IP Library › Granted Patent US 9,556,169
Granted Patent B2
US 9,556,169 · App. 14/443,609 · Granted Jan 31, 2017

Compounds and compositions for the treatment of parasitic diseases

Inventors: Arnab Kumar Chatterjee (San Diego, CA); Advait Suresh Nagle (San Diego, CA); Prasuna Paraselli (San Diego, CA); Ravinder Reddy Kondreddi (Singapore, SG); Seh Yong Leong (Singapore, SG); Pranab Kumar Mishra (Holland, PA); Robert Joseph Moreau (Walnut Creek, CA); Jason Thomas Roland (San Diego, CA); Wei Lin Sandra Sim (Singapore, SG); Oliver Simon (Singapore, SG); Jocelyn Liying Tan (Singapore, SG); Bryan K S Yeung (Singapore, SG); Bin Zou (Singapore, SG); Venkatataiah Bollu (San Diego, CA)
Assignee: Novartis AG
C07D471/04C07D519/00
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Quick Facts
Patent No.
US 9,556,169
App. No.
14/443,609
Granted
Jan 31, 2017
Kind
B2
Abstract

The present invention provides compounds of formula I: or a pharmaceutically acceptable salt, tautomer, or stereoisomer, thereof, wherein the variables are as defined herein. The present invention further provides pharmaceutical compositions comprising such compounds and methods of using such compounds for treating, preventing, inhibiting, ameliorating, or eradicating the pathology and/or symptomology of a disease caused by a Plasmodium parasite, such as malaria.

Claims (217)

1. A compound of Formula I,

or a pharmaceutical acceptable salt, tautomer or stereoisomer thereof, wherein

n is 0, 1, 2 or 3;

p is 0, 1, 2 or 3;

L is selected from the group consisting of *—(CHR 3 ) 1-3 —, *—CHR 3 N(R 2 )—, *—CHR 3 O—, *—CHR 3 S—, *—CHR 3 S(O)—, *—CHR 3 N(R 2 )CHR 3 —, *—C(O)—, *—C(O)N(R 2 )—, *—C(O)N(R 2 )CHR 3 —, *—N(R 2 )—, *—N(R 2 )CHR 3 —, *—N(R 2 )C(O)—, *—N(R 2 )C(O)N(R 2 )—, *—N(R 2 )S(O) 2 —, wherein

* represents the point of attachment of L to the pyrazolo[1,5-a]pyridine fused ring depicted in Formula I;

each R 2 is independently selected from the group consisting of hydrogen, C 1-6 alkyl, haloC 1-6 alkyl, R—C 0-4 alkylene, and R—C 0-4 alkylene-C(O)—, wherein R is selected from the group consisting of hydroxyl, C 1-4 alkoxy, amino, C 1-4 alkylamino, C 3-6 cycloalkyl, C 4-6 heterocycloalkyl, and C 5-6 heteroaryl, wherein the C 3-6 cycloalkyl, C 4-6 heterocycloalkyl, and C 5-6 heteroaryl of R are each unsubstituted or substituted with 1-2 substituents independently selected from the group consisting of halo, amino, hydroxyl, C 1-4 alkyl, C 1-4 alkoxy, oxo, and C 5-6 heteroaryl; and

each R 3 is independently selected from the group consisting of hydrogen and C 1-4 alkyl;

Ring A is selected from the group consisting of C 6-10 aryl and C 5-10 heteroaryl;

Ring C is selected from the group consisting of C 6-10 aryl, C 6-10 heteroaryl, C 5-7 cycloalkyl, C 5-7 heterocycloalkyl, and fused bicyclyl comprising a C 5-6 heterocycloalky fused to a phenyl;

each R 1 is independently selected from the group consisting of halo, cyano, amino, C 1-4 alkyl, C 1-4 alkoxyl, halo-C 1-4 alkyl, —C(O)NR 7 R 8 , —NHC(O)R 11 , phenyl, and C 5-6 heteroaryl; wherein

the phenyl and C 5-6 heteroaryl of R 1 are each unsubstituted or substituted with 1-2 substituents independently selected from the group consisting of C 1-4 alkyl, amino, halo, and C 1-4 alkylamino;

R 7 and R 8 are each independently selected from hydrogen, C 1-4 alkyl and haloC 1-4 alkyl;

R 11 is C 1-6 alkyl, unsubstituted or substituted with 1-2 substituents independently selected from the group consisting of amino, C 3-6 cycloalkyl and C 4-6 heterocycloalkyl;

R 17 is selected from the group consisting of cyano, halo, C 1-4 alkyl, halo-C 1-4 alkyl, oxo, C 3-6 cycloalkyl, and —SO 2 —C 1-4 alkyl.

