- Design, synthesis, and biological evaluation of new inhibitors of the endocannabinoid uptake: Comparison with effects on fatty acid amidohydrolase
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A new series of arachidonic acid derivatives were synthesized and evaluated as inhibitors of the endocannabinoid uptake. Most of them are able to inhibit anandamide uptake with IC50 values in the low micromolar range (IC50 = 0.8-24 μM). ln general, the compounds had only weak effects upon CB1, CB2, and VR1 receptors (Ki > 1000-10000 nM). In addition, there was no obvious relationship between the abilities of the compounds to affect anandamide uptake and to inhibit anandamide metabolism by fatty acid amidohydrolase (FAAH; IC50 = 30-113 μM). This indicates that the compounds do not exert their effects secondarily to FAAH inhibition. It is hoped that these compounds, particularly the most potent in this series (compound 5, UCM707, with IC50 values for anandamide uptake and FAAH of 0.8 and 30 μM, respectively), will provide useful tools for the elucidation of the role of the anandamide transporter system in vivo.
- López-Rodríguez, María L.,Viso, Alma,Ortega-Gutiérrez, Silvia,Fowler, Christopher J.,Tiger, Gunnar,De Lago, Eva,Fernández-Ruiz, Javier,Ramos, José A.
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- Highly diastereoselective N-acyliminium ion cyclization reactions of a tethered furan
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The acid catalysed cyclization reactions of tethered furan-4,5- dihydroxypyrrolid-2-ones and furan-4,5-diacetoxypyrrolid-2-ones, via their corresponding N-acyliminium ion intermediates, have been studied. In the case of the tethered furan-3,4-dihydroxypyrrolid-2-one 16, having a two carbon tether, the linearly fused tricyclic compound 18 was formed with high cis selectivity (cis/trans=84:16) when BF3·OEt2 was used as a catalyst. However, when the cyclization reaction was carried out on the related tethered furan-4,5-diacetoxypyrrolid-2-one 17, the linearly fused tricyclic compound 20 was formed as a single diastereoisomer with trans selectivity. In contrast, the attempted cyclization of the tethered furan-4,5-dihydroxypyrrolid- 2-one 26, having a one carbon tether, did not result in formation of the corresponding linearly fused tricyclic system, instead it formed the dimer 29 as a single diastereoisomer. Cyclization reactions of the related tethered furan-4,5-diacetoxypyrrolid-2-one 27 also failed to give the corresponding linearly fused tricyclic system or macrocycle.
- Shengule, Sudhir R.,Ryder, Gregory,Willis, Anthony C.,Pyne, Stephen G.
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- One-Pot Cascade Synthesis of Fused Nitrogen-Containing Heterocycles in Aqueous Media - Utility of N -Protective Groups in Intramolecular Diels-Alder Reaction of Furan
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A metal-free, thermal, intramolecular Diels-Alder (IMDA) reaction of furan in aqueous media without the use of microwave irradiation was investigated. Protection of the amine functionality and the cycloaddition reaction were performed as a one-pot, two-component process. Various nitrogen-protecting groups and their electronic and steric effects on the cycloaddition reaction were studied. The protection-intramolecular Diels-Alder reaction sequence proceeds under environmentally benign aqueous conditions, which are tolerated by substrates with a broad range of nitrogen-protecting groups such as benzyloxycarbonyl (Cbz), trityl, tert-butoxycarbonyl (Boc), trifluoroacetyl, tosyl, mesyl, and p-nosyl [(4-nitrophenyl)sulfonyl]. This study allowed the development of a stereoselective, tandem allylamine isomerization-Diels-Alder cycloaddition sequence leading to the rapid assembly of complex nitrogen-containing heterocycles in a simple one-pot process.
- Demircan, Aydin,Kandemir, Muhammet K.,Colak, Medine,Karaarslan, Muhsin
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- Condensed polycyclic pyridone derivative and application thereof
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The invention belongs to the field of medicines, and particularly relates to a fused polycyclic pyridone derivative as shown in a formula I, pharmaceutically acceptable salts, solvates, including hydrates, polycrystals, prodrugs, eutectics, tautomers and stereoisomers thereof, and application of the fused polycyclic pyridone derivative and the pharmaceutically acceptable salts, the solvates, the tautomers and the stereoisomers. Particularly, the compound provided by the invention can be used as an anti-influenza drug with a CEN inhibition effect.
