| 摘要 |
The present invention relates to a process for the preparation of selective renal compounds, which, in one of the embodiments, are pro-drugs that are converted, preferentially in the kidney, into compounds able to block the angiotensin II (AII) receptors. These pro- drugs are conjugates formed from two components, namely, a first component supplied by an AII antagonist compound and a second component which can be cleaved from the first component when both components are chemically bound inside the conjugate. The two components are chemically bound by means of a bond which is selectively cleaved in the kidney, by an enzyme for example. The AII antagonist compound released is then available for blocking the AII receptors in the kidney. Conjugates of particular interest are the glutamyl derivatives of biphenylmethyl- 1H-substituted imidazole compounds, including the 5-[[4'- [2-butyl-4-chloro-5-(hydroxymethyl)-1H-imidazol-1- ylmethyl][1,1'-biphenyl]-2-yl]carbonyl]hydrazide of N- acetyl-L-glutamic acid, of which an example is presented below <IMAGE> Said process involves performing a reaction between the precursors of the first and second residues, in which one of the precursors must contain a reactive acid moiety, and the other precursor must contain a reactive amino moiety, so as to obtain a conjugate which has a cleavable bond, in which any of the precursors of the first and second residues can contain such reactive acid or amino moieties.
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