- Preparation of alkylation agents for bulged DNA microenvironments
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A designed molecule with capacity to alkylate DNA bulges has been prepared from readily available starting materials. The spirocyclic template utilized was designed on the basis of established architectures, and equipped with a mustard alkylating group. Preliminary studies confirm alkylation of specific bulged sequences, paving the way for second generation substrates with higher affinity.
- Fouad, Farid S.,Xi, Zhen,Goldberg, Irving H.,Jones, Graham B.
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Read Online
- An efficient and convenient protocol for the synthesis of 1,1-difluoro-6-nitro-2,3-dihydro-1 H -indene derivatives
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A convenient and efficient synthesis of gem-difluorinated compounds is reported. The synthetic route toward various 2-substituted and 3-substituted 1,1-difluoro-6-nitro-2,3-dihydro-1H-indene derivatives is described starting from commercially available indanone. The key gem-difluorination step is accomplished in good yield by treatment of in situ generated bromine fluoride (BrF) with a dithioketal. A plausible mechanism discussing the competition between substitution and elimination is provided to rationalize the outcome of the reactions of the 3-brominated compounds with different amines. Georg Thieme Verlag Stuttgart New York.
- Zhang, Dongfeng,Li, Peng,Lin, Ziyun,Huang, Haihong
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Read Online
- Synthesis of haloindenes
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The subject invention provides an expedited synthesis of 5, 6, and 7-iodoindenes from the corresponding aminoindan-1-ones in more than 70% yield, employing readily available precursors and reagents. A three-step sequence involves diazotization-iodination of aminoindan-1-one followed by reduction and dehydration. The method has a general character and can be extended for the preparation of various 4-, 5-, 6- or 7-haloindenes using different halogen sources for diazotization-halogenation reaction.
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Page/Page column 4; 16
(2021/03/24)
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- METHODS FOR MAKING QUINOLINYLDIAMINES
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The present disclosure provides methods for making quinolinyldiamine products from quinolinyl starting materials. In addition, the quinolinyldiamines can be used as ligands or ligand precursors for catalysts, e.g. for use in olefin polymerization.
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Paragraph 0273-0274
(2020/03/23)
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- Iodoindenes: Synthesis and application to cross-coupling
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An expeditious synthesis of 5-, 6-, and 7-iodoindenes from the corresponding aminoindan-1-ones in more than 70% yield employing readily available precursors and ubiquitous reagents is reported. The 4-iodoindene has been prepared analogously in 40% overall yield. A three-step sequence involves diazotization-iodination of aminoindan-1-one followed by the reduction and dehydration. The iodoindenes serve as effective substrates for the regioselective Stille coupling with vinyl stannanes but isomeric mixtures are produced during Sonogashira coupling with alkynes in the presence of triethylamine.
- Howlader, A. Hasan,Diaz, Keili,Mebel, Alexander M.,Kaiser, Ralf I.,Wnuk, Stanislaw F.
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- BRD4-JAK2 INHIBITORS
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Disclosed herein are compounds that are inhibitors of BDR4 and their use in the treatment of cancer. Methods of screening for selective inhibitors of BDR4 are also disclosed. In certain aspects, disclosed are compounds of Formula I, II, and II.
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Page/Page column 41-42
(2020/03/29)
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- ARYL-PHOSPHORUS-OXYGEN COMPOUND AS EGFR KINASE INHIBITOR
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Disclosed is a class of new aryl-phosphorus-oxygen compounds as shown in formula (I) as EGFR kinase inhibitors, and pharmaceutically acceptable salts thereof.
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Paragraph 0318; 0319
(2020/06/16)
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- Discovery of N-indanyl benzamides as potent RORγt inverse agonists
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The retinoic acid receptor-related orphan receptor-gamma-t (RORγt) is a promising therapeutic target for treatment of Th17 cell-mediated autoimmune diseases. Based on a scaffold hopping/conformational restriction strategy, a series of N-indanyl benzamides as novel RORγt inverse agonists was discovered. Exploration of structure-activity relationship on the piperazine ring, benzoyl moiety and cyclopentyl moiety of N-indanyl benzamides 2a and 2d led to identification of potent RORγt inverse agonists. Compound 5c with (S)-enantiomer was found having an IC50 of 153.7 nM in Fluorescence Resonance Energy Transfer (FRET) assay, and an IC50 of 47.1 nM in mouse Th17 cell differentiation assay, which represents a promising starting point for developing potent small molecule RORγt inverse agonists. Binding modes of the two enantiomers 5c and 5d in RORγt ligand binding domain were also discussed.
