Back to results
US 5,631,376 AGranted
Retroviral protease inhibiting compounds
AssigneeAbbott Laboratories
InventorsDaniel W. Norbeck, Hing L. Sham, Dale J. Kempf, Chen Zhao
Life of this patent
Estimating the term…
Abstract
A retroviral protease inhibiting compound of the formula: ##STR1## is disclosed.
Claims10
A compound of the formula:
- ##STR13## wherein R.sub.1 and R.sub.2 are independently selected from:
- (i) hydrogen,
- (ii) loweralkyl,
- (iii) aryl,
- (iv) thioalkoxyalkyl,
- (v) (aryl)alkyl,
- (vi) cycloalkyl,
- (vii) cycloalkylalkyl,
- (viii) hydroxyalkyl,
- (ix) alkoxyalkyl,
- (x) aryloxyalkyl,
- (xi) haloalkyl,
- (xii) carboxyalkyl,
- (xiii) alkoxycarbonylalkyl,
- (xiv) aminoalkyl,
- (xv) (N-protected)aminoalkyl,
- (xvi) alkylaminoalkyl,
- (xvii) ((N-protected)(alkyl)amino)alkyl,
- (xviii) dialkylaminoalkyl,
- (xix) guanidinoalkyl,
- (xx) loweralkenyl,
- (xxi) heterocyclic,
- (xxii) (heterocyclic)alkyl,
- (xxiii) arylthioalkyl,
- (xxiv) arylsulfonylalkyl,
- (xxv) (heterocyclic)thioalkyl,
- (xxvi) (heterocyclic)sulfonylalkyl,
- (xxvii) (heterocyclic)oxyalkyl,
- (xxviii) arylalkoxyalkyl,
- (xxix) arylthioalkoxyalkyl,
- (xxx) arylalkylsulfonylalkyl,
- (xxxi) (heterocyclic)alkoxyalkyl,
- (xxxii) (heterocyclic)thioalkoxyalkyl,
- (xxxiii) (heterocyclic)alkylsulfonylalkyl,
- (xxxiv) cycloalkyloxyalkyl,
- (xxxv) cycloalkylthioalkyl,
- (xxxvi) cycloalkylsulfonylalkyl,
- (xxxvii) cycloalkylalkoxyalkyl,
- (xxxviii) cycloalkylthioalkoxyalkyl,
- (xxxix) cycloalkylalkylsulfonylalkyl,
- (xl) aminocarbonyl,
- (xli) alkylaminocarbonyl,
- (xlii) dialkylaminocarbonyl,
- (xliii) aroylalkyl,
- (xliv) (heterocyclic)carbonylalkyl,
- (xlv) polyhydroxyalkyl,
- (xlvi) aminocarbonylalkyl,
- (xlvii) alkylaminocarbonylalkyl,
- (xlviii) dialkylaminocarbonylalkyl,
- (xlix) aryloxyalkyl and
- (l) alkylsulfonylalkyl,
- Y is ##STR14## a is 0-3;
- c is 1-2;
- R.sub.4 ' is hydrogen or loweralkyl;
- R.sub.4 is selected from:
- (i) hydrogen,
- (ii) loweralkyl,
- (iii) aryl,
- (iv) thioalkoxyalkyl,
- (v) (aryl)alkyl,
- (vi) cycloalkyl,
- (vii) cycloalkylalkyl,
- (viii) hydroxyalkyl,
- (ix) alkoxyalkyl,
- (x) aryloxyalkyl,
- (xi) haloalkyl,
- (xii) carboxyalkyl,
- (xiii) alkoxycarbonylalkyl,
- (xiv) aminoalkyl,
- (xv) (N-protected)aminoalkyl,
- (xvi) alkylaminoalkyl,
- (xvii) ((N-protected)(alkyl)amino)alkyl,
- (xviii) dialkylaminoalkyl,
- (xix) guanidinoalkyl,
- (xx) loweralkenyl,
- (xxi) heterocyclic,
- (xxii) (heterocyclic)alkyl,
- (xxiii) arylthioalkyl,
- (xxiv) arylsulfonylalkyl,
- (xxv) (heterocyclic)thioalkyl,
- (xxvi) (heterocyclic)sulfonylalkyl,
- (xxvii) (heterocyclic)oxyalkyl,
- (xxviii) arylalkoxyalkyl,
- (xxix) arylthioalkoxyalkyl,
- (xxx) arylalkylsulfonylalkyl,
- (xxxi) (heterocyclic)alkoxyalkyl,
- (xxxii) (heterocyclic)thioalkoxyalkyl,
- (xxxiii) (heterocyclic)alkylsulfonylalkyl,
- (xxxiv) cycloalkyloxyalkyl,
- (xxxv) cycloalkylthioalkyl,
- (xxxvi) cycloalkylsulfonylalkyl,
- (xxxvii) cycloalkylalkoxyalkyl,
- (xxxviii) cycloalkylthioalkoxyalkyl,
- (xxxix) cycloalkylalkylsulfonylalkyl,
- (xl) aminocarbonyl,
- (xli) alkylaminocarbonyl,
- (xlii) dialkylaminocarbonyl,
- (xliii) aroylalkyl,
