IP Library Granted Patent US 7,153,855
Granted Patent B2
US 7,153,855 · App. 10/468,729 · Granted Dec 26, 2006

Pyrazolopyridinyl pyrimidine therapeutic compounds

Assignee: SmithKline Beecham Corporation
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Quick Facts
Patent No.
US 7,153,855
App. No.
10/468,729
Granted
Dec 26, 2006
Kind
B2
Abstract

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

Claims (151)

1. A compound of formula (I):

wherein:

R 1 is selected from the group consisting of halo, —NR 7 R 8 , Ay, —NR 7 Ay, Het, —NHR 10 Het, —NHHet and —NHR 10 Ay;

each R 7 and R 8 are the same or different and are independently selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, cycloalkenyl, —R 10 cycloalkyl, —R 10 OR 9 , —NR 9 R 11 , —R 10 NR 9 R 11 , —R 10 C(O)R 9 , —C(O)R 9 , —C(O)R 10 Ay, —C(O)R 10 Het, —CO 2 R 9 , —R 10 CO 2 R 9 , —C(O)NR 9 R 11 , —R 10 C(O)NR 9 R 11 , —R 10 C(O)Ay, —R 10 C(O)Het, —C(S)NR 9 R 11 , —R 10 C(S)NR 9 R 11 , —R 10 NHC(NH)NR 9 R 11 , —R 10 NHC(O)R 10 Het, —R 10 NHC(O)R 10 CO 2 R 9 , —R 10 NHC(NCO 2 R 9 )NHCO 2 R 9 , —R 10 NHC(O)NHSO 2 R 9 , —R 10 NHC(O)NHSO 2 Ay, —R 10 NHC(O)NHSO 2 Het, —R 10 C(NH)NR 9 R 11 , —C(NH)NR 9 R 11 , —SO 2 NR 9 R 11 , —R 10 SO 2 NR 9 R 11 , —R 10 NHSO 2 R 9 , —SO 2 R 10 , —R 10 SO 2 R 10 , —R 10 NHCOR 9 , —R 10 SO 2 NHCOR 9 , —R 10 NHP(O)(OR 9 ) 2 , —R 10 OP(O)(OR 9 ) 2 and —R 10 OP(O)(OR 10 Ay) 2 ;

each R 9 and R 11 are the same or different and are independently selected from the group consisting of H, alkyl, cycloalkyl, —R 10 cycloalkyl, —R 10 OH, —R 10 (OR 10 ) w where w is 1–10, and —R 10 NR 10 R 10 ;

each R 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 2 is selected from the group consisting of halo, alkyl, cycloalkyl, alkenyl, cycloalkenyl, —NR 7 R 8 , —OR 7 , —OAy, —S(O) n R 9 , —S(O) n Ay, —R 10 NR 7 R 8 , —R 10 NR 7 Ay, Ay, Het, —NHHet, —NHR 10 Het, —OHet and —OR 10 Het;

n is 0, 1 or 2;

Y is N;

R 3 and R 4 are the same or different and are each independently selected from the group consisting of H, halo, alkyl, cycloalkyl, alkenyl, Ay, —OR 7 , —OAy, —R 10 OR 7 , —R 10 OAy, —NR 7 R 8 , —NR 7 Ay, —R 10 NR 7 R 8 , —R 10 NR 7 Ay, —C(O)R 7 , —C(O)Ay, —CO 2 R 7 , —CO 2 Ay, —SO 2 NHR 9 , Het, —NHHet and —NHR 10 Het;

