- A novel luciferin-based bright chemiluminescent probe for the detection of reactive oxygen species
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This communication reports the synthesis, chemiluminescence properties, and biological application of KEIO-BODIPY-imidazopyrazine (KBI), a yellow-green chemiluminescent probe for the detection of reactive oxygen species (ROS) generated from living cells. The Royal Society of Chemistry 2009.
- Sekiya, Maki,Umezawa, Keitaro,Sato, Akemi,Citterio, Daniel,Suzuki, Koji
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Read Online
- Long-range proton-coupled electron transfer in phenol-Ru(2,2′- bipyrazine)32+ dyads
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Two dyads in which either 4-cyanophenol or un-substituted phenol is connected via a p-xylene spacer to a Ru(bpz)32+ (bpz = 2,2′-bipyrazine) complex were synthesized and investigated. Selective photo-excitation of Ru(bpz)32+ at 532 nm in a CH 3CN-H2O mixture leads to the formation of 4-cyanophenolate or phenolate along with Ru(bpz)32+ in its electronic ground state. This apparent photoacid behavior can be understood on the basis of a reaction sequence comprised of an initial photoinduced proton-coupled electron transfer (PCET) during which 4-cyanophenol or phenol is oxidized and deprotonated, followed by a thermal electron transfer event in the course of which 4-cyanophenoxyl or phenoxyl is reduced by Ru(bpz)3+ to 4-cyanophenolate or phenolate. Conceptually, this reaction sequence is identical to a sequence of photoinduced charge-separation and thermal charge-recombination events as observed previously for many electron transfer dyads, with the important difference that the initial photoinduced electron transfer process is proton-coupled. The dyad containing 4-cyanophenol reacts via concerted-proton electron transfer (CPET) whereas the dyad containing un-substituted phenol appears to react predominantly via a stepwise PCET mechanism. Long-range PCET is a key reaction in photosystem II. Understanding the factors that govern the kinetics of long-range PCET is desirable in the broader context of light-to-energy conversion by means of proton-electron separation across natural or artificial membranes.
- Bronner, Catherine,Wenger, Oliver S.
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Read Online
- Efficient Halogenation of 2-Aminopyrazine
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2-Aminopyrazine was halogenated with NIS, NCS, and NBS under different reaction conditions. Chlorination and bromination were achieved with good yields by using acetonitrile as the solvent. However, iodination was only obtained in poor yields. Undoubtedly, the best conditions for both mono-and dihalogenation were the use of NBS, acetonitrile, and microwave assistance for short periods. 3,5-Dibromo-2-Aminopyrazine is an excellent functionalized starting material for the synthesis of nitrogen heterocycles.
- Grima, Josep,Lizano, Enric,Pujol, M. Dolors
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p. 2000 - 2003
(2019/10/22)
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- CHEMILUMINESCENT IMIDAZOPYRAZINONE-BASED PHOTOSENSITIZERS WITH AVAILABLE SINGLET AND TRIPLET EXCITED STATES
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The present application describes the development of novel photosensitizers that can undergo self-excitation due to a chemiluminescent reaction, to produce readily-available singlet and/or triplet states and are composed by an imidazopyrazinone core. This core is functionalized with a variety of chromophores and spin converters, allowing to modulate the optical and photosensitizing properties. In one application, the chemiluminescent reaction is triggered by the superoxide anion, overexpressed in tumors, and by molecular oxygen, in aprotic solvents. The photosensitizers can be used in photodynamic therapy of cancer, without the need for external light sources and when triggered by a tumor marker, superoxide anion, while eliminating the restrictions of this therapy associated with tumor size and localization. The emission of light during the self-excitation reaction, and the resulting non-autofluorescence and low background noise, allow their use in tumor diagnostics. The photosensitizers can also be used without light sources and metal elements in photocatalysis reactions.
