Pharmaceutically active compounds

Claim 2

A process for producing a compound represented by the formulas I and II, and pharmaceutically acceptable acid addition, basic addition and quarternary amine salts thereof and pharmaceutically acceptable solvates thereof, wherein each Z is independently tetiary butyl, phenyl, naphthyl or adamantyl; substituted phenyl, wherein the substituents are one or more of halogen, lower alkoxy, phenoxy, nitrile, nitro, phenylsulfonyl, loweralkylsulfonyl, oxazol-2-yl, lower alkanoyl, benzoyl, lower alkoxycarbonyl, lower alkyl, lower alkylthio, phenyl, phenylaminothiocarbonyl, or lower alkylaminothiocarbonyl; 4 to 6 membered unsubstituted or substituted heterocyclic ring containing at least one nitrogen with the remaining members being at least one carbon and optionally sulfur or oxygen, wherein the substituents are one or more of carboxyl, hydroxymethyl, lower alkyl, loweralkylcarbonyl or aryl lower alkyl; X and Y are each independently a bond, -0-, each Q is independently a divalent substituted or unsubstituted, straight or branched chain lower alkanediyl, lower alkanediyl-cycloalkanidiyl-lower alkaneidyl, lower alkanediyl, lower alkynediyl, phenylene, dihydrofurandiyl, tetrahydrofurandiyl, tetrahydropyrandiyl, or, loweralkanediyl-tetrahydrofurandiyl-loweralkanediyl, wherein the substituents are one or more of hydroxy, epoxy, fluorine, chlorine, azide, or amino; W is a monovalent substitued or unsubstituted aryl group or a heterocyclic single or fused ring containing from 4 to 10 ring atoms, at least one hetero atom of which is a nitrogen atom and the remaining ring atoms being at least one carbon and optionally sulfur or oxygen, wherein the substituents are one or more of hydroxy, oxo, amino, carbamoyl, carboxyl, nitrile, nitro, lower alkoxy carbonyl, halogen, sulfamyl, lower alkyl, lower alkylthio, lower aldoxy, hydroxyloweralkyl, lower alkoxycarbonylloweralkyl, amino loweralkyl, carboxyloweralkyl, guanidino, thioureido, lower alkylsulfonylamino, aminocarbonylloweralkyl, allyloxycarbonylmethyl or carbamoyloxyloweralkyl; with the proviso that W cannot be substituted or unsubstituted isoxazolyl, and W' is divalent W, characterized in that either; (A) to produce a compound of formula I, a compound of the formula Z-X-Q'-L wherein Z and X are as defined previously, Q' is the same as Q defined previously, or, provided Q in fomula I is to contain at least one of the groups wherein each R is independently hydrogen or lower alkyl, Q' may also be the same as Q defined previously minus at least one of the groups and L' is a leaving group, with a compound having the formula L 2- Y'-W" wherein L 2 is a leaving group, W" is as defined for W previously or a tautomer thereof, and Y' is the same as Y defined previously, or, provided Q in formula I is to contain at least one of the groups wherein each R is independently hydrogen or loweralkyl, Y' may also be the same as Y defined previously plus at least one of the groups or (B) to produce a compound of formula II and possibly a compound of formula I, at least one compound of the formula Z-X-Q'-L' wherein Z, X. Q', and L' are as defined previously is reacted with a compound of the formula L 3 -Y'-W"'-Y'-L 4 wherein L 3 and L 4 are leaving groups, each Y' is independently as defined above, and W"' is divalent W' as defined above or (C) to produce a compound of formula I, wherein Z and W are the same and X and Y are the same, reacting a compound of the formula L 2 -Y'-W" wherein Y' and W" are as defined in previously and L 2 is a leaving group, with a compound of the formula L 5 -Q"-L 6 wherein L 5 and L 6 are leaving groups and Q" is divalent Q' as defined above, wherein in the above processes, any reactive groups are protected if necessary or desired, the above processes followed if necessary or desired by (i) removal of any protecting groups, (ii) conversion of a compound so produced to another compound of formula I or II, (iii) if more than one compound of formulas I or II is produced, separation of the compounds so produced, or (iv) conversion of any of the compounds so produced to an acid addition, basic addition, or quaternary amine salt or pharmaceutically acceptable solvate thereof.

