Pyrazolopyridinyl pyrimidine therapeutic compounds Number:7,153,855 from the United States Patent and Trademark Office (PTO) owispatent The present invention provides compounds of formula (I): ##STR00001## pharmaceutical compositions containing the same, processes for preparing the same and their use as pharmaceutical agents.<H Pyrazolopyridinyl, therapeutic, Pyrazolopyridin, 7153855.html, Patent, pto, 7153855

Title: Pyrazolopyridinyl pyrimidine therapeutic compounds

Abstract: The present invention provides compounds of formula (I): ##STR00001## pharmaceutical compositions containing the same, processes for preparing the same and their use as pharmaceutical agents.

Patent Number: 7,153,855 Issued on 12/26/2006 to Boyd, et al.

Inventors: Boyd; F. Leslie (Durham, NC), Gudmundsson; Kristjan (Durham, NC), Johns; Brian A (Durham, NC)
Assignee: SmithKline Beecham Corporation (Philadelphia, PA)

Appl. No.: 10/468,729

Filed: March 5, 2002

PCT Filed: March 05, 2002

PCT No.: PCT/US02/06552

371(c)(1),(2),(4) Date: August 22, 2003

PCT Pub. No.: WO02/072581

PCT Pub. Date: September 19, 2002

Current U.S. Class: 514/235.8 ; 514/252.18; 514/274; 514/275; 544/122; 544/316; 544/331

Current International Class: C07D 471/04 (20060101); A61K 31/435 (20060101); C07D 401/04 (20060101)

Field of Search: 544/122,316,331 514/235.8,274,252.18,275

References Cited [Referenced By]

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Primary Examiner: Rao; Deepak
Attorney, Agent or Firm: Morgan; Lorie Ann

Parent Case Text

CROSS REFERENCES TO RELATED APPLICATIONS

This application is a 371 Application of PCT/US02/06552, filed 5 Mar. 2002, which claims priority to U.S. Application Ser. No. 60/274,297, filed 8 Mar. 2001.

Claims

The invention claimed is:

1. A compound of formula (I): ##STR00171## wherein: R.sup.1 is selected from the group consisting of halo, --NR.sup.7R.sup.8, Ay, --NR.sup.7Ay, Het, --NHR.sup.10Het, --NHHet and --NHR.sup.10Ay; each R.sup.7 and R.sup.8 are the same or different and are independently selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, cycloalkenyl, --R.sup.10cycloalkyl, --R.sup.10OR.sup.9, --NR.sup.9R.sup.11, --R.sup.10NR.sup.9R.sup.11, --R.sup.10C(O)R.sup.9, --C(O)R.sup.9, --C(O)R.sup.10Ay, --C(O)R.sup.10Het, --CO.sub.2R.sup.9, --R.sup.10CO.sub.2R.sup.9, --C(O)NR.sup.9R.sup.11, --R.sup.10C(O)NR.sup.9R.sup.11, --R.sup.10C(O)Ay, --R.sup.10C(O)Het, --C(S)NR.sup.9R.sup.11, --R.sup.10C(S)NR.sup.9R.sup.11, --R.sup.10NHC(NH)NR.sup.9R.sup.11, --R.sup.10NHC(O)R.sup.10Het, --R.sup.10NHC(O)R.sup.10CO.sub.2R.sup.9, --R.sup.10NHC(NCO.sub.2R.sup.9)NHCO.sub.2R.sup.9, --R.sup.10NHC(O)NHSO.sub.2R.sup.9, --R.sup.10NHC(O)NHSO.sub.2Ay, --R.sup.10NHC(O)NHSO.sub.2Het, --R.sup.10C(NH)NR.sup.9R.sup.11, --C(NH)NR.sup.9R.sup.11, --SO.sub.2NR.sup.9R.sup.11, --R.sup.10SO.sub.2NR.sup.9R.sup.11, --R.sup.10NHSO.sub.2R.sup.9, --SO.sub.2R.sup.10, --R.sup.10SO.sub.2R.sup.10, --R.sup.10NHCOR.sup.9, --R.sup.10SO.sub.2NHCOR.sup.9, --R.sup.10NHP(O)(OR.sup.9).sub.2, --R.sup.10OP(O)(OR.sup.9).sub.2 and --R.sup.10OP(O)(OR.sup.10Ay).sub.2; each R.sup.9 and R.sup.11 are the same or different and are independently selected from the group consisting of H, alkyl, cycloalkyl, --R.sup.10cycloalkyl, --R.sup.10OH, --R.sup.10(OR.sup.10).sub.w where w is 1 10, and --R.sup.10NR.sup.10R.sup.10; each R.sup.10 is the same or different and is independently selected from the group consisting of alkyl, cycloalkyl, alkenyl, cycloalkenyl and alkynyl; Ay is aryl; Het is a 5- or 6-membered heterocyclic or heteroaryl group; R.sup.2 is selected from the group consisting of halo, alkyl, cycloalkyl, alkenyl, cycloalkenyl, --NR.sup.7R.sup.8, --OR.sup.7, --OAy, --S(O).sub.nR.sup.9, --S(O).sub.nAy, --R.sup.10NR.sup.7R.sup.8, --R.sup.10NR.sup.7Ay, Ay, Het, --NHHet, --NHR.sup.10Het, --OHet and --OR.sup.10Het; n is 0, 1 or 2; Y is N; R.sup.3 and R.sup.4 are the same or different and are each independently selected from the group consisting of H, halo, alkyl, cycloalkyl, alkenyl, Ay, --OR.sup.7, --OAy, --R.sup.10OR.sup.7, --R.sup.10OAy, --NR.sup.7R.sup.8, --NR.sup.7Ay, --R.sup.10NR.sup.7R.sup.8, --R.sup.10NR.sup.7Ay, --C(O)R.sup.7, --C(O)Ay, --CO.sub.2R.sup.7, --CO.sub.2Ay, --SO.sub.2NHR.sup.9, Het, --NHHet and --NHR.sup.10Het; q is 0, 1, 2, 3, 4 or 5; and each R.sup.5 is the same or different and is independently selected from the group consisting of halo, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, --R.sup.10cycloalkyl, Ay, --NHR.sup.10Ay, Het, --NHHet, --NHR.sup.10Het, --OR.sup.7, --OAy, --OHet, --R.sup.10OR.sup.9, --NR.sup.7R.sup.8, --NR.sup.7Ay, --R.sup.10NR.sup.7R.sup.8, --R.sup.10NR.sup.7Ay, --R.sup.10C(O)R.sup.9, --C(O)R.sup.9, --CO.sub.2R.sup.9, --R.sup.10CO.sub.2R.sup.9, --C(O)NR.sup.7R.sup.8, --C(O)Ay, --C(O)NR.sup.7Ay, --C(O)Het, --C(O)NHR.sup.10Het --R.sup.10C(O)NR.sup.9R.sup.11, --C(S)NR.sup.9R.sup.11, --R.sup.10C(S)NR.sup.9R.sup.11, --R.sup.10NHC(NH)NR.sup.9R.sup.11, --C(NH)NR.sup.7R.sup.8, --C(NH)NR.sup.7Ay, --R.sup.10C(NH)NR.sup.9R.sup.11, --S(O).sub.2NR.sup.7R.sup.8, --S(O).sub.2NR.sup.7Ay, --R.sup.10SO.sub.2NHCOR.sup.9, --R.sup.10SO.sub.2NR.sup.9R.sup.11, --R.sup.10SO.sub.2R.sup.9, --S(O).sub.nR.sup.9, cyano, nitro and azido; or two adjacent R.sup.5 groups together with the atoms to which they are bonded form a C.sub.5-6 cycloalkyl or aryl; wherein when q is 1 and R.sup.5 is in the para position, R.sup.5 is not halo; and or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 wherein R.sup.1 is selected from the group consisting of --NR.sup.7R.sup.8, Ay, --NR.sup.7Ay, Het, --NHR.sup.10Het, --NHHet and --NHR.sup.10Ay.