2. The compound of claim 1 , wherein L is selected from the group consisting of *—C(O)N(R 2 )— and *—N(R 2 )C(O)—, wherein each R 2 is independently selected from hydrogen, C 1-4 alkyl, and R—C 0-4 alkylene, and wherein R is selected from the group consisting of C 1-4 alkylamino, C 3-6 cycloalkyl, C 4-6 heterocycloalkyl and C 5-6 heteroaryl, each of which is unsubstituted or substituted with 1-2 substituents independently selected from the group consisting of halo, amino, hydroxyl, C 1-4 alkyl, C 1-4 alkoxy, oxo, and C 5-6 heteroaryl.

3. The compound of claim 1 , wherein L is selected from *—C(O)N(CH 3 )—*—C(O)N(CH 2 CH 3 )—, *—C(O)N(CH(CH 3 ) 2 )—, *—C(O)N(NH(CH 3 ))—, and *—N(CH 3 )C(O)—.

4. The compound according to claim 1 , wherein Ring A is selected from the group consisting of phenyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolopyridinyl, and indazolyl, each of which is unsubstituted or substituted by (R 1 ) n .

5. The compound according to claim 1 , wherein Ring C is selected from the group consisting of

each of which is unsubstituted or substituted by (R 17 ) p .

6. The compound according to claim 1 , wherein Ring C is selected from the group consisting of phenyl and pyridinyl, each of which is unsubstituted or substituted by (R 17 ) p .

7. The compound according to claim 1 , wherein each R 1 is independently selected from the group consisting of trifluoromethyl, cyano, —NH 2 —, —C(O)NH 2 , —C(O)NHCH 3 , —C(O)N(CH 3 ) 2 , and —NHC(O)CH(NH 2 )(CH 3 ).

8. The compound according to claim 1 , wherein each R 17 is independently selected from the group consisting of cyano, halo, C 1-4 alkyl, haloC 1-4 alkyl, —SO 2 —C 1-4 alkyl, and C 3-6 cycloalkyl.

9. The compound of claim 1 , wherein the compound is of Formula Ia:

or a pharmaceutical acceptable salt, tautomer or stereoisomer thereof,

wherein

n is 1 or 2;

n is 1 or 2;

Ring A is phenyl, pyridinyl, or pyrimidinyl;

Ring C is phenyl or pyridinyl;

L is *—C(O)NR 2 — or *—NR 2 C(O)—, wherein R 2 is selected from hydrogen, C 1-4 alkyl, C 1-4 alkylamino-(C 0-4 )alkylene, C 3-6 cycloalkyl-(C 0-4 )alkylene, C 4-6 heterocycloalkyl-(C 0-4 )alkylene, wherein the C 4-6 heterocycloalkyl is selected from the group consisting of piperazinyl, morpholinyl, thiomorpholinyl, tetrahydropyranyl, and oxetanyl, and wherein the C 3-6 cycloalkyl is selected from cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl;

each R 1 is independently *—C(O)NR 7 R 8 or —NH 2 —, wherein R 7 and R 8 are each independently hydrogen or C 1-4 alkyl; and

R 17 is selected from the group consisting of cyano, halo, —NH 2 —, —C(O)NH 2 , —C(O)NH(CH 3 ), and —C(O)N(CH 3 ) 2 .

10. The compound of claim 9 , wherein L is selected from *—C(O)N(CH 3 )—*—C(O)N(CH 2 CH 3 )—, *—C(O)N(CH(CH 3 ) 2 )—, *—C(O)N(NH(CH 3 ))—, and *—N(CH 3 )C(O)—.

