Inhibitors of diacylglycerol O-acyltransferase type 1 enzyme
View Patent ↗The present invention relates to compounds of formula (I): wherein R 1 , R 2 , and R 3 , are defined herein. Pharmaceutical compositions and methods for treating DGAT-1 related diseases or conditions are also disclosed.
1. A method for treating a disorder selected from the group consisting of type 2 diabetes, obesity, elevated plasma triglycerides, metabolic syndrome, non-alcoholic steatohepatitis, and non-alcoholic fatty liver disease, said method comprising the step of administering to a subject in need thereof a compound of formula (I),
or a pharmaceutically acceptable salt thereof, wherein
R 1 is hydrogen or alkyl;
R 2 is hydrogen;
R 3 is cycloalkyl, aryl, heteroaryl, heterocycle, —(CR a R b ) m —R 4 , —C(O)OR 5 , —C(R 5 )═N—O(R y ), —C(O)—R 5 , or —C(O)—N(R 5 )(R 6 );
m is 1, 2, 3 or 4;
R a , at each occurrence, is independently hydrogen, halogen, alkyl, alkenyl, haloalkyl, —OR 7a , —N(R 8 )(R 9 ), —C(O)OR 7b , —C(O)—R 7b , —C(O)—N(R 8 )(R 9 ), —(CR c R d ) p —OR 7a , —(CR c R d ) p —N(R 8 )(R 9 ), —(CR c R d ) p —C(O)OR 7b , —(CR c R d ) p —C(O)—R 7b , —(CR c R d ) p —C(O)—N(R 8 )(R 9 ), aryl, heteroaryl, cycloalkyl, or heterocycle;
R b , at each occurrence, is independently hydrogen, halogen, alkyl, alkenyl, haloalkyl, —C(O)OR 7b , —C(O)—R 7b , —C(O)—N(R 8 )(R 9 ), —(CR c R d ) p —OR 7a , —(CR c R d ) p —N(R 8 )(R 9 ), —(CR c R d ) p —C(O)OR 7b , —(CR c R d ) p —C(O)—R 7b , —(CR c R d ) p —C(O)—N(R 8 )(R 9 ), aryl, heteroaryl, cycloalkyl, or heterocycle;
optionally, R a and R b together is ═CH 2 ;
R c and R d , at each occurrence, are each independently hydrogen halogen, alkyl, or haloalkyl;
R y is hydrogen, alkyl, haloalkyl, cycloalkyl, aryl, heteroaryl, heterocycle, cycloalkylalkyl, arylalkyl, heteroarylalkyl, or heterocyclealkyl;
R 4 is hydrogen, alkyl, haloalkyl, cycloalkyl, aryl, heteroaryl, or heterocycle, provided that when R 4 is hydrogen, alkyl or haloalkyl, then at least one R a is —OR 7a , —N(R 8 )(R 9 ), —C(O)OR 7b , —C(O)—R 7b , —C(O)—N(R 8 )(R 9 ), —(CR c R d ) p —OR 7a , —(CR c R d ) p —N(R 8 )(R 9 ), —(CR c R d ) p —C(O)OR 7b , —(CR c R d ) p —C(O)—R 7b , or —(CR c R d ) p —C(O)—N(R 8 )(R 9 ); or R a and R b together is ═CH 2 ;
R 5 , at each occurrence, is independently alkyl, haloalkyl cycloalkyl, aryl, heteroaryl, heterocycle, cycloalkylalkyl, arylalkyl, heteroarylalkyl, or heterocyclealkyl;
