Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Phosphorus containing other than solely as part of an...
Patent
1993-01-19
1994-10-18
Bernhardt, Emily
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Phosphorus containing other than solely as part of an...
544244, 549221, 556405, 556482, 558177, A61K 31675, C07F 96561
Patent
active
053568869
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to compounds having antiviral activity, to processes for their preparation and to their use as pharmaceuticals.
Coll. Czech. Chem. Commun., 1988, 53, 2753 (Rosenberg et. al.) describes phosphonylalkyl derivatives of adenine.
EP-A-343133 (Medivir Aktiebolag) discloses a group of phosphonylalkyl purine derivatives which are described as having antiviral activity.
EP-A-404296 (Beecham group p.l.c.), published 27.12.90, describes a group of phosphonylalkoxy purine derivatives having antiviral activity.
A novel, structurally distinct class of compounds has now been discovered, these compounds being phosphonylalkenyl or phosphonylalkenyloxy derivatives of purine, and also having antiviral activity.
Accordingly, the present invention provides a compound of formula (I), or a pharmaceutically acceptable salt thereof: ##STR3## wherein X is --CH.sub.2 O or --CH.sub.2 ; ##STR4## wherein R.sub.5 and R.sub.6 are independently selected from hydrogen, C.sub.1-6 alkyl and optionally substituted phenyl.
When R.sub.1 is hydroxy and R.sub.2 is amino, the compound of formula (I) is a guanine derivative;
When R.sub.1 is amino and R.sub.2 is hydrogen, the compound of formula (I) is an adenine derivative;
When R.sub.1 is hydroxy and R.sub.2 is hydrogen, the compound of formula (I) is a hypoxanthine derivative; and is a 2,6-diaminopurine derivative.
Often, the compound of formula (I) is a guanine or adenine derivative.
Suitable examples of the acyl group in R.sub.3 when acyloxymethyl, include carboxylic acyl, Such as C.sub.1-7 alkanoyl and benzoyl optionally substituted in the phenyl ring as defined below for R.sub.5 /R.sub.6. Preferred acyl groups include acetyl, propionyl, butyryl, heptanoyl and hexanoyl.
Suitable examples of R.sub.5 and R.sub.6 include hydrogen, methyl, ethyl, n- and iso-propyl, n-, sec-, iso- and tert-butyl, and phenyl optionally substituted by one, two or three groups or atoms selected from halogen, such as fluoro, chloro, bromo, and C.sub.1-4 alkyl or C.sub.1-4 alkoxy wherein the alkyl moiety is selected from those listed for R.sub.5 /R.sub.6 above.
Examples of pharmaceutically acceptable salts of the compound of formula (I) are acid addition salts formed with a pharmaceutically acceptable acid such as hydrochloric acid, orthophosphoric acid and sulphuric acid. Pharmaceutically acceptable salts also include those formed with organic bases, preferably with amines, such as ethanolamines or diamines; and alkali metals, such as sodium and potassium.
As the compound of formula (I) contains a phosphonate group, suitable salts include metal salts, such as alkali metal salts, for example sodium or potassium, alkaline earth metal salts such as calcium or magnesium and ammonium or substituted ammonium salts, for example those with lower alkylamines such as triethylamine, hydroxy-lower alkylamines such as 2-hydroxyethylamine, bis-(2-hydroxyethyl)amine or tris-(2-hydroxyethyl)amine.
It will be appreciated that some of the compounds of formula (I), especially those wherein R.sub.3 is other than hydrogen, have an asymmetric centre, and therefore are capable of existing in more than one stereoisomeric form. The invention extends to each of these forms individually and to mixtures thereof, including racemates. The isomers may be separated conventionally by chromatographic methods or using a resolving agent. Alternatively, the individual isomers may be prepared by asymmetric synthesis using chiral intermediates.
It will also be appreciated that, since the compounds of formula (I) contain a R.sub.4 HC.dbd.CH moiety, they are capable of existing in E and Z (trans and cis) forms. The invention extends to each of these forms and to mixtures thereof.
The compounds of formula (I) including their alkali metal salts may form solvates such as hydrates and these are included wherever a compound of formula (I) or a salt thereof is herein referred to.
It will be appreciated that, when R.sub.1 is hydroxy in formula (I) the compound exists in the predominant tautomeric form of structure (IA): ##STR5##
The inv
REFERENCES:
patent: 4910307 (1990-03-01), Wyatt
patent: 5055458 (1991-10-01), Bailey et al.
Collection of Czechoslovak Chm. Commun., vol. 53, No. 11B, Nov. 1988, I. Rosenberg et al., pp. 2753-2777.
Harnden Michael R.
Parratt Martin J.
Beecham Group p.l.c.
Bernhardt Emily
Lentz Edward T.
Stercho Yuriy P.
Suter Stuart R.
LandOfFree
Antiviral phosphono-alken derivatives of purines does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Antiviral phosphono-alken derivatives of purines, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Antiviral phosphono-alken derivatives of purines will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2372534