- (xliv) (heterocyclic)carbonylalkyl,
- (xlv) polyhydroxyalkyl,
- (xlvi) aminocarbonylalkyl,
- (xlvii) alkylaminocarbonylalkyl,
- (xlviii) dialkylaminocarbonylalkyl,
- (xlix) aryloxyalkyl and
- (l) alkylsulfonylalkyl,
- wherein heterocyclic is selected from pyridyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, furanyl, thienyl, tetrahydrofuranyl, tetrahydrothienyl and tetrahydro[2H]pyranyl and wherein the heterocyclic is unsubstituted or monosubstituted or disubstituted with substituents independently selected from hydroxy, halo, amino, alkylamino, dialkylamino, alkoxy, polyalkoxy, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, --COOH, --SO.sub.3 H, loweralkenyl and loweralkyl;
- R.sub.5 and R.sub.6 are --C(T)--G--R.sub.7 wherein at each occurrence T is independently selected from O and S;
- at each occurrence G is independently selected from --CH.sub.2 --, --O--, --S-- and --N(R.sub.8)-- wherein at each occurrence R.sub.8 is independently selected from hydrogen, loweralkyl and cycloalkyl;
- and at each occurrence R.sub.7 is independently selected from:
- (i) heterocyclic and (ii) (heterocyclic)alkyl, wherein at each occurrence the heterocyclic is unsubstituted or monosubstituted or disubstituted with substituents independently selected from hydroxy, halo, amino, alkylamino, dialkylamino, alkoxy, polyalkoxy, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, --COOH, --SO.sub.3 H, loweralkenyl and loweralkyl;
- or a pharmaceutically acceptable salt, ester or prodrug thereof.
108 more elements
A compound of the formula:
- ##STR15## wherein R.sub.1 and R.sub.2 are independently selected from:
- (i) hydrogen,
- (ii) loweralkyl,
- (iii) aryl,
- (iv) thioalkoxyalkyl,
- (v) (aryl)alkyl,
- (vi) cycloalkyl,
- (vii) cycloalkylalkyl,
- (viii) hydroxyalkyl,
- (ix) alkoxyalkyl,
- (x) aryloxyalkyl,
- (xi) haloalkyl,
- (xii) carboxyalkyl,
- (xiii) alkoxycarbonylalkyl,
- (xiv) aminoalkyl,
- (xv) (N-protected)aminoalkyl,
- (xvi) alkylaminoalkyl,
- (xvii) ((N-protected)(alkyl)amino)alkyl,
- (xviii) dialkylaminoalkyl,
- (xix) guanidinoalkyl,
- (xx) loweralkenyl,
- (xxi) heterocyclic,
- (xxii) (heterocyclic)alkyl,
- (xxiii) arylthioalkyl,
- (xxiv) arylsulfonylalkyl,
- (xxv) (heterocyclic)thioalkyl,
- (xxvi) (heterocyclic)sulfonylalkyl,
- (xxvii) (heterocyclic)oxyalkyl,
- (xxviii) arylalkoxyalkyl,
- (xxix) arylthioalkoxyalkyl,
- (xxx) arylalkylsulfonylalkyl,
- (xxxi) (heterocyclic)alkoxyalkyl,
- (xxxii) (heterocyclic)thioalkoxyalkyl,
- (xxxiii) (heterocyclic)alkylsulfonylalkyl,
- (xxxiv) cycloalkyloxyalkyl,
- (xxxv) cycloalkylthioalkyl,
- (xxxvi) cycloalkylsulfonylalkyl,
- (xxxvii) cycloalkylalkoxyalkyl,
- (xxxviii) cycloalkylthioalkoxyalkyl,
- (xxxix) cycloalkylalkylsulfonylalkyl,
- (xl) aminocarbonyl,
- (xli) alkylaminocarbonyl,
- (xlii) dialkylaminocarbonyl,
- (xliii) aroylalkyl,
- (xliv) (heterocyclic)carbonylalkyl,
- (xiv) polyhydroxyalkyl,
- (xlvi) aminocarbonylalkyl,
- (xlvii) alkylaminocarbonylalkyl,
- (xlviii) dialkylaminocarbonylalkyl,
- (xlix) aryloxyalkyl and
- (l) alkylsulfonylalkyl,