3. The compound according to claim 1 wherein R.sup.1 is selected from the group consisting of --NR.sup.7R.sup.8 and Het.

4. The compound according to claim 1 wherein R.sup.2 is selected from the group consisting of --NR.sup.7R.sup.8, --OR.sup.7, --OAy, --S(O).sub.nR.sup.9, --S(O).sub.nAy, --R.sup.10NR.sup.7R.sup.8, --R.sup.10NR.sup.7Ay, Ay, Het, --NHR.sup.10Het, --NHHet, --OHet and --OR.sup.10Het.

5. The compound according to claim 1 wherein R.sup.2 is selected from the group consisting of --NR.sup.7R.sup.8 and Het.

6. The compound according to claim 1 wherein R.sup.3 and R.sup.4 are the same or different and are each independently selected from the group consisting of H, halo, alkyl, --OR.sup.7, --R.sup.10OR.sup.7, --NR.sup.7R.sup.8, --R.sup.10NR.sup.7R.sup.8, --CO.sub.2R.sup.7 and Ay.

7. The compound according to claim 1 wherein R.sup.3 and R.sup.4 are each H.

8. The compound according to claim 1 wherein q is 0 or 1.

9. The compound according to claim 1 wherein each R.sup.5 is the same or different and is independently selected from the group consisting of halo, alkyl, alkenyl, --OR.sup.7, --CO.sub.2R.sup.9, --NR.sup.7R.sup.8, --C(O)NR.sup.7R.sup.8, Ay, --NHR.sup.10Ay, Het, --S(O).sub.2NR.sup.7R.sup.8, cyano, nitro and azido.

10. The compound according to claim 1 wherein each R.sup.5 is the same or different and is independently selected from the group consisting of halo, alkyl, --OR.sup.7, --NR.sup.7R.sup.8 and cyano.

