Hiroki,Takeda, Norihiko,Ueda, Masafumi
-
supporting information
p. 43 - 47
(2021/12/17)
-
- SUBSTITUTED TETRAHYDROPYRANOINDOLES, DERIVATIVES THEREOF, AND THEIR METHODS OF SYNTHESIS AND USE
-
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.
- -
-
Paragraph 0160; 0161
(2021/01/25)
-
- 4-Alkyl-1,2,4-triazole-3-thione analogues as metallo-β-lactamase inhibitors
-
In Gram-negative bacteria, the major mechanism of resistance to β-lactam antibiotics is the production of one or several β-lactamases (BLs), including the highly worrying carbapenemases. Whereas inhibitors of these enzymes were recently marketed, they only target serine-carbapenemases (e.g. KPC-type), and no clinically useful inhibitor is available yet to neutralize the class of metallo-β-lactamases (MBLs). We are developing compounds based on the 1,2,4-triazole-3-thione scaffold, which binds to the di-zinc catalytic site of MBLs in an original fashion, and we previously reported its promising potential to yield broad-spectrum inhibitors. However, up to now only moderate antibiotic potentiation could be observed in microbiological assays and further exploration was needed to improve outer membrane penetration. Here, we synthesized and characterized a series of compounds possessing a diversely functionalized alkyl chain at the 4-position of the heterocycle. We found that the presence of a carboxylic group at the extremity of an alkyl chain yielded potent inhibitors of VIM-type enzymes with Ki values in the μM to sub-μM range, and that this alkyl chain had to be longer or equal to a propyl chain. This result confirmed the importance of a carboxylic function on the 4-substituent of 1,2,4-triazole-3-thione heterocycle. As observed in previous series, active compounds also preferentially contained phenyl, 2-hydroxy-5-methoxyphenyl, naphth-2-yl or m-biphenyl at position 5. However, none efficiently inhibited NDM-1 or IMP-1. Microbiological study on VIM-2-producing E. coli strains and on VIM-1/VIM-4-producing multidrug-resistant K. pneumoniae clinical isolates gave promising results, suggesting that the 1,2,4-triazole-3-thione scaffold worth continuing exploration to further improve penetration. Finally, docking experiments were performed to study the binding mode of alkanoic analogues in the active site of VIM-2.
- Gavara, Laurent,Legru, Alice,Verdirosa, Federica,Sevaille, Laurent,Nauton, Lionel,Corsica, Giuseppina,Mercuri, Paola Sandra,Sannio, Filomena,Feller, Georges,Coulon, Rémi,De Luca, Filomena,Cerboni, Giulia,Tanfoni, Silvia,Chelini, Giulia,Galleni, Moreno,Docquier, Jean-Denis,Hernandez, Jean-Fran?ois
-
supporting information
(2021/06/15)
-
- Synthesis of CF3-Containing Spirocyclic Indolines via a Red-Light-Mediated Trifluoromethylation/Dearomatization Cascade
-
A red-light-mediated nPr-DMQA+-catalyzed cascade intramolecular trifluoromethylation and dearomatization of indole derivatives with Umemoto's reagent has been developed. This protocol provides a facile and efficient approach for the construction of functionalized and potentially biologically important CF3-containing 3,3-spirocyclic indolines with moderate to high yields and excellent diastereoselectivities under mild conditions. The success of multiple gram-scale (1 and 10 g) experiments further highlights the robustness and practicality of this protocol and the merit of the employment of red light. Mechanistic studies support the formation of a crucial CF3 radical species and a dearomatized benzyl carbocation intermediate.
- Gianetti, Thomas L.,Mei, Liangyong,Moutet, Jules,Stull, Savannah M.
-
supporting information
p. 10640 - 10653
(2021/07/31)
-
- Electrochemical Hydrogenation with Gaseous Ammonia
-
As a carbon-free and sustainable fuel, ammonia serves as high-energy-density hydrogen-storage material. It is important to develop new reactions able to utilize ammonia as a hydrogen source directly. Herein, we report an electrochemical hydrogenation of alkenes, alkynes, and ketones using ammonia as the hydrogen source and carbon electrodes. A variety of heterocycles and functional groups, including for example sulfide, benzyl, benzyl carbamate, and allyl carbamate were well tolerated. Fast stepwise electron transfer and proton transfer processes were proposed to account for the transformation.
