- Microwave synthesis of 1-aryl-1H-pyrazole-5-amines
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A microwave-mediated synthesis of 1H-pyrazole-5-amines utilizing 1 M HCl at 150 °C was developed in order to provide products in a matter of minutes with minimal purification. Most reactions are complete in only 10 min and can be isolated via a simple filtration without the need for further purification by column chromatography or recrystallization. This method tolerates a range of functional groups and can be performed on milligram to gram scales.
- Everson, Nikalet,Yniguez, Kenya,Loop, Lauren,Lazaro, Horacio,Belanger, Briana,Koch, Grant,Bach, Jordan,Manjunath, Aashrita,Schioldager, Ryan,Law, Jarvis,Grabenauer, Megan,Eagon, Scott
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- Synthesis of chiral nopinane annelated 3-methyl-1-aryl-1H-pyrazolo[3,4-b]pyridines by condensation of pinocarvone oxime with 1-aryl-1H-pyrazol-5-amines
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Chiral 1H-pyrazolo[3,4-b]pyridines fused with nopinane frame were obtained by FeCl3-catalyzed assembling of pinocarvone oxime and 1-aryl-1H-pyrazol-5-amines. Chemical structures of new compounds were solved by NMR spectroscopy and confirmed by quantum chemical calculations and X-ray crystallography.
- Ustimenko, Yulia P.,Agafontsev, Alexander M.,Komarov, Vladislav Yu.,Tkachev, Alexey V.
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- Facile, novel and efficient synthesis of new pyrazolo[3,4-b]pyridine products from condensation of pyrazole-5-amine derivatives and activated carbonyl groups
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An efficient synthesis of novel ethyl-1,3,4-triphenyl-1H-pyrazolo[3,4-b]pyridine-6-carboxylate products has been achieved via condensation of pyrazole-5-amine derivatives and activated carbonyl groups, in refluxing acetic acid. This process has been found to be useful in the preparation of new N-fused heterocycle products in good to excellent yields.
- Ghaedi,Bardajee,Mirshokrayi,Mahdavi,Shafiee,Akbarzadeh
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- In situ click chemistry generation of cyclooxygenase-2 inhibitors
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Cyclooxygenase-2 isozyme is a promising anti-inflammatory drug target, and overexpression of this enzyme is also associated with several cancers and neurodegenerative diseases. The amino-acid sequence and structural similarity between inducible cyclooxygenase-2 and housekeeping cyclooxygenase-1 isoforms present a significant challenge to design selective cyclooxygenase-2 inhibitors. Herein, we describe the use of the cyclooxygenase-2 active site as a reaction vessel for the in situ generation of its own highly specific inhibitors. Multi-component competitive-binding studies confirmed that the cyclooxygenase-2 isozyme can judiciously select most appropriate chemical building blocks from a pool of chemicals to build its own highly potent inhibitor. Herein, with the use of kinetic target-guided synthesis, also termed as in situ click chemistry, we describe the discovery of two highly potent and selective cyclooxygenase-2 isozyme inhibitors. The in vivo anti-inflammatory activity of these two novel small molecules is significantly higher than that of widely used selective cyclooxygenase-2 inhibitors.
- Bhardwaj, Atul,Kaur, Jatinder,Wuest, Melinda,Wuest, Frank
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- Efficient catalyst-free tricomponent synthesis of new spiro[cyclohexane-1,4′-pyrazolo[3,4-e][1, 4]thiazepin]-7′(6′H)-ones
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A series of spirocyclohexane-1,4′-pyrazolothiazepinones were synthesized by one-pot multicomponent cyclocondensation reactions between 5-amino-1-arylpyrazoles, cyclohexanone and mercaptoacetic acid with good yields and easy purification protocols. Some control experiments involving isolation of reaction intermediates were performed leading to the proposal of three alternative mechanistic pathways conducting to the named spiroheterocycles. All target molecules were fully characterized by IR, NMR, melting point and HRMS.
