- Syntheses and pharmacokinetic evaluations of four metabolites of 2-(4-(2-((1H-benzo[d]imidazol-2-yl)thio)ethyl)piperazin-1-yl)-N-(6-methyl-2,4-bis-(methylthio)pyridin-3-yl)acetamide hydrochloride [K-604], an acyl-CoA:cholesterol O-acyltransferase-1 inhibi
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We synthesized and identified four metabolites of acyl-coenzyme A:cholesterol O-acyltransferase (ACAT)-1 inhibitor, K-604 (1). Two of the metabolites M1 and M2, were prepared from 1 using a combination reagent of hydrogen peroxide and sodium tungstate wit
- Miura, Toru,Ohgiya, Tadaaki,Omichi, Kozo,Shibuya, Kimiyuki,Tsunenari, Yoshihiko
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- Phenacylation of 6-methyl-beta-nitropyridin-2-ones and further heterocyclization of products
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Reaction between the derivatives of 6-methyl-beta-nitropyridin-2-one and phenacyl bromides was studied, and the yields observed were extremely low. The pyridones were converted via chloropyridines to methoxyderivatives, which were N-phenacylated. N-Phenacyl derivatives of 4,6-dimethyl-5-nitropyridin-2-one under the action of base gave 5-hydroxy-8-nitroindolizine and under acidic conditions gave 5-methyl-6-nitrooxazole[3,2-a]pyridinium salt, which underwent recycization with MeONa to 5-methoxy-8-nitroindolizine.
- Babaev, Eugene V.,Rybakov, Victor B.
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- Ethanol compound used as FGFR inhibitor
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The invention discloses an ethanol compound used as a FGFR inhibitor. The invention provides the compound as shown in a formula I which is described in the specification or a pharmaceutically acceptable salt thereof, a preparation method for the compound and application of the compound as a medicine to treatment of cancers.
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- Synthesis of some fluorine-containing pyridinealdoximes of potential use for the treatment of organophosphorus nerve-agent poisoning
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Fluoroheterocyclic aldoximes were screened as therapeutic agents for the treatment of anticholinesterase poisoning. 2-Fluoropyridine-3- and -6-aldoxime, and 3-fluoropyridine-2- and -4-aldoxime, were synthesised. Attempts to obtain 3,5,6-trifluoropyridine-2,4-bis(aldoxime) and -2-aldoxime, however, proved unsuccessful. Pentafluorobenzaldoxime was prepared by oximation of pentafluorobenzaldehyde. Acid dissociation constants (pKa) and second-order rate constants (kox-) of the fluorinated pyridinealdoximes towards sarin were measured. 2,3,5,6-Tetrafluoropyridine-4- aldoxime had the best profile: its kox- approached that of the therapeutic oxime P2S (310 vs. 120 l mol-1 min-1), but its higher pKa (9.1 vs. 7.8) fell short of the target figure of 8 required for reactivation of inhibited acetylcholinesterase in vivo. N-alkylation of the fluorinated pyridine-aldoximes may reduce their pK a nearer to 8 and enhance their therapeutic potential. Crown Copyright
- Timperley, Christopher M.,Banks, R. Eric,Young, Ian M.,Haszeldine, Robert N.
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p. 541 - 547
(2011/09/15)
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- Synthesis and structure-activity relationships of N3-pyridylpyrazinones as corticotropin-releasing factor-1 (CRF1) receptor antagonists
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A series of N3-pyridylpyrazinones was investigated as corticotropin-releasing factor-1 receptor antagonists. It was observed that the binding affinity of analogues containing a pyridyl group was influenced not only by the substitution pattern on the pyridyl group, but also by the pKa of the pyridyl nitrogen. Analogues containing a novel 6-(difluoromethoxy)-2,5-dimethylpyridin-3-amine group were among the most potent N3-pyridylpyrazinones synthesized. The synthesis and SAR of N3-pyridylpyrazinones is described herein.
- Hartz, Richard A.,Ahuja, Vijay T.,Schmitz, William D.,Molski, Thaddeus F.,Mattson, Gail K.,Lodge, Nicholas J.,Bronson, Joanne J.,Macor, John E.
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scheme or table
p. 1890 - 1894
(2010/07/06)
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- INHIBITORS OF JANUS KINASES
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The instant invention provides for compounds that inhibit the four known mammalian JAK kinases (JAK1, JAK2, JAK3 and TYK2) and PDK1. The invention also provides for compositions comprising such inhibitory compounds and methods of inhibiting the activity of JAK1, JAK2, JAK3, TYK2 and PDK1 by administering the compound to a patient in need of treatment for myeloproliferative disorders or cancer.
