Claims
- 1. A compound of formula (I) or (I-1): ##STR7## wherein R.sup.1 is H, CH.sub.3 or CH.sub.2 OH; R.sup.2 is H or OH; R.sup.3 is H or OH; or R.sup.2 and R.sup.3 together form a bond; R.sup.4 is amino, cyclopropylamino, cyclobutylamino, isopropylamino, tert-butylamino or --NR.sup.8 R.sup.9 where R.sup.8 and R.sup.9 together with the nitrogen atom to which they are attached form a 4, 5 or 6-membered heterocyclic ring; R.sup.5 is H; and R.sup.6 and R.sup.7 are Cl, excluding the compound (.+-.)-(1R*, 2S*, 3 S*, 5S*)-5-�5,6-Dichloro-2-(cyclopropylamino)-1H-benzimidazol-1-yl!-3-(hyroxyomethyl)-1,2-cyclopentanediol provided that at least one of R.sup.1, R.sup.2 and R.sup.3 is or contains OH; and
- pharmaceutically acceptable derivatives thereof.
- 2. A compound as claimed in claim 1 in which R.sup.2 is OH.
- 3. A compound according to claim 2 wherein R.sup.4 is cyclopropylamino, isopropylamino or tert-butylamino.
- 4. A compound according to claim 3 wherein R.sup.4 is isopropylamino or tert-butylamino.
- 5. A compound according to claim 1 of Formula (IA) or (IA-1) ##STR8## wherein R.sup.2 is H or OH; R.sup.4 is amino, cyclopropylamino, isopropylamino, tert-butylamino, or
- --NR.sup.8 R.sup.9 where R.sup.8 and R.sup.9 together with the nitrogen- atom to which they are attached form a 4, 5 or 6 membered heterocyclic ring; R.sup.5 is H; and R.sup.6 and R.sup.7 are Cl, excluding excluding the compound (.+-.)-(1R*, 2S*, 3S*, 5S*)-5-�5,6-Dichloro-2-(cyclopropylamino)-1H-benzimidazol-1-yl!-3-(hyroxyomethyl)-1,2-cyclopentanediol and pharmaceutically acceptable derivatives thereof.
- 6. A compound of claim 5 wherein R.sup.4 is cyclopropylamino, isopropylamino or tert-butylamino; R.sup.5 is H; and R.sup.6 and R.sup.7 are both Cl; and the pharmaceutically acceptable derivatives thereof.
- 7. A compound of claim 6 wherein R.sup.4 is isopropylamino or tert-butylamino.
- 8. A compound according to claim 1 which is selected from
- (1 R, 2S, 3S, 5S)-5-�5,6-Dichloro-2-(cyclopropylamino)-1H-benzimidazol-1-yl!-3-(hydroxymethyl)-1,2-cyclopentanediol
- (1R, 2S, 3S, 5S)-5-�5,6-Dichloro-2-(isopropylamino)-1H-benzimidazol-1-yl!-3-(hydroxymethyl)-1,2-cyclopentanediol
- (.+-.)-(1R*, 2S*, 3S*, 5S*)-5-(5,6-Dichloro-2-amino-1H-benzimidazol-1-yl)-3-(hydroxymethyl)-1 ,2-cyclopentanediol
- (.+-.)-(1R*, 2R*, 4S*)-2-(2-Cyclopropylamino-5,6-dichloro-1H-benzimidazol-1-yl)-4-(hydroxymethyl)cyclopentanol
- (.+-.)-(1R*, 2S*, 3S*, 5S*)-5-�5,6-Dichloro-2-(cyclobutylamino)-1H-benzimidazol-1-yl!-3-(hydroxymethyl)-1,2-cyclopentanediol
- (.+-.)-(1R*, 2S*, 3S*, 5S*)-5-�5,6-Dichloro-2-(1azetidinyl)-1H-benzimidazol-1-yl!-3-(hydroxymethyl)-1,2-cyclopentanediol