q is 0, 1, 2, 3, 4 or 5; and

each R 5 is the same or different and is independently selected from the group consisting of halo, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, —R 10 cycloalkyl, Ay, —NHR 10 Ay, Het, —NHHet, —NHR 10 Het, —OR 7 , —OAy, —OHet, —R 10 OR 9 , —NR 7 R 8 , —NR 7 Ay, —R 10 NR 7 R 8 , —R 10 NR 7 Ay, —R 10 C(O)R 9 , —C(O)R 9 , —CO 2 R 9 , —R 10 CO 2 R 9 , —C(O)NR 7 R 8 , —C(O)Ay, —C(O)NR 7 Ay, —C(O)Het, —C(O)NHR 10 Het —R 10 C(O)NR 9 R 11 , —C(S)NR 9 R 11 , —R 10 C(S)NR 9 R 11 , —R 10 NHC(NH)NR 9 R 11 , —C(NH)NR 7 R 8 , —C(NH)NR 7 Ay, —R 10 C(NH)NR 9 R 11 , —S(O) 2 NR 7 R 8 , —S(O) 2 NR 7 Ay, —R 10 SO 2 NHCOR 9 , —R 10 SO 2 NR 9 R 11 , —R 10 SO 2 R 9 , —S(O) n R 9 , cyano, nitro and azido; or

 two adjacent R 5 groups together with the atoms to which they are bonded form a C 5-6 cycloalkyl or aryl;

wherein when q is 1 and R 5 is in the para position, R 5 is not halo; and

or a pharmaceutically acceptable salt thereof.

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

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

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

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

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

7. The compound according to claim 1 wherein R 3 and R 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 5 is the same or different and is independently selected from the group consisting of halo, alkyl, alkenyl, —OR 7 , —CO 2 R 9 , —NR 7 R 8 , —C(O)NR 7 R 8 , Ay, —NHR 10 Ay, Het, —S(O) 2 NR 7 R 8 , cyano, nitro and azido.

10. The compound according to claim 1 wherein each R 5 is the same or different and is independently selected from the group consisting of halo, alkyl, —OR 7 , —NR 7 R 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]pyridin-3-yl]-2-pyrimidinamine,

4-[2-(4-Methoxyphenyl)-7-(1-pyrrolidinyl)pyrazolo[1,5-a]pyridin-3-yl]-2-pyrimidinamine,

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-yl]phenol,

2-[4-(Allyloxy)phenyl]-N-cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimidinyl]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]-pyrazolo[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-methoxy)-phenyl]pyrazolo[1,5-a]pyridin-7-amine,

2-[4-(Cyclobutylmethoxy)phenyl]-N-cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimidinyl]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-pyrimidinyl}-N-butylamine,

N-Butyl-3-[2-(butylamino)-4-pyrimidinyl]-2-[4-(cyclohexylamino)phenyl]-pyrazolo[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-phenylpyrazolo[1,5-a]pyridin-7-amine,

2-{4-[Bis(cyclopropylmethyl)amino]phenyl}-N-butyl-3-[2-(butylamino)-4-pyrimidinyl]pyrazolo[1,5-a]pyridin-7-amine,

N-butyl-3-[2-(butylamino)-4-pyrimidinyl]-2-{4-[(cyclopropylmethyl)amino]phenyl}-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]pyrazolo[1,5-a]pyridin-7-amine,

2-(3-Bromophenyl)-N-cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimidinyl]pyrazolo[1,5-a]pyridin-7-amine,

4-[2-(3-Bromophenyl)-7-(1-pyrrolidinyl)pyrazolo[1,5-a]pyridin-3-yl]-N-cyclopentyl-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-pyrimidinamine,

2-[1,1′-Biphenyl]-3-yl-N-cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimidinyl]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]-pyrazolo[1,5-a]pyridin-7-amine,

N-Cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimidinyl]-2-[3-(3-thienyl)phenyl]pyrazolo-[1,5-a]pyridin-7-amine,

N-Cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimidinyl]-2-[3-(2-thienyl)-phenyl]pyrazolo[1,5-a]pyridin-7-amine,

2-(3-Aminophenyl)-N-cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimidinyl]pyrazolo[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]-pyrazolo[1,5-a]pyridin-2-yl}phenyl)methanesulfonamide,

4-[2-(3-Aminophenyl)-7-(1-pyrrolidinyl)pyrazolo[1,5-a]pyridin-3-yl]-N-cyclopentyl-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]pyridin-3-yl]-2-pyrimidinyl}-N-cyclopentylamine,

2-(3-Bromo-4-chlorophenyl)-N-cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimidinyl]-pyrazolo[1,5-a]pyridin-7-amine,

2-(3-Amino-4-chlorophenyl)-N-cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimidinyl]pyrazolo[1,5-a]pyridin-7-amine,