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Page/Page column 26; 27
(2019/11/19)
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- Discovery of pyrimidine nucleoside dual prodrugs and pyrazine nucleosides as novel anti-HCV agents
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To explore the application potential of dual prodrug strategies in the development of anti-HCV agents, a variety of sofosbuvir derivatives with modifications at the C4 or N3 position of the uracil moiety were designed and synthesized. Some compounds exhibited potent anti-HCV activities, such as 4e and 8a–8c with similar EC50 values (0.20–0.22 μM) comparative to that of sofosbuvir (EC50 = 0.18 μM) in a genotype 1b based replicon Huh-7 cell line. Moreover, 8b displayed a good human plasma stability profile, and was easily metabolized in human liver microsomes expectantly. On the other hand, aiming to discover novel anti-HCV nucleosides, pyrazin-2(1H)-one nucleosides and their phosphoramidate prodrugs were investigated. Several active compounds were discovered, such as 25e (EC50 = 7.3 μM) and S-29b (EC50 = 19.5 μM). This kind of nucleosides were interesting and would open a new avenue for the development of antiviral agents.
- Guo, Shuang,Xu, Mingshuo,Guo, Qi,Zhu, Fuqiang,Jiang, Xiangrui,Xie, Yuanchao,Shen, Jingshan
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p. 748 - 759
(2019/01/26)
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- REDUCTION OF PRO-INFLAMMATORY HDL USING A LEUKOTRIENE INHIBITOR
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A method involving the administration of a therapeutically effective amount of a leukotriene inhibitor, a pharmaceutically acceptable salt, a pharmaceutically acceptable N-oxide, a pharmaceutically active metabolite, a pharmaceutically acceptable prodrug, or pharmaceutically acceptable solvate thereof to a human for reducing a level of pro-inflammatory HDL in the human. Various examples of leukotriene inhibitors, including 3-[3-tert-butylsulfanyl-1-[4-(6-ethoxy-pyridin- 3-yl)-benzyl]-5-(5-methyl-pyridin-2-ylmethoxy)-1H-indol-2-yl]-2, 2-dimethyl-propionic acid, are disclosed for administration for the reduction of pro-inflammatory HDL in a human. Reduction of pro-inflammatory HDL by the leukotriene inhibitor may include conversion of at least a portion of pro-inflammatory HDL to anti-inflammatory HDL.
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Paragraph 00202
(2018/09/12)
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- NOVEL COMPOUNDS AS GPR119 AGONISTS
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The present invention relates to novel compounds of formula (I) as GPR119 agonist, composition compositions containing such compounds and method of preparation thereof.
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Paragraph 0589-0590
(2017/10/26)
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- NEW ANTI-MALARIAL AGENTS
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The present invention is related to a use of aminopyrazine derivatives in the manufacture of a medicament for preventing or treating malaria. Specifically, the present invention is related to aminopyrazine derivatives useful for the preparation of a pharmaceutical formulation for the inhibition of malaria parasite proliferation.
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Page/Page column 16; 18-19
(2017/02/09)
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- Identification of a Potential Antimalarial Drug Candidate from a Series of 2-Aminopyrazines by Optimization of Aqueous Solubility and Potency across the Parasite Life Cycle
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Introduction of water-solubilizing groups on the 5-phenyl ring of a 2-aminopyrazine series led to the identification of highly potent compounds against the blood life-cycle stage of the human malaria parasite Plasmodium falciparum. Several compounds displayed high in vivo efficacy in two different mouse models for malaria, P. berghei-infected mice and P. falciparum-infected NOD-scid IL-2Rnull mice. One of the frontrunners, compound 3, was identified to also have good pharmacokinetics and additionally very potent activity against the liver and gametocyte parasite life-cycle stages.
