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

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 R–R, R, R, R–Ris not hydrogen, Ror Ror Ris not methyl, or Ris not CH, then Ris selected from the group consisting of hydrogen, a halogen, COOH, C–Ccarboxylic acids, C–Cacyl halides, C–Cacyl residues, C–Cesters, C–Csecondary amides, (C–C)(C–C) tertiary amides, (C–C)(C–C) cyclic amides, (C–C) amines, C–Calcohols, (C–C)(C–C) ethers, C–Calkyls, C–Csubstituted alkyls, C–Calkenyls, C–Csubstituted alkenyls, and C–Caryls. If all R–R, R, R, R–Rare hydrogen, R, R, and Rare each methyl, and Ris CH, then Ris selected from hydrogen, a halogen, C–Ccarboxylic acids, C–Cacyl halides, C–Cacyl residues, C–Cesters, C–Csecondary amides, (C–C)(C–C) tertiary amides, C–Calcohols, (C–C)(C–C) ethers other than methyl-acetyl ether, C–Calkyls, C–Csubstituted alkyls, C–Calkenyls, C–Csubstituted alkenyls, and C–Caryls. Rand Rare each separately selected from hydrogen, a halogen, C–Calkyl, C–Csubstituted alkyls, C–Calkenyl, C–Csubstituted alkenyl, C–Calkynyl, C–Cacyl, C–Calcohol, and C–Caryl. R–R, R, R, and R–Rare each separately selected from hydrogen, a halogen, C–Calkyl, C–Csubstituted alkyls, C–Calkenyl, C–Csubstituted alkenyl, C–Calkynyl, and C–Caryl. Ris selected from hydrogen, a halogen, C–Calkyl, C–Csubstituted alkyls, C–Calkenyl, C–Csubstituted alkenyl, and C–Calkynyl. Ris selected from hydrogen, a halogen, CH, C–Calkyl, C–Csubstituted alkyl, C–Calkenyl, C–Csubstituted alkenyl, C–Calcohol, and C–Caryl. 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.