IP Library Granted Patent US 10,172,840
Granted Patent B2
US 10,172,840 · App. 15/584,459 · Granted Jan 8, 2019

Bach1 inhibitors in combination with Nrf2 activators and pharmaceutical compositions thereof

Inventor: Otis Clinton Attucks (Winston-Salem, NC)
Assignee: vTv Therapeutics LLC
A61K31/437A61K31/428A61K31/56Y02A50/395
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Quick Facts
Patent No.
US 10,172,840
App. No.
15/584,459
Granted
Jan 8, 2019
Kind
B2
Abstract

The disclosure provides pharmaceutical compositions comprising Bach1 Inhibitors and Nrf2 Activators. The disclosure also provides methods of treating diseases such as psoriasis, multiple sclerosis, and COPD comprising administering a Bach1 Inhibitor and a Nrf2 Activator to a subject in need thereof.

Claims (206)

1. A method of treatment of a condition, comprising administering an Nrf2 activator and a Bach1 Inhibitor to a subject in need thereof,

wherein the condition is selected from the group consisting of psoriasis, scleroderma, chronic kidney disease (CKD), asthma, chronic obstructive pulmonary disorder (COPD), fibrosis, inflammatory arthritis disease, inflammatory bowel disease (IBD), multiple sclerosis, clinically isolated syndrome (CIS), amyotrophic lateral sclerosis, Alzheimer's disease, dementia, Huntington's disease, and Parkinson's disease;

wherein the Nrf2 Activator is selected from the group consisting of

a fumaric acid mono- and/or dialkyl ester, methyl 2-cyano-3,12-dioxooleana-1,9(11)dien-28-oate, ethyl 2-cyano-3,12-dioxooleana-1,9(11)dien-28-oate, 2-cyano-3,12-dioxooleana-1,9(11)dien-28-oic acid, 1[2-Cyan-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole, and 2-cyano-N-methyl-3,12-dioxooleana-1,9(11)-dien-28 amide,

wherein the Bach1 Inhibitor is a compound of Formula (I) or a pharmaceutically acceptable salt thereof,

wherein

X 1 is ═CH—;

G is hydrogen, —C 1-8 alkyl, —C 3-10 cycloalkyl, —C 1-6 alkylene-C 3-10 cycloaklyl, heterocyclyl, —C 1-6 alkylene-C 3-10 heterocyclyl, phenyl, heteroaryl, or NR h R k , where the alkyl, alkylene, cycloalkyl, heterocyclyl, phenyl, and heteroaryl groups are optionally substituted one or more times with substituents independently selected from R c ; or G is —CH 2 Y 3 , —CH 2 CH 2 Y 3 , —CH 2 CH 2 CH 2 Y 3 , —CH(CH 3 )CH 2 Y 3 , —CH 2 CH(Y 3 )CH 3 , —CH(Y 3 )CH 3 , —CH 2 C(Y 3 )(CH 3 ) 2 , —C(Y 3 )(CH 3 ) 2 , or

where Y 3 is cyclopropyl, —CF 3 , —OCF 3 , —OCH 3 , —OCH 2 CH 3 , —F, —Cl, —OH, —O(CH 2 ) 2 —OH, —O(CH 2 ) 2 —F, —SCH 3 , —S(O) 2 —CH 3 , —SCH 2 CH 3 , —S(O) 2 CH 2 CH 3 , —NH—CH 3 , —NH—CH 2 CH 3 , —N(CH 3 ) 2 , tetrahydropyran-4-yl, tetrahydrofuran-2-yl, morpholin-2-yl, morpholin-4-yl, piperidin-1-yl, 4-hydroxy-piperidin-1-yl, 3-hydroxy-piperidin-1-yl, —NH—C(O)—CH 3 , —NH—C(O)—CH 2 CH 3 , tetrahydrofuran-2-yl-methyloxy, or —C(O)—Y 4 , where Y 4 is —OH, —OCH 3 , —OCH 2 CH 3 , —OC(CH 3 ) 3 , —NH 2 , —NH—CH 3 , —NH—CH 2 CH 3 , —N(CH 3 ) 2 , —N(CH 2 CH 3 ) 2 , morpholin-4-yl, 4-methyl-piperazin-1-yl, pyrrolidin-1-yl, or piperazin-1-yl;

L is —CH 2 —C(O)N(R 6 )—, —C(O)N(R 6 )—, —C(O)—O—, —SO 2 —, —C(O)—, heteroarylene optionally substituted one or more times with substituents independently selected from R x , or heterocyclylene optionally substituted one or more times with substituents independently selected from R x ; or the group -L-G is -cyano;

R 1 is hydrogen, R a , phenyl, or heteroaryl, where the phenyl and heteroaryl groups are optionally substituted one or more times with substituents independently selected from R x ;

