FIELD: chemistry.
SUBSTANCE: present invention relates to 1,3,4-oxadiazole derivatives having histone deacetylase 6 (HDAC6) inhibitory activity, specifically to a compound of formula I or a pharmaceutically acceptable salt thereof, in which L1, L2 and L3 each independently represents -(C0-C1alkyl)-; a, b and c are each independently CR4 and R4 is -H; Z is N, O or is absent, wherein when Z is absent, R2 is also absent, and L2 and L3 are directly connected; R1 is -CF2 or -CX3; R2 is -H, -(C1-C4alkyl) or -C(=O)-RA, wherein when Z is O, R2 is absent; RA is
, 
or 
;
Y is N, when Y is N, each of RY1, RY2 and RY4 independently represents -(C1-C4alkyl), -(C3-C7 cycloalkyl), -(C2-C6heterocycloalkyl), containing an N or O atom in the ring, -C(=O)-(C1-C4alkyl), -C(=O)-O(C1-C4alkyl), -C(=O)-NRA3RA4, -C(=O)-(C3-C7cycloalkyl), -C(=O)-(C2-C6heterocycloalkyl), containing one O atom in the ring, -S(=O)2-(C1-C4alkyl), -C4-C5heteroaryl, containing one or two N atoms in a ring, or
,
where at least one H -(C1-C4alkyl), -(C3-C7cycloalkyl) and -C(=O)-(C1-C4 alkyl) can be substituted with -X or -OH; and W is CH2 or O; m and n each independently represents integer 1 or 2; Ra-Rd each independently represents -H; R3 is -(C3-C7 cycloalkyl), -adamantyl, -C6aryl, -C5heteroaryl containing one N atom in the ring, or C7heteroaryl containing two O atoms in the ring, where at least one -H -C6aryl or -C5heteroaryl containing one N atom in the ring, each can be independently substituted with groups -X, -(C1-C4 alkyl), -O(C1-C4 alkyl), -(C=O)-(C1-C4 alkyl), -CF3, or -S(=O)2-(C1-C4alkyl); RA3 and RA4 each independently represents -(C1-C4alkyl); and X is F, Cl or Br. Invention also relates to a pharmaceutical composition, a method of inhibiting HDAC6 and use for preparing a drug for inhibiting HDAC6 based on said compounds.
EFFECT: obtaining alternative compounds having inhibitory activity to HDAC6, which can be used in medicine for treating HDAC6-mediated diseases.
13 cl, 5 tbl, 158 ex
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