- Chemotherapeutic agents: Part XXIII - Synthesis of π-deficient pyrimidines and fused pyrimidines as leishmanicides
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Various ?-deficient pyrimidines and fused purimidines have been synthesized and evaluated for their leishmanicidal activity against L. donovani.
- Ram, Vishnu J,Haque, Navedul,Nath, Mahendra
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p. 754 - 759
(2007/10/02)
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- Synthesis of Pyrimidine Derivatives by the Reaction of Ketene Dithioacetals with Amides
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Reactions of methyl 2-cyano-3,3-bis(methylthio)acrylate (1a) with carboxamides 2a-g in the presence of sodium hydride in a mixture of benzene and N,N-dimethylacetamide took place displacement with the methylthio group to give the corresponding methyl 3-N-acylamino-2-cyano-3-(methylthio)acrylates 3a-g which were readily converted to the corresponding pyrimidine derivatives at reflux in methanol in good yields.Reactions of 2-cyano-3,3-bis(methylthio)acrylonitrile (1b) with the carboxamides 2a-f gave directly pyrimidine-5-carbonitrile derivatives 7a-f.Ketene dithioacetals 1a,b smoothly reacted with thioamide 2g or urea 2h,i to give the expected pyrimidine derivatives 9,10a,b.Polyfunctionalized pyrimidines, thus obtained, were also used for the synthesis of fused pyrimidine derivatives.
- Kohra, Shinya,Tominaga, Yoshinori,Hosomi, Akira
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p. 959 - 968
(2007/10/02)
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- Chemistry and Positive Inotropic Effect of Pelrinone and Related Derivatives. A Novel Class of 2-Methylpyrimidones as Inotropic Agents
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A novel series of pyrimidine derivatives was synthesized and evaluated for positive inotropic activity.Inotropic and chronotropic effects were determined in vitro in cat papillary muscle and right atrium, respectively.Selected compounds were then evaluated in vivo in a dog heart failure model.Changes in ventricular dP/dt, heart rate, and blood pressure were monitored.Several of these agents produced relatively minor changes in heart rate.This class of agents demonstrated a varying degree of vasodilator effects concomitant with increases in ventricular contractility.The most potent analogues, 9, 48, and 49, were evaluated orally in conscious dogs with implanted Konisberg pressure transducers, and their effect on left ventricular dP/dt was compared with that of milrinone.Mechanistically, the agents of this novel class appear not to mediate their effect either via β-receptors or inhibition of Na(+)/K(+)-ATPase.A major component of their inotropic effect is mediated by the inhibition of cardiac phosphodiesterase (PDE)-Fr.III.This was clearly demonstrated by 9, 48, and 49.Compound 48 was found to be the most potent inhibitor of PDE-Fr.III from among the compounds tested in this assay.
- Bagli, Jehan,Bogri, T.,Palameta, B.,Rakhit, S.,Peseckis, S.,et al.
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p. 814 - 823
(2007/10/02)
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