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-.alpha. modulators, and thus are useful in the treatment of various diseases. ##STR00001## wherein the R groups are defined as follows: if any R.sub.3 R.sub.5, R.sub.7, R.sub.8, R.sub.11 R.sub.13 is not hydrogen, R.sub.2 or R.sub.6 or R.sub.9 is not methyl, or R.sub.10 is not CH.sub.2, then R.sub.1 is selected from the group consisting of hydrogen, a halogen, COOH, C.sub.1 C.sub.12 carboxylic acids, C.sub.1 C.sub.12 acyl halides, C.sub.1 C.sub.12 acyl residues, C.sub.1 C.sub.12 esters, C.sub.1 C.sub.12 secondary amides, (C.sub.1 C.sub.12)(C.sub.1 C.sub.12) tertiary amides, (C.sub.1 C.sub.12)(C.sub.1 C.sub.12) cyclic amides, (C.sub.1 C.sub.12) amines, C.sub.1 C.sub.12 alcohols, (C.sub.1 C.sub.12)(C.sub.1 C.sub.12) ethers, C.sub.1 C.sub.12 alkyls, C.sub.1 C.sub.12 substituted alkyls, C.sub.2 C.sub.12 alkenyls, C.sub.2 C.sub.12 substituted alkenyls, and C.sub.5 C.sub.12 aryls. If all R.sub.3 R.sub.5, R.sub.7, R.sub.8, R.sub.11 R.sub.13 are hydrogen, R.sub.2, R.sub.6, and R.sub.9 are each methyl, and R.sub.10 is CH.sub.2, then R.sub.1 is selected from hydrogen, a halogen, C.sub.1 C.sub.12 carboxylic acids, C.sub.1 C.sub.12 acyl halides, C.sub.1 C.sub.12 acyl residues, C.sub.2 C.sub.12 esters, C.sub.2 C.sub.12 secondary amides, (C.sub.1 C.sub.12)(C.sub.1 C.sub.12) tertiary amides, C.sub.2 C.sub.12 alcohols, (C.sub.1 C.sub.12)(C.sub.1 C.sub.12) ethers other than methyl-acetyl ether, C.sub.2 C.sub.12 alkyls, C.sub.1 C.sub.12 substituted alkyls, C.sub.2 C.sub.12 alkenyls, C.sub.2 C.sub.12 substituted alkenyls, and C.sub.2 C.sub.12 aryls. R.sub.2 and R.sub.9 are each separately selected from hydrogen, a halogen, C.sub.1 C.sub.12 alkyl, C.sub.1 C.sub.12 substituted alkyls, C.sub.2 C.sub.12 alkenyl, C.sub.2 C.sub.12 substituted alkenyl, C.sub.2 C.sub.12 alkynyl, C.sub.1 C.sub.12 acyl, C.sub.1 C.sub.12 alcohol, and C.sub.5 C.sub.12 aryl. R.sub.3 R.sub.5, R.sub.7, R.sub.8, and R.sub.11 R.sub.13 are each separately selected from hydrogen, a halogen, C.sub.1 C.sub.12 alkyl, C.sub.1 C.sub.12 substituted alkyls, C.sub.2 C.sub.12 alkenyl, C.sub.2 C.sub.12 substituted alkenyl, C.sub.2 C.sub.12 alkynyl, and C.sub.5 C.sub.12 aryl. R.sub.6 is selected from hydrogen, a halogen, C.sub.1 C.sub.12 alkyl, C.sub.1 C.sub.12 substituted alkyls, C.sub.2 C.sub.12 alkenyl, C.sub.2 C.sub.12 substituted alkenyl, and C.sub.2 C.sub.12 alkynyl. R.sub.10 is selected from hydrogen, a halogen, CH.sub.2, C.sub.1 C.sub.6 alkyl, C.sub.1 C.sub.6 substituted alkyl, C.sub.2 C.sub.6 alkenyl, C.sub.2 C.sub.6 substituted alkenyl, C.sub.1 C.sub.12 alcohol, and C.sub.5 C.sub.12 aryl. 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.

Nereus Pharmaceuticals, Inc.