11. The compound of claim 1 , wherein the compound, or a pharmaceutical acceptable salt, tautomer or stereoisomer thereof, is selected from the group consisting of:

N-(4-cyanophenyl)-N-methyl-3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;

4-fluoro-N-methyl-N-((3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]yridine-5-yl)methyl)aniline;

N-(4-chlorophenyl)-N-methyl-3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-(4-fluorophenyl)-N-methyl-3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-methyl-N-(5-methylpyridin-2-yl)-3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;

4-chloro-N-methyl-N-((3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]yridine-5-yl)methyl)aniline;

N,5-dimethyl-N-((3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]yridine-5-yl)methyl)yridine-2-amine;

5-((4-fluorophenoxy)methyl)-3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridine;

N-(4-cyanophenyl)-N-(2-methoxyethyl)-3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-(4-cyanophenyl)-N-(2-(dimethylamino)ethyl)-3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-(4-cyanophenyl)-N-((tetrahydro-2H-pyran-4-yl)methyl)-3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-(4-(methylsulfonyl)phenyl)-N-((tetrahydro-2H-pyran-4-yl)methyl)-3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-(5-cyanopyridin-2-yl)-N-methyl-3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-methyl-N-(5-methylpyridin-3-yl)-3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;

5-(((5-methylpyridin-2-yl)oxy)methyl)-3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridine;

5-(4-fluorophenethyl)-3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridine;

N-(4-cyanophenyl)-N-methyl-3-(1-methyl-1H-indazol-5-yl)pyrazolo[1,5-a]pyridine-5-carboxamide;

3-(6-acetamidopyridin-3-yl)-N-(4-cyanophenyl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;

3-(4-carbamoylphenyl)-N-(4-cyanophenyl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;

3-(4-carbamoylphenyl)-N-(4-fluorophenyl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;

5-(((4-fluorophenyl)thio)methyl)-3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridine;

5-(((4-fluorophenyl)sulfinyl)methyl)-3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridine;

3-(4-(1H-pyrazol-5-yl)phenyl)-N-(4-cyanophenyl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;

N-(4-cyanophenyl)-N-methyl-3-(5-(trifluoromethyl)pyridine-2-yl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-(5-cyanopyridin-2-yl)-N-methyl-3-(5-(trifluoromethyl)pyridine-2-yl)pyrazolo[1,5-a]pyridine-5-carboxamide;

(S)-3-(4-(2-aminopropanamido)phenyl)-N-(4-cyanophenyl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;

3-(5-carbamoylpyridin-2-yl)-N-(4-cyanophenyl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;

4-cyano-N-methyl-N-(3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]yridine-5-yl)benzamide;

4-fluoro-N-methyl-N-(3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]yridine-5-yl)benzamide;

4-cyano-N-methyl-N-(3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridine-5-yl)benzenesulfonamide;

4-fluoro-N-methyl-N-(3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridine-5-yl)benzenesulfonamide;

3-(4-carbamoylphenyl)-N-(5-cyanopyridin-2-yl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide; N-methyl-3-(4-(trifluoromethyl)phenyl)-N-(5-(trifluoromethyl)yridine-2-yl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-methyl-N-(5-(methylsulfonyl)pyridine-2-yl)-3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-(4-fluorobenzyl)-3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]yridine-5-amine

N-(4-fluorobenzyl)-3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]yridine-5-amine;

N-methyl-6-(trifluoromethyl)-N-(3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]yridine-5-yl)nicotinamide;

N-methyl-5-(trifluoromethyl)-N-(3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]yridine-5-yl)picolinamide;

4-cyano-N-((tetrahydro-2H-pyran-4-yl)methyl)-N-(3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridin-5-yl)benzamide;

N-(4-cyanophenyl)-N-methyl-3-(1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[1,5-a]pyridine-5-carboxamide;

3-(6-aminopyridin-3-yl)-N-(4-cyanophenyl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;

3-(4-aminophenyl)-N-(4-cyanophenyl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;

3-(4-(2-aminoacetamido)phenyl)-N-(4-cyanophenyl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;