- Le Manach, Claire,Nchinda, Aloysius T.,Paquet, Tanya,Gonzàlez Cabrera, Diego,Younis, Yassir,Han, Ze,Bashyam, Sridevi,Zabiulla, Mohammed,Taylor, Dale,Lawrence, Nina,White, Karen L.,Charman, Susan A.,Waterson, David,Witty, Michael J.,Wittlin, Sergio,Botha, Mari?tte E.,Nondaba, Sindisiswe H.,Reader, Janette,Birkholtz, Lyn-Marie,Jiménez-Díaz, María Belén,Martínez, María Santos,Ferrer, Santiago,Angulo-Barturen, Inìigo,Meister, Stephan,Antonova-Koch, Yevgeniya,Winzeler, Elizabeth A.,Street, Leslie J.,Chibale, Kelly
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p. 9890 - 9905
(2016/11/19)
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- MONOSUBSTITUTED DIAZABENZIMIDAZOLE CARBENE METAL COMPLEXES FOR USE IN ORGANIC LIGHT EMITTING DIODES
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An organic electronic device, preferably an organic light-emitting diode (OLED), comprising at least one metal-carbene complex comprising one, two or three specific bidentate diazabenzimidazole carbene ligands;a light-emitting layer comprising said metal-carbene complex as emitter material, preferably in combination with at least one host material;the use of said metal-carbene complex in an OLED;an apparatus selected from the group consisting of stationary visual display units, mobile visual display units, illumination units, units in items of clothing, units in handbags, units in accessoires, units in furniture and units in wallpaper comprising said organic electronic device, preferably said OLED, or said light-emitting layer;the metal-carbene complex comprising one, two or three specific bidentate diazabenzimidazole carbene ligands mentioned above and a process for the preparation of said metal-carbene complex.
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Page/Page column 92; 93
(2015/01/16)
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- INHIBITORS OF RENAL OUTER MEDULLARY POTASSIUM CHANNEL
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Novel spirocyclic compounds of formula I: and pharmaceutically acceptable salts thereof are disclosed as inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention. Pharmaceutical compositions and methods of treatment are also included.
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Page/Page column 68
(2015/07/15)
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- INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL
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Novel spirocyclic compounds of formula I: and pharmaceutically acceptable salts thereof are disclosed as inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention. Pharmaceutical compositions and methods of treatment are also included.
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Page/Page column 69
(2015/07/15)
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- QUINOLONE DERIVATIVES AS FIBROBLAST GROWTH FACTOR INHIBITORS
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Compounds of formula (Ι') that are Fibroblast Growth Factor Inhibitors (FGFR) and are therefore useful for the treatment of diseases treatable by inhibition of FGFR are disclosed. Also disclosed are pharmaceutical compositions containing such compounds and processes for preparing such compounds.
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Page/Page column 94
(2014/12/09)
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- Nitrogen bicyclic compounds as inhibitors for Scyl1 and Grk5
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The present invention relates to compounds assumed to be capable of modulating the activity of the proteins ScyI1 and Grk5, thereby regulating the expression and/or release of insulin as well as to pharmaceutical compositions containing such compounds and the use thereof especially for the treatment of a metabolic disease such as diabetes, obesity and impaired adipogenesis.
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Paragraph 0177; 0178
(2015/01/18)
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- ANTI -MALARIAL AGENTS
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The present invention is related to a use of aminopyrazine derivatives in the manufacture of a medicament for preventing or treating malaria. Specifically, the present invention is related to aminopyrazine derivatives useful for the preparation of a pharmaceutical formulation for the inhibition of malaria parasite proliferation.
