- Thermally and Magnetically Robust Triplet Ground State Diradical
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High spin (S = 1) organic diradicals may offer enhanced properties with respect to several emerging technologies, but typically exhibit low singlet triplet energy gaps and possess limited thermal stability. We report triplet ground state diradical 2 with a large singlet-triplet energy gap, ?"EST ≥ 1.7 kcal mol-1, leading to nearly exclusive population of triplet ground state at room temperature, and good thermal stability with onset of decomposition at a160 °C under inert atmosphere. Magnetic properties of 2 and the previously prepared diradical 1 are characterized by SQUID magnetometry of polycrystalline powders, in polystyrene glass, and in other matrices. Polycrystalline diradical 2 forms a novel one-dimensional (1D) spin-1 (S = 1) chain of organic radicals with intrachain antiferromagnetic coupling of J′/k = a14 K, which is associated with the N···N and N···O intermolecular contacts. The intrachain antiferromagnetic coupling in 2 is by far strongest among all studied 1D S = 1 chains of organic radicals, which also makes 1D S = 1 chains of 2 most isotropic, and therefore an excellent system for studies of low-dimensional magnetism. In polystyrene glass and in frozen benzene or dibutyl phthalate solution, both 1 and 2 are monomeric. Diradical 2 is thermally robust and is evaporated under ultrahigh vacuum to form thin films of intact diradicals on silicon substrate, as demonstrated by X-ray photoelectron spectroscopy. Based on C-K NEXAFS spectra and AFM images of the a1.5 nm thick films, the diradical molecules form islands on the substrate with molecules stacked approximately along the crystallographic a-axis. The films are stable under ultrahigh vacuum for at least 60 h but show signs of decomposition when exposed to ambient conditions for 7 h.
- Gallagher, Nolan,Zhang, Hui,Junghoefer, Tobias,Giangrisostomi, Erika,Ovsyannikov, Ruslan,Pink, Maren,Rajca, Suchada,Casu, Maria Benedetta,Rajca, Andrzej
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Read Online
- A Diastereoselective Route to Benzoannelated Bridged Sultams
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A practical diastereoselective method for the synthesis of benzoannelated tri- and tetracyclic bridged sultams has been developed. The synthetic route employs widely available, substituted -iodoanilines and is based on intramolecular Michael addition followed by cycloalkylation with dihaloalkanes, or vice versa. The target compounds were isolated in good yields and the diastereoselectivity of the reaction could be easily controlled by the order of Michael addition and cycloalkylation steps.
- Klochkova, Anastasiia A.,Rassadin, Valentin A.,Sokolov, Victor V.
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supporting information
p. 4484 - 4494
(2021/08/13)
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- New Indolo[3,2-b]indole based small organic molecules for Organic Thin Film Transistors (OTFTs): A combined experimental and DFT Study
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Synthesis of new indolo[3,2-b]indoles (5a- 5j) in presence of Ag-doped ZnO and (Diacetoxyiodo) benzene system under visible-light have been reported. All the new fused linear heterocyclic indolo[3,2-b]indole systems (5a- 5j) thoroughly characterized by spectroscopic methods like mass, UV-visible, NMR and C, H, N elemental analysis. Further, their photophysical properties were carried out by combined experimental and theoretical studies. Thermogravimetric studies are carried out to confirm the thermal stability of molecules. The frontier molecular orbitals of molecules are characterized with the help of cyclic voltammetry. Additionally, the compounds of series 5 were used for the fabrication of organic thin-film transistors, which indicated the hole mobilities in the range of 0.11 – 0.85 cm2/Vs and with on/off ratio 105 on ODTS-SiO2 substrate at 50 °C and are also supported by DFT studies.
- Puli, Venkat Swamy,Subburu, Mahesh,Bhongiri, Yadagiri,Tripathi, Anuj,Prasad,Chatterjee, Anindita,Pola, Someshwar,Chetti, Prabhakar
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- Modular counter-Fischer?indole synthesis through radical-enolate coupling
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A single-electron transfer mediated modular indole formation reaction from a 2-iodoaniline derivative and a ketone has been developed. This transition-metal-free reaction shows a broad substrate scope and unconventional regioselectivity trends. Moreover, important functional groups for further transformation are tolerated under the reaction conditions. Density functional theory studies reveal that the reaction proceeds by metal coordination, which converts a disfavored 5-endo-trig cyclization to an accessible 7-endo-trig process.