R 2 is R b ;

R 3 is hydrogen, —C 1-6 alkyl, or —C 1-6 alkylene-C 3-10 cycloaklyl, where the alkyl, alkylene, and cycloalkyl groups are optionally substituted one or more times with substituents independently selected from R z ;

R 4 is —C 1-6 alkyl or —C 1-6 alkylene-C 3-10 cycloaklyl, where the alkyl, alkylene, and cycloalkyl groups are optionally substituted one or more times with substituents independently selected from R y ;

R 6 is hydrogen, —C 1-6 alkyl, —C 1-6 alkylene-C 3-10 cycloaklyl, where the alkyl, alkylene, and cycloalkyl groups are optionally substituted one or more times with substituents independently selected from R x ;

R a is

a) -halogen,

b) —C 1-6 alkyl,

c) —C 3-10 cycloalkyl,

d) -heterocyclyl,

e) -cyano,

f) —CF 3 ,

g) —OCF 3 ,

h) —O—R d ,

i) —S(O) w —R d ,

j) —S(O) 2 O—R d ,

k) —NR d R e ,

l) —C(O)—R d ,

m) —C(O)—O—R d ,

n) —OC(O)—R d ,

o) —C(O)NR d R e ,

p) —C(O)-heterocyclyl,

q) —NR d C(O)R e ,

r) —OC(O)NR d R e ,

s) —NR d C(O)OR d , or

t) —NR d C(O)NR d R e ,

where the alkyl, cycloalkyl, and heterocyclyl groups are optionally substituted one or more times with substituents independently selected from R y ;

R b is

a) -halogen,

b) —C 1-6 alkyl,

c) —C 3-10 cycloalkyl,

d) -heterocyclyl,

e) -phenyl,

f) -heteroaryl,

g) -cyano,

h) —CF 3 ,

i) —OCF 3 ,

j) —O—R f ,

k) —S(O) w —R f ,

l) —S(O) 2 O—R f ,

m) —NR f R g ,

n) —C(O)—R f ,

o) —C(O)—O—R f ,

p) —OC(O)—R f ,

q) —C(O)NR f R g ,

r) —C(O)-heterocyclyl,

s) —NR f C(O)R g ,

t) —OC(O)NR f R g ,

u) —NR f C(O)OR f , or

v) —NR f C(O)NR f R g ,

where the alkyl, cycloalkyl, heterocyclyl, phenyl, and heteroaryl groups are optionally substituted one or more times with substituents independently selected from R z ;

R c is

a) -halogen,

b) —C 1-6 alkyl,

c) —C 3-10 cycloalkyl,

d) -heterocyclyl,

e) -cyano,

f) —CF 3 ,

g) —OCF 3 ,

h) —O—R h ,

i) —S(O) w —R h ,

j) —S(O) 2 O—R h ,

k) —NR h R k ;

l) —C(O)—R h ,

m) —C(O)—O—R h ,

n) —OC(O)—R h ,

o) —C(O)NR h R k ,

p) —C(O)-heterocyclyl,

q) —NR h C(O)R k ,

r) —OC(O)NR h R k ,

s) —NR h C(O)OR k ,

t) —NR h C(O)NR h R k ,

u) —NR h S(O) w R k ,

v) -phenyl,

w) -heteroaryl, or

x) —O—(C 1-4 alkylene)-O—(C 1-4 alkylene)-N(R h )C(O)—OR k ,

where the alkylene, alkyl, cycloalkyl, heterocyclyl, phenyl, and heteroaryl groups are optionally substituted one or more times with substituents independently selected from R x ;

R d and R e are independently hydrogen, C 1-6 alkyl, or C 3-10 cycloalkyl, where the alkyl and cycloalkyl groups are optionally substituted one or more times with substituents independently selected from R y ; or, if R d and R e are both attached to the same nitrogen atom, together with that nitrogen atom may optionally form a heterocyclic ring selected from the group consisting of azetidino, pyrrolidino, pyrazolidino, imidazolidino, oxazolidino, isoxazolidino, thiazolidino, isothiazolidino, piperidino, piperazino, morpholino, thiomorpholino, and azepano, where each ring is optionally substituted one or more times with substituents independently selected from R y ;

R f and R g are independently hydrogen, C 1-6 alkyl, C 3-10 cycloalkyl, phenyl, or heteroaryl, where the alkyl, cycloalkyl, phenyl, and heteroaryl groups are optionally substituted one or more times with substituents independently selected from R z ; or, if R f and R g are both attached to the same nitrogen atom, together with that nitrogen atom may optionally form a heterocyclic ring selected from the group consisting of azetidino, pyrrolidino, pyrazolidino, imidazolidino, oxazolidino, isoxazolidino, thiazolidino, isothiazolidino, piperidino, piperazino, morpholino, thiomorpholino, and azepano, where each ring is optionally substituted one or more times with substituents independently selected from R z ;

