Bivalent ligands for the treatment of neurological disorders

A pharmaceutical composition comprising at least one bivalent ligand of Formula I,

• wherein
• R1 and R2 may be the same or different, and are independently selected from:
• H;
• a saturated or unsaturated, branched or unbranched, substituted or unsubstituted carbon group or chain comprising from 1-20 carbon atoms;
• NO−;
• NO−2;
• CO;
• COR8 wherein R8 is H or a saturated or unsaturated, branched or unbranched, substituted or unsubstituted carbon group or chain comprising from 1-20 carbon atoms;
• SO3−2;
• and SO4−2;
• R3 may be present or absent and may be H;
• H2;
• O;
• alkyl;
• —COOR9 where R9 is C1-12alkyl;
• CR10 where R10 is a cyclic or polycyclic saturated or unsaturated homo- or heterocyclic ring system comprising 1, 2, 3, 4, or more rings with from 3 to 7 atoms per ring in the system;
• R1 and R5 may be present or absent;
• may be the same or different, and are independently selected from H;
• halogen;
• a saturated or unsaturated, branched or unbranched, substituted or unsubstituted carbon group or chain comprising from 1-20 carbon atoms;
• a cyclic or polycyclic saturated or unsaturated homo- or heterocyclic ring system comprising 1, 2, 3, 4, or more rings with from 3 to 7 atoms per ring in the system, which may be fused to one or more atoms of the triazole ring;
• and a heteroatomic group;
• R6 and R7 may be the same or different, and are independently selected from:
• H;
• halogen;
• a saturated or unsaturated, branched or unbranched, substituted or unsubstituted carbon group or chain comprising from 1-20 carbon atoms;
• a cyclic or polycyclic saturated or unsaturated homo- or heterocyclic ring system comprising 1, 2, 3, 4, or more rings with from 3 to 7 atoms per ring in the system, which may be fused to one or more atoms of the hexane ring;
• and a heteroatomic group;
• X=a branched or unbranched, saturated or unsaturated carbon chain comprising from 1-20 carbon atoms, and may include a heteroatomic group;
• as well as salts, protonated and unprotonated and stereoisomeric forms thereof;
• and
• a physiologically compatible carrier.

A method of treating neuroAIDS in a subject in need thereof, comprising

• administering to said subject a therapeutically effective amount of at least one bivalent ligand of Formula I,
• wherein
• R1 and R2 may be the same or different, and are independently selected from:
• H;
• a saturated or unsaturated, branched or unbranched, substituted or unsubstituted carbon group or chain comprising from 1-20 carbon atoms;
• NO−;
• NO−2;
• CO;
• COR8 wherein R8 is H or a saturated or unsaturated, branched or unbranched, substituted or unsubstituted carbon group or chain comprising from 1-20 carbon atoms;
• SO3−2;
• and SO4−2;
• R3 may be present or absent and may be H;
• H2;
• O;
• C1-12alkyl;
• —COOR9 where R9 is C1-12alkyl;
• CR10 where R10 is a cyclic or polycyclic saturated or unsaturated homo- or heterocyclic ring system comprising 1, 2, 3, 4, or more rings with from 3 to 7 atoms per ring in the system;
• R4 and R5 may be present or absent;
• may be the same or different, and are independently selected from H;
• halogen;
• a saturated or unsaturated, branched or unbranched, substituted or unsubstituted carbon group or chain comprising from 1-20 carbon atoms;
• a cyclic or polycyclic saturated or unsaturated homo- or heterocyclic ring system comprising 1, 2, 3, 4, or more rings with from 3 to 7 atoms per ring in the system, which may be fused to one or more atoms of the triazole ring;
• and a heteroatomic group;
• R6 and R7 may be the same or different, and are independently selected from:
• H;
• halogen;
• a saturated or unsaturated, branched or unbranched, substituted or unsubstituted carbon group or chain comprising from 1-20 carbon atoms;
• a cyclic or polycyclic saturated or unsaturated homo- or heterocyclic ring system comprising 1, 2, 3, 4, or more rings with from 3 to 7 atoms per ring in the system, which may be fused to one or more atoms of the hexane ring;
• and a heteroatomic group;
• and
• X a branched or unbranched, saturated or unsaturated carbon chain comprising from 1-20 carbon atoms, and may include a heteroatomic group;
• as well as salts, protonated and unprotonated and stereoisomeric forms thereof.

A method of blocking entry of a human immunodeficiency virus (HIV) into an astrocyte, comprising

• exposing said astrocyte to at least one bivalent ligand of Formula I,
• wherein
• R1 and R2 may be the same or different, and are independently selected from:
• H;
• a saturated or unsaturated, branched or unbranched, substituted or unsubstituted carbon group or chain comprising from 1-20 carbon atoms;
• NO−;
• NO−2;
• CO;
• COR8 wherein R8 is H or a saturated or unsaturated, branched or unbranched, substituted or unsubstituted carbon group or chain comprising from 1-20 carbon atoms;
• SO3−2;
• and SO4−2;
• R3 may be present or absent and may be H;
• H2;
• O;
• C1-12alkyl;
• —COOR9 where R9 is C1-12alkyl;
• CR10 where R10 is a cyclic or polycyclic saturated or unsaturated homo- or heterocyclic ring system comprising 1, 2, 3, 4, or more rings with from 3 to 7 atoms per ring in the system;
• R4 and R5 may be present or absent;
• may be the same or different, and are independently selected from H;
• halogen;
• a saturated or unsaturated, branched or unbranched, substituted or unsubstituted carbon group or chain comprising from 1-20 carbon atoms;
• a cyclic or polycyclic saturated or unsaturated homo- or heterocyclic ring system comprising 1, 2, 3, 4, or more rings with from 3 to 7 atoms per ring in the system, which may be fused to one or more atoms of the triazole ring;
• and a heteroatomic group;
• R6 and R7 may be the same or different, and are independently selected from:
• H;
• halogen;
• a saturated or unsaturated, branched or unbranched, substituted or unsubstituted carbon group or chain comprising from 1-20 carbon atoms;
• a cyclic or polycyclic saturated or unsaturated homo- or heterocyclic ring system comprising 1, 2, 3, 4, or more rings with from 3 to 7 atoms per ring in the system, which may be fused to one or more atoms of the hexane ring;
• and a heteroatomic group;
• and
• X=a branched or unbranched, saturated or unsaturated carbon chain comprising from 1-20 carbon atoms, and may include a heteroatomic group;
• as well as salts, protonated and unprotonated and stereoisomeric forms thereof.