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Page/Page column 29-30
(2013/08/28)
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- Structure-activity-relationship studies around the 2-amino group and pyridine core of antimalarial 3,5-diarylaminopyridines lead to a novel series of pyrazine analogues with oral in vivo activity
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Replacement of the pyridine core of antimalarial 3,5-diaryl-2- aminopyridines led to the identification of a novel series of pyrazine analogues with potent oral antimalarial activity. However, other changes to the pyridine core and replacement or substitution of the 2-amino group led to loss of antimalarial activity. The 3,5-diaryl-2-aminopyrazine series showed impressive in vitro antiplasmodial activity against the K1 (multidrug resistant) and NF54 (sensitive) strains of Plasmodium falciparum in the nanomolar IC50 range of 6-94 nM while also demonstrating good in vitro metabolic stability in human liver microsomes. In the Plasmodium berghei mouse model, this series generally exhibited good efficacy at low oral doses. One of the frontrunner compounds, 4, displayed potent in vitro antiplasmodial activity with IC 50 values of 8.4 and 10 nM against the K1 and NF54 strains, respectively. When evaluated in P. berghei-infected mice, compound 4 was completely curative at an oral dose of 4 × 10 mg/kg.
- Younis, Yassir,Douelle, Frederic,González Cabrera, Diego,Le Manach, Claire,Nchinda, Aloysius T.,Paquet, Tanya,Street, Leslie J.,White, Karen L.,Zabiulla, K. Mohammed,Joseph, Jayan T.,Bashyam, Sridevi,Waterson, David,Witty, Michael J.,Wittlin, Sergio,Charman, Susan A.,Chibale, Kelly
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supporting information
p. 8860 - 8871
(2013/12/04)
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- Exploring the structural landscape of 2-aminopyrazines via co-crystallizations
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A correlation between the electrostatic charge on the hydrogen-bond acceptor sites of 2-aminopyrazine derivatives and the ability of the compound to form intermolecular hydrogen bonds with carboxylic acids in the solid state has been established. The charge on the hydrogen-bond acceptor can be modulated which leads to a predictable lowering of the supramolecular yield of the reaction. The outcome of all reactions was screened using IR spectroscopy, and twelve new crystal structures are reported to verify the spectroscopic assignments, and to examine the exact nature of the primary intermolecular interactions. The binding preference of carboxylic acids towards the two possible binding sites of 2-aminopyrazines has also been examined, and the main driving force for the assembly of the heteromer between bases and carboxylic acids is the two-point O-H...N/O...H-N synthon. However, seven out of twelve times carboxylic acids also bind via a single-point O-H...N synthons. This 'synthon crossover' is unavoidable due to highly competitive binding sites present in the N-heterocyclic bases chosen.
- Aakeroey, Christer B.,Chopade, Prashant D.,Ganser, Claudia,Rajbanshi, Arbin,Desper, John
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p. 5845 - 5853
(2012/10/29)
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- Chemical synthesis of coelenterazine and its analogs: New route by four segment-couplings
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A novel and improved synthetic route includes four segment-couplings toward coelenterazine and its analogs as luminescent molecules. Regio- and chemo-selective cross coupling reactions using palladium catalysts with 5-iodo-3-bromo-2-aminopyrazine have enabled providing various aminopyrazine derivatives having different substituents. The improved synthesis of coelenterazine and its analogs employed advanced condensation with the aminopyrazines using various keto-acetal segments, which resulted in much higher yields to give the final imidazopyrazinone heterocycles than the previous method using keto-aldehydes.
- Chou, Chun-Ming,Tung, Yu-Wen,Lin, Meng-I,Chan, Diana,Phakhodee, Wong,Isobe, Minoru
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p. 1323 - 1339
(2013/08/15)
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- OXAZOLE AND ISOXAZOLE CRAC MODULATORS
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The present invention relates to compounds of Formula (I) along with processes for their preparation that are useful for treating, preventing and/or managing the diseases, disorders, syndromes or conditions associated with the modulation of CRAC. The invention further relates to methods of treating, preventing managing and/or lessening the diseases, disorders, syndromes or conditions associated with the modulation of CRAC of Formula (I).
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Page/Page column 62-63
(2012/05/19)
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- Facile synthesis and supramolecular chemistry of hydrogen bond/halogen bond-driven multi-tasking tectons
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Hydrogen bonds and halogen bonds can be used as synthetic vectors without structural interference as long as the primary molecular recognition events are designed around a careful combination of geometric and electrostatic complementarity. In addition, a one-step procedure for the synthesis of tectons equipped with powerful hydrogen- and halogen-bond donors is presented. The Royal Society of Chemistry 2011.
