- Design, Synthesis, and Structural Analysis of Divalent NI Compounds and Identification of a New Electron-Donating Ligand
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The dative-bond representation (L→E) in compounds with main group elements (E) has triggered extensive debate in the recent past. The scope and limits of this nonclassical coordination bond warrant comprehensive exploration. Particularly compounds with (L
- Bharatam, Prasad V.,Arfeen, Minhajul,Patel, Neha,Jain, Priyanka,Bhatia, Sonam,Chakraborti, Asit K.,Khullar, Sadhika,Gupta, Vijay,Mandal, Sanjay K.
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Read Online
- Synthesis of NHC complexes by oxidative addition of 2-chloro-N- methylbenzimidazole
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The oxidative addition of 2-chloro-N-methylbenzimdazole to complexes of type [M(PPh3)4] yields after N-protonation compounds with NH,NMe-substituted NHC ligands. For M = Pd complex compound trans-[3]BF 4 was obtained, while the oxidative addition for M = Pt yielded a mixture of cis-[4]BF4 (major) and trans-[4]BF4 (minor).
- Koesterke, Tim,Pape, Tania,Hahn, F. Ekkehardt
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Read Online
- Intermolecular [2 + 2] Photocycloaddition of α,β-Unsaturated Sulfones: Catalyst-Free Reaction and Catalytic Variants
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2-Aryl-1-sulfonyl-substituted cyclobutanes were prepared in an intermolecular [2 + 2] photocycloaddition from various α,β-unsaturated sulfones and olefins upon irradiation at λ = 300 nm (26 examples, 60-99% yield). Lewis acids catalyzed the [2 + 2] photocycloaddition of 2-benzimidazolyl styryl sulfones. At short wavelengths, the latter substrates underwent C-S bond cleavage but AlBr3 (5 mol %) allowed for an intermolecular reaction with 2,3-dimethyl-2-butene at longer wavelengths. A chiral-at-metal Lewis acid (2 mol %) facilitated an enantioselective reaction (up to 77% ee).
- Jeremias, Noah,Mohr, Lisa-Marie,Bach, Thorsten
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supporting information
p. 5674 - 5678
(2021/08/03)
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- Structure-Activity Relationship Studies Reveal New Astemizole Analogues Active against Plasmodium falciparum in Vitro
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In the context of drug repositioning and expanding the existing structure-activity relationship around astemizole (AST), a new series of analogues were designed, synthesized, and evaluated for their antiplasmodium activity. Among 46 analogues tested, compounds 21, 30, and 33 displayed high activities against asexual blood stage parasites (PfNF54 IC50 = 0.025-0.043 μM), whereas amide compound 46 additionally showed activity against late-stage gametocytes (stage IV/V; PfLG IC50 = 0.6 ± 0.1 μM) and 860-fold higher selectivity over hERG (46, SI = 43) compared to AST. Several analogues displaying high solubility (Sol > 100 μM) and low cytoxicity in the Chinese hamster ovary (SI > 148) cell line have also been identified.
- Birkholtz, Lyn-Marie,Chibale, Kelly,Coertzen, Dina,Ferger, Richard,Kumar, Malkeet,Mambwe, Dickson,Njoroge, Mathew,Reader, Janette,Taylor, Dale,Van Der Watt, Mari?tte
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supporting information
p. 1333 - 1341
(2021/08/24)
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- Tuneable Redox Chemistry and Electrochromism of Persistent Symmetric and Asymmetric Azine Radical Cations
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Molecular organic radicals have been intensively studied in the last decades, due to their interesting optical, magnetic and redox properties. Here we report the synthesis and characterisation of persistent organic radicals from one-electron oxidation of redox-active azines (RAAs), composed of two guanidinyl or related groups. By connecting two different groups together, asymmetric compounds result. In this way a series of compounds with varying redox potential is obtained that could be oxidised reversibly to the mono- and the dicationic charge states. The accessible redox states were fully determined by chemical redox reactions. The standard Gibbs free energy change for disproportionation of the radical monocation into the dication and the neutral molecule in solution, estimated from cyclovoltammetric measurements, varies between 43 and 71 kJ mol?1. While the neutral RAAs absorb predominately UV light, the radical monocations display strong absorptions covering almost the entire visible region and extending for some compounds into the NIR region. A detailed analysis of this highly reversible electrochromism is presented, and the fast switching characteristics are demonstrated in an electrochromic test device.
