US 10,040,749 B2Granted

Opsin-binding ligands, compositions and methods of use

AssigneeBikam Pharmaceuticals, Inc.

InventorsDavid S. Garvey, Judd Berman, Tan Quach

Life of this patent

Estimating the term…

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.

Claims6

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) deuterium;
R4 is:
1) hydrogen,
2) lower alkyl,
3) lower haloalkyl, or
4) deuterium;
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;
or Ri and Rj taken together are oxo (═O);
B is:
1) oxygen,
2) NR5, or
3) CRqRs;
Rq and Rs are each independently:
1) hydrogen,
2) hydroxyl, or
3) lower alkyl;
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;
or
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 is not one of the following compounds:
CAS NO.
STRUCTURE
NAME
873379- 08-9
2,2,6-trimethyl-N-(p- tolyl)cyclohexane-1- carboxamide
693243- 53-7
2,2,6-trimethyl-N- phenylcyclohexane-1- carboxamide
130741- 00-3
2-(3-isopropyl-2,4,5- trimethoxyphenyl)-1- (2,6,6-trimethylcyclohex- 1-en-1-yl)ethan-1-one
90858- 26-7
4-isopropyl-2-(2-(2,6,6- trimethylcyclohex-1- en-1-yl)ethyl)phenol
90858- 25-6
4-isopropyl-1-methoxy-2- (2-(2,6,6-trimethylcyclohex- 1-en-1-yl)ethyl)benzene
80994- 28-1
1-methoxy-4-(2-(2,6,6- trimethylcyclohex-1- en-1-yl)ethyl)benzene
80994- 24-7
1-methoxy-4-(2-(2,6,6- trimethylcyclohex-1- en-1-yl)ethyl)benzene
64158- 72-1
2-isopropyl-1-methoxy-4- (2-(2,6,6-trimethylcyclohex- 1-en-1-yl)ethyl)benzene
64158- 62-9
2-(3-isopropyl-4- methoxyphenyl)-1-(2,6,6- trimethylcyclohex-1-en-1- yl)ethan-1-one
63512- 95-8
2-isopropyl-3,4-dimethoxy- 1-(2-(2,6,6- trimethylcyclohex- 1-en-1-yl)ethyl)benzene
63512- 94-7
2-(2-isopropyl-3,4- dimethoxyphenyl)-1-(2,6,6- trimethylcyclohex-1-en-1- yl)ethan-1-one
63512- 93-6
2-(2-isopropyl-4- methoxyphenyl)-1-(2,6,6- trimethylcyclohex-1-en-1- yl)ethan-1-ol
59665- 69-9
2-(4-isopropyl-3- methoxyphenyl)-1-(2,6,6- trimethylcyclohex-1-en- 1-yl)ethan-1-one
59665- 68-8
2-(4-isopropyl-3- methoxyphenyl)-1-(2,6,6- trimethylcyclohex-1-en- 1-yl)ethan-1-ol
59665- 64-4
2-phenyl-1-(2,6,6- trimethylcyclohex-1-en- 1-yl)ethan-1-one
59665- 63-3
2-phenyl-1-(2,6,6- trimethylcyclohex-1-en- 1-yl)ethan-1-ol
26112- 36-7
1-methoxy-3-(2-((1S,6S)- 2,2,6- trimethylcyclohexyl)ethyl)- benzene.

96 more elements

A compound selected from the group consisting of:

3-(trifluoromethyl)-N-((2,6,6-trimethylcyclohex-1-enyl)methyl)aniline hydrochloride (Compound 1);
3-methyl-N-((2,6,6-trimethylcyclohex-1-enyl)methyl)aniline (Compound 2);
3-((2,6,6-trimethylcyclohex-1-enyl)methylamino)benzamide (Compound 3);
3-((2,6,6-trimethylcyclohex-1-enyl)methylamino)benzonitrile (Compound 4);
3-chloro-N-((2,6,6-trimethylcyclohex-1-enyl)methyl)aniline (Compound 5);
1-methyl-3-((2, 6,6-trimethylcyclohex-1-enyl)methoxy)benzene (Compound 6);
1-fluoro-3-((2,6, 6-trimethylcyclohex-1-enyl)methoxy)benzene (Compound 7);
1-chloro-3-((2, 6,6-trimethylcyclohex-1-enyl)methoxy)benzene (Compound 8);
1-(trifluoromethyl)-3-((2,6, 6-trimethylcyclohex-1-enyl)methoxy) benzene (Compound 9);
3-fluoro-N-((2,6,6-trimethylcyclohex-1-enyl)methyl)aniline hydrochloride (Compound 10);
N-methyl-3-(trifluoromethyl)-N-((2,6,6-trimethylcyclohex-1-enyl)methyl)aniline hydrochloride (Compound 11);
3-(trifluoromethyl)-N-(((1R,6S)-2,2,6-trimethylcyclohexyl)methyl)aniline hydrochloride (Compound 12);
3-fluoro-N-methyl-N-((2,6,6-trimethylcyclohex-1-enyl)methyl)aniline (Compound 13);
3-((2,6,6-trimethylcyclohex-1-enyl)methoxy)benzonitrile (Compound 14);
4-fluoro-3-methyl-N-((2,6,6-trimethylcyclohex-1-enyl)methyl)aniline hydrochloride (Compound 15);
1-(3-fluorophenyl)-2-(2,6,6-trimethylcyclohex-1-enyl)ethanol (Compound 16);
1-(3-fluorophenyl)-2-(2,6,6-trimethylcyclohex-1-enyl)ethanone (Compound 17);
1-(3-chlorophenyl)-2-(2,6,6-trimethylcyclohex-1-enyl)ethanol (Compound 18);
1-(3-chlorophenyl)-2-(2,6,6-trimethylcyclohex-1-enyl)ethanone (Compound 19);
1-(3-(trifluoromethyl)phenyl)-2-(2,6,6-trimethylcyclohex-1-enyl)ethanol (Compound 20);
2-m-tolyl-1-(2,6,6-trimethylcyclohex-1-enyl)ethanol (Compound 21);
2-(3-(trifluoromethyl)phenyl)-1-(2,6,6-trimethylcyclohex-1-enyl)ethanol (Compound 22);
2-(4-fluoro-3-(trifluoromethyl)phenyl)-1-(2,6,6-trimethylcyclohex-1-enyl)ethanol (Compound 23);
2-fluoro-4((2,6,6-trimethylcyclohex-1-enyl)methoxy) benzonitrile (Compound 24);
1-(3-fluoro-4-(trifluoromethoxy)phenyl)-2-(2,6,6-trimethylcyclohex-1-enyl)ethanol (Compound 25);
1-(3-fluoro-4-(trifluoromethyl)phenyl)-2-(2,6,6-trimethylcyclohex-1-enyl)ethanol (Compound 26);
1-(3,4-dichlorophenyl)-2-(2,6,6-trimethylcyclohex-1-enyl)ethanol (Compound 27);
2-fluoro-1-methyl-4-((2,6,6-trimethylcyclohex-1-enyl)methoxy)benzene (Compound 28);
1,2-difluoro-4-((2,6,6-trimethylcyclohex-1-enyl)methoxy) benzene (Compound 29);
2-(3,4-dimethylphenyl)-1-(2,6,6-trimethylcyclohex-1-enyl)ethanol (Compound 30);
3-methoxy-N-((2,6,6-trimethylcyclohex-1-enyl)methyl)aniline hydrochloride (Compound 31);
N-((6,6-dimethylcyclohex-1-enyl)methyl)-3-fluoroaniline hydrochloride (Compound 32);
N-((6,6-dimethylcyclohex-1-enyl)methyl)-3-fluoro-N-methylaniline hydrochloride (Compound 33);
