Antiviral purine derivatives and process for their preparation

Claim 2

A compound of formula (I) according to claim I, wherein R, and R2 are both hydrogen and R 3 is CH 2 OH, and derivatives thereof as defined in claim I.

Claim 3

A compound of formula (I) according to claim I, wherein R, is hydrogen and R 2 and R 3 are both CH 2 OH, and derivatives thereof as defined in claim 1.

Claim 4

A compound of formula (I) according to claim I, wherein R, is hydrogen, R 2 is hydroxy and R 3 is CH 2 OH, and derivatives thereof as defined in claim I.

Claim 5

A compound of formula (I) according to claim I, wherein R, is CH 2 0H, R 2 is hydrogen and R 3 is CH 2 OH, and derivatives thereof as defined in claim I.

Claim 6

A compound of formula (I) according to claim I, wherein R, and R 2 are both hydrogen and R 3 is CH-(OH)CH 2 OH, and derivatives thereof as defined in claim I.

Claim 7

A compound according to any of claims I to 6 wherein R 4 is hydroxy.

Claim 8

A compound according to any one of claims I to 6 wherein R 4 is hydrogen.

Claim 9

A compound according to any one of claims I to 8 wherein OH groups in R,, R2, and/or R 3 are in the form of an acyl derivative thereof wherein the acyl derivative(s) is/are an acetate, hexanoate or benzoate.

Claim 10

9-(3-Hydroxyprop-1-oxy)guanine, 9-(3-acetoxyprop-l-oxy)guanine, 9-(3-benzoyloxyprop-1-oxy)guanine, 2-amino-6-ethoxy-9-(3-hydroxyprop-1-oxy)purine, 9-(3-hydroxy-2-hydroxymethylprop-l-oxy)guanine, 9-(2,3-dihydroxyprop-1-oxy)guanine, 2-amino-9-(2,3-dihydroxyprop-l-oxy)purine, 9-(1,4-dihydroxybut-2-oxy)guanine, 2-amino-9-(1,4-dihydroxybut-2-oxy)purine, 2-amino-9-(3-hydroxyprop-1-oxy)purine, 9-(3-hexanoyloxyprop-l-oxy)guanine, 2-amino-9-(1,4-diacetaxybut-2-oxy)purine, 2-amino-9-(1,4-dibutyryloxybut-2-oxy)purine, (R)-9-(1,4-dihydroxybut-2-oxy)guanine, (S)-9-(1,4-dihydroxybut-2-oxy)guanine, 2-amino-9-(3-hydroxy-2-hydroxymethylprop-1-oxy)purine, 9-(3-acetoxy-2-acetoxymethylprop-l-oxy)-2-aminopurine, 2-amino-(3-propionyloxy-2-propionyloxymethylprop-l-oxy)purine, 2-amino-(3-benzoyloxy-2-benzoyloxymethylprop-l-oxy)purine, 2-amino-9-(3-hydroxy-2-hydroxymethylprop-l-oxy)-6-methoxypurine, 2,6-diamino-9-(3-hydroxy-2-hydroxymethylprop-I-oxy)purine, 9-(3-acetoxyprop-l-oxyr2-aminopurine, 2-amino-9-(3-hexanoyloxyprop-l-oxy)purine, 2-amino-9-(3-benzoyloxyprop-l-oxy)purine, (S)-9-(1,4-diacetoxybut-2-oxy)guanine, 2-amino-9-(2,3-dihydroxyprop-l-oxy)-6-methoxypurine, (R)-9-(2,3-dihydroxyprop-l-oxy)guanine, 9-(3,4-dihydroxybut-l-oxy)guanine, 2-amino-9-(3,4-dihydroxybut-l-oxy)purine, (R)-2-amino-9-(2,3-dihydroxyprop-l-oxy)purine or (S)-9-(2,3-dihydroxyprop-l-oxy)guanine.

Claim 11

II. A process for the preparation of a compound of formula (I) according to claim I or a pharmaceutically acceptable salt thereof, which process comprises cyclising a compound of formula (II):

Claim 12

wherein L is a sulphur leaving group or NH 2 , Y is a protecting group and R,', R 2 ' and R 3 ' anr R,, R 2 and R 3 respectively or R,, R 2 and/or R 3 wherein OH groups are protected; and thereafter, when R 4 in the desired compound of formula (I) is other than hydroxy, converting an R 4 hydroxy group to chloro, followed by either (i) reduction to R 4 is hydrogen, (ii) replacement of chloro by NH 2 to give R. is amino; or (iii) reaction with OR 5 - ion to give R 4 is OR 5 ; and deprotecting Y and converting R 1 ' to R,, R 2 ' to R 2 and R 3 ' to R 3 when desired or necessary, and optionally forming a pharmaceutically acceptable salt, O-acyl, phosphate, cyclic acetal or cyclic carbonate derivative thereof.

Claim 13

A process for the preparation of a compound of formula (I) according to claim I or a pharmaceutically acceptable salt thereof, which process comprises converting the chloro group in a compound of formula (VI): wherein R 6 is hydrogen or an N-protecting group, and R,', R 2 ' and R 3 ' are as defined in claim II, by either (i) hydrolysis to give R 4 as hydroxy, (ii) reduction to give a compound of formula (I) wherein R 4 is hydrogen, (iii) replacement of chloro by NH 2 to give R 4 is amino; or (iv) reaction with OR 5 - to give a compound of formula (1) wherein R. is OR s , and thereafter converting R,' to R 1 , R 2 ' to R 2 and/or R 3 ' to R 3 when necessary, and/or optionally forming a pharmaceutically acceptable salt or derivative thereof as defined in claim I.

Claim 14

A process for the preparation of a comopund of formula (I) according to claim I, which process comprises the deprotection of a compound of formula (I) as defined in claim I, wherein any OH groups in R,, R 2 and/or R 3 are in protected form; and thereafter optionally forming a pharmaceutically acceptable salt or derivative thereof as defined in claim I.

Claim 15

A compound of formula (II) as defined in claim II.

Claim 16

A compound of formula (V): wherein R,', R 2 ' and R 3 ' are as defined in claim II.

Claim 17

A compound of formula (VI) as defined in claim 12.

Claim 18

A compound of formula (VIII): wherein R 6 is formyl, and R,', R 2 ', and R 3 ' are as defined in claim II.

Claim 19

A compound of formula (IV): wherein R,', R 2 ', and R 3 ', are as defined in claim II, other than compounds wherein R 2 ' and R 3 ' are protected OH groups wherein OH groups on adjacent carbon atoms are replaced by a bond.

Claim 20

A compound of formula (I) as defined in claim I, except that R,, R2 and/or R 3 are in protected form as defined for R,', R 2 'and/or R 3 ' in claim II.

Claim 21

The intermediate compound of formula (II), (V), (VI), (VIII) or (IV), as defined in claims 14 to 18, or the intermediate compound according to claim 19, for the preparation of any compound according to claim 10.

Claim 22

A pharmaceutical composition comprising a compound according to any one of claims I to 10, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

Claim 23

A compound according to any one of claims I to 10, or a pharmaceutically acceptable salt thereof, for use as an active therapeutic substance.

Claim 24

A compound according to any one of claims I to 10, or a pharmaceutically acceptable salt thereof, for use in the treatment of viral infections.

Claim 25

Use of a compound according to any one of claims I to 10, or a pharmaceutically acceptable salt thereof, in the mamnufacture of a medicament for the treatment of viral infections.