wherein each of the cycloalkyl, aryl, heteroaryl, heterocycle, cycloalkyl moiety of the cycloalkylalkyl, aryl moiety of the arylalkyl, heteroaryl moiety of the heteroarylalkyl, and heterocycle moiety of the heterocyclealkyl, as represented by R 3 , R a , R b , R 4 , R 5 , and R y is independently unsubstituted or further substituted with 1, 2, 3, 4 or 5 substituents selected from the group consisting of alkyl, halogen, haloalkyl, oxo, —OR 10 , —S(R 14 ), —S(O) 2 R 15 , —S(O) 2 N(R 11 )(R 12 ), —N(R 11 )(R 12 ), —C(O)OR 10 , —C(O)O(trialkylsilylalkyl), —C(O)N(R 11 )(R 12 ), —(CR e R f ) q —OR 10 , —(CR e R f ) q —N(R 11 )(R 12 ), —(CR e R f ) q —C(O)OR 10 , —(CR e R f ) q —C(O)N(R 11 )(R 12 ), G 1 , and ═N—O(R 10 );
R 6 , R 9 and R 12 , at each occurrence, are each independently hydrogen, alkyl or haloalkyl;
R 7a , at each occurrence, is each independently hydrogen, alkyl, haloalkyl, —N═C(H)R 13a , —(CR g R h ) r —C(O)OR 13 , or G 1 ;
R 7b and R 10 , at each occurrence, are each independently hydrogen, alkyl, haloalkyl, —(CR g R h ) r —C(O)OR 13 , or G 1 ;
R 8 and R 11 , at each occurrence, are each independently hydrogen, alkyl, haloalkyl, —S(O) 2 —R 13a , —S(O) 2 —N(R 13 )(R 14 ), —C(O)OR 13 , —C(O)N(R 13 )(R 14 ), or G 1 ;
p, q, and r, at each occurrence, are each independently 1, 2, 3, or 4;
R e , R f , R g , and R h , at each occurrence, are each independently hydrogen, halogen, alkyl, or haloalkyl;
R 14 , at each occurrence, is independently hydrogen, alkyl or haloalkyl;
R 15 , at each occurrence, is independently alkyl, haloalkyl, or G 1 ;
R 13 , at each occurrence, is independently hydrogen, alkyl, haloalkyl, or G 1 ;
R 13a , at each occurrence, is independently alkyl, haloalkyl, or G 1 ; and
G 1 , at each occurrence, is independently aryl, heteroaryl, cycloalkyl, heterocycle, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocyclealkyl, wherein the aryl, heteroaryl, cycloalkyl, heterocycle, aryl moiety of the arylalkyl, heteroaryl moiety of the heteroarylalkyl, cycloalkyl moiety of the cycloalkylalkyl, and heterocycle moiety of the heterocyclealkyl, are each independently unsubstituted or further substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of alkyl, halogen, —CN, —NO 2 , —OH, —O(alkyl), —NH 2 , —N(H)(alkyl), —N(alkyl) 2 , —C(O)OH, —C(O)O(alkyl), —C(O)NH 2 , —C(O)N(H)(alkyl), —C(O)N(alkyl) 2 , haloalkyl, and alkyl substituted with one substituent selected from the group consisting of —CN, —NO 2 , —OH, —O(alkyl), —NH 2 , —N(H) (alkyl), —N (alkyl) 2 , —C(O)OH, —C(O)O(alkyl), —C(O)NH 2 , —C(O)N(H)(alkyl), and —C(O)N(alkyl) 2 .
2. The method of claim 1 further comprising the step of co-administering with one or more pharmaceutical agents selected from the group consisting of DPPIV inhibitor, incretin mimetic, metformin, fenofibrate, rimonabant, sibutramine, orlistat, nicotinic acid, and a statin.