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Paragraph 0189-0192; 0194
(2021/06/06)
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- Unified Synthesis of Polycyclic Alkaloids by Complementary Carbonyl Activation**
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A complementary dual carbonyl activation strategy for the synthesis of polycyclic alkaloids has been developed. Successful applications include the synthesis of tetracyclic alkaloids harmalanine and harmalacinine, pentacyclic indoloquinolizidine alkaloid nortetoyobyrine, and octacyclic β-carboline alkaloid peganumine A. The latter synthesis features a protecting-group-free assembly and an asymmetric disulfonimide-catalyzed cyclization. Furthermore, formal syntheses of hirsutine, deplancheine, 10-desbromoarborescidine A, and oxindole alkaloids rhynchophylline and isorhynchophylline have been achieved. Finally, a concise synthesis of berberine alkaloid ilicifoline B was completed.
- Christmann, Mathias,He, Guoli,List, Benjamin
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supporting information
p. 13591 - 13596
(2021/05/07)
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- LIVER X RECEPTORS (LXR) MODULATORS
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The present invention relates to sulfonamide-, sulfinamide- or sulfonimidamide containing compounds which bind to the liver X receptor (LXRa and/or LXR?) and act preferably as inverse agonists of LXR.
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- Identification of 4-(2-furanyl)pyrimidin-2-amines as Janus kinase 2 inhibitors
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Janus kinases inhibitor is considered to have therapeutic potential for the treatment of oncology and immune-inflammatory diseases. Two series of 4-(2-benzofuranyl)pyrimidin-2-amine and 4-(4,5,6,7-tetrahydrofuro[3,2-c]pyridin-2-yl)pyrimidin-2-amine derivatives have been designed and synthesized. Primary SAR studies resulted in the discovery of a novel class of 4,5,6,7-tetrahydrofuro[3,2-c]pyridine based JAK2 inhibitors with higher potency (IC50of 0.7 nM) and selectivity (>30 fold) to JAK3 kinase than tofacitinib.
- Wang, Yazhou,Huang, Wei,Xin, Minhang,Chen, Pan,Gui, Li,Zhao, Xinge,Tang, Feng,Wang, Jia,Liu, Fei
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- ORGANIC METAL COMPOUND, ORGANIC LIGHT-EMITTING DEVICES EMPLOYING THE SAME
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Organic metal compounds, and organic light-emitting devices employing the same are provided. The organic metal compound has a chemical structure represented by formula (I): wherein each R1 is independent and can be hydrogen, C1-12 al
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Paragraph 0025
(2017/07/26)
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- Substituted furyl and piperidine derivative synthesis method
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The invention discloses a new method for synthesis of substituted furo-piperidine derivatives. The substituted furo-piperidine derivatives are synthesized based on furfural compound raw material which is cheap and easy to get and after a series of simple and practicable unit operations of condensation, reduction, Pictet-spengler reaction and the like.
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Paragraph 0039; 0040; 0042; 0043; 0044
(2017/01/05)
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- Compounds with cardiac myosin activating function and pharmaceutical composition containing the same for treating or preventing heart failure
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The present invention relates to a compound having a cardiotonic activating function and a pharmaceutical composition containing the same. The composition comprising the compound according to the present invention is effective in preventing or treating heart failure. In addition, the compound is represented by chemical formula 2 or is pharmaceutically acceptable salt thereof.COPYRIGHT KIPO 2016
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- Compounds with cardiac myosin activating function and pharmaceutical composition containing the same for treating or preventing heart failure
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Disclosed are a compound having cardiotonic activity and a pharmaceutical composition containing the same, and the composition containing the compound, according to the present invention, is useful for preventing and treating heart failure.COPYRIGHT KIPO 2016
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- COMPOUNDS, COMPOSITIONS AND METHODS USEFUL FOR CHOLESTEROL MOBILISATION
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The invention relates to classes of pharmaceutically-active heterocyclic compounds and pharmaceutically acceptable salts, and hydrates thereof, and compositions comprising the same. The invention also relates to methods for treating or preventing a disease or disorder, which comprises administering a therapeutically or prophylactically effective amount a compound described herein.