- Werr, Marco,Kaifer, Elisabeth,Wadepohl, Hubert,Himmel, Hans-J?rg
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supporting information
p. 12981 - 12990
(2019/11/05)
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- Multistage Antiplasmodium Activity of Astemizole Analogues and Inhibition of Hemozoin Formation as a Contributor to Their Mode of Action
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A drug repositioning approach was leveraged to derivatize astemizole (AST), an antihistamine drug whose antimalarial activity was previously identified in a high-throughput screen. The multistage activity potential against the Plasmodium parasite's life cycle of the subsequent analogues was examined by evaluating against the parasite asexual blood, liver, and sexual gametocytic stages. In addition, the previously reported contribution of heme detoxification to the compound's mode of action was interrogated. Ten of the 17 derivatives showed half-maximal inhibitory concentrations (IC50s) of 50 100). Screening of AST and its analogues against gametocytes revealed their moderate activity (IC50: 1-5 μM) against late stage P. falciparum gametocytes, while the evaluation of activity against P. berghei liver stages identified one compound (3) with 3-fold greater activity than the parent AST compound. Mechanistic studies showed a strong correlation between in vitro inhibition of β-hematin formation by the AST derivatives and their antiplasmodium IC50s. Analyses of intracellular inhibition of hemozoin formation within the parasite further yielded signatures attributable to a possible perturbation of the heme detoxification machinery.
- Kumar, Malkeet,Okombo, John,Mambwe, Dickson,Taylor, Dale,Lawrence, Nina,Reader, Janette,Van Der Watt, Mari?tte,Fontinha, Diana,Sanches-Vaz, Margarida,Bezuidenhout, Belinda C.,Lauterbach, Sonja B.,Liebenberg, Dale,Birkholtz, Lyn-Marie,Coetzer, Theresa L.,Prudêncio, Miguel,Egan, Timothy J.,Wittlin, Sergio,Chibale, Kelly
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p. 303 - 315
(2019/01/15)
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- T -BuONa-mediated direct C-H halogenation of electron-deficient (hetero)arenes
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An efficient halogenation of electron-deficient (hetero)arenes is described. The reaction utilizes common t-BuONa as a catalyst (for iodination) or a promoter (for bromination and chlorination), and perfluorobutyl iodide, CBr4 or CCl4 as the readily-available halogenating agents, respectively. The protocol features broad scope, high efficiency, mild conditions and gram scalability. An ionic pathway involving halogen bond formation and halophilic attack is proposed. The utility of the resulting iodinated heteroarenes is demonstrated in visible light-mediated Caryl-Caryl cross-coupling reaction.
- Liu, Xia,Zhao, Xin,Liang, Fushun,Ren, Baoyi
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supporting information
p. 886 - 890
(2018/02/19)
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- Benzoxaborolane compounds and preparation method thereof
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The invention relates to benzoxaborolane compounds and pharmaceutically acceptable salts or solvates thereof. The structure of the compounds is shown in the description, wherein B is boron; X is selected from oxygen, sulfur, nitrogen and hydrogen; R1 is s
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Paragraph 0049-0051
(2019/01/08)
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- CALPAIN MODULATORS AND THERAPEUTIC USES THEREOF
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Disclosed herein are small molecule calpain modulator compositions, pharmaceutical compositions, the use and preparation thereof.
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Paragraph 1372
(2018/04/17)
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- Method for preparing halogenated (hetero) aromatic hydrocarbons
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The invention relates to a method for preparing halogenated (hetero) aromatic hydrocarbons. The halogenated (hetero) aromatic hydrocarbons are prepared from cheap and easily available perfluorobutyl iodide, carbon tetrabromide and carbon tetrachloride as iodinated, brominated and chlorinated reagents respectively under the action of alkali catalysis (promotion). The method comprises the following steps: firstly, (hetero) aromatic hydrocarbons, a halogenated reagent and an inorganic base are placed in an organic solvent, stirred at room temperature and monitored with TLC until a substrate disappears, and the reaction is stopped; then, a reaction mixed solution is poured into water and extracted, an organic phase is dried, and the organic solvent is removed under reduced pressure; finally, silica-gel column chromatography is performed on a crude product, and a product is obtained. Purification can also be performed by recrystallization. The method has the advantages that the synthetic route is wide in substrate range, raw materials and reagents are cheap and easily available, operation is simple, conditions are mild, yield is high, energy consumption is reduced, the reaction route is safe, gram-grade preparation can be performed and the like.