- Chung, Hyunho,Kim, Jeongyun,Gonzalez-Montiel, Gisela A.,Cheong, Paul Ha-Yeon,Lee, Hong Geun
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supporting information
p. 1096 - 1102
(2021/01/26)
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- 5, 10-dihydroindolo [3, 2-b] indole derivative and synthesis method and application thereof
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The invention discloses a synthesis method of a 5, 10-dihydroindolo [3, 2-b] indole derivative, the method comprises the following steps: mixing a 2-((2-halogen phenyl) ethynyl)-N, N-dimethylaniline derivative (II), N, N-di-tert-butyl diazacycloketone (III), a palladium catalyst, a monophosphine ligand, alkali and a first organic solvent, and carrying out a diamidation reaction under the protection of inert gas to realize the synthesis of the 5, 10-dihydroindolo [3, 2-b] indole derivative(I). The method is easy to operate, mild in reaction condition and high in reaction yield, and the synthesized 5, 10-dihydroindolo [3, 2-b] indole derivative can be used for preparing an organic light-emitting device.
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Paragraph 0152; 0154-0155
(2021/07/17)
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- Cu(II)-Promoted Cascade Synthesis of Fused Imidazo-Pyridine-Carbonitriles
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A Cu(II)-promoted synthesis of an aza-fused N-heterocycle having a benz-imidazopyridine scaffold is developed via an addition-cyclization reaction followed by an Ullmann-type C-N coupling between o-iodoanilines and γ-ketodinitriles. This protocol features a broad substrate scope, giving products in 32-84% yields. The compounds show excellent photoluminescence properties having two absorption maxima in the region between 270-280 and 338-350 nm and emission maxima in the range of 502-533 nm. The HOMO-LUMO energy gap of 3.49-3.57 eV was determined using Gaussian 09 at the B3LYP/6-31G (d, p) basis set level. We also demonstrated a few postsynthetic modifications.
- Rakshit, Amitava,Dhara, Hirendra Nath,Alam, Tipu,Dahiya, Anjali,Patel, Bhisma K.
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supporting information
p. 17504 - 17510
(2021/11/18)
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- A novel DMSO-assisted regioselective iodination of aniline analogues
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A metal- and oxidant-free electrophilic iodination of aniline analogues was achieved in high to excellent yields at room temperature in MTBE with 0 or 3.5 equivalents of DMSO. Examined substituents include N-alkyl, N,N-dialkyl, N-morpholinyl and N-piperazinyl as well as methyl, Br, CN and CO2CH3 aryl ring substitutions.
- Bovonsombat, Pakorn,Lorpaiboon, Wanutcha,Laoboonchai, Sarocha,Sriprachaya-anunt, Prima,Yimkosol, Warangkana,Siriphatcharachaikul, Natthapatch,Siricharoensang, Pornpawit,Kangwannarakul, Terawee,Maeda, Jin,Losuwanakul, Satreerat,Mahesh Abhyankar, Maitraye
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- Intramolecular Hydroamination of Selenoalkynes to 2-Selenylindoles in the Absence of Catalyst
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In this work, a series of 2-chalcogenylindoles was synthesized by an efficient methodology, starting from chalcogenoalkynes, including a previously unreported tellurium indole derivative. For the first time, these 2-substituted chalcogenylindoles were obtained in the absence of metal catalyst or base, under thermal conditions only. In addition, the results described herein represent a methodology with inverse regioselectivity for the chalcogen functionalization of indoles.
- Coelho, Felipe L.,Gil, Eduarda S.,Gon?alves, Paulo F. B.,Campo, Leandra F.,Schneider, Paulo H.
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supporting information
p. 8157 - 8162
(2019/05/29)
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- Base-Promoted Aerobic Oxidation/Homolytic Aromatic Substitution Cascade toward the Synthesis of Phenanthridines
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The current protocol represents a transition metal-free synthesis of polysubstituted phenanthridines from abundant starting materials like benzhydrol and 2-iodoaniline derivatives. The reaction involves sequential oxidation of alcohol and direct condensation reaction with the amine resulting in a C?N bond formation followed by a radical C?C coupling in a cascade sequence. The used base potassium tert-butoxide plays a dual role in dehydrogenation and homolytic aromatic substitution reaction. Using this methodology, twenty substituted phenanthridine derivatives were synthesized with up to 85% isolated yield. (Figure presented.).