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Page/Page column 168
(2012/05/05)
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- THERAPEUTIC AGENT FOR CEREBRAL INFARCTION
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The invention provides a therapeutic drug for ischemic stroke. The therapeutic drug has the formula (I) wherein each symbol is as defined herein, or a pharmacologically acceptable salt thereof, or a solvate thereof, as an active ingredient.
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- General and efficient strategy for erythrinan and homoerythrinan alkaloids: Syntheses of (±)-3-demethoxyerythratidinone and (±)- erysotramidine
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A general and efficient strategy to both aromatic-type and nonaromatic-type erythrinan and homoerythrinan alkaloids has been developed. This approach involves a key two-step sequence, an alkylation of a ketone with various N-substituted iodoacetamides fol
- Gao, Shuanhu,Tu, Yong Qiang,Hu, Xiangdong,Wang, Shaohua,Hua, Rongbao,Jiang, Yijun,Zhao, Yuming,Fan, Xiaohui,Zhang, Shuyu
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p. 2373 - 2376
(2007/10/03)
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- Catalytic N-sulfonyliminium ion-mediated cyclizations to α-vinyl-substituted isoquinolines and β-carbolines and applications in metathesis
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Catalytic Sn(OTf)2-induced cyclization of linear, aryl-containing allylic N,O-acetals produced vinyl-substituted tetrahydroisoquinolines and tetrahydro-1H-β-carbolines. The usefulness of the vinyl moiety in the resulting products was demonstrated via the synthesis of various key building blocks for alkaloid structures. The α-vinyl moiety was utilized in a [2,3] sigmatropic rearrangement, in ring-closing metathesis and a cross-metathesis-based synthesis of vincantril, an antianoxia agent, and a synthetic member of the vincamine type natural products.
- Kinderman, Sape S.,Wekking, Monique M. T.,Van Maarseveen, Jan H.,Schoemaker, Hans E.,Hiemstra, Henk,Rutjes, Floris P. J. T.
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p. 5519 - 5527
(2007/10/03)
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- Pyrimidine derivatives as IL-8 receptor antagonists
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Compounds containing the pyrimidine nucleus and their use to treat diseases and conditions related to inappropriate Interleukin-8 receptor activity are disclosed. The compounds are of the formula I In these compounds, Q is preferably unsubstituted and substituted heterocyclyl; U is usually hydrogen or fluorine; and V is preferably hydrogen, halogen, alkyl, —O—alkyl or —S-alkyl. A representative example is:
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- Benzazepine and benzothiazepine derivatives
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Vasodilating activity is exhibited by compounds having the formula STR1 and the pharmaceutically acceptable salts thereof, wherein X is --CH2 -- or --S--; R1 is STR2 or --O--Y3 ; R2 is heterocyclo or heteroaryl;
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- PREPARATION OF N-ALKADIENYL N-E-2-ARYLETHENYLCARBAMATES VIA SULFOXIDE ELIMINATION IN A SYNTHETIC APPROACH TO LYCORINE
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N-E-2-Arylethenylcarbamates have been prepared in good yields from N-carbamates via sulfoxide elimination towards nitrogen.
- Jung, Michael E.,Miller, Steven J.
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p. 839 - 853
(2007/10/02)
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- PO-Activated Olefination and Conversion of Aldehydes and Ketones to Higher Amines; II. Synthesis of Arylethylamines
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The transformation of arylcarboxaldehydes and/or - ketones 2 by three different routes into arylethylamines 3 and/or 4 is reported.According to the first route, the intermediate iminophosphonates 9 react through a classical PO-activated olefination.The second and the third involve the rearrangement of the iminophosphonates 9 into the vinylphosphoramidates 12.
- Heymes, A.,Chekroun, I.
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p. 245 - 249
(2007/10/02)
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