- (.+-.)-(1R*, 2S*, 3R*, 5R*)-5-�5,6-Dichloro-2-(cyclopropylamino)-1H-benzimidazol-1-yl!-3-(hydroxymethyl)-1,2-cyclopentanediol
- (.+-.)-(1R*, 2S*, 3R*, 5S*)-5-�5,6-Dichloro-2-(cyclopropylamino)-1H-benzimidazol-1-yl!-3-methyl-1,2-cyclopentanediol
- (1R, 2S, 3S, 5S)-5-�2-(tert-Butylamino)-5,6-dichloro-1H-benzimidazol-1-yl!-3-(hydroxymethyl)-1,2-cyclopentanediol
- (.+-.)-(1R*, 2S*, 3S*, 5S*)-5-�2-(tert-Butylamino)-5,6-dichloro-1H-benzimidazol-1-yl!-3-(hydroxymethyl)-1,2-cyclopentanediol
- (.+-.)-(1R*, 2S*, 3 S*, 5S*)-5-�5,6-Dichloro-2-(isopropylamino)-1H-benzimidazol-1-yl!-3 -(hydroxymethyl)-1 ,2-cyclopentanediol
- (1S,2R,3R,5R)-5-�-5,6-Dichloro-2-(isopropylamino)-1H-benzimidazol-1-yl!-3-(hydroxymethyl)-1,2-cyclopentanediol;
- (1 S,2R,3R,5R)-5-�2-tert-butylamino)-5,6-dichloro-1H-benzimidazol-1-yl!-3-(hydroxymethyl)-1,2-cyclopentanediol;
- (.+-.)-(1R*, 2S*, 3S*, 5S*)-5-�5,6-Dichloro-2-(1-azetidinyl)-1H-benzimidazol-1-yl!-3-(hydroxymethyl)-1,2-cyclopentanediol;
- (1R, 2S, 3S, 5S)-5-�5,6-Dichloro-2-(1-azetidinyl)-1H-benzimidazol-1-yl!-3-(hydroxymethyl)-1,2-cyclopentanediol; and
- (1S, 2R, 3R, 5R)-5-�5,6-Dichloro-2-(1-azetidinyl-1H-benzimidazol-1-yl!!-3-(hydroxymethyl)-1,2-cyclopentanediol and pharmaceutically acceptable derivatives thereof.
- 9. A method for the treatment of a herpes viral infection in a subject which comprises treating the subject with a therapeutically effective amount of at least one compound of formula (I) or (I-1) (as defined in claim 1) or a pharmaceutically acceptable derivative thereof.
- 10. A method according to claim 9 wherein the herpes viral infection is a cytomegalovirus infection.
- 11. A method according to claim 9 wherein said compound is selected from
- (1R, 2S, 3S, 5S)-5-�5,6-Dichloro-2-(cyclopropylamino)-1H-benzimidazol-1-yl!-3-(hydroxymethyl)-1,2-cyclopentanediol
- (1R, 2S, 3S, 5S)-5-�5,6-Dichloro-2-(isopropylamino)-1H-benzimidazol-1-yl!-3-(hydroxymethyl)-1,2-cyclopentanediol
- (.+-.)-(1R*, 2S*, 3S*, 5S*)-5-(5,6-Dichloro-2-amino-1H-benzimidazol-1-yl)-3-(hydroxymethyl)-1,2-cyclopentanediol
- (.+-.)-(1R*, 2R*, 4S*)-2-(2-Cyclopropylamino-5,6-dichloro-1H-benzimidazol-1-yl)-4-(hydroxymethyl)cyclopentanol
- (.+-.)-(1R*, 2S*, 3S*, 5S*)-5-�5,6-Dichloro-2-(cyclobutylamino)-8H-benzimidazol-1-yl!-3-(hydroxymethyl)-1,2-cyclopentanediol
- (.+-.)-(1R*, 2S*, 3S*, 5S*)-5-�5,6-Dichloro-2-(1-azetidinyl)-1H-benzimidazol-1-yl!-3-(hydroxymethyl)-1,2-cyclopentanediol
- (.+-.)-(1R*, 2S*, 3R*, 1R*)-5-�5,6-Dichloro-2-(cyclopropylamino)-1H-benzimidazol-1-yl!-3-(hydroxymethyl)-1,2-cyclopentanediol
- (.+-.)-(1R*, 2S*, 3R*, 5S*)-5-�5,6-Dichloro-2-(cyclopropylamino)-1H-benzimidazol-1-yl!-3 -methyl- 1,2-cyclopentanediol
