Heterotricyclic cage compounds, processes for their production, pharmaceutical compositions containing them, and their use as medicinal antiviral agents

Claim 2

A compound of the formula: wherein A 1 is a single bond, a C 2 -C 5 alkylene group or a C 1 -C 5 alkylidene group, A 2 is a C 2 -C 3 alkylene group or a C l -C 3 alkylidene group, A3 is a C 2 -C 4 alkylene group or a C 1 -C 4 alkylidene group, X is -O- or -SO n - (wherein n is O, 1 or 2), R 1 is a hydrogen atom, a C 1 -C 5 alkyl group, a C 3 -C 5 alkenyl group and R 2 is a hydrogen atom, a C 1 -C 5 alkyl group, a C 3 -C 5 alkenyl group, a C 2 -C 5 alkanoyl group, a C 2 -C 5 alkoxycarbonyl group, a benzyloxycarbonyl group, or when taken together with the adjacent nitrogen atom, R 1 and R 2 form a five or six-membered heterocyclic group, or a non-toxic salt thereof.

Claim 3

A compound as claimed in claim 1, of the formula: wherein All is a single bond or a methylene group, AA 21 is a methylene group or an ethylene group, A 31 is a methylene group or an ethylene group, X, R 1 and R 2 are each as defined in claim 1, or a non-toxic salt thereof.

Claim 4

A compound as claimed in claim 2, of the formula: wherein A 11 . A 21 , A 31 and X are each as stated in claim 2, R 1 is a hydrogen atom, a C 1 -C 5 alkyl group, a C 3 -C 5 alkenyl group, and R 21 is a hydrogen atom, a C 1 -C 5 alkyl group, a C 3 -C 5 alkenyl group or a C 2 -C 5 alkoxycarbonyl group, or a non-toxic salt thereof.

Claim 5

A compound as claimed in claim 3, of the formula: Wherein A 11 , A 21 , A 31 and R 21 are each as defined in claim 3, R 11 is a hydrogen atom or a C 1 -C 5 alkyl group, and X 1 is -O- or -S-, or a non-toxic salt thereof.

Claim 6

A compound as claimed in claim 4, of the formula: wherein A 11 , A 21 and A 31 are each as defined in claim 4, or a non-toxic salt thereof.

Claim 7

A process for producing a compound of the formula: wherein A 1 , A 2 , A 3 , R 1 and R 2 are each as defined in claim 1 and X 1 is -O- or -S-, which comprises reducing a) a compound of the formula: wherein A 2 , A3 and X 1 are each as defined above and A 12 is a single bond, a C 2 -C 4 alkylene group or a C 1 -C 4 alkylidene group, with a metal hydride compound or hydrogen gas in the presence of a catalyst; or b) a compound of the formula: wherein A 12 , A 2 , A 3 , R 1 and X 1 are each as defined above and R 22 is a hydrogen atom, a C 1 -C 5 alkyl group, a C 3 -C 5 alkenyl group, or when taken together with the adjacent nitrogen atom, R 1 and R 22 may form a five or six-membered heterocyclic group, with a metal hydride compound; or c) a compound of the formula: where-in A 1 , A 2 , A 3 , R 1 , and X 1 are each as defined above and R 3 is a C 1 -C 4 alkyl group, with a metal hydride compound; or d) a compound of the formula: wherein A 1 , A 2 , A 3 , R 1 and X 1 are each as defined above and R 4 is a hydrogen atom, a C 1 -C 4 alkyl group or a C 2 -C 4 alkenyl group, with a metal hydride compound; or e) a compound of the formula: wherein A 2 , A3, A 12 and X 1 are each as defined above and R 5 is a hydrogen atom or a C 1 -C 4 alkyl group, with a metal hydride compound or hydrogen gas in the presence of a catalyst; or f) a compound of the formula: wherein A 1 , A 2 , A 3 and X 1 are each as defined above, with a metal hydride compound or hydrogen gas in the presence of a catalyst; or g) a compound of the formula: wherein A 2 , A 3 , A 12 , R 5 and X 1 are each as defined above, with a reducing agent in the presence of an amine compound of the formula: wherein R 1 and R 22 are each as defined above.

