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US 2009/0221584 A1Published application
Bisaryl-sulfonamides
AssigneeAmgen Inc.
InventorsPhilippe Bergeron, Christopher N. Farthing, Stuart D. Jones, John W. Liebeschuetz, Sarah E. Lively, Lawrence R. McGee, Sharon McKendry, David Sheppard, Stephen C. Young
Life of this patent
Estimating the term…
Abstract
Compounds, compositions and methods are provided that are useful in the treatment or prevention of a condition or disorder mediated by PPARγ or PPARδ. In particular, the compounds of the invention modulate the function of PPARγ or PPARδ. The subject methods are particularly useful in the treatment and/or prevention of diabetes, obesity, hypercholesterolemia, rheumatoid arthritis and atherosclerosis.
Claims76
A compound having the formula (I):
- wherein
- Ar is a member selected from the group consisting of phenyl, naphthyl and pyridyl;
- each of which is optionally substituted with from one to three R8 substituents, wherein each R8 is a member independently selected from the group consisting of halogen, cyano, nitro, (C1-C8)alkyl, (C1-C8)alkoxy, (C1-C8)haloalkyl, (C1-C8)haloalkoxy, (C2-C8) alkenyl, (C2-C8) alkynyl, hydroxyl and NR12R13;
- B is aryl or heteroaryl;
- each of which is optionally substituted with from one to two R9 substituents, wherein each R9 is a member independently selected from the group consisting of halogen, nitro, (C1-C8)alkyl, (C1-C8)alkoxy and NR12R13;
- L is selected from the group consisting of O, S(O)k, CRaRb and C(O);
- each Ra or Rb is independently selected from the group consisting of hydrogen, cyano, nitro, and (C1-C8) alkyl;
- W is independently C(R3) or N;
- X is independently C(R4) or N;
- Y is independently C(R5) or N;
- Z is independently C(R6) or N, wherein at least one of W, X, Y and Z is N and at least one W, X, Y and Z is other than N;
- R1 is selected from the group consisting of hydrogen, (C1-C8)alkyl, (C2-C8)heteroalkyl and aryl(C1-C8)alkyl;
- R2 is selected from the group consisting of hydrogen, halogen, cyano, nitro, NR12R13 and S(O)mR7;
- each R3, R4, R5, or R6 is a member independently selected from the group consisting of hydrogen, hydroxy, halogen, cyano, nitro, NR12R13, (C1-C8)alkyl, halo(C1-C8)alkyl, hydroxy(C1-C8)alkyl, (C3-C8)cycloalkyl, (C1-C8)alkoxy, (C1-C8)thioalkoxy, (C2-C8)heteroalkyl, aryl, heteroaryl, —C(O)R11, —CO2R11, —C(O)N R12R13, —C(O)CH2CN, —X1Q1, X2R11 and X2NR12R13;
- each X1 is independently selected from the group consisting of (C1-C2)alkylene and C(O);
- and
- each Q′ is independently selected from the group consisting of pyrrolidinyl, piperidinyl, and morpholinyl;
- R7 is selected from the group consisting of (C1-C8)alkyl, (C3-C8)cycloalkyl, (C1-C8)haloalkyl, aryl, NR12R13, (C3-C8)heterocycloalkyl, X2—C(O)OR15, X2—C(O)N(R15)2, and —X2—NR12R13;
- each X2 is (C1-C8)alkylene;
- each R11 is independently selected from the group consisting of hydrogen, (C1-C8)alkyl, (C2-C8)alkenyl, (C3-C8)cycloalkyl, (C2-C8)heteroalkyl, aryl, heteroaryl, heteroaryl(C1-C8)alkyl, (C3-C8) heterocycloalkyl and aryl(C1-C8)alkyl;
- each R12 and R13 is independently selected from the group consisting of hydrogen, (C1-C8)alkyl, (C2-C8) alkenyl, (C3-C8)cycloalkyl, (C2-C8)heteroalkyl, (C1-C8)alkoxy, aryl and aryl(C1-C8)alkyl;
- optionally, R12 and R13 are combined with the nitrogen to which each is attached to form a 3-, 4-, 5-, 6- or 7-membered ring which can be saturated or unsaturated and contain 0 to 2 additional heteroatoms selected from N, O and S;
- wherein said ring is optionally substituted with from one to four substituents selected from the group consisting of hydroxy, oxo, and (C1-C8)alkyl;
- each R15 is independently selected from the group consisting of H, (C1-C8)alkyl, (C2-C8)alkenyl and (C3-C8)cycloalkyl;
- and
- the subscripts k and m are independently 0 to 2.