(R)-3-(4-(2-aminopropanamido)phenyl)-N-(4-cyanophenyl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;

(S)-3-(4-(2-amino-3-methylbutanamido)phenyl)-N-(4-cyanophenyl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;

(S)-3-(4-(2-amino-2-cyclohexylacetamido)phenyl)-N-(4-cyanophenyl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;

3-(4-fluorophenyl)-1-methyl-1-(3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridin-5-yl)urea;

6-(1,1-difluoroethyl)-N-methyl-N-(3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridin-5-yl)nicotinamide;

6-cyclopropyl-N-methyl-N-(3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridin-5-yl)nicotinamide;

4-cyclopropyl-N-methyl-N-(3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridin-5-yl)benzamide;

5-fluoro-N-methyl-N-(3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridin-5-yl)picolinamide;

N-methyl-4-(methylsulfonyl)-N-(3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridin-5-yl)benzamide;

N-(5-cyanopyridin-2-yl)-N-methyl-3-(1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[1,5-a]pyridine-5-carboxamide;

3-(6-aminopyridin-3-yl)-N-(5-cyanopyridin-2-yl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;

4-chloro-N-methyl-N-(3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridin-5-yl)benzamide;

N-(3-(4-carbamoylphenyl)pyrazolo[1,5-a]pyridin-5-yl)-4-fluoro-N-methylbenzamide

4-fluoro-N-methyl-N-(3-(4-(5-(methylamino)-1,3,4-thiadiazol-2-yl)phenyl)pyrazolo[1,5-a]pyridin-5-yl)benzamide;

N-methyl-N-(5-(methylsulfonyl)pyridin-2-yl)-3-(1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-(5-cyanopyridin-2-yl)-N-methyl-3-(5-methylpyridin-2-yl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-(5-cyanopyridin-2-yl)-3-(5-methoxypyridin-2-yl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;

3-(5-carbamoylpyridin-2-yl)-N-(5-cyanopyridin-2-yl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;

3-(4-carbamoylphenyl)-N-methyl-N-(5-(trifluoromethyl)pyridin-2-yl)pyrazolo[1,5-a]pyridine-5-carboxamide;

3-(4-carbamoylphenyl)-N-methyl-N-(5-methylpyridin-2-yl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-(4-fluorophenyl)-N-methyl-3-(4-(methylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;

4-(5-(1-(methyl(5-methylpyridin-2-yl)amino)ethyl)pyrazolo[1,5-a]pyridin-3-yl)benzamide;

4-(5-(1-(7-fluoro-3-oxo-2H-benzo[b][1,4]oxazin-4(3H)-yl)ethyl)pyrazolo[1,5-a]pyridin-3-yl)benzamide;

N-(4-cyanophenyl)-N-methyl-3-(4-(methylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-(4-(5-(1-(methyl(5-methylpyridin-2-yl)amino)ethyl)pyrazolo[1,5-a]pyridin-3-yl)phenyl)acetamide;

3-(4-acetamidophenyl)-N-(5-cyanopyridin-2-yl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;

4-(5-(7-fluoro-3,4-dihydro-2H-benzo[b][1,4]oxazine-4-carbonyl)pyrazolo[1,5-a]pyridin-3-yl)benzamide;

4-(5-(7-fluoro-3-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazine-4-carbonyl)pyrazolo[1,5-a]pyridin-3-yl)benzamide;

4-(5-(7-fluoro-3,4-dihydro-2H-benzo[b][1,4]oxazine-4-carbonyl)pyrazolo[1,5-a]pyridin-3-yl)-N-methylbenzamide;

4-(5-(7-fluoro-3-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazine-4-carbonyl)pyrazolo[1,5-a]pyridin-3-yl)-N-methylbenzamide;

N-(5-cyanopyridin-2-yl)-N-methyl-3-(4-(methylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-(5-cyanopyridin-2-yl)-3-(4-(methylcarbamoyl)phenyl)-N-(oxetan-3-yl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-(1-(1H-pyrazol-1-yl)propan-2-yl)-3-(4-carbamoylphenyl)-N-(5-cyanopyridin-2-yl)pyrazolo[1,5-a]pyridine-5-carboxamide;

