Method of lowering CRP and reducing systemic inflammation

A method for lowering plasma CRP levels comprising administering to a mammal, in need thereof, an effective amount of a compound of the formula:

• 20
• wherein
• n and m independently are integers from 2 to 9;
• R1, R2, R3, and R4 independently are C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, and R1 and R2 together with the carbon to which they are attached, and R3 and R4 together with the carbon to which they are attached, independently can complete a carbocyclic ring having from 3 to 6 carbons;
• Y1 and Y2 independently are COOH, CHO, tetrazole, and COOR5 where R5 is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, substituted alkyl, alkenyl, or alkynyl;
• and where the alkyl, alkenyl, and alkynyl groups may be substituted with one or two groups selected from halo, hydroxy, C1-C6 alkoxy, and phenyl;
• or a pharmaceutically acceptable salt thereof.

A method for lowering plasma CRP levels comprising administering to a mammal, in need thereof, an effective amount of a pharmaceutical composition comprising a compound of the formula:

• 21
• wherein
• n and m independently are integers from 2 to 9;
• R1, R2, R3, and R4 independently are C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, and R1 and R2 together with the carbon to which they are attached, and R3 and R4 together with the carbon to which they are attached, independently can complete a carbocyclic ring having from 3 to 6 carbons;
• Y1 and Y2 independently are COOH, CHO, tetrazole, and COOR5 where R5 is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, substituted alkyl, alkenyl, or alkynyl;
• and where the alkyl, alkenyl, and alkynyl groups may be substituted with one or two groups selected from halo, hydroxy, C1-C6 alkoxy, and phenyl,
• or a pharmaceutically acceptable salt thereof;
• and a pharmaceutically acceptable diluent, carrier, or excipient.

A method for reducing systemic inflammation comprising administering to a mammal, in need thereof, an effective amount of a compound of the formula:

• 22
• wherein
• n and m independently are integers from 2 to 9;
• R1, R2, R3, and R4 independently are C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, and R1 and R2 together with the carbon to which they are attached, and R3 and R4 together with the carbon to which they are attached, independently can complete a carbocyclic ring having from 3 to 6 carbons;
• Y1 and Y2 independently are COOH, CHO, tetrazole, and COOR5 where R5 is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, substituted alkyl, alkenyl, or alkynyl;
• and where the alkyl, alkenyl, and alkynyl groups may be substituted with one or two groups selected from halo, hydroxy, C1-C6 alkoxy, and phenyl, or a pharmaceutically acceptable salt thereof.

A method for reducing systemic inflammation comprising administering to a mammal, in need thereof, an effective amount of a pharmaceutical composition comprising a compound of the formula:

• 23
• wherein
• n and m independently are integers from 2 to 9;
• R1, R2, R3, and R4 independently are C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, and R1 and R2 together with the carbon to which they are attached, and R3 and R4 together with the carbon to which they are attached, independently can complete a carbocyclic ring having from 3 to 6 carbons;
• Y1 and Y2 independently are COOH, CHO, tetrazole, and COOR5 where R5 is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, substituted alkyl, alkenyl, or alkynyl;
• and where the alkyl, alkenyl, and alkynyl groups may be substituted with one or two groups selected from halo, hydroxy, C1-C6 alkoxy, and phenyl,
• or a pharmaceutically acceptable salt thereof;
• and a pharmaceutically acceptable diluent, carrier, or excipient.

A method of inhibiting proinflammatory cytokine induced CRP production in a mammal comprising administering to a mammal an effective amount of a compound of the formula:

• 24
• wherein
• n and m independently are integers from 2 to 9;
• R1, R2, R3, and R4 independently are C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, and R1 and R2 together with the carbon to which they are attached, and R3 and R4 together with the carbon to which they are attached, independently can complete a carbocyclic ring having from 3 to 6 carbons;
• Y1 and Y2 independently are COOH, CHO, tetrazole, and COOR5 where R5 is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, substituted alkyl, alkenyl, or alkynyl;
• and where the alkyl, alkenyl, and alkynyl groups may be substituted with one or two groups selected from halo, hydroxy, C1-C6 alkoxy, and phenyl,
• or a pharmaceutically acceptable salt thereof.

A method of inhibiting proinflammatory cytokine induced CRP production in a mammal comprising administering to a mammal an effective amount of a pharmaceutical composition comprising a compound of the formula:

• 25
• wherein
• n and m independently are integers from 2 to 9;
• R1, R2, R3, and R4 independently are C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, and R1 and R2 together with the carbon to which they are attached, and R3 and R4 together with the carbon to which they are attached, independently can complete a carbocyclic ring having from 3 to 6 carbons;
• Y1 and Y2 independently are COOH, CHO, tetrazole, and COOR5 where R5 is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, substituted alkyl, alkenyl, or alkynyl;
• and where the alkyl, alkenyl, and alkynyl groups may be substituted with one or two groups selected from halo, hydroxy, C1-C6 alkoxy, and phenyl,
• or a pharmaceutically acceptable salt thereof;
• and a pharmaceutically acceptable diluent, carrier, or excipient.