- trans-2,6-, 3,6- And 4,6-diaza-5,6,6a,7,8,12b-hexahydrobenzophenanthrene-10,11-diols as dopamine agonists
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The title compounds were synthesized by replacing the thiophene moiety of A-86929(2a) with variously substituted pyridines. Dopamine D-1 and D-2 binding and adenylate cyclase assays indicate that 4,6-diaza compounds 15 are potent and selective full D1 agonists when R1 is H or a small substituent and R2=H, with D1 binding affinity and adenylate cyclase functional potency equivalent to that of A-86929(2a).
- Gu, Yu Gui,Bayburt, Erol K.,Michaelides, Michael R.,Lin, Chun Wei,Shiosaki, Kazumi
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Read Online
- One-pot homo- and cross-coupling of diazanaphthalenes via C-H substitution: Synthesis of Bis- and Tris-diazanaphthalenes
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The transition metal-free coupling reactions of unactivated diazanaphthalenes were studied using only lithium tetramethylpiperidine (LiTMP) reagent. Symmetrical and nonsymmetrical bis-diazanaphthalenes were synthesized in moderate to high yield by homo- and cross-coupling of related monomers. In addition, the single-step synthesis of diquinoxalino [2,3-a: 2', 3'c] phenazine and 2,2': 3', 2″ - terquinoxaline using the appropriate equivalent amount of LiTMP was performed. The products were characterized by means of NMR spectroscopy and HRMS spectrometry.
- Ucar, Sefa,Dastan, Arif
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supporting information
p. 4013 - 4022
(2020/09/21)
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- Five-membered azole heterocyclic compound and its preparation method, pharmaceutical composition and use thereof
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The present invention relates to a five-membered azole heterocycle compound represented by the following general formula (I), a preparation method of the five-membered azole heterocycle compound, a drug composition of the five-membered azole heterocycle compound, and a use of the five-membered azole heterocycle compound in preparation of drugs for prevention or treatment of TGR5-mediated diseases. The formula (I) is represented by the instruction.
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Paragraph 0138; 0139
(2017/02/28)
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- NRF2 REGULATORS
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Provided are aryl analogs,pharmaceutical compositions containing them and their use as NRF2 regulators.
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Page/Page column 202; 203
(2017/01/02)
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- ARYL ETHER-BASE KINASE INHIBITORS
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The present disclosure is generally directed to compounds which can inhibit AAK1 (adaptor associated kinase 1), compositions comprising such compounds, and methods for inhibiting AAK1.
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Page/Page column 55
(2015/03/28)
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- Synthesis and σ receptor affinity of regioisomeric spirocyclic furopyridines
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In order to investigate systematically the effect of the position of the pyridine N-atom on the σ1 receptor affinity four regioisomeric furopyridines 2a-d were synthesized and pharmacologically evaluated. The key steps of the synthesis comprise bromine/lithium exchange at regioisomeric bromopyridinecarbaldehyde acetals 7a-d, subsequent addition to 1-benzylpiperidin-4-one and cyclization. The regioisomeric acetals 7a-d were obtained either by o-metalation of bromopyridines 5b and 5c or by oxidation of bromopicolines 3a and 3d. In radioligand binding studies the regioisomeric furopyridines 2a-d showed 7- to 12-fold lower σ1 affinity than the benzofuran analog 1. The reduced σ1 affinity of the furopyridines 2a-d is explained with the reduced electron density of the pyridine ring. Since the four regioisomeric furopyridines show almost the same σ1 affinity (Ki = 4.9-10 nM), a directed interaction of the pyridine N-atom with the receptor protein can be excluded.
- Miyata, Kengo,Schepmann, Dirk,Wünsch, Bernhard
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p. 709 - 716
(2014/07/22)
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- Design, synthesis, and structure-activity relationships of 3,4,5-trisubstituted 4,5-dihydro-1,2,4-oxadiazoles as TGR5 agonists
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Given its role in the mediation of energy and glucose homeostasis, the G-protein-coupled bile acid receptor1 (TGR5) is considered a potential target for the treatment of type2 diabetes mellitus and other metabolic disorders. By thorough analysis of diverse structures of published TGR5 agonists, a hypothetical ligand-based pharmacophore model was built, and a new class of potent TGR5 agonists, based on the novel 3,4,5-trisubstituted 4,5-dihydro-1,2,4-oxadiazole core, was discovered by rational design. Three distinct synthetic methods for constructing 4,5-dihydro-1,2,4-oxadiazoles and extensive structure-activity relationship studies are reported herein. Compound (R)-54n, the structure of which was determined by single-crystal X-ray diffraction and quantum chemical solid-state TDDFT-ECD calculations, showed the best potency, with an EC50 value of 1.4nM toward hTGR5. Its favorable properties invitro warrant further investigation.
- Zhu, Junjie,Ye, Yangliang,Ning, Mengmeng,Mandi, Attila,Feng, Ying,Zou, Qingan,Kurtan, Tibor,Leng, Ying,Shen, Jianhua
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supporting information
p. 1210 - 1223
(2013/07/26)
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- Aryl Ether-Base Kinase Inhibitors
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The present disclosure is generally directed to compounds which can inhibit AAK1 (adaptor associated kinase 1), compositions comprising such compounds, and methods for inhibiting AAK1.