- Maiti, Debabrata,Halder, Atreyee,De Sarkar, Suman
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supporting information
p. 4941 - 4948
(2019/11/03)
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- Molecular Scaffolds as Double-Targeting Agents For the Diagnosis and Treatment of Neuroblastoma
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The selective delivery of therapeutic and imaging agents to tumoral cells has been postulated as one of the most important challenges in the nanomedicine field. Meta-iodobenzilguanidine (MIBG) is widely used for the diagnosis of neuroblastoma (NB) due to its strong affinity for the norepinephrine transporter (NET), usually overexpressed on the membrane of malignant cells. Herein, a family of novel Y-shaped scaffolds has been synthesized, which have structural analogues of MIBG covalently attached at each end of the Y-structure. The cellular uptake capacity of these double-targeting ligands has been evaluated in vitro and in vivo, yielding one specific Y-shaped structure that is able to be engulfed by the malignant cells, and accumulates in the tumoral tissue, at significantly higher levels than the structure containing only one single targeting agent. This Y-shaped ligand can provide a powerful tool for the current treatment and diagnosis of this disease.
- Villaverde, Gonzalo,Alfranca, Arantzazu,Gonzalez-Murillo, áfrica,Melen, Gustavo J.,Castillo, Rafael R.,Ramírez, Manuel,Baeza, Alejandro,Vallet-Regí, María
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supporting information
p. 3067 - 3072
(2019/01/14)
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- LIGANDS FOR ENHANCED IMAGING AND DRUG DELIVERY TO NEUROBLASTOMA CELLS
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The present invention concerns aminobenzylguanidine derivative ligands specifically targeting neuroblastoma cells with an improved cellular uptake. The improved cellular uptake provides for the therapeutic and diagnostic use of the ligands in neuroblastoma-related diseases.
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Page/Page column 19-20
(2019/10/23)
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- One-pot ortho-amination of aryl C-H bonds using consecutive iron and copper catalysis
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A one-pot approach for ortho-coupling of arenes with non-actived N-nucleophiles has been developed using sequential iron and copper catalysis. Regioselective ortho-activation of anisoles, anilines and phenols was achieved through iron(iii) triflimide catalysed iodination, followed by a copper(i)-catalysed, ligand-assisted coupling reaction with N-heterocycle, amide and sulfonamide-based nucleophiles. The synthetic utility of this one-pot, two-step method for the direct amination of ortho-aryl C-H bonds was demonstrated with the late-stage functionalisation of 3,4-dihydroquinolin-2-ones. This allowed the preparation of a TRIM24 bromodomain inhibitor and a series of novel analogues.
- Henry, Martyn C.,McGrory, Rochelle,Faggyas, Réka J.,Mostafa, Mohamed A. B.,Sutherland, Andrew
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p. 4629 - 4639
(2019/05/17)
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- Synthesis of 5-Cyano-Tryptophan as a Two-Dimensional Infrared Spectroscopic Reporter of Structure
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A concise synthesis of protected 5-cyano-l-tryptophan (Trp5CN) has been developed for 2D IR spectroscopic investigations within either peptides or proteins. To assess the potential of differently substituted cyano-tryptophans, several model cya
- Chalyavi, Farzaneh,Gilmartin, Philip H.,Schmitz, Andrew J.,Fennie, Michael W.,Tucker, Matthew J.
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supporting information
p. 7528 - 7532
(2018/06/04)
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- Synthesis of carbazoles based on gold-copper tandem catalysis
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An efficient synthetic method for carbazoles has been developed employing diazo anilinoalkynes as substrates. Sequential activation of the orthogonal functional groups embedded in diazo anilinoalkyne substrates by tandem gold-copper catalysis leads to the formation of highly substituted carbazoles. Substrate scope reveals a broad tolerability toward the substitution on aryl groups.
- Choi, Subin,Srinivasulu, Vunnam,Ha, Sujin,Park, Cheol-Min
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supporting information
p. 3481 - 3484
(2017/03/29)
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- Revisiting the Gold-Catalyzed Dimerization of 2-Ethynylanilines: A Room-Temperature and Silver-Free Protocol for the Synthesis of Multifunctional Quinolines
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A room temperature and silver-free protocol for the formation of quinolines from 2-ethynylanilines through a dimerization event was achieved using a dinuclear gold catalyst, Au2(BIPHEP)(NTf2)2. The reaction is inherently modular, allowing for the incorporation of peripheral substituents at any site of the quinoline product. The reaction is readily applied to other heterocyles also as exemplified by the preparation of naphthyridines. Competition reactions to determine the reactivity of dissimilar alkynes demonstrated that the product ratio of dimerization vs intermolecular addition is rather dependent on the electronic nature of aryl substituent on the alkynes. However, control experiments with substrates possessing internal alkynes resulted in cycloisomerization instead of expected dimerization, which is indicative of possible steric influence of the alkyne terminus in the reaction outcome.
