Pyridylfuran and pyridylthiophene compounds

Abstract

A compound of the formula: and its pharmaceutically effective salts, wherein R 1 and R 2 are independently selected from the following: (a) hydrogen, halo, R 5 —, C 2-6 alkenyl, C 2-6 alkynyl, hydroxy-R 5 —, R 5 —O—R 5 —, or the like; (b) Ar—, Ar—R 5 —, Ar—C 2-6 alkenyl, Ar—C 2-6 alkynyl, Ar—O—, Ar—O—R 5 — or the like; (c) R 5 —C(O)—, —NO 2 , cyano, NH 2 —C(O)—, R 5 —NH—C(O)—, (R 5 ) 2 —N—C(O)—, Ar—C(O)— or the like; and (d) R 5 —C(O)—NH—, Ar—C(O)—NH— or the like; wherein Ar is optionally substitued aryl or heteroaryl such as phenyl and pyridyl; and wherein R 5 is optionally halo-substituted C 1-6 alkyl; R 3 is selected from the following: (e) cyano, formyl, tetrazolyl, triazolyl, imidazolyl, oxazolyl, thiazolyl, R 5 —C(O)—, C 2-6 alkenyl-C(O)—, C 2-6 alkynyl-C(O)—, R 5 —C(O)—R 5 —, or the like; (f) R 5 —C(O)—NH—, Ar—C(O)—NH—, or the like; (g) R 5 —S—, R 5 —S(O)—, R 5 —NH—S(O) 2 —, or the like; and (h) Ar—C(O)—, Ar—R 5 —C(O)—, Ar—C 2-6 alkenylene-C(O)— or the like; or two of R 1 , R 2 and R 3 together form a group of the formula -A 1 -B 1 -A 2 - or -A 1 -B 1 -A 3 -B 2 -A 2 - such as cyclic alkyl optionally substitued with oxo; R 4 is hydrogen, halo, R 5 —C(O)— and the like; X is O, S, S(O) or S(O) 2 ; m is 0, 1, 2, 3 or 4. The present invention also provides processes for the preparation thereof, the use thereof in treating cytokine mediated diseases and/or cell adhesion molecule (CAM) mediated diseases and pharmaceutical compositions for use in such therapy.

1 . A compound of the formula:  
       
         
           
           
               
               
           
         
       
       and its pharmaceutically effective salts, wherein 
 R 1  and R 2  are independently selected from the following: 
 (a) hydrogen, halo, R 5 —, R 6 —, C 2-6  alkenyl, C 2-6  alkynyl, hydroxy-R 5 —, R 5 —O—, R 5 —S—, hydroxy-R 6 —, R 5 —O—R 5 —, mercapto-R 5 —, R 5 —S—R 5 —, —NH 2 , R 5 —NH—, R 6 —NH—, (R 5 ) 2 —N— or heterocyclic optionally substituted by one or two substituents selected from C 1-4  alkyl, phenyl and pyridyl;  
 (b) Ar—, Ar—R 5 —, Ar—C 2-6  alkenyl, Ar—C 2-6  alkynyl, Ar—O—, Ar—O—Ar—, Ar—O—Ar—O—, Ar—O—R 5 —, Ar—R 5 —O—, Ar—S—, Ar—R 5 —S—, Ar—NH—, (Ar) 2 —R 5 —, Ar—R 5 —NH—, Ar—R 5 —N(R 5 )— or (Ar) 2 —N—;  
 (c) R 5 —C(O)—, —NO 2 , cyano, NH 2 —C(O)—, R 5 —NH—C(O)—, (R 5 ) 2 —N—C(O)—, Ar—C(O)—, (Ar—R 5 ) 2 —N—C(O)—, Ar—R 3 —C(O)—, Ar—NH—C(O)—, Ar—R 5 —NH—C(O)—, R 5 —S(O) 2 — or R 5 —S(O)—; and  
 (d) R 5 —C(O)—NH—, Ar—C(O)—NH—, Ar—R 5 —C(O)—NH— or H 2 N—C(O)—NH—;  
 