- Becerra-Rivas, Christian,Cuervo-Prado, Paola,Orozco-Lopez, Fabian
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- Structural development of 1H-pyrazolo-[3,4-b]pyridine-4-carboxylic acid derivatives as human peroxisome proliferator-activated receptor alpha (PPARα)-selective agonists
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We previously reported that 1H-pyrazolo-[3,4-b]pyridine-4-carboxylic acid derivative 6 is an agonist of human peroxisome proliferator-activated receptor alpha (hPPARα). Here, we prepared a series of 1H-pyrazolo-[3,4-b]pyridine-4-carboxylic acid derivatives in order to examine the structure-activity relationships (SAR). SAR studies clearly indicated that the steric bulkiness of the substituent on 1H-pyrazolo-[3,4-b]pyridine ring, the position of the distal hydrophobic tail part, and the distance between the distal hydrophobic tail part and the acidic head part are critical for hPPARα agonistic activity. These SAR results are somewhat different from those reported for fibrate-class hPPARα agonists. A representative compound (10f) was as effective as fenofibrate in reducing the elevated plasma triglyceride levels in a high-fructose-fed rat model.
- Miyachi, Hiroyuki,Yuzuriha, Tomohiro,Tabata, Ryotaro,Fukuda, Syohei,Nunomura, Kazuto,Lin, Bangzhong,Kobayashi, Tadayuki,Ishimoto,Doi, Takefumi,Tachibana, Keisuke
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- Visible-light enabled C4-thiocyanation of pyrazoles by graphite-phase carbon nitride (g-C3N4)
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Thiocyanation is an important and effective way to form C[sbnd]S bonds in organic synthetic methodology. Especially, thiocyanation of pyrazole attracts the attention of many researchers because sulfur-containing compounds are widely applied in many crucial fields such as organic materials, agrochemistry, nanotechnology, etc. Herein, we described A rapid metal- and additive-free method for C(sp2)-H thiocyanation of pyrazoles under visible light at room temperature by using a sustainable catalyst of graphite-phase carbon nitride (g-C3N4) and a thiocyanating agent of ammonium thiocyanate. The method presents many advantages, such as usage of eco-friendly photoredox catalyst, a wide range of substrates and a good yield of products, etc.
- Pan, Junyi,Liu, Cheng,Wang, Jianqiang,Dai, Yunqiao,Wang, Shengyu,Guo, Cheng
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supporting information
(2021/07/14)
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- Identification of novel scaffold using ligand and structure based approach targeting shikimate kinase
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Tuberculosis (TB) remains a major global health problem. It causes ill-health among millions of people each year and rank as the second leading cause of death from an infectious disease worldwide, after the human immunodeficiency virus (HIV). Shikimate kinase is one of the major enzymes targeted for TB. Most approaches to overcome TB were based on synthesis and screening of a known compounds to obtain a few representatives with desired potency. In this study, we have applied a virtual screening approach which combines ligand- and structure-based approaches to screen a large library of compounds as a starting point for the identification of new scaffolds for the development of shikimate kinase inhibitors. The combined approach has identified 2 new scaffolds as potential inhibitors of shikimate kinase. To prove the approach, few of the molecules and their derivatives, a total of 17 compounds, were synthesized. The compounds were tested for biological activity and shows moderate activity against shikimate kinase. The shikimate kinase enzyme inhibition study reveals that the compounds showed inhibition (IC50) at concentrations of 50 μg/mL (Compounds 21, 22, 24, 25, 26, 27, 30, 32, 34) and 25 μg/mL (14, 19, 23, 31, 33).
- Rahul Reddy,Krishnasamy, Sivakumar Kullampalayam,Kathiravan
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- Discovery, synthesis and characterization of a series of (1-alkyl-3-methyl-1H-pyrazol-5-yl)-2-(5-aryl-2H-tetrazol-2-yl)acetamides as novel GIRK1/2 potassium channel activators
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The present study describes the discovery and characterization of a series of 5-aryl-2H-tetrazol-3-ylacetamides as G protein-gated inwardly-rectifying potassium (GIRK) channels activators. Working from an initial hit discovered during a high-throughput screening campaign, we identified a tetrazole scaffold that shifts away from the previously reported urea-based scaffolds while remaining effective GIRK1/2 channel activators. In addition, we evaluated the compounds in Tier 1 DMPK assays and have identified a (3-methyl-1H-pyrazol-1-yl)tetrahydrothiophene-1,1-dioxide head group that imparts interesting and unexpected microsomal stability compared to previously-reported pyrazole head groups.
