| 主权项 |
1. A method for treatment of a disease selected from an inflammatory disease, an inflammatory condition, an autoimmune disease and cancer comprising administering a therapeutically effective amount of a compound having formula I: R1 and R2 are each independently selected from hydrogen, deuterium, halogen, hydroxyl and alkoxy, or R1 and R2 together form ═O; R3 is hydrogen or alkyl; R4 is cycloalkyl, cycloalkenyl, aryl, heterocyclyl or heteroaryl, where R4 is optionally substituted with one or more, in one embodiment, one to three, in another embodiment, one, two or three groups selected from Q1; each Q1 is independently deuterium, halo, cyano, oxo, thioxo, alkyl, haloalkyl, aminoalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, cycloalkenylalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, heterocyclylalkyl, —RuORx, —RuORuN(Ry)(Rz), —RuN(Ry)(Rx), —RuSRx, —RuC(J)Rx, —RuC(J)ORx, —RuC(J)N(Ry)(Rx), —RuS(O)tRw, —RuNRx)C(J)Rx, —RuNRx)C(J)ORx, —RuNRx)S(O)tRw, ═NORd, or —C(═NRy)N(Ry)ORx, where the alkyl, haloalkyl, aminoalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, and heterocyclyl groups are optionally substituted with one or more Q3 groups, in one embodiment, one to three Q3 groups; each Q3 is independently selected from deuterium, halo, hydroxyl, alkyl, haloalkyl and hydroxyalkyl; Y is —(CR5R6)q—; R5 and R6 are each independently hydrogen, deuterium, halo, alkyl, haloalkyl or hydroxyalkyl; Z is O, S or NR7; R7 is hydrogen, deuterium or alkyl; each W is independently CR8 or N; R8 is hydrogen, deuterium, halo, haloalkyl or alkyl; ring A is a aryl, heteroaryl or heterocyclyl optionally substituted with one to four substituents selected from Q2; W1 is N or C; W2 is N, NR9a or CR9b; W3 is N, NR10a or CR10b; W4 is N, NR11a or CR11b; R9a, R9b, R10a, R10b, R11a and R11b are selected as follows:
i) R9a, R10a and R11a are each independently hydrogen, deuterium or alkyl and R9b, R10b and R11b are each independently hydrogen or Q2; orii) R9a and R10b, R9a and R10a, R9b and R10b, R9b and R10a, R10a and R11a, R10b and R11a, R10a and R11b or R10b and R11b together with the atoms to which they are attached form an aryl, heteroaryl or heterocyclyl ring, optionally substituted with one or more, in one embodiment, one to three, in another embodiment, one, two or three groups selected from Q2; and the remainder of R9a or R11a is hydrogen, deuterium or alkyl; and the remainder of R9b or R11b is hydrogen or Q2; oriii) R9a and R10b, R9a and R10a, R9b and R10b, R9b and R10a, R10a and R11a, R10b and R11a, R10a and R11b or R10b and R11b together with the atoms to which they are attached form an aryl, heteroaryl or heterocyclyl ring optionally fused to a phenyl ring optionally substituted with one or more, in one embodiment, one to three, in another embodiment, one, two or three groups selected from Q2; and the remainder of R9a or R11a is hydrogen or alkyl and the remainder of R9b or R11b is hydrogen or Q2;each Q2 is independently halo, deuterium, cyano, oxo, thioxo, alkyl, haloalkyl, haloalkenyl, aminoalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, cycloalkenylalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, heterocyclylalkyl, —RuORx, —RuORuORx, —RuORuN(Ry)(Rz), —RuN(Ry)(Rz), —RuSRx, —RuC(J)Rx, —RuC(J)ORx, —RuC(J)N(Ry)(Rx), —RuC(J)RuN(Ry)(Rz), —RuC(J)N(Ry)ORx, —C(═NRx)Rx′—RuS(O)tRw, —RuNRx)C(J)Rx, —RuNRx)C(J)ORx, —RuNRx)S(O)tRw or —C(═NRy)N(Ry)ORx, where the alkyl, haloalkyl, aminoalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, and heterocyclyl groups are optionally substituted with one or more groups Q4; in one embodiment, one to three Q4 groups, each Q4 is independently selected from halo, deuterium, hydroxyl, alkyl, haloalkyl and hydroxyalkyl; Rd is hydrogen or alkyl; each Ru is independently alkylene, alkenylene or a direct bond; Rw is alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, cycloalkenylalkyl, heterocyclyl, heterocyclylalkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl; each Rx is independently hydrogen, alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, cycloalkenylalkyl, heterocyclyl, heterocyclylalkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl; Ry and Rz are each independently selected from (i) or (ii) below: (i) Ry and Rz are each independently hydrogen, alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, cycloalkenylalkyl, heterocyclyl, heterocyclylalkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl; or (ii) Ry and Rz, together with the nitrogen atom to which they are attached, form a heterocyclyl or heteroaryl, optionally substituted with one or more, in one embodiment, one, two or three Q7 groups; each Q7 is independently selected from halo, deuterium, oxo, thioxo, hydroxy, alkoxy, alkyl, haloalkyl, hydroxyalkyl, aminoalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, cycloalkenylalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl and heterocyclylalkyl; J is O, NRx or S; each t is independently an integer from 0-2; n is 1 or 2; and q is an integer from 0-4, wherein the compounds are selected such that: i) when W is CH; W1 is C; Z is S; R1 is hydrogen, or hydroxyl and R2 is hydrogen, or R1 and R2 together form ═O; then ring A is not pyridine; ii) when W is CH; W1 is N; Z is S; R1 and R2 are hydrogen, then ring A is not pyrrolidine; iii) when W is CH, Z is NH, R1 and R2 together form ═O, q is 0, and R4 is pyridinyl, then ring A is not phenyl, iv) when W is CH, Z is NH, R1 and R2 together form ═O, q is 0, and R4 is phenyl, then ring A is not pyrrolidine, and v) when Z is N, one of R1 and R2 is methyl and the other of R1 and R2 is H, q is 0, and R3 is pyridine, and W1 is N, ring A cannot be piperidine, 1,2,3,4-tetrahydroisoquinoline, or isoindoline. |