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Paragraph 0121
(2013/09/26)
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- Synthesis of 1-phenyl- and 1-pyridyl-3-pyridoazepines by reductive cyclization of diarylacetonitriles
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Several pyrido[2,3-d]azepines and pyrido[3,4-d]azepines, novel aza analogs of the pharmacologically relevant 1-aryl-3-benzazepines, were synthesized by assembling the azepine ring by reductive cyclization of (2-methoxyvinyl)pyridinyl(aryl)acetonitrile derivatives, which were easily derived from contiguously substituted bromo(2-methoxyvinyl)pyridines and the corresponding arylacetonitriles.
- de la Fuente, M. Carmen,Domínguez, Domingo
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scheme or table
p. 3653 - 3658
(2009/09/08)
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- An intra/intermolecular suzuki sequence to benzopyridyloxepines containing geometrically pure exocyclic tetrasubstituted alkenes
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(Chemical Equation Presented) A route to enable the preparation of 5-benzylidenyl-benzopyridyloxepine analogues was developed to continue our research in the field of nuclear hormone receptor modulators. The key steps are1) a syn-stereoselective diboratio
- Carson, Matthew W.,Giese, Matthew W.,Coghlan, Michael J.
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supporting information; experimental part
p. 2701 - 2704
(2009/05/26)
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- Therapeutic Pyrazolyl Thienopyridines
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The present invention provides for compounds of Formula I, and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, R5, R6, and R7 have any of the values defined therefor in the specification, and pharmaceutically acceptable salts thereof, that are useful as therapeutic agents in the treatment of TGFβ-mediated conditions, including cancer and fibrotic disorders. Also provided are pharmaceutical compositions comprising one or more compounds of Formula I.
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Page/Page column 20
(2008/06/13)
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- Synthesis and SAR of novel 2-arylthiazolidinones as selective analgesic N-type calcium channel blockers
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A series of new N-type (Cav2.2) calcium channel blockers derived from the 'hit' structures 2-(3-bromo-4-fluorophenyl)-3-(2-pyridin-2-ylethyl)thiazolidin-4-one 9 and its 2-[4-(4-bromophenyl)pyridin-3-yl]-3-isobutyl analogue 10 is described. Exte
- Knutsen, Lars J.S.,Hobbs, Christopher J.,Earnshaw, Christopher G.,Fiumana, Andrea,Gilbert, Jenny,Mellor, Sarah L.,Radford, Fleur,Smith, Nichola J.,Birch, Philip J.,Russell Burley,Ward, Stuart D.C.,James, Iain F.
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p. 662 - 667
(2007/10/03)
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- β-Substituted cyclohexanecarboxamide cathepsin K inhibitors: Modification of the 1,2-disubstituted aromatic core
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Further SAR study around the central 1,2-disubstituted phenyl of the previously disclosed Cat K inhibitor (-)-1 has demonstrated that the solvent exposed P2-P3 linker can be replaced by various 5- or 6-membered heteroaromatic rings. While some potency loss was observed in the 6-membered heteroaromatic series (IC50 = 1 nM for pyridine-linked 4 vs 0.5 nM for phenyl-linked (±)-1), several inhibitors showed a significantly decreased shift in the bone resorption functional assay (10-fold for pyridine 4 vs 53-fold for (-)-1). Though this shift was not reduced in the 5-membered heteroaromatic series, potency against Cat K was significantly improved for thiazole 9 (IC50 = 0.2 nM) as was the pharmacokinetic profile of N-methyl pyrazole 10 over our lead compound (-)-1.
- Robichaud, Joel,Bayly, Christopher I.,Black, W. Cameron,Desmarais, Sylvie,Leger, Serge,Masse, Frederic,McKay, Daniel J.,Oballa, Renata M.,Paquet, Julie,Percival, M. David,Truchon, Jean-Francois,Wesolowski, Gregg,Crane, Sheldon N.
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p. 3146 - 3151
(2008/02/05)
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- NOVEL QUINOLINE DERIVATIVES AS POTASSIUM ION CHANNEL OPENERS
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ABSTRACT The present invention is directed to novel quinoline derivatives, pharmaceutical compositions containing them and their use in the treatment of disorders related to ion channels such as potassium channels.
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Page/Page column 44
(2008/06/13)
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- NOVEL PYRIDINE DERIVATIVES AS POTASSIUM ION CHANNEL OPENERS
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The present invention is directed to novel pyridine derivatives, pharmaceutical compositions containing them and their use in the treatment of disorders related to ion channels such as potassium channels.
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Page/Page column 44
(2008/06/13)
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- 4-Piperidinecarboxamide modulators of vanilloid VR1 receptor
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This invention is directed to vanilloid receptor VR1 ligands. More particularly, this invention relates to hetero isonipecotic amides that are potent modulators of VR1 which are useful for the treatment and prevention of disease conditions in mammals.
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Page/Page column 54
(2010/11/08)
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- General synthetic method for naphthyridines and their N-oxides containing isoquinolinic nitrogen
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Substituted naphthyridines containing isoquinolinic nitrogen were synthesized by the reaction of o-ethynylpyridinecarbaldehydes with ammonia. The synthesis of their N-oxides was also achieved by a basic cyclization reaction of the same pyridine derivatives via the corresponding oximes.
- Numata, Atsushi,Kondo, Yoshinori,Sakamoto, Takao
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p. 306 - 311
(2007/10/03)
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- MAXONINE: STRUCTURE CORRECTION AND SYNTHESIS
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The structure for the pentacyclic alkaloid maxonine is revised from 1 to 17.Compound 17 was prepared by total synthesis and shown identical to the natural product.
- Kelly, T. Ross,Xu, Wei,Sundaresan, Jayashree
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p. 6173 - 6176
(2007/10/02)
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