3-(6-amino-5-fluoropyridin-3-yl)-N-(4-cyanophenyl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;

3-(4-amino-3,5-dimethylphenyl)-N-(4-cyanophenyl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;

3-(6-amino-5-methylpyridin-3-yl)-N-(4-cyanophenyl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;

3-(4-carbamoylphenyl)-N-(4-cyanocyclohexyl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;

3-(2-aminopyrimidin-5-yl)-N-(4-cyanophenyl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;

3-(6-amino-5-(trifluoromethyl)pyridin-3-yl)-N-(5-cyanopyridin-2-yl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;

3-(6-amino-5-cyanopyridin-3-yl)-N-(5-cyanopyridin-2-yl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;

3-(6-amino-5-chloropyridin-3-yl)-N-(5-cyanopyridin-2-yl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;

3-(6-amino-5-(dimethylcarbamoyl)pyridin-3-yl)-N-(5-cyanopyridin-2-yl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;

3-(6-amino-5-methoxypyridin-3-yl)-N-(5-cyanopyridin-2-yl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;

3-(4-carbamoylphenyl)-N-(4-chloro-2-formylphenyl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;

N-(5-Cyanopyridin-2-yl)-N-ethyl-3-(4-(methylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-(5-cyanopyridin-2-yl)-N-isopropyl-3-(4-(methylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;

5-(5-(1-(4-cyanophenyl)-2-methylhydrazinecarbonyl)pyrazolo[1,5-a]pyridin-3-yl)-N-methyl picolinamide;

N-(5-cyanopyridin-2-yl)-N-cyclopropyl-3-(4-(methylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-(5-cyanopyridin-2-yl)-N-methyl-3-(4-(methylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-ethyl-N-(5-fluoropyridin-2-yl)-3-(4-(methylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide; and

N-ethyl-3-(4-(methylcarbamoyl)phenyl)-N-(5-(trifluoromethyl)pyridin-2-yl)pyrazolo[1,5-a]pyridine-5-carboxamide.

12. The compound of claim 1 , wherein the compound, a pharmaceutical acceptable salt, tautomer, or stereoisomer thereof, is selected from the group consisting of:

3-(4-carbamoylphenyl)-N-(5-cyanopyridin-2-yl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;

N-(4-cyanophenyl)-N-methyl-3-(1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[1,5-a]pyridine-5-carboxamide;

3-(6-aminopyridin-3-yl)-N-(4-cyanophenyl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;

(R)-3-(4-(2-aminopropanamido)phenyl)-N-(4-cyanophenyl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;

N-(5-cyanopyridin-2-yl)-N-methyl-3-(1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-(5-cyanopyridin-2-yl)-N-methyl-3-(4-(methylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;

3-(2-aminopyrimidin-5-yl)-N-(4-cyanophenyl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide; and

3-(6-amino-5-(dimethylcarbamoyl)pyridin-3-yl)-N-(5-cyanopyridin-2-yl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide.

13. The compound of claim 1 , wherein the compound, a pharmaceutical acceptable salt, tautomer, or stereoisomer thereof, is selected from the group consisting of:

N-(5-Cyanopyridin-2-yl)-N-ethyl-3-(4-(methylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-(5-cyanopyridin-2-yl)-N-isopropyl-3-(4-(methylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;

5-(5-(1-(4-cyanophenyl)-2-methylhydrazinecarbonyl)pyrazolo[1,5-a]pyridin-3-yl)-N-methyl picolinamide;

N-(5-cyanopyridin-2-yl)-N-cyclopropyl-3-(4-(methylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-(5-cyanopyridin-2-yl)-N-methyl-3-(4-(methylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-ethyl-N-(5-fluoropyridin-2-yl)-3-(4-(methylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-ethyl-3-(4-(methylcarbamoyl)phenyl)-N-(5-(trifluoromethyl)pyridin-2-yl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-(4-Cyanophenyl)-N-methyl-3-(6-(methylcarbamoyl)pyridin-3-yl)pyrazolo[1,5-a]pyridine-5-carboxamide 3-(5-Amino-6-chloropyridin-3-yl)-N-(5-cyanopyridin-2-yl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;