- Sharma, Swagat,Kozek, Krystian A.,Abney, Kristopher K.,Kumar, Sushil,Gautam, Nagsen,Alnouti, Yazen,David Weaver,Hopkins, Corey R.
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supporting information
p. 791 - 796
(2019/02/06)
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- Identification, design and synthesis of novel pyrazolopyridine influenza virus nonstructural protein 1 antagonists
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Nonstructural protein 1 (NS1) plays a crucial function in the replication, spread, and pathogenesis of influenza virus by inhibiting the host innate immune response. Here we report the discovery and optimization of novel pyrazolopyridine NS1 antagonists that can potently inhibit influenza A/PR/8/34 replication in MDCK cells, rescue MDCK cells from cytopathic effects of seasonal influenza A strains, reverse NS1-dependent inhibition of IFN-β gene expression, and suppress the slow growth phenotype in NS1-expressing yeast. These pyrazolopyridines will enable researchers to investigate NS1 function during infection and how antagonists can be utilized in the next generation of treatments for influenza infection.
- Patnaik, Samarjit,Basu, Dipanwita,Southall, Noel,Dehdashti, Seameen,Wan, Kanny K.,Zheng, Wei,Ferrer, Marc,Taylor, Mercedes,Engel, Daniel A.,Marugan, Juan Jose
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supporting information
p. 1113 - 1119
(2019/03/08)
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- Multi-component synthesis of 3-substituted indoles and their cyclisation to α-carbolines: Via I2-promoted intramolecular C2 oxidative amination/aromatisation at room temperature
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Condensation of indoles, aldehydes and pyrazol-5-amine in the presence of ceric ammonium nitrate gives 3-substituted indoles. These then cyclise to α-carbolines at room temperature through I2-promoted intramolecular C2 amination and aromatisation in open air. A plausible mechanism is proposed based on some controlled experiments.
- Deka, Bhaskar,Baruah, Pranjal K.,Deb, Mohit L.
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supporting information
p. 7806 - 7810
(2018/11/21)
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- One-pot three-component synthesis of a series of 4-aroyl-1,6-diaryl-3-methyl-1H-pyrazolo[3,4-b]pyridine-5-carbonitriles in the presence of aluminum oxide as a nanocatalyst
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[Figure not available: see fulltext.] One-pot three-component reaction of arylglyoxals, 3-aryl-3-oxopropanenitriles, and 5-amino-1-aryl-3-methylpyrazoles using various solvent systems and different catalysts under reflux conditions afforded the corresponding 4-aroyl-1,6-diaryl-3-methyl-1H-pyrazolo[3,4-b]- pyridine-5-carbonitrile derivatives. The best yields (70–91%) were obtained using Al2O3 as a nanocatalyst in H2O–EtOH, 1:1, under reflux conditions. The simplicity of workup procedure, the novelty of pyrazolopyridines, green solvent system, easy preparation of a nanocatalyst, and good to excellent yields of the products are the advantages of this synthetic strategy. The structures of all products were confirmed by FT-IR, 1H and13C NMR, and mass spectral data.
- Arlan, Fatemeh Majidi,Khalafy, Jabbar,Maleki, Ramin
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- Synthesis of new conjugates 1H-Pyrazolo[3,4-b]pyridine-phosphoramidate and evaluation against leishmania amazonensis
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In this research three series of substituted 1H-pyrazolo[3,4-b]pyridine phosphoramidates were synthesized and characterized by infrared,1H,13C, and31P nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry. The products were obtained in good yields (67-83percent) under mild conditions by nucleophilic aromatic substitution reaction of aminoalkylphosphoramidates over 4-chloro-1H-pyrazolo[3,4-b]pyridines. These compounds were evaluated as antileishmanials against Leishmania amazonensis promastigotes in vitro. Among all, compounds of a series showed expressive antileishmanial activity. Two of them emerged as the most active, with IC50 values of 6.44 ± 1.49 and 12.25 ± 0.68 μM. The cytotoxicity of this series was assessed on murine cells and presented values similar to the reference drug pentamidine.
