Delving into the Latest Updates on RPH-3048 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

Potassium

Mechanism

Potassium modulators(Potassium modulators)

Therapeutic Areas

Cardiovascular Diseases

Active Indication-

Inactive Indication

Heart FailureHypertension

Originator Organization

Röhm GmbH

Active Organization-

Inactive Organization

Röhm GmbH

Drug Highest PhaseDiscontinuedPreclinical

First Approval Date-

Regulation-

Structure

Molecular FormulaC13H14N8O2S

InChIKeyJPTJKCDJKMOCBI-UHFFFAOYSA-N

CAS Registry142731-14-4

2,4,7-Triamino-6-(4-methanesulfonamidophenyl) pteridine (RPH 3048) is a new acidic triamterene derivative. Relevant physico-chemical constants were determined (solubility at pH 7.4 = 3.7 mg/l; logP at pH 7.4 = 0.2) and pharmacokinetic as well as pharmacodynamic properties were investigated, using male Wistar rats. After intravenous application of the test substances urine was collected, its volume and electrolyte composition determined, and the urine recovery of the drugs was analysed. The comparison of RPH 3048 with triamterene (CAS 396-01-0) revealed almost equipotent natriuretic and potassium-retaining effects for both drugs and an additional relative magnesium-sparing activity of RPH 3048. The urine recovery of RPH 3048 after 6 h was higher (20.6%) than that of triamterene (12.9%). No metabolite of RPH 3048 could be detected in the urine whereas a triamterene metabolite was found. Due to its good solubility in alkaline medium RPH 3048 could be dissolved (at pH 11-12) and then administered intravenously together with a loop diuretic (furosemide). Urinary electrolyte excretion following administration of two different combinations of RPH 3048 and furosemide (combination A: 12.5 mumol/kg RPH 3048 and 25 mumol/kg furosemide; combination B: 25 mumol/kg RPH 3048 and 25 mumol/kg furosemide) was compared to urinary electrolyte excretion of a control group and a group only treated with furosemide (25 mumol/kg). The additional application of RPH 3048 reduced in both groups potassium and magnesium excretion to control level but did not compromise furosemide induced natriuresis. In contrast to earlier investigations these results suggest that it is possible to develop acidic triamterene derivatives with potent antikaliuretic effects.

100 Deals associated with RPH-3048

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