Tri-cyclic pyrazolopyridine kinase inhibitors
View Patent ↗The present invention relates to compounds of tri-cyclic pyrazolopyridine useful as inhibitors of protein kinase. The invention also provides pharmaceutically acceptable compositions containing such compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders. The invention also provides processes for preparing compounds of the inventions.
1. A compound represented by the following structural formula:
or a pharmaceutically acceptable salt thereof, wherein:
R 1 is —H, halogen, —OR′, —N(R′) 2 , —C(O)OR′, —C(O)N(R′) 2 , —NR′C(O)R′, —NR′C(O)OR′, —CN, —NO 2 , C1-C10 aliphatic optionally and independently substituted with one or more J a , or C3-C8 cycloaliphatic optionally and independently substituted with one or more J b ;
R 2 is —H, halogen , —CN, —NO 2 , —OR′, —N(R′) 2 , —C(O)OR′, —C(O)N(R′) 2 , —NR′C(O)R′, —NR′C(O)OR′, C1-C10 aliphatic optionally and independently substituted with one or more J a , or C3-C8 cycloaliphatic optionally and independently substituted with one or more J b ;
ring B is a pyridyl; and ring B is optionally substituted with one Y and independently further optionally and independently substituted with one or more J c ;
Y is —Y1-Q1;
Y1 is absent, or C1-10 aliphatic, wherein up to three methylene units of Y1 are optionally and independently replaced with G′ wherein G′ is —O—, —C(O)—, —N(R′)—, or —S(O) p —; and Y1 is optionally and independently substituted with one or more J d ;
Q1 is absent, or a C3-8 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur; and Q1 is optionally and independently substituted with one or more J b ; wherein when B is substituted with Y then Y1 and Q1 are not both absent;
ring C is a 3-8-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8-12 membered saturated, partially unsaturated, or fully unsaturated bicyclic ring system having 0-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur; and ring C is optionally substituted with one Z and independently further optionally and independently substituted with one or more J b ;
Z is —Y2-Q2;
Y2 is absent, or C1-10 aliphatic, wherein up to three methylene units of Y2 are optionally and independently replaced with G′ wherein G′ is —O—, —C(O)—, —N(R′)—, or —S(O) p —; and Y2 is optionally and independently substituted with one or more J d ;
Q2 is absent, C3-8 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8-12 membered saturated, partially unsaturated, or fully unsaturated bicyclic ring system having 0-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur; and Q2 is optionally and independently substituted with one or more J e ; wherein when C is substituted with Z then Y2 and Q2 are not both absent;
each R′ is independently —H, or C1-C6 alkyl optionally and independently substituted with one or more J a ;
each J a is independently halogen, —OR, —N(R) 2 , —C(O)R, —C(O)OR, —C(O)N(R) 2 , —NRC(O)R, —NRC(O)OR, —CN, —NO 2 , or oxo;
each J b is independently halogen, —OR, —N(R) 2 , —C(O)R, —C(O)OR, —C(O)N(R) 2 , —NRC(O)R, —NRC(O)OR, —CN, —NO 2 , oxo, or C1-C6 alkyl optionally and independently substituted with one or more J a ; or
two J b groups on the same atom can join together to form a C3-8 membered partially unsaturated, or fully unsaturated monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the ring is optionally and independently substituted with one or more J a ;
each J c is independently halogen, —OR′, —N(R′) 2 , —C(O)R, —C(O)OR′, —C(O)N(R′) 2 , —NR′C(O)R′, —NR′C(O)OR′, —CN, —NO 2 , or C1-C10 aliphatic optionally and independently substituted with one or more J a , or C3-C8 cycloaliphatic optionally and independently substituted with one or more J b ;
each J d is independently halogen, —OH, —N(H) 2 , —C(O)H, —C(O)OH, —C(O)N(H) 2 , —NHC(O)H, —NHC(O)OH, —CN, or —NO 2 ;
each J e is independently halogen, —OH, —N(H) 2 , —C(O)H, —C(O)OH, —C(O)N(H) 2 , —NHC(O)H, —NHC(O)OH, —CN, —NO 2 , oxo, C1-10 aliphatic, wherein up to three methylene units are optionally and independently replaced with G′ wherein G′ is —O—, —C(O)—, —N(R′)—, or —S(O) p — and the aliphatic group is optionally and independently substituted with one or more J d , or J e is C3-8 cycloaliphatic optionally and independently substituted with one ore more J b ;
each R is independently —H or C1-C6 alkyl; and
each p is independently 0, 1, or 2.
