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US 6,187,771 B1Granted
Tricyclic compounds for the inhibition of the ICE/ced-3 protease family of enzymes
AssigneeIdun Pharmaceuticals, Inc.
InventorsDonald S. Karanewsky, Steven D. Linton
Life of this patent
Estimating the term…
Abstract
This invention is directed to novel tricyclic ICE/ced-3 family inhibitor compounds. The invention is also directed to pharmaceutical compositions of such tricyclic compounds, plus the use of such compositions in the treatment of patients suffering inflammatory, autoimmune and neurodegenerative diseases, and for the prevention of ischemic injury.
Claims27
A method for treating an autoimmune disease comprising administering an effective amount of a compound, or a pharmaceutical composition containing the compound, to a patient in need of such treatment, wherein the compound has the following formula:
- wherein:
- n is 1 or 2;
- m is 1 or 2;
- A is R2CO—, R3—O—CO—, or R4SO2—,
- or a group of the formula:
- R1 is a hydrogen atom, alkyl or phenylalkyl,
- R2 is alkyl, cycloalkyl, (cycloalkyl)alkyl, phenyl, phenylalkyl, substituted phenyl, (mono- or di-substituted phenyl)alkyl, five- or six-membered heteroaryl, or (five- or six-membered heteroaryl)alkyl;
- R3 is alkyl, cycloalkyl (cycloalkyl)alkyl, phenylalkyl, or (mono- or di-substituted phenyl)alkyl;
- R4 is alkyl, cycloalkyl, (cycloalkyl)alkyl, phenyl, phenylalkyl, substituted phenyl, (mono- or di-substituted phenyl)alkyl, five- or six-membered heteroaryl, or (five- or six-membered heteroaryl)alkyl;
- R5 is alkyl, cycloalkyl, (cycloalkyl)alkyl, phenyl, phenylalkyl, substituted phenyl, (mono- or di-substituted phenyl)alkyl, five- or six-membered heteroaryl, or (five- or six-membered heteroaryl)alkyl;
- R6 is alkyl, cycloalkyl, (cycloalkyl)alkyl, phenylalkyl or (mono- or di-substituted phenyl)alkyl;
- R7 is alkyl, cycloalkyl, (cycloalkyl)alkyl, phenyl, phenylalkyl, substituted phenyl, (mono- or di-substituted phenyl)alkyl, five- or six-membered heteroaryl, or (five- or six-membered heteroaryl)alkyl;
- and
- R8 is an amino acid side chain of a naturally occurring α-amino acid or a non-protein α-amino acid;
- and
- B is a hydrogen atom, a deuterium atom, alkyl, cycloalkyl, (cycloalkyl)alkyl, phenyl, phenylalkyl, substituted phenyl, (mono- or di-substituted phenyl)alkyl, five- or six-membered heteroaryl, (five- or six-membered heteroaryl)alkyl, or halomethyl;
- a group of the formula:
- —CH2XR9;
- a group of the formula:
- —CH2—O—CO— (five- or six-membered heteroaryl);
- or
- a group of the formula:
- —CH2—O—PO—(R10)R11;
- R9 is phenyl, substituted phenyl, phenylalkyl, (mono- or di-substituted phenyl)alkyl, five- or six-membered heteroaryl, or (five- or six-membered heteroaryl)alkyl;
- and X is an oxygen or a sulfur atom;
- and
- R10 and R11 are independently alkyl, cycloalkyl phenyl, substituted phenyl, phenylalkyl, or (mono- or di-substituted phenyl)alkyl;
- or a pharmaceutically-acceptable salt thereof.
25 more elements
A method for treating an inflammatory disease comprising administering an effective amount of a compound, or a pharmaceutical composition containing the compound, to a patient in need of such treatment, wherein the compound has the following formula:
- wherein:
- n is 1 or 2;
- m is 1 or 2;
- A is R2CO—, R3—O—CO—, or R4SO2—,
- or a group of the formula:
- R1 is a hydrogen atom, alkyl or phenylalkyl;
- R2 is alkyl, cycloalkyl, (cycloalkyl)alkyl, phenyl, phenylalkyl, substituted phenyl, (mono- or di-substituted phenyl)alkyl, five- or six-membered heteroaryl, or (five- or six-membered heteroaryl)alkyl;
- R3 is alkyl, cycloalkyl, (cycloalkyl)alkyl, phenylalkyl, or (mono- or di-substituted phenyl)alkyl;
- R4 is alkyl, cycloalkyl, (cycloalkyl)alkyl, phenyl, phenylalkyl, substituted phenyl, (mono- or di-substituted phenyl)alkyl, five- or six-membered heteroaryl, or (five- or six-membered heteroaryl)alkyl;
- R5 is alkyl, cycloalkyl, (cycloalkyl)alkyl, phenyl, phenylalkyl. substituted phenyl, (mono- or di-substituted phenyl)alkyl, five- or six-membered heteroaryl, or (five- or six-membered heteroaryl)alkyl;
- R6 is alkyl, cycloalkyl, (cycloalkyl)alkyl, phenylalkyl, or (mono- or di-substituted phenyl)alkyl;
- R7 is alkyl, cycloalkyl, (cycloalkyl)alkyl, phenyl, phenylalkyl, substituted phenyl, (mono- or di-substituted phenyl)alkyl, five- or six-membered heteroaryl, or (five- or six-membered heteroaryl)alkyl;
- and
- R8 is an amino acid side chain of a naturally occurring α-amino acid or a non-protein α-amino acid;
- and
- B is a hydrogen atom, a deuterium atom, alkyl, cycloalkyl, (cycloalkyl)alkyl, phenyl, phenylalkyl, substituted phenyl, (mono- or di-substituted phenyl)alkyl, five- or six-membered heteroaryl, (five- or six-membered heteroaryl)alkyl, or halomethyl;
- a group of the formula:
- —CH2XR9;
- a group of the formula:
- —CH2—O—CO— (five- or six-membered heteroaryl);
- or
- a group of the formula:
- —CH2—O—PO—(R10)R11;
- R9 is phenyl, substituted phenyl, phenylalkyl, (mono- or di-substituted phenyl)alkyl five- or six-membered heteroaryl, or (five- or six-membered heteroaryl)alkyl;
- and X is an oxygen or a sulfur atom;
- and
- R10 and R11 are independently alkyl, cycloalkyl, phenyl, substituted phenyl, phenylalkyl or (mono- or di-substituted phenyl)alkyl;
- or a pharmaceutically-acceptable salt thereof.
25 more elements
Dependencies are inferred from the claim text.