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US 6,649,593 B1Granted
Modulators of SREBP processing
AssigneesTularik Inc., Board of Regents, The University of Texas Systems
InventorsJuan C. Jaen, Leping Li, Michael S. Brown, Joseph L. Goldstein, Dong Cheng
Life of this patent
Estimating the term…
Abstract
Compounds, compositions and methods are provided for the inhibition of S1 protease and for the modulation of cholesterol homeostasis in a cell.
Claims12
A compound of the formula:
- R1—C(═O)-Aa1-Aa2-Aa3-R2
- wherein
- R1 is a member selected from the group consisting of (C1-C6)alkyl, aryl(C1-C6)alkyl, aryl, (C1-C6)alkylamino, aryl(C1-C6)alkylamino, (C1-C6)alkoxy, and aryl(C1-C6)alkoxy;
- Aa1 is an amino acid selected from the group consisting of 3-(amidino)phenylglycine, 4-(amidino)phenylglycine, 3-(amidino)phenylalanine, 4-(amidino)phenylalanine, R and K;
- Aa2 is an amino acid selected from the group consisting of S, R and N;
- Aa3 is an amino acid selected from the group consisting of M, V and L;
- R2 is a radical selected from the group consisting of
- wherein
- X is a member selected from the group consisting of O, NH and N—(C1-C4)alkyl;
- the subscript n′ is an integer of from 0 to 4;
- R11 and R12 are members independently selected from the group consisting of H, (C1-C8)alkyl, aryl, and aryl(C1-C6)alkyl;
- or taken together R11 and R12 form a five- to seven-membered ring;
- R13 is a member selected from the group consisting of H, CF3, CH2Y, heteroaryl, CONHR16 and CO2R16;
- wherein Y is a leaving group and R16 is selected from the group consisting of H and (C1-C4)alkyl;
- and
- R14 and R15 are members independently selected from the group consisting of H, (C1-C6)alkyl, aryl, and aryl(C1-C6)alkyl.
13 more elements
A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of the formula:
- R1—C(═O)-Aa1-Aa2-Aa3-R2
- wherein
- R1 is a member selected from the group consisting of (C1-C6)alkyl, aryl(C1-C6)alkyl, aryl, (C1-C6)alkylamino, aryl(C1-C6)alkylamino, (C1-C6)alkoxy, and aryl(C1-C6)alkoxy;
- Aa1 is an amino acid selected from the group consisting of 3-(amidino)phenylglycine, 4-(amidino)phenylglycine, 3-(amidino)phenylalanine, 4-(amidino)phenylalanine, R and K;
- Aa2 is an amino acid selected from the group consisting of S, R and N;
- Aa3 is an amino acid selected from the group consisting of M, V and L;
- R2 is a radical selected from the group consisting of
- wherein
- X is a member selected from the group consisting of O, NH and N—(C1-C4)alkyl;
- the subscript n′ is an integer of from 0 to 4;
- R11 and R12 are members independently selected from the group consisting of H, (C1-C8)alkyl, aryl, and aryl(C1-C6)alkyl;
- or taken together R11 and R12 form a five- to seven-membered ring;
- R13 is a member selected from the group consisting of H, CF3, CH2Y, heteroaryl, CONHR16 and CO2R16;
- wherein Y is a leaving group and R16 is selected from the group consisting of H and (C1-C4)alkyl;
- and
- R14 and R15 are members independently selected from the group consisting of H, (C1-C6)alkyl, aryl, and aryl(C1-C6)alkyl.
13 more elements
Dependencies are inferred from the claim text.