3. A method for treating a disorder selected from the group consisting of type 2 diabetes, obesity, elevated plasma triglycerides, metabolic syndrome, non-alcoholic steatohepatitis, and non-alcoholic fatty liver disease, said method comprising the step of administering to a subject in need thereof a pharmaceutical composition comprising a compound of formula (I),
or a pharmaceutically acceptable salt thereof, wherein
R 1 is hydrogen or alkyl;
R 2 is hydrogen;
R 3 is cycloalkyl, aryl, heteroaryl, heterocycle, —(CR a R b ) m —R 4 , —C(O)OR 5 , —C(R 5 )═N—O(R y ), —C(O)—R 5 , or —C(O)—N(R 5 )(R 6 );
m is 1, 2, 3 or 4;
R a , at each occurrence, is independently hydrogen, halogen, alkyl, alkenyl, haloalkyl, —OR 7a , —N(R 8 )(R 9 ), —C(O)OR 7b , —C(O)—R 7b , —C(O)—N(R 8 )(R 9 ), —(CR c R d ) p —OR 7a , —(CR c R d ) p —N(R 8 )(R 9 ), —(CR c R d ) p —C(O)OR 7b , —(CR c R d ) p —C(O)—R 7b , —(CR c R d ) p —C(O)—N(R 8 )(R 9 ), aryl, heteroaryl, cycloalkyl, or heterocycle;
R b , at each occurrence, is independently hydrogen, halogen, alkyl, alkenyl, haloalkyl, —C(O)OR 7b , —C(O)—R 7b , —C(O)—N(R 8 )(R 9 ), —(CR c R d ) p —OR 7a , —(CR c R d ) p —N(R 8 )(R 9 ), —(CR c R d ) p —C(O)OR 7b , —(CR c R d ) p —C(O)—R 7b , —(CR c R d ) p —C(O)—N(R 8 )(R 9 ), aryl, heteroaryl, cycloalkyl, or heterocycle;
optionally, R a and R b together is ═CH 2 ;
R c and R d , at each occurrence, are each independently hydrogen halogen, alkyl, or haloalkyl;
R y is hydrogen, alkyl, haloalkyl, cycloalkyl, aryl, heteroaryl, heterocycle, cycloalkylalkyl, arylalkyl, heteroarylalkyl, or heterocyclealkyl;
R 4 is hydrogen, alkyl, haloalkyl, cycloalkyl, aryl, heteroaryl, or heterocycle, provided that when R 4 is hydrogen, alkyl or haloalkyl, then at least one R a is —OR 7a , —N(R 8 )(R 9 ), —C(O)OR 7b , —C(O)—R 7b , —C(O)—N(R 8 ) (R 9 ), —(CR c R d ) p —OR 7a , —(CR c R d ) p —N(R 8 )(R 9 ), —(CR c R d ) p —C(O)OR 7b , —(CR c R d ) p —C(O)—R 7b , or —(CR c R d ) p —C(O)—N(R 8 )(R 9 ); or R a and R b together is ═CH 2 ;
R 5 , at each occurrence, is independently alkyl, haloalkyl cycloalkyl, aryl, heteroaryl, heterocycle, cycloalkylalkyl, arylalkyl, heteroarylalkyl, or heterocyclealkyl;
wherein each of the cycloalkyl, aryl, heteroaryl, heterocycle, cycloalkyl moiety of the cycloalkylalkyl, aryl moiety of the arylalkyl, heteroaryl moiety of the heteroarylalkyl, and heterocycle moiety of the heterocyclealkyl, as represented by R 3 , R a , R b , R 4 , R 5 , and R y , is independently unsubstituted or further substituted with 1, 2, 3, 4 or 5 substituents selected from the group consisting of alkyl, halogen, haloalkyl, oxo, —OR 10 , —S(R 14 ), —S(O) 2 R 15 , —S(O) 2 N(R 11 )(R 12 ), —N(R 11 )(R 12 ), —C(O)OR 10 , —C(O)O(trialkylsilylalkyl), —C(O)N(R 11 )(R 12 ), —(CR e R f ) q —OR 10 , —(CR e R f ) q —N(R 11 )(R 12 ), —(CR e R f ) q —C(O)OR 10 , —(CR e R f ) q —C(O)N(R 11 )(R 12 ), G 1 , and ═N—O(R 10 );
R 6 , R 9 and R 12 , at each occurrence, are each independently hydrogen, alkyl or haloalkyl;
R 7a , at each occurrence, is each independently hydrogen, alkyl, haloalkyl, —N═C(H)R 13a , —(CR g R h ) r —C(O)OR 13 , or G 1 ;
