Heterocyclic substituted-phenoxyalkyl-isoxazoles and-furans, their preparation and use as antiviral agents

Claim 2

1 . A compound of the formula wherein: Y is an alkylene bridge of 3-9 carbon atoms; Z is N or HC; R is hydrogen or lower-alkyl of 1-3 carbon atoms, with the proviso that when Z is N, R is lower-alkyl; R 1 and R 2 are each hydrogen, halogen, methyl, nitro, lower-alkoxycarbonyl or trifluoromethyl; and Het is or where n is 2 or 3; and R 3 , R 4 and R 5 are hydrogen or lower-alkyl of 1 - 3 carbon atoms; or a pharmaceutically acceptable acid-addition salt of a basic member thereof.

Claim 3

A compound according to claim 1, of the formula

Claim 4

A compound according to claim 2, wherein Het is a furanyl, thienyl or pyridinyl group.

Claim 5

A compound according to claim 3, which is 5-{5-[2,6-dichloro-4-(2-furanyl)phenoxy]-pentyl}-3-methylisoxazole, 5- {5-[2,6-dimethyl-4-(5-methyl-2-furanyl)phenoxy] pentyl}-3-methylisoxazole, 5-{5-[2,6-dichloro-4-(2-thienyl)phenoxy]pentyl}-3-methylisoxazole, or 5-{5-[2,6-dichloro-4-(2-pyridinyl)phenoxy]pentyl}-3-methylisoxazole.

Claim 6

A process for preparing a compound according to any one of claims 1 to 4, which comprises (a) reacting a compound of the formula wherein Hal is chlorine, bromine or iodine, with an alkali metal salt of a compound of the formula or (b) to prepare a compound wherein Het is any of the aromatic type heterocyclic groups included in the definition 4 of Het in claim 1, reacting a compound of the formula where Hal' is bromine or iodine, with a compound of the formula (R')3Sn-Hef where R' is lower-alkyl of 1-6 carbon atoms, and Het' is any of the aromatic type heterocyclic groups included in the definition of Het in claim 1; in the presence of a palladium complex catalyst; (c) to prepare a compound according to claim 1, wherein Het is a 4,5-dihydro-lH-imidazolyl group, heating a compound of the formula with ethylenediamine in acid medium; (d) to prepare a compound according to claim 1, wherein Het is a 2-thiazolyl group, converting a compound of Formula IX to the corresponding thioamide with hydrogen sulfide in pyridine, and then reacting the thioamide with a haloalkanone, R 3 CH(Hal)-CO-R 4 ; (e) to prepare a compound according to claim 1, wherein Het is a tetrazole group, reacting a compound of Formula IX with sodium azide to give a tetrazole wherein R 3 is hydrogen, and, if desired, treating said tetrazole with a lower-alkyl halide in the presence of a base to give both isomeric tetrazoles wherein R 3 is lower-alkyl; (f) to prepare a compound according to claim 1, wherein Het is a group of the formula reacting a benzaldehyde derivative of the formula with ethylene glycol or propylene glycol; and, if desired, converting a basic compound obtained to an acid-addition salt thereof.

Claim 7

A process according to claim 5, wherein in alternative (b) the palladium complex catalyst is dichlorobis(triphenylphosphine)palladium.

Claim 8

A compound of the Formula V (herein) wherein R, Y and Z have the meanings given in claim 1; R 1 ' and R 2 ' are halogen, methyl nitro, lower-alkoxycarbonyl or trifluoromethyl; and Hal' is bromine or iodine.

Claim 9

8 . A compound according to claim 7, wherein R = CH 3 , Y = (CH 2 ) 5 and Z is N.

Claim 10

A composition for combating viruses which comprises an antivirally effective amount of a compound according to any one of claims 1-4, in admixture with a suitable carrier or diluent.