 wherein Ar is aryl or heteroaryl optionally substituted with one or two substituents selected from C 1-4  alkyl, halo-substituted C 1-4  alkyl, halo-substituted C 1-4  alkoxy, C 1-4  alkylthio, nitro, hydroxy, amino and halo; and  
 wherein R 5  is C 1-6  alkyl optionally substituted by up to four halogen atoms and R 6  is C 3-8  cycloalkyl optionally substituted by up to four halogen atoms;  
 R 3  is selected from the following: 
 (e) R 6 , R 5 , cyano, formyl, R 5 —C(O)—, R 6 —C(O)—, C 2-6  alkenyl-C(O)—, C 2-6  alkynyl-C(O)—, R 5 —C(O)—R 5 —, R 6 —C(O)—R 5 —, R 5 —C(O)—R 6 —, R 6 —C(O)—R 6 —, C 2-6  alkenyl-C(O)—R 5 —, C 2-6  alkynyl-C(O)—R 5 —, R 5 —C(O)—C 2-6  alkenylene-, R 5 —C(O)—C 2-6  alkynylene-, R 5 —O—C(O)—R 5 —, R 6 —O—C(O)—R 5 —, R 3 —O—C(O)—C 2-6  alkenylene-, R 5 —O—C(O)—C 2-6  alkynylene-, R 5 —S—C(O)—, R 5 —O—C(O)—, H 2 N—C(O)—, H 2 N—C(O)—R 5 —, R 5 —NH—C(O)—, R 6 —NH—C(O)—, R 5 —NH—C(O)—, R 6 —NH—C(O)—R 5  (R 5 ) 2 —N—C(O)—, (R 5 ) 2 —N—C(O)—R 5 —, H 2 N—C(O)—C 2-6  alkenylene-, R 5 —NH—C(O)—C 2-6  alkenylene-, R 6 —NH—C(O)—C 2-6  alkenylene-, (R 5 ) 2 —N—C(O)—C 2-6  alkenylene-, R 5 —O—R 5 —O—, R 5 —O—R 5 —, HO—R 5 —, R 5 —O—R 6 —, HO—R 6 — or Ar;  
 (f) R 5 —C(O)—NH—, Ar—C(O)—NH—, Ar—R 5 —C(O)—NH—, —NH 2 , R 5 —NH—, (R 5 ) 2 —N—, —R 6 —NH 2 , —R 5 —NH 2 , R 5 —NH—R 5 , R 6 —NH—R 5 —, R 5 —NH—R 6 —, (R 5 ) 2 —N—R 5 —, H 2 N—C(O)—NH—, R 5 —NH—C(O)—NH—, (R 5 ) 2 —N—C(O)—NH—, Ar—NH—C(O)—NH—, (Ar) 2 —N—C(O)—NH—, HO—N═C(R 5 )—, HO—N═C—, HO—N═CH—R 5 —, HO—N═CH—R 6 —, R 5 —C(O)—O—N═CH—, R 5 O—N═CH—, R 6 O—N═CH—, R 5 —N═C(R 5 )—, R 6 O—N═C(R 5 )—, R 3 O—N═C(R 6 )—, R 5 O—N═CH—R 5 —, R 6 O—N═CH—R 5 —, R 5 O—N═CH—R 6 —, R 6 O—N═CH—R 6 —, HO—NH—, R 5 O—NH—, HO—N(R 5 )—, R 5 O—N(R 5 )—, HO—NH—R 5 —, R 5 O—NH—R 5 —, HO—N(R 5 )—R 5 — or R 5 O—N(R 5 )—R 5 —;  
 (g) R 5 —S—, Ar—S—, R 5 —S(O)—, R 5 —NH—S(O) 2 —, R 5 —S(O) 2 —, —S(O) 2 NH 2 , —S(O)NH 2 , R 5 —NH—S(O)—, Ar—S(O)—, Ar—R 5 —S(O)—, Ar—S(O) 2 —, C 2-6  alkenyl-S(O) 2 —, C 2-6  alkynyl-S(O) 2 —, Ar—R 5 —S(O) 2 —, Ar—NH—S(O) 2 —, Ar—R 5 —NH—S(O) 2 —, Ar—NH—S(O)— or Ar—R 5 —NH—S(O)—; and  
 (h) Ar—C(O)—, Ar—R 5 —C(O)—, Ar—C(O)—R 5 —, Ar—C(O)—R 6 —, Ar—C(O)—C 2-6  alkenylene-, Ar—R 5 —C(O)—, Ar—R 5 —C(O)—R 5 —, Ar—R 5 —C(O)—C 2-6  alkenylene-, Ar—C 2-6  alkenylene-C(O)—, Ar—C 2-6  alkynylene-C(O)—, Ar—C 2-6  alkenylene-C(O)—R 5 —, Ar—C 2-6  alkynylene-C(O)—R 5 —, Ar—O—R 5 —C(O)—, Ar—S—R 5 —C(O)—, Ar—R 5 —S—C(O)—, Ar—NH—C(O)—, Ar—R 5 —NH—C(O)—, (Ar) 2 —C 2-6  alkenylene-C(O)—, (Ar) 2 —C 2-6  alkynylene-C(O)—, (Ar) 2 —R 5 —S—C(O)—, (Ar) 2 —N—C(O)— or (Ar) 2 —R 5 —NH—C(O)—;  
 