N-((2,2-dimethylcyclohexyl)methyl)-3-fluoroaniline hydrochloride (Compound 34);
N-((2,2-dimethylcyclohexyl)methyl)-3-fluoro-N-methylaniline hydrochloride (Compound 35);
3-methyl-N-(((1R,6S)-2,2,6-trimethylcyclohexyl)methyl)aniline hydrochloride (Compound 36);
3-chloro-N-(((1R,6S)-2,2,6-trimethylcyclohexyl)methyl)aniline hydrochloride (Compound 37);
3-fluoro-N-(((1R,6S)-2,2,6-trimethylcyclohexyl)methyl)aniline hydrochloride (Compound 38);
3-fluoro-N-methyl-N-(((1R,6S)-2,2,6-trimethylcyclohexyl)methyl)aniline hydrochloride (Compound 39);
3-ethoxy-N-((2,6,6-trimethylcyclohex-1-enyl)methyl)aniline hydrochloride (Compound 40);
3-isopropoxy-N-((2,6,6-trimethylcyclohex-1-enyl)methyl)aniline hydrochloride (Compound 41);
1-ethyl-3-((2,6,6-trimethylcyclohex-1-enyl)methoxy)benzene (Compound 42);
1-methoxy-3-((2,6,6-trimethylcyclohex-1-enyl)methoxy) benzene (Compound 43);
1-ethoxy-3-((2,6,6-trimethylcyclohex-1-enyl)methoxy)benzene (Compound 44);
(R)-2-m-tolyl-1-((1R,6S)-2,2,6-trimethylcyclohexyl)ethanol (Compound 45);
2-m-tolyl-1-((1R,6S)-2,2,6-trimethylcyclohexyl)ethanone (Compound 46);
3-ethyl-N-((2,6,6-trimethylcyclohex-1-enyl)methyl)aniline hydrochloride (Compound 47);
N-((2,6,6-trimethylcyclohex-1-enyl)methyl)benzo[d][1,3]dioxol-5-amine hydrochloride (Compound 48);
2,2-difluoro-N-((2,6,6-trimethylcyclohex-1-enyl)methyl)benzo[d][1,3]dioxol-5-amine hydrochloride (Compound 49);
1-fluoro-3((2,5,5-trimethylcyclopent-1-enyl)methoxy)benzene (Compound 50);
3-fluoro-N-((2,5,5-trimethylcyclopent-1-enyl)methyl)aniline hydrochloride (Compound 51);
5-((2,6,6-trimethylcyclohex-1-enyl)methoxy) benzo[d][1,3]dioxole (Compound 52);
1-fluoro-3-(((1R,6S)-2,2,6-trimethylcyclohexyl)methoxy) benzene (Compound 53);
1-chloro-3-(((1R,6S)-2,2,6-trimethylcyclohexyl)methoxy) benzene (Compound 54);
1,2-difluoro-4-4(1R,6S)-2,2,6-trimethylcyclohexyl)methoxy) benzene (Compound 55);
1-fluoro-3-((3,3,6,6-tetramethylcyclohex-1-enyl)methoxy) benzene (Compound 56);
3-fluoro-N-((3,3,6,6-tetramethylcyclohex-1-enyl)methyl)aniline hydrochloride (Compound 57);
1-((3-fluorophenoxy)methyl)-7,7-dimethylcyclohept-1-ene (Compound 58);
N-((7,7-dimethylcyclohept-1-enyl)methyl)-3-fluoroaniline hydrochloride (Compound 59);
(3-fluorophenyl)((2,6,6-trimethylcyclohex-1-enyl)methyl) sulfane (Compound 60);
N-((7,7-dimethylcyclohept-1-enyl)methyl)-3-fluoro-N-methylaniline hydrochloride (Compound 61);
3-fluoro-N-methyl-N-((3,3,6,6-tetramethylcyclohex-1-enyl)methyl)aniline hydrochloride (Compound 62);
3-fluoro-N-((2,2,5,5-tetramethylcyclohexyl)methyl)aniline hydrochloride (Compound 63);
(R)-2-(3-fluorophenyl)-1-((1R,6S)-2,2,6-trimethylcyclohexyl) ethanol (Compound 64);
and
2-(3-fluorophenyl)-1-((1R,6S)-2,2, 6-trimethylcyclohexyl) ethanone (Compound 65)
including all pharmaceutically acceptable salts, solvates and hydrates thereof.

