| 主权项 |
1. A method of treatment of an inflammatory or autoimmune disease comprising administering a therapeutically effective amount of a compound having formula (I): or pharmaceutically acceptable salts, solvates or hydrates thereof, wherein
R1 and R2 are selected from (i), (ii), (iii), (iv) and (v) as follows:
(i) R1 and R2 together form ═O, ═S, ═NR9 or ═CR10R11;(ii) R1 and R2 are both —OR8, or R1 and R2, together with the carbon atom to which they are attached, form dioxacycloalkyl;(iii) R1 is hydrogen or halo; and R2 is halo; and(iv) R1 is alkyl, alkenyl, alkynyl, cycloalkyl or aryl, wherein the alkyl, alkenyl, alkynyl, cycloalkyl and aryl is optionally substituted with one or more substitutents selected from halo, cyano, alkyl, —RxORw, —RxS(O)qRv, —RxNRyRz and —C(O)ORw; and R2 is hydrogen, halo or —OR8; and(v) R1 is halo, deutero, —OR12, —NR13R14, or —S(O)qR15; and R2 is hydrogen, deutero, alkyl, alkenyl, alkynyl, cycloalkyl or aryl, wherein the alkyl, alkenyl, alkynyl, cycloalkyl and aryl, is optionally substituted with one or more substitutents selected from halo, cyano, alkyl, —RxORw, —RxS(O)qRv and —RxNRyRz;R3 is hydrogen, halo, alkyl, cyano, haloalkyl, cycloalkyl, cycloalkylalkyl, hydroxy or alkoxy;R4 and R5 are each independently hydrogen or alkyl;each R6 is independently selected from halo, alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyl, —RxOR18, —RxNR19R20, and —RxS(O)qRv;each R7 is independently halo, alkyl, haloalkyl or —RxORw;R8 is alkyl, alkenyl or alkynyl;R9 is hydrogen, alkyl, haloalkyl, hydroxy, alkoxy or amino;R10 is hydrogen or alkyl;R11 is hydrogen, alkyl, haloalkyl or —C(O)OR8;R12 is selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, —C(O)Rv, —C(O)ORw and —C(O)NRyRz, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, aralkyl, heteroaryl and heteroaralkyl are each optionally substituted with one or more substituents independently selected from halo, oxo, alkyl, hydroxy, alkoxy, amino and alkylthio;R13 and R14 are selected as follows:(i) R13 is hydrogen or alkyl; and R14 is selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, alkoxy, —C(O)Rv, —C(O)ORw, —C(O)NRyRz and —S(O)qRv, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, aralkyl, heteroaryl and heteroaralkyl are each optionally substituted with one or more substituents independently selected from halo, oxo, alkyl, hydroxy, alkoxy, amino and alkylthio; or(ii) R13 and R14, together with the nitrogen atom to which they are attached, form heterocyclyl or heteroaryl wherein the heterocyclyl or heteroaryl is optionally substituted with one or more substituents independently selected from halo, alkyl, hydroxy, alkoxy, amino and alkylthio and wherein the heterocyclyl is also optionally substituted with oxo;R15 is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, —C(O)NRyRz or —NRyRz, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, aralkyl, heteroaryl and heteroaralkyl are each optionally substituted with one or more substituents independently selected from halo, oxo, alkyl, hydroxy, alkoxy, amino and alkylthio;R18 is hydrogen, alkyl, haloalkyl, hydroxyC2-6alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, aralkyl, heteroaryl or heteroarylalkyl; wherein R18 is optionally substituted with 1 to 3 groups Q1, each Q1 independently selected from alkyl, hydroxyl, halo, haloalkyl, alkoxy, aryloxy, alkoxyalkyl, alkoxycarbonyl, alkoxysulfonyl, hydroxycarbonyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, haloaryl and amino;R19 and R20 are selected as follows:
(i) R19 and R20 are each independently hydrogen or alkyl; or(ii) R19 and R20, together with the nitrogen atom to which they are attached, form a heterocyclyl or heteroaryl which is optionally substituted with 1 to 2 groups each independently selected from halo, alkyl, haloalkyl, hydroxyl and alkoxy;each Rx is independently alkylene or a direct bond;Rv is hydrogen, alkyl, alkenyl or alkynyl;Rw is independently hydrogen, alkyl, alkenyl, alkynyl or haloalkyl;Ry and Rz are selected as follows:
(i) Ry and Rz are each independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl or haloalkyl;(ii) Ry and Rz, together with the nitrogen atom to which they are attached, form a heterocyclyl or heteroaryl which is optionally substituted with 1 to 2 groups each independently selected from halo, alkyl, haloalkyl, hydroxyl and alkoxy;n is 0-4;p is 0-5; andeach q is independently 0, 1 or 2, wherein the disease is selected from graft-versus-host disease, kidney disease, multiple sclerosis, thyroiditis, type 1 diabetes, psoriasis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, systemic lupus erythematosis, arthritis, osteoarthritis, rheumatoid arthritis, osteoporosis and asthma. |