 wherein Ar, R 5  and R 6  are as defined above; or  
 two of R 1  , R 2  and R 3  together form a group of the formula -A 1 -B 1 -A- 2  or -A 1 -B 1 -A 3 -B 2 -A 2 - which, together with the carbon atoms to which A 1  and A 2  are attached, defines a ring having 4 to 8 ring atoms, the ring optionally being substituted with acetyl, —C(O)—OH, —C(O)—NH 2 , —C(O)—OR 5 , —C(O)—NHR 5 , hydroxy, R 5 —, C 1-4  alkoxy, R 5 —NH—, R 6 —NH—, (R 5 ) 2 N—, piperidino, piperazino, pyrrolidino or Ar, wherein A 1  and A 2  are independently a direct bond or C 1-6  alkylene and A 3  is C 1-4  alkylene and B 1  and B2 are independently a direct bond, O, S, S(O), S(O) 2 , C(O) or NR 5 ;  
 R 4  is selected from the following: 
 (i) hydrogen, halo, R 5 —, hydroxy-R 5 — or R 5 —O—R 5 —; and  
 (j) R 5 —C(O)—, R 5 —O—C(O)— or R 5 —NH—C(O)—; or  
 
 two of R 4  which are attached to adjacent carbon atoms on the pyridine ring complete a fused benzene ring, the benzene ring being optionally substituted with one or two substituents selected from C 1-4  alkyl, halo-substituted C 1-4  alkyl, halo-substituted C 1-4  alkoxy, nitro, hydroxy, amino and halo;  
 wherein R 5  is as defined above;  
 X is O, S, S(O) or S(O) 2 ;  
 m is 0, 1, 2, 3 or 4; and  
 the nitrogen atom of the pyridyl ring attached to the 5-position of the furan or the thiophene ring is optionally replaced by a N oxide group.  
 
     
     
         2 . A compound according to  claim 1 , wherein the heterocyclic is selected from piperidino, piperidinyl, piperazinyl, pyrrolidinyl, imidazolidinyl and morpholino; and the aryl or heteroaryl is selected from phenyl, naphthyl, pyridyl, quinolyl, thienyl, furyl, pyrrolyl, indolyl, benzothienyl and benzofuryl.  
     
     
         3 . A compound according to  claim 2 , wherein R 1  is selected from group (a), (b) and (c); R 2  is selected from group (a), (b) and (c); R 3  is selected from group (e), (f), (g) and (h); and R 4  is selected from group (i); or two of R 1 , R 2  and R 3  together form a group of the formula -A 1 -B 1 -A 2 - or -A 1 -B 1 -A 3 -B 2 -A 2 -; X is O or S; and m is —0, 1 or 2.  
     