64 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) deuterium;
R4 is:
1) hydrogen,
2) lower alkyl,
3) lower haloalkyl, or
4) deuterium;
Ra and Rb are each independently:
1) hydrogen, or
2) —CH3;
T is:
4) —CH2—,
5) —CH2CH2—, or
6) absent;
Ri and Rj are each independently:
1) hydrogen,
2) hydroxyl, or
3) lower alkyl;
or Ri and Rj taken together are oxo (═O);
B is:
1) oxygen,
2) NR5, or
3) CRqRs;
Rq and Rs are each independently:
1) hydrogen,
2) hydroxyl, or
3) lower alkyl;
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;
or
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 is not one of the following compounds:
CAS NO.
STRUCTURE
NAME
873379-08-9
2,2,6-trimethyl-N-(p-tolyl)cyclohexane-1- carboxamide
693243-53-7
2,2,6-trimethyl-N-phenylcyclohexane-1- carboxamide
130741-00-3
2-(3-isopropyl-2,4,5-trimethoxyphenyl)-1- (2,6,6-trimethylcyclohex-1-en-1-yl)ethan-1-one
90858-26-7
4-isopropyl-2-(2-(2,6,6-trimethylcyclohex-1- en-1-yl)ethyl)phenol
90858-25-6
4-isopropyl-1-methoxy-2-(2-(2,6,6- trimethylcyclohex-1-en-1-yl)ethyl)benzene
80994-28-1
1-methoxy-4-(2-(2,6,6-trimethylcyclohex-1- en-1-yl)ethyl)benzene
80994-24-7
1-methoxy-4-(2-(2,6,6-trimethylcyclohex-1- en-1-yl)ethyl)benzene
64158-72-1
2-isopropyl-1-methoxy-4-(2-(2,6,6- trimethylcyclohex-1-en-1-yl)ethyl)benzene
64158-62-9
2-(3-isopropyl-4-methoxyphenyl)-1-(2,6,6- trimethylcyclohex-1-en-1-yl)ethan-1-one
63512-95-8
2-isopropyl-3,4-dimethoxy-1-(2-(2,6,6- trimethylcyclohex-1-en-1-yl)ethyl)benzene
63512-94-7
2-(2-isopropyl-3,4-dimethoxyphenyl)-1-(2,6,6- trimethylcyclohex-1-en-1-yl)ethan-1-one
63512-93-6
2-(2-isopropyl-4-methoxyphenyl)-1-(2,6,6- trimethylcyclohex-1-en-1-yl)ethan-1-ol
59665-69-9
2-(4-isopropyl-3-methoxyphenyl)-1-(2,6,6- trimethylcyclohex-1-en-1-yl)ethan-1-one
59665-68-8
2-(4-isopropyl-3-methoxyphenyl)-1-(2,6,6- trimethylcyclohex-1-en-1-yl)ethan-1-ol
59665-64-4
2-phenyl-1-(2,6,6-trimethylcyclohex-1-en-1-yl) ethan-1-one
59665-63-3
2-phenyl-1-(2,6,6-trimethylcyclohex-1-en-1-yl) ethan-1-ol
26112-36-7
1-methoxy-3-(2-((1S,6S)-2,2,6- trimethylcyclohexyl)ethyl)benzene.