- Tian, Jinlong,Sun, Nannan,Yu, Mingcheng,Gu, Xianfeng,Xie, Qiong,Shao, Liming,Liu, Jin,Liu, Li,Wang, Yonghui
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- Benzo heterocyclic derivatives, their preparation and their use in medicine (by machine translation)
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The present invention relates to benzo heterocyclic derivatives, their preparation and their use in medicine. In particular, the invention relates to a general formula (I) indicated by the compound, the compound has anti-tumor of the use, the inhibition of angiogenesis and as the role of the HIF - 1 α inhibitors in the medical application. Wherein the general formula (I) of each substituent in the definition in the description of the same. (by machine translation)
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Page/Page column 18
(2018/09/21)
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- Design, synthesis and evaluation of indene derivatives as retinoic acid receptor α agonists
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A series of novel indene-derived retinoic acid receptor α (RARα) agonists have been designed and synthesized. The use of receptor binding, cell proliferation and cell differentiation assays demonstrated that most of these compounds exhibited moderate RARα binding activity and potent antiproliferative activity. In particular, 4-((3-isopropoxy-2,3-dihydro-1H-inden-5-yl)-carbamoyl) benzoic acid (36d), which showed a moderate binding affinity, exhibited a great potential to induce the differentiation of NB4 cells (68.88% at 5 μM). Importantly, our work established indene as a promising skeleton for the development of novel RARα agonists.
- Guan, Xianghong,Luo, Peihua,He, Qiaojun,Hu, Yongzhou,Ying, Huazhou
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- THERAPEUTIC COMPOUNDS
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The invention provides compounds of formula (I): wherein, A, C, D, X, and Y have any of the values defined in the specification, and salts thereof. The compounds are SIRT2 inhibitors and are useful for treating SIRT2 associated conditions.
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Paragraph 0264; 0265
(2017/01/23)
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- Recyclable Hypervalent-Iodine-Mediated Dehydrogenative α,β′-Bifunctionalization of β-Keto Esters under Metal-Free Conditions
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We have developed a method for recyclable hypervalent-iodine-mediated direct dehydrogenative α,β′- bifunctionalization of β-ketoesters and β-diketones under metal-free conditions, which affords a straightforward way to synthesize benzo-fused 2,3-dihydrofurans. This efficient, mild method, which has a wide substrate scope and good functional-group tolerance, was used for the multistep synthesis of the protected aglycone of a naturally occurring phenolic glycoside. A mechanism involving Michael addition to an enone intermediate and subsequent oxidative cyclization is proposed.
- Duan, Ya-Nan,Cui, Li-Qian,Zuo, Lin-Hong,Zhang, Chi
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supporting information
p. 13052 - 13057
(2015/09/07)
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- Non-conventional methodologies in the synthesis of 1-indanones
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1-Indanones have been successfully prepared by means of three different non-conventional techniques, namely microwaves, high-intensity ultrasound and a Q-tube reactor. A library of differently substituted 1-indanones has been prepared via one-pot intramolecular Friedel-Crafts acylation and their efficiency and "greenness" have been compared.
- Oliverio, Manuela,Nardi, Monica,Costanzo, Paola,Cariati, Luca,Cravotto, Giancarlo,Giofre, Salvatore Vincenzo,Procopio, Antonio
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p. 5599 - 5610
(2014/06/10)
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- Protein Kinase Inhibitors
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The present invention relates to compounds of Formula I: as well as pharmaceutically acceptable salts, hydrates, isomers, or solvates thereof, wherein the variables are described herein. The present invention further relates to pharmaceutical compositions which comprise the compounds of Formula I, and to methods for inhibiting protein kinase and methods of treating diseases, such as cancers, inflammation.
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Paragraph 0298; 0441; 0442
(2014/02/16)
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- Thiosemicarbazones derived from 1-indanones as new anti-Trypanosoma cruzi agents
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In the present work, we synthesized a series of thiosemicarbazones derived from 1-indanones with good anti-Trypanosoma cruzi activity. Most of them displayed remarkable trypanosomicidal activity. All the compounds showed nonspecific cytotoxicity on human erythrocytes. The ability of the new compounds to inhibit cruzipain, the major cysteine protease of T. cruzi, was also explored. Thiosemicarbazones 12 and 24 inhibited this enzyme at the dose assayed. This interaction was also studied in terms of molecular docking.
- Caputto, María E.,Fabian, Lucas E.,Benítez, Diego,Merlino, Alicia,Ríos, Natalia,Cerecetto, Hugo,Moltrasio, Graciela Y.,Moglioni, Albertina G.,González, Mercedes,Finkielsztein, Liliana M.