N-(4-Chlorophenyl)-N-methyl-3-(4-(methylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;

3-(4-Carbamoylphenyl)-N-(4-chlorophenyl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;

4-(5-((5-Cyanopyridin-2-yl)(methyl)carbamoyl)pyrazolo[1,5-a]pyridin-3-yl)benzoic acid;

N-(5-Cyanopyridin-2-yl)-3-(4-((2-hydroxyethyl)carbamoyl)phenyl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;

N-Methyl-3-(4-(methylcarbamoyl)phenyl)-N-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;

3-(4-((2-Aminoethyl)carbamoyl)phenyl)-N-(5-cyanopyridin-2-yl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;

3-(4-Carbamoylphenyl)-N-(4-cyanophenyl)-N-(2-hydroxyethyl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-(5-Cyanopyridin-2-yl)-3-(4-(methylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;

3-(6-Chloro-5-(methylsulfonamido) pyridin-3-yl)-N-(5-cyanopyridin-2-yl)-N-methylpyrazolo [1,5-a]pyridine-5-carboxamide;

3-(2-Aminopyridin-4-yl)-N-(5-cyanopyridin-2-yl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;

N-(4-Chlorophenyl)-N-methyl-3-(6-(methylcarbamoyl)pyridin-3-yl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-(4-Cyanophenyl)-N-(2-hydroxyethyl)-3-(4-(methylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-(5-(2-Aminoethoxy)pyridin-2-yl)-N-methyl-3-(4-(methylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-(5-Cyanopyridin-2-yl)-N-cyclobutyl-3-(4-(methylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-(5-Cyanopyridin-2-yl)-N-methyl-3-(4-(piperidin-4-ylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-(5-Cyanopyridin-2-yl)-N-methyl-3-(4-((2-(methylamino)ethyl)carbamoyl)phenyl)pyrazolo [1,5-a]pyridine-5-carboxamide;

N-(5-cyanopyridin-2-yl)-3-(4-((2-(dimethylamino)ethyl)carbamoyl)phenyl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;

N-(4-Chlorophenyl)-N-cyclopropyl-3-(4-(methylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-(5-Cyanopyridin-2-yl)-N-(cyclopropylmethyl)-3-(4-(methylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-(4-Cyanophenyl)-N-cyclopropyl-3-(4-(methylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-(tert-Butyl)-N-(5-cyanopyridin-2-yl)-3-(4-(methylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;

3-(4-Carbamoylphenyl)-N-(5-cyanopyridin-2-yl)-N-cyclopropylpyrazolo[1,5-a]pyridine-5-carboxamide;

N-(5-Cyanopyridin-2-yl)-N-cyclopropyl-3-(4-(isopropylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-(6-Methoxypyridin-3-yl)-N-methyl-3-(4-(methylcarbamoyl)phenyl)pyrazolo[1,5-a] pyridine-5-carboxamide;

N-(5-Cyanopyridin-2-yl)-N-cyclopropyl-3-(4-(cyclopropylcarbamoyl)phenyl)pyrazolo[1,5a]pyridine-5-carboxamide;

N-(5-Chloropyridin-2-yl)-N-cyclopropyl-3-(4-(methylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-Cyclopropyl-N-(5-fluoropyridin-2-yl)-3-(4-(methylcarbamoyl)phenyl)pyrazolo[1,5 a] pyridine-5-carboxamide;

N-(5-Cyanopyridin-2-yl)-N-cyclopentyl-3-(4-(methylcarbamoyl)phenyl)pyrazolo[1,5-a] pyridine-5-carboxamide;

N-(5-Cyanopyridin-2-yl)-N-cyclopropyl-3-(4-(ethylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;

6-(N-Cyclopropyl-3-(4-(methylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamido) nicotinic acid;