96 more elements

A composition comprising a therapeutically effective amount of a compound selected from the group consisting of:

3-(trifluoromethyl)-N-((2,6,6-trimethylcyclohex-1-enyl)methyl)aniline hydrochloride (Compound 1);
3-methyl-N-((2,6,6-trimethylcyclohex-1-enyl)methyl)aniline (Compound 2);
3-((2,6,6-trimethylcyclohex-1-enyl)methylamino)benzamide (Compound 3);
3-((2,6,6-trimethylcyclohex-1-enyl)methylamino)benzonitrile (Compound 4);
3-chloro-N-((2,6,6-trimethylcyclohex-1-enyl)methyl)aniline (Compound 5);
1-methyl-3-((2, 6,6-trimethylcyclohex-1-enyl)methoxy)benzene (Compound 6);
1-fluoro-3-((2,6, 6-trimethylcyclohex-1-enyl)methoxy)benzene (Compound 7);
1-chloro-3-((2, 6,6-trimethylcyclohex-1-enyl)methoxy)benzene (Compound 8);
1-(trifluoromethyl)-3-((2,6, 6-trimethylcyclohex-1-enyl)methoxy) benzene (Compound 9);
3-fluoro-N-((2,6,6-trimethylcyclohex-1-enyl)methyl)aniline hydrochloride (Compound 10);
N-methyl-3-(trifluoromethyl)-N-((2,6,6-trimethylcyclohex-1-enyl)methyl)aniline hydrochloride (Compound 11);
3-(trifluoromethyl)-N-(((1R,6S)-2,2,6-trimethylcyclohexyl)methyl)aniline hydrochloride (Compound 12);
3-fluoro-N-methyl-N-((2,6,6-trimethylcyclohex-1-enyl)methyl)aniline (Compound 13);
3-((2,6,6-trimethylcyclohex-1-enyl)methoxy)benzonitrile (Compound 14);
4-fluoro-3-methyl-N-((2,6,6-trimethylcyclohex-1-enyl)methyl)aniline hydrochloride (Compound 15);
1-(3-fluorophenyl)-2-(2,6,6-trimethylcyclohex-1-enyl)ethanol (Compound 16);
1-(3-fluorophenyl)-2-(2,6,6-trimethylcyclohex-1-enyl)ethanone (Compound 17);
1-(3-chlorophenyl)-2-(2,6,6-trimethylcyclohex-1-enyl)ethanol (Compound 18);
1-(3-chlorophenyl)-2-(2,6,6-trimethylcyclohex-1-enyl)ethanone (Compound 19);
1-(3-(trifluoromethyl)phenyl)-2-(2,6,6-trimethylcyclohex-1-enyl)ethanol (Compound 20);
2-m-tolyl-1-(2,6,6-trimethylcyclohex-1-enyl)ethanol (Compound 21);
2-(3-(trifluoromethyl)phenyl)-1-(2,6,6-trimethylcyclohex-1-enyl)ethanol (Compound 22);
2-(4-fluoro-3-(trifluoromethyl)phenyl)-1-(2,6,6-trimethylcyclohex-1-enyl)ethanol (Compound 23);
2-fluoro-4((2,6,6-trimethylcyclohex-1-enyl)methoxy) benzonitrile (Compound 24);
1-(3-fluoro-4-(trifluoromethoxy)phenyl)-2-(2,6,6-trimethylcyclohex-1-enyl)ethanol (Compound 25);
1-(3-fluoro-4-(trifluoromethyl)phenyl)-2-(2,6,6-trimethylcyclohex-1-enyl)ethanol (Compound 26);
1-(3,4-dichlorophenyl)-2-(2,6,6-trimethylcyclohex-1-enyl)ethanol (Compound 27);
2-fluoro-1-methyl-4-((2,6,6-trimethylcyclohex-1-enyl)methoxy)benzene (Compound 28);
1,2-difluoro-4-((2,6,6-trimethylcyclohex-1-enyl)methoxy) benzene (Compound 29);
2-(3,4-dimethylphenyl)-1-(2,6,6-trimethylcyclohex-1-enyl)ethanol (Compound 30);
3-methoxy-N-((2,6,6-trimethylcyclohex-1-enyl)methyl)aniline hydrochloride (Compound 31);
N-((6,6-dimethylcyclohex-1-enyl)methyl)-3-fluoroaniline hydrochloride (Compound 32);
N-((6,6-dimethylcyclohex-1-enyl)methyl)-3-fluoro-N-methylaniline hydrochloride (Compound 33);
