Nuclear transport modulators and uses thereof

A compound of formula I′:

• or a pharmaceutically acceptable salt thereof, wherein:
• each is independently a double or single bond with the proviso that two adjacent double bonds do not exist;
• n=1 or 2;
• m=0, 1
• each of X1′, X2′, X3′ and X4′ is independently selected from N,N(R2′), O, S, and C(R2′), as valency permits, wherein at least one of X1′, X2′, X3′ and X4′ is either N or N(R2′);
• A′ is phenyl, an 8-10 membered bicyclic aryl ring, a 5-6 membered monocyclic heteroaryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein A′ is optionally substituted with one or more R1′ substituents;
• each R1′ is independently selected from the group of halogen (F, Cl, Br, I), —NO2, —CN, —ORa, —SRa, —N(Ra)2, —N3, or -L1-R;
• each R2′ is independently selected from —H,
• halogen (F, Cl, Br, I), —NO2, —CN, —ORa, —SRa, —N(Ra)2, —N3, or -L1-R;
• each WG′ is independently selected from the group consisting of —H, —F, —CF3, —NO2, —CN, —C(O)R3′, —C(O)OR3′, —S(O)R3′, —SO2R3′, —C(O)N(R3′)2 and —C(NOR3′)R4′;
• each R3′ and R4′ is independently -L1-R;
• each R is independently optionally substituted C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, haloalkyl, phenyl, a 3-7 membered saturated or partially unsaturated cycloalkyl ring, an 8-10 membered bicyclic saturated, partially unsaturated or aryl carbocyclic ring, a 4-7-membered saturated or partially unsaturated heterocycloalkyl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• a 5-6 membered monocyclic heteroaryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• or an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• or:
• two R on the same nitrogen are taken together with their intervening atoms to form a 4-7 membered heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulphur L1 is a covalent bond or an optionally substituted bivalent C1-6 hydrocarbon chain, wherein one or more methylene units of L1 is optionally and independently replaced by -Cy-, —O—, —S—, —N(Ra)—, —C(O)—, —C(O)N(Ra)—, —N(Ra)C(O)N(Ra)—, —N(Ra)C(O)—, —N(Ra)C(O)O—, —OC(O)N(Ra)—, —S(O)—, —S(O)2—, —S(O)2N(Ra)—, —N(Ra)S(O)2—, —OC(O)— or —C(O)O—;
• -Cy- is an optionally substituted bivalent ring selected from a 3-7 membered saturated or partially unsaturated cycloalkylene ring, a 4-7-membered saturated or partially unsaturated heterocycloalkylene ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, phenylene, a 5-6 membered monocyclic heteroarylene having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, an 8-10 membered bicyclic arylene, or an 8-10 membered bicyclic heteroarylene having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• and
• each Ra is independently —H, —R or —C(O)R;
• provided that the compound is not one disclosed in Van Neck et al. Bioorgan. Med. Chem. 16 (2008) 9487-9497.