     
         4 . A compound according to  claim 3 , wherein R 1  is Ar—O—, Ar—O—Ar—O—, Ar—R 5 —N(R 5 )—, R 5 —S(O) 2 —, R 5 —S(O)—, hydrogen, R 5 —S—, R 5 —O—, heterocyclic selected from piperidino, piperidinyl, piperazinyl and morpholino, the heterocyclic group being optionally substituted by one or two C 1-4  alkyl, phenyl or pyridyl, halo, R 5 —, R 5 —C(O)—or Ar optionally substituted with C 1-4  alkyl, hydroxy, nitro, C 1-4  alkylthio, halo-substituted C 1-4  alkyl, C 1-4  alkoxy or halo; R 2  is hydrogen, halo, R 5 —, Ar— or R 5 —C(O)—, wherein the aryl or heteroaryl ring of Ar is optionally substituted with C 1-4  alkyl, hydroxy, nitro or halo; R 3  is R 5 —, R 5 —C(O)—, Ar, R 5 —NH—C(O)—, R 5 —C(O)—NH—, cyano, formyl, R 5 —O—C(O)—R 5 —, R 5 O—C(O)—, H 2 N—C(O)—, H 2 N—C(O)—R 5 —, HO—N═CH—, R 5 O—N═CH—, R 5 —C(O)—O—N═CH—, HO—NH—R 5 —, Ar—C(O)— or Ar—S(O) 2 —; R 2  and R 3  are at the 4 and 3-positions of the furan or the thiophene ring, respectively; or two of R 1 , R 2  and R 3  together form a group of the formula -A 1 -B 1 -A 2 - or -A 1 -B 1 -A 3 -B 2 -A 2 - which, together with the carbon atoms to which A 1  and A 2  are attached, defines a ring having 5 to 7 ring atoms, the ring optionally being substituted with acetyl, hydroxy, R 5 —, C 1-4  alkoxy, wherein A 1  and A 2  are independently a direct bond or C 1-6  alkylene and A 3  is C 1-4  alkylene and B 1  and B 2  are independently a direct bond, O, S, S(O) or C(O); and m is 0.  
     
     
         5 . A compound according to  claim 4 , wherein R 1  is hydrogen, fluoro, chloro, C 1-4  alkyl, C 1-4  alkylthio, C 1-4 alkyl-C(O)—, phenoxy optionally substituted with one or two fluorine atoms, piperidino, piperazinyl optionally substituted by C 1-4  alkyl, morpholino, halophenoxyphenoxy, phenyl-C 1-4  alkyl-N(C 1-4  alkyl)-, C 1-4  alkyl-S(O) 2 —, phenyl, pyridyl or thienyl, wherein the phenyl, pyridyl or thienyl is optionally substituted with C 1-4  alkyl, C 1-4  alkylthio, C 1-4  alkoxy, hydroxy, trifluoromethyl, fluoro or chloro; R 2  is hydrogen, chloro, fluoro, C 1-4  alkyl, phenyl, pyridyl or C 1-4  alkyl-C(O)—; R 3  is C 1-4  alkyl, fluoro-C 1-4  alkyl, difluoro-C 1-4  alkyl, cyano, C 1-4  alkyl-O—C(O)—C 1-4  alkyl, C 1-4  alkyl-O—C(O)—, H 2 N—C(O)—, H 2 N—C(O)—C 1-4  alkyl, C 1-4  alkyl-NH—C(O)—, C 1-4  alkyl-C(O)—O—N═CH—, C 1-4  alkyl-O—N═CH—, HO—NH—C 1-4  alkyl, HO—N═C—, pyrrolyl-S(O) 2 —, phenyl-C(O)—, formyl, C 1-4  alkyl-C(O)—, phenyl, pyridyl, C 1-4  alkyl-NH—C(O)— or C 1-4  alkyl-C(O)—NH—; -A 1 -B-A 2 - is C 1-6  alkylene-C(O)—C 1-6  alkylene, C 1-6  alkylene-C(O)— or —S—CH(acetyl)-C 1-4  alkylene; and -A 1 -B 1 -A 3 -B 2 -A 2 - is C 1-6  alkylene-S—C(O)—.  
     