Claim 3

The process of claim 1 wherein the compound produced has the formula Z 1 -X 1 -Q 1 -W 1 and pharmaceutically acceptable acid addition salts thereof, wherein Q' is lower alkanediyl or 5, 6 or 7 carbons; lower alkynediyl of 6, 7 or 8 carbon atoms: or methylcyclohexylmethyl; W 1 is unsubstituted or substituted imidazol-1-yl, purin-9-yl, imidazol-2-yl, wherein said substituents are one or more of loweralkyl, hydroxyloweralkyl, nitro, loweralkoxycarbonyl, carboxymethyl or aminocarbonyl- methyl; X 1 is and Z 1 is or

Claim 4

The process of claim 1 wherein the compound produced has the formula wherein Ri, R 2 and R 3 are each independently hydrogen, hydroxyloweralkyl or lower alkyl with the proviso that when one of R 2 and R 3 is lower alky, the other is hydrogen.

Claim 5

A process of claim 1 wherein the compound produced as the formula Z 2 -X 2 -Q 2 -Y 2 -W 2 pharmaceutically acceptable acid addition salts or quarternary amine salts thereof, wherein Z 2 is phenyl; substituted phenyl wherein the substituents are independently one or more of halogen, lower alkylthio, loweralkylsulfonyl, lower alkoxy, oxazol-2-yl, phenoxy; imidazo-1-yl; lower alkyl substituted imidazo-1-yl; or tert-butyl; X 2 is a bond. -O-, or -SOr Q 2 is loweralkanediyl of 6 or 7 carbon atoms optionally substituted by -OH; loweralkynediyl of 6 to 8 carbon atoms; or methylcyclohexylmethyl; Y 2 is a bond, -S-or -SOr; W 2 is imidazol-1-yl; substituted imidazol-1-yl wherein the substitutents are independently one or more of lower alkyl, hydroxyloweralkyl, aminoloweralkyl or loweralkyoxycarbonyl; imidazol-2-yl, imidazol-4-yl; imidazol-5-yl; substituted imidazol-2-yl. -4-yl or -5-yl, wherein the substituents are independently one or more of lower alkyl or allyloxycarbonyl methyl: pyrrolidin-1-yl; benzimidazol-1-yl; 1,4-dihydro-4-oxo-7-methyl-1,8-3-carboxyl-naphthyridin-1-yl; purin-9-yl; pyridin-2-yl; pyrazol-1-yl; or benzimidazol-2-yl.

Claim 6

A process of claim 1 wherein the compound produced as the formula Z 3 -X 3 -Q 3 -W 3 and pharmaceutically acceptable acid addition salts or quarternary amine salts thereof, wherein W 3 is R 4 is hydrogen, loweralkyl or hydroxy lower alkyl; R 5 is loweralkyl; R 6 and R 7 are independently one or more of hydrogen, loweralkyl, aminoloweralkyl or nitro: Z 3 is X 3 is Q 3 is lower alkanediyl of 5, 6, or 7 carbon atoms optionally substituted by -OH.

