Pde4 inhibitor compound and medical use thereof
AssigneeSuzhou Longbotai Pharmaceuticals Co., Ltd.
InventorsShuxin Li, Hengying Yang, Sheng Kuang, Sifan She, Kuiwang Wu, Shiwei Li
Life of this patent
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Abstract
A class of PDE4 inhibitor compounds, and an isomer, solvate, deuterated derivative, or pharmaceutically acceptable salt thereof. A drug that comprises the compound, isomer, solvate, deuterated derivative, and pharmaceutically acceptable salt thereof, and a use thereof in preparing a drug for treating diseases related to PDE4 inhibition, such as autoimmune diseases and cancer.
Claims20
A compound of formula (I) and an isomer, solvate, deuterated derivative or pharmaceutically acceptable salt thereof:
- wherein:
- X1 is selected from N or CH;
- one of X2, X3, and X4 is selected from N, and the others are CH;
- X is selected from O, —N(R6), and —CH(R6)—;
- R is selected from hydrogen, C1-C3 alkyl, and C3-C6 cycloalkyl, and may be substituted with halogen;
- R1, R2, and R3 are each independently selected from hydrogen, halogen, hydroxyl, —CN, —NH2, C1-C6 alkyl, C1-6 alkoxy, C1-C6 alkylamino, C2-6 alkenyl, C3-6 cycloalkenyl, 3- to 6-membered heterocycloalkenyl, C3-C6 cycloalkyl, 3- to 6-membered heterocycloalkyl, phenyl, 5-to 6-membered heteroaryl, and —COOR8, which may be substituted with halogen, C1-C6 alkyl, optionally halogenated C1-C6 alkyl, C3-C6 cycloalkyl, or optionally halogenated C3-C6 cycloalkyl;
- R4 and Rare independently selected from C1-C6 alkyl and C3-C6 cycloalkyl, and may be optionally substituted with deuterium, tritium, or halogen;
- R6 is selected from H, halogen, hydroxyl, CN, —NH2, COOH, and R7-L1-, or selected from C1-6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, 3- to 6-membered heterocycloalkyl, phenyl, 5-to 6-membered heteroaryl, —COOR9, —SO2R10, —SO2NHR11, and —NHCONHR12, which may be substituted with halogen, C1-C6 alkyl, optionally halogenated C1-C6 alkyl, C3-C6 cycloalkyl, or optionally halogenated C3-C6 cycloalkyl;
- R7 is selected from C3-C6 cycloalkyl, 3- to 6-membered heterocycloalkyl, 3- to 6-membered heterocycloalkenyl, phenyl, 5- to 6-membered heteroaryl, and —COOR8, and may be substituted with halogen, C1-C6 alkyl, or C3-C6 cycloalkyl;
- L1 is selected from —CH2—, —CH2CH2—, O, S, and NH;
- R8, R9, R10, R11, and R12 are C1-C6 alkyl, halogenated C1-C6 alkyl, or C3-C6 cycloalkyl.
A compound of formula (II) and an isomer, solvate, deuterated derivative or pharmaceutically acceptable salt thereof:
- wherein:
- Y1 is selected from N or CH;
- one of Y2, Y3, and Y4 is selected from N, and the others are CH;
- R13 is selected from C1-C3 alkyl and C1-C6 cycloalkyl, and may be substituted with halogen;
- R14, R15, and R16 are independently selected from hydrogen, halogen, hydroxyl, CN, —NO2, —NH2, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylamino, C1-C6 alkylamido, C3-C6 cycloalkylamido, C2-C6 alkenyl, C3-C6 cycloalkenyl, 3- to 6-membered heterocycloalkenyl, C3-C6 cycloalkyl, 3- to 6-membered heterocyclyl, phenyl, and 5- to 6-membered heteroaryl, which may be optionally substituted with halogen, C3-C6 cycloalkyl, C1-C8 alkoxy, C3-C8 cycloalkoxy, 3- to 12-membered heterocyclyl, C1-C8 alkylamino, di(C1-C8 alkyl) substituted amino, phenyl, or 5- to 6-membered heteroaryl;
- R17 and R18 are independently selected from C1-C6 alkyl and C3-C6 cycloalkyl, and may be optionally substituted with deuterium, tritium, or halogen.
A compound of formula (III) and an isomer, solvate, deuterated derivative or pharmaceutically acceptable salt thereof:
- wherein:
- R19 is selected from C1-C3 alkyl and C3-C6 cycloalkyl, and may be substituted with halogen;
- R20 and R21 are each selected from hydrogen, halogen, C1-C8 alkyl, C1-C8 alkoxy, hydroxyl, cyano, nitro, —NHC(O)R26, —NHSO2R26, or —NR24R25;
- R22 and R23 are independently selected from C1-C6 alkyl, and may be optionally substituted with deuterium, tritium, or halogen;
- R24 and R25 are each selected from hydrogen, C1-C8 alkyl, C6-C12 aryl, C(O)R26, and SO2R26;
- alternatively, R24 and R25 are taken together with the N to which they are attached to form a 4- to 8-membered ring or —CH2CH2ZCH2CH2—;
- Z is selected from O, S, and NR26;
- R26 is hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl, or C1-C8 alkylamino, and may be optionally substituted with halogen, C1-C8 alkoxy, C3-C8 cycloalkoxy, 3- to 12-membered heterocyclyl, C1-C8 alkylamino, or di(C1-C8 alkyl) substituted amino.
Dependencies are inferred from the claim text.