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EP0457326A1 Expired / Lapsed EP ⏱️ 0.0 years remaining

Antiviral agents

Assignee: Syntex USA LLC
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Filing: 1991-05-16
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Granted: —
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Expires: 2011-05-16
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Abstract

Abstract Nucleoside compounds of the formula wherein: B is a purine or a pyrimidine; X and X' are H, OH or F, provided that at least one is H; Y and Y' are H, OH, OCH₃ or F, provided that at least one is H; Y' and Z together form a cyclic phosphate ester, provided that Y is H; or Z is where n is zero, one, two or three; and Z' is N₃ or OCH₃; provided that when X' and Y' are OH and Z' is N₃, B is not cytosine, when X' and Y' are OH and Z' is OCH₃, B is not uracil, adenine or cytosine, and when Z' is N₃, X' is H, and Y' is H, OH, OCH₃, or F, B is not purine, cytosine, uracil, or thymine; and the pharmaceutically acceptable esters, ethers and salts thereof, have been found to have potent antiviral activity with a high therapeutic ratio.

Inventors

  • 👤 Hans Maag
  • 👤 Ernest J. Prisbe
  • 👤 Julien P.H. Verheyden

Bibliographic Details

Application Number —
Jurisdiction EP
Data Source google_patents
Last Synchronized 2026-10-29 07:06
CPC Classifications
C; C07; C07H; C07H19/00; C07H19/02; C07H19/04; C07H19/06; C07H19/10; A; A61; A61K; A61K9/00; A61K9/10; A61K9/127; A61P; A61P31/00; A61P31/12; C07H19/16; C07H19/20