2. A compound of claim 1 , represented by the following structural formula:
or a pharmaceutically acceptable salt thereof, wherein:
R 1 is —H, halogen, —OR′, —N(R′) 2 , —C(O)OR′, —C(O)N(R′) 2 , —NR′C(O)R′, —NR′C(O)OR′, —CN, —NO 2 , C1-C10 aliphatic optionally and independently substituted with one or more J a , or C3-C8 cycloaliphatic optionally and independently substituted with one or more J b ;
R 2 is —H, halogen, —CN, —NO 2 , —OR′, —N(R′) 2 , —C(O)OR′, —C(O)N(R′) 2 , —NR′C(O)R′, —NR′C(O)OR′, C1-C10 aliphatic optionally and independently substituted with one or more J a , or C3-C8 cycloaliphatic optionally and independently substituted with one or more J b ;
ring B is pyridyl; and ring B is optionally substituted with one Y and independently further optionally and independently substituted with one or more J c ;
Y is —Y1-Q1;
Y1 is absent, or C1-10 aliphatic, wherein up to three methylene units of Y1 are optionally and independently replaced with G′ wherein G′ is —O—, —C(O)—, —N(R′)—, or —S(O) p —; and Y1 is optionally and independently substituted with one or more J d ;
Q1 is absent, or a C3-8 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur; and Q1 is optionally and independently substituted with one or more J b ; wherein Y1 and Q1 are not both absent;
ring C is a 3-8-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8-12 membered saturated, partially unsaturated, or fully unsaturated bicyclic ring system having 0-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur; and ring C is optionally substituted with one Z and independently further optionally and independently substituted with one or more J b ;
Z is —Y2-Q2;
Y2 is absent, or C1-10 aliphatic, wherein up to three methylene units of Y2 are optionally and independently replaced with G′ wherein G′ is —O—, —C(O)—, —N(R′)—, or —S(O) p —; and Y2 is optionally and independently substituted with one or more J d ;
Q2 is absent, C3-8 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8-12 membered saturated, partially unsaturated, or fully unsaturated bicyclic ring system having 0-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur; and Q2 is optionally and independently substituted with one or more J e ; wherein Y2 and Q2 are not both absent;
each R′ is independently —H, or C1-C6 alkyl optionally and independently substituted with one or more J a ;
each J a is independently halogen, —OR, —N(R) 2 , —C(O)OR, —C(O)N(R) 2 , —NRC(O)R, —NRC(O)OR, —CN, —NO 2 , or oxo;
each J b is independently halogen, —OR, —N(R) 2 , —C(O)OR, —C(O)N(R) 2 , —NRC(O)R, —NRC(O)OR, —CN, —NO 2 , oxo, or C1-C6 alkyl optionally and independently substituted with J a ; or
two J b groups on the same atom can join together to form a C3-8 membered partially unsaturated, or fully unsaturated monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the ring is optionally and independently substituted with one or more J a ; each J c is independently halogen, —OR′, —N(R′) 2 , —C(O)OR′, —C(O)N(R′) 2 , —NR′C(O)R′, —NR′C(O)OR′, —CN, —NO 2 , or C1-C10 aliphatic optionally and independently substituted with one or more J a , or C3-C8 cycloaliphatic optionally and independently substituted with one or more J b ;
each J d is independently halogen, —CN, or —NO 2 ;
each J e is independently halogen, —CN, —NO 2 , oxo, C1-10 aliphatic, wherein up to three methylene units are optionally and independently replaced with G′ wherein G′ is —O—, —C(O)—, —N(R′)—, or —S(O) p — and the aliphatic group is optionally and independently substituted with one or more J d , or J e is C3-8 cycloaliphatic optionally and independently substituted with one ore more J b ;
each R is independently —H or C1-C6 alkyl; and
each p is independently 0, 1, or 2.
