Renin inhibitors, processes for preparing them, methods for using them, and compositions containing them
AssigneeWarner-Lambert Company
InventorsAnnette M. Doherty, Harriet W. Hamilton, John C. Hodges, Joseph T. Repine, Ila Sircar
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Abstract
The invention concerns novel renin-inhibitory peptides which are useful for treating renin-associated hypertension, congestive heart failure, hyperaldosteronism and diseases caused by retroviruses including HTLV-I and -III. Processes for preparing the peptides, novel intermediates useful in the preparation thereof, compositions containing them, and methods of using them are included. Also included is a diagnostic method which uses the compounds to determine the presence of renin-associated hypertension, congestive heart failure, or hyperaldosteronism.
Claims2
A process for the preparation of a peptide of the formula
- A--X--Y--W--U I
- or a pharmaceutically acceptable acid addition salt thereof wherein
- A is ##STR116## wherein R and R' are each independently hydrogen, benzyl or lower alkyl;
- X is PHE, HOMOPHE, TYR, TYR(OMe), CYCLOHEXYLALA, LEU, NAPHTHYLALA, TRP, HIS, or (NMe)PHE;
- Y is GLN, HIS, LEU, PGY, MET, MET(O), MET(O.sub.2), TZA, ALG, PPG, CPM, EMG, BYG, NIA, PHA, ##STR117## wherein B is a carbon chain of from 3 to 6 carbon atoms which is saturated, unsaturated, or acetylenic;
- R and R' are each independently hydrogen, benzyl, or lower alkyl;
- W is STA, CYSTA, PHSTA, CHSTA, ASTA, ACYS, DFSTA, DFKSTA, DFCYS, DFKCYS, DFCHS, DFKCHS;
- and
- U is ##STR118## which comprises reacting at least two equivalents of a sulfamyl chloride with at least one equivalent of amino acid as in X, an inorganic aqueous base and a water-miscible organic solvent to give a sulfamyl-amino acid, followed by coupling of the latter to the -Y-W-U fragment and if desired, converting to a pharmaceutically acceptable acid addition salt thereof.
A process for the preparation of a peptide of the formula
- A--X--Y--W--U I
- or a pharmaceutically acceptable acid addition salt thereof wherein
- A is ##STR119## wherein R and R' are each independently hydrogen, benzyl or lower alkyl;
- x is PHE, HOMOPHE, TYR, TYR(OMe), CYCLOHEXYLALA, LEU, NAPHTHYLALA, TRP, HIS, or (NMe)PHE;
- Y is GLN, HIS, LEU, PGY, MET, MET(O), MET(O.sub.2), TZA, ALG, PPG, CPM, EMG, BYG, NIA, PHA, ##STR120## wherein B is a carbon chain of from 3 to 6 carbon atoms which is saturated, unsaturated, or acetylenic;
- R and R' are each independently hydrogen benzyl or lower alkyl;
- W is STA, CYSTA, PHSTA, CHSTA, ASTA, ACYS, DFSTA, DFKSTA, DFCYS, DFKCYS, DFCHS, DFKCHS;
- and
- U is ##STR121## which comprises reacting at least two equivalents of a sulfamyl chloride with at least one equivalent of amino acid as in X, an inorganic aqueous base and a water-miscible organic solvent to give a sulfamyl-amino acid, followed by coupling of the latter to the --Y--W--U fragment and if desired, converting to a pharmaceutically acceptable acid addition salt thereof.
Dependencies are inferred from the claim text.