- Li, Jin,He, Lingfeng,Liu, Xu,Cheng, Xu,Li, Guigen
-
supporting information
p. 1759 - 1763
(2019/01/16)
-
- COMPOUNDS FOR TREATING RAC-GTPASE MEDIATED DISORDER
-
This disclosure relates to certain compounds that are effective in the treatment of a Rac-GTPase mediated disorder (e.g., acute lymphoblastic or chronic myelogenous leukemia), as well as methods for the manufacture of and the use of these compounds (e.g.,
- -
-
Page/Page column 33
(2019/08/08)
-
- A Cooperative Hydrogen Bond Donor–Br?nsted Acid System for the Enantioselective Synthesis of Tetrahydropyrans
-
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.
-
supporting information
p. 17225 - 17229
(2018/12/05)
-
- Radical-Mediated Dearomatization of Indoles with Sulfinate Reagents for the Synthesis of Fluorinated Spirocyclic Indolines
-
The dearomative introduction of trifluoromethyl and 1,1-difluoroethyl radicals, generated from their corresponding sulfinate salts, into the C2 position of indole derivatives allows the diastereoselective synthesis of three-dimensional 3,3-spirocyclic indolines over C-H functionalized indoles.
- Ryzhakov, Dmytro,Jarret, Maxime,Guillot, Régis,Kouklovsky, Cyrille,Vincent, Guillaume
-
p. 6336 - 6339
(2017/12/08)
-
- Ethyl 2-cyano-2-(2-nitrobenzenesulfonyloxyimino)acetate (o -NosylOXY): A recyclable coupling reagent for racemization-free synthesis of peptide, amide, hydroxamate, and ester
-
Ubiquitousness of amide and ester functionality makes coupling reactions extremely important. Although numerous coupling reagents are available, methods of preparation of the common and efficient reagents are cumbersome. Those reagents generate a substantial amount of chemical waste and lack recyclability. Ethyl 2-cyano-2-(2-nitrobenzenesulfonyloxyimino)acetate (o-NosylOXY), the first member of a new generation of coupling reagents, produces byproducts that can be easily recovered and reused for the synthesis of the same reagent, making the method more environmentally friendly and cost-effective. The synthesis of amides, hydroxamates, peptides, and esters using this reagent is described. The synthesis of the difficult sequences, for example, the islet amyloid polypeptide (22-27) fragment (with a C-terminal Gly, H-Asn-Phe-Gly-Ala-Ile-Leu-Gly-NH 2) and acyl carrier protein (65-74) fragment (H-Val-Gln-Ala-Ala-Ile- Asp-Tyr-Ile-Asn-Gly-OH), following the solid-phase peptide synthesis (SPPS) protocol and Amyloid β (39-42) peptide (Boc-Val-Val-IIe-Ala-OMe), following solution-phase strategy is demonstrated. Remarkable improvement is noticed with respect to reaction time, yield, and retention of stereochemistry. A mechanistic investigation and recyclability are also described.
- Dev, Dharm,Palakurthy, Nani Babu,Thalluri, Kishore,Chandra, Jyoti,Mandal, Bhubaneswar
-
p. 5420 - 5431
(2014/07/08)
-
- Synthesis and biological screening of 5-(alkyl(1H-indol-3-yl))-2- (substituted)-1,3,4-oxadiazoles as antiproliferative and anti-inflammatory agents
-
A series of 5-(alkyl(1H-indol-3-yl))-2-(substituted)-1,3,4-oxadiazoles were efficiently synthesized by oxidative cyclisation of N0 -benzylidene-(1H-indol- 3-yl)alkane hydrazides using di(acetoxy)iodobenzene. N0 -Benzylidene-(1H-indol- 3-yl)alkane hydrazid
- Rapolu, Sreevani,Alla, Manjula,Bommena, Vittal Rao,Murthy, Ramalinga,Jain, Nishant,Bommareddy, Venkata Ramya,Bommineni, Madhava Reddy
-
-
- Metabolism and metabolites of dithiocarbamates in the plant pathogenic fungus leptosphaeria maculans
-
Synthetic compounds containing a dithiocarbamate group are known to have a variety of biological effects and applications including antifungal, herbicidal, and insecticidal application. Leptosphaeria maculans is a fungal pathogen of crucifers able to detoxify efficiently the only plant natural product containing a dithiocarbamate group, the phytoalexin brassinin. To evaluate the effects of dithiocarbamates on L. maculans, a number of structurally diverse S-methyl dithiocarbamates containing indolyl, biphenyl, and benzimidazolyl moieties were synthesized, and their antifungal activities and metabolism by L. maculans were investigated. All dithiocarbamates were transformed by L. maculans through hydrolysis to the corresponding amines, which were less antifungal than the parent compounds. Two dithiocarbonates were shown to be much less antifungal than the corresponding dithiocarbamates. Results of this investigation indicate that S-methyl dithiocarbamates are not useful inhibitors of L. maculans and that their rates of transformation by L. maculans did not correlate with the antifungal activity of the particular compound.