2-[4-(Benzylamino)phenyl]-N-butyl-3-[2-(butylamino)-4-pyrimidinyl]-pyrazolo[1,5-a]pyridin-7-amine,

N-Cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimidinyl]-2-(3-methylphenyl)pyrazolo[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-methylphenyl)pyrazolo[1,5-a]pyridin-7-amine,

3-[2-(Cyclopentylamino)-4-pyrimidinyl]-N-isopropyl-2-(3-methylphenyl)pyrazol[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)pyrazolo[1,5-a]pyridin-7-amine,

3-[2-(Cyclopentylamino)-4-pyrimidinyl]-N-isopropyl-2-(3-methoxyphenyl)pyrazolo[1,5-a]pyridin-7-amine,

3-[2-(Cyclopentylamino)-4-pyrimidinyl]-2-(3-methoxyphenyl)-N,N-dimethylpyrazolo[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-(cyclopropylmethoxy)phenyl]pyrazolo[1,5-a]pyridin-7-amine,

N-Cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimidinyl]-2-(3-fluorophenyl)pyrazolo[1,5-a]pyridin-7-amine,

2-(3-Chlorophenyl)-N-cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimidinyl]pyrazolo[1,5-a]pyridin-7-amine,

N-Cyclopentyl-3-[2-(cyclopropylamino)-4-pyrimidinyl]-2-(4-methoxyphenyl)pyrazolo[1,5-a]pyridin-7-amine,

3-[2-(Cyclopentylamino)-4-pyrimidinyl]-2-(4-methoxyphenyl)-N-[2-(4-morpholinyl)ethyl]pyrazolo[1,5-a]pyridin-7-amine,

3-[2-(Cyclopentylamino)-4-pyrimidinyl]-N-cyclopropyl-2-(4-methoxyphenyl)pyrazolo[1,5-a]pyridin-7-amine,

N-Cyclopentyl-4-[2-(4-methoxyphenyl)-7-(4-morpholinyl)pyrazolo[1,5-a]pyridin-3-yl]-2-pyrimidinamine,

3-[2-(Cyclopentylamino)-4-pyrimidinyl]-N-(2-methoxyethyl)-2-(4-methoxyphenyl)pyrazolo[1,5-a]pyridin-7-amine,

N-Cyclopropyl-4-[2-(4-methoxyphenyl)-7-(4-morpholinyl)pyrazolo[1,5-a]pyridin-3-yl]-2-pyrimidinamine,

3-[2-(Cyclopropylamino)-4-pyrimidinyl]-N-(2-methoxyethyl)-2-(4-methoxyphenyl)pyrazolo[1,5-a]pyridin-7-amine,

3-[2-(Cyclopropylamino)-4-pyrimidinyl]-2-(4-methoxyphenyl)-N-[2-(4-morpholinyl)ethyl]pyrazolo[1,5-a]pyridin-7-amine,

N-Cyclopropyl-3-[2-(cyclopropylamino)-4-pyrimidinyl]-2-(4-methoxyphenyl)pyrazolo[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-(cyclopropylmethoxy)phenyl]pyrazolo[1,5-a]pyridin-7-amine,

2-[4-(Allyloxy)phenyl]-N-cyclopentyl-3-[2-(cyclopropylamino)-4-pyrimidinyl]pyrazolo[1,5-a]pyridin-7-amine,

N-Cyclopropyl-3-[2-(cyclopropylamino)-4-pyrimidinyl]-2-[4-(cyclopropylmethoxy)phenyl]pyrazolo[1,5-a]pyridin-7-amine,

2-[4-(Allyloxy)phenyl]-N-cyclopropyl-3-[2-(cyclopropylamino)-4-pyrimidinyl]pyrazolo[1,5-a]pyridin-7-amine,

N-Butyl-3-[2-(butylamino)pyrimidin-4-yl]-2-{4-[(4-methoxybenzyl)amino]phenyl}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]pyrazolo[1,5-a]pyridin-7-amine,

2-(3-Bromophenyl)-3-[2-(cyclopentylamino)-4-pyrimidinyl]-N-cyclopropylpyrazolo[1,5-a]pyridin-7-amine,