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Paragraph 0067; 0068
(2018/03/24)
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- SMALL MOLECULE REGULATORS OF STEROID RECEPTOR COACTIVATORS AND METHODS OF USE THEREOF
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Small molecule regulators of steroid receptor coactivator (SRC) family proteins are provided, as well as methods for their use in treating or preventing SRC-related diseases. The SRC-related diseases can include cancer, metabolic disorders, human immunodeficiency virus, neurodegenerative disorders, and/or inflammatory diseases. Also provided are methods for regulating SRC family proteins in a cell.
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Paragraph 0266; 0267
(2017/10/27)
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- Selective C-H trifluoromethylation of benzimidazoles through photoredox catalysis
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The protocol presented here is a new strategy for visible light induced C-H trifluoromethylation at C4 of benzimidazoles using Togni's reagent in the presence of fac-Ir(ppy)3. Its advantages are its operational simplicity, mild reaction conditions, low catalyst loading and wide substrate scope in which electron-withdrawing, electron-donating groups and different protecting groups are tolerated.
- Gao, Guo-Lin,Yang, Chao,Xia, Wujiong
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supporting information
p. 1041 - 1044
(2017/02/05)
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- Discovery of a Selective Aurora A Kinase Inhibitor by Virtual Screening
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Here we report the discovery of a selective inhibitor of Aurora A, a key regulator of cell division and potential anticancer target. We used the atom category extended ligand overlap score (xLOS), a 3D ligand-based virtual screening method recently developed in our group, to select 437 shape and pharmacophore analogs of reference kinase inhibitors. Biochemical screening uncovered two inhibitor series with scaffolds unprecedented among kinase inhibitors. One of them was successfully optimized by structure-based design to a potent Aurora A inhibitor (IC50 = 2 nM) with very high kinome selectivity for Aurora kinases. This inhibitor locks Aurora A in an inactive conformation and disrupts binding to its activator protein TPX2, which impairs Aurora A localization at the mitotic spindle and induces cell division defects. This phenotype can be rescued by inhibitor-resistant Aurora A mutants. The inhibitor furthermore does not induce Aurora B specific effects in cells.
- Kilchmann, Falco,Marcaida, Maria J.,Kotak, Sachin,Schick, Thomas,Boss, Silvan D.,Awale, Mahendra,G?nczy, Pierre,Reymond, Jean-Louis
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p. 7188 - 7211
(2016/09/09)
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- 2-Benzazolyl-4-Piperazin-1- Ylsulfonylbenzenecarbohydroxamic acids as novel selective histone deacetylase-6 inhibitors with antiproliferative activity
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We have screened our compound collection in an established cell based assay that measures the derepression of an epigenetically silenced transgene, the locus derepression assay. The screen led to the identification of 4-[4-(1-methylbenzimidazol-2-yl)piperazin-1- yl]sulfonylbenzenecarbohydroxamic acid (9b) as an active which was found to inhibit HDAC1. In initial structure activity relationships study, the 1-methylbenzimidazole ring was replaced by the isosteric heterocycles benzimidazole, benzoxazole, and benzothiazole and the position of the hydroxamic acid substituent on the phenyl ring was varied. Whereas compounds bearing a para substituted hydroxamic acid (9a-d) were active HDAC inhibitors, the meta substituted analogues (8a-d) were appreciably inactive. Compounds 9a-d selectively inhibited HDAC6 (IC50 = 0.1-1.0μM) over HDAC1 (IC50 = 0.9-6μM) and moreover, also selectively inhibited the growth of lung cancer cells vs. patient matched normal cells. The compounds induce a cell cycle arrest in the S-phase while induction of apoptosis is neglible as compared to controls. Molecular modeling studies uncovered that the MMGBSA energy for interaction of 9a-d with HDAC6 was higher than for HDAC1 providing structural rationale for the HDAC6 selectivity.