23 more elements
-5. (canceled)
A compound having a formula selected from the group consisting of:
- wherein
- Ar is a member selected from the group consisting of phenyl, naphthyl and pyridyl;
- each of which is optionally substituted with from one to three R8 substituents, wherein each R8 is a member independently selected from the group consisting of halogen, cyano, nitro, (C1-C8)alkyl, (C1-C8)alkoxy, (C1-C8)haloalkyl, (C1-C8)haloalkoxy, (C2-C8) alkenyl, (C2-C-8) alkynyl, hydroxyl and NR12R13.
- B is aryl or heteroaryl;
- each of which is optionally substituted with from one to two R9 substituents, wherein each R9 is a member independently selected from the group consisting of halogen, nitro, (C1-C8)alkyl, (C1-C8)alkoxy and NR12R13;
- L is selected from the group consisting of O, S(O)k, CRaRb and C(O);
- each Ra or Rb is independently selected from the group consisting of hydrogen, cyano, nitro, and (C1-C8) alkyl;
- R1 is selected from the group consisting of hydrogen, (C1-C8)alkyl, (C2-C8)heteroalkyl and aryl(C1-C8)alkyl;
- R2 is selected from the group consisting of hydrogen, halogen, cyano, nitro, NR12R13 and S(O)mR7;
- each R3, R4, R5, or R6 is a member independently selected from the group consisting of hydrogen, hydroxy, halogen, cyano, nitro, NR12R13, (C1-C8)alkyl, halo(C1-C8)alkyl, hydroxy(C1-C8)alkyl, (C3-C8)cycloalkyl, (C1-C8)alkoxy, (C1-C8)thioalkoxy, (C2-C8)heteroalkyl, aryl, heteroaryl, —C(O)R11, —CO2R11, —C(O)NR12R13, —C(O)CH2CN, —X1Q1, X2OR11 and X2NR12R13;
- each X1 is independently selected from the group consisting of (C1-C2)alkylene and C(O);
- and
- each Q1 is independently selected from the group consisting of pyrrolidinyl, piperidinyl, and morpholinyl;
- R7 is selected from the group consisting of (C1-C8)alkyl, (C3-C8)cycloalkyl, (C1-C8)haloalkyl, aryl, NR12R13, (C3-C8)heterocycloalkyl, X2—C(O)OR15, X2—C(O)N(R15)2, and —X2—NR12R13;
- each X2 is (C1-C8)alkylene;
- each R11 is independently selected from the group consisting of hydrogen, (C1-C8)alkyl, (C2-C8)alkenyl, (C3-C8)cycloalkyl, (C2-C8)heteroalkyl, aryl, heteroaryl, heteroaryl(C1-C8)alkyl, (C3-C8) heterocycloalkyl and aryl(C1-C8)alkyl;
- R12 and R13 are independently selected from the group consisting of hydrogen, (C1-C8)alkyl, (C2-C8) alkenyl, (C3-C8)cycloalkyl, (C2-C8)heteroalkyl, (C1-C8)alkoxy, aryl and aryl(C1-C8)alkyl;
- optionally, R12 and R13 are combined with the nitrogen atom to which each is attached to form a 3-, 4-, 5-, 6- or 7-membered ring which can be saturated or unsaturated and contain 0 to 2 additional heteroatoms selected from N, O and S;
- wherein said ring is optionally substituted with from one to four substituents selected from the group consisting of hydroxy, oxo, and (C1-C8)alkyl;
- each R15 is selected from the group consisting of H, (C1-C8)alkyl, (C2-C8)alkenyl and (C3-C8)cycloalkyl;
- and
- the subscripts k and m are independently 0 to 2.