- Praveen, Chandrasekar,Perumal
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p. 855 - 864
(2016/03/15)
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- IMIDAZOLE BIARYL COMPOUNDS AS S-NITROSOGLUTATHIONE REDUCTASE INHIBITORS
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The present disclosure is directed to compounds of formula (Ie) and pharmaceutically acceptable salts thereof, wherein A, B, R1, R2, m, n, X1, X2, X3 and X4 are as defined herein, which are active as inhibitors of S-Nitrosoglutathione reductase (GSNOR). These compounds prevent, inhibit, or suppress the action of GSNOR and are therefore useful in the treatment of GSNOR mediated diseases, disorders, syndromes or conditions such as, e.g., pulmonary hypertension, acute respiratory distress syndrome (ARDS), asthma, bronchospasm, cough, pneumonia, pulmonary fibrosis, interstitial lung diseases, cystic fibrosis and chronic obstructive pulmonary disease (COPD).
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Page/Page column 139; 138
(2016/04/20)
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- ALKYNE COMPOUNDS AS S-NITROSOGLUTATHIONE REDUCTASE INHIBITORS
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Provided are compounds of formula (Ia) and pharmaceutically acceptable salts thereof, wherein A, B, R 1, R 2, m and n are as defined herein, which are active as inhibitors of S-Nitrosoglutathione reductase (GSNOR). These compounds prevent, inhibit, or suppress the action of GSNOR and are therefore useful in the treatment of GSNOR mediated diseases, disorders, syndromes or conditions such as, e.g., pulmonary hypertension, acute respiratory distress syndrome (ARDS), asthma, bronchospasm, cough, pneumonia, pulmonary fibrosis, interstitial lung diseases, cystic fibrosis and chronic obstructive pulmonary disease (COPD).
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Page/Page column 122
(2016/05/02)
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- Batch and Flow Synthesis of Pyrrolo[1,2-a]-quinolines via an Allene-Based Reaction Cascade
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An efficient reaction cascade delivering a series of pyrrolo[1,2-a]quinolines bearing phosphonate or phosphine oxide moieties is presented. This sequence exploits the in situ transformation of propargylic alcohols into transient allenes by means of a strategic [2,3]-sigmatropic rearrangement followed by trapping of the resulting allenes by an adjacent pyrrole ring. Furthermore, the initial small scale batch process was successfully translated into a continuous flow process allowing efficient preparation of selected pyrrolo[1,2-a]quinolines on multigram scale without any safety concerns due to the reaction's inherent exothermic profile.
- Baumann, Marcus,Baxendale, Ian R.
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p. 10806 - 10816
(2015/11/18)
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- ORGANIC COMPOUNDS
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Novel benzofuran derivatives are disclosed. The derivatives have S1P1 receptor activity and/or disease modifying activity and find use in the treatment of conditions or diseases associated with the immune, vascular and nervous systems in animals and/or humans
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Page/Page column 56
(2014/05/24)
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- NEW COMPOUNDS FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES
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This invention provides novel compounds and the novel compounds for use as a medicine, more in particular for the prevention or treatment of neurodegenerative disorders, more specifically certain neurological disorders, such as disorders collectively known as tauopathies, and disorders characterised by cytotoxic α-synuclein amyloidogenesis. The present invention also relates to the use of said novel compounds for the manufacture of medicaments useful for treating such neurodegenerative disorders. The present invention further relates to pharmaceutical compositions including said novel compounds and to methods for the preparation of said novel compounds. The compounds have the formula (A1) wherein R1, R2, R4, R6, E, n, Y1, Y2, Y3, Y4, Y5, L, B, R8, and m are as defined in the claims.
