- MATRIX METALLOPROTEINASE (MMP) INHIBITORS AND METHODS OF USE THEREOF
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Hydantoin based compounds useful as inhibitors of matrix metalloproteinases (MMPs), particularly macrophage elastase (MMP-12) are described. Also described are related compositions and methods of using the compounds to inhibit MMP-12 and treat diseases mediated by MMP-12, such as asthma, chronic obstructive pulmonary disease (COPD), emphysema, acute lung injury, idiopathic pulmonary fibrosis (IPF), sarcoidosis, systemic sclerosis, liver fibrosis, nonalcoholic steatohepatitis (NASH), arthritis, cancer, heart disease, inflammatory bowel disease (IBD), acute kidney injury (AKI), chronic kidney disease (CKD), Alport syndrome, and nephritis.
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Paragraph 0262-0263
(2021/05/21)
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- MATRIX METALLOPROTEINASE (MMP) INHIBITORS AND METHODS OF USE THEREOF
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Hydantoin based compounds useful as inhibitors of matrix metalloproteinases (MMPs), particularly macrophage elastase (MMP-12) are described. Also described are related compositions and methods of using the compounds to inhibit MMP-12 and treat diseases mediated by MMP-12, such as asthma, chronic obstructive pulmonary disease (COPD), emphysema, acute lung injury, idiopathic pulmonary fibrosis (IPF), sarcoidosis, systemic sclerosis, liver fibrosis, nonalcoholic steatohepatitis (NASH), arthritis, cancer, heart disease, inflammatory bowel disease (IBD), acute kidney injury (AKI), chronic kidney disease (CKD), Alport syndrome, and nephritis.
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Paragraph 0653-0654
(2019/12/02)
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- Preparation method of 2-(4-bromo-1-methyl-1H-pyrazol-5-yl)ethanamine
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The invention relates to a preparation method of 2-(4-bromo-1-methyl-1H-pyrazol-5-yl)ethanamine. The method comprises the following steps: reacting 1-methylpyrazole used as a raw material to obtain 1-methyl-1H-pyrazole-5-carbaldehyde; adding piperidine and pyridine to obtain a solid 3-(1-methyl-1H-pyrazole-5-yl) acrylic acid; further, adding palladium on carbon into a methanol solution, and introducing hydrogen to obtain 3-(1-methyl-1H-pyrazol-5-yl) propionic acid; furthermore, reacting under roles of bromine and saturated sodium sulphite solution, and performing spinning drying to obtain a solid 3-(4-bromo-1-methyl-1H-pyrazol-5-yl) propionic acid; adding thionyl chloride, tetrahydrofuran, and stronger ammonia water, reacting, dissolving out methyl alcohol, purifying silica gel, eluting ethyl acetate in sequence to obtain 3-(4-bromo-1-methyl-1H-pyrazol-5-yl) propanamide; finally adding NaOH and bromine, and performing ice-bath to obtain 2-(4-bromo-1-methyl-1H-pyrazol-5-yl)ethanamine. The method has the advantages of being clear in steps, little in waste, high in yield, easy to operate and capable of saving raw materials.
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Paragraph 0019; 0022; 0023; 0030; 0031
(2017/08/30)
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- PYRIMIDINE PDE10 INHIBITORS
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The present invention is directed to pyrimidine compounds which are useful as therapeutic agents for the treatment of central nervous system disorders associated with phosphodiesterase 10 (PDE10). The present invention also relates to the use of such compounds for treating neurological and psychiatric disorders, such as schizophrenia, psychosis or Huntington's disease, and those associated with striatal hypofunction or basal ganglia dysfunction.
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Page/Page column 47
(2014/06/11)
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- Spin transition in the molecular heterospin complex of Cu(hfac)2 with 4,4,5,5-tetramethyl-2-(1-methylpyrazol-5-yl)-4,5-dihydroimidazole-1-oxyl 3-oxide
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The synthesis, structure, and magnetic properties of the products of the reaction for Cu(hfac)2 (hfac is hexafluoroacetylacetonate) with spin-labeled nitronyl nitroxides 4,4,5,5-tetramethyl-2-(1-R-1H-pyrazol-5-yl)-3- imidazoline-1-oxyl 3-oxides L5/R (R = Me, Et, Pr, Bu), viz., binuclear complex [Cu(hfac)2L5/Me]2 and chain polymer complexes [Cu(hfac)2L5/R]n, are described. The polymer heterospin chains are built according to head-to-head (R = Me, Et, Pr, Bu) and head-to-tail (R = Pr, Bu) motifs. Compound [Cu(hfac)2L5/Me]2 is characterized by the ability to reveal the reversible effect of thermally induced spin transition at a temperature about 75 K (without hysteresis). In the set of heterospin CuII compounds with spin-labeled pyrazoles, this is the earlier unknown example of a molecular complex exhibiting a similar magnetic anomaly.
