- Synthesis method of 3-aminopyridine formaldehyde
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The invention discloses a synthesis method of 3-aminopyridine formaldehyde, which comprises the following steps of: carrying out a cutius rearrangement reaction on 2-bromonicotinic acid serving as a raw material to obtain tert-butyl (2-bromopyridine-3-yl) carbamate, carrying out a Grignard reaction to obtain tert-butyl (2-formyl pyridine-3-yl) carbamate, and finally carrying out a hydrolysis reaction to obtain 3-aminopyridine formaldehyde. The synthesis method overcomes the defects of expensive raw materials, low yield, use of microwave reaction and other conditions, difficulty in amplification and the like in the existing synthesis process, and has the advantages of simple synthesis route, reasonable process selection, low raw material cost, simple and easily available raw materials, convenience in operation and post-treatment, high total yield, no use of highly toxic reagents, easiness in amplification, and realization of mass production.
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Paragraph 0015-0017
(2021/02/20)
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- FERROPORTIN INHIBITORS AND METHODS OF USE
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The subject matter described herein is directed to Ferroportin inhibitor compounds of Formula I and pharmaceutical salts thereof, methods of preparing the compounds, pharmaceutical compositions comprising the compounds and methods of administering the compounds for prophylaxis and/or treatment of diseases caused by a lack of hepcidin or iron metabolism disorders, particularly iron overload states, such as thalassemia, sickle cell disease and hemochromatosis.
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Paragraph 0354; 0355
(2020/07/07)
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- AMINE OR (THIO)AMIDE CONTAINING LXR MODULATORS
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The present invention relates to derivatives of formula (I) which bind to the liver X receptor (LXRα and/or LXRβ) and act preferably as inverse agonists of LXR.
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Page/Page column 84
(2019/02/06)
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- SEVEN-MEMBERED SULFONAMIDES AS MODULATORS OF RAR-RELATED ORPHAN RECEPTOR-GAMMA (RORγ, NR1F3)
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The invention provides modulators for the orphan nuclear receptor RORγ and methods for treating RORγ mediated diseases by administration of these novel RORγ modulators to a human or a mammal in need thereof. Specifically, the present invention provides compounds of Formula (1) and the enantiomers, diastereomers, tautomers, solvates and pharmaceutically acceptable salts thereof as well as pharmaceutical compositions comprising said compounds as an active ingredient.
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Page/Page column 51
(2013/05/22)
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- NOVEL TRPV3 MODULATORS
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Disclosed herein are modulators of TRPV3 of formula (II): wherein G1, X1, X2, X3, X4, X5, G2, Ra, Rb, and u are as defined in the specification. Composition
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Paragraph 1676; 1677
(2013/06/04)
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- NOVEL TRPV3 MODULATORS
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Disclosed herein are modulators of TRPV3 of formula (II): wherein G1, X1, X2, X3, X4, X5, G2, Ra, Rb, and u are as defined in the specification. Composition
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Paragraph 203; 204
(2013/05/21)
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- TRICYCLIC ANTAGONISTS OF PROSTAGLANDIN D2 RECEPTORS
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Described herein are compounds that are antagonists of PGD2 receptors. Also described are pharmaceutical compositions and medicaments that include the compounds described herein that are antagonists of PGD2 receptors. Also described herein are methods of
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Page/Page column 85
(2009/12/23)
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- Impact of metal coordination on cytotoxicity of 3-aminopyridine-2- carboxaldehyde thiosemicarbazone (Triapine) and novel insights into terminal dimethylation
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The first metal complexes of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (Triapine) were synthesized. Triapine was prepared by a novel three-step procedure in 64% overall yield. In addition, a series of related ligands, namely, 2-formylpyridine thiosemicarbazone, 2-acetylpyridine thiosemicarbazone, 2-pyridineformamide thiosemicarbazone, and their N 4-dimethylated derivatives (including the N4-dimethylated analogue of Triapine) were prepared, along with their corresponding gallium(III) and iron(III) complexes with the general formula [M(L)2] +, where HL is the respective thiosemicarbazone. The compounds were characterized by elemental analysis, 1H and 13C NMR, IR and UV-vis spectroscopies, mass spectrometry, and cyclic voltammetry. In addition, Triapine and its iron(III) and gallium(III) complexes were studied by X-ray crystallography. All ligands and complexes were tested for their in vitro antiproliferative activity in two human cancer cell lines (41M and SK-BR-3), and structure-activity relationships were established. In general, the coordination to gallium(III) increased the cytotoxicity while the iron(III) complexes show reduced cytotoxic activity compared to the metal-free thiosemicarbazones. Selected compounds were investigated for the capacity of inhibiting ribonucleotide reductase by incorporation of 3H-cytidine into DNA.
- Kowol, Christian R.,Trondl, Robert,Heffeter, Petra,Arion, Vladimir B.,Jakupec, Michael A.,Roller, Alexander,Galanski, Markus,Berger, Walter,Keppler, Bernhard K.