- Wang, Lei,Kofler, Marina,Brosch, Gerald,Melesina, Jelena,Sippl, Wolfgang,Martinez, Elisabeth D.,Easmon, Johnny
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- A Developability-Focused Optimization Approach Allows Identification of in Vivo Fast-Acting Antimalarials: N -[3-[(Benzimidazol-2-yl)amino]propyl]amides
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Malaria continues to be a major global health problem, being particularly devastating in the African population under the age of five. Artemisinin-based combination therapies (ACTs) are the first-line treatment recommended by the WHO to treat Plasmodium falciparum malaria, but clinical resistance against them has already been reported. As a consequence, novel chemotypes are urgently needed. Herein we report a novel, in vivo active, fast-acting antimalarial chemotype based on a benzimidazole core. This discovery is the result of a medicinal chemistry plan focused on improving the developability profile of an antichlamydial chemical class previously reported by our group. (Graph Presented).
- Keurulainen, Leena,Vahermo, Mikko,Puente-Felipe, Margarita,Sandoval-Izquierdo, Elena,Crespo-Fernández, Benigno,Guijarro-López, Laura,Huertas-Valentín, Leticia,De Las Heras-Due?a, Laura,Leino, Teppo O.,Siiskonen, Antti,Ballell-Pages, Lluís,Sanz, Laura M.,Casta?eda-Casado, Pablo,Jiménez-Díaz, M. Belén,Martínez-Martínez, María S.,Viera, Sara,Kiuru, Paula,Calderón, Félix,Yli-Kauhaluoma, Jari
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supporting information
p. 4573 - 4580
(2015/06/25)
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- Highly efficient tandem syntheses of unsymmetrically substituted isomeric S,N-disubstituted-2-mercaptobenzimidazoles
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Highly efficient tandem syntheses of unsymmetrically substituted isomeric S,N-disubstituted-2-mercaptobenzimidazoles have been developed. The structures of 6a-d and isomeric compounds 9a-d have been synthesized from 2-mercaptobenzimidazole using tandem synthesis. The structures of 6a-d and isomeric compounds 9a-d have been established by spectral and analytical data, and by unambiguous syntheses.
- Rao, S. Srinivas,Reddy, Ch Venkata Ramana,Dubey
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p. 829 - 832
(2015/06/30)
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- Design and synthesis of prostate cancer antigen-1 (PCA-1/ALKBH3) inhibitors as anti-prostate cancer drugs
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A series of 1-aryl-3,4-substituted-1H-pyrazol-5-ol derivatives was synthesized and evaluated as prostate cancer antigen-1 (PCA-1/ALKBH3) inhibitors to obtain a novel anti-prostate cancer drug. After modifying 1-(1H-benzimidazol-2-yl)-3,4-dimethyl-1H-pyrazol-5-ol (1), a hit compound found during random screening using a recombinant PCA-1/ALKBH3, 1-(1H-5- methylbenzimidazol-2-yl)-4-benzyl-3-methyl-1H-pyrazol-5-ol (35, HUHS015), was obtained as a potent PCA-1/ALKBH3 inhibitor both in vitro and in vivo. The bioavailability (BA) of 35 was 7.2% in rats after oral administration. As expected, continuously administering 35 significantly suppressed the growth of DU145 cells, which are human hormone-independent prostate cancer cells, in a mouse xenograft model without untoward effects.
- Nakao, Syuhei,Mabuchi, Miyuki,Shimizu, Tadashi,Itoh, Yoshihiro,Takeuchi, Yuko,Ueda, Masahiro,Mizuno, Hiroaki,Shigi, Naoko,Ohshio, Ikumi,Jinguji, Kentaro,Ueda, Yuko,Yamamoto, Masatatsu,Furukawa, Tatsuhiko,Aoki, Shunji,Tsujikawa, Kazutake,Tanaka, Akito
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p. 1071 - 1074
(2014/03/21)
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- CYANOGUANIDINES AND THEIR USE AS ANTIVIRAL AGENTS
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This disclosure relates to: (a) compounds and salts thereof that, inter alia, inhibit RSV infection and/or replication; (b) intermediates useful for the preparation of such compounds and salts; (c) compositions comprising such compounds and salts; (d) methods for preparing such intermediates, compounds, salts, and compositions; (e) methods of use of such compounds, salts, and compositions; and (f) kits comprising such compounds, salts, and compositions.
