Diuretics structure

Muzolimine (710), a 1-substituted 2-pyrazolin-5-one derivative, is a highly active diuretic, differing from the structures of other diuretics since it contains neither a sulfonamide nor a carboxyl group. It has a saluretic effect similar to furosemide and acts in the proximal tubule and in the medullary portion of the ascending limb of the loop of Henle. Pharmacokinetic studies in dogs, healthy volunteers and in patients with renal insufficiency show that the compound is readily absorbed after oral administration (B-80MI40406). 

Cyclopent-2-en-l-one, 2-hydroxy-3-methyl-synthesis, 3, 693 Cyclopentenone, 4-methoxy-formation, 1, 423 Cyclopenthiazide as diuretic, 1, 174 Cyclopent[2,3-d]isoxazol-4-one structure, 6, 975 Cyclophane conformation, 2, 115 photoelectron spectroscopy, 2, 140 [2,2]Cyclophane conformation, 2, 115 Cyclophanes nomenclature, 1, 27 Cyclophosphamide as pharmaceutical, 1, 157 reviews, 1, 496 Cyclopiloselloidin synthesis, 3, 743 Cyclopolymerization heterocycle-forming, 1, 292-293 6H-Cyclopropa[5a,6a]pyrazolo[l,5-a]pyrimidine pyrazoles from, 5, 285 Cydopropabenzopyran synthesis, 3, 700 Cyclopropachromenes synthesis, 3, 671 Cyclopropa[c]dnnolines synthesis, 7, 597 Cyclopropanation by carbenes... 

Each era of medicinal chemistry has been marked by intensive concentration on some structural type in a large number of laboratories. One need only look back in this book to the tables of sulfonamides, barbiturates, and thiazide diuretics, noting the small time span covered by the references to each list. The benzodiazepines have provided such a focus for the past decade. 

Therapeutic Function Diuretic Chemical Name 6-phenyl-2,4,7-pteridinetriamine Common Name Ademine pterophene Structural Formula ... 

Agents acting in the proximal tubule are seldom used to treat hypertension. Treatment is usually initiated with a thiazide-type diuretic. Chlorthalidone and indapamide are structurally different from thiazides but are functionally related. If renal function is severely impaired (i.e., serum creatinine above 2.5 mg/dl), a loop diuretic is needed. A potassium-sparing agent may be given with the diuretic to reduce the likelihood of hypokalemia. 

I have noted that NPPB is structurally related to loop diuretics of the furosemide (Fig. 2) type. These latter compounds bind to the Na 2CNK -cotransporter [16] and inhibit NaCl reabsorption in the TAL segment and NaCl secretion in epithelia such as the colonic crypt cell and rectal gland of Squalus acanthias [15]. We were able to show that only minor modification of the NPPB molecule on one side and of furosemide on the other led to compounds with altered selectivities [70,91-93]. One prototype of an intermediate blocker, i.e., a substance blocking both Na 2Cl K -cotransport and CP-channels, is torasemide (Fig. 2). Hence we have performed a systematic study in order to define the constraints defining the effectiveness of this class of substances [91]. 

The imidazole ring system provides the nucleus for two diuretic agents with structures unusual for that activity. Reaction of the N-cyanoaniline 140 (obtainable from the aniline (139) and cyanogen bromide) with N-methylchloroacetamide leads to the heterocycle 142. The sequence can be rationalized by... 

Ditrimethylolpropane, 2 47 physical properties of, 2 48t Ditungsten boride, 25 386 Ditungsten trisilicide, 25 386 Diucardin, molecular formula and structure, 5 162t Diuloses, 4 711 Diuretics, 22 867 Diuril, 5 168... 

Diazoxide (II) has been known since the early 1960 s (9.) and must be considered as a well known lead. It bears a structural resemblance to the diuretic agent, chlorothiazide (XIX) but, unlike chlorothiazide, it is non-diuretic. Analogs have been prepared by scientists at Schering (10) and by a group in Italy (11). The Italian group reported that compound XX lowers blood pressure and heart rate intravenously in rats but causes... 

Dietary salt restriction was one of the first successful therapeutic maneuvers for the reduction of blood pressure. During the past two decades, a variety of pharmacologic agents have been developed which promote diuresis by interfering with the tubular reabsorption of sodium. Although diuretic agents differ significantly in chemical structure and in their mechanism of action on the renal tubule, they all have in common the ability to decrease blood pressure. 

The thiazide diuretics possess antihypertensive properties, in part consequent upon electrolyte and plasma-volume changes but mainly resulting from a direct cardiovascular depressant effect. This is clearly illustrated by the non-diuretic thiazide, diazoxide, which is an effective hypotensive [326b, c]. It is not therefore, surprising that both these properties should be found (in varying proportions) in other, structurally related, compounds. One particular line of research, aimed at modification of the thiazide heterocycle (the o-chlorobenzenesulphonamide moiety was untouched as it was believed essential to activity-the subsequent advent of ethacrynic acid questions this belieO examined first the corresponding... 

Diuretics, interaction with lithium, 36 65-66 Divalent cations hydration shell, 34 211 structure, 34 210-212... 

Receptors can mediate the action of endogenous signalling compounds and may therefore be viewed as regulatory proteins. Such receptors are the physiological targets for neurotransmitters and hormones. Other types of receptors include enzyme proteins, transport proteins and structural proteins. For example, statins inhibit an enzyme catalysing the synthesis of cholesterol and loop diuretics inhibit an enzyme that facilitates the re-uptake of salt in primary urine. 

Thiazide diuretics consist of two distinct groups those containing a benzothiadiazine ring, such as hydrochlorothiazide and chlorothiazide, referred to as thiazide diuretics, and those that lack this heterocyclic structure but contain an unsubstituted sulfonamide group. The latter are called thiazidelike diuretics they include metolazone, xipamide, and indapamide. The major thiazide and thiazidelike drugs available in the United States are bendrofiumethiazide, benzthiazide, chlorothiazide, hydrochlorothiazide, hydroflumethiazide, methyclothiazide, polythiazide, and trichlormethiazide and chlorthalidone, indapamide, metolazone, and quinethazone, respectively. 

The uricosuric drugs (or urate diuretics) are anions that are somewhat similar to urate in structure therefore, they can compete with uric acid for transport sites. Small doses of uricosuric agents will actually decrease the total excretion of urate by inhibiting its tubular secretion. The quantitative importance of the secretory... 

It is noteworthy that sulfanilamide structural modifications have led to other valuable classes of drugs already discussed, including the hypoglycemic sulfonylureas and the diuretic carbonic anhydrase inhibitors. 

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