US 2015/0038574 A1 · Opsin-Binding Ligands, Compositions and Methods of Use

Abstract

Compounds and compositions are disclosed that are useful for treating ophthalmic conditions caused by or related to production of toxic visual cycle products that accumulate in the eye, such as dry adult macular degeneration, as well as conditions caused by or related to the misfolding of mutant opsin proteins and/or the mis-localization of opsin proteins. Compositions of these compounds alone or in combination with other therapeutic agents are also described, along with therapeutic methods of using such compounds and/or compositions. Methods of synthesizing such agents are also disclosed.

Claims22

Dependent claims

A compound having the structure of Formula I,

wherein A is:
R1 and R2 are independently:
1) hydrogen,
2) —CH3, or
3) —CH2CH3;
R3 is:
1) hydrogen,
2) —CH3,
3) —CH2CH3, or
4) deuteron;
R4 is:
1) hydrogen,
2) lower alkyl,
3) lower haloalkyl, or
4) deuteron;
Ra and Rb are each independently:
1) hydrogen, or
2) —CH3;
T is:
1) —CH2—,
2) —CH2CH2—, or
3) absent;
Ri and Rj are each independently:
1) hydrogen,
2) hydroxyl, or
3) lower alkyl;
Ri and Rj taken together are oxo (═O);
B is:
1) oxygen,
2) S(O)n
3) NR5, or
4) CRqRs;
wherein n is 0, 1 or 2;
Rq and Rs are each independently:
1) hydrogen,
2) hydroxyl, or
3) lower alkyl;
wherein Rg and Rs can be combined as oxo (═O);
R5 is:
1) hydrogen, or
2) lower alkyl;
Re, Rf Rg, Rh and Rk are each independently:
1) hydrogen;
2) lower alkyl;
3) lower haloalkyl
4) halogen;
5) nitro;
6) hydroxy
7) alkoxy;
8) nitrile;
9) carboxamido;
10) arylcarbonyl;
11) carbamoyl;
12) amidyl;
13) amino;
14) alkylcarbonyl;
or
15) urea;
Re and Rf taken together are:
1) —OCH2O—, or
2) —OCF2O—;
and provided that if R1 and/or R2 are hydrogen then each of Ra and Rb must be selected from methyl or ethyl
including all pharmaceutically acceptable salts, solvates and hydrates thereof,
and provided that said compound does not include a member of the Excluded Compound Group.

61 more elements

A composition, comprising a therapeutically effective amount of a compound of Formula I in a pharmaceutically acceptable carrier:

wherein A is:
R1 and R2 are independently:
1) hydrogen,
2) —CH3, or
3) —CH2CH3;
R3 is:
1) hydrogen,
2) —CH3,
3) —CH2CH3, or
4) deuteron;
R4 is:
1) hydrogen,
2) lower alkyl,
3) lower haloalkyl, or
4) deuteron;
Ra and Rb are each independently:
1) hydrogen, or
2) —CH3;
T is:
1) —CH2—,
2) —CH2CH2—, or
3) absent;
Ri and Rj are each independently:
1) hydrogen,
2) hydroxyl, or
3) lower alkyl;
Ri and Rj when taken together are oxo (═O);
B is:
1) oxygen,
2) S(O)n
3) NR5, or
4) CRqRs;
wherein n is 0, 1 or 2;
Rq and Rs are each independently:
1) hydrogen,
2) hydroxyl, or
3) lower alkyl;
wherein Rq and Rs can be combined as oxo (═O);
R5 is:
1) hydrogen, or
2) lower alkyl;
Re, Rf Rg, Rh and Rk are each independently:
1) hydrogen;
2) lower alkyl;
3) lower haloalkyl
4) halogen;
5) nitro;
6) hydroxy
7) alkoxy;
8) nitrile;
9) carboxamido;
10) arylcarbonyl;
11) carbamoyl;
12) amidyl;
13) amino;
14) alkylcarbonyl;
or
15) urea;
Re and Rf when taken together are:
1) —OCH2O—, or
2) —OCF2O—;
and provided that if R1 and/or R2 are hydrogen then each of Ra and Rb must be selected from methyl or ethyl
including all pharmaceutically acceptable salts, solvates and hydrates thereof,
and provided that said compound does not include a member of the Excluded Compound Group.

61 more elements

A method of treating or preventing an ophthalmic condition in a subject at risk thereof or afflicted therewith, comprising administering to the subject an effective amount of a compound having the structure of Formula I

wherein A is:
R1 and R2 are independently:
1) hydrogen,
2) —CH3, or
3) —CH2CH3;
R3 is:
1) hydrogen,
2) —CH3,
3) —CH2CH3, or
4) deuteron;
R4 is:
1) hydrogen,
2) lower alkyl,
3) lower haloalkyl, or
4) deuteron;
Ra and Rb are each independently:
1) hydrogen, or
2) —CH3;
T is:
1) —CH2—,
2) —CH2CH2—, or
3) absent;
Ri and Rj are each independently:
1) hydrogen,
2) hydroxyl, or
3) lower alkyl;
and Ri and Rj taken together are oxo (═O);
B is:
1) oxygen,
2) S(O)n
3) NR5, or
4) C RqRs;
wherein n is 0, 1 or 2;
Rq and Rs are each independently:
1) hydrogen,
2) hydroxyl, or
3) lower alkyl;
wherein Rq and Rs can be combined as oxo (═O);
R5 is:
1) hydrogen, or
2) lower alkyl;
Re, Rf Rg, Rh and Rk are each independently:
1) hydrogen;
2) lower alkyl;
3) lower haloalkyl
4) halogen;
5) nitro;
6) hydroxy
7) alkoxy;
8) nitrile;
9) carboxamido;
10) arylcarbonyl;
11) carbamoyl;
12) amidyl;
13) amino;
14) alkylcarbonyl;
or
15) urea;
Re and Rf taken together are:
1) —OCH2O—, or
2) —OCF2O—;
and provided that if R1 and/or R2 are hydrogen then each of Ra and Rb must be selected from methyl or ethyl
including all pharmaceutically acceptable salts, solvates and hydrates thereof.

60 more elements

Dependencies are inferred from the claim text.

Opsin-Binding Ligands, Compositions and Methods of Use

Life of this patent

Opsin-Binding Ligands, Compositions and Methods of Use

Life of this patent

Abstract

Claims22