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US 9,751,888 B2Granted
Heterocyclic compounds and uses thereof
AssigneeInfinity Pharmaceuticals, Inc.
InventorsAlfredo C. Castro, Catherine A. Evans, Somarajannair Janardanannair, Andre Lescarbeau, Tao Liu, Martin R. Tremblay
Life of this patent
Estimating the term…
Abstract
Compounds and pharmaceutical compositions that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including PI3 kinase activity, are described herein.
Claims19
A compound of Formula (I′):
- or an enantiomer, a mixture of enantiomers, or a mixture of two or more diastereomers thereof, or a pharmaceutically acceptable form thereof, wherein
- B is (C1-C4)alkylene-R18;
- R3 is alkyl, cycloalkyl, heterocyclyl, fluoroalkyl, heteroalkyl, alkoxy, amido, amino, acyl, acyloxy, sulfinyl, sulfonyl, sulfoxide, sulfone, sulfonamido, halo, cyano, aryl, heteroaryl, hydroxyl, or nitro;
- each R5 is independently hydrogen, alkyl or halogen;
- R8 is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heteroalkyl, alkoxy, amido, amino, acyl, acyloxy, sulfonamido, halo, cyano, hydroxyl or nitro;
- R9 is hydrogen, alkyl, cycloalkyl, heterocyclyl, or heteroalkyl;
- Wd is heterocyclyl, aryl, cycloalkyl, or heteroaryl, each of which is substituted with one or more R10, R11, R12, or R13;
- R10, R11, R12, and R13 are each independently hydrogen, alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkoxy, heterocyclyloxy, amido, amino, acyl, acyloxy, alkoxycarbonyl, sulfonamido, halo, cyano, hydroxyl, nitro, phosphate, urea, carbonate, or NR′R″ wherein R′ and R″ together with the nitrogen to which they are attached form a cyclic moiety;
- R18 is aryl, heteroaryl, alkynyl, —OR19, —NHS(O)2R20,—NR20C(O)OR21, —NR20C(O)R21, —NR20C(O)NR21R22, —NR20R21, —S(O)2R20, or —S(O)2NR20R21;
- R19 is alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl;
- R20 is hydrogen, amino, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl;
- R21 is hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl;
- and
- R22 is hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl;
- or when R21 and R22 are attached to one nitrogen, the R21 and R22 together with the nitrogen to which they are attached form a 3- to 7-membered heterocyclyl ring;
- wherein aryl contains 6 to 14 ring carbon atoms;
- wherein heteroaryl contains 5 to 18 ring atoms and contains 1 to 6 ring heteroatoms independently selected from nitrogen, oxygen, phosphorous, and sulfur;
- wherein heterocyclyl contains 3 to 18 ring atoms and contains at least one ring heteroatom selected from nitrogen, oxygen, phosphorous, and sulfur;
- and
- wherein the compound is not one of the following compounds:
17 more elements
A compound of Formula (I):
- or an enantiomer, a mixture of enantiomers, or a mixture of two or more diastereomers thereof, or a pharmaceutically acceptable form thereof, wherein
- B is hydrogen, alkyl, amino, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is substituted with 0, 1, 2, 3, or 4 occurrence(s) of R2;
- each R2 is independently alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkoxy, amido, amino, acyl, acyloxy, alkoxycarbonyl, sulfonamido, halo, cyano, hydroxyl, nitro, phosphate, urea, or carbonate;
- R3 is (i) —(CH2)n—C(═R23)—R24, wherein R23 is O or N—R25, wherein R25 is OH;
- and R24 is (C1-C3)alkyl;
- or (ii) —(CH2)n—R26 or —O—(CH2)n—R26, wherein R26 is
- n is 0, 1, 2, 3, or 4;
- R8 is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heteroalkyl, alkoxy, amido, amino, acyl, acyloxy, sulfonamido, halo, cyano, hydroxyl or nitro;
- R9 is hydrogen, alkyl, cycloalkyl, heterocyclyl, or heteroalkyl;
- Wd is heterocyclyl, aryl, cycloalkyl, or heteroaryl, each of which is substituted with one or more R10, R11, R12, or R13;
- and
- R10, R11, R12, and R13 are each independently hydrogen, alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkoxy, heterocyclyloxy, amido, amino, acyl, acyloxy, alkoxycarbonyl, sulfonamido, halo, cyano, hydroxyl, nitro, phosphate, urea, carbonate, or NR′R″ wherein R′ and R″ together with the nitrogen to which they are attached form a cyclic moiety;