19 more elements
A compound having the formula (VIII):
- or a pharmaceutically acceptable salt thereof, wherein
- Ar is a member selected from the group consisting of phenyl, naphthyl and pyridyl;
- each of which is optionally substituted with from one to three R8 substituents, wherein each R8 is a member independently selected from the group consisting of halogen, cyano, nitro, (C1-C8)alkyl, (C1-C8)alkoxy, (C1-C8)haloalkyl, (C1-C8)haloalkoxy, (C2-C8) alkenyl, (C2-C8) alkynyl, hydroxyl and NR12R13;
- L is selected from the group consisting of O, S(O)k, CRaRb and C(O);
- each Ra or Rb is independently selected from the group consisting of hydrogen, cyano, nitro, and (C1-C8) alkyl;
- W is independently C(R3) or N;
- X is independently C(R4) or N;
- Y is independently C(R5) or N;
- Z is independently C(R6) or N, wherein at least one of W, X, Y and Z is N and at least one W, X, Y and Z is other than N;
- each R3, R4, R5, or R6 is a member independently selected from the group consisting of hydrogen, hydroxy, halogen, cyano, nitro, NR12R13, (C1-C8)alkyl, halo(C1-C8)alkyl, hydroxy(C1-C8)alkyl, (C3-C8)cycloalkyl, (C1-C8)alkoxy, (C1-C8)thioalkoxy, (C2-C8)heteroalkyl, heteroaryl, —C(O)R11, —CO2R11, —C(O)NR12R13, —C(O)CH2CN, —X1Q1, X2OR11 and X2NR12R13;
- each X1 is independently selected from the group consisting of (C1-C2)alkylene and C(O);
- each Q1 is independently selected from the group consisting of pyrrolidinyl, piperidinyl, and morpholinyl;
- R7 is selected from the group consisting of (C1-C8)alkyl, (C3-C8)cycloalkyl, (C1-C8)haloalkyl, aryl, NR12R13, (C3-C8)heterocycloalkyl, X2—C(O)OR15, X2—C(O)N(R15)2, and —X2—NR12R13;
- each X2 is (C1-C8)alkylene;
- each R9 is a member independently selected from the group consisting of halogen, nitro, (C1-C8)alkyl, (C1-C8)alkoxy and NR12R13;
- each R11 is independently selected from the group consisting of hydrogen, (C1-C8)alkyl, (C2-C8)alkenyl, (C3-C8)cycloalkyl, (C2-C8)heteroalkyl, aryl, heteroaryl, heteroaryl(C1-C8)alkyl, (C3-C8) heterocycloalkyl and aryl(C1-C8)alkyl;
- R12 and R13 are independently selected from the group consisting of hydrogen, (C1-C8)alkyl, (C2-C8) alkenyl, (C3-C8)cycloalkyl, (C2-C8)heteroalkyl, (C1-C8)alkoxy, aryl and aryl(C1-C8)alkyl;
- optionally, R12 and R13 are combined with the nitrogen atom to which each is attached to form a 3-, 4-, 5-, 6- or 7-membered ring which can be saturated or unsaturated and contain 0 to 2 additional heteroatoms selected from N, O and S;
- wherein said ring is optionally substituted with from one to four substituents selected from the group consisting of hydroxy, oxo, and (C1-C8)alkyl;
- each R15 is selected from the group consisting of H, (C1-C8)alkyl, (C2-C8)alkenyl and (C3-C8)cycloalkyl;
- and
- the subscripts k, l, m, and q are independently 0 to 2.
19 more elements
-56. (canceled)
A compound having the formula (X):
- R5 is H or (C1-C8)alkyl;
- R6 is H or (C1-C8)alkyl;
- L is selected from the group consisting of O, S(O)k, CRaRb and C(O);
- each Ra or Rb is independently selected from the group consisting of hydrogen, cyano, nitro, and (C1-C8) alkyl;
- R7 is selected from the group consisting of (C1-C8)alkyl, NR12R13, and (C3-C8)heterocycloalkyl;
- each R8 is a member independently selected from the group consisting of halo, (C1-C8)alkyl, and halo(C1-C8)alkyl;
- each R9 is a member independently selected from the group consisting of halogen, nitro, (C1-C8)alkyl, (C1-C8)alkoxy and NR12R13;
- each R12 and R13 are independently selected from the group consisting of hydrogen, (C1-C8)alkyl, (C2-C8) alkenyl, (C3-C8)cycloalkyl, (C2-C8)heteroalkyl, (C1-C8)alkoxy, aryl and aryl(C1-C8)alkyl;
- optionally, R12 and R13 are combined with the nitrogen atom to which each is attached to form a 3-, 4-, 5-, 6- or 7-membered ring which can be saturated or unsaturated and contain 0 to 2 additional heteroatoms selected from N, O and S;
- wherein said ring is optionally substituted with from one to four substituents selected from the group consisting of hydroxy, oxo, and (C1-C8)alkyl;
- the subscript q is an integer of from 0 to 2;
- and
- the subscript p is an integer of from 0 to 3.