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Paragraph 0653-0654
(2013/10/22)
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- NOVEL COMPOUNDS FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES
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This invention provides novel compounds and the novel compounds for use as a medicine, more in particular for the prevention or treatment of neurodegenerative disorders, more specifically certain neurological disorders, such as disorders collectively known as tauopathies, and disorders characterised by cytotoxic α-synuclein amyloidogenesis. The present invention also relates to the use of said novel compounds for the manufacture of medicaments useful for treating such neurodegenerative disorders. The present invention further relates to pharmaceutical compositions including said novel compounds and to methods for the preparation of said novel compounds. The compounds have the formula (A1), wherein R1, R2, R4, R5, R6, E, n, Y1, Y2, Y3, Y4, Y5, B, R8, and m are as defined in the claims.
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Paragraph 0510; 0532-0533; 0569-0570
(2013/11/06)
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- NEW COMPOUNDS FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES
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This invention provides novel compounds and the novel compounds for use as a medicine, more in particular for the prevention or treatment of neurodegenerative disorders, more specifically certain neurological disorders, such as disorders collectively known as tauopathies, and disorders characterised by cytotoxic α-synuclein amyloidogenesis. The present invention also relates to the use of said novel compounds for the manufacture of medicaments useful for treating such neurodegenerative disorders. The present invention further relates to pharmaceutical compositions including said novel compounds and to methods for the preparation of said novel compounds. The compounds have the formula (A1) wherein R1, R2, R4, R6, E, n, Y1, Y2, Y3, Y4, Y5, L, B, R8, and m are as defined in the claims.
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Page/Page column 89
(2012/06/30)
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- NOVEL COMPOUNDS FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES
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This invention provides novel compounds and the novel compounds for use as a medicine, more in particular for the prevention or treatment of neurodegenerative disorders, more specifically certain neurological disorders, such as disorders collectively known as tauopathies, and disorders characterised by cytotoxic α-synuclein amyloidogenesis. The present invention also relates to the use of said novel compounds for the manufacture of medicaments useful for treating such neurodegenerative disorders. The present invention further relates to pharmaceutical compositions including said novel compounds and to methods for the preparation of said novel compounds. The compounds have the formula (A1), wherein R1, R2, R4, R5, R6, E, n, Y1, Y2, Y3, Y4, Y5, B, R8, and m are as defined in the claims.
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Page/Page column 81
(2012/06/30)
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- Environmental friendly method for the iodination of moderately active arenes
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An effective and environmental friendly method for the iodination of various moderately active methoxy arenes, phenols and anilines using hydrogen peroxide and acidified sodium periodate in aqueous ethanol medium is reported. The extent of iodination is e
- Sathiyapriya
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experimental part
p. 41 - 43
(2011/11/13)
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- Synthesis and evaluation of a series of C5′-substituted duocarmycin SA analogs
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The synthesis and evaluation of a key series of analogs of duocarmycin SA, bearing a single substituent at the C5′ position of the DNA binding subunit, are described.
- Robertson, William M.,Kastrinsky, David B.,Hwang, Inkyu,Boger, Dale L.
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supporting information; experimental part
p. 2722 - 2725
(2011/07/06)
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- INDOLE AMIDE DERIVATIVES AND RELATED COMPOUNDS FOR USE IN THE TREATMENT OF NEURODEGENERATIVE DISEASES
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This invention provides novel compounds and the novel compounds for use as a medicine, more in particular for the prevention or treatment of neurodegenerative disorders, more specifically certain neurological disorders, such as disorders collectively known as tauopathies, and disorders characterised by cytotoxic α-synuclein amyloidogenesis. The present invention also relates to the use of said novel compounds for the manufacture of medicaments useful for treating such neurodegenerative disorders. The present invention further relates to pharmaceutical compositions including said novel compounds and to methods for the preparation of said novel compounds.
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Page/Page column 190
(2010/12/29)
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- Synthesis and structural optimization of multiple H-bonding region of diarylalkyl (thio)amides as novel TRPV1 antagonists
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Structural optimization of multiple H-bonding region and structure-activity relationship of diarylalkyl amides/thioamides as novel TRPV1 antagonists are described. In particular, we identified amide 34o and thioamides 35o and 35r, of which antagonistic activities were highly enhanced by an incorporation of cyano or vinyl-substituent to the multiple H-bonding region. They exhibited potent 45Ca2+ uptake inhibitions in rat DRG neuron with IC50s of 25, 32 and 28 nM, respectively.