- (1R, 2S, 3S, 5S)-5-�2-(tert-Butylamino)-5,6-dichloro-1H-benzimidazol-1-yl!-3-(hydroxymethyl)-1,2-cyclopentanediol
- (.+-.)-(1R*, 2S*, 3S*, 5S*)-5-�2-(tert-Butylamino)-5,6-dichloro-1H-benzimidazol-1-yl!-3-(hydroxymethyl)-1,2-cyclopentanediol
- (.+-.)-(1 R*, 2S*, 3S*, 5S*)-5-�5,6-Dichloro-2-(isopropylamino)-1H-benzimidazol-1-yl!-3-(hydroxymethyl)-1,2-cyclopentanediol
- (1S,.sup.2 R,3R,5R)-5-�5,6-Dichloro-2-(isopropylamino)-1H-benzimidazol-1-yl!-3-(hydroxymethyl)-1,2-cyclopentanediol;
- (1S,2R,3R,5R)-5-�2-tert-butylamino)-5,6-dichloro-1H-benzimidazol-1 -yl!-3-(hydroxymethyl)-1,2-cyclopentanediol;
- (.+-.)-(1R*, 2S*, 3S*, 5S*)-5-�5,6-Dichloro-2-(1-azetidinyl)-1H-benzimidazol-1-yl!-3-(hydroxymethyl)-1,2-cyclopentanediol;
- (1R, 2S, 3S, 5S)-5-�5,6-Dichloro-2-(1-azetidinyl)-1H-benzimidazol-1-yl!-3-(hydroxymethyl)-1,2-cyclopentanediol; and
- (1S, 2R, 3R, 5R)-5-�5,6-Dichloro-2-(1-azetidinyl-1H-benzimidazol-1-yl!!-3-(hydroxymethyl)-1,2-cyclopentanediol, and pharmaceutically acceptable derivatives thereof.
- 12. Pharmaceutical formulations comprising at least one compound of formula (I) or (I-1) (as defined in claim 1) or a pharmaceutically acceptable derivative thereof together with at least one pharmaceutically acceptable carrier or excipient.
- 13. A pharmaceutical formulation according to claim 13 wherein said compound is selected from
- (1R, 2S, 3S, 5S)-5-�5,6-Dichloro-2-(cyclopropylamino)-1H-benzimidazol-1-yl!-3-hydroxymethyl)-1,2-cyclopentanediol
- (1R, 2S, 3S, 5S)-5-�5,6-Dichloro-2-(isopropylamino)-1H-benzimidazol-1-yl!-3-(hydroxymethyl)-1,2-cyclopentanediol
- (.+-.)-(1R*, 2S*, 3S*, 5S*)-5-(5,6-Dichloro-2-amino-1H-benzimidazol-1-yl)-3-(hydroxymethyl)-1,2-cyclopentanediol
- (.+-.)-(1R*, 2R*, 4S*)-2-(2-Cyclopropylamino-5,6-dichloro-1H-benzimidazol-1-yl)-4-(hydroxymethyl)cyclopentanol
- (.+-.)-(1R*, 2S*, 3S*, 5S*)-5-�5,6-Dichloro-2-(cyclobutylamino)-1H-benzimidazol-1-yl!-3-(hydroxymethyl)-1,2-cyclopentanediol
- (.+-.)-(1R*, 2S*, 3S*, 5S*)-5-�5,6-Dichloro-2-( 1-azetidinyl)-1H-benzimidazol-1-yl!-3-(hydroxymethyl)-1,2-cyclopentanediol
- (.+-.)-(1R*, 2S*, 3R*, 5R*)-5-�5,6-Dichloro-2-(cyclopropylamino)-1H-benzimidazol-1-yl!-3-(hydroxymethyl)-1,2-cyclopentanediol
- (.+-.)-(1R*, 2S*, 3R*, 5S*)-5-�5,6-Dichloro-2-(cyclopropylamino)-1H-benzimidazol-1-yl!-3-methyl-1,2-cyclopentanediol
- (1 R, 2S, 38, 5S)-5-�2-(tert-Butylamino)-5,6-dichloro-1H-benzimidazol-1-yl!-3-(hydroxymethyl)-1,2-cyclopentanediol
- (.+-.)-(1R*, 2S*, 3S*, 5S*)-5-�2-(tert-Butylamino)-5,6-dichloro-1H-benzimidazol-1-yl!-3-(hydroxymethyl)-1,2-cyclopentanediol
- (.+-.)-(1R*, 2S*, 3S*, 5S*)-5-�5,6-Dichloro-2-(isopropylamino)-1H-benzimidazol-1-yl!-3-(hydroxymethyl)-1,2-cyclopentanediol
- and pharmaceutically acceptable derivatives thereof.