11. A compound selected from the group consisting of: N-Cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimidinyl]-2-(4-methoxyphenyl)-- pyrazolo[1,5-a]pyridin-7-amine, N-Cyclopentyl-4-[2-(4-methoxyphenyl)-7-(1-pyrrolidinyl)pyrazolo[1,5-a]pyr- idin-3-yl]-2-pyrimidinamine, 4-[2-(4-Methoxyphenyl)-7-(1-pyrrolidinyl)pyrazolo[1,5-a]pyridin-3-yl]-2-p- yrimidinamine, 4-{7-(Cyclopentylamino)-3-[2-(cyclopentylamino)-4-pyrimidinyl]pyrazolo-[1- ,5-a]pyridin-2-yl}phenol, 4-[3-[2-(Cyclopentylamino)-4-pyrimidinyl]-7-(1-pyrrolidinyl)pyrazolo[1,5-- a]pyridin-2-yl]phenol, 4-[3-(2-Amino-4-pyrimidinyl)-7-(1-pyrrolidinyl)pyrazolo[1,5-a]pyridin-2-y- l]phenol, 2-[4-(Allyloxy)phenyl]-N-cyclopentyl-3-[2-(cyclopentylamino)-4-p- yrimidinyl]pyrazolo-[1,5-a]pyridin-7-amine, Ethyl (4-{7-(cyclopentylamino)-3-[2-(cyclopentylamino)-4-pyrimidinyl]-pyrazolo[- 1,5-a]pyridin-2-yl}phenoxy)acetate, 2-(4-Butoxyphenyl)-N-cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimidinyl]-p- yrazolo[1,5-a]pyridin-7-amine, N-Cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimidinyl]-2-(4-isobutoxyphenyl- )pyrazolo-[1,5-a]pyridin-7-amine, N-Cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimidinyl]-2-[4-(cyclopropyl-me- thoxy)-phenyl]pyrazolo[1,5-a]pyridin-7-amine, 2-[4-(Cyclobutylmethoxy)phenyl]-N-cyclopentyl-3-[2-(cyclopentylamino)-4-p- yrimidinyl]pyrazolo[1,5-a]pyridin-7-amine, N-Cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimidinyl]-2-(4-phenoxyphenyl)-- pyrazolo[1,5-a]pyridin-7-amine, 2-[1,1'-Biphenyl]-4-yl-N-butyl-3-[2-(butylamino)-4-pyrimidinyl]pyrazolo-[- 1,5-a]pyridin-7-amine, N-{4-[2-(4-Aminophenyl)-7-(butylamino)pyrazolo[1,5-a]pyridin-3-yl]-2-pyri- midinyl}-N-butylamine, N-Butyl-3-[2-(butylamino)-4-pyrimidinyl]-2-[4-(cyclohexylamino)phenyl]-py- razolo[1,5-a]pyridin-7-amine, N-Butyl -3-[2-(butylamino)-4-pyrimidinyl]-2-(4-isopropenylphenyl)-pyrazolo[1,5-a]- pyridin-7-amine, 2-(4-Anilinophenyl)-N-butyl-3-[2-(butylamino)-4-pyrimidinyl]pyrazolo[1,5-- a]pyridin-7-amine, 2-(4-Anilinophenyl)-N-butyl-3-[2-(butylamino)-4-pyrimidinyl]-N-phenylpyra- zolo[1,5-a]pyridin-7-amine, 2-{4-[Bis(cyclopropylmethyl)amino]phenyl}-N-butyl-3-[2-(butylamino)-4-pyr- imidinyl]pyrazolo[1,5-a]pyridin-7-amine, N-butyl-3-[2-(butylamino)-4-pyrimidinyl]-2-{4-[(cyclopropylmethyl)amino]p- henyl}-pyrazolo[1,5-a]pyridin-7-amine, N-Butyl -3-[2-(butylamino)-4-pyrimidinyl]-2-[4-(dimethylamino)phenyl]-pyrazolo[1,- 5-a]pyridin-7-amine, 2-(2-Bromophenyl)-N-cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimidinyl]pyr- azolo[1,5-a]pyridin-7-amine, 2-(3-Bromophenyl)-N-cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimidinyl]pyr- azolo[1,5-a]pyridin-7-amine, 4-[2-(3-Bromophenyl)-7-(1-pyrrolidinyl)pyrazolo[1,5-a]pyridin-3-yl]-N-cyc- lopentyl-2-pyrimidinamine, N-[3-(2-Amino-4-pyrimidinyl)-2-(3-bromophenyl)pyrazolo[1,5-a]pyridin-7-yl- ]-N-cyclopentylamine, 4-[2-(3-Bromophenyl)-7-(1-pyrrolidinyl)pyrazolo[1,5-a]pyridin-3-yl]-2-pyr- imidinamine, 2-[1,1'-Biphenyl]-3-yl-N-cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimidiny- l]pyrazolo-[1,5-a]pyridin-7-amine, 4-[2-[1,1'-Biphenyl]-3-yl-7-(1-pyrrolidinyl)pyrazolo[1,5-a]pyridin-3-yl]-- N-cyclopentyl-2-pyrimidinamine, N-Cyclopentyl -3-[2-(cyclopentylamino)-4-pyrimidinyl]-2-[3-(4-pyridinyl)phenyl]-pyrazol- o[1,5-a]pyridin-7-amine, N-Cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimidinyl]-2-[3-(3-thienyl)phen- yl]pyrazolo-[1,5-a]pyridin-7-amine, N-Cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimidinyl]-2-[3-(2-thienyl)-phe- nyl]pyrazolo[1,5-a]pyridin-7-amine, 2-(3-Aminophenyl)-N-cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimidinyl]pyr- azolo[1,5-a]pyridin-7-amine, N-(3-{7-(Cyclopentylamino)-3-[2-(cyclopentylamino)-4-pyrimidinyl]pyrazolo- [1,5-a]pyridin-2-yl}phenyl)acetamide, N-(3-{7-(Cyclopentylamino)-3-[2-(cyclopentylamino)-4-pyrimidinyl]-pyrazol- o[1,5-a]pyridin-2-yl}phenyl)methanesulfonamide, 4-[2-(3-Aminophenyl)-7-(1-pyrrolidinyl)pyrazolo[1,5-a]pyridin-3-yl]-N-cyc- lopentyl-2-pyrimidinamine, N-cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimidinyl]-2-phenylpyrazolo-[1,- 5-a]pyridin-7-amine, 3-{7-(Cyclopentylamino)-3-[2-(cyclopentylamino)-4-pyrimidinyl]pyrazolo[1,- 5-a]pyridin-2-yl}benzonitrile, 3-{7-(Cyclopentylamino)-3-[2-(cyclopentylamino)-4-pyrimidinyl]-pyrazolo[1- ,5-a]pyridin-2-yl}benzamide, 3-{7-(Cyclopentylamino)-3-[2-(cyclopentylamino)-4-pyrimidinyl]pyrazolo-[1- ,5-a]pyridin-2-yl}benzoic acid, N-{4-[2-(3-Bromo-4-methoxyphenyl)-7-(cyclopentylamino)pyrazolo[1,5-a]pyri- din-3-yl]-2-pyrimidinyl}-N-cyclopentylamine, 2-(3-Bromo-4-chlorophenyl)-N-cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimi- dinyl]-pyrazolo[1,5-a]pyridin-7-amine, 2-(3-Amino-4-chlorophenyl)-N-cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimi- dinyl]pyrazolo[1,5-a]pyridin-7-amine, 2-[4-(Benzylamino)phenyl]-N-butyl-3-[2-(butylamino)-4-pyrimidinyl]-pyrazo- lo[1,5-a]pyridin-7-amine, N-Cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimidinyl]-2-(3-methylphenyl)py- razolo[1,5-a]pyridin-7-amine, 4-[7-Chloro-2-(3-methylphenyl)pyrazolo[1,5-a]pyridin-3-yl]-N-cyclopentyl-- 5,6-dimethyl-2-pyrimidinamine, N-cyclopentyl-3-[2-(cyclopentylamino)-5,6-dimethyl-4-pyrimidinyl]-2-(3-me- thylphenyl)pyrazolo[1,5-a]pyridin-7-amine, 3-[2-(Cyclopentylamino)-4-pyrimidinyl]-N-isopropyl-2-(3-methylphenyl)pyra- zol[1,5-a]pyridin-7-amine, 4-[7-Chloro-2-(3-methoxyphenyl)pyrazolo[1,5-a]pyridin-3-yl]-N-cyclopentyl- -2-pyrimidinamine, N-Cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimidinyl]-2-(3-methoxyphenyl)p- yrazolo[1,5-a]pyridin-7-amine, 3-[2-(Cyclopentylamino)-4-pyrimidinyl]-N-isopropyl-2-(3-methoxyphenyl)pyr- azolo[1,5-a]pyridin-7-amine, 3-[2-(Cyclopentylamino)-4-pyrimidinyl]-2-(3-methoxyphenyl)-N,N-dimethylpy- razolo[1,5-a]pyridin-7-amine, 3-{7-(Cyclopentylamino)-3-[2-(cyclopentylamino)-4-pyrimidinyl]pyrazolo[1,- 5-a]pyridin-2-yl}phenol, N-Cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimidinyl]-2-[3-(cyclopropylmet- hoxy)phenyl]pyrazolo[1,5-a]pyridin-7-amine, N-Cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimidinyl]-2-(3-fluorophenyl)py- razolo[1,5-a]pyridin-7-amine, 2-(3-Chlorophenyl)-N-cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimidinyl]py- razolo[1,5-a]pyridin-7-amine, N-Cyclopentyl-3-[2-(cyclopropylamino)-4-pyrimidinyl]-2-(4-methoxyphenyl)p- yrazolo[1,5-a]pyridin-7-amine, 3-[2-(Cyclopentylamino)-4-pyrimidinyl]-2-(4-methoxyphenyl)-N-[2-(4-morpho- linyl)ethyl]pyrazolo[1,5-a]pyridin-7-amine, 3-[2-(Cyclopentylamino)-4-pyrimidinyl]-N-cyclopropyl-2-(4-methoxyphenyl)p- yrazolo[1,5-a]pyridin-7-amine, N-Cyclopentyl-4-[2-(4-methoxyphenyl)-7-(4-morpholinyl)pyrazolo[1,5-a]pyri- din-3-yl]-2-pyrimidinamine, 3-[2-(Cyclopentylamino)-4-pyrimidinyl]-N-(2-methoxyethyl)-2-(4-methoxyphe- nyl)pyrazolo[1,5-a]pyridin-7-amine, N-Cyclopropyl-4-[2-(4-methoxyphenyl)-7-(4-morpholinyl)pyrazolo[1,5-a]pyri- din-3-yl]-2-pyrimidinamine, 3-[2-(Cyclopropylamino)-4-pyrimidinyl]-N-(2-methoxyethyl)-2-(4-methoxyphe- nyl)pyrazolo[1,5-a]pyridin-7-amine, 3-[2-(Cyclopropylamino)-4-pyrimidinyl]-2-(4-methoxyphenyl)-N-[2-(4-morpho- linyl)ethyl]pyrazolo[1,5-a]pyridin-7-amine, N-Cyclopropyl-3-[2-(cyclopropylamino)-4-pyrimidinyl]-2-(4-methoxyphenyl)p- yrazolo[1,5-a]pyridin-7-amine, 4-[3-[2-(Cyclopentylamino)-4-pyrimidinyl]-7-(cyclopropylamino)pyrazolo[1,- 5-a]pyridin-2-yl]phenol, 4-{7-(Cyclopentylamino)-3-[2-(cyclopropylamino)-4-pyrimidinyl]pyrazolo[1,- 5-a]pyridin-2-yl}phenol, 4-{7-(Cyclopropylamino)-3-[2-(cyclopropylamino)-4-pyrimidinyl]pyrazolo[1,- 5-a]pyridin-2-yl}phenol, 3-[2-(Cyclopentylamino)-4-pyrimidinyl]-N-cyclopropyl-2-[4-(cyclopropylmet- hoxy)phenyl]pyrazolo[1,5-a]pyridin-7-amine, 2-[4-(Allyloxy)phenyl]-N-cyclopentyl-3-[2-(cyclopropylamino)-4-pyrimidiny- l]pyrazolo[1,5-a]pyridin-7-amine, N-Cyclopropyl-3-[2-(cyclopropylamino)-4-pyrimidinyl]-2-[4-(cyclopropylmet- hoxy)phenyl]pyrazolo[1,5-a]pyridin-7-amine, 2-[4-(Allyloxy)phenyl]-N-cyclopropyl-3-[2-(cyclopropylamino)-4-pyrimidiny- l]pyrazolo[1,5-a]pyridin-7-amine, N-Butyl-3-[2-(butylamino)pyrimidin-4-yl]-2-{4-[(4-methoxybenzyl)amino]phe- nyl}pyrazolo[1,5-a]pyridin-7-amine, N-Butyl-3-[2-(butylamino)pyrimidin -4-yl]-2-(4-morpholin-4-yl phenyl)pyrazolo[1,5-a]pyridin-7-amine, 2-(3-Bromophenyl)-N-cyclopentyl-3-[2-(cyclopropylamino)-4-pyrimidinyl]pyr- azolo[1,5-a]pyridin-7-amine, 2-(3-Bromophenyl)-3-[2-(cyclopentylamino)-4-pyrimidinyl]-N-cyclopropylpyr- azolo[1,5-a]pyridin-7-amine, 2-(3-Bromophenyl)-N-cyclopropyl-3-[2-(cyclopropylamino)-4-pyrimidinyl]pyr- azolo[1,5-a]pyridin-7-amine, Methyl N-[3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(4-methoxyphenyl)pyrazolo[1,5- -a]pyridin-7-yl]glycinate, 5-[(3aS,4S,6aR)-2-Oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl]-N-(4-{7-(bu- tylamino)-3-[2-(butylamino)pyrimidin-4-yl]pyrazolo[1,5-a]pyridin-2-yl}phen- yl)pentanamide, N-[3-[2-(Cyclopentylamino)pyrimidin-4-yl]-2-(4-methoxyphenyl)pyrazolo[1,5- -a]pyridin-7-yl]butane-1,4-diamine, 5-[(3aS,4S,6aR)-2-Oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl]-N-(4-{[3-[2- -(cyclopentylamino)pyrimidin-4-yl]-2-(4-methoxyphenyl)pyrazolo[1,5-a]pyrid- in-7-yl]amino}butyl)pentanamide, 3-[2-(Cyclopentylamino)pyrimidin-4-yl]-2-(4-methoxyphenyl)pyrazolo[1,5-a]- pyridin-7-amine, N,N'-di-tert-butoxycarbonyl-N-(4-{[3-[2-(cyclopentylamino)pyrimidin-4-yl]- -2-(4-methoxyphenyl)pyrazolo[1,5-a]pyridin-7-yl]amino}butyl)guanidine, N-(4-{[3-[2-(Cyclopentylamino)pyrimidin-4-yl]-2-(4-methoxyphenyl)pyrazolo- [1,5-a]pyridin-7-yl]amino}butyl)guanidine, N-(4-{[3-[2-(Cyclopentylamino)pyrimidin-4-yl]-2-(4-methoxyphenyl)pyrazolo- [1,5-a]pyridin-7-yl]amino}butyl)methanesulfonamide, N-{[(4-{[3-[2-(Cyclopentylamino)pyrimidin-4-yl]-2-(4-methoxyphenyl)pyrazo- lo[1,5-a]pyridin-7-yl]amino}butyl)amino]carbonyl}-4-methylbenzenesulfonami- de, 4-[(4-{[3-[2-(Cyclopentylamino)pyrimidin-4-yl]-2-(4-methoxyphenyl)pyra- zolo[1,5-a]pyridin-7-yl]amino}butyl)amino]-4-oxobutanoic acid, Diethyl 4-{[3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(4-methoxyphenyl)pyrazolo[1,- 5-a]pyridin-7-yl]amino}butylamidophosphate, 4-{[3-[2-(Cyclopentylamino)pyrimidin-4-yl]-2-(4-methoxyphenyl)pyrazolo[1,- 5-a]pyridin-7-yl]amino}butan-1-ol, Dibenzyl 4-{[3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(4-methoxyphenyl)pyrazolo[1,- 5-a]pyridin-7-yl]amino}butyl phosphate, 4-{[3-[2-(Cyclopentylamino)pyrimidin-4-yl]-2-(4-methoxyphenyl)pyrazolo[1,- 5-a]pyridin-7-yl]amino}butyl phosphate diammonium salt, 2-(3-Azidophenyl)-N-cyclopentyl-3-[2-(cyclopentylamino)pyrimidin-4-yl]pyr- azolo[1,5-a]pyridin-7-amine, 3-[2-(Cyclopentylamino)-4-pyrimidinyl]-2-(4-methoxyphenyl)-N-[2-oxo-2-(1-- pyrrolidinyl)ethyl]pyrazolo[1,5-a]pyridin-7-amine, N-(2-{[3-[2-(Cyclopentylamino)-4-pyrimidinyl]-2-(4-methoxyphenyl)pyrazolo- [1,5-a]pyridin-7-yl]amino}ethyl)methanesulfonamide, N.sup.1-[3-[2-(Cyclopentylamino)-4-pyrimidinyl]-2-(4-methoxyphenyl)pyrazo- lo[1,5-a]pyridin-7-yl]-1,2-ethanediamine, N-Cyclopentyl-4-[2-(3-fluorophenyl)-7-(4-morpholinyl)pyrazolo[1,5-a]pyrid- in-3-yl]-2-pyrimidinamine, N-Cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimidinyl]-2-[3-(trifluoromethy- l)phenyl]pyrazolo[1,5-a]pyridin-7-amine, 2-(3-Chlorophenyl)-N-cyclopropyl-3-[2-(cyclopropylamino)-4-pyrimidinyl]py- razolo[1,5-a]pyridin-7-amine, 2-(3-Chlorophenyl)-N-cyclopentyl-3-[2-(cyclopropylamino)-4-pyrimidinyl]py- razolo[1,5-a]pyridin-7-amine, 2-(3-Chlorophenyl)-3-[2-(cyclopentylamino)-4-pyrimidinyl]-N-cyclopropylpy- razolo[1,5-a]pyridin-7-amine, N-Cyclopentyl-3-[2-(cyclopropylamino)-4-pyrimidinyl]-2-(3-fluorophenyl)py- razolo[1,5-a]pyridin-7-amine, 4-[2-(3-Chlorophenyl)-7-(4-morpholinyl)pyrazolo[1,5-a]pyridin-3-yl]-N-cyc- lopentyl-2-pyrimidinamine, 2-(3-Chlorophenyl)-3-[2-(cyclopentylamino)-4-pyrimidinyl]-N-(2-methoxyeth- yl)pyrazolo[1,5-a]pyridin-7-amine, 3-[2-(Cyclopentylamino)-4-pyrimidinyl]-N-cyclopropyl-2-(3-fluorophenyl)py- razolo[1,5-a]pyridin-7-amine, 3-[2-(Cyclopentylamino)-4-pyrimidinyl]-2-(3-fluorophenyl)-N-(2-methoxyeth- yl)pyrazolo[1,5-a]pyridin-7-amine, and pharmaceutically acceptable salts thereof.