10 more elements
-64. (canceled)
A compound having the formula (XII):
- wherein
- L is selected from the group consisting of O, S(O)k, CRaRb and C(O);
- each Ra or Rb is independently selected from the group consisting of hydrogen, cyano, nitro, and (C1-C8) alkyl;
- R7 is selected from the group consisting of (C1-C8)alkyl, NR12R13, and (C3-C8)heterocycloalkyl;
- each R8 is a member independently selected from the group consisting of halo, (C1-C8)alkyl, and halo(C1-C8)alkyl;
- each R9 is a member independently selected from the group consisting of halogen, nitro, (C1-C8)alkyl, (C1-C8)alkoxy and NR12R13;
- each R12 and R13 are independently selected from the group consisting of hydrogen, (C1-C8)alkyl, (C2-C8) alkenyl, (C3-C8)cycloalkyl, (C2-C8)heteroalkyl, (C1-C8)alkoxy, aryl and aryl(C1-C8)alkyl;
- optionally, R12 and R13 are combined with the nitrogen atom to which each is attached to form a 3-, 4-, 5-, 6- or 7-membered ring which can be saturated or unsaturated and contain 0 to 2 additional heteroatoms selected from N, O and S;
- wherein said ring is optionally substituted with from one to four substituents selected from the group consisting of hydroxy, oxo, and (C1-C8)alkyl;
- the subscript q is an integer of from 0 to 2;
- and
- the subscript p is an integer of from 0 to 3.
9 more elements
-72. (canceled)
A compound having the formula:
- (XIII)
- L is selected from the group consisting of O, S(O)k, CRaRb and C(O);
- each Ra or Rb is independently selected from the group consisting of hydrogen, cyano, nitro, and (C1-C8) alkyl;
- R4 is selected from the group consisting of H, (C1-C8) alkyl, halo(C1-C8)alkyl;
- (C1-C8)alkoxy, —CO2R11, —C(O)NR12R13, hydroxy(C1-C8)alkyl and C(O)R11;
- R7 is selected from the group consisting of (C1-C8)alkyl, NR12R13, and (C3-C8)heterocycloalkyl;
- R8 is halogen;
- each R9 is a member independently selected from the group consisting of halogen, nitro, (C1-C8)alkyl, (C1-C8)alkoxy and NR12R13;
- each R11 is independently selected from the group consisting of hydrogen, (C1-C8)alkyl, (C2-C8)alkenyl, (C3-C8)cycloalkyl, (C2-C8)heteroalkyl, aryl, heteroaryl, heteroaryl(C1-C8)alkyl, (C3-C8) heterocycloalkyl and aryl(C1-C8)alkyl;
- each R12 and R13 are independently selected from the group consisting of hydrogen, (C1-C8)alkyl, (C2-C8) alkenyl, (C3-C8)cycloalkyl, (C2-C8)heteroalkyl, (C1-C8)alkoxy, aryl and aryl(C1-C8)alkyl;
- optionally, R12 and R13 are combined with the nitrogen atom to which each is attached to form a 3-, 4-, 5-, 6- or 7-membered ring which can be saturated or unsaturated and contain 0 to 2 additional heteroatoms selected from N, O and S;
- wherein said ring is optionally substituted with from one to four substituents selected from the group consisting of hydroxy, oxo, and (C1-C8)alkyl;
- the subscript q is an integer of from 0 to 2;
- and
- the subscript p is an integer of from 0 to 3.
12 more elements
-80. (canceled)
A compound having the formula (XIV):
- wherein
- Ar is selected from the group consisting of phenyl, naphthyl and pyridyl optionally substituted with from one to four R8 substituents, wherein each R8 is independently selected from the group consisting of halogen, cyano, (C1-C8)alkyl, (C1-C8)haloalkyl, (C1-C8)alkoxy, (C1-C8)haloalkoxy, (C2-C8)alkenyl and (C2-C8)alkynyl;
- B is aryl or heteroaryl;
- optionally substituted with from one to two R9 substituents selected from the group consisting of halogen, nitro, (C1-C8)alkyl, (C1-C8)alkoxy and NR12R13.