- Pedras, M. Soledade C.,Sarma-Mamillapalle, Vijay K.
-
experimental part
p. 7792 - 7798
(2012/10/08)
-
- Highly efficient InBr3 catalyzed michael addition of indoles to α,β-Unsaturated Esters
-
A highly efficient synthetic strategy toward Michael addition of indoles to α,β-unsaturated esters has been developed using Lewis acid InBr 3 as catalyst. The reactions generated 3-substituted indoles in high yields with excellent regio-selecti
- Liu, Ping,Chen, Wei,Ren, Kai,Wang, Lei
-
experimental part
p. 2399 - 2403
(2011/09/21)
-
- Indolyl-3-acetaldoxime dehydratase from the phytopathogenic fungus Sclerotinia sclerotiorum: Purification, characterization, and substrate specificity
-
The purification and characterization of indolyl-3-acetaldoxime dehydratase produced by the plant fungal pathogen Sclerotinia sclerotiorum is described. The substrate specificity indicates that it is an indolyl-3-acetaldoxime dehydratase (IAD, EC 4.99.1.6), which catalyzes transformation of indolyl-3-acetaldoxime to indolyl-3-acetonitrile. The enzyme showed Michaelis-Menten kinetics and had an apparent molecular mass of 44 kDa. The amino acid sequence of IAD, determined using LC-ESI-MS/MS, identified it as the protein SS1G-01653 from S. sclerotiorum. IADSs was highly homologous (84% amino acid identity) to the hypothetical protein BC1G-14775 from Botryotinia fuckeliana B05.10. In addition, similarity to the phenylacetaldoxime dehydratases from Gibberella zeae (33% amino acid identity) and Bacillus sp. (20% amino acid identity) was noted. The specific activity of IADSs increased about 17-fold upon addition of Na2S2O4 under anaerobic conditions, but in the absence of Na2S2O 4 no significant change was observed, whether aerobic or anaerobic conditions were used. As with other aldoxime dehydratases isolated from microbes, the role of IADSs in fungal plant pathogens is not clear, but given its substrate specificity, it appears unlikely that IADSs is a general xenobiotic detoxifying enzyme.
- Pedras, M. Soledade C.,Minic, Zoran,Thongbam, Premila D.,Bhaskar, Vangala,Montaut, Sabine
-
experimental part
p. 1952 - 1962
(2011/06/26)
-
- Synthesis of N-aryl-3-(indol-3-yl)propanamides and their immunosuppressive activities
-
N-Aryl-3-(indol-3-yl)propanamides were synthesized and their immunosuppressive activities were evaluated. This study highlighted the promising potency of 3-[1-(4-chlorobenzyl)-1H-indol-3-yl]-N-(4-nitrophenyl) propanamide 15 which exhibited a significant i
- Giraud, Francis,Marchand, Pascal,Carbonnelle, Delphine,Sartor, Michael,Lang, Fran?ois,Duflos, Muriel
-
scheme or table
p. 5203 - 5206
(2010/10/03)
-
- N-ACYLHYDRAZONE DERIVATIVES USEFUL AS MODULATORS OF NICOTINIC ACETYLCHOLINE RECEPTORS
-
This invention relates to N-acylhydrazone derivatives (I), which are found to be useful as modulators of the nicotinic acetylcholine receptors. Due to their pharmacological profile the compounds of the invention may be useful for the treatment of diseases
- -
-
Page/Page column 19
(2009/06/27)
-
- Synthesis of 2-alkyl-substituted chromone derivatives using microwave irradiation
-
A base-promoted condensation between 2-hydroxyacetophenones and aliphatic aldehydes has been studied. The reaction has been optimized to afford 2-alkyl-substituted 4-chromanones in an efficient manner using microwave heating. Performing the reaction using
- Friden-Saxin, Maria,Pemberton, Nils,Da Silva Andersson, Krystle,Dyrager, Christine,Friberg, Annika,Grotli, Morten,Luthman, Kristina
-
supporting information; experimental part
p. 2755 - 2759
