- A convenient synthesis of 1-aryl- and 1-alkyl-1,4,5,6-tetrahydropyridazin-3(2H)-ones
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Aryl- and alkylhydrazines react with readily available cyclopropanedicarboxylate (2) in refluxing acetonitrile to afford the corresponding 1-substituted 1,4,5,6-tetrahydropyridazin-3(2H)-ones (5) directly via nitrogen-carbon bond formation, cyclization and decarboxylation of the cyclized intermediates.
- Hwang, Ki-Jun,Park, Kyung-Ho
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p. 219 - 222
(2007/10/02)
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- 5-lipoxygenase inhibitors: The synthesis and structure-activity relationships of a series of 1-phenyl-3-pyrazolidinones
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A series of analogues of the 5-lipoxygenase inhibitor 1-phenyl-3-pyrazolidinone (phenidone, 1a) has been prepared via two complementary new synthetic methods. The reaction of various electrophiles with the dianion of 1a or with an N-silylpyrazolidinone anion gave the desired 4-substituted pyrazolidinones (Scheme I and II). A new procedure was developed for the resolution of 4-substituted pyrazolidinones (Scheme V). A regression study on 21 compounds in this series showed a correlation of increased inhibitor potency (pIC50) with increased compound lipophilicity (log P) and with an N-phenyl electronic effect as measured by the 13C NMR chemical shift parameter CNMR1' (R2 = 0.79). The most potent 5-lipoxygenase inhibitor in this series was 4-(ethylthio)-1-phenyl-3-pyrazolidinone (1n) with an IC50 of 60 nM. Another member of this series, 4-(2-methoxyethyl)-1-phenyl-3-pyrazolidinone (1f, IC50 = 0.48 μM), although less potent than 1n, was better tolerated in the whole animal relative to phenidone (1a) and also displayed good oral activity in two models of 5-lipoxygenase inhibition. On the basis of a structure-activity relationship study, a mechanism for the inhibition of 5-lipoxygenase by this class of inhibitors was proposed.
- Hlasta,Casey,Ferguson,Gangell,Heimann,Jaeger,Kullnig,Gordon
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p. 1560 - 1570
(2007/10/02)
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- PREPARATION OF N-ARYLAMINO-2-PYRROLIDONES FROM ARYLHYDRAZIDES OF γ-CHLOROBUTYRIC ACID
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Intramolecular alkylation of the arylhydrazides of γ-chlorobutyric acid in the presence of sodium ethoxide leads to the formation of N-arylamino-2-pyrrolidones.The direction of the reaction is not altered by the absence of a substituent on the aniline nitrogen atom.In the case of a p-nitrophenyl-hydrazide, O-alkylation is observed.
- Blokhina, A. V.,Boronin, V. G.,Druzhinina, V. V.,Zhestkov, V. P.,Portnov, Yu. N.
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p. 395 - 399
(2007/10/02)
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- 1,4,5,6-TETRAHYDRO-1-PHENYLPYRIDAZIN-3(2H)-ONE, A HOMOLOGUE OF PHENIDONE
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The title compound is synthesised in 3 steps from phenyl hydrazine, and its properties are reported.
- Dowlatshahi, Hossein A.
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p. 1253 - 1260
(2007/10/02)
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