4-Bromomethylcoumarins, prepared by the reaction of phenols and 4-bromoethyl acetoacetate, were reacted with primary aromatic amines to yield 4-anilinomethylcoumarins. The spectral properties and antimicrobial activities against five micro-organisms are reported.
The flow of current associated with depolarizations of the giant axon of Loligo has been described in two previous papers (Hodgkin, Huxley & Katz, 1952; Hodgkin & Huxley, 1952). These experiments were concerned with the effect of sudden displacements of the membrane potential from its resting level (V =0) to a new level (V = Vj). This paper describes the converse situation in which the membrane potential is suddenly restored from V = V1 to V = 0. It also deals with certain aspects of the more general case in which V is changed suddenly from V1 to a new value V2. The experiments may be conveniently divided into those in which the period of depolarization is brief compared to the time scale of the nerve and those in which it is relatively long. The first group is largely concerned with movements of sodium ions and the second with movements of potassium ions. METHODS The apparatus and method were similar to those described by Hodgkin et al. (1952). The only new technique employed was that on some occasions two pulses, beginning at the same moment but lasting for different times, were applied to the feedback amplifier in order to give a wave form of the type shown in Fig. 6. The amplitude of the shorter pulse was proportional to V1-V2, while the amplitude of the longer pulse was proportional to V,. The resulting changes in membrane potential consisted of a step of amplitude V1, during the period when the two pulses overlap, followed by a second step of amplitude V,. RESULTS Experiments with relatively brief depotarizations Discontinuities in the sodium current The effect of restoring the membrane potential after a brief period of depolarization is illustrated by Fig. 1. Record A gives the current associated with a maintained depolarization of 41 mV. As in previous experiments, this consisted of a wave of inward current followed by a maintained phase of
The title nucleoside 5 was prepared by a condensation of the silylated heterocycle thieno[2,3-d]pyrimidin-4-one (1) with 1-O-acetyl-2,3,5-tri-O-benzoyl-beta-D-ribofuranose (2a) in the presence of a Lewis acid or with 2,3,5-tri-O-acetyl-D-ribofuranosyl bromide (2b) in the presence of mercuric oxide and mercuric bromide. The site of ribosylation and anomeric configuration of this nucleoside were established by 1H NMR. The synthesis of 3-beta-D-ribofuranosylpyrrolo[2,3-d]pyrimidin-4-one (8), 1-phenyl-5-beta-D-ribofuranosylpyrazolo[3,4-d]pyrimidin-4-one (9), 5-methyl-3-beta-D-ribofuranosylthieno[2,3-d]pyrimidin-4-one (10), and 2-methyl-6-beta-D-ribofuranosyltriazolo[5,4-d]pyrimidin-7-one (11) is also described. The title compound inhibited the growth of murine L-1210 leukemic cells in vitro with an ID50 of 3 X 10(-5)M. The growth inhibition could not be prevented by uridine, cytidine, thymidine, deoxycytidine, cytosine, hypoxanthine, or uridine and hypoxanthine together. On the other hand, inhibition of adenosine kinase by 10(-7) M 5-iodotubercidin prevented the cytotoxic effect. Also a subline of L-1210 cells resistant to several cytotoxic adenosine analogues was also resistant to this nucleoside. Thus it appears that this compound 5 may act as an adenosine analogue.
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