N-((2,2-dimethylcyclohexyl)methyl)-3-fluoroaniline hydrochloride (Compound 34);
N-((2,2-dimethylcyclohexyl)methyl)-3-fluoro-N-methylaniline hydrochloride (Compound 35);
3-methyl-N-(((1R,6S)-2,2,6-trimethylcyclohexyl)methyl)aniline hydrochloride (Compound 36);
3-chloro-N-(((1R,6S)-2,2,6-trimethylcyclohexyl)methyl)aniline hydrochloride (Compound 37);
3-fluoro-N-(((1R,6S)-2,2,6-trimethylcyclohexyl)methyl)aniline hydrochloride (Compound 38);
3-fluoro-N-methyl-N-(((1R,6S)-2,2,6-trimethylcyclohexyl)methyl)aniline hydrochloride (Compound 39);
3-ethoxy-N-((2,6,6-trimethylcyclohex-1-enyl)methyl)aniline hydrochloride (Compound 40);
3-isopropoxy-N-((2,6,6-trimethylcyclohex-1-enyl)methyl)aniline hydrochloride (Compound 41);
1-ethyl-3-((2,6,6-trimethylcyclohex-1-enyl)methoxy)benzene (Compound 42);
1-methoxy-3-((2,6,6-trimethylcyclohex-1-enyl)methoxy) benzene (Compound 43);
1-ethoxy-3-((2,6,6-trimethylcyclohex-1-enyl)methoxy)benzene (Compound 44);
(R)-2-m-tolyl-1-(1R,6S)-2,2,6-trimethylcyclohexyl)ethanol (Compound 45);
2-m-tolyl-1-((1R,6S)-2,2,6-trimethylcyclohexyl)ethanone (Compound 46);
3-ethyl-N-((2,6,6-trimethylcyclohex-1-enyl)methyl)aniline hydrochloride (Compound 47);
N-((2,6,6-trimethylcyclohex-1-enyl)methyl)benzo[d][1,3]dioxol-5-amine hydrochloride (Compound 48);
2,2-difluoro-N-((2,6,6-trimethylcyclohex-1-enyl)methyl)benzo[d][1,3]dioxol-5-amine hydrochloride (Compound 49);
1-fluoro-3-((2,5,5-trimethylcyclopent-1-enyl)methoxy)benzene (Compound 50);
3-fluoro-N-((2,5,5-trimethylcyclopent-1-enyl)methyl)aniline hydrochloride (Compound 51);
5-((2,6,6-trimethylcyclohex-1-enyl)methoxy) benzo[d][1,3]dioxole (Compound 52);
1-fluoro-3-(((1R,6S)-2,2,6-trimethylcyclohexyl)methoxy) benzene (Compound 53);
1-chloro-3-(((1R,6S)-2,2,6-trimethylcyclohexyl)methoxy) benzene (Compound 54);
1,2-difluoro-4-4(1R,6S)-2,2,6-trimethylcyclohexyl)methoxy) benzene (Compound 55);
1-fluoro-3-((3,3,6,6-tetramethylcyclohex-1-enyl)methoxy) benzene (Compound 56);
3-fluoro-N-((3,3,6,6-tetramethylcyclohex-1-enyl)methyl)aniline hydrochloride (Compound 57);
1-((3-fluorophenoxy)methyl)-7,7-dimethylcyclohept-1-ene (Compound 58);
N-((7,7-dimethylcyclohept-1-enyl)methyl)-3-fluoroaniline hydrochloride (Compound 59);
(3-fluorophenyl)((2,6,6-trimethylcyclohex-1-enyl)methyl) sulfane (Compound 60);
N-((7,7-dimethylcyclohept-1-enyl)methyl)-3-fluoro-N-methylaniline hydrochloride (Compound 61);
3-fluoro-N-methyl-N-((3,3,6,6-tetramethylcyclohex-1-enyl)methyl)aniline hydrochloride (Compound 62);
3-fluoro-N-((2,2,5,5-tetramethylcyclohexyl)methyl)aniline hydrochloride (Compound 63);
(R)-2-(3-fluorophenyl)-1-((1R,6S)-2,2,6-trimethylcyclohexyl) ethanol (Compound 64);
and
2-(3-fluorophenyl)-1-((1R,6S)-2,2,6-trimethylcyclohexyl) ethanone (Compound 65)
including all pharmaceutically acceptable salts, solvates and hydrates thereof, and in a pharmaceutically acceptable carrier.