3. A compound of claim 2 , represented by the following structural formula:
or a pharmaceutically acceptable salt thereof, wherein:
R 1 is —H, halogen, —OR′, —N(R′) 2 , —C(O)OR′, —C(O)N(R′) 2 , —NR′C(O)R′, —NR′C(O)OR′, —CN, —NO 2 , C1-C10 aliphatic optionally and independently substituted with one or more J a , or C3-C8 cycloaliphatic optionally and independently substituted with one or more J b ;
R 2 is —H, halogen, —CN, —NO 2 , —OR′, —N(R′) 2 , —C(O)OR′, —C(O)N(R′) 2 , —NR′C(O)R′, —NR′C(O)OR′, C1-C10 aliphatic optionally and independently substituted with one or more J a , or C3-C8 cycloaliphatic optionally and independently substituted with one or more J b ;
ring B is pyridyl; and ring B is optionally substituted with one Y and independently further optionally and independently substituted with one or more J c ;
Y is —Y1-Q1;
Y1 is absent, or C1-10 aliphatic, wherein up to three methylene units of Y1 are optionally and independently replaced with G′ wherein G′ is —O—, —C(O)—, —N(R′)—, or —S(O) p —; and Y1 is optionally and independently substituted with one or more J d ;
Q1 is absent, or a C3-8 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur; and Q1 is optionally and independently substituted with one or more J b ; wherein Y1 and Q1 are not both absent;
ring C is a 3-8-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8-12 membered saturated, partially unsaturated, or fully unsaturated bicyclic ring system having 0-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur; and ring C is optionally substituted with one Z and independently further optionally and independently substituted with one or more J b ;
Z is —Y2-Q2;
Y2 is absent, or C1-10 aliphatic, wherein up to three methylene units of Y2 are optionally and independently replaced with G′ wherein G′ is —O—, —C(O)—, —N(R′)—, or —S(O) p —; and Y2 is optionally and independently substituted with one or more J d ;
Q2 is absent, C3-8 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8-12 membered saturated, partially unsaturated, or fully unsaturated bicyclic ring system having 0-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur; and Q2 is optionally and independently substituted with one or more J e ; wherein Y2 and Q2 are not both absent;
each R′ is independently —H, or C1-C6 alkyl optionally and independently substituted with one or more J a ;
each J a is independently halogen, —OR, —N(R) 2 , —C(O)OR, —C(O)N(R) 2 ; —NRC(O)R, —NRC(O)OR, —CN, —NO 2 , or oxo;
each J b is independently halogen, —OR, —N(R) 2 , —C(O)OR, —C(O)N(R) 2 ; —NRC(O)R, —NRC(O)OR, —CN, —NO 2 , oxo, or C1-C6 alkyl optionally and independently substituted with J a ;
each J c is independently halogen, —OR′, —N(R′) 2 , —C(O)OR′, —C(O)N(R′) 2 , —NR′C(O)R′, —NR′C(O)OR′, —CN, —NO 2 , or C1-C10 aliphatic optionally and independently substituted with one or more J a , or C3-C8 cycloaliphatic optionally and independently substituted with one or more J b ;
each J d is independently halogen, —CN, or —NO 2 ;
each J e is independently halogen, —CN, —NO 2 , oxo, C1-10 aliphatic, wherein up to three methylene units are optionally and independently replaced with G′ wherein G′ is —O—, —C(O)—, —N(R′)—, or —S(O) p — and the aliphatic group is optionally and independently substituted with one or more J d , or J e is C3-8 cycloaliphatic optionally and independently substituted with one ore more J b ;
each R is independently —H or C1-C6 alkyl; and
each p is independently 0, 1, or 2.
