Chemical compounds

US7018989B2 · kind B2 · utility

Assignee

• University College Cardiff Consultants Limited · GB

Inventors

• Christopher McGuigan · Cardiff, GB
• Jan Balzarini · Heverlee, BE

Key dates

• Filing date: Aug 12, 2002
• Grant date: Mar 28, 2006
• Expiry date: Aug 12, 2022

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07H19/20
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Aryl substituted phosphoryl derivatives of the formula In which Ar is phenyl, naphthyl, or pyridyl, Y is O or S, X1 is O, NR3, S, CR3R4, CR3W1 or CW1W2, X2 and X6 are a bond or X6 is CH2 and X2 is O, NR3, S, CR3R4, CR3W1 or CW1W2, R3 and R4 are H, alkyl or phenyl, groups, W1 and W2 are heteroatoms, X3 is alkylene, X4 is oxygen or CH2, X5 is a bond or CH2, Z is O, NR5, S, alkyl or phenyl, R5 is H, alkyl or phenyl, J is H, alkyl, phenyl, or a heterocyclic or polycyclic group, Q is O, NR6, S, CR6R7, CR6W3 or CW3W4, R6 and R7 are H, alkyl or phenyl, and W3 and W4 are hetero atoms, T1 and T2 are H or CH2R8, R8 is H, OH or F, or T1 and T2 together are —CH═CH— or —C(R9)(R10)C(R11)(R12)—, R9 is H, halogeno, CN, NH2, CO-alkyl, or alkyl, R10, R11, and R12 are H, N3, halogen, CN, NH2, CO-alkyl, or alkyl, and B is a purine or pyrimidine base, have antiviral activity, as for example against HIV. Particularly preferred are thymine and adenine derivatives of amino acid phenoxyphosphoroamidates. A typical embodiment is 2′,3′-dideoxy-2′,3′-didehydrothymidine 5′-(phenyl methoxy alaninyl) phosphoroamidate which can be prepared from phenyl methoxy alaninyl phosphorochloridate and 2′,3′-dideoxy-2′,3′-d…