Quantitative Structure-Activity Relationships in Cytokinin Agonistic and Antagonistic Pyrido[2,3-d]pyrimidine Derivates: Insights into Receptor Topology

1区 · 医学

Article

作者: Murakami, Shigeru ; Matsubara, Satoshi ; Iwamura, Hajime ; Koshimizu, Koichi

2-(Methylthio)pyrido[2,3-d]pyrimidines having various alkylamino and anilino substituents at the 4-position were prepared and tested for their cytokinin agonistic and antagonistic activities by the tobacco callus bioassay. The alkyl series of compounds showed anticytokinin activity, whereas the anilino derivatives exhibited both cytokinin and anticytokinin activities depending on the structure and position of the benzene substituents. Quantitative structure-activity analyses were carried out for each class and for the combined set of compounds with use of physicochemical parameters and regression analysis, indicating that the quality of activity, agonistic or antagonistic, as well as the extent of activity, is significantly affected by the steric features of the molecule. On the basis of the present results and previous quantitative analyses on cytokinins and other classes of anticytokinins, a dimensional map for the cytokinin receptor site can be drawn, which can serve as the basis for the design of novel agonists and antagonists.

Arzneimittel-Forschung

Preliminary pharmacokinetics of a new pyridopyrimidine derivative

作者: Roch, M. J. ; Ochoa, M. C. ; Perez, M. J.

The pharmacokinetics of the diuretic and antihypertensive agent 4-anilino-2-methylthiopyrido[2,3-d]pyrimidine (MD-39-AM) following a single i.v. or oral administration to male rats at 6-24 mg/kg was studied.The plasma levels vs. time plots were described by an open two-compartment model.The drug was rapidly absorbed and peak concentrations in plasma were reached within 1 h after a single oral administration.The absolute bioavailability calculated on the basis of AUC_0-∞ was estimated to be ∼90%.Plasma levels suggested that the product kinetics was dose-dependent.

Arzneimittel-Forschung

Diuretic and hypotensive activities of 4-anilino derivatives of 2-methylthiopyrido[2,3-d]pyrimidines

作者: Fernandez, F. J. ; Martinez-Merino, V. ; Sammartin, C. ; Monge, A. ; Artigas, P. ; Bellver, C. ; Ochoa, M. C.

The synthesis of a series of 12 compounds referring to 4-anilino-2-methylthiopyrido [2,3-d]pyrimidines (I; R = H, Bu, OMe, OH, Cl, NO₂, etc.), and the results of a study of their diuretic, saliuretic and antihypertensive activities are reported.Most of this compounds showed significant diuretic activity at the dosage of 3-324 mg/kg.I (R = H) remained active to a dosage of 1 mg/kg.The diuretic activity of these compounds implied an increase in the Na⁺ excretion.Some of the most active diuretics have been studied for antihypertensive effect.

100 项与 MD-39-AM 相关的药物交易

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