- wherein aryl contains 6 to 14 ring carbon atoms;
- wherein heteroaryl contains 5 to 18 ring atoms and contains 1 to 6 ring heteroatoms independently selected from nitrogen, oxygen, phosphorous, and sulfur;
- wherein heterocyclyl contains 3 to 18 ring atoms and contains at least one ring heteroatom selected from nitrogen, oxygen, phosphorous, and sulfur;
- and
- wherein the compound is not one of the following compounds:
14 more elements
A compound of Formula (I):
- or an enantiomer, a mixture of enantiomers, or a mixture of two or more diastereomers thereof, or a pharmaceutically acceptable form thereof, wherein
- B is hydrogen, alkyl, amino, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is substituted with 0, 1, 2, 3, or 4 occurrence(s) of R2;
- each R2 is independently alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkoxy, amido, amino, acyl, acyloxy, alkoxycarbonyl, sulfonamido, halo, cyano, hydroxyl, nitro, phosphate, urea, or carbonate;
- R3 is alkyl, cycloalkyl, heterocyclyl, fluoroalkyl, heteroalkyl, alkoxy, amido, amino, acyl, acyloxy, sulfinyl, sulfonyl, sulfoxide, sulfone, sulfonamido, alkylsulfonyl, halo, cyano, aryl, heteroaryl, hydroxyl, or nitro;
- R8 is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heteroalkyl, alkoxy, amido, amino, acyl, acyloxy, sulfonamido, halo, cyano, hydroxyl or nitro;
- R9 is hydrogen, alkyl, cycloalkyl, heterocyclyl, or heteroalkyl;
- Wd is
- wherein aryl contains 6 to 14 ring carbon atoms;
- wherein heteroaryl contains 5 to 18 ring atoms and contains 1 to 6 ring heteroatoms independently selected from nitrogen, oxygen, phosphorous, and sulfur;
- wherein heterocyclyl contains 3 to 18 ring atoms and contains at least one ring heteroatom selected from nitrogen, oxygen, phosphorous, and sulfur;
- and
- wherein when Wd is
- then B is not a group selected from an alkyl, a unsubstituted cyclopropyl, a unsubstituted cyclohexyl, a unsubstituted phenyl, and a phenyl substituted with one or two fluoro.
10 more elements
A compound of Formula (II-A):
- or an enantiomer, a mixture of enantiomers, or a mixture of two or more diastereomers thereof, or a pharmaceutically acceptable form thereof, wherein
- B is alkyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is substituted with 0, 1, 2, 3, or 4 occurrence(s) of R2, provided that when B is heteroalkyl, heterocyclyl, or heteroaryl, none of the heteroatoms contained therein can be the point of attachment to the quinazolione ring;
- each R2 is independently alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkoxy, amido, amino, acyl, acyloxy, alkoxycarbonyl, sulfonamido, halo, cyano, hydroxyl, nitro, phosphate, urea, or carbonate;
- R3 is hydrogen, halogen, alkyl, alkoxyl, cycloalkyl, heterocyclyl, aryl, 5-membered heteroaryl, CN, or amino;
- each R5 is independently hydrogen, alkyl or halogen, provided that when R3 is hydrogen, at least one of R5 is alkyl or halogen;
- R9 is alkyl, cycloalkyl, heterocyclyl, or heteroalkyl;
- Wd is heterocyclyl or heteroaryl, each of which is substituted with one or more R10, R11, R12, or R13, provided that when B is alkyl, Wd cannot be thiophene;
- and
- R10, R11, R12, and R13 are each independently hydrogen, alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkoxy, heterocyclyloxy, amido, amino, acyl, acyloxy, alkoxycarbonyl, sulfonamido, halo, cyano, hydroxyl, nitro, phosphate, urea, carbonate, or NR′R″ wherein R′ and R″ together with the nitrogen to which they are attached form a cyclic moiety;
- wherein aryl contains 6 to 14 ring carbon atoms;
- wherein heteroaryl contains 5 to 18 ring atoms and contains 1 to 6 ring heteroatoms independently selected from nitrogen, oxygen, phosphorous, and sulfur;
- wherein heterocyclyl contains 3 to 18 ring atoms and contains at least one ring heteroatom selected from nitrogen, oxygen, phosphorous, and sulfur;
- and
- with the proviso that the compound is not:
11 more elements
Dependencies are inferred from the claim text.