- Medeiros, Antonia C. R. F.,Borges, Julio C.,Becker, Klaus M.,Rodrigues, Raquel F.,Leon, Leonor L.,Canto-Cavalheiro, Marilene,Bernardino, Alice M. R.,De Souza, Marcos C.,Pedrosa, Leandro F.
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p. 159 - 167
(2017/12/08)
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- Antiplatelet activity, molecular docking and QSAR study of novel N′-arylmethylidene-3-methyl-1-phenyl-6-p-chlorophenyl-1H-pyrazolo[3,4-b] pyridine-4-carbohydrazides
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Abstract: A series of novel N′-arylmethylidene-3-methyl-1-phenyl-6-p-chlorophenyl-1H-pyrazolo[3,4-b]pyridine-4-carbohydrazide (2a–2t) has been synthesized from hydrazide (1). The structures of newly synthesized compounds were confirmed by FT-IR, EI-MS, 1H NMR and 13C NMR techniques. The title compounds were evaluated for antioxidant and antiplatelet aggregation effect induced by arachidonic acid (AA) and collagen. All the compounds have exhibited high antioxidant potential and antiplatelet activity but (2c, 2e, 2f, 2g, 2i, 2m, 2o and 2q) have revealed superlative antiplatelet activity. The molecular docking against cyclooxygenase-1 and 2 (COX-1 and COX-2) and quantitative structure-activity relationship (QSAR) were performed in describing their antiplatelet potential against AA and collagen along with antioxidant potential determined by ABTS, DPPH and iron chelating methods. The molecular docking study exhibited that compounds (2c, 2e, 2f, 2g, 2i, 2l, 2m, 2o and 2q) were found to be active against COX-1 while 2o compound also showed activity against COX-2. Compounds 2g and 2l were found to have higher energy stabilization values in comparison to Aspirin. Computational evaluations both molecular docking and QSAR are in good agreement with antiplatelet and antioxidant activities of the compounds (2a–2t). All the compounds especially 2g, 2l, 2m might be promising antiplatelet agents and might be helpful in the synthesis of new drugs for the treatment of cardiovascular and anti-inflammatory diseases. Graphical Abstract: [InlineMediaObject not available: see fulltext.].
- Ramzan, Ayesha,Siddiqui, Sara,Irfan, Ahmad,Al-Sehemi, Abdullah G.,Ahmad, Aftab,Verpoort, Francis,Chughtai, Adeel H.,Khan, Misbahul A.,Munawar, Munawar A.,Basra, Muhammad Asim Raza
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p. 388 - 405
(2017/10/07)
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- Hexahydrospiro-pyrazolo[3,4-b]pyridine-4,1′-pyrrolo[3,2,1-ij]quinolines Derived from 5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-1,2-dione
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The tricyclic isatin, 5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-1,2-dione (1), reacts with a combination of an aryl cyanomethyl ketone 8 and a 5-amino-1-arylpyrazole 7 to generate spirocyclic products 9.
- Saatluo, Bahman Ebrahimi,Baradarani, Mehdi M.,Joule, John A.
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p. 1176 - 1182
(2018/03/21)
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- Microwave-assisted one-pot synthesis in water of carbonylpyrazolo[3,4-: B] pyridine derivatives catalyzed by InCl3 and sonochemical assisted condensation with aldehydes to obtain new chalcone derivatives containing the pyrazolopyridinic moiety
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Pyrazolo[3,4-b]pyridine derivatives have been synthesized via one-pot condensation of 3-methyl-1-phenyl-1H-pyrazolo-5-amine (1), formaldehyde (as paraformaldehyde) (2) and β-diketones (3) under microwave irradiation in aqueous media catalyzed by InCl3. This process has been found to be useful in the preparation of new N-fused heterocycle products in good to excellent yields. Further treatment of pyrazolopyridines (4a and 4e) with aldehyde aromatics (5a-l) afforded chalcone analogs.