     
         6 . A compound according to  claim 5 , wherein R 1  is chloro, methyl, ethyl, phenyl, 4-pyridyl, isopropyl, isobutyl, acetyl, hydrogen, 4-methoxyphenyl, 4-chlorophenyl, 4-trifluorophenyl, 4-fluorophenyl, thienyl, 4-methylthiophenyl, morpholino, 4-methylpiperazinyl, N-benzyl-N-methylamino, phenoxy, 3-(4-fluorophenoxy)-phenoxy, methyl-S(O) 2 —, methylthio, piperidino, 2-fluorophenyl, 2-fluorophenoxy, 2,5-difluorophenoxy or 4-fluorophenoxy; R 2  is hydrogen, methyl, ethyl, acetyl, pyridyl or phenyl; R 3  is methyl, ethyl, pyridyl, acetyl, propanoyl, acetamino, methylaminocarbonyl, 1-hydroxyethyl, methoxycarbonyl, pyrrolinine-1-sulfonyl, cyano, phenyl-C(O)—, formyl, HO—N═C—, CH 3 —C(O)—(CH 2 ) 2 —, (CH 3 ) 2 N—C(O)—(CH 2 ) 2 —, ethoxy-C(O)—(CH 2 ) 2 —, methylamino-C(O)—, CH 3 —C(O)—O—N═CH—, H 2 N—C(O)—, isopropoxy-C(O)—, CH 3 O—N═CH—, difluoromethyl, fluoromethyl, HO—NH—CH 2 — or H 2 N—C(O)—(CH 2 ) 2 —; -A 1 -B-A 2 - is selected form —(CH 2 ) 3 —C(O)—, —(CH 2 ) 2 —C(CH 3 ) 2 —C(O)—, —C(CH 3 ) 2 —(CH 2 ) 2 —C(O)—, —(CH 2 ) 4 —C(O)—, —(CH 2 ) 2 —C(O)—, —S—CH(acetyl)-CH(CH 3 )— and —C(O)—(CH 2 ) 2 —; and -A 1 -B-A 3 -B 2 -A 2 - is —CH 2 —CH(CH 3 )—O—C(O)—.  
     
     
         7 . A compound according to  claim 6 , wherein R 1  is chloro, methyl, ethyl, phenyl, 4-pyridyl, isopropyl, isobutyl or acetyl; R 2  is hydrogen, methyl, ethyl or acetyl; R 3  is methyl, ethyl, pyridyl, acetyl or propanoyl; and -A 1 -B-A 2 - is —(CH 2 ) 2 —C(O)— or —(CH 2 ) 3 —C(O)—.  
     