- Li, Fu-Nan,Kim, Nam-Jung,Chang, Dong-Jo,Jang, Jaebong,Jang, Hannah,Jung, Jong-Wha,Min, Kyung-Hoon,Jeong, Yeon-Su,Kim, Sun-Young,Park, Young-Ho,Kim, Hee-Doo,Park, Hyeung-Geun,Suh, Young-Ger
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experimental part
p. 8149 - 8160
(2010/03/25)
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- TETRAHYDROCYCLOPENTA[B]INDOL-3-YL CARBOXYLIC ACID DERIVATIVES USEFUL IN THE TREATMENT OF AUTOIMMUNE AND INFLAMMATORY DISORDERS
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The present invention relates to certain (1,2,4-oxadiazol-3-yl)-1,2,3,4-tetrahydrocyclo-penta[b]indol-3-yl carboxylic acid derivatives of Formula (Ia) and pharmaceutically acceptable salts thereof, which exhibit useful pharmacological properties, for example, as agonists of the S1P1 receptor. Also provided by the present invention are pharmaceutical compositions containing compounds of the invention, and methods of using the compounds and compositions of the invention in the treatment of S1P1 associated disorders, for example, psoriasis, rheumatoid arthritis, Crohn's disease, transplant rejection, multiple sclerosis, systemic lupus erythematosus, ulcerative colitis, type I diabetes, acne, microbial infections or diseases and viral infections or diseases.
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Page/Page column 80
(2009/07/18)
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- Donors and acceptors based on triangular dehydrobenzo[12]annulenes: Formation of a triple-layered rosette structure by a charge-transfer complex
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We present here the results of studies of the synthesis and properties of donors and acceptors based on triangular dehydrobenzo[12]annulene ([12]DBA) system as a π core. These studies were aimed at controlling the supramolecular crystal structure. Toward
- Tahara, Kazukuni,Fujita, Takumi,Sonoda, Motohiro,Shiro, Motoo,Tobe, Yoshito
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supporting information; experimental part
p. 14339 - 14345
(2009/03/11)
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- Rhodium-catalyzed cycloisomerization: Formation of indoles, benzofurans, and enol lactones
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(Chemical Equation Presented) Internal affairs: Indoles, benzofurans, and enol lactones are formed chemoselectively from the rhodium-catalyzed cyclo-isomerization reaction of easily prepared alkynyl aniline substrates (see scheme, cod = cycloocta-1,5-diene, DMF = N,N-dimethylformamide). The reaction may proceed by nucleophilic capture of a vinylidene intermediate. Indoles are formed under mild conditions using low catalyst loadings.
- Trost, Barry M.,McClory, Andrew
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p. 2074 - 2077
(2008/02/14)
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- Preparation of polyfunctional arylmagnesium reagents bearing a triazene moiety. A new carbazole synthesis
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(Chemical Equation Presented) The reaction of iodo- or bromo-substituted aryltriazenes with i-PrMgCl·LiCl generates the corresponding magnesiated derivatives which react with various electrophiles (acid chlorides, 3-iodoenones, allylic halides, aldehydes)
- Liu, Ching-Yuan,Knochel, Paul
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p. 2543 - 2546
(2007/10/03)
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- Novel potent antagonists of transient receptor potential channel, vanilloid subfamily member 1: Structure-activity relationship of 1,3-diarylalkyl thioureas possessing new vanilloid equivalents
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Recently, 1,3-diarylalkyl thioureas have merged as one of the promising nonvanilloid TRPV1 antagonists possessing excellent therapeutic potential in pain regulation. In this paper, the full structure-activity relationship for TRPV1 antagonism of a novel series of 1,3-diarylalky thioureas is reported. Exploration of the structure-activity relationship, by systemically modulating three essential pharmacophoric regions, led to six examples of 1,3-dibenzyl thioureas, which exhibit Ca2+ uptake inhibition in rat DRG neuron with IC50 between 10 and 100 nM.
- Suh, Young-Ger,Lee, Yong-Sil,Min, Kyung-Hoon,Park, Ok-Hui,Kim, Jin-Kwan,Seung, Ho-Sun,Seo, Seung-Yong,Lee, Bo-Young,Nam, Yeon-Hee,Lee, Kwang-Ok,Kim, Hee-Doo,Park, Hyeung-Geun,Lee, Jeewoo,Oh, Uhtaek,Lim, Ju-Ok,Kang, Sang-Uk,Kil, Min-Jung,Koo, Jae-Yeon,Shin, Song Seok,Joo, Yung-Hyup,Kim, Jin Kwan,Jeong, Yeon-Su,Kim, Sun-Young,Park, Young-Ho
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p. 5823 - 5836
(2007/10/03)
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- Novel 3,4-Dihydroquinolin-2(1H)-one inhibitors of human glycogen phosphorylase a
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The preparation of a series of substituted indoles coupled to six- and seven-membered cyclic lactams is described and their role as human glycogen phosphorylase a inhibitors discussed. The SAR of the indole moiety and lactam ring are presented.
