Anti-viral pyrimidine nucleoside analogues

Patent metadata

Field	Value
Publication number	US-2016244476-A1
Application number	US-201615141992-A
Country	US
Kind code	A1
Filing date	Apr 29, 2016
Priority date	Apr 17, 2000
Publication date	Aug 25, 2016
Grant date	—

Abstract

A compound of formula (I) wherein Ar can be one six-membered or two fused six-membered aromatic rings; R 8 and R 9 can be hydrogen, alkyl, cycloalkyl, halogens, amino, alkylamino, dialkylamino, nitro, cyano, alkyoxy, aryloxy, thiol, alkylthiol, arythiol, or aryl; Q can be O, S or CY 2 , where Y may be H, alkyl or halogens; X can be O, NH, S, N-alkyl, (CHR 2 ) m where m is 1 to 10, and CY 2 ; Z can be O, S, NH, or N-alkyl; U″ is H and U′ can be H or CH 2 ; wherein: T can be OH, H, halogens, O-alkyl, O-acyl, O-aryl, CN, NH 2 or N 3 ; T′ and T″ can be H or halogen; and W can be H or a phosphate group. Compounds show anti-viral activity, for example with respect to varicella zoster virus.

First claim

What is claimed is:

1 . A compound having the formula:

wherein
Ar is an, optionally substituted, aromatic ring system, the aromatic ring system comprising one six-membered aromatic ring or two fused six-membered aromatic rings;
R 8 and R 9 are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, halogens, amino, alkylamino, dialkylamino, nitro, cyano, alkoxy, aryloxy, thiol, alkylthiol, arylthiol, and aryl;
Q is selected from the group consisting of O, S and CY 2 , where Y may be the same or different and is selected from H, alkyl and halogens;
X is selected from the group consisting of O, NH, S, N-alkyl, (CH 2 ) m where m is 1 to 10, and CY 2 where Y may be the same or different and is selected from hydrogen, alkyl and halogens;
Z is selected from the group consisting of O, S, NH, and N-alkyl;
U″ is H and U′ is selected from H and CH 2 T, or U′ and U″ are joined so as to form a ring moiety including Q wherein U′-U″ together is respectively selected from the group consisting of —CTH—CT′T″ and —CT′=CT′—, so as to provide ring moieties selected from the group consisting of:

wherein:
T is selected from the group consisting of OH, H, halogens, a-alkyl, a-acyl, a-aryl, CN, NH 2 and N 3 ;
T′ is selected from the group consisting of H and halogens and, where more than one T′ is present, they may be the same or different;
T″ is selected from the group consisting of H and halogens; and
W is selected from the group consisting of H, a phosphate group and a pharmacologically acceptable salt, derivative or pro-drug thereof;
with the provisos that:
(1) when T is OAc and T′ and T″ are present and are H, Ar is not 4-(2-benzoxazolyl)phenyl; and
(2) when Q, X and Z are each 0, and R 8 , R 9 , T′, T″ and W are each H and T is OH or O-acyl, Ar is:
one six-membered carbocyclic aromatic ring substituted by one or more moieties independently selected from the group consisting of alkyl, aryl, cycloalkyl, chlorine, bromine, iodine, cyano, alkylamino, dialkylamino, alkoxy, aryloxy, alkylthio and arylthio, any of which alkyl, cycloalkyl or aryl moieties may be substituted by one or more members selected from the group consisting of chlorine, bromine, iodine, CN, CO 2 alkyl (C 1 to C 6 ), CONH 2 , CONH alkyl (C 1 to C 6 ), SR, S alkyl (C 1 to C 6 ) and NO 2 ;
one six-membered aromatic ring system which contains one, two, three or four hetero atoms and which ring system may be optionally substituted; or
two fused six-membered aromatic rings, which may be optionally substituted.

2 . A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable excipient.

3 . A method of prophylaxis or treatment of a viral infection comprising administering to a patient in need of such treatment an effective dose of a compound of claim 1 .

Assignees

• Rega Found
• Univ College Cardiff Consultants Ltd

Inventors

• Mcguigan Christopher
• Balzarini Jan

Classifications

• A61P31/12

  Antivirals · CPC title

• C07H19/14

  Pyrrolo-pyrimidine radicals · CPC title

• A61K31/706

  containing six-membered rings with nitrogen as a ring hetero atom · CPC title

• C07D498/04

  Ortho-condensed systems · CPC title

• C07H19/10

  with the saccharide radical esterified by phosphoric or polyphosphoric acids · CPC title