64 more elements

Dependencies are inferred from the claim text.

Facts

Application: 14/361,445Filed 29 Nov 2012 · us provisional application
Priority: 1 Dec 2011
Published: US 2015/0038574 A15 Feb 2015
Granted: 7 Aug 2018
Term ends: Not estimatedThe source records don’t support an estimate.

Classification26 codes

C07C 211/52
Having amino groups bound to only one six-membered aromatic ring: the carbon skeleton being further substituted by halogen atoms or by nitro or…
A61P 27/02
Drugs for disorders of the senses: ophthalmic agents
A61P 43/00
Drugs for specific purposes, not provided for in groups a61p1/00-a61p41/00
C07C 33/50
Halogenated unsaturated alcohols: containing six-membered aromatic rings and other rings

Family

Application61/565,741Us provisional application · filed 1 Dec 2011
US 2015/0038574 A1Pre-grant publication · published 5 Feb 2015
US 10,040,749 B2This patent

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Abstract

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) deuterium;
R4 is:
1) hydrogen,
2) lower alkyl,
3) lower haloalkyl, or
4) deuterium;
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;
or Ri and Rj taken together are oxo (═O);
B is:
1) oxygen,
2) NR5, or
3) CRqRs;
Rq and Rs are each independently:
1) hydrogen,
2) hydroxyl, or
3) lower alkyl;
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;
or
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 is not one of the following compounds:
CAS NO.
STRUCTURE
NAME
873379- 08-9
2,2,6-trimethyl-N-(p- tolyl)cyclohexane-1- carboxamide
693243- 53-7
2,2,6-trimethyl-N- phenylcyclohexane-1- carboxamide
130741- 00-3
2-(3-isopropyl-2,4,5- trimethoxyphenyl)-1- (2,6,6-trimethylcyclohex- 1-en-1-yl)ethan-1-one
90858- 26-7
4-isopropyl-2-(2-(2,6,6- trimethylcyclohex-1- en-1-yl)ethyl)phenol
90858- 25-6
4-isopropyl-1-methoxy-2- (2-(2,6,6-trimethylcyclohex- 1-en-1-yl)ethyl)benzene
80994- 28-1
1-methoxy-4-(2-(2,6,6- trimethylcyclohex-1- en-1-yl)ethyl)benzene
80994- 24-7
1-methoxy-4-(2-(2,6,6- trimethylcyclohex-1- en-1-yl)ethyl)benzene
64158- 72-1
2-isopropyl-1-methoxy-4- (2-(2,6,6-trimethylcyclohex- 1-en-1-yl)ethyl)benzene
64158- 62-9
2-(3-isopropyl-4- methoxyphenyl)-1-(2,6,6- trimethylcyclohex-1-en-1- yl)ethan-1-one
63512- 95-8
2-isopropyl-3,4-dimethoxy- 1-(2-(2,6,6- trimethylcyclohex- 1-en-1-yl)ethyl)benzene
63512- 94-7
2-(2-isopropyl-3,4- dimethoxyphenyl)-1-(2,6,6- trimethylcyclohex-1-en-1- yl)ethan-1-one
63512- 93-6
2-(2-isopropyl-4- methoxyphenyl)-1-(2,6,6- trimethylcyclohex-1-en-1- yl)ethan-1-ol
59665- 69-9
2-(4-isopropyl-3- methoxyphenyl)-1-(2,6,6- trimethylcyclohex-1-en- 1-yl)ethan-1-one
59665- 68-8
2-(4-isopropyl-3- methoxyphenyl)-1-(2,6,6- trimethylcyclohex-1-en- 1-yl)ethan-1-ol
59665- 64-4
2-phenyl-1-(2,6,6- trimethylcyclohex-1-en- 1-yl)ethan-1-one
59665- 63-3
2-phenyl-1-(2,6,6- trimethylcyclohex-1-en- 1-yl)ethan-1-ol
26112- 36-7
1-methoxy-3-(2-((1S,6S)- 2,2,6- trimethylcyclohexyl)ethyl)- benzene.

96 more elements

Facts

Application

14/361,445Filed 29 Nov 2012 · us provisional application

Priority

1 Dec 2011

Published

US 2015/0038574 A15 Feb 2015

Granted

7 Aug 2018

Term ends

Not estimatedThe source records don’t support an estimate.

Classification26 codes

C07C 211/52
Having amino groups bound to only one six-membered aromatic ring: the carbon skeleton being further substituted by halogen atoms or by nitro or…
A61P 27/02
Drugs for disorders of the senses: ophthalmic agents
A61P 43/00
Drugs for specific purposes, not provided for in groups a61p1/00-a61p41/00
C07C 33/50
Halogenated unsaturated alcohols: containing six-membered aromatic rings and other rings