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experimental part
p. 6818 - 6826
(2011/12/22)
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- Study on the synthesis, reduction and reductive amination of nitroindan-1-ones. Preparation of N-β-hydroxyethyl derivatives of 6-aminoindan-1-one and Indan-1,6-diamine
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Synthesis of 6-aminoindan-1-one and 7-amino-5,6-dimethoxyindan-1-one by nitration of corresponding indanones, followed by selective palladium catalyzed reduction under mild conditions has been described. Reactions of the amines with oxirane leading to N.N-bis-(β-hydroxyethyl) derivatives were performed. The study of reductive amination of 6-nitroindan-1-one and 5,6-dimethoxy-7- nitroindan-1-one via azines to the corresponding amines as well as synthesis of N,N-bis-(β-hydroxyethyl) derivatives of the amines was also described.
- Wodnicka,Kwiecien
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experimental part
p. 2133 - 2140
(2009/04/11)
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- Aryl sulfonamido indane inhibitors of the Kv1.5 ion channel
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A collection of aryl sulfonamido indanes based on the lead compound 1 was synthesized and evaluated for Kv1.5 inhibitory activity. Kv1.5 inhibitors have the potential to be atrium-selective agents for treatment of atrial fibrillation. (1R,2R)-1 has an IC50 of 0.033 μM against Kv1.5 and is selective against other cardiac ion channels, including hERG.
- Gross, Michael F.,Beaudoin, Serge,McNaughton-Smith, Grant,Amato, George S.,Castle, Neil A.,Huang, Christine,Zou, Anruo,Yu, Weifeng
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p. 2849 - 2853
(2008/02/11)
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- Constrained 7-fluorocarboxychromone-4-aminopiperidine based Melanin-concentrating hormone receptor 1 antagonists: The effects of chirality on substituted indan-1-ylamines
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The incorporation of constrained tertiary amines into an existing class of N-benzyl-4-aminopiperidinyl chromone-based MCHr1 antagonists led to the identification of a series of chiral racemic compounds that displayed good to excellent functional potency, binding affinity, and selectivity over the hERG channel. Further separation of two distinct chiral racemic compounds into their corresponding pairs of enantiomers revealed a considerable selectivity for MCHr1 for one configuration, in addition to a striking difference in oral exposure between one pair of enantiomers in diet-induced obese mice. Oral administration of the most potent compound in this class in the same animal model led to significant reduction of fat mass in a semi-chronic model for weight loss.
- Souers, Andrew J.,Iyengar, Rajesh R.,Judd, Andrew S.,Beno, David W.A.,Gao, Ju,Zhao, Gang,Brune, Michael E.,Napier, James J.,Mulhern, Mathew M.,Lynch, John K.,Freeman, Jennifer C.,Wodka, Dariusz,Chen, Chong J.,Falls, H. Doug,Brodjian, Sevan,Dayton, Brian D.,Diaz, Gilbert J.,Bush, Eugene N.,Shapiro, Robin,Droz, Brian A.,Knourek-Segel, Victoria,Hernandez, Lisa E.,Marsh, Kennan C.,Reilly, Regina M.,Sham, Hing L.,Collins, Christine A.,Kym, Philip R.
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p. 884 - 889
(2007/10/03)
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- TRICYCLIC COMPOUND AND PHARMACEUTICAL USE THEREOF
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The present invention provides a compound represented by the formula which is useful as an agent for the prophylaxis or treatment of diseases related to the action of melatonin, or a salt thereof and the like.
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Page/Page column 126
(2008/06/13)
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- M4 agonists/5HT7 antagonists with potential as antischizophrenic drugs: Serominic compounds
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Chronic low-dose treatment of rats with the psychomimetic drug, phencyclidine, induces regionally specific metabolic and neurochemical changes in the CNS that mirror those observed in the brains of schizophrenic patients. Recent evidence suggests that drugs targeting serotoninergic and muscarinic receptors, and in particular 5-HT7 antagonists and M4 agonists, exert beneficial effects in this model of schizophrenia. Compounds that display this combined pattern of activity we refer to as serominic compounds. Based upon leads from natural product screening, we have designed and synthesised such serominic compounds, which are principally arylamidine derivatives of tetrahydroisoquinolines, and shown that they have the required serominic profile in ligand binding assays and show potential antipsychotic activity in functional assays.
- Suckling, Colin J.,Murphy, John A.,Khalaf, Abedawn I.,Zhou, Sheng-ze,Lizos, Dimitris E.,van Nhien, Albert Nguyen,Yasumatsu, Hiroshi,McVie, Allan,Young, Louise C.,McCraw, Corinna,Waterman, Peter G.,Morris, Brian J.,Pratt, Judith A.,Harvey, Alan L.
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p. 2649 - 2655
(2008/02/02)
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- ENZYME MODULATORS AND TREATMENTS
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Novel compounds and methods of using those compounds for the treatment of inflammatory conditions, hyperproliferative diseases, cancer, and diseases characterized by hypervascularization are provided. In a preferred embodiment, modulation of the activation state of p38 kinase protein ab1 kinase protein, bcr-ab1 kinase protein, braf kinase protein, VEGFR kinase protein, or PDGFR kinase protein comprises the step of contacting said kinase protein with the novel compounds.