- Polo, Efrain,Ferrer-Pertuz, Karoll,Trilleras, Jorge,Quiroga, Jairo,Gutiérrez, Margarita
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p. 50044 - 50055
(2017/11/14)
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- Multicomponent Dipolar Cycloaddition Strategy: Combinatorial Synthesis of Novel Spiro-Tethered Pyrazolo[3,4-b]quinoline Hybrid Heterocycles
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The stereoselective syntheses of a library of novel spiro-tethered pyrazolo[3,4-b]quinoline-pyrrolidine/pyrrolothiazole/indolizine-oxindole/acenaphthene hybrid heterocycles have been achieved through the 1,3-dipolar cycloaddition of azomethine ylides generated in situ from α-amino acids and 1,2-diketones to dipolarophiles derived from pyrazolo[3,4-b]quinoline derivatives.
- Sumesh, Remani Vasudevan,Muthu, Muthumani,Almansour, Abdulrahman I.,Suresh Kumar, Raju,Arumugam, Natarajan,Athimoolam,Jeya Yasmi Prabha, E. Arockia,Kumar, Raju Ranjith
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supporting information
p. 262 - 270
(2016/06/01)
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- Process for the preparation of teneligliptin
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A process for the preparation of teneligliptin.
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Page/Page column 25
(2017/01/02)
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- HETEROCYCLE SUBSTITUTED AMINO-PYRIDINE COMPOUNDS AND METHODS OF USE THEREOF
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The present disclosure relates to heterocycle substituted amino-pyridine compounds. The present disclosure also relates to pharmaceutical compositions containing these compounds and methods of treating cancer by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present disclosure also relates to the use of such compounds for research or other non-therapeutic purposes.
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Paragraph 0431; 0432
(2016/04/20)
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- SMALL MOLECULE INHIBITORS OF MCL-1 AND USES THEREOF
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This invention is in the field of medicinal chemistry. In particular, the invention relates to a new class of small-molecules having pyrazolopyridine structure which function as inhibitors of Mcl-1 protein, and their use as therapeutics for the treatment of cancer and other diseases.
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Paragraph 0140
(2015/10/28)
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- TrkA KINASE INHIBITORS, COMPOSITIONS AND METHODS THEREOF
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The present invention is directed to benzyl urea compounds of formula (I) which are tropomyosin-related kinase (Trk) family protein kinase inhibitors, and hence may be useful in the treatment of pain, inflammation, cancer, restenosis, atherosclerosis, psoriasis, thrombosis, a disease, disorder, injury, or malfunction relating to dysmyelination or demyelination or a disease or disorder associated with abnormal activities of nerve growth factor (NGF) receptor Trk-A, Trk-B and/or Trk-C.
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(2015/04/15)
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- TrkA KINASE INHIBITORS, COMPOSITIONS AND METHODS THEREOF
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The present invention is directed to benzyl urea compounds of formula (I) which are tropomyosin-related kinase (Trk) family protein kinase inhibitors, and hence may be useful in the treatment of pain, inflammation, cancer, restenosis, atherosclerosis, psoriasis, thrombosis, a disease, disorder, injury, or malfunction relating to dysmyelination or demyelination or a disease or disorder associated with abnormal activities of nerve growth factor (NGF) receptor Trk-A, Trk-B and/or Trk-C.
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Page/Page column 31
(2015/04/15)
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- TrkA KINASE INHIBITORS,COMPOSITIONS AND METHODS THEREOF
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The present invention is directed to substituted five membered heteroaryl benzamide compounds compounds of formula (I), which are tropomyosin-related kinase (Trk) family protein kinase inhibitors, and hence are useful in the treatment of pain, inflammation, cancer, restenosis, atherosclerosis, psoriasis, thrombosis, a disease, disorder, injury, or malfunction relating to dysmyelination or demyelination or a disease or disorder associated with abnormal activities of nerve growth factor (NGF) receptor TrkA.
