Diuretic activity

In an interesting application, the charge density at the ring junction in [2,3-d] and [3,4-d] derivatives was related to the diuretic activity of the compounds (79MI21501). 

Isoxazoles (630a) have reported diuretic activity (75JAP(K)7595272), while (630b) have reported hypolipemic activity (77USP4032644) and (630c) have CNS effects. 

H-1 -Benzoxocin, 3,4,5,6-tetrahydro-synthesis, 7, 668 Benzoxocinones synthesis, 7, 669 Benzoxocinones, dihydrosynthesis, 7, 669 Benzpyrinium bromide as pharmaceutical, 1, 158 Benzquinamide as pharmaceutical, 1, 147 Benzthiazide diuretic activity, 3, 1084 Benzthiazuron as herbicide, 1, 188 Benztropine... 

Pyrimido[4,5-d]pyrimidine, 2,4,7-triamino-5-phenyl-diuretic activity, 3, 368... 

Diuretic activity can be retained in the face of replacement of one of the sulfonamide groups by a carboxylic acid or amide. Reaction of the dichlorobenzoic acid, 174, with chlorsulfonic acid gives the sulfonyl chloride, 175 this is then converted to the amide (176). Reaction of that compound with furfuryl ine leads to nucleophilic aromatic displacement of the highly activated chlorine at the 2 position. There is thus obtained the very potent diuretic furosemide (177). ... 

Cyclization of the intermediate, 182, by means of ethyl orthoformate takes a quite different course. The nitrogen on the aromatic ring in this case becomes one of the exocyclic groups to afford the chorazanil (185) a compound that shows diuretic activity. 

The sulfonamide group has been used successfully to confer diuretic activity to both aromatic and simple heterocyclic compounds. 

Methylation of nitrogen at the 2 position also proves to be consistent with diuretic activity. Condensation of 160 with urea affords the heterocycle, 193. Treatment of this compound with methyl iodide and base effects alkylation on the more acidic ring nitrogen (194). Basic hydrolysis then gives the N-methylated aminosulfonamide (195). Condensation of this with chloroacetalde-... 

Tyrosine hydroxylase 1 Thiazide diuretics, a group of drugs with moderate diuretic activity, includes hydrochlorothiazide, chlorthalidone, and xipamide. They decrease active reabsorption of sodium and accompanying chloride by binding to the chloride site of the electroneutral Na+/CF cotransport system in the distal convoluted tubule and inhibiting its action. 

Caffeine is a mild to potent CNS stimulant, with the degree of its stimulating effect dependent on the dose administered. Caffeine stimulates the CNS at all levels, including the cerebral cortex, die medulla, and the spinal cord. Caffeine has mild analeptic (respiratory stimulating) activity. Other actions include cardiac stimulation (which may produce tachycardia), dilatation of coronary and peripheral blood vessels, constriction of cerebral blood vessels, and skeletal muscle stimulation. Caffeine also has mild diuretic activity. 

Figure 46-1. The nephron is the functional unit of the kidney. Note the various tubules, the site of most diuretic activity. The loop of Henle is the site of action for the loop diuretics. Thiazide diuretics ad at the ascending portion of the loop of Henle and the distal tube of the nephron.

Numerousherbai diureticsare available as over-the-counter (OTQ products. Most plants and herbal extracts available as OTCdiureticsare nontoxic. However, most are either ineffective or no more effective than caffeine. The following are selected herbals reported to possess diuretic activity cetery, chicory, sassafras juniper berries St. John s wort, foxglove, horsetail, licorice, dandelion, digital is purpurea, ephedra, hibiscus parsley, and elderberry. 

Hydrazides also containing a metasulfonamide function are known to exhibit diuretic activity. Substitution of an N-aminodihydroindole for the hydrazine is consistent with this activity. Preparation of one such agent is carried out by reaction of 2-methyl-N-aminoindoline (44) with 3-sulfamoyl-4-chlorobenzoyl chloride (45), leading to the diuretic indapamide (46). ... 

Changing the substitution pattern on the carbo-cyclic ring of the benzothiadiazine diuretics is well known to have a marked effect on the qualitative biological activity. Thus, the direct analogue of the diuretic chlorothiazide (199) in which chlorine replaces one sulfonamide group, diazoxide (200), shows negligible diuretic activity instead the compound is a potent antihypertensive vasodilator. 

Galati EM, Tripodo, MM, Trovato A, Miceli N and Monforte MT. 2002. Biological effect of Opuntia ficus-indica (L) Mill (Cactacea) waste matter. Note I diuretic activity. J Ethnopharmacol 79(1) 17—21. 

Affinine (27) shows a little CNS depression and no analgesic, antipyretic, antiedema and diuretic activity (21). Affinisine (16) is a CNS depressant at 50 mg/kg po in the mouse and possesses a moderate analgesic activity and no... 

It has been claimed 635) that the copper complex of Paludrine has antirheumatic and anti-inflammatory properties, and that Paludrine possesses 431) diuretic activity. 

Gefarnate, a mixture of stereoisomers, was shown to lack both water-retaining and diuretic activity, to have no effect on blood pressure, respiration, blood-sugar. 

Pharmacological actions - 5-Alkyl derivatives of (LXVI) are also cited as having diuretic activity [431]. Certain 1,3-dimethyl-6-alkylaminouracils are reported to have diuretic activity similar to that of theophylline [432]. 1,3-Dimethyl-5-ethyl-6-(methylamino)uracil (LXVII) was found to be among the most active of the compounds tested. Diuretic and hypotensive activity are also claimed with anils of 5-amino derivatives, such as (LXVIII) [433]. 

Ureido derivatives of l-alkenyl-3-alkyl-6-aminouracils, such as (LXXI), are reported to have particular activity as appetite inhibitors. They also have anti-secretory, anti-iritic and mild diuretic activities [438]. The related 5-sulphon-amides, such as (LXXII), are said to inhibit the appetite without producing other pharmacological responses such as pressor-depressor, or diuretic effects [439]. 

These compounds competitively inhibit phosphodiesterase, resulting in an increase in cyclic AMP (see Box 14.3) and subsequent release of adrenaline. This leads to the major effects a stimulation of the central nervous system (CNS), a relaxation of bronchial smooth muscle, and induction of diuresis. These effects vary in the three compounds. Caffeine is the best CNS stimulant, and has weak diuretic action. Theobromine has little stimulant action, but has more diuretic activity and also muscle relaxant properties. Theophylline also has low stimulant action and is an effective diuretic, but it relaxes smooth muscle better than caffeine or theobromine. 

One of the side effects noted in the clinical use of the sulfonamide antibacterial agents was a diuretic effect caused by inhibition of the enzyme carbonic anhydrase. Attempts to capitalize on this side effect so as to obtain agents with greatly enhanced diuretic activity first met success when a heterocyclic ring was substituted for the benzene ring of the sulfonamide. Treatment of the hydrazine derivative, 151, with phosgene leads... 

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