R h and R k are independently hydrogen, C 1-6 alkyl, C 3-10 cycloalkyl, heterocyclyl, phenyl, or heteroaryl, where the alkyl, cycloalkyl, heterocyclyl, phenyl, and heteroaryl groups are optionally substituted one or more times with substituents independently selected from R x ; or, if R h and R k are both attached to the same nitrogen atom, together with that nitrogen atom may optionally form a heterocyclic ring selected from the group consisting of azetidino, pyrrolidino, pyrazolidino, imidazolidino, oxazolidino, isoxazolidino, thiazolidino, isothiazolidino, piperidino, piperazino, morpholino, thiomorpholino, and azepano, where each ring is optionally substituted one or more times with substituents independently selected from R x ;

R y is

a) -halogen,

b) —NH 2 ,

c) -cyano,

d) -carboxy,

e) -hydroxy,

f) -thiol,

g) —CF 3 ,

h) —OCF 3 ,

i) —C(O)—NH 2 ,

j) —S(O) 2 —NH 2 ,

k) oxo,

l) —C 1-6 alkyl, optionally substituted one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C 1-6 alkyl, —NH 2 , —NH—C 1-6 alkyl, and —N(C 1-6 alkyl) 2 ,

m) -heterocyclyl optionally substituted one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C 1-6 alkyl, —NH 2 , —NH—C 1-6 alkyl, and —N(C 1-6 alkyl) 2 ,

n) —C 3-10 cycloalkyl optionally substituted one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C 1-6 alkyl, —NH 2 , —NH—C 1-6 alkyl, and —N(C 1-6 alkyl) 2 ,

o) —O—C 1-6 alkyl optionally substituted one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C 1-6 alkyl, —NH 2 , —NH—C 1-6 alkyl, and —N(C 1-6 alkyl) 2 ,

p) —O—C 3-10 cycloalkyl optionally substituted one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C 1-6 alkyl, —NH 2 , —NH—C 1-6 alkyl, and —N(C 1-6 alkyl) 2 ,

q) —NH—C 1-6 alkyl optionally substituted one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C 1-6 alkyl, —NH 2 , —NH—C 1-6 alkyl, and —N(C 1-6 alkyl) 2 ,

r) —N(C 1-6 alkyl) 2 optionally substituted one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C 1-6 alkyl, —NH 2 , —NH—C 1-6 alkyl, and —N(C 1-6 alkyl) 2 ,

s) —C(O)—C 1-6 alkyl, optionally substituted one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C 1-6 alkyl, —NH 2 , —NH—C 1-6 alkyl, and —N(C 1-6 alkyl) 2 ,

t) —C(O)—O—C 1-6 alkyl, optionally substituted one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C 1-6 alkyl, —NH 2 , —NH—C 1-6 alkyl, and —N(C 1-6 alkyl) 2 ,

u) —S—C 1-6 alkyl, optionally substituted one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C 1-6 alkyl, —NH 2 , —NH—C 1-6 alkyl, and —N(C 1-6 alkyl) 2 ,

v) —S(O) 2 —C 1-6 alkyl, optionally substituted one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C 1-6 alkyl, —NH 2 , —NH—C 1-6 alkyl, and —N(C 1-6 alkyl) 2 ,

w) —C(O)—NH—C 1-6 alkyl, optionally substituted one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C 1-6 alkyl, —NH 2 , —NH—C 1-6 alkyl, and —N(C 1-6 alkyl) 2 ,

x) —C(O)—N(C 1-6 alkyl) 2 , optionally substituted one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C 1-6 alkyl, —NH 2 , —NH—C 1-6 alkyl, and —N(C 1-6 alkyl) 2 ,

y) —S(O) 2 —NH—C 1-6 alkyl, optionally substituted one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C 1-6 alkyl, —NH 2 , —NH—C 1-6 alkyl, and —N(C 1-6 alkyl) 2 ,

z) —S(O) 2 —N(C 1-6 alkyl) 2 , optionally substituted one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C 1-6 alkyl, —NH 2 , —NH—C 1-6 alkyl, and —N(C 1-6 alkyl) 2 ,

aa) —NH—C(O)—C 1-6 alkyl, optionally substituted one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C 1-6 alkyl, —NH 2 , —NH—C 1-6 alkyl, and —N(C 1-6 alkyl) 2 , or

bb) —NH—S(O) 2 —C 1-6 alkyl, optionally substituted one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C 1-6 alkyl, —NH 2 , —NH—C 1-6 alkyl, and —N(C 1-6 alkyl) 2 ;