R 7b and R 10 , at each occurrence, are each independently hydrogen, alkyl, haloalkyl, (CR g R h ) r —C(O)OR 13 , or G 1 ;
R 8 and R 11 , at each occurrence, are each independently hydrogen, alkyl, haloalkyl, —S(O) 2 —R 13a , —S(O) 2 —N(R 13 )(R 14 ), —C(O)OR 13 , —C(O)N(R 13 )(R 14 ), or G 1 ;
p, q, and r, at each occurrence, are each independently 1, 2, 3, or 4;
R e , R f , R g , and R h , at each occurrence, are each independently hydrogen, halogen, alkyl, or haloalkyl;
R 14 , at each occurrence, is independently hydrogen, alkyl or haloalkyl;
R 15 , at each occurrence, is independently alkyl, haloalkyl, or G 1 ;
R 13 , at each occurrence, is independently hydrogen, alkyl, haloalkyl, or G 1 ;
R 13a , at each occurrence, is independently alkyl, haloalkyl, or G 1 ; and
G 1 , at each occurrence, is independently aryl, heteroaryl, cycloalkyl, heterocycle, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocyclealkyl, wherein the aryl, heteroaryl, cycloalkyl, heterocycle, aryl moiety of the arylalkyl, heteroaryl moiety of the heteroarylalkyl, cycloalkyl moiety of the cycloalkylalkyl, and heterocycle moiety of the heterocyclealkyl, are each independently unsubstituted or further substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of alkyl, halogen, —CN, —NO 2 , —OH, —O(alkyl), —NH 2 , —N(H)(alkyl), —N(alkyl) 2 , —C(O)OH, —C(O)O(alkyl), —C(O)NH 2 , —C(O)N(H)(alkyl), —C(O)N(alkyl) 2 , haloalkyl, and alkyl substituted with one substituent selected from the group consisting of —CN, —NO 2 , —OH, —O(alkyl), —NH 2 , —N(H)(alkyl), —N(alkyl) 2 , —C(O)OH, —C(O)O(alkyl), —C(O)NH 2 , —C(O)N(H)(alkyl), and —C(O)N(alkyl) 2 ,
in combination with a pharmaceutically acceptable carrier.
4. The method of claim 1 , wherein R 3 is cycloalkyl or heterocycle.
5. The method of claim 1 , wherein R 3 is formula (a)
wherein
R 1k and R 2k together with the carbon atom to which they are attached form a cycloalkyl or a heterocycle ring, each of which is optionally further substituted with 1, 2, 3, 4 or 5 substituents selected from the group consisting of alkyl, halogen, haloalkyl, oxo, —OR 10 , —S(R 14 ), —S(O) 2 R 15 , —S(O) 2 N(R 11 )(R 12 ), —N(R 11 )(R 12 ), —C(O)OR 10 , —C(O)O(trialkylsilylalkyl), —C(O)N(R 11 )(R 12 ), —(CR e R f ) q —OR 10 , —(CR e R f ) q —N(R 11 )(R 12 ), —(CR e R f ) q —C(O)OR 10 , —(CR e R f ) q —C(O)N(R 11 )(R 12 ), and ═N—O(R 10 ;
R 3k is —OR 10 , —N(R 11 )(R 12 ), —C(O)OR 10 , or —C(O)O(trialkylsilylalkyl); and
R e , R f , q, R 10 , R 11 , R 12 , R 14 , and R 15 are as defined in claim 1 .
6. The method of claim 1 , wherein R 3 is aryl, unsubstituted or substituted, with 1, 2, 3, 4 or 5 substituents selected from the group consisting of alkyl, haloalkyl, halogen, —OR 10 , —S(R 14 ), —S(O) 2 R 15 , —S(O) 2 N(R 11 )(R 12 ), —N(R 11 )(R 12 ), —C(O)OR 10 , —C(O)O(trialkylsilylalkyl), —C(O)N(R 11 )(R 12 ), —(CR e R f ) q —OR 10 , —(CR e R f ) q —N(R 11 )(R 12 ), —(CR e R f ) q —C(O)OR 10 , —(CR e R f ) q —C(O)N(R 11 )(R 12 ), and G 1 , and R e , R f , q, R 10 , R 11 , R 12 , R 14 , R 15 , and G 1 are as defined in claim 1 .