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Page/Page column 396
(2008/06/13)
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- Sulfonamides having antiangiogenic and anticancer activity
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Compounds having methionine aminopeptidase-2 inhibitory (MetAP2) are described. Also described are pharmaceutical compositions comprising the compounds, methods of treatment using the compounds, methods of inhibiting angiogenesis, and methods of treating cancer.
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- COMPOUNDS HAVING SEROTONIN 5-HT17 RECEPTOR ANTAGONIST ACTIVITY AND MUSCARINIC M4 RECEPTOR AGONIST ACTIVITY AND THEIR USE IN THE TREATMENT OF PSYCHOTIC DISORDERS
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The present invention relates to novel treatments for schizophrenia, based on the concept of identifying agents capable of selectively binding to the serotonin 5-HT7 and muscarinic M4 receptors and the use of such compounds in treating schizophrenia. The present invention also relates to novel amidine compounds for treating schizophrenia, a method of manufacturing such compounds, pharmaceutical formulations comprising said compounds, as well as medical uses and methods of treatment using said compounds.
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Page/Page column 45
(2008/06/13)
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- Sulfonamides having antiangiogenic and anticancer activity
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Compounds having methionine aminopeptidase-2 inhibitory (MetAP2) are described. Also described are pharmaceutical compositions comprising the compounds, methods of treatment using the compounds, methods of inhibiting angiogenesis, and methods of treating cancer.
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- Indanylidenes. 1. Design and synthesis of (E)-2-(4,6-difluoro-1-indanylidene)acetamide, a potent, centrally acting muscle relaxant with antiinflammatory and analgesic activity
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The design of rigid cyclic analogues derived from cinnamamide 1, (E)-N-cyclopropyl-3-(3-fluorophenyl)prop-2-enamide, and β-methylcinnamamide 2, (E)-N-cyclopropyl-3-(3-fluorophenyl)but-2-enamide, has led to the discovery of the potent, centrally acting muscle relaxant (E)-2-(4,6-difluoro-1-indanylidene)acetamide, 17. Compound 17 also possesses potent antiinflammatory and analgesic activity. This paper describes the synthesis and the muscle relaxant, antiinflammatory, and analgesic structure-activity relationships of 17 and 67 of its analogues. Compound 17 has been taken into phase I clinical trials.
- Musso, David L.,Cochran, Felicia R.,Kelley, James L.,McLean, Ed W.,Selph, Jeffrey L.,Rigdon, Greg C.,Orr, G. Faye,Davis, Ronda G.,Cooper, Barrett R.,Styles, Virgil L.,Thompson, James B.,Hall, William R.
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p. 399 - 408
(2007/10/03)
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- Photoaddition of Water and Alcohols to 3-Nitrostyrenes. Structure-Reactivity and Solvent Effects
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The photoadditions of water and several alcohols to the triplet excited states of 3-nitrostyrenes 1, 3-5, and 8 to give the corresponding anti-Markovnikov addition products are reported.Both 3- and 4-nitrostilbenes (6 and 7, respectively) do not undergo photoaddition on direct or sensitized irradiation in aqeous or alcohol solutions; only trans to cis photoisomerisation is observed.It is proposed that for the nitrostilbenes, efficient twisting of the alkene in the triplet excited state competes favorably with photoaddition.The efficient photoaddition of the water and methanol observed for 5-nitroindene (8)-the alkene moiety of which cannot attain an orthogonal ("twisted") state-is taken as additional evidence that these photoadditions probably occur via the planar triplet state and that twisting results in only deactivation to the ground state.The use of cosolvents (CH3CN and HCONH2) on several photoadditions is also reported.For example, use of CH3CN cosolvent in aqueous solution decreases the efficiency of photohydration in the parent 3-nitrostyrene (1) but is observed to enhance the efficiency of reaction (until about 40-70 mol percent CH3CN, depending on the substrate) for 3, 4, and 8.Quantum yields for photohydration and photoaddition of alcohols are reported for several systems.
- Wan, Peter,Davis, Michael J.,Teo, Mary-Anne
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p. 1354 - 1359
(2007/10/02)
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- Monoquaternary neuromuscular blocking agents based on 1 tetralone and 1 indanone
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The preparation of three isomeric 1 tetralone hydrazones and three isomeric 1 indanone hydrazones possessing a single quaternary ammonium center is described. Several of the compounds possessed significant neuromuscular blocking activity, and two approached suxamethonium in potency. 1H NMR evidence obtained from a study of the N,N dimethylhydrazones indicated that the hydrazones adopted an E configuration in solution.
- Biggs,Casy,Chu,Coutts
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p. 472 - 475
(2007/10/06)
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