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US 9,518,065 B2Granted
IRAK inhibitors and uses thereof
AssigneeNimbus Iris, Inc.
InventorsDonna Romero, Craig E. Masse, Shaughnessy Robinson, Jeremy Robert Greenwood, Geraldine C. Harriman
Life of this patent
Estimating the term…
Abstract
The present invention provides compounds of the general formula I: or a pharmaceutically acceptable salt thereof, wherein each variable is as defined and described herein, as inhibitors of one or more interleukin-1 receptor-associated kinases (“IRAK”).
Claims14
A compound of formula I:
- or a pharmaceutically acceptable salt thereof, wherein:
- Q is N;
- X is N and Y is C—Rx;
- Ring A is a 3-7 membered saturated or partially unsaturated carbocyclic ring;
- R1 is Cy;
- each R1′ is independently —R2, halogen, —CN, —NO2, —OR, —SR, —N(R)2, —S(O)2R, —S(O)2N(R)2, —S(O)R, —C(O)R, —C(O)OR, —C(O)N(R)2, —C(O)N(R)OR, —N(R)C(O)OR, —N(R)C(O)N(R)2, Cy, or —N(R)S(O)2R;
- each Cy is an optionally substituted ring selected from a 3-7 membered saturated or partially unsaturated carbocyclic ring or a 4-10 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
- each R is independently hydrogen, or an optionally substituted group selected from C1-6 aliphatic, phenyl, 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or:
- two R groups on the same nitrogen are taken together with their intervening atoms to form a 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the nitrogen, independently selected from nitrogen, oxygen, or sulfur;
- each R2 is independently an optionally substituted group selected from C1-6 aliphatic, phenyl, 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
- Rx is hydrogen, —R2, —CN, —NO2, halogen, —C(O)N(R)2, —C(O)OR, —C(O)R, —N(R)2, —NH[Ar], —OR, or —S(O)2N(R)2;
- Rz is hydrogen, —N(R)2, or —NH[Ar];
- [Ar] is a 5-membered heteroaromatic ring substituted by m instances of R1′;
- L1 is a covalent bond or a C1-6 bivalent hydrocarbon chain wherein one or two methylene units of the chain are optionally and independently replaced by —N(R)—, —N(R)C(O)—, —C(O)N(R)—, —N(R)S(O)2—, —S(O)2N(R)—, —O—, —C(O)—, —OC(O)—, —C(O)O—, —S—, —S(O)— or —S(O)2—;
- m is 0-4;
- and
- n is 1.
14 more elements
A compound of formula I:
- or a pharmaceutically acceptable salt thereof, wherein:
- Q is N;
- X is N and Y is C—Rx;
- Ring A is a cyclohexyl ring;
- each R1 and R1′ is independently —R2, halogen, —CN, —NO2, —OR, —SR, —N(R)2, —S(O)2R, —S(O)2N(R)2, —S(O)R, —C(O)R, —C(O)OR, —C(O)N(R)2, —C(O)N(R)OR, —N(R)C(O)OR, —N(R)C(O)N(R)2, Cy, or —N(R)S(O)2R;
- or R1 is selected from one of the following formulas:
- or
- two R1 groups are taken together with their intervening atoms to form an optionally substituted 4-7 membered fused, spiro-fused, or bridged bicyclic ring having 0-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
- each Cy is an optionally substituted ring selected from a 3-7 membered saturated or partially unsaturated carbocyclic ring or a 4-10 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
- each R is independently hydrogen, or an optionally substituted group selected from C1-6 aliphatic, phenyl, 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or:
- two R groups on the same nitrogen are taken together with their intervening atoms to form a 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the nitrogen, independently selected from nitrogen, oxygen, or sulfur;
- each R2 is independently an optionally substituted group selected from C1-6 aliphatic, phenyl, 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
- Rx is hydrogen, —R2, —CN, —NO2, halogen, —C(O)N(R)2, —C(O)OR, —C(O)R, —N(R)2, —NH[Ar], —OR, or —S(O)2N(R)2;
- Rz is hydrogen, —N(R)2, or —NH-pyrazolyl, wherein the pyrazolyl ring is substituted with m instances of R1′;
- [Ar] is a phenyl or heteroaromatic ring substituted by m instances of R1′;
- L1 is —N(R)— or —O—;
- m is 0-4;
- and
- n is 0-4.
16 more elements
A compound selected from any one of the following, or a pharmaceutically acceptable salt thereof:
Dependencies are inferred from the claim text.