7. The method of claim 1 , wherein R 3 is —(CR a R b ) m —R 4 , wherein
R a , at each occurrence, is independently hydrogen, halogen, alkyl, alkenyl, haloalkyl, —OR 7a , —N(R 8 )(R 9 ), —C(O)OR 7b , —C(O)—R 7b , —C(O)—N(R 8 )(R 9 ), —(CR c R d ) p —OR 7a , —(CR c R d ) p —N(R 8 )(R 9 ), —(CR c R d ) p —C(O)OR 7b , —(CR c R d ) p —C(O)—R 7b , —(CR c R d ) p —C(O)—N(R 8 )(R 9 ), aryl, heteroaryl, cycloalkyl, or heterocycle;
R b , at each occurrence, is independently hydrogen, halogen, alkyl, alkenyl, haloalkyl, —C(O)OR 7b , —C(O)—R 7b , —C(O)—N(R 8 )(R 9 ), —(CR c R d ) p —OR 7a , —(CR c R d ) p —N(R 8 )(R 9 ), —(CR c R d ) p —C(O)OR 7b , —(CR c R d ) p —C(O)—R 7b , —(CR c R d ) p —C(O)—N(R 8 )(R 9 ), aryl, heteroaryl, cycloalkyl, or heterocycle;
or R a and R b together is ═CH 2 ; and
m, p, R c , R d , R 4 , R 7a , R 8 , and R 9 are as defined claim 1 .
8. The method of claim 7 , wherein R a and R b , at each occurrence, are each independently hydrogen, alkyl, alkenyl, halogen or haloalkyl, and R 4 is cycloalkyl, aryl, heteroaryl, or heterocycle.
9. The method of claim 1 , wherein R 3 is formula (b)
wherein
R a and R b , at each occurrence, are each independently hydrogen, halogen, alkyl, alkenyl, or haloalkyl;
R 1k and R 2k together with the carbon atom to which they are attached form a cycloalkyl or heterocycle ring, wherein each of the ring is independently unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of alkyl, halogen, haloalkyl, oxo, —OR 10 , —S(R 14 ), —S(O) 2 R 15 , —S(O) 2 N(R 11 )(R 12 ), —N(R 11 )(R 12 ), —C(O)OR 10 , —C(O)O(trialkylsilylalkyl), —C(O)N(R 11 )(R 12 ), —(CR e R f ) q —OR 10 , —(CR e R f ) q —N(R 11 )(R 12 ), —(CR e R f ) q —C(O)OR 10 , —(CR e R f ) q —C(O)N(R 11 )(R 12 ), and ═N—O(R 10 );
R 3k is —OR 10 , —N(R 11 )(R 12 ), or —C(O)OR 10 ; and
R e , R f , q, R 10 , R 11 , R 12 , R 14 , and R 15 are as defined in claim 1 .
10. The method of claim 1 , wherein R 3 is formula (c)
wherein
R b is hydrogen, halogen, alkyl, alkenyl, —C(O)OR 7b , haloalkyl, aryl, heteroaryl, cycloalkyl, or heterocycle;
R a is OR 7a , N(R 8 )(R 9 ), or —C(O)OR 7b ;
or R a and R b together is ═CH 2 ;
R 4 is hydrogen, alkyl, haloalkyl, cycloalkyl, aryl, heteroaryl, or heterocycle; and
R 7a , R 7b , R 8 , and R 9 are as defined in claim 1 .
11. The method of claim 1 , wherein
R 7a is hydrogen, C 1-6 alkyl, haloalkyl, —(CR g R h ) r —C(O)OR 13 , unsubstituted or substituted phenyl; and
R 13 , R g , R h , R 7b , and R 9 are each independently hydrogen, C 1-6 alkyl, or haloalkyl.