- 14. A process for the preparation of preparation of compounds of formulae (I) and (a-1 (as defined in claim 1) alone or in combination with their mirror image enantiomers, and their pharmaceutically acceptable derivatives which comprises (A) reacting ##STR9## or the mirror image enantiomer thereof, with a) either a compound of formula R.sup.4 CO.sub.2 H wherein R.sup.4 is H, C.sub.1-4 alkyl or C.sub.1-4 perfluoroalkyl or a compound of formula R.sup.4 C(OR).sub.3 wherein R.sup.4 is H, C.sub.1-4 alkyl or C.sub.1-4 perfluoroalkyl and R is C.sub.1-4 alkyl to form a compound of formula (IA) or (IA-1) in which R.sup.4 is H; or
- b) cyanogen bromide to form a compound of formula (IA) or (IA-1) in which R.sup.4 is NH.sub.2 ;
- (B)
- a) converting a compound of formula (IA) or (IA-1) in which R.sup.4 is hydrogen into a farther compound of formula (IA) or (IA-1) in which R.sup.4 is a leaving group; or
- b) converting a compound of formula (IA) or (IA-1) in which R.sup.4 is Cl, Br or I into a further compound of formula (IA) or (IA-1) in which R.sup.4 is an amino or substituted amino group --NR.sup.8 R.sup.9 as defined above: or
- (C) reacting a compound of formula ##STR10## (wherein R.sup.4, R.sup.5, R.sup.6 and R.sup.7 are as herebefore defined) or a functional equivalent thereof with a compound of formula ##STR11## wherein R.sup.1, R.sup.2 and R.sup.3 are as defined above and L is a leaving group, to form a compound of formula (IA) or (IA-1) in which R.sup.4 is hydrogen, halogen or the --NR.sup.8 R.sup.9 and optionally converting a compound of formula (IA) or (IA-1) into a pharmaceutically acceptable derivative thereof.
CROSS REFERENCE TO RELATED APPLICATIONS
This application is a 35 USC 371 of PCT/US95/11366 filed Sep. 11, 1995. This application is a continuation-in-part of application Ser. No. 08/304,006 filed Sep. 9, 1994, now U.S. Pat. No. 5,534,535 which in turn is a 35 USC 371 of PCT/GB93/00479 filed Mar. 8, 1993.
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
102e Date |
371c Date |
PCT/US95/11366 |
9/11/1995 |
|
|
4/7/1997 |
4/7/1997 |
Publishing Document |
Publishing Date |
Country |
Kind |
WO96/07646 |
3/14/1996 |
|
|
US Referenced Citations (1)
Number |
Name |
Date |
Kind |
5534535 |
Townsend et al. |
Jul 1996 |
|
Foreign Referenced Citations (1)
Number |
Date |
Country |
9607646 |
Mar 1996 |
WOX |
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
304006 |
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