12. A pharmaceutical composition comprising a compound according to claim 1.

13. The pharmaceutical composition according to claim 12 further comprising a pharmaceutically acceptable carrier or diluent.

14. The pharmaceutical composition according to claim 12 further comprising an antiviral agent selected from the group consisting of aciclovir and valaciclovir.

15. A method for the treatment of a herpes viral infection selected from HSV-1 and HSV-2 in an animal, said method comprising administering to the animal a therapeutically effective amount of a compound according to claim 1.

16. A method for the treatment of a condition or disease associated with a herpes viral infection selected from HSV-1 and HSV-2 in an animal, comprising administering to the animal a therapeutically effective amount of a compound according to claim 1.

17. A process for preparing the compound according to claim 1 wherein R.sup.2 is selected from the group consisting of alkyl, cycloalkyl, alkenyl, cycloalkenyl, --NR.sup.7R.sup.8, --OR.sup.7, Ay, --OAy, --S(O).sub.nR.sup.9, --S(O).sub.nAy, --R.sup.10NR.sup.7R.sup.8, --R.sup.10NR.sup.7Ay, Het, --NHHet, --NHR.sup.10Het, --OHet, and --OR.sup.10Het, and R.sup.3 and R.sup.4 are H, said process comprising reacting a compound of formula (IX): ##STR00172## with an amine of formula (X): ##STR00173##

18. A process for preparing the compound according to claim 1 wherein R.sup.2 is selected from the group consisting of alkyl, cycloalkyl, alkenyl, cycloalkenyl, --NR.sup.7R.sup.8, --OR.sup.7, Ay, --OAy, --S(O).sub.nR.sup.9, --S(O).sub.nAy, --R.sup.10NR.sup.7R.sup.8, --R.sup.10NR.sup.7Ay, Het, --NHHet, --NHR.sup.10Het, --OHet, and --OR.sup.10Het; R.sup.3 is selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, --R.sup.10OR.sup.7, --R.sup.10OAy, --NR.sup.7R.sup.8 where R.sup.7 and R.sup.8 are not H, Ay, --NR.sup.7Ay where R.sup.7 is not H, --R.sup.10NR.sup.7R.sup.8, --R.sup.10NR.sup.7Ay, --C(O)R.sup.7, --C(O)Ay, --CO.sub.2R.sup.7, --CO.sub.2Ay, --SO.sub.2NHR.sup.9 and Het; and R.sup.4 is H, said process comprising reacting a compound of formula (XVI): ##STR00174## with an amine of formula (X): ##STR00175##

19. A process for preparing the compound according to claim 1 wherein and R.sup.2 is selected from the group consisting of alkyl, cycloalkyl, alkenyl, cycloalkenyl, --NR.sup.7R.sup.8, --OR.sup.7, Ay, --OAy, --S(O).sub.nR.sup.9, --S(O).sub.nAy, --R.sup.10NR.sup.7R.sup.8, --R.sup.10NR.sup.7Ay, Het, --NHHet, --NHR.sup.10Het, --OHet, and --OR.sup.10Het, said process comprising the steps of: a) reacting a compound of formula (XX): ##STR00176## with an amine of formula (X): ##STR00177## to prepare an intermediate compound; and b) oxidizing the intermediate compound.