- L is selected from the group consisting of O, S(O)k, CRaRb and C(O);
- each Ra or Rb is independently selected from the group consisting of hydrogen, cyano, nitro, and (C1-C8) alkyl;
- R1 is selected from the group consisting of hydrogen, (C1-C8)alkyl, (C2-C8)heteroalkyl and aryl(C1-C8)alkyl;
- each R3, R4, R5, or R6 is a member independently selected from the group consisting of hydrogen, hydroxy, halogen, cyano, nitro, NR12R13, (C1-C8)alkyl, halo(C1-C8)alkyl, hydroxy(C1-C8)alkyl, (C3-C8)cycloalkyl, (C1-C8)alkoxy, (C1-C8)thioalkoxy, (C2-C8)heteroalkyl, aryl, heteroaryl, CN, —C(O)R11, —CO2R11, —C(O)NR12R13, —C(O)CH2CN, —X1Q1, X2OR11 and X2NR12R13;
- optionally, adjacent R3, R4, R5, or R6 groups can be combined to form an additional 5- or 6-membered fused ring which can be saturated or unsaturated;
- wherein at least one of R3, R4, R5, or R6 is not hydrogen;
- R7 is selected from the group consisting of (C1-C8)alkyl, (C3-C8)cycloalkyl, (C1-C8)haloalkyl, aryl, NR12R13, (C3-C8)heterocycloalkyl, X2—C(O)OR15, X2—C(O)N(R15)2, and —X2—NR12R13;
- each X2 is (C1-C8)alkylene;
- each R11 is independently selected from the group consisting of hydrogen, (C1-C8)alkyl, (C2-C8)alkenyl, (C3-C8)cycloalkyl, (C2-C8)heteroalkyl, aryl, heteroaryl, heteroaryl(C1-C8)alkyl, (C3-C8) heterocycloalkyl and aryl(C1-C8)alkyl;
- each R12 and R13 are independently selected from the group consisting of hydrogen, (C1-C8)alkyl, (C2-C8) alkenyl, (C3-C8)cycloalkyl, (C2-C8)heteroalkyl, (C1-C8)alkoxy, aryl and aryl(C1-C8)alkyl;
- optionally, R12 and R13 are combined with the nitrogen atom to which each is attached to form a 3-, 4-, 5-, 6- or 7-membered ring which can be saturated or unsaturated and contain 0 to 2 additional heteroatoms selected from N, O and S;
- wherein said ring is optionally substituted with from one to four substituents selected from the group consisting of hydroxy, oxo, and (C1-C8)alkyl;
- each R15 is independently selected from the group consisting of H, (C1-C8)alkyl, (C2-C8)alkenyl and (C3-C8)cycloalkyl;
- and
- the subscript k is 0 to 2.
16 more elements
-102. (canceled)
A compound having the formula (XV):
- or a pharmaceutically acceptable salt thereof, wherein
- Ar is a member selected from the group consisting of phenyl, naphthyl and pyridyl;
- each of which is optionally substituted with from one to three R8 substituents, wherein each R8 is a member independently selected from the group consisting of halogen, cyano, nitro, (C1-C8)alkyl, (C1-C8)alkoxy, (C1-C8)haloalkyl, (C1-C8)haloalkoxy, (C2-C8) alkenyl, (C2-C8) alkynyl, hydroxyl and NR12R13;
- L is selected from the group consisting of O, S(O)k, CRaRb and C(O);
- each Ra or Rb is independently selected from the group consisting of hydrogen, cyano, nitro, and (C1-C8) alkyl;
- U is selected from the group consisting of N and CH;
- V is selected from the group consisting of N and CH;
- each R4 or R5 is a member independently selected from the group consisting of hydrogen, hydroxy, halogen, cyano, nitro, NR12R13, (C1-C8)alkyl, halo(C1-C8)alkyl, hydroxy(C1-C8)alkyl, (C3-C8)cycloalkyl, (C1-C8)alkoxy, (C1-C8)thioalkoxy, (C2-C8)heteroalkyl, heteroaryl, —C(O)R11, —CO2R11, —C(O)NR12R13, —C(O)CH2CN, —X1Q1, X2OR11 and X2NR12R13;
- optionally, adjacent R groups selected from R3, R4, R5 and R6 can be combined to form an additional 5- or 6-membered fused ring which can be saturated or unsaturated;
- each X1 is independently selected from the group consisting of (C1-C2)alkylene and C(O);
- each Q1 is independently selected from the group consisting of pyrrolidinyl, piperidinyl, and morpholinyl;
- R7 is a member selected from the group consisting of
