Interleukin-1 and tumor necrosis factor-α modulators,...

Details Interleukin-1 and tumor necrosis factor-α modulators,... Interleukin-1 and tumor necrosis factor-α modulators,...

2006-10-10

2006-10-10

Davis, Zinna N. (Department: 1625)

Organic compounds -- part of the class 532-570 series

Organic compounds

Carboxylic acid esters

C560S116000, C562S498000, C562S499000

Reexamination Certificate

active

07119223

ABSTRACT:
Novel compounds are disclosed that have the following chemical structures, and prodrug esters and acid-addition salts thereof, that are useful as Interleukin-1 and Tumor Necrosis Factor-α modulators, and thus are useful in the treatment of various diseases.wherein the R groups are defined as follows: if any R3–R5, R7, R8, R11–R13is not hydrogen, R2or R6or R9is not methyl, or R10is not CH2, then R1is selected from the group consisting of hydrogen, a halogen, COOH, C1–C12carboxylic acids, C1–C12acyl halides, C1–C12acyl residues, C1–C12esters, C1–C12secondary amides, (C1–C12)(C1–C12) tertiary amides, (C1–C12)(C1–C12) cyclic amides, (C1–C12) amines, C1–C12alcohols, (C1–C12)(C1–C12) ethers, C1–C12alkyls, C1–C12substituted alkyls, C2–C12alkenyls, C2–C12substituted alkenyls, and C5–C12aryls. If all R3–R5, R7, R8, R11–R13are hydrogen, R2, R6, and R9are each methyl, and R10is CH2, then R1is selected from hydrogen, a halogen, C1–C12carboxylic acids, C1–C12acyl halides, C1–C12acyl residues, C2–C12esters, C2–C12secondary amides, (C1–C12)(C1–C12) tertiary amides, C2–C12alcohols, (C1–C12)(C1–C12) ethers other than methyl-acetyl ether, C2–C12alkyls, C1–C12substituted alkyls, C2–C12alkenyls, C2–C12substituted alkenyls, and C2–C12aryls. R2and R9are each separately selected from hydrogen, a halogen, C1–C12alkyl, C1–C12substituted alkyls, C2–C12alkenyl, C2–C12substituted alkenyl, C2–C12alkynyl, C1–C12acyl, C1–C12alcohol, and C5–C12aryl. R3–R5, R7, R8, and R11–R13are each separately selected from hydrogen, a halogen, C1–C12alkyl, C1–C12substituted alkyls, C2–C12alkenyl, C2–C12substituted alkenyl, C2–C12alkynyl, and C5–C12aryl. R6is selected from hydrogen, a halogen, C1–C12alkyl, C1–C12substituted alkyls, C2–C12alkenyl, C2–C12substituted alkenyl, and C2–C12alkynyl. R10is selected from hydrogen, a halogen, CH2, C1–C6alkyl, C1–C6substituted alkyl, C2–C6alkenyl, C2–C6substituted alkenyl, C1–C12alcohol, and C5–C12aryl. Pharmaceutical compositions comprising, and uses of, therapeutically effective amounts of the aove compounds and their prodrug esters, and a pharmaceutically acceptable carrier, are also disclosed, and are useful as, for example, anti-inflammatory analgesics, in treating immune disorders, as anti-cancer and anti-tumor agents, and in the treatment of cardiovascular disease, skin redness, and viral infection. Completely synthetic and semi-synthetic methods of making these compounds and their analogs, are also disclosed.

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