12. The method of claim 1 , wherein R 3 is formula (d)
wherein
R 1b is hydrogen, alkyl, alkenyl, halogen, —C(O)OR 7b , haloalkyl, aryl, heteroaryl, cycloalkyl, or heterocycle, R 1a is OR 7a , N(R 8 )(R 9 ) or —C(O)OR 7b , and R 2a and R 2b , at each occurrence, are independently hydrogen, halogen, alkyl, alkenyl, or haloalkyl; or
R 2b is hydrogen, alkyl, alkenyl, halogen, —C(O)OR 7b , haloalkyl, aryl, heteroaryl, cycloalkyl, or heterocycle, R 2a is OR 7a , N(R 8 )(R 9 ) or —C(O)OR 7b , and R 1a and R 1b , at each occurrence, are independently hydrogen, halogen, alkyl, alkenyl, or haloalkyl;
each of the aryl, heteroaryl, cycloalkyl, or heterocycle as represented by R 1b and R 2b is independently unsubstituted or further substituted with 1, 2, 3, 4 or 5 substituents selected from the group consisting of 1, 2, 3, 4 or 5 substituents selected from the group consisting of alkyl, halogen, haloalkyl, oxo, —OR 10 , —S(R 14 ), —S(O) 2 R 15 , —S(O)N(R 11 )(R 12 ), —N(R 11 )(R 12 ), —C(O)OR 10 , —C(O)O(trialkylsilylalkyl), —C(O)N(R 11 )(R 12 ), —(CR e R f ) q —OR 10 , —(CR e R f ) q —N(R 11 )(R 12 ), —(CR e R f ) q —C(O)OR 10 , —(CR e R f ) q —C(O)N(R 11 )(R 12 ), G 1 , and ═N—O(R 10 );
R 4 is hydrogen, alkyl, haloalkyl, cycloalkyl, aryl, heteroaryl, or heterocycle; and
R 7a , R 7b , R 8 , R e , R f , R 9 , R 10 , R 11 , R 12 , R 14 , R 15 , and q, are as defined in claim 1 .
13. The method of claim 1 , wherein R 3 is —C(O)—R 5 .
14. The method of claim 1 , wherein the compound of formula (I) is selected from the group consisting of
6-[(4-aminophenyl)ethynyl]-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine;
6-(cyclohexylethynyl)-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine;
5-methyl-6-(4-phenylbut-1-ynyl)[1,2,4]triazolo[1,5-a]pyrimidin-7-amine;
1-[(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)ethynyl]cyclopentanol;
1-[(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)ethynyl]cyclohexanol;
4-[(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)ethynyl]tetrahydro-2H-pyran-4-ol;
4-(7-amino-5-methyl[1,2,4]triazolo[1,5a]pyrimidin-6-yl)-2-cyclopentylbut-3-yn-2-ol;
4-(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)-2-phenylbut-3-yn-2-ol;
4-(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)-1,1,1-trifluoro-2-phenylbut-3-yn-2-ol;
3-(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)-1,1-diphenylprop-2-yn-1-ol;
3-(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)-1-phenylprop-2-yn-1-ol;
6-(3-cyclohexylprop-1-ynyl)-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine;
3-(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)-1-cyclopropyl-1-phenylprop-2-yn-1-ol;
6-[(4-methoxyphenyl)ethynyl]-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine;
3-(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)-1,1-bis(4-chlorophenyl)prop-2-yn-1-ol;
5-methyl-6-(3-morpholin-4-yl-3-phenylprop-1-ynyl)[1,2,4]triazolo[1,5-a]pyrimidin-7-amine;
3-(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)-1-(1-methylcyclohexyl)-1-phenylprop-2-yn-1-ol;
3-(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)-1-(3,4′-dichloro-1,1′-biphenyl-4-yl)prop-2-yn-1-ol;
1-(7 amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)-3-(1,1′-biphenyl-4-yl)-4,4-dimethylpent-1-yn-3-ol;
methyl 4-(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)-2-hydroxy-2-phenylbut-3-ynoate;
N-{1-[(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)ethynyl]cyclohexyl}-3-chlorobenzenesulfonamide;
N-{4-[(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)ethynyl]phenyl}-N′-(3-chlorophenyl)urea;
(1R,4R)-2-[(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)ethynyl]-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol;
(1Z)-2-[3-(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)prop-2-ynyl]-4-tert-butylcyclohexanone oxime;
4-(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)-2-(4-isopropyl-2-methylcyclopentyl)but-3-yn-2-ol;
methyl {[3-(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)-1-phenylprop-2-ynyl]oxy}acetate;
{[3-(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)-1-phenylprop-2-ynyl]oxy}acetic acid;
{2-[(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)ethynyl]phenyl}methanol;
{3-[3-(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)-1-hydroxy-1-methylprop-2-ynyl]-2,2-dimethylcyclobutyl}acetic acid;
4-(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)-2-cyclobutylbut-3-yn-2-ol;