- X2—C(O)OR15 and X2—C(O)N(R15)2;
- each X2 is (C1-C8)alkylene;
- each R9 is a member independently selected from the group consisting of halogen, nitro, (C1-C8)alkyl, (C1-C8)alkoxy and NR12R13;
- each R11 is independently selected from the group consisting of hydrogen, (C1-C8)alkyl, (C2-C8)alkenyl, (C3-C8)cycloalkyl, (C2-C8)heteroalkyl, aryl, heteroaryl, heteroaryl(C1-C8)alkyl, (C3-C8) heterocycloalkyl and aryl(C1-C8)alkyl;
- each R12 and R13 are independently selected from the group consisting of hydrogen, (C1-C8)alkyl, (C2-C8) alkenyl, (C3-C8)cycloalkyl, (C2-C8)heteroalkyl, (C1-C8)alkoxy, aryl and aryl(C1-C8)alkyl;
- optionally, R12 and R13 are combined with the nitrogen atom to which each is attached to form a 3-, 4-, 5-, 6- or 7-membered ring which can be saturated or unsaturated and contain 0 to 2 additional heteroatoms selected from N, O and S;
- wherein said ring is optionally substituted with from one to four substituents selected from the group consisting of hydroxy, oxo, and (C1-C8)alkyl;
- each R15 is selected from the group consisting of H, (C1-C8)alkyl, (C2-C8)alkenyl and (C3-C8)cycloalkyl;
- R16 is H or (C1-C8)alkyl;
- each R23 is a member independently selected from the group consisting of H and (C1-C8)alkyl;
- Q is N;
- T is CHR16, NR16, O, or S(O)l;
- the subscript l is an integer of from 0 to 2;
- and
- the subscripts k, l, m, and q are independently 0 to 2.
24 more elements
-126. (canceled)
A compound having the formula (XVI):
- wherein
- L is selected from the group consisting of O, S(O)k, CRaRb and C(O);
- each Ra or Rb is independently selected from the group consisting of hydrogen, cyano, nitro, and (C1-C8) alkyl;
- each R3, R4, R5 and R6 is independently selected from the group consisting of H, (C1-C8) alkyl, halo(C1-C8)alkyl;
- (C1-C8)alkoxy;
- CN, —CO2R11, —C(O)NR12R13, hydroxy(C1-C8)alkyl;
- COEt, and C(O)R11;
- L is selected from the group consisting of O, S(O)k, CRaRb and C(O);
- each Ra or Rb is independently selected from the group consisting of hydrogen, cyano, nitro, and (C1-C8) alkyl;
- R7 is a member selected from the group consisting of:
- X2—C(O)OR15 and X2—C(O)N(R15)2;
- each X2 is (C1-C8)alkylene;
- each R9 is a member independently selected from the group consisting of halogen, nitro, (C1-C8)alkyl, (C1-C8)alkoxy and NR12R13
- each R11 is independently selected from the group consisting of hydrogen, (C1-C8)alkyl, (C2-C8)alkenyl, (C3-C8)cycloalkyl, (C2-C8)heteroalkyl, aryl, heteroaryl, heteroaryl(C1-C8)alkyl, (C3-C8) heterocycloalkyl and aryl(C1-C8)alkyl;
- each R12 and R13 are independently selected from the group consisting of hydrogen, (C1-C8)alkyl, (C2-C8) alkenyl, (C3-C8)cycloalkyl, (C2-C8)heteroalkyl, (C1-C8)alkoxy, aryl and aryl(C1-C8)alkyl;
- optionally, R12 and R13 are combined with the nitrogen atom to which each is attached to form a 3-, 4-, 5-, 6- or 7-membered ring which can be saturated or unsaturated and contain 0 to 2 additional heteroatoms selected from N, O and S;
- wherein said ring is optionally substituted with from one to four substituents selected from the group consisting of hydroxy, oxo, and (C1-C8)alkyl;
- each R15 is selected from the group consisting of H, (C1-C8)alkyl, (C2-C8)alkenyl and (C3-C8)cycloalkyl;
- R16 is H or (C1-C8)alkyl;
- each R23 is a member independently selected from the group consisting of H and (C1-C8)alkyl;
- Q is N;
- T is CHR16, NR16, O, or S(O)l;
- the subscript l is an integer of from 0 to 2;
- and
- the subscripts k, l, m, and q are independently 0 to 2.
22 more elements
-132. (canceled)
(canceled)
-168. (canceled)
Dependencies are inferred from the claim text.