Claim 7

The process of claim 1 wherein the compound produced is: 1-[6-(2-chloro-4-methoxyphenyl)hexyl]imidazole; 2-{[6-(2-chloro-4-methoxyphenoxy)hexyl]thio}-4,5-dihydrothiozole-4-one; 5-{[6-(2-chloro-4-methoxyphenoxy)hexyl]thio}-1-methyltetrazole; 2-{[6-(2-chloro-4-methoxyphenoxy)hexyl]-thio}-3-pyridinol; 1-[6-(2-chloro-4-methoxyphenoxy)hexyl]-tetrazole; 2-[6-(2-chloro-4-methoxyphenoxy)hexyl]-tetrazole; 1-[6-(2-chloro-4-methoxyphenoxy)hexyl]-1,2,4-triazole; 1-[6-(2-chloro-4-methoxyphenoxy)hexyl]-5-amino-tetrazole; 2-[6-(2-chloro-4-methoxyphenoxy)hexyl]-5-amino-tetrazole; 5-{[6-(2-chloro-4-methoxyphenoxy)hexyl]-amino}-tetrazole; 1,3-di-[6-(2-chloro-4-methoxyphenoxy)hexyl]-1,2,3,4-tetrahydropyrimidine-2,4-dione; 1-[6-(2-chloro-4-methoxyphenoxy)hexyl]-1,2,3,4-tetrahydropyrimidine-2.4-dione; 1-[6-(2-chloro-4-methoxyphenoxy)hexyl]-4-hydroxymethylimidazole; 1-[6-(2-chloro-4-methoxyphenoxy)hexyl]-5-hydroxymethylimidazole; 1-[6-(2-chloro-4-methoxyphenoxy)hexyl]-2-methylimidazole; 1-[6-(2-chloro-4-methoxyphenoxy)hexyl]-4-nitroimidazole: 2-[7-(2-chloro-4-methoxyphenoxy)heptyl]-pyridine; 1-{6-[4-(4,5-dihydro-2-oxazolyl)phenoxy]-hexyl]imidazole; 1-[7-(2-chloro-4-methoxyphenoxy)heptyl]-imidazole; 1-[5-(2-chloro-4-methoxyphenoxy)pentyl]-imidazole; 1-[10-(2-chloro-4-methoxyphenoxy)decyl]-imidazole; 5-[7-(1-imidazolyl)-heptyl]-3-methylizoxazole; 1-[6-(2-chloro-4-methoxyphenoxy)hexyl]-benzimidazole; 1-[6-(2-chloro-4-methoxyphenoxy)hexyl]-2-hydroxybenzimidazole; N,N'-bis-[6-(2-chloro-4-methoxyphenoxy)hexyl]-2-benzimidazolone; 1-[6-(2-chloro-4-methoxyphenoxy)hexyl]-4-hydroxymethylimidazole; 1-[6-(2-chloro-4-methoxyphenoxy)hexyl]-5-hydroxymethylimidazole; 1-[6-(2-chloro-4-methoxyphenoxy)hexyl]-pyrrolidine; 1-[6-(1-imidazolyl)hexyl]-2-imidazole; sodium 1-[6-(2-chloro-4-methoxyphenoxy)hexyl]-1,4-dihydro-4-oxo-7-methyl-1.8-naphthyridine-3-carboxylate: 1-[6-(2-methyl-1-imidazolyl)hexyl]-2-methylimidazole; 1-[6-(2-chloro-4-methoxyphenoxy)hexyl]-3-pyrazole; 1-[6-(2-chloro-4-methoxyphenoxy)hexyl]-5-pyrazole; 9-[6-(2-chloro-4-methoxyphenoxy)hexyl]purine; 7-[6-(2-chloro-4-methoxyphenoxy)hexyl]purine; 1-[6-(2-chloro-4-methoxyphenoxy)hexyl]-4-methyl-5-hydroxymethylimidazole: 1-[6-(2-chloro-4-methoxyphenoxy)hexyl]-5-methyl-4-hydroxymethylimidazole; 1-[6-(2-chloro-4-methoxyphenoxy)hexyl]-2-ethylimidazole; 1-[6-(2-chloro-4-methoxyphenoxy)-1-hexylthio]-benzimidazole; 1-[6-(2-chloro-4-methoxyphenoxy)hexyl]-4-methyl-2-ethylimidazole; 1-[6-(2-chloro-4-methoxyphenoxy)hexyl]-5-methyl-2-ethylimidazole; 1-[3-(2-chloro-4-methoxyphenoxy)propyl]-imidazole; 2-[7-(2-chloro-4-methoxyphenoxy)heptyl]-1-methylimidazole; 2-[7-(2-chloro-4-methoxyphenoxy)heptyl]-imidazole; 2-[7-(2-chloro-4-methoxyphenoxy)heptyl]-1-butylimidazole; 1-[6-(4-phenoxyphenoxy)hexyl]imidazole; dimethyl 