Claims Analysis

Total Claims: 9
Claim 1
Independent Claim 141 words
A compound of the formula wherein: B is a purine or a pyrimidine; X and X' are H, OH or F, provided that at least one is H; Y and Y' are H, OH, OCH₃ or F, provided that at least one is H; Y' and Z together form a cyclic phosphate ester, provided that Y is H; or Z is where n is zero, one, two or three; and Z' is N₃ or OCH₃; provided that when   X' and Y' are OH and Z' is N₃, B is not cytosine, when   X' and Y' are OH and Z' is OCH₃, B is not uracil, adenine or cytosine, and when   Z' is N₃, X' is H, and Y' is H, OH, OCH₃, or F, B is not purine, cytosine, uracil, or thymine; and the pharmaceutically acceptable esters, ethers and salts thereof.
Claim 2
Dependent Claim 13 words
The compound of Claim 1, where B is 5-halo-2,4-dioxopyrimidine, preferably 5-chloro-2,4-dioxopyrimidine or 5-bromo-2,4-dioxopyrimidine.
Claim 3
Dependent Claim 11 words
The compound of Claim 2, where Z' is N₃ or OCH₃.
Claim 4
Dependent Claim 10 words
A compound of Claim 1 selected from 1-(4-azido-2-deoxy-β-D-erythro-pentofuranosyl)-5-chloro-2,4-dioxopyrimidine and 1-(4-azido-2-deoxy-β-D-erythro-pentofuranosyl)-5-bromo-2,4-dioxopyrimidine.
Claim 5
Dependent Claim 19 words
A pharmaceutical composition comprising a pharmaceutically acceptable non-toxic excipient and a compound of any of Claims 1 to 4.
Claim 6
Dependent Claim 15 words
The pharmaceutical composition of Claim 5 comprising a second compound that is an antiviral agent.
Claim 7
Dependent Claim 15 words
The pharmaceutical composition of Claim 6 where said second compound is acyclovir, ganciclovir or foscarnet.
Claim 8
Dependent Claim 98 words
The use of a compound represented by the formula wherein: B is a 5-halo-2,4-dioxopyrimidine; X and X' are H, OH or F, provided that at least one is H; Y and Y' are H, OH, OCH₃ or F, provided that at least one is H; Y' and Z together form a cyclic phosphate ester, provided that Y is H; or Z is where n is zero, one, two or three; and Z' is N₃ or OCH₃; and the pharmaceutically acceptable esters, ethers and salts thereof, in the manufacture of a medicament for treating viral, bacterial or fungal infections.
Claim 9
Dependent Claim 723 words
A process for preparing a compound of formula I wherein: B is a purine or a pyrimidine; X and X' are H, OH or F, provided that at least one is H; Y and Y' are H, OH, OCH₃ or F, provided that at least one is H; Y' and Z together form a cyclic phosphate ester, provided that Y is H; or Z is where n is zero, one, two or three; and Z' is N₃ or OCH₃; provided that when   X' and Y' are OH and Z' is N₃, B is not cytosine, when   X' and Y' are OH and Z' is OCH₃, B is not uracil, adenine or cytosine, and when   Z' is N₃, X' is H, and Y' is H, OH, OCH₃, or F, B is not purine, cytosine, uracil, or thymine; and the pharmaceutically acceptable esters, ethers and salts thereof, which comprises a) reacting a compound of formula II wherein: B' is the same as B in Formula I, or an acylated equivalent thereof; R is methyl or an acyl group such as anisoyl, benzoyl, acetyl or furan-2-carbonyl; X is H or F; X'' is H, F, or the group -O-R; and Z is methylene with a leaving group such as iodo or bromo; provided that when Z' is iodomethyl and X'' is -O-R and R is benzoyl, B' is not N⁴-benzoylcytosine; with an oxidizing agent, followed by the addition of a base; or b) reacting a compound of the formula wherein: B is a purine or pyrimidine; R³ is lower alkyl; X and X' are H, OH or F, provided that at least one is H; and Y and Y' are H, OH, OCH₃ or F, provided that at least one is H; with a silylating agent and a base followed by an azide in the presence of a Lewis acid catalyst; or c) reacting a compound of the formula wherein: B is a purine or pyrimidine; X and X' are H, OH or F, provided that at least one is H; and Y and Y' are H, OH, OCH₃ or F, provided that at least one is H; with an oxidizing agent to form a compound of Formula I wherein Z' HO-H₂C- and Z is R³-O-; or d) reacting a compound of the formula wherein: B is a purine or pyrimidine; R³ is lower alkyl; X and X' are H, OH or F, provided that at least one is H; and Y is H, OH, OCH₃ or F; with a halogenating agent; or e) reacting a compound of formula I wherein n is zero, with a phosphorylating agent to give a compound of formula I wherein n is one or three; or f) reacting a compound of formula I wherein n is one with a cyclizing agent to give a compound of formula I wherein Y' and Z together form a cyclic phosphate; or g) reacting a compound of formula II with phosphonous acid or a salt of a di-lower alkyl phosphonate to form a compound of formula I wherein Z is (R'O)₂P(O)CH₂-; or h) reacting a compound of formula I with a protecting agent, followed by reaction with a strong base followed by reaction with an alkyl halide, followed by deprotection, to give a compound of formula I wherein Y' is an ether; or i) reacting a compound of formula I with a pyridine catalyst and an acid chloride to give the corresponding ester of a compound of formula I; or j) reacting a compound of formula I with a pharmaceutically acceptable base to form the corresponding base addition salt of formula I; or k) reacting a base addition salt of a compound of formula I with an acid to form the free compound of formula I; or l) reacting a compound of formula I with a pharmaceutically acceptable acid to form the corresponding acid addition salt of formula I; or m) reacting an acid addition salt of a compound of formula I with a base to form the free compound of formula I; or n) converting a pharmaceutically acceptable acid or base salt of a compound of formula I to another pharmaceutically acceptable acid or base salt of a compound of formula I; or o) converting an ester or ether of a compound of formula I to the corresponding free compound of formula I.

References Cited (Backward Citations)

US3910885A Cited
EP0371366A1 Cited

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