2-(3-Bromophenyl)-N-cyclopropyl-3-[2-(cyclopropylamino)-4-pyrimidinyl]pyrazolo[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-(butylamino)-3-[2-(butylamino)pyrimidin-4-yl]pyrazolo[1,5-a]pyridin-2-yl}phenyl)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]pyridin-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)pyrazolo[1,5-a]pyridin-7-yl]amino}butyl)amino]carbonyl}-4-methylbenzenesulfonamide,

4-[(4-{[3-[2-(Cyclopentylamino)pyrimidin-4-yl]-2-(4-methoxyphenyl)pyrazolo[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]pyrazolo[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 1 -[3-[2-(Cyclopentylamino)-4-pyrimidinyl]-2-(4-methoxyphenyl)pyrazolo[1,5-a]pyridin-7-yl]-1,2-ethanediamine,

N-Cyclopentyl-4-[2-(3-fluorophenyl)-7-(4-morpholinyl)pyrazolo[1,5-a]pyridin-3-yl]-2-pyrimidinamine,

N-Cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimidinyl]-2-[3-(trifluoromethyl)phenyl]pyrazolo[1,5-a]pyridin-7-amine,

2-(3-Chlorophenyl)-N-cyclopropyl-3-[2-(cyclopropylamino)-4-pyrimidinyl]pyrazolo[1,5-a]pyridin-7-amine,

2-(3-Chlorophenyl)-N-cyclopentyl-3-[2-(cyclopropylamino)-4-pyrimidinyl]pyrazolo[1,5-a]pyridin-7-amine,

2-(3-Chlorophenyl)-3-[2-(cyclopentylamino)-4-pyrimidinyl]-N-cyclopropylpyrazolo[1,5-a]pyridin-7-amine,

N-Cyclopentyl-3-[2-(cyclopropylamino)-4-pyrimidinyl]-2-(3-fluorophenyl)pyrazolo[1,5-a]pyridin-7-amine,

4-[2-(3-Chlorophenyl)-7-(4-morpholinyl)pyrazolo[1,5-a]pyridin-3-yl]-N-cyclopentyl-2-pyrimidinamine,

2-(3-Chlorophenyl)-3-[2-(cyclopentylamino)-4-pyrimidinyl]-N-(2-methoxyethyl)pyrazolo[1,5-a]pyridin-7-amine,

3-[2-(Cyclopentylamino)-4-pyrimidinyl]-N-cyclopropyl-2-(3-fluorophenyl)pyrazolo[1,5-a]pyridin-7-amine,

3-[2-(Cyclopentylamino)-4-pyrimidinyl]-2-(3-fluorophenyl)-N-(2-methoxyethyl)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 2 is selected from the group consisting of alkyl, cycloalkyl, alkenyl, cycloalkenyl, —NR 7 R 8 , —OR 7 , Ay, —OAy, —S(O) n R 9 , —S(O) n Ay, —R 10 NR 7 R 8 , —R 10 NR 7 Ay, Het, —NHHet, —NHR 10 Het, —OHet, and —OR 10 Het, and R 3 and R 4 are H, said process comprising reacting a compound of formula (IX):

with an amine of formula (X):

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

with an amine of formula (X):

19. A process for preparing the compound according to claim 1 wherein and R 2 is selected from the group consisting of alkyl, cycloalkyl, alkenyl, cycloalkenyl, —NR 7 R 8 , —OR 7 , Ay, —OAy, —S(O) n R 9 , —S(O) n Ay, —R 10 NR 7 R 8 , —R 10 NR 7 Ay, Het, —NHHet, —NHR 10 Het, —OHet, and —OR 10 Het, said process comprising the steps of:

a) reacting a compound of formula (XX):

 with an amine of formula (X):

 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):

wherein X 1 is chloro, bromo or iodo;

with a compound of formula XXIV:

wherein M 2 is selected from the group consisting of —B(OH) 2 , —B(ORa) 2 , —B(Ra) 2 , —Sn(Ra) 3 , Zn-halide, ZnRa, and Mg-halide where Ra is alkyl or cycloalkyl and halide is halo.

Continuity (2)
Provisional Application 6027429700 · Mar 8, 2001
Related Publication 20050049260A1 · Mar 3, 2005