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Page/Page column 74
(2010/01/12)
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- Heterocyclic FXR binding compounds
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The present invention relates to compounds which bind to the NR1H4 receptor (FXR) and act as agonists or partial agonists of the NR1H4 receptor (FXR). The invention further relates to the use of the compounds for the preparation of a medicament for the treatment of diseases and/or conditions through binding of said nuclear receptor by said compounds, and to a process for the synthesis of said compounds.
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Page/Page column 23
(2008/06/13)
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- TETRAHYDROISOQUINOLINE COMPOUND AND MEDICINAL USE THEREOF
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The present invention provide a tetrahydroisoquinoline compound having a superior ACAT-inhibitory activity and/or anti-oxidation action, particularly, novel compound represented by the formula (I) (wherein each symbol is as described in the specification) and a pharmaceutically acceptable salt thereof.
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Page/Page column 21
(2010/11/28)
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- ANDROGEN RECEPTOR MODULATORS
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Treatment of Diseases caused by Disturbances of the Activity of the Androgen Receptor uses of compounds of Formula (I): (as defined herein), for the treatment of diseases caused by disturbances of the activity of androgen receptor are provided: Formula (I). Isolated compounds of Formula (I) are also provided.
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- PYRROLOPYRIDINE-2-CARBOXYLIC ACID AMIDE INHIBITORS OF GLYCOGEN PHOSHORYLASE
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Compounds represented by Formula (I): or pharmaceutically acceptable salts thereof, are inhibitors of glycogen phosphorylase and are useful in the prophylactic or therapeutic treatment of diabetes, hyperglycemia, hypercholesterolemia, hyperinsulinemia, hyperlipidemia, hypertension, atherosclerosis or tissue ischemia e.g. myocardial ischemia, and as cardioprotectants.
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- 5-HT1F agonists
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The present invention relates to a compound of formula (I): or a pharmaceutical acid addition salt thereof; which is useful for activating 5-HT1freceptors and inhibiting protein extravasation in a mammal.
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- Inhibitors of farnesyl protein transferase
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The present invention comprises benzodiazepine compounds having farnesyl transferase inhibitory activity.
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- SUBSTITUTED HETEROAROMATIC 5-HT1F AGONISTS
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This invention provides novel 5-HT 1F agonists of the Formula STR1 in which X, Y, E, R, A, B, and n are as defined in the specification, which are useful for the treatment of migraine and associated disorders.
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- Substituted heteroaromatic 5-HT 1F agonists
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This invention provides novel 5-HT1Fagonists of the Formula in which X, Y, E, R, A, B, and n are as defined in the specification, which are useful for the treatment of migraine and associated disorders.
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- Pyrido[3,2-e][1,4]diazepines - Synthesis and anti-HIV-1-activity tests
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Starting from the commercially available 6-methyl-2-pyridylamine (1) the pyrido[3,2-e][1,4]diazepine 14a was synthesized in 12 steps with 7% total yield. 14a, the N-methyl derivative 14b, the thiolactam 15a, the amidine 16, and the 1,2,4-triazole 17 were tested for anti-HIV-1-activity. None of the compounds tested possesses antiviral activity comparable to that of zidovudine (3'-azido-3'-desoxythymidine = AZT).
- Gorlitzer,Wilpert,Rubsamen-Waigmann,Suhartono,Wang,Immelmann
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p. 247 - 255
(2007/10/02)
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- Chemotherapeutically effective nitro compounds. III. Nitropyridines, nitroimidazopyridines and related compounds
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New 2 nitropyridines and 3 nitropyridines, and 3 nitroimidazo [1,2 a] pyridines and related compounds (together 106) were synthesized and tested for their chemotherapeutic efficacy against trichomonads, amoebas and other organisms, such as Eimeria tenella, bacteria, fungi and helminths. Several 2 nitropyridines revealed a detectable systemic effect against Entamoeba histolytica (extraintestinal amoebiasis of the golden hamster) and also a weak activity against Trichomonas fetus in the NMRI mouse. Only a few 3 nitropyridines showed a marked systemic effect against trichomonads. Of the 3 nitroimidazo [1,2 a] pyridines, only the electroneutral carboxylic acid amide group exhibited a pronounced activity, exclusively against trichomonads; however, the activity was nullified by electronegative, electropositive and other electroneutral substituents. As they were not superior in chemotherapeutic respect compared to the known standard preparations (metronidazole), no further tests were carried out with the most effective compounds.
- Winkelmann,Raether,Hartung,Wagner
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