1-[6-(2-chloro-4-methoxyphenoxy)hexyl]-4.5-imidazole dicarboxylate: 1-[6-(2-chloro-4-methoxyphenoxy)hexyl]-4,5-di(hydroxymethyl)imidazole: trans 1-[(2-chloro-4-methoxyphenoxy)methyl]4-[(1-imidazolyl)methyl]cyclohexane: 1-(9,9-dimethyl-dec-7-ynyl)-imidazole; 1-[6-(2-chloro-4-methoxyphenoxy)hexyl]-3-methylimidazolium iodide; 1-[6-(2-chloro-4-methoxyphenoxy)hexyl]-4-aminomethylimidazole; 1-[6-(2-chloro-4-methoxyphenoxy)hexyl]-5-aminomethylimidazole; 1-[6-(2-chloro-4-methoxyphenoxy)hexyl]-4,5-dimethylimidazole; 1-[6-(2-chloro-4-methoxyphenoxy)hexyl]-2-hydroxymethylimidazole; 1-allyloxycarbonylmethyl-2-[7-(2-chloro-4-methoxyphenoxy)heptyl]imidazole: 1-carboxymethyl-2-[7-(2-chloro-4-methoxyphenoxy)heptyl]imidazole; 1-[6-(2-chloro-4-methoxyphenoxy)-hex-2-ynyl]imidazole; 1 -acetamido-2-[7-(2-chloro-4-methoxyphenoxy)heptyl]imidazole; 1-(2-hydroxyethyl)-2-[7-(2-chloro-4-methoxyphenoxy)heptyl]imidazole; 1-(8-phenyl-oct-7-ynyl)imidazole; 1-[6-hydroxy-6-(2-chloro-4-methylyphenyl)hexyl]imidazole; 1-[7-oxy-7-(4-methoxyphenyl)heptyl]imidazole; 1-[7-hydroxy-7-(4-methoxyphenyl)heptyl]imidazole; 1-[7-(4-methoxyphenyl)-hept-6-enyl]-imidazole hydrochloride; 1-[7-hydroxyimino-7-(4-methoxyphenyl)heptyl]imidazole 1-[7-(4-methoxyphenyl)heptyl]imidazole; 1-[7-oxo-7-(4-methylthiophenyl)heptyl]imidazole 1-[7-hydroxyimino-7-(4-methylthiophenyl)heptyl]imidazole 1-[7-hydroxyimino-7-(4-methylthiophenyl)heptyl]imidazole 1-[7-hydroxy-7-(4-methylthiophenyl)heptyllimidazole; 1-[7-oxo-7-(4-methylsulfonylphenyl)heptyl]imidazole; 1-[7-methoxyimino-7-(4-methylsulfonylphenyl)heptyl]imidazole; 1-[7-hydroxyimino-7-(4-methylsulfonylphenyl)heptyl]imidazole; 1-[7-hydroxy-7-(4-methylsulfonylphenyl)heptyl]imidazole; N-[6-(1-imidazolyl)hexanoyl]-1-adamantanamine: 1-[6-(5-chloro-2-methoxy-4-methylhenyl)hexyl]imidazole; 1-[6-(3-chloro-6-methoxy-2-methylphenyl)hexyl]imidazole; 1-[6-oxy-6-(4-methoxyphenyl)hexyl]imidazole; 1-[6-oxy-6-(2,4-dimethoxyphenyl)hexyl]imidazole; 1-[6-hydroxy-6-(2.4-dimethoxyphenyl)hexyl]imidazole; 1-[6-(2,4-dimethoxyphenyl)hex-5-enyl]-imidazole hydrochloride; 1-[6-oxy-6-(2-chloro-4-methoxyphenyl)hexyl]imidazole; 1-[6-hydroxy-6-(4-methoxyphenyl)hexyl]imidazole; 1-[6-(4-methoxyphenyl)hex-5-enyl]-imidazole hydrochloride; 1-[6-hydroxy-6-(2-chloro-4-methoxyphenyl)hexyllimidazole; 1-[6-(4-methoxyphenyl)hexyl]imidazole; 1-[6-(naphthalene-2-oxy)hexyl]imidazole; 1-[6-(4-methylthiophenoxy)hexyl]imidazole; 1-[6-(4-methylsulfonylphenoxy)hexyl]imidazole; 1-[6-(4-methoxyphenylthio)hexyl]imidazole; and 1-[6-(4-methoxyphenylsulfonyl)hexyl]imidazole.

Claim 8

The use of a compound of formulas I or II produced by the process of any one of claims 1 to 6 for preparing a pharmaceutical composition useful for treating viral infections or inflammation, or for inhibiting platelet activating factor.