     
         8 . A compound according to  claim 1 , being one of the following: 
 3-acetyl-2,4-dimethyl-5-(4-pyridyl)furan;    3-methyl-4-oxo-2-(4-pyridyl)-4,5,6,7-tetrahydrobenzofuran;    3-acetyl-4-methyl-2-phenyl-5-(4-pyridyl)furan;    3-acetoamino-2,4-dimethyl-5-(4-pyridyl)furan;    2,4-dimethyl-3-methylaminocarbonyl-5-(4-pyridyl)furan;    4-oxo-2-(4-pyridyl)-3,5,5-trimethyl-4,5,6,7-tetrahydrobenzofuran;    4-oxo-2-(4-pyridyl)-3,7,7-trimethyl-4,5,6,7-tetrahydrobenzofuran;    3-methyl-4-oxo-2-(4-pyridyl)cyclohepteno(b)furan;    3-acetyl-2-isobutyl-4-methyl-5-4-pyridyl)furan hydrochloride;    6,7-dihydro-3,6-dimethyl-2-(4-pyridyl)-furo[3,2-c]pyran-4-one;    3-ethyl-7,7-dimethyl-4-oxo-2-(4-pyridyl)-4,5,6,7-tetrahydrobenzofuran;    7,7-dimethyl-3-phenyl-4-oxo-2-(4-pyridyl)-4,5,6,7-tetrahydrobenzofuran;    2-acetyl-4-methyl-3,5-di(4-pyridyl)thiophene;    2-acetyl-3-methyl-4,5-di(4-pyridyl)thiophene;    3-acetyl-4-methyl-2,5-di(4-pyridyl)thiophene;    4-oxo-2-(4-pyridyl)-4,5,6,7-tetrahydro-benzo(b)thiophene;    3-acetyl-5-chloro-4-methyl-2-(4-pyridyl)thiophene;    3-acetyl-2,4-dimethyl-5-(4-pyridyl)thiophene;    3-acetyl-4-methyl-2-phenyl-5-(4-pyridyl)thiophene;    3-methyl-4-oxo-2-(4-pyridyl)-4,5,6,7-tetrahydrobenzothiophene;    2,5-di(4-pyridyl)-3)-(1-hydroxyethyl)-4-methylthiophene;    1,3-di(4-pyridyl)-5,6-dihydro-4H-cyclopenta(c)thiophen-4-one;    2,5-di(4-pyridyl)-3-methoxycarbonylthiophene;    3-acetyl-2,5-di(4-pyridyl)thiophene;    2,5-di(4-pyridyl)-3-(pyrrolidine-1-sulfonyl)thiophene;    2,5-di(4-pyridyl)-3-ethyl-4-methylthiophene dihydrochloride;    4-acetyl-3-methyl-2-(4-pyridyl)thiophene;    3-acetyl-2-(4-methoxyphenyl)-4-methyl-5-(4-pyridyl)thiophene hydrochloride;    3-cyano-2,5-di(4-pyridyl)thiophene;    3-acetyl-2-(4-chlorophenyl)-4-methyl-5-(4-pyridyl)thiophene hydrochloride;    3-acetyl-4-methyl-2-(4-trifluoromethylphenyl)-5-(4-pyridyl)thiophene hydrochloride;    3-acetyl-2-(4-fluorophenyl)-4-methyl-5-(4-pyridyl)thiophene;    3-benzoyl-2,5-di(4-pyridyl)thiophene;    2,5-di(4-pyridyl)-4-methylthiophene-3-carbaldehyde;    3-acetyl-4-methyl-5-(4-pyridyl)-2-(3-thienyl)thiophene;    3-acetyl-4-methyl-5-(4-pyridyl)-2-(4-methylthiophenyl)thiophene;    3-acetyl-2-(4-morpholino)-5-(4-pyridyl)thiophene;    3-acetyl-2-(4-methylpiperazin-1-yl)-5-(4-pyridyl)thiophene;    2,5-di(4-pyridyl)-4-methylthiophene-3-carbaldehyde oxime dihydrochloride;    3-acetyl-2-(N-benzyl-N-methylamino)-5-(4-pyridyl)thiophene hydrochloride;    1,3-di(4-pyridyl)-4,5,6,7-tetrahydrobenzo(c)thiophen-4-one;    3-acetyl-2-phenoxy-5-(4-pyridyl)thiophene;    2-acetyl-3,4-dimethyl-5-(4-pyridyl)thieno[2,3-b]thiophene;    3-acetyl-2-{3-(4-fluorophenoxy)phenoxy}-5-(4-pyridyl)thiophene hydrochloride;    1-chloro-3-(4-pyridyl)-4,5,6,7-tetrahydrobenzo(c)thiophen-4-one;    3-methanesulfonyl-1-(4-pyridyl)-4,5,6,7-tetrahydrobenzo(c)thiophen-4-one;    3-methylthio-1-(4-pyridyl)-4,5,6,7-tetrahydrobenzo(c)thiophen-4-one;    [2,5-di-(4-pyridyl)-3-thienyl]butan-3-one;    N,N-dimethyl-3-[2,5-di-(4-pyridyl)-3-thienyl]propionamide;    3-acetyl-2-(1-piperidino)-5-(4-pyridyl)thiophene;    ethyl 3-[2,5-di-(4-pyridyl)-3-thienyl]propionate dihydrochloride;    N-methyl-{2,5-di(4-pyridyl)thiophen-3-yl}carboxamide;    3-(2-fluorophenyl)-1-(4-pyridyl)-5,6-dihydro-4H-cyclopenta(c)thiophene-4-one;    1-chloro-3-(4-pyridyl)-5,6-dihydro-4H-cyclopenta(c)thiophene-4-one;    O-acethyl-2,5-di(4-pyridyl)-4methylthiophene-3-carbaldehyde oxime;    3-acetyl-2-(2-fluorophenoxy)-5-(4-pyridyl)thiophene;    3-acetyl-2-(2,5-difluorophenoxy)-5-(4-pyridyl)thiophene;    3-(4-fluorophenyl)-1-(4-pyridyl)-5,6-dihydro-4H-cyclopenta(c)thiophene-4-one;    2,5-di(4-pyridyl)-3-thiophenecarboxamide;    3-(isopropyloxycarbonyl)-2,5-di(4-pyridyl)thiophene;    O-methyl-2,5-di(4-pyridyl)-4-methylthiophene-3-carbaldehyde oxime dihydrochloride;    3-acetyl-2-(4-fluorophenoxy)-5-(4-pyridyl)thiophene;    1-(4-pyridyl)-3-(3-pyridyl)-5,6-dihydro-4H-cyclopenta(c)thiophene-4-one;    3-difluoromethyl-2,5-di(4-pyridyl)-4-methylthiophene;    2,5-di(4-pyridyl)-3-fluoromethyl-4-methylthiophene;    1-(4-pyridyl)-3-(4-trifluoromethylphenyl)-5,6-dihydro-4H-cyclopenta(c)thiophene-4-one;    1-(4-fluorophenyl)-3-(4-pyridyl)-5,6-dihydro-4H-cyclopenta(c)thiophene-4-one;    3-(N-benzyl-N-methylamino)-1-(4-pyridyl)-5,6-dihydro-4H-cyclopenta(c)thiophene-4-one;    [2,5-di(4-pyridyl)-4-methylthiophen-3-yl]methylhydroxylamine trihydrochloride; and    3-[2,5-di-(4-pyridyl)-3-thienyl]propionamide.    
     