20. A process for preparing the compound according to claim 1, said process comprising reacting a compound of formula (XXII): ##STR00178## wherein X.sup.1 is chloro, bromo or iodo; with a compound of formula XXIV: ##STR00179## wherein M.sup.2 is selected from the group consisting of --B(OH).sub.2, --B(ORa).sub.2, --B(Ra).sub.2, --Sn(Ra).sub.3, Zn-halide, ZnRa, and Mg-halide where Ra is alkyl or cycloalkyl and halide is halo.

Description

BACKGROUND OF THE INVENTION

The present invention relates to novel compounds, pharmaceutical formulations comprising these compounds, and the use of these compounds in therapy. More particularly, the present invention relates to compounds for the prophylaxis and treatment of herpes viral infections.

Of the DNA viruses, those of the herpes group are the sources of the most common viral illnesses in man. The group includes herpes simplex virus types 1 and 2 (HSV), varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpes virus type 6 (HHV-6), human herpes virus type 7 (HHV-7) and human herpes virus type 8 (HHV-8). HSV-1 and HSV-2 are some of the most common infectious agents of man. Most of these viruses are able to persist in the host's neural cells; once infected, individuals are at risk of recurrent clinical manifestations of infection which can be both physically and psychologically distressing.

Herpes simplex viruses (HSV-1 and -2) are the causative agents of herpes labialis and genital herpes. HSV infection is often characterised by extensive and debilitating lesions of the skin, mouth and/or genitals. Primary infections may be subclinical although tend to be more severe than infections in individuals previously exposed to the virus. Ocular infection by HSV can lead to keratitis or cataracts thereby endangering the host's sight. Infection in the new-born, in immunocompromised patients or penetration of the infection into the central nervous system can prove fatal. In the US alone, 40 million individuals are infected with HSV-2, a number that is expected to increase to 60 million by 2007. Over 80% of individuals infected with HSV-2 are unaware they carry and spread the virus, and of those diagnosed less than 20% received oral therapies. The net result is that less than 5% of the infected population are treated. Likewise of the 530 million individuals worldwide who carry HSV-1, 81% of the symptomatic population remain untreated. No cure exists for HSV infection, and once infected, individuals carry the virus for life in a dormant state. Reactivation of the virus from latency occurs periodically and may be triggered by stress, environmental factors, and/or suppression of the host immune system. Currently, the use of nucleoside analogs such as valaciclovir (VALTREX.RTM.) and aciclovir (ZOVIRAX.RTM.) is the standard of care for managing genital herpes virus outbreaks.

Varacella zoster virus (VZV) (also know as herpes zoster virus) is a herpes virus which causes chickenpox and shingles. Chickenpox is the primary disease produced in a host without immunity, and in young children is usually a mild illness characterised by a vesicular rash and fever. Shingles or zoster is the recurrent form of the disease which occurs in adults who were previously infected with VZV. The clinical manifestations of shingles are characterised by neuralgia and a vesicular skin rash that is unilateral and dermatomal in distribution. Spread of inflammation may lead to paralysis or convulsions. Coma can occur if the meninges become affected. VZV is of serious concern in patients receiving immunosuppressive drugs for transplant purposes or for treatment of malignant neoplasia and is a serious complication of AIDS patients due to their impaired immune system.

In common with other herpes viruses, infection with CMV leads to a lifelong association of virus and host. Congenital infection following infection of the mother during pregnancy may give rise to clinical effects such as death or gross disease (microcephaly, hepatosplenomegaly, jaundice, mental retardation), retinitis leading to blindness or, in less severe forms, failure to thrive, and susceptibility to chest and ear infections. CMV infection in patients who are immunocompromised for example as a result of malignancy, treatment with immunosuppressive drugs following transplantation or infection with Human Immunodeficiency Virus, may give rise to retinitis, pneumonitis, gastrointestinal disorders and neurological diseases. CMV infection is also associated with cardiovascular diseases and conditions including restenosis and atherosclerosis.

The main disease caused by EBV is acute or chronic infectious mononucleosis (glandular fever). Examples of other EBV or EBV associated diseases include lymphoproliferative disease which frequently occurs in persons with congenital or acquired cellular immune deficiency, X-linked lymphoproliferative disease which occurs namely in young boys, EBV-associated B-cell tumours, Hodgkin's disease, nasopharyngeal carcinoma, Burkitt lymphoma, non-Hodgkin lymphoma, thymomas and oral hairy leukoplakia. EBV infections have also been found in association with a variety of epithelial-cell-derived tumours of the upper and lower respiratory tracts including the lung. EBV infection has also been associated with other diseases and conditions including chronic fatigue syndrome, multiple sclerosis and Alzheimer's disease.

HHV-6 has been shown to be a causative agent of infantum subitum in children and of kidney rejection and interstitial pneumonia in kidney and bone marrow transplant patients, respectively, and may be associated with other diseases such as multiple sclerosis. There is also evidence of repression of stem cell counts in bone marrow transplant patients. HHV-7 is of undetermined disease aetiology.

Hepatitis B virus (HBV) is a viral pathogen of world-wide major importance. The virus is aetiologically associated with primary hepatocellular carcinoma and is thought to cause 80% of the world's liver cancer. Clinical effects of infection with HBV range from headache, fever, malaise, nausea, vomiting, anorexia and abdominal pains. Replication of the virus is usually controlled by the immune response, with a course of recovery lasting weeks or months in humans, but infection may be more severe leading to persistent chronic liver disease outlined above.

BRIEF SUMMARY OF THE INVENTION

According to a first aspect of the invention there is provided the compound of formula (I):

