John Edmund Arrowsmith
Pfizer
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Featured researches published by John Edmund Arrowsmith.
European Journal of Medicinal Chemistry | 1991
David Alker; John Edmund Arrowsmith; Simon F. Campbell; Peter E. Cross
Abstract The preparation of a range of 1,4-dihydropyridine analogues of amlodipine has been undertaken and their calcium antagonist activities on rat aorta have been evaluated. Increasing the size of the C5 ester group dramatically reduces calcium antagonist activity, a trend which would be compatible with the carbonyl group of that ester binding to the DHP receptor. Amlodipine analogues with extended C3 ester substituents also have lower potency than amlodipine, possibly because of disruption of a favourable interaction between the protonated amino group on the 2-substituent and the DHP receptor. Replacement of the 6-methyl substituent in amlodipine by alkoxyalkyl groups or electron-withdrawing groups is also detrimental to calcium antagonist activity.
Annual Reports in Medicinal Chemistry | 1990
John Edmund Arrowsmith; Peter E. Cross
Publisher Summary The cardiac arrhythmia suppression trial (CAST) study is designed to test the hypothesis that the suppressing asymptomatic premature ventricular beats with Class I anti-arrhythmic drugs would prolong the survival. The three drugs studied (encainide, flecainide, and moricizine) are chosen because they already had been shown to suppress the premature ventricular beats in post MI patients. Other anti-arrhythmic drugs, such as quinidine, procainamide, disopyramide mexilitene, and tocainide are not used, because previous studies suggests that they do not suppress arrhythmias as effectively or that the adverse effects precluded their long-term use in most patients. This chapter discusses the CAST study and its implications, and then gives an update on the Class I and Class III agents. The Class I antiarrhythmic agents, pirmenol, cibenzolin, and ethmozine (moricizine); the IC agents, encainide, flecainide, and propafenone; and the IB agents, mexiletine, and tocainide, have been discussed in this chapter. All Class I drugs are Na + channel inhibitors and they decrease the fast inward Na + current; they reduce the conduction velocity (V max ) in those cardiac structures, in which resting potential is negative to −60 mV. The sub-classes differ with respect to their mode of action on Na + channels and in their effects on action potential duration (APD). Class III agents exert their primary anti-arrhythmic activity by prolonging the cardiac action potential duration, and thereby the effective refractory period (ERP) with no effect on conduction. These electrophysiological changes are brought about by the blockade of cardiac potassium channels; this mechanism is not associated with the depression of the contractile function of the heart and may result in a slight enhancement of the contractile force.
Drug Discovery Today | 2012
Paul Morgan; Piet H. van der Graaf; John Edmund Arrowsmith; Doug Feltner; Kira S. Drummond; Craig D. Wegner; Steve D.A. Street
Journal of Medicinal Chemistry | 1986
John Edmund Arrowsmith; Simon F. Campbell; Peter Edward Cross; John Kendrick Stubbs; Roger A. Burges; Donald G. Gardiner; Kenneth J. Blackburn
Archive | 1987
Peter E. Cross; Geoffrey Noel Thomas; John Edmund Arrowsmith
Journal of Medicinal Chemistry | 1990
Peter Edward Cross; John Edmund Arrowsmith; Geoffrey Noel Thomas; Michael Gwilt; Roger A. Burges; Alan J. Higgins
Journal of Medicinal Chemistry | 1989
John Edmund Arrowsmith; Simon F. Campbell; Peter Edward Cross; Roger A. Burges; Donald G. Gardiner
Archive | 1985
John Edmund Arrowsmith; Simon F. Campbell; Peter E. Cross; Roger P. Dickinson
Archive | 1987
John Edmund Arrowsmith; Peter E. Cross; Geoffrey Noel Thomas
Archive | 1990
John Edmund Arrowsmith; Peter E. Cross; Geoffrey Noel Thomas