     
         9 . A compound according to  claim 8 , being one of the following: 
 3-acetyl-2,4-dimethyl-5-(4-pyridyl)furan;    3-methyl-4-oxo-2-(4-pyridyl)-4,5,6,7-tetrahydrobenzofuran;    4-oxo-2-(4-pyridyl)-3,7,7-trimethyl-4,5,6,7-tetrahydrobenzofuran;    3-ethyl-7,7-dimethyl-4-oxo-2-(4-pyridyl)-4,5,6,7-tetrahydrobenzofuran;    3-acetyl-4-methyl-2,5-di(4-pyridyl)thiophene;    1,3-di(4-pyridyl)-5,6-dihydro-4H-cyclopenta(c)thiophen-4-one;    2,5-di(4-pyridyl)-3-methoxycarbonylthiophene;    3-acetyl-2,5-di(4-pyridyl)thiophene;    2,5-di(4-pyridyl)-3-ethyl-4-methylthiophene dihydrochloride;    3-acetyl-2-(4-chlorophenyl)-4-methyl-5-(4-pyridyl)thiophene hydrochloride;    3-acetyl-4-methyl-2-(4-trifluoromethylphenyl)-5-(4-pyridyl)thiophene hydrochloride;    3-acetyl-2-(4-fluorophenyl)-4-methyl-5-(4-pyridyl)thiophene:    3-benzoyl-2,5-di(4-pyridyl)thiophene;    2,5-di(4-pyridyl)-4-methylthiophene-3-carbaldehyde;    2,5-di(4-pyridyl)-4-methylthiophene-3-carbaldehyde oxime dihydrochloride;    1,3-di(4-pyridyl)-4,5,6,7-tetrahydrobenzo(c)thiophen-4-one;    3-methylthio-1-(4-pyridyl)-4,5,6,7-tetrahydrobenzo(c)thiophen-4-one;    [2,5-di-(4-pyridyl)-3-thienyl]butan-3-one;    N,N-dimethyl-3-[2,5-di-(4-pyridyl)-3-thienyl]propionamide;    O-acetyl-2,5-di(4-pyridyl)-4-methylthiophene-3-carbaldehyde oxime;    3-(isopropyloxycarbonyl)-2,5-di(4-pyridyl)thiophene;    O-methyl-2,5-di(4-pyridyl)-4-methylthiophene-3-carbaldehyde oxime dihydrochloride;    3-difluoromethyl-2,5-di(4-pyridyl)-4-methylthiophene;    2,5-di(4-pyridyl)-3-fluoromethyl-4-methylthiophene;    [2,5-di(4-pyridyl)-4-methylthiophen-3-yl]methylhydroxylamine trihydrochloride; and    3-(2,5-di-(4-pyridyl)-3-thienyl]propionamide.    
     
