Renal-selective biphenylmethyl imidazole angiotensin II antagoni

Details Renal-selective biphenylmethyl imidazole angiotensin II antagoni Renal-selective biphenylmethyl imidazole angiotensin II antagoni

1991-12-19

1994-04-12

Higel, Floyd D.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

514398, 514399, 514400, 514215, 5142358, 548251, 548252, 548253, 548254, 5483164, 5483245, 5483251, 5483265, 5483281, 5483335, 5483345, 5483351, 5483381, 5483385, 544370, 544139, A61K 31415, A61K 31495, C06D24104, C06D23354, C06D25704, C06D26530

Patent

active

053026101

ABSTRACT:
Renal-selective compounds are described which, in one embodiment, are prodrugs preferentially converted in the kidney to compounds capable of blocking angiotensin II (AII) receptors. These prodrugs are conjugates formed from two components, namely, a first component provided by an AII antagonist compound and a second component which is capable of being cleaved from the first component when both components are chemically linked within the conjugate. The two components are chemically linked by a bond which is cleaved selectively in the kidney, for example, by an enzyme. The liberated AII antagonist compound is then available to block AII receptors within the kidney. Conjugates of particular interest are glutamyl derivatives of biphenylmethyl 1H-substituted imidazole compounds, of which N-acetyl-L-glutamic acid, 5-[[4'-[2-butyl-4-chloro-5-(hydroxymethyl)-1H-imidazol-1-ylmethyl][1,1'-bi phenyl]-2-yl]carbonyl]hydrazide (shown below) is an example: ##STR1##

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