- MEDICINAL COMPOSITIONS IMPROVED IN SOLUBLITY IN WATER
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Solid dispersions are provided comprising an HER2 inhibitor which is hardly or not soluble in water and a hydrophilic polymer. These solid dispersions have been improved in the solubility of the HER2 inhibitor, oral absorption and bioavailability in blood
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Page/Page column 34
(2010/11/29)
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- MEDICINAL COMPOSITIONS HAVING IMPROVED ABSORBABILITY
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An HER2 inhibitor having an average particle size of about 3 μm or less or a composition containing the same which has improved HER2 inhibitor-absorbability.
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Page/Page column 38-39
(2010/11/29)
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- Inhibition of uridine phosphorylase: Synthesis and structure-activity relationships of aryl-substituted 5-benzyluracils and 1-[(2- hydroxyethoxy)methyl]-5-benzyluracils
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A series of 1-[(2-hydroxyethoxy)methyl]-5-benzyluracils were synthesized and tested for inhibition of murine liver uridine phosphorylase (UrdPase). Inhibitors of UrdPase are reported to enhance the chemotherapeutic utility of 5-fluoro-2'-deoxyuridine and 5-fluorouracil and to ameliorate zidovudine- induced anemia in animal models. We prepared a series of 5-aryl-substituted analogues of 5-benzylacyclouridine (BAU), a good inhibitor of UrdPase (IC50 of 0.46 μM), to develop a compound with enhanced potency and improved pharmacokinetics. The first phase of structure-activity relationship studies on a series of 32 aryl-substituted 5-benzyluracils found several 5-(3- alkoxybenzyl) analogues of 5-benzyluracil with enhanced potency. The acyclovir side chain, the (2-hydroxyethoxy)methyl group, was substituted on the more potent aryl-substituted 5-benzyluracils. The two most potent compounds, 10y (3-propoxy) and 10dd (3-sec-butoxy), were inhibitors of UrdPase with IC50s of 0.047 and 0.027 μM, respectively. Six compounds were tested in vivo for effects on steady-state concentrations of circulating uridine in rats. Plasma uridine levels were elevated 3-9-fold by compound levels that ranged from 8 to 50 μM.
- Orr,Musso,Boswell,Kelley,Joyner,Davis,Baccanari
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p. 3850 - 3856
(2007/10/02)
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- Regioselective synthesis of 1,8-dihydroxytetralins through a tandem reduction/intramolecular hydroxyalkylation of 4-(3-hydroxyphenyl)alkanoates
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A series of 4-(3-hydroxyphenyl)butanoates 3 has been prepared and transformed into 1,8-dihydroxytetralins of general formula 2 by treatment with 2 equivalents of DIBALH followed by quenching with aqueous NH4Cl. A possible mechanism for this novel totally regioselective intramolecular hydroxyalkylation is suggested and the factors affecting the stability of 1,8-dihydroxytetralins 2 are also discussed.
- Guanti, Giuseppe,Banfi, Luca,Riva, Renata
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p. 11945 - 11966
(2007/10/02)
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- Tandem Reduction / Intramolecular Hydroxyalkylation of (3-Hydroxyphenyl)alkanoates: a New Regioselective Approach to 1,8-Dihydroxytetralins
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4-(3-hydroxyphenyl)-butanoates 4, on treatment with DIBALH, followed by hydrolytic work-up, undergo a novel completely regioselective intramolecular hydroxyalkylation reaction to give 1,8-dihydroxytetralins.The yield of the reaction depends heavily on the structure of starting material, best results being achieved with 3,3-disubstituted butanoates.
- Guanti, Giuseppe,Banfi, Luca,Narisano, Enrica,Riva, Renata,Thea, Sergio
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p. 3919 - 3922
(2007/10/02)
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- SYNTHESIS AND CHEMISTRY OF AN IRON(III) TETRAPHENYLPORPHYRIN WITH A COVALENTLY-ATTACHED PHENOLATE TAIL
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We report the synthesis of a phenolate-tailed iron(III) tetraphenylporphyrin, 1.The phenolate ligand is covalently-attached to the porphyrin ring and is coordinated to the iron(III) center.This phenolate ligand increases the rate of oxygen atom transfer to the metal center.
- Nee, Michael W.,Kim, Chongwoo A.,Garg, Sandhya,Griffith, Michael C.,Mizoue, Laura S.,et al.
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p. 5345 - 5348
(2007/10/02)
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- PHENYL ALKYLAMINOPYRIMIDONES
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The compounds are phenyl alkylaminopyrimidones which are histamine H. sub.2-antagonists. A specific compound of the present invention is 2-[2-[3-(dimethylaminomethyl)benzylthio]ethylamino]-5-(6-methyl-3-pyridylme thyl)-4-pyrimidone.
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- GUANIDINOTHIAZOLYL DERIVATIVES
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The compounds are guanidinothiazolyl derivatives which are histamine H. sub.2-antagonists. A specific compound of the present invention is 2-2-(2-guanidino-4-thiazolylmethylthio)ethylamino!-5-(6-methyl-3-pyridylmethy l)-4-pyrimidone.
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- ISOUREAS AND ISOTHIOUREAS
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The compounds are isoureas and isothioureas which have an O-or S-alkylpyrimidone substituent and which are histamine H 2-antagonists and antiinflammatory agents. A specific compound of this invention is 2-[5-(O-isoureido)pentylamino]-5-(6-methyl-3-pyridylmethyl)-4-pyrimidone.
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- Pyrimidine compounds
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The compounds are substituted pyrimidine compounds which are histamine H2 -antagonists. A specific compound of the present invention is 2-[2-(5-dimethylaminomethyl)-2-furylmethylthio)ethylamino]-5-(3-pyridylmethyl)-4-pyrimidone.
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