Claims
- 1. A compound of the formula: ##STR18## wherein X is O Y is C.sub.1 to C.sub.6 alkylene which is unsubstituted or substituted with one or two substituents independently selected from C.sub.1 to C.sub.7 loweralkyl, C.sub.1 to C.sub.7 alkoxy and C.sub.1 to C.sub.7 thioalkoxy; and R.sub.1 is --NHR.sub.2 wherein R.sub.2 is hydrogen, C.sub.1 to C.sub.7 alkanoyl, C.sub.1 to C.sub.7 hydroxyalkyl, formyl, C.sub.1 to C.sub.7 alkoxycarbonyl, aroyl wherein aroyl is --C(O)R.sub.6 wherein R.sub.6 is phenyl, naphthyl, tetrahydronaphthyl, indanyl or indenyl, --C(O)NHR.sub.17 wherein R.sub.17 is hydrogen or C.sub.1 to C.sub.7 loweralkyl, --C(S)NHR.sub.18 wherein R.sub.18 is hydrogen or C.sub.1 to C.sub.7 loweralkyl, --C(.dbd.N--CN)--NHR.sub.19 wherein R.sub.19 is hydrogen or C.sub.1 to C.sub.7 loweralkyl, --C(.dbd.N--CN)--SR.sub.22 wherein R.sub.22 is C.sub.1 to C.sub.7 loweralkyl, ##STR19## --C(O)O-benzyl, --SO.sub.2 NR.sub.26a R.sub.26b wherein R.sub.26a and R.sub.26b are independently selected from C.sub.1 to C.sub.7 loweralkyl or --SO.sub.2 R.sub.27 wherein R.sub.27 is C.sub.1 to C.sub.7 loweralkyl; or a pharmaceutically acceptable salt or prodrug ester thereof.
- 2. The compound of claim 1 wherein X is O and R.sub.1 is --NHR.sub.2 wherein R.sub.2 is hydrogen, C.sub.1 to C.sub.7 hydroxyalkyl, --C(O)NHR.sub.17 wherein R.sub.17 is hydrogen or C.sub.1 to C.sub.7 loweralkyl, --C(S)NHR.sub.18 wherein R.sub.18 is hydrogen or C.sub.1 to C.sub.7 loweralkyl, --C(.dbd.N--CN)--NHR.sub.19 wherein R.sub.19 is hydrogen or C.sub.1 to C.sub.7 loweralkyl, --C(.dbd.N--CN)--SR.sub.22 wherein R.sub.22 is C.sub.1 to C.sub.7 loweralkyl, ##STR20## --C(O)O-benzyl, --SO.sub.2 NR.sub.26a R.sub.26b wherein R.sub.26a and R.sub.26b are independently selected from C.sub.1 to C.sub.7 loweralkyl or --SO.sub.2 R.sub.27 wherein R.sub.27 is C.sub.1 to C.sub.7 loweralkyl.
- 3. A compound selected from the group consisting of:
- N-(3-(2-Hydroxyethyl)amino)propyl) 5(S)-(2(S)-(1(S)-(4-(methoxymethoxy)piperidin-1-yl)carbonyl-2-phenyl)ethoxyhexanamido)-6-cyclohexyl-4(S)-hydroxy-2(S)-isopropylhexanamide;
- N-(3-(Aminocarbonylamino)propyl) 5(S)-2(S)-(1(S)-(4-(methoxymethoxy)piperidin-1-yl)carbonyl-2-phenyl)ethoxyhexanamido)-6-cyclohexyl-4(S)-hydroxy-2(S)-isopropylhexanamide;
- N-(3-(Aminothionylamino)propyl) 5(S)-(2(S)-(1(S)-(4-(methoxymethoxy)piperidin-1-yl)carbonyl-2-phenyl)ethoxyhexanamido)-6-cyclohexyl-4(S)-hydroxy-2(S)-isopropylhexanamide;
- N-(2-amino-2-methylpropyl) 5(S)-(2(S)-(1(S)-(4-(methoxymethoxy)piperidin-1-yl)carbonyl-2-phenyl)ethoxyhexanamido)-6-cyclohexyl-4(S)-hydroxy-2(S)-isopropylhexanamide;
- N-(2-Aminoethyl) 5(S)-(2(S)-(4-(methoxymethoxy)piperidin-1-yl)carbonyl-2-phenyl)ethoxyhexanamido)-6-cyclohexyl-4(S)-hydroxy-2-(S)-isopropylhexanamide;
- N-(4-Aminobutyl) 5(S)-(2(S)-(4-(methoxymethoxy)piperidin-1-yl)carbonyl-2-phenyl)ethoxyhexanamido)-6-cyclohexyl-4(S)-hydroxy-2-(S)-isopropylhexanamide;
- N-(5-Aminopentyl) 5(S)-(2(S)-(4-(methoxymethoxy)piperidin-1-yl)carbonyl-2-phenyl)ethoxyhexanamido)-6-cyclohexyl-4(S)-hydroxy-2-(S)-isopropylhexanamide;
- N-(3-Amino-3-methylbutyl) 5(S)-(2(S)-(1(S)-(4-(methoxymethoxy)piperidin-1-yl)carbonyl-2-phenyl)ethoxyhexanamido)-6-cyclohexyl-4(S)-hydroxy-2(S)-isopropylhexanamide;
- N-(2-Ureido)ethyl 5(S)-(2(S)-(1(S)-(4-(methoxymethoxy)piperidin-1-yl)carbonyl-2-phenyl)ethoxyhexanamido)-6-cyclohexyl-4(S)-hydroxy-2(S)-isopropylhexanamide;