- Rosauer, Keith G.,Ogawa, Anthony K.,Willoughby, Chris A.,Ellsworth, Kenneth P.,Geissler, Wayne M.,Myers, Robert W.,Deng, Qiaolin,Chapman, Kevin T.,Harris, Georgianna,Moller, David E.
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p. 4385 - 4388
(2007/10/03)
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- Synthesis, cytotoxicity, and antiplasmodial and antitrypanosomal activity of new neocryptolepine derivatives
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On the basis of the original lead neocryptolepine or 5-methyl-5H-indolo[2,3-b]quinoline, an alkaloid from Cryptolepis sanguinolenta, derivatives were prepared using a biradical cyclization methodology. Starting from easily accessible educts, this approach allowed the synthesis of hitherto unknown compounds with a varied substitution pattern. As a result of steric hindrance, preferential formation of the 3-substituted isomers over the 1-substituted isomers was observed when cyclizing N-(3-substituted-phenyl)-N′-[2-(2-trimethylsilylethynyl)phenyl] carbodiimides. All compounds were evaluated for their activity against chloroquine-sensitive as well as chloroquine-resistant Plasmodium falciparum strains, for their activity against Trypanosoma brucei and T. cruzi, and for their cytotoxicity on human MRC-5 cells. Mechanisms of action were investigated by testing heme complexation using ESI-MS, inhibition of β-hematin formation, DNA interactions (DNA-methyl green assay and linear dichroism), and inhibition of human topoisomerase II. Neocryptolepine derivatives with a higher antiplasmodial activity and a lower cytotoxicity than the original lead have been obtained. This selective antiplasmodial activity was associated with inhibition of β-hematin formation. 2-Bromoneocryptolepine was the most selective compound with an IC50 value against chloroquine-resistant P. falciparum of 4.0 μM in the absence of cytotoxicity (IC50 > 32 μM). Although cryptolepine, a known lead for antimalarials also originally isolated from Cryptolepis sanguinolenta, was more active (IC50 = 2.0 μM), 2-bromoneocryptolepine showed a low affinity for DNA and no inhibition of human topoisomerase II, in contrast to cryptolepine. Although some neocryptolepine derivatives showed a higher antiplasmodial activity than 2-bromocryptolepine, these compounds also showed a higher affinity for DNA and/or a more pronounced cytotoxicity. Therefore, 2-bromoneocryptolepine is considered as the most promising lead from the present work for new antimalarial agents. In addition, 2-bromo-, 2-nitro-, and 2-methoxy-9-cyanoneocryptolepine exhibited antitrypanosomal activity in the micromolar range in the absence of obvious cytotoxicity.
- Jonckers, Tim H. M.,Van Miert, Sabine,Cimanga, Kanyanga,Bailly, Christian,Colson, Pierre,De Pauw-Gillet, Marie-Claire,Van den Heuvel, Hilde,Claeys, Magda,Lemière, Filip,Esmans, Eddy L.,Rozenski, Jef,Quirijnen, Ludo,Maes, Louis,Dommisse, Roger,Lemière, Guy L. F.,Vlietinck, Arnold,Pieters, Luc
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p. 3497 - 3508
(2007/10/03)
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- 2-(2-Hydroxy-3-alkoxyphenyl)-1H-benzimidazole-5-carboxamidine derivatives as potent and selective urokinase-type plasminogen activator inhibitors
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The development of potent and selective urokinase-type plasminogen activator (uPA) inhibitors based on the lead molecule 2-(2-hydroxy-3-ethoxyphenyl)-1H-benzimidazole-5-carboxamidine (3a) is described.
