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US 6,191,147 B1Granted
Pyrazole compounds and uses thereof
AssigneesPPD Discovery, Inc., Duke University
InventorsBradley B. Brown, Patrick J. Casey, Casey Pritchard Purdy, Zita Latona, Sarah Tavares
Life of this patent
Estimating the term…
Abstract
The present invention is directed to compounds of the formula: and pharmaceutically acceptable salts thereof, to pharmaceutical compositions comprising same, and to methods for inhibiting protein prenylation in an organism using the same, where R1, R2, R3, R4, R5, R6, R7 and X are defined herein.
Claims82
A compound of the formula:
- or a pharmaceutically-acceptable salt thereof, wherein
- X is —NR8R9, —OH, C1-C6 alkoxide, C6-C20 aryloxide, C7-C20 arylalkoxide;
- R1 is H, C5-C20 aryl or C6-C20 arylalkyl;
- R2 is N-heteroaryl or C3-C20 aryl containing at least one nitrogen substituent;
- R3 is H or C1-C6 alkyl;
- R4 is a moiety of the formula —[C(R10R11)]n— or —Ar1—N(R12)—C(═O)—[C(R10R11)]n—;
- R6 is an amino acid side-chain or a derivative thereof;
- R7 is H or C1-C6 alkyl;
- each of R5, R8, R9 and R12 is independently H, C1-C4 alkyl, C6-C20 aryl, an amide protecting group, an amino acid side-chain or a derivative thereof, or a peptide, peptoid or mixtures thereof having 1 to about 5 monomeric residues;
- each of R10 and R11 is independently H, halide or C1-C4 alkyl;
- Ar1 is C5-C20 aryl;
- and
- n is an integer from 0 to 20, provided that when R2 is phenyl containing at least one nitrogen substituent and R4 is —[C(R10R11)]n—, X is —NR8R9.
10 more elements
A pharmaceutical composition comprising:
- (a) a compound of the formula:
- or a pharmaceutically-acceptable salt thereof, wherein
- X is —NR8R9, —OH, C1-C6 alkoxide, C6-C20 aryloxide, C7-C20 arylalkoxide;
- R1 is H, C5-C20 aryl or C6-C20 arylalkyl;
- R2 is N-heteroaryl or C3-C20 aryl containing at least one nitrogen substituent;
- R3 is H or C1-C6 alkyl;
- R4 is a moiety of the formula —[C(R10R11)]n— or —Ar1—N(R12)—C(═O)—[C(R10R11)]n—;
- R6 is an amino acid side-chain or a derivative thereof;
- R7 is H or C1-C6 alkyl;
- each of R5, R8, R9 and R12 is independently H, C1-C4 alkyl, C6-C20 aryl, an amide protecting group, an amino acid side-chain or a derivative thereof, or a peptide, peptoid or mixtures thereof having 1 to about 5 monomeric residues;
- each of R10 and R11 is independently H, halide or C1-C4 alkyl;
- Ar1 is C5-C20 aryl;
- and
- n is an integer from 0 to 20, provided that when R2 is phenyl containing at least one nitrogen substituent and R4 is —[C(R10R11)]n—, X is —NR8R9;
- and
- (b) a pharmaceutically-acceptable carrier.
13 more elements
A method for inhibiting protein prenylation comprising contacting an isoprenoid transferase with a compound of the formula:
- or a pharmaceutically-acceptable salt thereof, wherein
- X is —NR8R9, —OH, C1-C6 alkoxide, C6-C20 aryloxide, C7-C20 arylalkoxide;
- R1 is H, C5-C20 aryl or C6-C20 arylalkyl;
- R2 is N-heteroaryl or C3-C20 aryl containing at least one nitrogen substituent;
- R3 is H or C1-C6 alkyl;
- R4 is a moiety of the formula —[C(R10R11)]n— or —Ar1—N(R12)—C(═O)—[C(R10R11)]n—;
- R6 is an amino acid side-chain or a derivative thereof;
- R7 is H or C1-C6 alkyl;
- each of R5, R8, R9 and R12 is independently H, C1-C4 alkyl, C6-C20 aryl, an amide protecting group, an amino acid side-chain or a derivative thereof, or a peptide, peptoid or mixtures thereof, having about 1 to about 5 monomeric residues;
- each of R10 and R11 is independently H, halide or C1-C4 alkyl;
- Ar1 is C5-C20 aryl;
- and
- n is an integer from 0 to 20, provided that when R2 is phenyl containing at least one nitrogen substituent and R4 is —[C(R10R11)]n—, X is —NR8R9;
- and
- wherein said compound inhibits protein prenylation in said organism.
12 more elements
Dependencies are inferred from the claim text.