- Aakeroey, Christer B.,Chopade, Prashant D.,Ganser, Claudia,Desper, John
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supporting information; experimental part
p. 4688 - 4690
(2011/06/20)
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- IMIDAZO[1,2-α]PYRAZIN-3(7H)-ONE DERIVATIVES BEARING A NEW ELECTRON-RICH STRUCTURE
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The present invention relates to compound of formula I : and their use as chemiluminescent and/or bioluminescent reagents.
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Page/Page column 27
(2011/02/24)
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- Chromophore and Polymer Capable of Detecting the Presence of Various Neurotoxins and Method of Use
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Applicants have produced a chromophore and a polymer that are highly sensitive to the presence of various agents, including organophosphates, pesticides, neurotoxins, metal ions, some explosives, and biological toxins. The detection is accomplished by detecting a change in the fluorescence characteristics of the chromophore or polymer when in the presence of the agent to be detected. The chromophore and polymer may be incorporated into sensors of various types, and they are adaptable for potential field use in areas where detection of these types of agents is desired.
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Page/Page column 6
(2011/02/25)
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- RuII multinuclear metallosupramolecular rack-type architectures of polytopic hydrazone-based ligands: Synthesis, structural features, absorption spectra, redox behavior, and near-infrared luminescence
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A novel class of polytopic hydrazone-based ligands was synthesized. They gave heteroleptic RuII polynuclear rack-like complexes of formula [Runterpyn molecular strand)]2n+ (terpy = 2,2′:6′,2″-terpyridine). The new rack-like systems can be viewed as being made of two identical or roughly identical peripheral subunits separated by several similar metal-containing spacer subunits. The presence of pyrazine or pyrimidine units within the molecular multitopic strands introduces additional chemical diversity; whereas a pyrimidine unit leads to appended orthogonal subunits that are on the same side with regard to the main molecular strand, a pyrazine unit leads to orthogonal subunits that lie on different sides. Mixing pyrazine and pyrimidine units within the same (bridging) molecular strand also allows peculiar and topographically controlled geometries to be obtained. Redox studies provided evidence that each species undergoes reversible redox processes at mild potentials, which can be assigned to specific subunits of the multicomponent arrays. Non-negligible electronic coupling takes place among the various subunits, and some electron derealization ex-tending over the overall bridging molecular strand takes place. In particular, oxidation data suggest that the systems can behave as p-type "molecular wires" and reduction data indicate that n-type electron conduction can occur within the multimetallic framework. All the multinuclear racks exhibit 3MLCT emission, both at 77 K in rigid matrix and at 298 K in fluid solution, which takes place in the near-infrared region (emission maxima in the 1000-1100 nm region), and is quite structured. Rigidity of the molecular structures and derealization within the large bridging ligands are proposed to contribute to the occurrence of the rather uncommon MLCT infrared emission, which is potentially interesting for optical communication devices.
- Stadler, Adrian-Mihail,Puntoriero, Fausto,Nastasi, Francesco,Campagna, Sebastiano,Lehn, Jean-Marie
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scheme or table
p. 5645 - 5660
(2010/07/16)
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- FUSED BICYCLIC COMPOUNDS AS INHIBITORS FOR PI3 KINASE
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The invention relates to compounds of formula (I) for the regulation of phosphoinositides 3-kinases activity and related diseases.
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Page/Page column 106
(2010/09/18)
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- 3 -AZABICYCLO [4.1.0] HEPTANES USED AS OREXIN ANTAGONISTS
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This invention relates to 3-azabicyclo[4.1.0] heptane derivatives (I) and their use as orexin receptor antagonists.