##STR00002## wherein: R.sup.1 is selected from the group consisting of halo, --NR.sup.7R.sup.8, Ay, --NR.sup.7Ay, Het, --NHR.sup.10Het, NHHet and --NHR.sup.10Ay; each R.sup.7 and R.sup.8 are the same or different and are independently selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, cycloalkenyl, --R.sup.10cycloalkyl, --R.sup.10OR.sup.9, --R.sup.10NR.sup.9R.sup.11, --R.sup.10C(O)R.sup.9, --C(O)R.sup.9, --C(O)R.sup.10Ay, --C(O)R.sup.10Het, --CO.sub.2R.sup.9, --R.sup.10CO.sub.2R.sup.9, --C(O)NR.sup.9R.sup.11, --R.sup.10C(O)NR.sup.9R.sup.11, --R.sup.10C(O)Ay, --R.sup.10C(O)Het, --C(S)NR.sup.9R.sup.11, --R.sup.10C(S)NR.sup.9R.sup.11, --R.sup.10NHC(NH)NR.sup.9R.sup.11, --R.sup.10NHC(O)R.sup.10Het, --R.sup.10NHC(O)R.sup.10CO.sub.2R.sup.9, --R.sup.10NHC(NCO.sub.2R.sup.9)NHCO.sub.2R.sup.9, --R.sup.10NHC(O)NHSO.sub.2R.sup.9, --R.sup.10NHC(O)NHSO.sub.2Ay, --R.sup.10NHC(O)NHSO.sub.2Het, --R.sup.10C(NH)NR.sup.9R.sup.11, --C(NH)NR.sup.9R.sup.11, --SO.sub.2NR.sup.9R.sup.11, --R.sup.10SO.sub.2NR.sup.9R.sup.11, --R.sup.10NHSO.sub.2R.sup.9, --SO.sub.2R.sup.10, --R.sup.10SO.sub.2R.sup.10, --R.sup.10NHCOR.sup.9, --R.sup.10SO.sub.2NHCOR.sup.9, --R.sup.10NHP(O)(OR.sup.9).sub.2, --R.sup.10OP(O)(OR.sup.9).sub.2 and --R.sup.10OP(O)(OR.sup.10Ay).sub.2; each R.sup.9 and R.sup.11 are the same or different and are independently selected from the group consisting of H, alkyl, cycloalkyl, --R.sup.10cycloalkyl, --R.sup.10OH, --R.sup.10(OR.sup.10).sub.w where w is 1 10, and --R.sup.10NR.sup.10R.sup.10; each R.sup.10 is the same or different and is independently selected from the group consisting of alkyl, cycloalkyl, alkenyl, cycloalkenyl, and alkynyl; Ay is aryl; Het is a 5- or 6-membered heterocyclic or heteroaryl group; R.sup.2 is selected from the group consisting of halo, alkyl, cycloalkyl, alkenyl, cycloalkenyl, --NR.sup.7R.sup.8, --OR.sup.7, --OAy, --S(O).sub.nR.sup.9, --S(O).sub.nAy, --R.sup.10NR.sup.7R.sup.8, --R.sup.10NR.sup.7Ay, Ay, Het, --NHHet, --NHR.sup.10Het, --OHet and --OR.sup.10Het; n is 0, 1 or 2; Y is N or CH; R.sup.3 and R.sup.4 are the same or different and are each independently selected from the group consisting of H, halo, alkyl, cycloalkyl, alkenyl, Ay, --OR.sup.7, --OAy, --R.sup.10OR.sup.7, --R.sup.10OAy, --NR.sup.7R.sup.8, --NR.sup.7Ay, --R.sup.10NR.sup.7R.sup.8, --R.sup.10NR.sup.7Ay, --C(O)R.sup.7, --C(O)Ay, --CO.sub.2R.sup.7, --CO.sub.2Ay, --SO.sub.2NHR.sup.9, Het, --NHHet and NHR.sup.10Het; q is 0, 1, 2, 3, 4 or 5; and each R.sup.5 is the same or different and is independently selected from the group consisting of halo, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, --R.sup.10cycloalkyl, Ay, --NHR.sup.10Ay, Het, --NHHet, --NHR.sup.10Het, --OR.sup.7, --OAy, --OHet, --R.sup.10OR.sup.9, --NR.sup.7R.sup.8, --NR.sup.7Ay, --R.sup.10NR.sup.7R.sup.8, --R.sup.10NR.sup.7Ay, --R.sup.10C(O)R.sup.9, --C(O)R.sup.9, --CO.sub.2R.sup.9, --R.sup.10CO.sub.2R.sup.9, --C(O)NR.sup.7R.sup.8, --C(O)Ay, --C(O)NR.sup.7Ay, --C(O)Het, --C(O)NHR.sup.10Het, --R.sup.10C(O)NR.sup.9R.sup.11, --C(S)NR.sup.9R.sup.11, --R.sup.10C(S)NR.sup.9R.sup.11, --R.sup.10NHC(NH)NR.sup.9R.sup.11, --C(NH)NR.sup.7R.sup.8, --R.sup.10C(NH)NR.sup.9R.sup.11, --S(O).sub.2NR.sup.7R.sup.8, --S(O).sub.2NR.sup.7Ay, --R.sup.10SO.sub.2NHCOR.sup.9, --R.sup.10SO.sub.2NR.sup.9R.sup.11, --R.sup.10SO.sub.2R.sup.9, --S(O).sub.nR.sup.9, cyano, nitro and azido; or two adjacent R.sup.5 groups together with the atoms to which they are attached form a C.sub.5-6 cycloalkyl or aryl; wherein when q is 1 and R.sup.5 is in the para position, R.sup.5 is not halo; wherein when Y is CH, R.sup.3 is not --NR.sup.7Ay; and pharmaceutically acceptable salts, solvates and physiologically functional derivatives thereof.

In another aspect of the invention there is provided a pharmaceutical composition comprising a compound of formula (I). In one embodiment, the pharmaceutical composition further comprises a pharmaceutically acceptable carrier or diluent. In one embodiment, the pharmaceutical composition further comprises an antiviral agent selected from the group consisting of aciclovir and valacicilovir.

In a third aspect of the invention, there is provided a method for the prophylaxis or treatment of herpes viral infections in an animal. The method comprises administering to the animal a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt, solvate or physiologically functional derivative thereof. The herpes viral infection can be any of herpes simplex virus 1, herpes simplex virus 2, cytomegalovirus, Epstein Barr virus, varacella zoster virus, human herpes virus 6, human herpes virus 7, and human herpes virus 8.

In a fourth aspect, there is provided a method for the treatment or prophylaxis of conditions or diseases associated with herpes viral infections in an animal. The method comprises administering to the animal a therapeutically effective amount of a compound of formula (I) or a salt, solvate or physiologically functional derivative thereof.

In another aspect, there is provided a process for preparing the compounds of formula (I) wherein Y is N, R.sup.2 is selected from the group consisting of alkyl, cycloalkyl, alkenyl, cycloalkenyl, Ay, --NR.sup.7R.sup.8, --OR.sup.7, --OAy, --S(O).sub.nR.sup.9, --S(O).sub.nAy, --R.sup.10NR.sup.7R.sup.8, --R.sup.10NR.sup.7Ay, Het, --NHHet, --NHR.sup.10Het, --OHet, and --OR.sup.10Het; and R.sup.3 and R.sup.4 are H. The process comprises reacting a compound of formula (IX):

##STR00003## with an amine of formula (X):

##STR00004##

In another aspect, the present invention provides a process for preparing the compounds of formula (I) wherein Y is N, R.sup.2 is selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, cycloalkenyl, Ay, --NR.sup.7R.sup.8, --OR.sup.7, --OAy, --S(O).sub.nR.sup.9, --S(O).sub.nAy, --R.sup.10NR.sup.7R.sup.8, --R.sup.10NR.sup.7Ay, Het, --NHHet, --NHR.sup.10Het, --OHet, and --OR.sup.10Het; R.sup.3 is selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, --R.sup.10OR.sup.7, --R.sup.10OAy, --NR.sup.7R.sup.8 where R.sup.7 and R.sup.8 are not H, Ay, --NR.sup.7Ay where R.sup.7 is not H, --R.sup.10NR.sup.7R.sup.8, --R.sup.10NR.sup.7Ay, --C(O)R.sup.7, --C(O)Ay, --CO.sub.2R.sup.7, --CO.sub.2Ay, --SO.sub.2NHR.sup.9 and Het; and R.sup.4 is H. The process comprises reacting a compound of formula (XVI):

##STR00005## with an amine of formula (X):

##STR00006##

In another aspect, the present invention provides a process for preparing the compounds of formula (I) wherein Y is N and R.sup.2 is selected from the group consisting of alkyl, cycloalkyl, alkenyl, cycloalkenyl, Ay, --NR.sup.7R.sup.8, --OR.sup.7, --OAy, --S(O).sub.nR.sup.9, --S(O).sub.nAy, --R.sup.10NR.sup.7R.sup.8, R.sup.10NR.sup.7R.sup.8, Het, --NHHet, --NHR.sup.10Het, --OHet, and --OR.sup.10Het. The process comprises the steps of: a) reacting a compound of formula (XX):

##STR00007## with an amine of formula (X):

##STR00008## to prepare an intermediate compound; and b) oxidizing the intermediate compound.