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Page/Page column 46
(2015/12/08)
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- One-pot, telescoped synthesis of N-aryl-5-aminopyrazoles from anilines in environmentally benign conditions
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An efficient synthetic approach to synthesize N-aryl-5-aminopyrazoles from anilines via a one-pot, telescoped reaction performed in entirely aqueous conditions has been developed. This protocol provides a rapid, convenient method to prepare N-aryl-5-aminopyrazoles, useful building blocks for the synthesis of several bicyclic nitrogen heterocycles, by avoiding the isolation of the toxic intermediate arylhydrazines and the use of a metallic reductant. The Royal Society of Chemistry 2014.
- Marinozzi, Maura,Marcelli, Gloria,Carotti, Andrea,Natalini, Benedetto
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p. 7019 - 7023
(2014/02/14)
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- Structure-activity relationship study of phenylpyrazole derivatives as a novel class of anti-HIV agents
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The structure-activity relationship of phenylpyrazole derivative 1 was investigated for the development of novel anti-HIV agents. Initial efforts revealed that the diazenyl group can be replaced by an aminomethylene group. In addition, we synthesized various derivatives by the reductive amination of benzaldehydes with 5-aminopyrazoles and carried out parallel structural optimization on the benzyl group and the pyrazole ring. This optimization led to a six-fold more potent derivative 32j than the lead compound 1, and this derivative has a 3′,4′-dichloro-(1,1′-biphenyl)-3-yl group.
- Mizuhara, Tsukasa,Kato, Takayuki,Hirai, Atsushi,Kurihara, Hideki,Shimada, Yasuhiro,Taniguchi, Masahiko,Maeta, Hideki,Togami, Hiroaki,Shimura, Kazuya,Matsuoka, Masao,Okazaki, Shiho,Takeuchi, Tomoki,Ohno, Hiroaki,Oishi, Shinya,Fujii, Nobutaka
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p. 4557 - 4561
(2013/08/23)
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- INDAZOLE COMPOUNDS USEFUL AS KETOHEXOKINASE INHIBITORS
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The present invention is directed to substituted indazole compounds, pharmaceutical compositions of these compounds and methods of use thereof. The compounds of the present invention are ketohexokinase (KHK) inhibitors, useful for treating or ameliorating a KHK mediated metabolic disorders and/or diseases such as obesity, Type II diabetes mellitus and Metabolic Syndrome X.
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Page/Page column 51
(2011/11/06)
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- The identification a novel, selective, non-steroidal, functional glucocorticoid receptor antagonist
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The identification of novel, potent, non-steroidal/small molecule functional GR antagonist GSK1564023A selective over PR is described. Associated structure-activity relationships and the process of optimisation of an initial HTS hit are also described.
- Rimland, Joseph,Dunne, Angela,Hunjan, Suchete S.,Sasse, Rosemary,Uings, Iain,Montanari, Dino,Caivano, Matilde,Shah, Poonam,Standing, David,Gray, David,Brown, David,Cairns, William,Trump, Ryan,Smith, Paul W.,Bertheleme, Nicolas,D'Alessandro, Pier,Gul, Sheraz,Vimal, Mythily,Smith, David N.,Watson, Stephen P.
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scheme or table
p. 2340 - 2343
(2010/08/22)
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- Approach to the library of fused pyridine-4-carboxylic acids by combes-type reaction of acyl pyruvates and electron-rich amino heterocycles
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A library of fused pyridine-4-carboxylic acids (including pyrazolo[3,4-b]pyridines, isoxazolo[5,4-b]pyridines, furo[2,3-b]pyridines, thieno[2,3-b]pyridines, and pyrido[2,3-d]pyrimidines) was generated by Combes-type reaction of acyl pyruvates and electron-rich amino heterocycles followed by hydrolysis of the ester. The library members were also demonstrated to undergo the standard combinatorial transformations including amide coupling and esterification, as well as less common heterocyclizations to 1,2,4-triazoles and 1,2,4-oxadiazoles.
- Volochnyuk, Dmitriy M.,Ryabukhin, Sergey V.,Plaskon, Andrey S.,Dmytriv, Yuri V.,Grygorenko, Oleksandr O.,Mykhailiuk, Pavel K.,Krotko, Dmitriy G.,Pushechnikov, Alexei,Tolmachev, Andrey A.
