- DUTPASE INHIBITORS
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Deoxyuridine derivatives of the formula (I) where R1 is H or various substituents; D is -NHCO-, -CONH-, -0-, -C(=O)-, -CH=CH, -CΞC-, -NR5-; R4 is hydrogen or various substituents; R5 is H, C1-C4 alkyl, C1-C4 alkanoyl; E is Si or C; R6, R7 and R8 are independently selected from C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl or a stable monocyclic, bicyclic or tricyclic ring system; G is -O-, -S-, -CHR10-, -C(=O)-; J is -CH2-, or when G is CHR10 may also be -O- or -NH-; R10 is H, F, -CH3, -CH2NH2, -CH2OH; -OH R11 is H, F, -CH3, -CH2 NH2, -CH2OH, CH(OH)CH3, CH(NH3)CH3; or R10 and R11 together define an olefinic bond, or together form a -CH2-group, thereby defining a cis or trans cyclopropyl group; have utility in the prophylaxis or treatment of protozoal diseases such as malaria.
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Page/Page column 50
(2008/06/13)
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- A new strategy for deprotonative functionalization of aromatics: Transformations with excellent chemoselectivity and unique regioselectivities using t-Bu-P4 base
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A new strategy for deprotonative functionalization of aromatics using t-Bu-P4 base has been developed, and highly chemoselective transformations have been achieved with unique regioselectivities. Copyright
- Imahori, Tatsushi,Kondo, Yoshinori
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p. 8082 - 8083
(2007/10/03)
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- Biological evaluation of 5-substituted pyrimidine derivatives as inhibitors of brassinosteroid biosynthesis
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A series of 5-substituted pyrimidine derivatives was synthesized, and their ability to inhibit brassinosteroid biosynthesis was tested. The biological activity of these compounds was evaluated by the cress stem elongation method. Among the synthesized com
- Wang, Jing-Ming,Asami, Tadao,Yoshida, Shigeo,Murofushi, Noboru
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p. 817 - 822
(2007/10/03)
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- Influence of some novel N-substituted azoles and pyridines on rat hepatic CYP3A activity
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A series of N-substituted heteroaromatic compounds structurally related to clotrimazole was synthesized, and the effects of these compounds on ethosuximide clearance in rats were determined as a measure of their abilities to induce cytochrome P4503A (CYP3A) activity. Ethosuximide clearance and in vitro erythromycin N-demethylase activity were shown to correlate. In this series, imidazole or other related heteroaromatic 'head groups' were linked to triphenylmethane or other phenylmethane derivatives. Within the series, it was found that 1-triphenylmethane-substituted imidazoles elicited the greatest increase in CYP3A activity, and that among the triphenylmethyl-substituted imidazoles, the highest activities were achieved by the substitution of F- or Cl- in either the meta or para position of one of the phenyl rings. Diphenylmethylsubstituted pyridine was effectively devoid of activity. Compounds eliciting the largest increase in CYP3A activity (viz. 1-[(3-fluorophenyl)diphenylmethyl]imidazole, 1-[(4- fluorophenyl)diphenylmethyl]imidazole, and 1-[tri-(4- fluorophenyl)methyl]imidazole) produced little or no increase in ethoxyresorufin O-dealkylase (EROD) activity (i.e. CYP1A), whereas benzylimidazole, which elicited only a small increase in CYP3A activity, produced an almost 9-fold increase in CYP1A activity. For a series of eleven compounds exhibiting a wide range of influence on CYP3A activity, a positive correlation was found between ethosuximide clearance and hepatic CYP3A mRNA levels.
- Slama, James T.,Hancock, Julie L.,Rho, Taikyun,Sambucetti, Lidia,Bachmann, Kenneth A.
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p. 1881 - 1892
(2008/04/18)
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- Aromatase Inhibition by 5-Substituted Pyrimidines and Dihydropirimidines
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The inhibition of estrogen biosynthesis has been suggested to be an effective treatment of hormone-dependent diseases, particularly breast cancer.Several series of 5-substituted pyrimidine derivatives have been synthesized and tested for their ability to inhibit the enzyme aromatase (estrogen synthetase).Compounds were evaluated in an in vitro assay that measured the inhibition of rat ovarian microsomal aromatase activity.Greatest inhibitory activity was achieved in the cases of diarylpyrimidinemethanols and diarylpyrimidinyl methanes which were substituted in the 4- and 4'-positions with electron-withdrawing substituents, particularly Cl.
- Taylor, Harold M.,Jones, C. David,Davenport, James D.,Hirsch, Kenneth S.,Kress, T.J.,Weaver, Dix
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p. 1359 - 1365
(2007/10/02)
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