4. The compound of claim 3 wherein:
R 1 is —H, halogen, C1-C10 aliphatic optionally and independently substituted with one or more J a , or C3-C8 cycloaliphatic optionally and independently substituted with one or more J b ; and
R 2 is —H, halogen, C1-C10 aliphatic optionally and independently substituted with one or more J a , or C3-C8 cycloaliphatic optionally and independently substituted with one or more J b .
5. The compound of claim 4 wherein:
R 2 is —H.
6. The compound of claim 5 wherein:
R 1 is —H, halogen or C1-C10 haloalkyl.
7. The compound of claim 6 wherein the compound represented by the following structural formula:
or a pharmaceutically acceptable salt thereof, wherein:
each q is independently 0 or 1; and
each t is independently 0, or 1-4.
8. The compound of claim 7 , wherein:
ring C is selected from the group consisting of cyclopropyl, cyclopentyl, cyclobutyl, cyclohexyl, cyclohexenyl, phenyl, pyridyl, pyrazinyl, pyrimidinyl, pyrrolyl, imidazolyl, pyrazolyl, oxazalolyl, oxadiazolyl, thiazolyl, thiadiazolyl, piperidinyl, piperazinyl, pyrrolidinyl, pyrazolidinyl, imidazolidinyl, azepanyl, diazepanyl, triazepanyl, azocanyl, diazocanyl, triazocanyl, indolyl, indazolyl, benzimidazolyl, quinolyl, quinoxalyl, indolinyl, oxazolidinyl, isoxazolidinyl, thiazolidinyl, isothiazolidinyl, oxazocanyl, oxazepanyl, azabicyclopentyl, azabicyclohexyl, azabicycloheptyl, azabicyclooctyl, azabicyclononyl, azabicyclodecyl, diazabicyclohexyl, diazabicycloheptyl, azetidinyl, isoindolinyl, isoindolyl, dihydroindazolyl, dihydrobenzimidazolyl, morpholinyl, tetrahydropyridyl, dihydropyridyl, tetrahydropyrazinyl, dihydropyrazinyl, tetrahydropyrimidinyl, dihydropyrimidinyl, dihydropyrrolyl, dihydropyrazolyl, dihydroimidazolyl, octahydropyrrolopyrazyl, octahydropyrrolopyridyl, octahydropyridopyrazyl, octahydropyridopyridyl, diazabicyclooctyl, diazabicyclononyl, diazabicyclodecyl, thiazepanyl, and thiazocanyl wherein each ring is optionally substituted with one Z and independently further and optionally substituted with one or more J b .
9. The compound of claim 7 , wherein
ring C is selected from the group consisting of cyclohexyl, diazabicyclooctyl, phenyl, pyridyl, pyrazinyl, pyrimidinyl, pyrrolyl, imidazolyl, pyrazolyl, oxazalolyl, oxadiazolyl, thiazolyl, azetidinyl, morpholinyl, azepanyl, diazabicycloheptyl, diazabicyclooctyl, indolyl, tetrahydropyridyl, dihydropyridyl, octahydropyrrolopyrazyl, octahydropyrrolopyridyl, octahydropyridopyrazyl, octahydropyridopyridyl, thiadiazolyl, piperidinyl, piperazinyl, pyrrolidinyl, diazepanyl, and oxazepanyl wherein each ring is optionally substituted with one Z and independently further and optionally substituted with one or more J b .
10. The compound of claim 7 , wherein
ring C is selected from the group consisting of cyclohexyl, 3,8-diazabicyclo[3.2.1.]octane, phenyl, pyridyl, piperidinyl, piperazinyl, diazepanyl, pyrrolidinyl, pyrrolyl, pyrrazolyl, azetidinyl, morpholinyl, azepanyl, 2,5 diazabicycloheptyl, diazabicyclooctyl, indolyl, tetrahydropyridyl, octahydro-1H-pyrrolo[2,3-b]pyrazyl, octahydropyrrolo[1,2-a]pyrazyl, and oxazepanyl wherein each ring is optionally substituted with one Z and independently further and optionally substituted with one or more J b .
11. The compound of claim 7 , wherein
ring C is selected from the group consisting of piperidinyl, piperazinyl, diazapanyl, pyrrolidinyl, azetidinyl, and azepanyl, wherein each ring is optionally substituted with one Z and independently further and optionally substituted with one or more J b .