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Page/Page column 60-61
(2010/11/05)
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- PYRAZIN-2-YL-PYRIDIN-2-YL-AMINE AND PYRAZIN-2-YL-PYRIMIDIN-4-YL-AMINE COMPOUNDS AND THEIR USE
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The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain biarylamine compounds (referred to herein as BAA compounds), and especially certain pyrazin- 2 - yl -pyridin- 2 -yl -amine and pyrazine - 2 - yl -pyrimidin- 4 - yl -amine compounds of formula (I), which, inter alia, inhibit Checkpoint Kinase 1 (CHK1 ) kinase function The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit CHK1 kinase function, and in the treatment of diseases and conditions that are mediated by CHK1. that are ameliorated by the inhibition of CHK1 kinase function, etc., including proliferative conditions such as cancer, etc., optionally in combination with another agent, for example, (a) a DNA topoisomerase I or Il inhibitor; (b) a DNA damaging agent; (c) an antimetabolite or TS inhibitor; (d) a microtubule targeted agent; and (e) ionisiπq radiation. wherein: -X= is independently -CRA5= or -N=; and the rest of the substituents are as specified in the claims.
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Page/Page column 169
(2009/05/29)
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- In vitro and in vivo studies of 6,8-(diaryl)imidazo[1,2-a]pyrazin-3(7H)-ones as new antioxidants
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A series of 5-aryl and 3,5-diaryl-2-amino-1,4-pyrazines and the derived imidazopyrazinones has been synthesized to study the chemical oxidative degradation of the bicyclic systems in vitro. Imidazopyrazinones mainly degraded following two independent pathways producing their precursors, namely aminopyrazines, and the corresponding amidopyrazines, respectively. Despite the fact that there is no influence of the substituent of the 3-aryl group on the ratio of the products aminopyrazine/amidopyrazine, diarylimidazopyrazinones and diarylaminopyrazines are good antioxidants in vivo. They protected against microvascular damages in ischemia/reperfusion with similar efficiencies.
- De Wael, Frederic,Jeanjot, Paul,Moens, Cedric,Verbeuren, Tony,Cordi, Alex,Bouskela, Eliete,Rees, Jean-Francois,Marchand-Brynaert, Jacqueline
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scheme or table
p. 4336 - 4344
(2009/11/30)
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- FUSED BICYCLOHETEROCYCLE SUBSTITUTED AZABICYCLIC ALKANE DERIVATIVES
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The invention relates to fused bicycloheterocycle substituted azabicyclic alkane derivatives, compositions comprising such compounds, and methods of treating conditions and disorders using such compounds and compositions.
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Page/Page column 25
(2008/06/13)
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- PYRIDINE AND PYRAZINE DERIVATIVES AS MNK KINASE INHIBITORS
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The present invention relates to compounds of the general formula (I) wherein X, Y, Z, A, Ar, R1, R2, R3, and R4 are as defined herein, which compounds are inhibitors of MNK2 and MNK1. The invention also relates to the use of the compounds in therapy, pharmaceutical compositions comprising the compounds, and the use of the compounds for the preparation of a medicament for the prophylaxis and treatment of disorders related to undesired activity of MNK1 and/or MNK2 kinases.
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Page/Page column 77
(2008/06/13)
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- 5-LIPOXYGENASE-ACTIVATING PROTEIN (FLAP) INHIBITORS
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Described herein are compounds and pharmaceutical compositions containing such compounds, which modulate the activity of 5-lipoxygenase-activating protein (FLAP). Also described herein are methods of using such FLAP modulators, alone and in combination with other compounds, for treating respiratory, cardiovascular, and other leukotriene-dependent or leukotriene mediated conditions or diseases.