- wherein heterocyclic is selected from pyridyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, furanyl, thienyl, tetrahydrofuranyl, tetrahydrothienyl and tetrahydro[2H]pyranyl and wherein the heterocyclic is unsubstituted or monosubstituted or disubstituted with substituents independently selected from hydroxy, halo, amino, alkylamino, dialkylamino, alkoxy, polyalkoxy, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, --COOH, --SO.sub.3 H, loweralkenyl and loweralkyl;
- R.sub.4 is selected from:
- (i) hydrogen,
- (ii) loweralkyl,
- (iii) aryl,
- (iv) thioalkoxyalkyl,
- (v) (aryl)alkyl,
- (vi) cycloalkyl,
- (vii) cycloalkylalkyl,
- (viii) hydroxyalkyl,
- (ix) alkoxyalkyl,
- (x) aryloxyalkyl,
- (xi) haloalkyl,
- (xii) carboxyalkyl,
- (xiii) alkoxycarbonylalkyl,
- (xiv) aminoalkyl,
- (xv) (N-protected)aminoalkyl,
- (xvi) alkylaminoalkyl,
- (xvii) ((N-protected)(alkyl)amino)alkyl,
- (xviii) dialkylaminoalkyl,
- (xix) guanidinoalkyl,
- (xx) loweralkenyl,
- (xxi) heterocyclic,
- (xxii) (heterocyclic)alkyl,
- (xxiii) arylthioalkyl,
- (xxiv) arylsulfonylalkyl,
- (xxv) (heterocyclic)thioalkyl,
- (xxvi) (heterocyclic)sulfonylalkyl,
- (xxvii) (heterocyclic)oxyalkyl,
- (xxviii) arylalkoxyalkyl,
- (xxix) arylthioalkoxyalkyl,
- (xxx) arylalkylsulfonylalkyl,
- (xxxi) (heterocyclic)alkoxyalkyl,
- (xxxii) (heterocyclic)thioalkoxyalkyl,
- (xxxiii) (heterocyclic)alkylsulfonylalkyl,
- (xxxiv) cycloalkyloxyalkyl,
- (xxxv) cycloalkylthioalkyl,
- (xxxvi) cycloalkylsulfonylalkyl,
- (xxxvii) cycloalkylalkoxyalkyl,
- (xxxviii) cycloalkylthioalkoxyalkyl,
- (xxxix) cycloalkylalkylsulfonylalkyl,
- (xl) aminocarbonyl,
- (xli) alkylaminocarbonyl,
- (xlii) dialkylaminocarbonyl,
- (xliii) aroylalkyl,
- (xliv) (heterocyclic)carbonylalkyl,
- (xlv) polyhydroxyalkyl,
- (xlvi) aminocarbonylalkyl,
- (xlvii) alkylaminocarbonylalkyl,
- (xlviii) dialkylaminocarbonylalkyl,
- (xlix) aryloxyalkyl and
- (l) alkylsulfonylalkyl,
- wherein heterocyclic is selected from pyridyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, furanyl, thienyl, tetrahydrofuranyl, tetrahydrothienyl and tetrahydro[2H]pyranyl and wherein the heterocyclic is unsubstituted or monosubstituted or disubstituted with substituents independently selected from hydroxy, halo, amino, alkylamino, dialkylamino, alkoxy, polyalkoxy, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, --COOH, --SO.sub.3 H, loweralkenyl and loweralkyl;
- R.sub.5 and R.sub.6 are --C(T)--G--R.sub.7 wherein at each occurrence T is independently selected from O and S;
- at each occurrence G is independently selected from --CH.sub.2 --, --O--, --S-- and --N(R.sub.8)-- wherein at each occurrence R.sub.8 is independently selected from hydrogen, loweralkyl and cycloalkyl;
- and at each occurrence R.sub.7 is independently selected from:
- (i) heterocyclic and (ii) (heterocyclic)alkyl;
- and wherein at each occurrence the heterocyclic is unsubstituted or monosubstituted or disubstituted with substituents independently selected from hydroxy, halo, amino, alkylamino, dialkylamino, alkoxy, polyalkoxy, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, --COOH, --SO.sub.3 H, loweralkenyl and loweralkyl;
- or
- a pharmaceutically acceptable salt, ester or prodrug thereof.