12. The compound of claim 7 , wherein ring C is represented a structural formula selected from the group consisting of:
q is 0 or 1; and
t is 0 or 1-4.
13. The compound of claim 7 , wherein ring C is represented by a structural formula selected from the group consisting of:
q is 0 or 1; and
t is 0 or 1-4.
14. The compound of claim 13 wherein ring C is represented by a structural formula represented by:
q is 0 or 1; and
t is 0 or 1-4.
15. The compound of claim 7 , wherein ring C is represented by a structural formula selected from the group consisting of:
q is 0 or 1; and
t is 0 or 1-4.
16. The compound of claim 15 wherein ring C is represented by a structural formula represented by:
q is 0 or 1; and
t is 0 or 1-4.
17. The compound of claim 15 wherein ring C is represented by a structural formula represented by:
q is 0 or 1; and
t is 0 or 1-4.
18. The compound of claim 17 wherein:
R 1 is halogen or C1-C10 haloalkyl.
19. The compound of claim 18 wherein:
ring B is pyridyl substituted with one Y and independently further and optionally and independently substituted with one or more J c .
20. The compound of claim 19 wherein:
ring B is pyridyl substituted with one Y.
21. The compound of claim 7 wherein:
ring C is selected from the group consisting of piperidinyl, piperazinyl, or diazepanyl, substituted with one Z and independently further and optionally substituted with one or more J b .
22. The compound of claim 21 wherein:
ring C is selected from the group consisting of piperidinyl, piperazinyl, or diazepanyl, substituted with one Z.
23. The compound of claim 7 wherein the compound represented by the following structural formula:
or a pharmaceutically acceptable salt thereof, wherein:
q is 1; and
each t is independently 0 or 1-4.
24. The compound of claim 23 wherein:
ring B is pyridyl substituted with one Y and independently further and optionally and independently substituted with one or more J c .
25. The compound of claim 24 wherein:
ring B is pyridyl substituted with one Y.
26. The compound of claim 25 wherein:
ring C is selected from the group consisting of piperidinyl, piperazinyl, or diazepanyl, substituted with one Z and independently further and optionally substituted with one or more J b .
27. The compound of claim 26 wherein:
ring C is selected from the group consisting of piperidinyl, piperazinyl, or diazepanyl, substituted with one Z.
28. The compound of claim 7 wherein the compound represented by the following structural formula:
or a pharmaceutically acceptable salt thereof, wherein:
q is 1; and
each t is independently 0 or 1-4.
29. The compound of claim 28 wherein:
ring B is pyridyl independently and optionally and independently substituted with one or more J c .
30. The compound of claim 29 wherein:
ring B is pyridyl.
31. The compound of claim 30 wherein:
ring C is selected from the group consisting of piperidinyl, piperazinyl, or diazepanyl, substituted with one Z and independently further and optionally substituted with one or more J b .
32. The compound of claim 30 wherein:
ring C is selected from the group consisting of piperidinyl, piperazinyl, or diazepanyl, substituted with one Z.
33. The compound of claim 7 wherein the compound represented by the following structural formula:
or a pharmaceutically acceptable salt thereof, wherein:
T is —CH 2 —, —CH(J b )-, —C(J b ) 2 -, —NH— or —N(J b )-;
t is 0, 1, or 2;
n is 0 or 1;
w is 0 or 1;
J c is CN, F, Cl or CF 3 ;
U is Z or J b
Z is Y2-Q2;
Y2 is absent or C1-6 alkyl optionally and independently substituted with one or more J d ;
Q2 is C1-C6 cyloalkyl having 0-1 heteroatoms optionally and independently substituted with one or more J e ;
J b is F, —OR, —N(R) 2 , —C(O)N(R), C1-6 alkyl optionally and independently substituted with one or more J a ;
J a is F, —OR, —N(R) 2 , or —C(O)N(R);
each R is independently —H or C1-C6 alkyl; and
each J d and J e is independently —OH, —NH 2 or F.