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supporting information; experimental part
p. 5032 - 5043
(2010/03/02)
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- BIPYRIDYL AMINES AND ETHERS AS MODULATORS OF METABOTROPIC GLUTAMATE RECEPTOR-5
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The present invention is directed to novel bipyridyl amine and ether compounds such as those of Formula (I): (I) (where R?1#191, R?2#191, R?3#191, X and Y are as defined herein) which are mGluR5 modulators useful in the treatment or prevention of diseases and conditions in which mGluR5 is involved, including but not limited to psychiatric and mood disorders such as schizophrenia, anxiety, depression, bipolar disorders, and panic, as well as in the treatment of pain, Parkinson’s disease, cognitive dysfunction, epilepsy, circadian rhythm and sleep disorders, such as shift-work induced sleep disorder and jet-lag, drug addiction, drug abuse, drug withdrawal, obesity and other diseases. The invention is also directed to pharmaceutical compositions comprising these compounds. This invention further provides a method of treatment of these disorders and conditions by the administration of an effective amount of these novel bipyridyl amine and/or ether compounds and/or compositions containing these compounds.
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Page/Page column 31
(2010/02/11)
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- 1,1,1-TRIFLUORO-4-PHENYL-4-METHYL-2-(1H-PYRROLO
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Compounds of Formula (IA), IB), IC), and (ID) wherein R1, R2, R3, R4, R5, and R6 are as respectively defined herein for Formula (IA), (IB), (IC), and (ID), or a tautomer, prodrug, solvate, or salt thereof; pharmaceutical compositions containing such compounds, and methods of modulating the glucocorticoid receptor function and methods of treating disease-states or conditions mediated by the glucocorticoid receptor function or characterized by inflammatory, allergic, or proliferative processes in a patient using these compounds.
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Page/Page column 165
(2010/02/11)
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- NK1 ANTAGONIST
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The invention is to a compound exhibiting neurokinin inhibitory properties, a pharmaceutical composition comprising same and a method of treatment for neurokinin-meditated conditions.Formula (I)
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Page/Page column 28
(2010/02/09)
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- FUNGAL CELL WALL SYNTHESIS GENE
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A reporter system reflecting the transport process that transports GPI-anchored proteins to the cell wall was constructed and compounds inhibiting this process were discovered. Further, genes conferring resistance to the above compounds were identified and methods of screening for compounds that inhibit the activity of the proteins encoded by these genes were developed.Therefore, through the novel compounds, the present invention showed that antifungal agents having a novel mechanism, i.e. inhibiting the process that transports GPI-anchored proteins to the cell wall, could be achieved.
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- Sulfonic acid sulfonylamino n-(heteroaralkyl)-azaheterocyclylamide compounds
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The compounds of formula I herein exhibit useful pharmacological activity and accordingly are incorporated into pharmaceutical compositions and used in the treatment of patients suffering from certain medical disorders. More specifically, they are inhibitors of the activity of Factor Xa. The present invention is directed to compounds of formula I, compositions containing compounds of formula I, and their use, for treating a patient suffering from, or subject to, a physiological condition which can be ameliorated by the administration of an inhibitor of the activity of Factor Xa.
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- Inhibitors of Cyclic AMP Phosphodiesterase. 3. Synthesis and Biological Evaluation of Pyrido and Imidazolyl Analogues of 1,2,3,5-Tetrahydro-2-oxoimidazoquinazoline
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Hybridization of structural elements of 1,2,3,5-tetrahydro-2-oxoimidazoquinazoline ring system common to the cyclic AMP (cAMP) phosphodiesterase (PDE) inhibitors lixazinone (RS-82856,1) and anagrelide (3) with complementary features of other PDE inhibitor cardiotonic agents prompted the design and synthesis of the title compounds 7a-d, 11, 12, and 13a,b.The necessary features of these compounds were determined within the framework of the proposed active-site models for the high affinity form of cAMP PDE inhibited by cGMP (type IV).Evaluation of these targets, both in vitro as inhibitors of platelet or cardiac type IV PDE or in vivo as inotropic agents in the pentobarbital-anesthetized dog model of congestive heart failure, showed that these structure possessed negligibly enhanced activities over the parent heterocyclic system, and remained significantly inferior to 1 in all respects.This difference is ascribed to the absence of the N-cyclohexyl-N-methylbutyramidyl-4-oxy side chain of 1.The proposal that the acidic lactam-type functionality, common to the type IV PDE inhibitor inotropic agents such as 4-6 and 8-10, mimics the polarizable cyclic phosphate moiety of cAMP suggested that the side chain of 1 may function as an effective surrogate for selected characteristics of the adenine portion of cAMP.However, the results of this study show that incorporation of adenine-like hydrogen-bonding functionalities common to other type IV PDE inhibitors into the 1,2,3,5-tetrahydro-2-oxoimidazoquinazoline system did not enhance activity to the levels observed for 1 analogues.These observations, coupled with the kinetic pattern of inhibition of type IV PDE observed for 1 and analogues, suggest that access to a secondary, lipophilic-tolerant binding site, possibly coincident with the adenine binding domain, and adjacent to the catalytic ribose-phosphate binding site of platelet and cardiac type IV PDE, is responsible for the increased potency of these compounds.
- Venuti, Michael C.,Stephenson, Robert A.,Alvarez, Robert,Bruno, John J.,Strosberg, Arthur M.
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p. 2136 - 2145
(2007/10/02)
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