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Page/Page column 121
(2014/01/17)
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- Synthesis and biological analysis of benzazol-2-yl piperazine sulfonamides as 11β-hydroxysteroid dehydrogenase 1 inhibitors
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In the last decade the inhibition of the enzyme 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) emerged as a promising new strategy to treat diabetes and several metabolic syndrome phenotypes. Using a molecular modeling approach and classical bioisosteric studies, we discovered a new class of 11β-HSD1 inhibitors bearing an arylsulfonylpiperazine scaffold. Optimization of the initial lead resulted in compound 11 that selectively inhibits 11β-HSD1 (IC50 = 0.7 μM).
- Hofer, Sandra,Kratschmar, Denise V.,Schernthanner, Brigitte,Vuorinen, Anna,Schuster, Daniela,Odermatt, Alex,Easmon, Johnny
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supporting information
p. 5397 - 5400
(2013/09/23)
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- HETEROBICYCLIC COMPOUNDS
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Heterobicyclic compounds of Formula (I): or a pharmaceutically-acceptable salt, tautomer, or stereoisomer thereof, as defined in the specification, and compositions containing them, and processes for preparing such compounds. Provided herein also are methods of treating disorders or diseases treatable by inhibition of PDE10, such as obesity, non-insulin dependent diabetes, schizophrenia, bipolar disorder, obsessive-compulsive disorder, Huntington's Disease, and the like.
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Paragraph 1009
(2013/09/12)
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- A green and simple synthesis of N-substituted-2-mercaptobenzimidazoles
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A green and simple synthesis of N-alkyl-2-mercaptobenzimidazoles 5 (R= CH3, C2H5, CH2Ph) under, different conditions has been developed from N-alkyl-2-chlorobenzimidazole (i.e. CH 3, C2H5, CH2Ph) 4 by reaction with thiourea by physical grinding or by using green solvents like ethanol, PEG-600, etc. or by using micro-wave irradiation technique. Copyright
- Rao, S Srinivas,Dubey,Kumari, Y Bharathi
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p. 1210 - 1213
(2013/10/08)
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- NOVEL TRPV3 MODULATORS
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Disclosed herein are modulators of TRPV3 of formula (II): wherein G1, X1, X2, X3, X4, X5, G2, Ra, Rb, and u are as defined in the specification. Composition
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Paragraph 2144; 2145
(2013/06/04)
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- NOVEL TRPV3 MODULATORS
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Disclosed herein are modulators of TRPV3 of formula (II): wherein G1, X1, X2, X3, X4, X5, G2, Ra, Rb, and u are as defined in the specification. Composition
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Paragraph 669; 670
(2013/05/21)
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- Ultrasound promoted simple and efficient N-alkylation of 2-substituted benzimidazoles
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N-Alkylation of 2-chlorobenzimidazole was carried out using different alkylating agents under ultrasound irradiation technique. These reactions were completed in shorter times and with higher percentage of yields. Among all the green solvents, triethanolamine was found to be very effective and also acts as a base. The above reaction conditions were extended to other 2-substituted benzimidazoles. Thus, a simple and efficient route for N-alkylation has been developed using ultrasound irradiation technique.
- Babu, P. N. Kishore,Devi, B. Rama,Dubey, P. K.