34. The compound of claim 33 wherein the compound represented by the following structural formula:
or a pharmaceutically acceptable salt thereof, wherein:
T is CHNH 2 or NH;
J c is F or CF 3 ;
U is Z or J b
Z is Y2-Q2;
Y2 is absent or C1-6 alkyl optionally and independently substituted with one or more J d ;
Q2 is C 1-C6 cyloalkyl optionally and independently substituted with one or more J e ;
J b is C 1-6 alkyl optionally and independently substituted with one or more J a ;
J a is —OH, —NH 2 or F; and
each J d and J e is independently —OH, —NH 2 or F.
35. The compound of claim 7 wherein the compound represented by the following structural formula:
or a pharmaceutically acceptable salt thereof, wherein:
T is —CH 2 —, —CH(J b )-, —C(J b ) 2 -, —NH— or —N(J b )-;
t is 0, 1, or 2;
w is 0 or 1;
J c is CN, F, Cl, or CF 3 ;
U is Z or J b
Z is Y2-Q2;
Y2 is absent or C1-6 alkyl optionally and independently substituted with one or more J d ;
Q2 is C1-C6 cyloalkyl having 0-1 heteroatoms optionally and independently substituted with one or more J e ;
J b is F, —OR, —N(R) 2 , —C(O)N(R), C1-6 alkyl optionally and independently substituted with one or more J a ;
J a is F, —OR, —N(R) 2 , or —C(O)N(R);
each R is independently —H or C1-C6 alkyl; and
each J d and J e is independently —OH, —NH 2 or F.
36. The compound of claim 35 wherein:
T is —CHNH 2 —, or —NH—.
37. The compound of claim 7 wherein the compound represented by the following structural formula:
or a pharmaceutically acceptable salt thereof, wherein:
T is —CH 2 —, —CH(J b )-, —C(J b ) 2 -, —NH— or —N(J b )-;
t is 0, 1, or 2;
w is 0 or 1;
J c is CN, F, CF 3 ; CH 2 OH, CH 2 (CH3)OH, or
U is Z or J b
Z is Y2-Q2;
Y2 is absent or C1-6 alkyl optionally and independently substituted with one or more J d ;
Q2 is C1-C6 cyloalkyl having 0-1 heteroatoms optionally and independently substituted with one or more J e ;
J b is F, —OR, —N(R) 2 , —C(O)N(R), C1-6 alkyl optionally and independently substituted with one or more J a ;
J a is F, —OR, —N(R) 2 , or —C(O)N(R);
each R is independently —H or C1-C6 alkyl; and
each J d and J e is independently —OH, —NH 2 or F.
38. The compound of claim 37 wherein:
T is —CHNH 2 —, or —NH—.
39. The compound of claim 7 wherein the compound represented by the following structural formula:
or a pharmaceutically acceptable salt thereof, wherein:
T is —CH 2 —, —CH(J b )-, —C(J b ) 2 -, —NH— or —N(J b )-;
t is 0, 1, or 2;
w is 0 or 1;
J c is CN, F, Cl, or CF 3 ;
U is Z or J b
Z is Y2-Q2;
Y2 is absent or C1-6 alkyl optionally and independently substituted with one or more J d ;
Q2 is absent or C3-C8 cyloalkyl having 0-1 heteroatoms optionally and independently substituted with one or more J e ;
J b is F, —OR, —N(R) 2 , —C(O)N(R), C1-6 alkyl optionally and independently substituted with one or more J a ;
J a is F, —OR, —N(R) 2 , or —C(O)N(R);
each R is independently —H or C1-C6 alkyl; and
each J d and J e is independently —OH, —NH 2 or F.
40. The compound of claim 35 wherein:
T is —CHNH 2 —, or —NH—.
41. The compound of claim 40 , wherein the compound is represented by the following structural formula:
or a pharmaceutically acceptable salt thereof.
42. A compound represented by a structural formula selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
43. A composition comprising a compound or pharmaceutically acceptable salt thereof according to claim 1 , and a pharmaceutically acceptable carrier, adjuvant, or vehicle.