In another aspect, the present invention provides a process for preparing the compounds of formula (I). The process comprises reacting a compound of formula (XXII):

##STR00009## with a compound of formula XXIV:

##STR00010## wherein X.sup.1 is chloro, bromo or iodo; and M.sup.2 is selected from the group consisting of --B(OH).sub.2, --B(ORa).sub.2, --B(Ra).sub.2, --Sn(Ra).sub.3, Zn-halide, ZnRa, and Mg-halide, where Ra is alkyl or cycloalkyl and halide is halo.

In another aspect, the present invention provides a process for preparing compounds of formula (VI):

##STR00011## wherein when q is 1 and R.sup.5 is in the para position, R.sup.5 is not halo.

The process comprises rearranging the compound of formula (V):

##STR00012##

As another aspect, the present invention provides a process for preparing compounds of formula (XXII-B)

##STR00013## wherein R.sup.13 is selected from the group consisting of --NR.sup.7R.sup.8, --NR.sup.7Ay, Het, --NHR.sup.10Het, --NHHet and --NHR.sup.10Ay and wherein when q is 1 and R.sup.5 is in the para position, R.sup.5 is not halo. The process comprises reacting a compound of formula (XXII-A):

##STR00014## with a compound of formula H--R.sup.13.

In another aspect, the present invention provides a radiolabeled compound of formula (I) or a pharmaceutically acceptable salt, solvate or physiologically functional derivative thereof. In one embodiment, the present invention provides a tritiated compound of formula (I) or a pharmaceutically acceptable salt, solvate or physiologically functional derivative thereof. In another aspect, the present invention provides a biotinylated compound of formula (I) or a pharmaceutically acceptable salt, solvate or physiologically functional derivative thereof.

In another aspect, the present invention provides a compound of formula (I) for use in therapy.

In yet another aspect, the present invention provides the use of a compound of formula (I) for the prophylaxis or treatment of herpes viral infections.

In yet another aspect, the present invention provides a compound of formula (I) for the prophylaxis or treatment of conditions or diseases associated with herpes viral infections in an animal.

In yet another aspect, the present invention provides the use of a compound of formula (I) for the preparation of a medicament for the prophylaxis or treatment of herpes viral infections in animals, preferrably humans.

In yet another aspect, the present invention provides the use of a compound of formula (I) for the preparation of a medicament for the treatment or prophylaxis of diseases or conditions associated with herpes viral infections in animals, preferrably humans.

In yet another aspect, the present invention provides a pharmaceutical composition comprising a compound of formula (I) for use in the prophylaxis or treatment of herpes viral infections in an animal.

DETAILED DESCRIPTION OF THE INVENTION

As used herein, "a compound of the invention" means a compound of formula (I) or a pharmaceutically acceptable salt, solvate, or physiologically functional derivative thereof. Similarly, with respect to isolatable intermediates such as compounds of formula (VI), (IX), (XVI), (XX), (XXII) and (XXII-B), the phrase "a compound of formula (number)" means a compound having that formula and pharmaceutically acceptable salts, solvates and physiologically functional derivatives thereof.

As used herein, the terms "alkyl" and "alkylene" refer to straight or branched hydrocarbon chains containing from 1 to 8 carbon atoms. Examples of "alkyl" as used herein include, but are not limited to, methyl, ethyl, n-propyl, n-butyl, n-pentyl, isobutyl, isopropyl, and tert-butyl. Examples of "alkylene" as used herein include, but are not limited to, methylene, ethylene, propylene, butylene, and isobutylene. "Alkyl also includes substituted alkyl (alkylene). The alkyl groups may be optionally substituted one or more times with a substituent selected from the group consisting of mercapto, nitro, cyano and halo. Trihalomethyl, such as trifluoromethyl is one particularly preferred alkyl group.

As used herein, the term "cycloalkyl" refers to a non-aromatic carbocyclic ring having from 3 to 8 carbon atoms and no carbon-carbon double bonds. "Cycloalkyl" includes by way of example cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl. "Cycloalkyl" also includes substituted cycloalkyl. The cycloalkyl may optionally be substituted on an available carbon with one or more substituents selected from the group consisting of mercapto, nitro, cyano, halo, and alkyl.

As used herein, the term "alkenyl" refers to straight or branched hydrocarbon chains containing from 2 to 8 carbon atoms and at least one and up to three carbon-carbon double bonds. Examples of "alkenyl" as used herein include, but are not limited to ethenyl and propenyl. "Alkenyl" also includes substituted alkenyl. The alkenyl groups may optionally be substituted on an available carbon with one or more substituents selected from the group consisting of mercapto, nitro, cyano, halo, and alkyl.

As used herein, the term "cycloalkenyl" refers to refers to a non-aromatic carbocyclic ring having from 3 to 8 carbon atoms (unless otherwise specified) and up to 3 carbon-carbon double bonds. "Cycloalkenyl" includes by way of example cyclobutenyl, cyclopentenyl and cyclohexenyl. "Cycloalkenyl" also includes substituted cycloalkenyl. The cycloalkenyl may optionally be substituted on an available carbon with one or more substituents selected from the group consisting of mercapto, nitro, cyano, halo, and alkyl.

As used herein, the term "alkynyl" refers to straight or branched hydrocarbon chains containing from 2 to 8 carbon atoms and at least one and up to three carbon-carbon triple bonds. Examples of "alkynyl" as used herein include, but are not limited to ethynyl and propynyl. "Alkynyl" also includes substituted alkynyl. The alkynyl groups may optionally be substituted on an available carbon with one or more substituents selected from the group consisting of mercapto, nitro, cyano, and halo.

The term "halo" or "halogen" refers to the elements fluorine, chlorine, bromine and iodine.

The term "aryl" refers to monocyclic carbocyclic groups and fused bicyclic carbocyclic groups having from 5 to 12 carbon atoms and having at least one aromatic ring. Examples of particular aryl groups include but are not limited to phenyl, and naphthyl. "Aryl" also includes substituted aryl. Aryl groups may be optionally substituted on an available carbon with one or more substituents selected from the group consisting of halo, alkyl (including perhaloalkyl), alkenyl, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, amino, mercapto, hydroxy, alkylhydroxy, alkylamine, cycloalkylamine, carboxy, carboxamide, sulfonamide, Het, amidine, cyano, nitro and azido. Preferred aryl groups according to the invention include but are not limited to phenyl and substituted phenyl.

The term "heterocyclic" (or "heterocycle") refers to a monocyclic saturated or unsaturated non-aromatic groups and fused bicyclic non-aromatic groups, having the specified number of members (total carbon atoms and heteroatoms) and containing 1, 2, 3 or 4 heteroatoms selected from N, O and S. Examples of particular heterocyclic groups include but are not limited to tetrahydrofuran, dihydropyran, tetrahydropyran, pyran, oxetane, thietane, 1,4-dioxane, 1,3-dioxane, 1,3-dioxalane, piperidine, piperazine, tetrahydropyrimidine, pyrrolidine, morpholine, thiomorpholine, thiazolidine, oxazolidine, tetrahydrothiopyran, tetrahydrothiophene, and the like. "Heterocyclic" also refers to substituted heterocyclic. The heterocyclic group may be optionally substituted on any available carbon or heteroatom, with one or more substituents selected from the group consisting of halo, alkyl (including perhaloalkyl), alkenyl, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, amino, mercapto, hydroxy, alkylhydroxy, alkylamine, cycloalkylamine, carboxy, carboxamide, sulfonamide, Het, amidine, cyano, nitro and azido. Preferred heterocyclic groups according to the invention include but are not limited to pyrrolidine, piperidine, morpholine, thiomorpholine and piperazine and substituted variants thereof.