- N-(2-(Thioureido)ethyl 5(S)-(2(S)-(1(S)-(4-(methoxymethoxy)piperidin-1-yl)carbonyl-2-phenyl)ethoxyhexanamido)-6-cyclohexyl-4(S)-hydroxy-2(S)-isopropylhexanamide;
- N-(2-Acetamidoethyl) 5(S)-(2(S)-(1(S)-(4-(methoxymethoxy)piperidin-1-yl)carbonyl-2-phenyl)ethoxyhexanamido)-6-cyclohexyl-4(S)-hydroxy-2(S)-isopropylhexanamide;
- N-(2-(S-Methyl-N'-cyanoisothioureido)ethyl) 5(S)-(2(S)-(1(S)-(4-(methoxymethoxy)piperidin-1-yl)carbonyl-2-phenyl)ethoxyhexanamido)-6-cyclohexyl-4(S)-hydroxy-2(S)-isopropylhexanamide;
- N-(2-(N'-cyanoureido)ethyl) 5(S)-(2(S)-(1(S)-(4-(methoxymethoxy)piperidin-1yl)carbonyl-2-phenyl)ethoxyhexanamido)-6-cyclohexyl-4(S)-hydroxy-2(S)-isopropylhexanamide;
- N-(2-(N-Methyl-N'-cyanoureido)ethyl) 5(S)-(2(S)-(1(S)-(4-(methoxymethoxy)piperidin-1-yl)carbonyl-2-phenyl)ethoxyhexanamido)-6-cyclohexyl-4(S)-hydroxy-2(S)-isopropylhexanamide;
- N-(2-((3-Amino-1H-1,2,4-triazol-5-yl)amino)ethyl) 2(S)-((3-(tert-butyloxycarbonyl)-2,2-dimethyl-4(S)-cyclohexylmethyl-5(S)-oxazolidinyl)methyl)-3-methylbutanamide;
- N-(2-((5-Amino-1,2,4-oxadiazol-5-yl)amino)ethyl) 2(S)-((3-(tert-butyloxycarbonyl)-2,2-dimethyl-4(S)-cyclohexylmethyl-5(S)-oxazolidinyl)methyl)-3methylbutanamide;
- N-(3-(S-Methyl-N'-cyanoisothioureido)propyl) 5(S)-(2(S)-(1(S)-(4-(methoxymethoxy)piperidin-1-yl)carbonyl-2-phenyl)ethoxyhexanamido)-6-cyclohexyl-4(S)-hydroxy-2(S)-isopropylhexanamide;
- N-(3-(N-Methyl-N'-cyanoureido)propyl) 5(S)-(2(S)-(1(S)-(4-(methoxymethoxy)piperidin-1-yl)carbonyl-2-phenyl)ethoxyhexanamido)-6-cyclohexyl-4(S)-hydroxy-2(S)-isopropylhexanamide;
- N-(3-(N'-cyanoureido)propyl) 5(S)-(2(S)-(1(S)-(4-(methoxymethoxy)piperidin-1-yl)carbonyl-2-phenyl)ethoxyhexanamido)-6-cyclohexyl-4(S)-hydroxy-2(S)-isopropylhexanamide;
- N-(3-((3-Amino-1H-1,2,4-triazol-5-yl)amino)propyl) 5(S)-(2(S)-(1(S)-(4-(methoxymethoxy)piperidin-1-yl)carbonyl-2-phenyl)ethoxyhexanamido)-6-cyclohexyl-4(S)-hydroxy-2(S)-isopropylhexanamide; and
- N-(3-((5-Amino-1,2,4-oxadiazol-5-yl)amino)propyl) 2(S)-((3-(tert-butyloxycarbonyl)-2,2-dimethyl-4(S)-cyclohexylmethyl-5(S)-oxazolidinyl)methyl)-3-methylbutanamide;
- or a pharmaceutically acceptable salt or prodrug ester thereof.
- 4. A method for treating hypertension or treating congestive heart failure comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of claim 1.
- 5. A pharmaceutical composition for treating hypertension or congestive heart failure, comprising a pharmaceutical carrier and a therapeutically effective amount of a compound of claim 1.
- 6. A method for inhibiting renin comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of claim 1.
Parent Case Info
This is a division of U.S. patent application Ser. No. 07.736,364, filed Jul. 31, 1991, now U.S. Pat. No. 5,244,910, which is a continuation-in-part of U.S. patent application Ser. No. 568,557, filed Aug. 15, 1990, now abandoned, which is incorporated herein by reference. This is also a continuation-in-part of U.S. patent application Ser. No. 680,811, filed Apr. 9, 1991, now U.S. Pat. No. 5,122,514, which is incorporated herein by reference.
US Referenced Citations (4)
Foreign Referenced Citations (2)
Number |
Date |
Country |
WO9003971 |
Apr 1990 |
WOX |
WO9005531 |
May 1990 |
WOX |
Divisions (1)
|
Number |
Date |
Country |
Parent |
736364 |
Jul 1994 |
|
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
568557 |
Aug 1990 |
|