Inhibition of memapsin 1 cleavage in the treatment of diabetes
AssigneeOklahoma Medical Research Foundation
InventorsJordan Tang, Xiangping Huang, Deborah Downs
Life of this patent
Estimating the term…
Abstract
Proteases such as memapsin-1 are import enzymes, playing roles in a variety of diseases including diabetes. The inventors have developed inhibitors of memapsin 1 and methods of use therefore in the treatment of disease.
Claims31
A method of inhibiting memapsin 1 activity comprising contacting a memapsin 1 enzyme with a compound having a formula selected from:
- wherein R1 is
- wherein R2 is heteroaryl(C≦8), heterocycloalkyl(C≦8), a substituted version of either of these groups, or
- wherein R3 is alkyl(C≦8) or a substituted version thereof;
- wherein R4 is hydrogen, alkyk(C≦8) or substituted alkyl(C≦8);
- wherein:
- R5 is
- wherein:
- R9 is hydrogen or halo;
- R10 is alkyl(C≦4);
- R6 is hydrogen, alkyl(C≦8), aralkyl(C≦8), or a substituted version of either of these groups;
- or a halogen;
- and
- R7 is:
- R8 is hydrogen, alkyl(C≦8), or
- wherein:
- R12 and R13 are each independently hydrogen, alkyl(C≦8), or alkylsulfonyl(C≦8);
- and
- wherein R11 is alkylthio(C≦8) or alkylsulfonyl(C≦8), or a pharmaceutically acceptable salt or tautomer of any of the above formulas.
A method of treating a mammalian subject with type 2 diabetes comprising administering to said subject a compound having a formula selected from:
- wherein R1 is
- wherein R2 is heteroaryl(C≦8), heterocycloalkyl(C≦8), a substituted version of either of these groups, or
- wherein R3 is alkyl(C≦8) or a substituted version thereof;
- wherein R4 is hydrogen, alkykl(C≦8) or substituted alkyl(C≦8);
- wherein:
- R5 is
- wherein:
- R9 is hydrogen or halo;
- R10 is alkyl(C≦4);
- R6 is hydrogen, alkyl(C≦8), aralkyl(C≦8), or a substituted version of either of these groups;
- or a halogen;
- and
- R7 is:
- R8 is hydrogen, alkyl(C≦8), or
- wherein:
- R12 and R13 are each independently hydrogen, alkyl(C≦8), or alkylsulfonyl(C≦8);
- and
- wherein R11 is alkylthio(C≦8) or alkylsulfonyl(C≦8), or a pharmaceutically acceptable salt or tautomer of any of the above formulas.
29-64. (canceled)
A method of increasing pancreatic beta cell mass in a mammalian subject comprising administering to said subject a compound having a formula selected from:
- wherein R1 is
- wherein R2 is heteroaryl(C≦8), heterocycloalkyl(C≦8), a substituted version of either of these groups, or
- wherein R3 is alkyl(C≦8) or a substituted version thereof;
- wherein R4 is hydrogen, alkyl(C≦8) or substituted alkyl(C≦8);
- wherein:
- R5 is
- wherein:
- R9 is hydrogen or halo;
- R10 is alkyl(C≦4);
- R6 is hydrogen, alkyl(C≦8), aralkyl(C≦8), or a substituted version of either of these groups;
- or a halogen;
- and
- R7 is:
- R8 is hydrogen, alkyl(C≦8), or
- wherein:
- R12 and R13 are each independently hydrogen, alkyl(C≦8), or alkylsulfonyl(C≦8);
- and
- wherein R11 is alkylthio(C≦8) or alkylsulfonyl(C≦8), or a pharmaceutically acceptable salt or tautomer of any of the above formulas.
(canceled)
Dependencies are inferred from the claim text.