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scheme or table
p. 510 - 517
(2010/09/05)
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- Identification and optimization of substituted 5-aminopyrazoles as potent and selective adenosine A1 receptor antagonists
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Potent and selective adenosine A1 receptor antagonists were disclosed. SAR and pharmacological profile of selected compounds were discussed.
- Griebenow, Nils,B?rfacker, Lars,Meier, Heinrich,Schneider, Dirk,Teusch, Nicole,Lustig, Klemens,Kast, Raimund,Kolkhof, Peter
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scheme or table
p. 5891 - 5894
(2010/11/18)
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- PHARMACEUTICAL COMPOSITIONS CONTAINING 1-METHYL-3,6,7,8-TETRAHYDROPIRAZOLO[3,4-b]PIRROLO[4,3-d]PYRIDINE-6,8-DIONE DERIVATIVES, USE, AND PROCESS FOR PREPARING THEM
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The present invention is related to new derivatives of 1-methyl-3,6,7,8- tetrahydropirazolo[3,4-b]pirrolo[4,3-d]piridin-6,8-dione nucleus, preferably heterocyclic derivatives, acting as hypnotics and analgesic in the central nervous system, being useful in the treatment of anxiety and central hyperalgesia, including: anxiety relief, central hyperalgesia relief in mammals, preferably humans. It is also described pharmaceutical compositions containing said compounds and preparation processes.
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Page/Page column 15
(2008/06/13)
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- Environment friendly reagents and process for halogenoalkylsulfinylation of organic compounds
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The invention concerns compounds corresponding to formula (I) : wherein:Y represents a group chosen from : a C1-C20, linear, branched or cyclic alkane di-yl, or alkene di-yl, or alkyne di-yl radical, wherein said alkane, alkene or alkyne chain can be substituted by one or more groups chosen from : a phenyl ring or a halogen atom, and said alkane, alkene or alkyne chain can comprise a sulfur bridge or an oxygen bridge ;R represents an alkyl group, linear or branched, comprising one to four carbon atoms and substituted by one or more, identical or different, halogen atoms ;a process for their preparation and their use as halogenoalkylsulfinylating agents.
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- Pyrazole urea-based inhibitors of p38 MAP kinase: From lead compound to clinical candidate
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We report on a series of N-pyrazole, N′-aryl ureas and their mode of binding to p38 mitogen activated protein kinase. Importantly, a key binding domain that is distinct from the adenosine 5′-triphoshate (ATP) binding site is exposed when the conserved activation loop, consisting in part of Asp168-Phe169-Gly170, adopts a conformation permitting lipophilic and hydrogen bonding interactions between this class of inhibitors and the protein. We describe the correlation of the structure-activity relationships and crystallographic structures of these inhibitors with p38. In addition, we incorporated another binding pharmacophore that forms a hydrogen bond at the ATP binding site. This modification affords significant improvements in binding, cellular, and in vivo potencies resulting in the selection of 45 (BIRB 796) as a clinical candidate for the treatment of inflammatory diseases.
- Regan, John,Moss, Neil,Pargellis, Chris,Pav, Sue,Proto, Alfred,Swinamer, Alan,Tong, Liang,Torcellini, Carol,Breitfelder, Steffen,Cirillo, Pier,Gilmore, Thomas,Graham, Anne G.,Hickey, Eugene,Klaus, Bernhard,Madwed, Jeffrey,Moriak, Monica
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p. 2994 - 3008
(2007/10/03)
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- Synthesis of N(1)-substituted 5-amino-3-methylpyrazoles
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With the aim of preparing new biologically active compounds a series of N(1)-substituted 5-amino-3-methylpyrazoles has been obtained from β-aminocrotononitrile and mono-substituted hydrazines.
- Nam,Grandberg,Sorokin
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p. 281 - 283
(2007/10/03)
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- Method for inhibiting neoplastic cells by exposure to substituted N-cycloalkylmethyl-1-H-pyrazolo (3,4-B) quinolone-4 amines
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A method for inhibiting neoplastic cells and related conditions by exposing them to substituted N-cycloalkylmethyl-1H-pyrazolo?3,4-b!quinolin-4-amines.