- Fokin,Kostina,Tret'yakov,Romanenko,Bogomyakov,Sagdeev,Ovcharenko
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p. 661 - 671
(2014/01/23)
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- Combination of two pharmacophoric systems: Synthesis and pharmacological evaluation of spirocyclic pyranopyrazoles with high σ1 receptor affinity
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The novel class of spirocyclic σ1 ligands 3 (6′,7′-dihydro-1′H-spiro[piperidine-4,4′-pyrano[4,3-c] pyrazoles]) was designed by the combination of the potent σ1 ligands 1 and 2 in one molecule. Thorough structure affinity relationship
- Schl?ger, Torsten,Schepmann, Dirk,Lehmkuhl, Kirstin,Holenz, J?rg,Vela, Jose Miguel,Buschmann, Helmut,Wünsch, Bernhard
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supporting information; experimental part
p. 6704 - 6713
(2011/12/04)
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- Method for the Production of N-Substituted (3-Dihalomethyl-1-Methyl-Pyrazole-4-yl) Carboxamides
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The present invention relates to a process for preparing N-substituted (3-dihalomethylpyrazol-4-yl)carboxamides of the formula (I) in which R1 is optionally substituted phenyl or C3-C7-cycloalkyl, R1a is hydrogen or fluorine, or R1a together with R1 is optionally substituted C3-C5-alkanediyl or C5-C7-cycloalkanediyl, R2 is C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl or C1-C4-alkoxy-C1-C2-alkyl, X is F or Cl and n is 0, 1, 2 or 3; which comprises A) providing a compound of the formula (II) in which X is F or Cl, Y is Cl or Br and R2 has one of the meanings given above and B) reacting a compound of the formula (II) with carbon monoxide and a compound of the formula (III) in which R1, R1a and n have one of the meanings given above; in the presence of a palladium catalyst; to intermediates used for the preparation according to the process according to the invention, and also to processes for their preparation.
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Page/Page column 16
(2010/07/10)
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- Spiro-pyrano-pyrazole derivatives
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The present invention relates to compounds of formula (I) having pharmacological activity towards the sigma (σ) receptor, and more particularly to some spiro-pyrano-pyrazole derivatives, to processes of preparation of such compounds, to pharmaceutical com
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Page/Page column 15; 45
(2008/12/04)
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- PYRAZOLE DERIVATIVES AS P2X7 MODULATORS
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The present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof: (I) wherein R1 represents C1-6 alkyl or C3-6 cycloalkyl, either of which is optionally substituted with 1, 2 or 3 ha
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Page/Page column 29
(2008/12/08)
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- Process for obtaining cizolirtine and its enantiomers
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A process is described for the preparation of a precursor alcohol of Cizolirtine, (±)-2-[phenyl(1-methyl-1H-pyrazol-5-yl)methoxy]-N,N-dimethylethanamine and its enantiomers, it comprises the asymmetric addition of a metalated phenyl reagent to an pyrazolc
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Page/Page column 9
(2010/11/08)
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- Process for obtaining enantiomers of thienylazolylalcoxyethanamines
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A process is described for the preparation of a precursor alcohol of (±)-2-[thienyl(1-methyl-1H-pyrazol-5-yl)methoxy]-NN-dimethyletanamine and in general for thyenylazolylalcoxyethanamines and their enantiomers. It comprises the asymmetric addition of a metalated thienyl reagent to a pyrazolcarbaldehyde in the presence of a chiral ligand to render chiral alcohols. The chiral alcohols are further O-alkylated to render the corresponding pharmaceutically active thyenylazolylalcoxyethanamines.
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Page/Page column 10
(2010/11/08)
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- PROCESS FOR OBTAINING ENANTIOMERS OF THIENYLAZOLYLALCOXYETHANAMINES
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A process is described for the preparation of a precursor alcohol of (±)-2-[thienyl(1-methyl-1H-pyrazol-5-yl)methoxy]-N,N-dimethyletanamine and in general for thienylazolylalcoxyethanamines and their enantiomers. The process involves asymmetric addition of a metalated thienyl reagent to a pyrazolcarbaldehyde in the presence of a chiral ligand to yield chiral alcohols. The chiral alcohols are further O-alkylated to yield the corresponding pharmaceutically active thienylazolylalcoxyethanamines.
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Page/Page column 3; 6-7
(2008/06/13)
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- 4(SPIROPIPERIDINYL)METHYL SUBSTITUTED PYRROLIDINES AS MODULATORS OF CHEMOKINE RECEPTOR ACTIVITY
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3-Substituted pyrrolidines having a spiropiperidinylmethyl substituent on the 4-position of the ring are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptors CCR-3 and/or CCR-5.
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- BENZAZEPINE DERIVATIVES, PROCESS FOR THE PREPARATION OF THE SAME AND USES THEREOF
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Compounds of the general formula (I): or salts thereof, which exhibit CCR5 antagonism and exert preventive and therapeutic effects against HIV infections: wherein R1 is a 5- to 6-membered aromatic ring which bears a substituent represented by the general formula: R-Z1-X-Z2- (wherein R1 is hydrogen or optionally substituted hydrocarbyl; X is optionally substituted alkylene; and Z1 and Z2 are each a heteroatom) and may be further substituted, with R being optionally bonded to the aromatic ring to form another ring; Y is optionally substituted imino; and R2 and R3 are each optionally substituted aliphatic hydrocarbyl or an optionally substituted hetero-alicyclic group.
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- Studies on β-lactam antibiotics, synthesis and antibacterial activity of novel 1β-methylcarbapenems related to FR21818: 5-membered ring analogs
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The synthesis and biological activity of the novel series of 1β-methylcarbapenems 1 are described. Most compounds displayed extremely potent antibacterial activity and high renal DHP-I stability. The best compound in this series, FR21818 (1a) displayed ex
- Azami, Hidenori,Barrett, David,Tanaka, Akira,Sasaki, Hiroshi,Matsuda, Keiji,Sakurai, Minora,Matsumoto, Yoshimi,Tawara, Shuichi,Chiba, Toshiyuki,Sakane, Kazuo
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p. 1409 - 1414
(2007/10/03)
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