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p. 5756 - 5758,3
(2020/09/14)
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- Designing Structural Motifs for Clickamers: Exploiting the 1,2,3-Triazole Moiety to Generate Conformationally Restricted Molecular Architectures
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Noncovalent interactions, especially hydrogen-bonding interactions as well as electrostatic forces, confined within one macromolecule are the key to designing foldamers that adopt well-defined conformations in solution. In the context of significant recent activities in the area of triazole-connected foldamers, so-called clickamers, we present a fundamental study that compares various model compounds that bear adjacent N-, O-, or F-heteroatom substituents. The interplay of attractive and repulsive interactions leads to rotational constraints around the single bonds attached to both the 1- and 4-positions of the 1,2,3-triazole moiety and should therefore be able to induce well-defined conformational preferences in higher oligomers and polymers, that is, foldamers. Various compounds were synthesized and characterized with regard to their preferred conformations in all three aggregation statesa-that is, in the gas phase, in solution as well as in the solid statea-by employing DFT calculations, NMR spectroscopic experiments, and X-ray crystallography, respectively. On the basis of the thus-obtained general understanding of the conformational behavior of the individual connection motifs, heterostructures were prepared from different motifs without affecting their distinct folding characteristics. Therefore, this work provides a kind of foldamer construction kit, which should enable the design of various clickamers with specific shape and incorporated functionality. A foldamer construction kit: Various heterostructures "clicked" together by structure-directing triazole moieties were investigated with regard to their conformational behavior. Different heteroatoms (X; see graphic) can be used to bias the conformation around the N(1)- and C(4)-connecting single bonds of the triazoles based on tunable noncovalent interactions.
- Zornik, Denise,Meudtner, Robert M.,Ela Malah, Tamer,Thiele, Christina M.,Hecht, Stefan
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supporting information; experimental part
p. 1473 - 1484
(2011/04/15)
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- NOVEL ORGANIC COMPOUND AND ORGANIC LIGHT-EMITTING DEVICE HAVING THE SAME
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The present invention provides a novel organic compound that is chemically stable and can be used as a host material for phosphorescence emission. The present invention provides a benzimidazolyl carbazole compound shown by Formula [1] described in the des
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Page/Page column 23-24
(2011/10/13)
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- Synthesis and in vitro cytotoxic evaluation of some thiazolylbenzimidazole derivatives
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A novel kind of thiazolylbenzimidazole derivatives were designed and synthesized and evaluated for their antitumor activity against SMMC-7721 and A549 cell lines. Most compounds showed good antitumor activities, and compound 11b displayed remarkable in vi
- Luo, Yu,Xiao, Feng,Qian, Shijing,Lu, Wei,Yang, Bo
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experimental part
p. 417 - 422
(2011/02/26)
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- BENZIMIDAZOLE DERIVATIVES USEFUL AS TRPM8 CHANNEL MODULATORS
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Disclosed are compounds, compositions and methods for treating various diseases, syndromes, conditions and disorders, including pain. Such compounds are represented by Formula I as follows: wherein R0, R1, R2, R3/sup
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Page/Page column 13
(2011/01/12)
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- (R)-(+)-N-methylbenzoguanidine ((R)-NMBG) catalyzed kinetic resolution of racemic secondary benzylic alcohols with free carboxylic acids by asymmetric esterification
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(R)-(+)-N-Methylbenzoguanidine ((R)-NMBG) was found to function as an efficient acyl-transfer catalyst for the kinetic resolution of racemic secondary benzylic alcohols in the presence of achiral carboxylic acids and pivalic anhydride. The use of a tertiary amine in this reaction is not necessary to attain good chemical yields of the products. It was determined that diphenylacetic acid could be employed as the most suitable acyl donor for achieving a high enantioselectivity for the kinetic resolution of the racemic secondary benzylic alcohols having normal aliphatic alkyl chains at the C-1 positions. On the other hand, a less-hindered carboxylic acid, such as 3-phenylpropanoic acid, functioned as a better acyl donor for the kinetic resolution of racemic secondary benzylic alcohols having branched aliphatic alkyl chains at the C-1 positions.
- Nakata, Kenya,Shiina, Isamu
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supporting information; experimental part
p. 7092 - 7096
(2011/11/04)
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- HYDROXYQUINOXALINECARBOXAMIDE DERIVATIVE
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The present invention provides a novel hydroxyquinoxaline carboxamide derivative that is useful for preventing and/or treating blood coagulation disorders. A compound represented by formula (i), or a pharmacologically acceptable salt thereof: wherein, each of R1 and R2 independently represents a group such as a hydrogen atom or a halogen atom; R3 represents a group such as a hydrogen atom; each of R4 and R5 independently represents a group such as a hydrogen atom, a halogen atom or a C1-4 alkyl group; each of R6 and R7 independently represents a hydrogen atom or a C1-4 alkyl group; X represents a group such as a C3-10 cycloalkyl group, C6-10 aryl group or a 5- to 10-membered heterocyclic group, which may be substituted with substituent(s) selected from substituent group α; Y represents a group such as -CO-, -O- or -NRa-, and Ra represents a group such as a hydrogen atom or a C1-4 alkyl group.
