Inhibition of interleukin-1 and tumor necrosis factor production by monocytes and/or macrophages

A method of inhibiting the production of interleukin-1 (IL-1) by monocytes and/or macrophages in a human in need thereof which comprises administering to such human an effective, IL-1 production inhibiting amount of a compound of the formula ##STR21## wherein:

• W.sub.1 is --(CR.sub.4 R.sub.5)--(CR.sub.6 R.sub.7)--, --CR.sub.5 .dbd.CR.sub.7 --, --N.dbd.CR.sub.7, --S(O).sub.m -- or --O--;
• n is 0 to 2;
• one of R.sub.1 and R.sub.0 is 4-pyridyl or C.sub.1-4 alkyl-4-pyridyl, provided that when R.sub.1 is C.sub.1-4 alkyl-4-pyridyl the alkyl substituent is located at the 2-position of the pyridine ring, and the other of R.sub.1 and R.sub.0 is
• (a) phenyl or monosubstituted phenyl wherein said substituent is C.sub.1-3 alkylthio, C.sub.1-3 alkylsulfinyl, C.sub.2-5 1-alkenyl-1-thio, C.sub.2-5 1-alkenyl-1-sulfinyl, C.sub.3-5 2-alkenyl-1-thio, C.sub.3-5 2-alkenyl-1-sulfinyl, 1-acyloxy-1-alkylthio, C.sub.1-4 alkyl or Z wherein Z is --S--S--Z.sub.1 and Z.sub.1 is phenyl or C.sub.1-9 alkyl;
• or
• (b) disubstituted phenyl wherein said substituents are, independently, C.sub.1-3 alkylthio or C.sub.1-4 alkyl;
• or
• (c) disubstituted phenyl wherein one of said substituents is C.sub.1-3 alkylsulfinyl, C.sub.2-5 1-alkenyl-1-thio, C.sub.2-5 1-alkenyl-1-sulfinyl, C.sub.3-5 2-alkenyl-1-thio, C.sub.3-5 2-alkenyl-1-sulfinyl or 1-acyloxy-1-alkylthio and the other is C.sub.1-2 alkoxy, halo, or C.sub.1-4 alkyl;
• (d) disubstituted phenyl wherein the substituents are the same and are C.sub.1-3 alkylsulfinyl, C.sub.2-5 1-alkenyl-1-thio, C.sub.2-5 1-alkenyl-1-sulfinyl, C.sub.3-5 2-alkenyl-1-thio, C.sub.3-5 2-alkenyl-1-sulfinyl or 1-acyloxy-1-alkylthio;
• or
• (e) monosubstituted phenyl wherein the substituent is ##STR22## t is 0 or 1;
• W.sub.1 and R.sub.1 are as defined above;
• provided that:
• (1.) when W.sub.1 is --(CR.sub.4 R.sub.5)--(CR.sub.6 R.sub.7)-- then
• n is 0 or 1;
• and
• R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8, and R.sub.9 are, independently, --H or C.sub.1-2 alkyl;
• or
• when n is 0, R.sub.4 and R.sub.5 together form an oxo;
• R.sub.4 and R.sub.5 may both be fluoro, or one of R.sub.4 and R.sub.5 is H and the other is OH;
• or
• (2.) when W.sub.1 is --CR.sub.5 .dbd.CR.sub.7 -- or --N.dbd.CR.sub.7 -- then
• n is 1;
• R.sub.3, R.sub.5, R.sub.7 and R.sub.9 are, independently, --H or C.sub.1-2 alkyl;
• and
• R.sub.2 and R.sub.8 together represent a double bond in the B ring such that the B ring is an aromatic pyridine or pyrimidine ring;
• (3.) when W.sub.1 is S(O).sub.m then
• m is 0, 1 or 2;
• n is 1 or 2;
• and
• R.sub.3 and R.sub.9 are, independently, --H or C.sub.1-2 alkyl;
• R.sub.2 and R.sub.8 are, independently, --H or C.sub.1-2 alkyl or R.sub.2 and R.sub.8 together represent a double bond in the B ring such that the B ring is an aromatic thiazole ring and
• m is 0 and n is 1;
• and
• (4) when W.sub.1 is --O-- then
• n is 1;
• R.sub.3 and R.sub.9 are, independently, --H or C.sub.1-2 alkyl;
• and
• R.sub.2 and R.sub.8 together represent a double bond in the B ring such that the B ring is an aromatic oxazole ring;
• or a pharmaceutically acceptable salt thereof.