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- Substituted N-cycloalkylmethyl-1H-pyrazolo(3,4-b)quinolin-4 amines and compositions and methods of use thereof
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Substituted N-cycloalkylmethyl-1H-pyrazolo[3,4-b]quinolin-4-amines, pharmaceutical compositions containing them and methods for a) effecting c-GMP-phosphodiesterase inhibition, b) treating heart failure and/or hypertension, c) reversing or reducing nitrate-induced tolerance and d) treating angina pectoris, congestive heart disease and myocardial infarction utilizing them.
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- Synthesis of Benzylidenaminopyrazoles and Bispyrazolopyridines
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5-Aminopyrazoles 1a-e react with aromatic aldehydes in boiling ethanol to yield azomethines 2a-n.Bispyrazolopyridines 7a-f are obtained by the reaction of 2a-f with an excess of aminopyrazole at higher temperatures via bisaminopyrazoles 5 and bispyrazolodihydropyridines 6.Structure and configuration of the products are assigned by n.m.r. spectroscopy.Reactions with replacement of the arylidene group on azomethine 2b suggest that the transformation of azomethines to bisaminopyrazoles occurs through a mechanism involving addition of the CH-acidic component, with subsequent elimination of aminopyrazole.
- Hennig, L.,Hofmann, J.,Alva-Astudillo, M.,Mann, G.
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p. 351 - 358
(2007/10/02)
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- Synthesis of pyrazolo[3,4-e][1,4]diazepine-4,7-diones with central nervous system activity
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The synthesis of 1-phenyl-5,8-dimethyl-1,4,5,6,7,8-hexahydro-pyrazolo[3,4-e][1,4] diazepin-4,7-dione and of 1-phenyl-3,5,8-trimethyl-1,4,5,6,7,8-hexahydro-pyrazolo[3,4-e] [1,4]diazepin-4,7-dione is described. These compounds exhibit activity on CNS in animals.
- Sprio,Caronna,Migliara,Petruso,Matera
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p. 809 - 818
(2007/10/02)
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- Applications of PMR Spectroscopy and Mass Spectrometry to Some Problems Concerning Synthetic Dyes : Part XXIV - Azo Dyes from 5-Aminopyrazole
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The first identification of a commercial disperse dye (CI Disperse Orange 56) as a 5-aminopyrazole derivative is reported.Contrary to statements in the literature, the PMR spectrum of the cationic dye obtained by the action of dimethyl sulphate on the azoic pigment shows that quaternization involves the heterocyclic -N= and not the NH2 group.
- Lahoti, Rajgopal J.
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p. 490 - 491
(2007/10/02)
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- Studies on the Synthesis of Heterocyclic Compounds. Part VI. The Action of Methyl Salicylate on Some 5-Aminopyrazoles
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Some 1-phenyl-3-R-5-aminopyrazoles reacted with methyl salicylate to give N-(1-phenyl-3-R-pyrazol-5-yl)-2-methoxybenzamides (3a,b,c), 1-phenyl-2-methyl-3-R-salicyloilimino-3-pyrazolines (4a,b,c) together with 1-phenyl-3-R-5-methylamino pyrazoles (5a,b,c).The structures of the new compounds 3 and 4 were determined on the basis of analytical and spectroscopic data as well as on the acid hydrolysis products.
- Daidone, Giuseppe,Plescia, Salvatore
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p. 747 - 750
(2007/10/02)
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- VILSMEIER-HAACK REACTION OF 5-AMINO- AND 5-ACYLAMINO-PYRAZOLES
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The Vilsmeier-Haack reaction of 5-aminopyrazole derivatives 1 was investigated in view of contradictory literature reports.Structure 2 of the products was proved both chemically and spectroscopically.The mechanism of the reaction was postulated on the basis of isolated intermediates 7 and 8. 5-Acylaminopyrazoles 9, 10 and 11 were found to give also 2 (and 7) under the Vilsmeier conditions by an acyl splitting reaction, proceeding probably via diacylamino derivatives 12.Compounds 2 provided a simple route to pyrazolopyrimidine derivatives 13 and 14 as well as to azomethine compounds 15-18.
- Simay, A.,Takacs, K.,Horvath, K.,Dvortsak, P.
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p. 127 - 140
(2007/10/02)
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