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Page/Page column 64
(2008/06/13)
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- Efficient synthesis of a highly selective NPY-5 receptor antagonist: A drug candidate for the treatment of obesity
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A concise and practical synthesis of highly selective NPY-5 receptor antagonist 1 is described. The animopyrazine intermediate 3 was synthesized via either monobromination of aminopyrazine or palladium-catalyzed regioselective debromination of dibromopyrazine followed by an efficient Suzuki-Miyaura coupling. For the preparation of the spirolactone piperidine 2, significantly improved yield was achieved by using a combination of n-BuMgCl and n-BuLi. This protocol also dramatically increased the thermal stability of the aryllithium intermediate and eliminated the requirement for costly cryogenic conditions. The union of the spirolactone piperidine 2 and aminopyrazine 3 via a carbonyl group was accomplished using phenyl chloroformate delivering the target molecule in high yield.
- Itoh, Takahiro,Kato, Shinji,Nonoyama, Nobuaki,Wada, Toshihiro,Maeda, Kenji,Mase, Toshiaki,Zhao, Matthew M.,Song, Jake Z.,Tschaen, David M.,McNamara, James M.
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p. 822 - 828
(2012/12/22)
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- HETEROARYL UREA DERIVATIVES USEFUL FOR INHIBITING CHKl
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Substituted urea compounds useful in the treatment of diseases and conditions related to DNA damage or lesions in DNA replication are disclosed. Methods of making the compounds, and their use as therapeutic agents, for example, in treating cancer and other diseases characterized by defects in DNA replication, chromosome segregation, or cell division, also are disclosed.
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Page/Page column 76; 77
(2008/06/13)
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- Alpha substituted carboxylic acids
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Alpha substituted carboxylic acids of formula (I):
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- Studies on pyrazines, Part 39.1 Synthesis and acidic hydrolysis of 2-hydroxy-5-methoxypyrazine
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2-Hydroxy-5-methoxypyrazine was synthesised in a three-step reaction sequence starting from aminopyrazine. The product was extensively destroyed on acidic workup without forming 2,5-dihydroxypyrazine.
- Sato, Nobuhiro,Mizuno, Akio
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p. 747 - 749
(2007/10/03)
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- Piperidinyl-and piperazinyl-sulfonylmethyl hydroxamic acids and their use as protease inhibitors
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This invention is directed generally to proteinase (also known as “protease”) inhibitors, and, more particularly, to piperidinyl- and piperazinyl-sulfonylmethyl hydroxamic acids that, inter alia, inhibit matrix metalloproteinase (also known as “matrix metalloprotease” or “MMP”) activity and/or aggrecanase activity. Such hydroxamic acids generally correspond in structure to the following formula: (wherein A1, A2, Y, E1, E2, E3, and Rx are as defined in this specification), and further include salts of such compounds. This invention also is directed to compositions of such hydroxamic acids, intermediates for the syntheses of such hydroxamic acids, methods for making such hydroxamic acids, and methods for treating conditions (particularly pathological conditions) associated with MMP activity and/or aggrecanase activity.
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- THIOPHENE HETEROARYL AMINES
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The present invention relates to thiophene heteroaryl amines and their pharmaceutically acceptable salts that modulate the activity of protein kinases and therefore are expected to be useful in the prevention and treatment of protein kinase related cellular disorders such as cancer. Formula (I).
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Page/Page column 47-48
(2010/02/14)
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- Urea kinase inhibitors
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Compounds having the formula are useful for inhibiting protein kinases. Also disclosed are methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.
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- Urea kinase inhibitors
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Compounds having the formula are useful for inhibiting protein kinases. Also disclosed are methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.
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Page/Page column 10
(2008/06/13)
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- ALPHA SUBSTITUTED CARBOXYLIC ACID AS PPAR MODULATORS
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Alpha substituted carboxylic acids of formula (I): wherein R' and R2 are as defined in the specification and R3 is A) formula (II); B) formula (III); C) formula (IV); and D) formula (V); wherein Y, Art, Are, AP, R4, R5, R6, R7, R6, R9, R9a, R10, R", R12, R17, ring A, and p are as defined in the specification; pharmaceutical compositions containing effective amounts of said compounds or their salts are useful for treating PPAR, specifically PPAR α/y related disorders, such as diabetes, dyslipidemia, obesity and inflammatory disorders.