N-(5-Carbamoylpyridin-2-yl)-N-cyclopropyl-3-(4-(methylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-Cyclopropyl-N-(3,4-difluorophenyl)-3-(4-(methylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-(5-Cyanopyridin-2-yl)-N-cyclopropyl-3-(4-(oxetan-3-ylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-Cyclopropyl-3-(4-(methylcarbamoyl)phenyl)-N-(5-(trifluoromethyl)pyridin-2-yl)pyrazolo [1,5-a]pyridine-5-carboxamide;

N-(5-Cyanopyridin-2-yl)-N-cyclopropyl-3-(5-(methylcarbamoyl)pyridin-2-yl)pyrazolo[1,5-a]pyridine-5-carboxamide;

3-(4-carbamoylphenyl)-N-(4-cyanophenyl)-N-cyclopropylpyrazolo[1,5-a]pyridine-5-carboxamide;

3-(4-Carbamoylphenyl)-N-cyclopropyl-N-(3,4-difluorophenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-Cyclopropyl-3-(4-(methylcarbamoyl)phenyl)-N-(5-methylpyridin-2-yl)pyrazolo[1,5-a] pyridine-5-carboxamide;

N-(4-Cyanophenyl)-N-cyclopropyl-3-(6-(methylcarbamoyl)pyridin-3-yl)pyrazolo[1,5-a] pyridine-5-carboxamide;

3-(6-Carbamoylpyridin-3-yl)-N-(4-cyanophenyl)-N-cyclopropylpyrazolo[1,5-a]pyridine-5-carboxamide;

3-(5-Carbamoylpyridin-2-yl)-N-(5-cyanopyridin-2-yl)-N-cyclopropylpyrazolo[1,5-a]pyridine-5-carboxamide;

N-(5-cyanopyridin-2-yl)-N-ethyl-3-(4-[N-methylsulfamoyl]phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-(4-Cyanophenyl)-N-cyclopropyl-3-(5-(methylcarbamoyl)pyridin-2-yl)pyrazolo[1,5-a] pyridine-5-carboxamide;

3-(5-Carbamoylpyridin-2-yl)-N-(4-cyanophenyl)-N-cyclopropylpyrazolo[1,5-a]pyridine-5-carboxamide;

N-(4-Chlorophenyl)-N-cyclopropyl-3-(6-(methylcarbamoyl)pyridin-3-yl)pyrazolo[1,5-a] pyridine-5-carboxamide;

N-(5-Cyanopyridin-2-yl)-N-cyclobutyl-3-(6-(methylcarbamoyl)pyridin-3-yl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-(4-Cyanophenyl)-N-cyclobutyl-3-(6-(methylcarbamoyl)pyridin-3-yl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-(4-Cyanophenyl)-N-isopropyl-3-(6-(methylcarbamoyl)pyridin-3-yl)pyrazolo[1,5-a]pyridine-5-carboxamide;

5-Cyano-N-cyclopropyl-N-(3-(4-(methylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridin-5-yl) picolinamide;

N-(5-Cyanopyridin-2-yl)-N-isopropyl-3-(6-(methylcarbamoyl)pyridin-3-yl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-(5-Cyano-6-methoxypyridin-2-yl)-N-cyclopropyl-3-(4-(methylcarbamoyl)phenyl)pyrazolo [1,5-a]pyridine-5-carboxamide;

N-(5-cyanopyridin-2-yl)-N-ethyl-3-(6-[methylcarbamoyl]pyridin-3-yl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-(5-fluoropyridin-2-yl)-N-isopropyl-3-(4-(methylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-Isopropyl-3-(6-(methylcarbamoyl)pyridin-3-yl)-N-(5-(trifluoromethyl)pyridin-2-yl)pyrazolo [1,5-a]pyridine-5-carboxamide;