     
         10 . A pharmaceutical composition for the treatment of a cytokine-mediated or CAM-mediated disorder or condition in a mammal, which comprises an amount of the compound of  claim 1 , or a pharmaceutically effective salt thereof, that is effective in treating such disorder or condition, and a pharmaceutically acceptable carrier.  
     
     
         11 . A pharmaceutical composition for the treatment of a disorder or condition selected from AIDS, ARC, arthritis, asthma, bone resorption disease, cachexia, cardiovascular disease, cerebral malaria, Crohn's disease, diabetes, fever or myalgia due to infection, gout, graft versus host reaction, inflammation of organs, inflammatory bowel disease, keloid formation, psoriasis, pulmonary inflammatory disease, respiratory distress syndrome, reperfusion injury, rhinitis, scar tissue formation, sepsis, septic shock, silicosis, toxic shock syndrome, transplant rejection, ulcerative colitis, rheumatoid arthritis, osteo arthritis, artherosclerosis, cancer, obesity, allergy, skin diseased, topical inflammatory disease states, viral infection and thrombosis, in a mammal, comprising an amount of the compound of  claim 1 , or a pharmaceutically effective salt thereof, that is effective in treating such disorder or condition, and a pharmaceutically acceptable carrier.  
     
     
         12 . A method for treating a disorder or condition, the treatment of which can be effected or facilitated by reducing or inhibiting a cytokine mediator or CAM mediator of said disorder or condition in a mammal, comprising administering to a mammal in need of such treatment an amount of a compound of  claim 1 , or a pharmaceutically effective salt thereof, that is effective in treating such disorder or condition.  
     
     
         13 . A method of treating a disorder or condition selected from AIDS, ARC, arthritis, asthma, bone resorption disease, cachexia, cardiovascular disease, cerebral malaria, Crohn's disease, diabetes, fever or myalgia due to infection, gout, graft versus host reaction, inflammation of organs, inflammatory bowel disease, keloid formation, psoriasis, pulmonary inflammatory disease, respiratory distress syndrome, reperfusion injury, rhinitis, scar tissue formation, sepsis, septic shock, silicosis, toxic shock syndrome, transplant rejection, ulcerative colitis, rheumatoid arthritis, osteo arthritis, artherosclerosis, cancer, obesity, allergy, skin diseased, topical inflammatory disease states, viral infection and thrombosis, in a mammal, comprising administering to a mammal in need of such treatment an amount of a compound of  claim 1 , or a pharmaceutically effective salt thereof, that is effective in treating such a disorder or condition.