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Page/Page column 74
(2010/12/29)
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- LTA4H modulators and uses thereof
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Leukotriene A4 hydrolase (LTA4H) inhibitors, compositions containing them, and methods of use for the inhibition of LTA4H enzyme activity and the treatment, prevention or inhibition of inflammation and/or conditions associated with inflammation.
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Page/Page column 29
(2008/12/07)
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- TRIAZOLE DERIVATIVES HAVING ANTIFUNGAL ACTIVITY, METHOD FOR THE PREPARATION THEREOF, AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
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A triazole derivative of formula 1 or a pharmaceutically acceptable salt, hydrate, solvate or isomer thereof is superior to the conventional antifungal drugs in antifungal activity against a wide spectrum of pathogenic fungi, and has advantageously low toxicity.
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Page/Page column 26
(2009/01/24)
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- AMINO-ALKYL-AMIDE DERIVATIVES AS CCR3 RECEPTOR LIGANDS
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The present invention relates to the CCR3 receptor ligands of the general formula (I), within them favourably to antagonists and to the salts, solvates and isomers thereof, to the pharmaceutical compositions containing them, to the use of the compounds of the general formula (I) and their salts, solvates and isomers, to the preparation of the compounds of the general formula (I) and their salts, solvates and isomers and to the new intermediates of the general formula (III).
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Page/Page column 29
(2010/11/26)
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- Aromatic homolytic substitution using solid phase synthesis
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Solid phase synthesis has been used to carry out intramolecular aromatic homolytic substitution with benzoimidazole precursors. The protocol attaches the radical precursors to the resins via the radical leaving groups (in the aromatic homolytic substitution). When the radical reactions are complete, the leaving group, unaltered starting material and reduced uncylised products remain attached to the resin, which facilitates easy separation of the cyclised products. Novel use of focussed microwave irradiation in solid phase radical reactions drastically shortens the reactions times. Tributylgermanium hydride has been used to replace the toxic and troublesome tributyltin hydride in the radical reactions.
- Allin, Steven M.,Bowman, W. Russell,Karim, Rehana,Rahman, Shahzad S.
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p. 4306 - 4316
(2007/10/03)
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- BENZIMIDAZOLE, BENZTHIAZOLE AND BENZOXAZOLE DERIVATIVES AND THEIR USE AS LTA4H MODULATORS
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Leukotriene A4 hydrolase (LTA4H) inhibitors of formula I, compositions containing them, and their use for the inhibition of LTA4H enzyme activity and the treatment, prevention or inhibition of inflammation and/or conditions associated with inflammation, wherein X is selected from the group consisting of NR5, O, and S, with R5 being one of the H and CH3; Y is selected from the group consisting of CH2 and O; R4 is selected from the group consisting of H, OCH3, Cl, F, Br, I, OH, NH2, CN, CF3.
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Page/Page column 79
(2010/02/10)
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- PROLINE DERIVATIVES AND USE THEREOF AS DRUGS
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The present invention aims at providing compounds having therapeutic effects due to a DPP-IV inhibitory action, and satisfactory as pharmaceutical products. The present inventors have found that derivatives having a substituent introduced into the γ-position of proline represented by the formula (I) wherein each symbol is as defined in the specification, have a potent DPP-IV inhibitory activity, and completed the present invention by increasing the stability.
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- Tetrahalogenomethanes: Simple reagents for the synthesis of monohalogenated and mixed dihalogenated aromatic heterocycles via metal-halogen exchange from lithium compounds
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Tetrabromo- or tetrachloromethane and 2-lithio derivatives of aromatic heterocycles rapidly produce the corresponding 2-bromo or 2-chloro derivatives in high yields through a metal-halogen exchange mechanism. This kind of reaction was also used to obtain, in good yields, 5-bromo-2-chlorothiazole and 5-bromo-2-chloro-N-methylimidazole.