- Mackman, Richard L.,Hui, Hon C.,Breitenbucher,Katz, Bradley A.,Luong, Christine,Martelli, Arnold,McGee, Danny,Radika, Kesavan,Sendzik, Martin,Spencer, Jeffrey R.,Sprengeler, Paul A.,Tario, James,Verner, Erik,Wang, Jing
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p. 2019 - 2022
(2007/10/03)
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- Cyclization of 1-(2-alkynylphenyl)-3,3-dialkyltriazenes: A convenient, high-yield synthesis of substituted cinnolines and isoindazoles
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A new route to isoindazoles and cinnolines through the cyclization of (2-alkynylphenyl)triazenes under neutral conditions is presented. The products that result from heating the starting triazenes depend on both the type of alkyne ortho to the triazene functionality and the temperature used. Butadiyne moieties ortho to dialkyltriazenes yield bis-isoindazole dimers when heated to 150 °C in MeI. A requirement for cyclization in MeI is that the (2-alkynylphenyl)triazene must contain a suitably electron-withdrawing substituent on the phenyl ring to deactivate the triazene toward methylation-induced decomposition to an iodoarene. Ethynyl moieties ortho to dialkyltriazenes yield both isoindazole dimers as well as 3-formylisoindazoles when subjected to the same conditions. Replacing MeI with 1,2-dichlorobenzene as solvent allows for the general cyclization of (2-ethynylphenyl)dialkyltriazenes. Heating to 170 °C results in a mixture of isoindazole and cinnoline products, whereas the cinnolines are produced exclusively in high yield at 200 °C. Alternatively, the isoindazoles can be obtained in good to excellent yield by stirring a 1,2-dichloroethane solution of the starting triazene with CuCl overnight at 50 °C.
- Kimball, David B.,Weakley, Timothy J. R.,Haley, Michael M.
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p. 6395 - 6405
(2007/10/03)
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- Halogenated antituberculosis agents
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Halogenated derivatives of two synthetic anti-tuberculosis agents, thioacetazone and p-aminosalicylic acid, have been synthesized. In general, the halogenated compound has the structure of Structure I: wherein X1is a halogen and X2is a second halogen or hydrogen, and Y is sulfur or oxygen; or, has the structure of Structure IV: wherein X1is a halogen and X2is a second halogen or hydrogen. Alternatively, the halogenated compounds may be pharmaceutically acceptable salts of these compounds. These halogenated derivatives possess anti-mycobacterial activity and are particularly useful for the treatment of Mycobacterium tuberculosis infections. In particular, fluorinated analogs of thioacetazone and p-amino-salicylic acid have been synthesized for use as anti-tuberculosis therapeutic agents either alone or in combination with other conventional anti-tuberculosis therapeutic agents.
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- Stereoselective synthesis of (E)-3-(methoxycarbonyl)methylene-1,3-dihydroindol-2-ones by palladium-catalyzed oxidative carbonylation of 2-ethynylanilines
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A direct synthesis of (E)-3-(methoxycarbonyl)methylene-1,3-dihydroindol-2-ones 2 by palladium-catalyzed oxidative carbonylation of 2-ethynylanilines 1 is reported. Reactions were carried out in MeOH as the solvent at 50-70°C in the presence of catalytic a
- Gabriele, Bartolo,Salerno, Giuseppe,Veltri, Lucia,Costa, Mirco,Massera, Chiara
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p. 4607 - 4613
(2007/10/03)
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- Convenient synthesis of 2-substituted indoles from 2-ethynylanilines with tetrabutylammonium fluoride
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The cyclization reaction of various 2-ethynylanilines, which were easily synthesized from 2-haloanilines by the palladium-catalyzed reaction with terminal alkynes, with tetrabutylammonium fluoride (TBAF) to yield 2-substituted indoles proceeded at refluxing or room temperature in THF in excellent yields without affecting the bromo, chloro, cyano, ethoxycarbonyl, and ethynyl groups.
- Yasuhara, Akito,Kanamori, Yuichi,Kaneko, Masashi,Numata, Atsushi,Kondo, Yoshinori,Sakamoto, Takao
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p. 529 - 534
(2007/10/03)
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- (4-Fluoro-3-iodobenzyl)guanidine, a Potential MIBG Analogue for Positron Emission Tomography
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The aims of this investigation were to develop a no-carrier-added (nca) synthesis of (4--fluoro-3-iodobenzyl)guanidine (FIBG) and to evaluate its potential as an MIBG analogue useful for positron emission tomography. FIBG was prepared in fo
- Vaidyanathan, Ganesan,Affleck, Donna J.,Zalutsky, Michael R.
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p. 3655 - 3662
(2007/10/02)
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