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Page 132-133
(2010/02/09)
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- BENZO ‘ D!AZEPINE DERIVATIVES FOR THE TREATMENT OF NEUROLOGICAL DISORDERS
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The present invention relates to benzazepine derivatives of formula ( I ) wherein: R1 represents -C3-7 cycloalkyl optionally substituted by C1-3 alkyl; having pharmacological activity, processes for their preparation, to compositions containing them and to their use in the treatment of neurological and psychiatric disorders.
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Page/Page column 24
(2010/02/07)
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- ARYLSULFONYLHYDROXAMIC ACID AND AMIDE DERIVATIVES AND THEIR USE AS PROTEASE INHIBITORS
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This invention is directed generally to hydroxamic acid and amide compounds (including salts of such compounds), and, more particularly, to aryl- and heteroaryl--arylsulfonylmethyl hydroxamic acids and amides that, inter alia, inhibit protease activity, particularly matrix metalloproteinase (also known as "matrix metalloprotease" or "MMP") activity and/or aggrecanase activity. These compounds generally correspond in structure to formula (I): wherein Al, A2, A3, El, E2, E3, and E4 are as defined in this patent. This invention also is directed to compositions of such compounds, intermediates for the syntheses of such compounds, methods for making such compounds, and methods for treating conditions associated with MMP activity and/or aggrecanase activity, particularly pathological conditions.
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- N-(heterocyclyl)benzene or pyridinesulphonamides as antithrombotic agents and anticoagulants
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Compounds of formula [I] in which: W may represent a —(CH2)2—, —(CH2)3—, —CH2—C≡C— or —CH2—CH═CH— group, R2 may in particular represent a piperidyl group, an optionally substituted 1,2,3,6-tetrahydropyridyl group, a hexahydro-1H-azepinyl group, an optionally substituted piperazinyl group or a morpholinyl group, R3 may in particular represent a group —COR1, A may in particular represent an optionally substituted phenyl group, a heterocycle or a cyclopentyl group, and B may in particular represent a pyridyl group, an aminopyrazinyl group, an aminopyridazinyl group, a pyrimidinyl group optionally substituted with an amino group, piperidyl group or an aminopyridyl group optionally substituted on the pyridine with a (C1-C4)alkyl or (C1-C4)alkoxy group, the amino group possibly also being substituted with a (C1-C4)alkyl group, their preparation and their therapeutic application.
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- Heterocyclo-alkylsulfonyl pyrazole derivatives as anti-inflammatory/analgesic agents
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The present invention relates to compounds of the formula wherein R2, R3, R6and A are defined as in the specification, to pharmaceutical compositions containing them and to their medicinal use. The compounds of the invention are useful in the treatment or alleviation of inflammation and other inflammation associated disorders, such as osteoarthritis, rheumatoid arthritis, colon cancer and Alzheimer's disease, in mammals (preferably humans, dogs, cats and livestock).
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- NOVEL RING TRANSFORMATIONS OF PYRAZINES BY INTRAMOLECULAR DIELS-ALDER REACTIONS
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Pyrazines carrying the ω-alkyne side-chain -XCH2CH2CH, (X = O,N,S,SO,SO2,C(CN)2) undergo on heating an intramolecular Diels-Alder reaction.Pyrazines with the electron donating atom (O,N or S) in the side-chain afford -fused pyridines as main products, whereas (3-butynylsulfinyl)pyrazine and (3-butynylsulfonyl)pyrazine are exclusively converted into -fused pyridines.A -fused pyridine is also the major product in the reaction of 2,5-bis(1,1-dicyano-4-pentynyl)pyrazine.
- De Bie, D.A.,Ostrowicz, A.,Geurtsen, G.,Van Der Plas, H.C.
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p. 2977 - 2984
(2007/10/02)
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