Hypertensive disease is not by chance considered to be one of the main problems in current medicine. This is not simply a disease, but it intrinsically decreases the quality of human life. Unfortunately, it is also a factor triggering a cascade of many pathological changes in various organs and tissues and leads to a whole series of other illnesses and pathological conditions, which contribute to widespread complications and a sharp increase in mortality. In the last decade, diuretics have secured a place in the treatment of arterial hypertension and chronic heart failure. Although being not strictly antihypertensive medicines, they lead to the elimination of a large amount of liquid from the organism thus lowering arterial pressure to a physiological norm [2, 3]. Indapamide is a particularly widely used medicine amongst this pharmacological group [4][5][6][7][8][9]. Our interest in this medicine is due not only to its biological properties. Its known structure [10] is a 2-methylindoline derivative. Quite recently, compounds with a high diuretic activity and clear antihypertensive and antiedematous properties have been found amongst 1-hydroxy-3-oxo-5,6-dihydro-3H-pyrrolo[3,2,1-ij]quinoline-2-carboxamides [11] structurally based on an unsubstituted indoline. From this there arose the idea of including methylated analogs of the above mentioned pyrroloquinolines into our search for novel diuretic compounds.
A comparative analysis of the effect of halo-substituted anilides of 6-hydroxy-4-oxo-2,4-dihydro-1H-pyrrolo[3,2,1-ij]quinoline-5-carboxylic acids on the urinary function of the kidney has shown that methylation of the pyrroline ring at position 2 leads to an increased diuretic effect. As a method for improving the pharmacological properties of this class of compounds, it deserves more detailed attention [2]. The most promising substance or structural leader in the group of unmethylated derivatives was found to be the 6-hydroxy-4-oxo-2,4-dihydro-1H-pyrrolo[3,2,1-ij]quinoline-5-carboxylic acid 4-methoxyanilide [3]. Hence it was quite logical that the next step in our study should be examination of the corresponding alkoxy-and hydroxyanilides of 6-hydroxy-2-methyl-4-oxo-2,4-dihydro-1H-pyrrolo[3,2,1-ij]quinoline-5-carboxylic acid 1a-j. O OH O OEt N Me O OH O N N H Me R N H 2 R 1a-j 2 1a R = 2-ОH; b R = 3-ОН; c R = 4-ОН; d R = 2-ОМе; e R = 3-ОМе; f R = 4-ОМе; g R = 2-Me-4-OMe; h R = 4-OEt; i R = 4-OPr; j R = 4-OC 6 H 13
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