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.