108 more elements
A compound of the formula:
- ##STR16## wherein R.sub.1 and R.sub.2 are independently selected from:
- (i) loweralkyl,
- (ii) aryl,
- (iii) (aryl)alkyl,
- (iv) cycloalkylalkyl,
- (v) heterocyclic and
- (vi) (heterocyclic)alkyl,
- wherein heterocyclic is selected from pyridyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, furanyl, thienyl, tetrahydrofuranyl, tetrahydrothienyl and tetrahydro[2H]pyranyl and wherein the heterocyclic is unsubstituted or monosubstituted or disubstituted with substituents independently selected from hydroxy, halo, amino, alkylamino, dialkylamino, alkoxy, polyalkoxy, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, --COOH, --SO.sub.3 H, loweralkenyl and loweralkyl;
- R.sub.4 is loweralkyl;
- and
- R.sub.5 and R.sub.6 are --C(O)--G--R.sub.7 wherein at each occurrence G is independently selected from --O--, --S-- and --N(R.sub.8)-- wherein at each occurrence R.sub.8 is independently selected from hydrogen, loweralkyl and cycloalkyl;
- and at each occurrence R.sub.7 is independently selected from (heterocyclic)alkyl wherein at each occurrence the heterocyclic is unsubstituted or monosubstituted or disubstituted with substituents independently selected from hydroxy, halo, amino, alkylamino, dialkylamino, alkoxy, polyalkoxy, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl,--COOH, --SO.sub.3 H, loweralkenyl and loweralkyl;
- or
- a pharmaceutically acceptable salt, ester or prodrug thereof.
11 more elements
A compound of the formula:
- ##STR17## wherein R.sub.1 and R.sub.2 are independently selected from:
- (i) cyclohexylmethyl,
- (ii) benzyl,
- (iii) substituted benzyl wherein the phenyl ring of the benzyl group is
- substituted with loweralkyl, halo, alkoxy, amino, alkylamino or dialkylamino, and
- (vi) (heterocyclic)alkyl,
- wherein heterocyclic is selected from pyridyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, furanyl, thienyl, tetrahydrofuranyl, tetrahydrothienyl and tetrahydro[2H]pyranyl and wherein the heterocyclic is unsubstituted or monosubstituted or disubstituted with substituents independently selected from hydroxy, halo, amino, alkylamino, dialkylamino, alkoxy, polyalkoxy, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, --COOH, --SO.sub.3 H, loweralkenyl and loweralkyl;
- R.sub.4 is loweralkyl;
- and
- R.sub.5 is --C(O)--G--R.sub.7 wherein G is --O-- or --N(CH.sub.3)-- and R.sub.7 is heterocyclicmethyl;
- and
- R.sub.6 is --C(O)--O--CH.sub.2 -heterocyclic;
- or a pharmaceutically acceptable salt, ester or prodrug thereof.
10 more elements
A compound selected from the group consisting of:
- 5S-N-((2-Pyridinyl)methoxycarbonyl)valinylamino-2-((N-3-pyridinyl)methoxyca rbonyl)amino-4S-hydroxy-1,6-diphenyl-2-azahexane;
- and
- 5S-N-((2-Pyridinyl)methoxycarbonyl)-L-valinylamino-2-N-((3-pyridinyl)methox ycarbonyl)amino-4S-hydroxy-1-p-methoxyphenyl-6-phenyl-2-azahexane;
- or a pharmaceutically acceptable salt, ester or prodrug thereof.
1 more element
Dependencies are inferred from the claim text.