(2009/08/15)
-
- Synthetic N-pyridinyl(methyl)-indol-3-ylpropanamides as new potential immunosuppressive agents
-
Several N-pyridinyl(methyl)-indol-3-ylpropanamides were synthesized and pharmacological evaluations of their immunosuppressive potential were performed. Among thirteen compounds tested in vitro on murine T proliferation, three showed interesting inhibitin
- Carbonnelle, Delphine,Lardic, Morgane,Dassonville, Alexandra,Verron, Elise,Petit, Jean-Yves,Duflos, Muriel,Lang, Francois
-
p. 686 - 693
(2008/02/11)
-
- Indole-3-propionamide and derivatives thereof
-
Indolepropionamide (IPAM) and related compounds, pharmaceutical or dietary compositions thereof and methods of using said compounds are disclosed for use as a preventative or therapeutic treatment for many conditions related to oxidative damage. Oxidative damage increases in aging and age related disorders and is widespread in many neurodegenerative conditions including Alzheimer's disease, Parkinson's disease and others. Indolepropionamide is a potent anti-oxidant and anti-aging molecule, with superior properties as compares to previously known compounds.
- -
-
Page/Page column 4
(2008/06/13)
-
- Efficient michael addition of indoles using bismuthyl perchlorate as catalyst
-
An efficient method for Michael addition of indoles hasbeen developed using bismuthyl perchlorate (BiOClO4·xH2O) as catalyst. The reaction proceeds to give 3-substituted indoles excellently stirring indoles and Michael acceptors in acetonitrile in the presence of the catalyst at room temperature or in much shorter reaction times under sonication at ambient temperature.{A figure is presented}.
- Mohammadpoor-Baltork, Iraj,Reza Memarian, Hamid,Reza Khosropour, Ahmad,Nikoofar, Kobra
-
p. 1837 - 1843
(2007/10/03)
-
- ZrCl4 catalyzed highly selective and efficient Michael addition of heterocyclic enamines with α,β-unsaturated olefins
-
Highly selective and efficient Michael additions of heterocyclic enamines, viz. indoles, pyrroles, and pyrazoles with α,β-unsaturated olefins using 2 mol % of ZrCl4 has been achieved.
- Kumar, Vijay,Kaur, Sukhdeep,Kumar, Subodh
-
p. 7001 - 7005
(2007/10/03)
-
- New N-pyridinyl(methyl)-indolalkanamides acting as topical inflammation inhibitors
-
The authors have described the synthetic way to new N-pyridinyl(methyl) indolylpropanamides acting as non acidic NSAIDs. Pharmacomodulation was carried out at N-1 and C-5 of the indole ring and at the level of the propanamide chain. N-(pyridin-3-ylmethyl)-3-[5-chloro-1-(4-chlorobenzyl)-indol-3-yl]propanamide 32 represents one of the most potent compounds evaluated in the TPA-induced mouse ear swelling assay, with a level of activity higher than that of ibuprofen and comparable to that of dexamethasone.
- Dassonville, Alexandra,Bretéché, Anne,Evano, Johan,Duflos, Muriel,Le Baut, Guillaume,Grimaud, Nicole,Petit, Jean-Yves
-
p. 5441 - 5444
(2007/10/03)
-
- Synthesis and pharmacological evaluation of (indol-3-yl)alkylamides as potent analgesic agents
-
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
-
p. 814 - 824
(2007/10/03)
-
- New N-(pyridin-4-yl)-(indol-3-yl)acetamides and propanamides as antiallergic agents
-
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
-
p. 638 - 648
(2007/10/03)
-
- Certain N-(pyridyl) indoles
-
Disclosed are compounds of formula I STR1 wherein Ar is 3- or 4-pyridyl or 3- or 4-pyridyl substituted by lower alkyl; R1 is hydrogen, halogen, trifluoromethyl, lower alkyl, hydroxy, acylated or etherified hydroxy, lower alkyl-(thio, sulfinyl o
- -
-
-