The term "heteroaryl" refers to aromatic monocyclic groups and aromatic fused bicyclic groups having the specified number of members (total carbon atoms and heteroatoms) and containing 1, 2, 3, or 4 heteroatoms selected from N, O and S. Examples of particular heteroaryl groups include but are not limited to furan, thiophene, pyrrole, imidazole, pyrazole, triazole, tetrazole, thiazole, oxazole, isoxazole, oxadiazole, thiadiazole, isothiazole, pyridine, pyridazine, pyrazine, pyrimidine, quinoline, isoquinoline, benzofuran, benzothiophene, indole, and indazole. "Heteroaryl" also includes substituted heteroaryl. The heteroaryl group may be optionally substituted on any available carbon or heteroatom with one or more substituents selected from the group consisting of halo, alkyl (including perhaloalkyl), alkenyl, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, amino, mercapto, hydroxy, alkylhydroxy, alkylamine, cycloalkylamine, carboxy, carboxamide, sulfonamide, Het, amidine cyano, nitro and azido. Preferred heteroaryl groups according to the invention include but are not limited to pyridine, furan, thiophene, pyrrole, imidazole, pyrazole, and pyrimidine and substituted variants thereof.

As used herein, the term "optionally" means that the subsequently described event(s) may or may not occur, and includes both event(s) which occur and events that do not occur.

The present invention provides compounds of formula (I):

##STR00015## wherein: R.sup.1 is selected from the group consisting of halo, --NR.sup.7R.sup.8, Ay, --NR.sup.7Ay, Het, --NHR.sup.10Het, --NHHet and --NHR.sup.10Ay; each R.sup.7 and R.sup.8 are the same or different and are independently selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, cycloalkenyl, --R.sup.10cycloalkyl, --R.sup.10OR.sup.9, --R.sup.10NR.sup.9R.sup.11, --R.sup.10C(O)R.sup.9, --C(O)R.sup.9, --C(O)R.sup.10Ay, --C(O)R.sup.10Het, --CO.sub.2R.sup.9, --R.sup.10CO.sub.2R.sup.9, --C(O)NR.sup.9R.sup.11, --R.sup.10C(O)NR.sup.9R.sup.11, --R.sup.10OC(O)Ay, --R.sup.10C(O)Het, --C(S)NR.sup.9R.sup.11, --R.sup.10C(S)NR.sup.9R.sup.11, --R.sup.10NHC(NH)NR.sup.9R.sup.11, --R.sup.10NHC(O)R.sup.10Het, --R.sup.10NHC(O)R.sup.10CO.sub.2R.sup.9, --R.sup.10NHC(NCO.sub.2R.sup.9)NHCO.sub.2R.sup.9, --R.sup.10NHC(O)NHSO.sub.2R.sup.9, --R.sup.10NHC(O)NHSO.sub.2Ay, --R.sup.10NHC(O)NHSO.sub.2Het, --R.sup.10C(NH)NR.sup.9R.sup.11, --C(NH)NR.sup.9R.sup.11, --SO.sub.2NR.sup.9R.sup.11, --R.sup.10SO.sub.2NR.sup.9R.sup.11, --R.sup.10NHSO.sub.2R.sup.9, --SO.sub.2R.sup.10, --R.sup.10SO.sub.2R.sup.10, --R.sup.10NHCOR.sup.9, --R.sup.10SO.sub.2NHCOR.sup.9, --R.sup.10NHP(O)(OR.sup.9).sub.2, --R.sup.10OP(O)(OR.sup.9).sub.2 and --R.sup.10OP(O)(OR.sup.10Ay).sub.2; each R.sup.9 and R.sup.11 are the same or different and are independently selected from the group consisting of H, alkyl, cycloalkyl, --R.sup.10cycloalkyl, --R.sup.10OH, --R.sup.10(OR.sup.10).sub.w wherein w is 1 10, and --R.sup.10NR.sup.10R.sup.10; each R.sup.10 is the same or different and is independently selected from the group consisting of alkyl, cycloalkyl, alkenyl, cycloalkenyl and alkynyl; Ay is aryl; Het is a 5- or 6-membered heterocyclic or heteroaryl group; R.sup.2 is selected from the group consisting of halo, alkyl, cycloalkyl, alkenyl, cycloalkenyl, --NR.sup.7R.sup.9, --OR.sup.7, --OAy, --S(O).sub.nR.sup.9, --S(O).sub.nAy, --R.sup.10NR.sup.7R.sup.8, --R.sup.10NR.sup.7Ay, Ay, Het, --NHHet, --NHR.sup.10Het, --OHet and --OR.sup.10Het; n is 0, 1 or 2; Y is N or CH; R.sup.3 and R.sup.4 are the same or different and are each independently selected from the group consisting of H, halo, alkyl, cycloalkyl, alkenyl, Ay, --OR.sup.7, --OAy, --R.sup.10OR.sup.7, --R.sup.10OAy, --NR.sup.7R.sup.8, --NR.sup.7Ay, --R.sup.10NR.sup.7R.sup.8, --R.sup.10NR.sup.7Ay, --C(O)R.sup.7, --C(O)Ay, --CO.sub.2R.sup.7, --CO.sub.2Ay, --SO.sub.2NHR.sup.9, Het, --NHHet and --NHR.sup.10Het; and q is 0, 1, 2, 3, 4 or 5; and each R.sup.5 is the same or different and is independently selected from the group consisting of halo, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, --R.sup.10cycloalkyl, Ay, --NHR.sup.10Ay, Het, --NHHet, --NHR.sup.10Het, --OR.sup.7, --OAy, --OHet, --R.sup.10OR.sup.9, --NR.sup.7R.sup.9, --NR.sup.7Ay, --R.sup.10NR.sup.7R.sup.8, --R.sup.10NR.sup.7Ay, --R.sup.10C(O)R.sup.9, --C(O)R.sup.9, --CO.sub.2R.sup.9, --R.sup.10CO.sub.2R.sup.9, --C(O)NR.sup.7R.sup.8, --C(O)Ay, --C(O)NR.sup.7Ay, --C(O)Het, --C(O)NHR.sup.10Het --R.sup.10C(O)NR.sup.9R.sup.11, --C(S)NR.sup.9R.sup.11, --R.sup.10C(S)NR.sup.9R.sup.11, --R.sup.10NHC(NH)NR.sup.9R.sup.11, --C(NH)NR.sup.7R.sup.8, --C(NH)NR.sup.7Ay, --R.sup.10C(NH)NR.sup.9R.sup.11, --S(O).sub.2NR.sup.7R.sup.8, --S(O).sub.2NR.sup.7Ay, --R.sup.10SO.sub.2NHCOR.sup.9, --R.sup.10SO.sub.2NR.sup.9R.sup.11, --R.sup.10SO.sub.2R.sup.9, --S(O).sub.nR.sup.9, cyano, nitro and azido; or two adjacent R.sup.5 groups together with the atoms to which they are bonded form a C.sub.5-6 cycloalkyl or aryl; wherein when q is 1 and R.sup.5 is in the para position, R.sup.5 is not halo; and wherein when Y is CH, R.sup.3 is not --NR.sup.7Ay; and pharmaceutically acceptable salts, solvates and physiologically functional derivatives thereof.

Preferred compounds of formula (I) include those compounds defined wherein at least one of R.sup.1 and R.sup.2 contains an aryl, heterocyclic or heteroaryl moiety. The groups Ay, --NR.sup.7Ay, Het, --NHR.sup.10Het, NHHet, --NHR.sup.10Ay, --OAy, --S(O).sub.nAy, R.sup.10NR.sup.7Ay, --OHet and --OR.sup.10Het are groups containing an aryl, heterocyclic or heteroaryl moieties. In another embodiment, preferred compounds of the present invention include those compounds defined wherein at least one of R.sup.1 and R.sup.2 contain a heterocyclic or heteroaryl moiety such as Het, --NHHet, --NHR.sup.10Het, --OHet, and --OR.sup.10Het.

Another preferred class of compounds of formula (I) include those compounds defined wherein neither R.sup.1 nor R.sup.2 contain an aryl, heterocyclic or heteroaryl moiety. In such embodiments, R.sup.1 is preferably --NR.sup.7R.sup.8, and R.sup.2 is preferably selected from the group consisting of H, halo, alkyl, cyclo