Claim 8

A process for producing a compound of the formula: wherein A 1 , A 2 and A 3 are each as defined in claim 1, X 1 is -0- or -S- and R 11 is a hydrogen atom or a C 1 -C 5 alkyl group, which comprises debenzylation and decarbonylation of a compound of the formula: wherein A 1 , A 2 , A3, R 11 and X 1 are each as defined above.

Claim 9

A process for producing a compound of the formula: wherein A 1 , A 2 , A 3 , X, R 1 and R 2 are each as defined in claim 1, which comprises reacting a compound of the formula: wherein A 1 , A 2 , A 3 and X are each as defined above and Z is the residue of a strong acid, with an amine compound of the formula: wherein R 1 and R 2 are each as defined above.

Claim 10

A process for producing a compound of the formula: wherein A 1 , A 2 , A3 and X are each as defined in claim 1 and R 11 is a hydrogen atom, or a C 1 -C 5 alkyl group, which comprises hydrolyzing a compound of the formula: wherein A 1 , A 2 , A 3 , R 11 and X are each as defined above and R 6 is a hydrogen atom, a C 1 -C 4 alkyl group, a C 1 -C 3 haloalkyl group, a C 1 -C 4 alkoxy group or a benzyloxy group.

Claim 11

A process for producing a compound of the formula: wherein A 1 , A 2 , A3 and X are each as defined in-claim 1, which comprises hydrolyzing a compound of the formula: wherein A 1 , A 2 , A3 and X are each as defined above.

Claim 12

ll. A process for producing a compound of the formula: wherein A 1 , A 2 , A3 and X are each as defined in claim 1 and R 23 is a hydrogen atom, a C 2 -C 5 alkoxycarbonyl group or a benzyloxycarbonyl group, which comprises treatment of a) a compound of the formula: wherein A 1 , A 2 , A 3 and X are each as defined above, with alkali hypohalite, followed by hydrolysis or treatment of the resulting rearrangement product (an isocyanate) with an alcohol compound of the formula: R 7 -OH (wherein R 7 is a C 1 - C4 alkyl group or a benzyl group); or b) a compound of the formula: wherein A 1 , A 2 , A 3 and X are each as defined above, under heating, followed by hydrolysis or treatment of the resulting rearrangement product (an isocyanate) with an alcohol compound of the formula: R 7 -OH (wherein R 7 is as defined above); c) a compound of the formula: wherein A 1 , A 2 , A 3 and X are each as defined above, under heating with or without a base, followed by hydrolysis or treatment of the resulting rearrangement product (an isocyanate) with an alcohol compound of the formula: R 7 -OH (wherein R 7 is as defined above).

Claim 13

A process for producing a compound of the formula: wherein A 2 , A 3 , R 1 and R 22 are each as defined in claim 1 and X 1 is -0- or -S-, which comprises reducing a) a compound of the formula: wherein A 2 , A 3 and X 1 are each as defined above, with a reducing agent in the presence of an amine of the formula: wherein R 1 and R 22 are each as defined above; or b) a compound of the formula: wherein A 2 , A 3 and X 1 are each as defined above, with a metal hydride compound or hydrogen gas in the presence of a catalyst.

Claim 14

A process for producing a compound of the formula: wherein A 1 , A 2 , A 3 , R 1 and R 2 are each as defined in claim 1 and m is 1 or 2, which comprises oxidizing a compound of the formula: wherein A 1 , A 2 , A 3 and R 2 are each as defined above.

Claim 15

A pharmaceutical composition which comprises as an active ingredient a pharmaceutically effective amount of at least one compound as claimed in claim 1, together with at least one pharmaceutical inert carrier or diluent.

Claim 16

Use of the compound claimed in claim 1 as a medicine.