The Regents of the University of California

Interleukin-1 and tumor necrosis factor-.alpha. modulators, synthesis of said modulators and their enantiomers and methods of using said modulators

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-.alpha. modulators, and thus are useful in the treatment of various diseases. ##STR00001## wherein the R groups are defined as follows: if any R.sub.3-R.sub.5, R.sub.7, R.sub.8, R.sub.11-R.sub.13 is not hydrogen, R.sub.2 or R.sub.6 or R.sub.9 is not methyl, or R.sub.10 is not CH.sub.2, then R.sub.1 is selected from the group consisting of hydrogen, a halogen, COOH, C.sub.1-C.sub.12 carboxylic acids, C.sub.1-C.sub.12 acyl halides, C.sub.1-C.sub.12 acyl residues, C.sub.1-C.sub.12 esters, C.sub.1-C.sub.12 secondary amides, (C.sub.1-C.sub.12)(C.sub.1-C.sub.12) tertiary amides, (C.sub.1-C.sub.12)(C.sub.1-C.sub.12) cyclic amides, (C.sub.1-C.sub.12) amines, C.sub.1-C.sub.12 alcohols, (C.sub.1-C.sub.12)(C.sub.1-C.sub.12) ethers, C.sub.1-C.sub.12 alkyls, C.sub.1-C.sub.12 substituted alkyls, C.sub.2-C.sub.12 alkenyls, C.sub.2-C.sub.12 substituted alkenyls, and C.sub.5-C.sub.12 aryls. If all R.sub.3-R.sub.5, R.sub.7, R.sub.8, R.sub.11-R.sub.13 are hydrogen, R.sub.2, R.sub.6, and R.sub.9 are each methyl, and R.sub.10 is CH.sub.2, then R.sub.1 is selected from hydrogen, a halogen, C.sub.1-C.sub.12 carboxylic acids, C.sub.1-C.sub.12 acyl halides, C.sub.1-C.sub.12 acyl residues, C.sub.2-C.sub.12 esters, C.sub.2-C.sub.12 secondary amides, (C.sub.1-C.sub.12)(C.sub.1-C.sub.12) tertiary amides, C.sub.2-C.sub.12 alcohols, (C.sub.1-C.sub.12)(C.sub.1-C.sub.12) ethers other than methyl-acetyl ether, C.sub.2-C.sub.12 alkyls, C.sub.1-C.sub.12 substituted alkyls, C.sub.2-C.sub.12 alkenyls, C.sub.2-C.sub.12 substituted alkenyls, and C.sub.2-C.sub.12 aryls. R.sub.2 and R.sub.9 are each separately selected from hydrogen, a halogen, C.sub.1-C.sub.12 alkyl, C.sub.1-C.sub.12 substituted alkyls, C.sub.2-C.sub.12 alkenyl, C.sub.2-C.sub.12 substituted alkenyl, C.sub.2-C.sub.12 alkynyl, C.sub.1-C.sub.12 acyl, C.sub.1-C.sub.12 alcohol, and C.sub.5-C.sub.12 aryl. R.sub.3-R.sub.5, R.sub.7, R.sub.8, and R.sub.11-R.sub.13 are each separately selected from hydrogen, a halogen, C.sub.1-C.sub.12 alkyl, C.sub.1-C.sub.12 substituted alkyls, C.sub.2-C.sub.12 alkenyl, C.sub.2-C.sub.12 substituted alkenyl, C.sub.2-C.sub.12 alkynyl, and C.sub.5-C.sub.12 aryl. R.sub.6 is selected from hydrogen, a halogen, C.sub.1-C.sub.12 alkyl, C.sub.1-C.sub.12 substituted alkyls, C.sub.2-C.sub.12 alkenyl, C.sub.2-C.sub.12 substituted alkenyl, and C.sub.2-C.sub.12 alkynyl. R.sub.10 is selected from hydrogen, a halogen, CH.sub.2, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 substituted alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.2-C.sub.6 substituted alkenyl, C.sub.1-C.sub.12 alcohol, and C.sub.5-C.sub.12 aryl. 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.

Disclosed herein are novel tricyclic diterpene compounds. These compounds, including their prodrug esters and acid-addition salts, are useful as Interleukin-1 and Tumor Necrosis Factor-.alpha. modulators, and thus are useful in the treatment of various diseases.Also disclosed are pharmaceutical compositions comprising a therapeutically effective amount of the novel compounds that are useful as 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 the compounds and their analogs are also disclosed, as are methods of using these synthetic and semi-synthetic compounds in the treatment of the above-listed disease states.

analgesic/necrosis

Interleukin-1 and tumor necrosis factor-.alpha. modulators, synthesis of said modulators and their enantiomers and methods of using said modulators

Interleukin-1 and tumor necrosis factor-.alpha. modulators, synthesis of said modulators and their enantiomers and methods of using said modulators

Tricyclic diterpene derivatives

科学に裏打ちされた最も完全な薬草データベース