- Boga, Carla,Del Vecchio, Erminia,Forlani, Luciano,Todesco, Paolo Edgardo
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p. 233 - 236
(2007/10/03)
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- A new synthesis of chloroheterocycles via metal-halogen exchange between trichloroacetyl derivatives and heteroaromatic lithium and Grignard reagents
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The reaction between 2-lithio derivatives of aromatic azaheterocycles and trichlorocetyl derivatives rapidly produces the corresponding 2-chloro derivatives in high yields through a metal-halogen exchange mechanism. The use of ethyl trichloroacetate can give better results with respect to those obtained with trichloroacetyl chloride, which probably involves dichloroketene formation. The reaction with Grignard reagents is more complex: in fact, 2-benzothiazolylmagnesium chloride with ethyl trichloroacetate or trichloroacetyl chloride gives 2-chlorobenzothiazole together with considerable amounts of ethyl 1,3-benzothiazole-2-carboxylate or 2-benzothiazolyl dichloromethyl ketone, respectively.
- Boga, Carla,Del Vecchio, Erminia,Forlani, Luciano,Milanesi, Lilia,Edgardo Todesco, Paolo
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p. 155 - 159
(2007/10/03)
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- New 2-piperazinylbenzimidazole derivatives as 5-HT3 antagonists. Synthesis and pharmacological evaluation
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A series of 2-piperazinylbenzimidazole derivatives were prepared and evaluated as 5-HT3 receptor antagonists. Their 5-HT3 receptor affinities were evaluated by radioligand binding assays, and their abilities to inhibit the 5-HT-induced Bezold-Jarisch reflex in anesthetized rats were determined. Compound 7e (lerisetron, pK(i) = 9.2) exhibited higher affinity for the 5- HT3 receptor than did tropisetron and granisetron, while compound 7q (pK(i) = 7.5) had very low affinity for this receptor, showing that substitution on the N1 atom of the benzimidazole ring is essential for affinity and activity. The effect of substitution on the aromatic ring of benzimidazole by several substituents in different positions is also discussed. A strong correlation between the 5-HT3 antagonistic activity of the studied compounds and the position of substitution on the aromatic ring was established. Thus, while the 4-methoxy derivative 7m showed weak affinity for the 5-HT3 receptor (pK(i) = 6.7), the 7-methoxy derivative 7n exhibited the highest affinity (pK(i) = 9.4). Compounds 7e and 7n are now under further investigation as drugs for the treatment of nausea and emesis evoked by cancer chemotherapy and radiation.
- Orjales, Aurelio,Mosquera, Ramón,Labeaga, Luis,Rodes, Rosa
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p. 586 - 593
(2007/10/03)
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- Pyridinium Betaines Derived from Thiazolo and Imidazoacridinones
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Four betaines derived from imidazo[4,5-a], imidazo[5,4-a] and thiazolo[5,4-a]acridine have been prepared in a six step procedure starting from 2-chlorobenzimidazoles and benzothiazoles. The 1H and 133C nmr has been used to characteri
- Galy, Jean-Pierre,Hanoun, Jean-Pierre,Pique, Valerie,Jagerovic, Nadine,Elguero, Jose
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p. 1781 - 1787
(2007/10/03)
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- Substituted arylsulfonamides and benzamides
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This invention relates to substituted arylsulfonamides and benzamides possessing aniarrhythmic activity, to pharmaceutical compositions and to methods for production thereof.
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- OXIDATION OF SOME HETARYLHYDRAZINES WITH SELENIUM DIOXIDE
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The oxidation of 2-benzimidazolyl- and 2-quinoxalinylhydrazines with selenium dioxide in hydrochloric acid in the presence of cuprous chloride leads to the formation of 2-chloro derivatives of the heterocycles.When the reaction is carried out in ethanol, 2-benzimidazolylhydrazines give symmetrical formazans.In both cases oxidation proceeds through a step involving the formation of hetarenediazonium salts.
- Sedov, Yu. A.
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p. 217 - 220
(2007/10/02)
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