Treatment of lysosomal storage disorders and other proteostatic diseases

A method of treating a proteostatic disease in a subject, comprising administering to a subject in need thereof an effective amount of an β-N-acetylglucosaminidase inhibitor of Formula (1)

• in which
• n represents an integer from 1 to 7, provided that where n>1 the ring may also contain at least one unsaturated C—C bond
• z represents an integer from 1 to (n+2)
• y represents 1 or 2
• R1 represents H;
• C1-15 alkyl, C1-15 alkenyl or C1-15 alkynyl, optionally substituted with one or more R2;
• oxygen or an oxygen containing group such that the compound is an N-oxide;
• C(O)OR3;
• C(O)NR3R4;
• SO2NR3;
• OH, OR3, or formyl
• R2 represents OH;
• OR3;
• ═O;
• NH2;
• N3;
• SH;
• SOxR3;
• halo;
• CN;
• NO2;
• NR3R4;
• (NR3)NR3R4;
• NH(NR3)NR3R4;
• CO2R4;
• OC(O)R3;
• CONR3R4;
• NR4C(O)R3;
• NR4SO2R3;
• P(O)(OR3)2;
• C1-15 alkyl or alkenyl optionally substituted with one or more OH, OR3, ═O, NH2, N3, SH, SOxR3, halo, CN, NO2, NR3R4, (NR3)NR3R4, NH(NR3)NR3R4, CO2R4, OC(O)R3, CONR3R4, NR4C(O)R3, NR4SO2R3, P(O)(OR3)2, aryl or carbocyclyl groups;
• carbocyclyl or aryl, either of which is optionally substituted with one or more OH, OR3, ═O, NH2, N3, SH, SOxR3 halo, CN, NO2, NR3R4, (NR3)NR3R4, NH(NR3)NR3R4, CO2R4, OC(O)R3, CONR3R4, NR4C(O)R3, NR4SO2R3, P(O)(OR3)2, C1-9 alkyl optionally substituted with one or more OH, OR3, ═O, NH2, N3, halo, CN, NO2, NR3R4, CO2R4, CONR3R4, aryl or carbocyclyl groups;
• O-glycosyl;
• C-glycosyl;
• O-sulfate;
• O-phosphate or a group which together with the endocyclic carbon forms a spiro ring, with the provisos that:
• (a) two OH groups may not be attached to the same endocyclic carbon atom;
• (b) where there is only one R2 substituent it contains an oxygen atom directly bonded to an endocyclic carbon atom;
• and (c) where z>1 any two R2 substituents may together form an optionally heterocyclic ring (for example a carbocycle, cyclic ether or acetal)
• R3 represents H;
• C1-6 alkyl, optionally substituted with one or more OH;
• aryl or C1-3 alkyl optionally substituted with aryl;
• SiR43 and
• R4 represents H;
• C1-6 alkyl, optionally substituted with one or more OH
• R3 and R4 may optionally form a 4 to 8 membered ring, containing one or more O, SOx or NR3 groups
• x represents an integer from 0 to 2
• or a pharmaceutically acceptable salt thereof.