4-(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)-2-(3-methylcyclobutyl)but-3-yn-2-ol;
5-methyl-6-(3-phenylprop-1-ynyl) [1,2,4]triazolo[1,5-a]pyrimidin-7-amine;
6-(3-cyclopentylprop-1-ynyl)-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine;
6-[(1-aminocyclohexyl)ethynyl]-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine;
3-(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)-1-cyclopentylprop-2-yn-1-ol;
3-(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)-1-(2,4-dichlorophenyl)prop-2-yn-1-ol;
4-(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)-1-cyclopentyl-2-methylbut-3-yn-2-ol;
{4-[(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)ethynyl]-4-hydroxycyclohexyl}acetic acid;
methyl {4-[(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)ethynyl]-4-hydroxycyclohexyl}acetate;
(1R,4S)-2-[(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)ethynyl]bicyclo[2.2.1]heptan-2-ol;
(1R,2S,4R)-2-[(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)ethynyl]-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol;
(1R,2R,4S)-2-[(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)ethynyl]-1,3,3-trimethylbicyclo[2.2.1]heptan-2-ol;
tert-butyl {4-[(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)ethynyl]-4-hydroxycyclohexyl}acetate;
(1S,2S,4R)-2-[(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)ethynyl]-1,3,3-trimethylbicyclo[2.2.1]heptan-2-ol;
(1S,2R,4S)-2-[(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)ethynyl]-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol;
1-[3-(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)prop-2-ynyl]cyclopentanol;
1-[(7-amino[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)ethynyl]cyclopentanol;
1-[3-(7-amino[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)prop-2-ynyl]cyclopentanol;
(1R,2S,4R)-2-[3-(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)prop-2-ynyl]-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol;
methyl 1-[3-(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)prop-2-ynyl]cyclohexanecarboxylate;
6-[3-(4-methoxyphenoxy)but-1-ynyl]-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine;
(1R)-3-(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)-1-phenylprop-2-yn-1-ol;
(1S)-3-(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)-1-phenylprop-2-yn-1-ol;
4-(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)-1-phenylbut-3-yn-1-ol;
(trans)-ethyl 2-[3-(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)-1-hydroxyprop-2-ynyl]cyclopropanecarboxylate;
1-[3-(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)prop-2-ynyl]cyclohexanecarboxylic acid;
1-[(7-amino-5-ethyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)ethynyl]cyclopentanol;
3-(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)-1-phenylprop-2-yn-1-one;
2-{3-[3-(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)-1-hydroxy-1-methylprop-2-ynyl]-2,2-dimethylcyclobutyl}acetamide;
(1R,2S,4R)-2-[(7-amino-5-ethyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)ethynyl]-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol;
1-[(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)ethynyl]cycloheptanol;
{[3-(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)-1-cyclopentylprop-2-ynyl]oxy}acetic acid;
({1-[(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)ethynyl]cyclopentyl}oxy)acetic acid;
3-(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)-1-cyclohexylprop-2-yn-1-ol;
methyl 4-[3-(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)-1-hydroxyprop-2-ynyl]cyclohexanecarboxylate;
4-[3-(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)-1-hydroxyprop-2-ynyl]cyclohexanecarboxylic acid;
{3-[3-(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)-1-methyleneprop-2-ynyl]-2,2-dimethylcyclobutyl}acetic acid;
methyl 1-[3-(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl) prop-2-ynyl]cyclopentanecarboxylate;
2-(trimethylsilyl)ethyl 1-[3-(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl) prop-2-ynyl]cyclohexanecarboxylate;
6-[(4-bromophenyl)ethynyl]-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine;
6-[(4-chlorophenyl)ethynyl]-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine;
methyl 2-{-4-[(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)ethynyl]phenyl}-2-methylpropanoate; and
ethyl 1-[4-(7-amino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)but-3-ynyl]-2-oxocyclopentanecarboxylate;
or a pharmaceutically acceptable salt thereof.