N-Isopropyl-3-(4-(methylcarbamoyl)phenyl)-N-(5-(trifluoromethyl)pyridin-2-yl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-(5-cyanopyridin-2-yl)-N-isopropyl-3-(5-(methylcarbamoyl)pyridin-2-yl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-(5-Cyanopyridin-2-yl)-N-cyclobutyl-3-(5-(methylcarbamoyl)pyridin-2-yl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-(5-fluoropyridin-2-yl)-N-isopropyl-3-(6-(methylcarbamoyl)pyridin-3-yl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-ethyl-3-(6-(methylcarbamoyl)pyridin-3-yl)-N-(5-(trifluoromethyl)pyridin-2-yl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-(5-cyanopyridin-2-yl)-N-ethyl-3-(4-(methylsulfonyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-ethyl-N-(5-fluoropyridin-2-yl)-3-(6-(methylcarbamoyl)pyridin-3-yl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-cyclobutyl-3-(4-(methylcarbamoyl)phenyl)-N-(5-(trifluoromethyl)pyridin-2-yl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N N-cyclobutyl-3-(6-(methylcarbamoyl)pyridin-3-yl)-N-(5-(trifluoromethyl)pyridin-2-yl)pyrazolo[1,5-a]pyridine-5-carboxamide;

N-(5-cyano-6-(2-hydroxyethoxy)pyridin-2-yl)-N-ethyl-3-(4-(methylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;

4-(5-(N-(5-Cyanopyridin-2-yl)-N-methylsulfamoyl)pyrazolo[1,5-a]pyridin-3-yl)-N-methyl benzamide;

4-(5-(N-(5-Cyanopyridin-2-yl)-N-cyclopropylsulfamoyl)pyrazolo[1,5-a]pyridin-3-yl)-N-methylbenzamide; and

4-(5-(N-(5-cyanopyridin-2-yl)-N-cyclopropylsulfamoyl)pyrazolo[1,5-a]pyridin-3-yl)benzamide.

14. A pharmaceutical composition comprising at least one compound of claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent or excipient.

15. A method for treating or preventing malaria, comprising administering to a subject a therapeutically effective amount of a compound according to claim 1 , wherein the administering may be in combination with a second agent.

16. A method for treating or preventing malaria, comprising administering to a subject a therapeutically effective amount of a pharmaceutical composition according to claim 14 , wherein the administering may be in combination with a second agent.

17. The method according to claim 16 , wherein the second agent is an antimalarial drug selected from artemisinin, artemether, artesunate, arteflene, dihydroartemisinin, chlorproguanil, trimethoprim, chloroquine, quinine, mefloquine, amodiaquine, atovaquone, proguanil, lumefantrine, piperaquine, pyronaridine, halofantrine, pyrimethamine-sulfadoxine, quinacrine, pyrimethamine-dapsone, quinidine, amopyroquine, sulphonamides, primaquine, ferroquine, tafenoquine, arterolane, and pyronaridine.

Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 4, 2015
From: NOVARTIS INSTITUTE FOR FUNCTIONAL GENOMICS, INC., DBA THE GENOMICS INSTITUTE OF THE NOVARTIS RESEARCH FOUNDATION
To: IRM LLC
Reel/Frame 036956/0762 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 4, 2015
From: NOVARTIS INSTITUTE FOR TROPICAL DISEASES PTE LTD.
To: NOVARTIS AG
Reel/Frame 036957/0051 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 4, 2015
From: CHATTERJEE, ARNAB KUMAR; NAGLE, ADVAIT SURESH; PARASELLI, PRASUNA; MISHRA, PRANAB KUMAR; MOREAU, ROBERT JOSEPH; ROLAND, JASON THOMAS; BOLLU, VENKATATAIAH
To: NOVARTIS INSTITUTE FOR FUNCTIONAL GENOMICS, INC., DBA THE GENOMICS INSTITUTE OF THE NOVARTIS RESEARCH FOUNDATION
Reel/Frame 037043/0549 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 4, 2015
From: KONDREDDI, RAVINDER REDDY; LEONG, SEH YONG; SIM, WEI LIN SANDRA; SIMON, OLIVER; TAN, LIYING JOCELYN; YEUNG, BRYAN KS; ZOU, BIN
To: NOVARTIS INSTITUTE FOR TROPICAL DISEASES PTE LTD.
Reel/Frame 037043/0602 →
Continuity (3)
Provisional Application 61728018 · Nov 19, 2012
Provisional Application 61847860 · Jul 18, 2013
Related Publication 20150344471A1 · Dec 3, 2015