R x is

a) -R y

b) -phenyl, optionally substituted one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C 1-6 alkyl, —NH 2 , —NH—C 1-6 alkyl, and —N(C 1-6 alkyl) 2 ,

c) -heteroaryl, optionally substituted one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C 1-6 alkyl, —NH 2 , —NH—C 1-6 alkyl, and —N(C 1-6 alkyl) 2 ,

d) —O-phenyl,

e) —O-heteroaryl,

f) —C(O)-phenyl,

g) —C(O)-heteroaryl,

h) —C(O)—O-phenyl, or

i) —C(O)—O-heteroaryl;

R z is

a) -R y

b) -phenyl,

c) -heteroaryl;

d) —O-phenyl,

e) —O-heteroaryl,

f) —C(O)-phenyl,

g) —C(O)-heteroaryl,

h) —C(O)—O-phenyl, or

i) —C(O)—O-heteroaryl;

v is an integer from 0 to 4, and

w is an integer from 0 to 2.

2. The method of claim 1 , wherein the Nrf2 activator is a selected from the group consisting of monomethyl hydrogen fumarate, dimethyl fumarate (DMF), monoethyl hydrogen fumarate, and diethyl fumarate.

3. The method of claim 1 , wherein the Nrf2 activator is methyl 2-cyano-3,12-dioxooleana-1,9(11)dien-28-oate.

4. The method of claim 1 , wherein subject is suffering from multiple sclerosis.

5. The method of claim 1 , wherein the Bach1 Inhibitor is a compound selected from the group consisting of:

1-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (2-ethoxy-ethyl)-amide;

1-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (2-methoxy-ethyl)-amide;

1-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethyl)-amide;

1-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (2-methoxy-2-methyl-propyl)-amide;

1-Methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (2-methoxy-ethyl)-amide;

1-Methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethyl)-amide;

2-(6-Chloro-benzothiazol-2-ylamino)-1-methyl-1H-benzoimidazole-5-carboxylic acid (2-methoxy-ethyl)-amide;

6-Fluoro-1-methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid ethylamide;

1-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid [2-(2-hydroxy-ethoxy)-ethyl]-amide;

1-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid [2-(2-fluoro-ethoxy)-ethyl]-amide;

1-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid ((S)-2-hydroxy-propyl)-amide;

1-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid ((R)-2-hydroxy-propyl)-amide;

6-Methoxy-1-methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (2-morpholin-4-yl-ethyl)-amide;

1-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid dimethylcarbamoylmethyl-amide;

2-(6-Chloro-benzothiazol-2-ylamino)-1-methyl-1H-benzoimidazole-5-carboxylic acid (2-ethoxy-ethyl)-amide;

1-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzimidazole-5-carboxylic acid (2-ethanesulfonyl-ethyl)-amide;

1-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzimidazole-5-carboxylic acid (3-methanesulfonyl-propyl)-amide;

2-(6-Chloro-benzothiazol-2-ylamino)-1-methyl-1H-benzimidazole-5-carboxylic acid dimethylcarbamoylmethyl-amide;

1-Methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzimidazole-5-carboxylic acid dimethylcarbamoylmethyl-amide;

1-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzimidazole-5-carboxylic acid (2-dimethylcarbamoyl-ethyl)-amide;

1-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzimidazole-5-carboxylic acid [2-(4-methyl-piperazin-1-yl)-2-oxo-ethyl]-amide;

1-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid ((S)-1-dimethylcarbamoyl-ethyl)-amide;

1-Ethyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (2-ethoxy-ethyl)-amide;

1-(2-Methoxy-ethyl)-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (2-ethoxy-ethyl)-amide;

2-(6-Chloro-benzothiazol-2-ylamino)-1-ethyl-1H-benzoimidazole-5-carboxylic acid (2-fluoro-ethyl)-amide;

2-(6-Chloro-benzothiazol-2-ylamino)-1-ethyl-1H-benzoimidazole-5-carboxylic acid (2-methoxy-ethyl)-amide;

1-Methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid ((R)-2-hydroxy-propyl)-amide;

1-Methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid ((S)-2-hydroxy-propyl)-amide;

2-(6-Chloro-benzothiazol-2-ylamino)-1-methyl-1H-benzoimidazole-5-carboxylic acid [2-(2-hydroxy-ethoxy)-ethyl]-amide;

1-Methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid [2-(2-hydroxy-ethoxy)-ethyl]-amide;

1-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid [2-(2-methoxy-ethoxy)-ethyl]-amide;

1-Methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid [2-(2-methoxy-ethoxy)-ethyl]-amide;

1-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid [2-(2-dimethylamino-ethoxy)-ethyl]-amide;

1-Methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (2-morpholin-4-yl-ethyl)-amide;

2-(6-Chloro-benzothiazol-2-ylamino)-1-methyl-1H-benzoimidazole-5-carboxylic acid (2-dimethylcarbamoyl-ethyl)-amide;

1-Methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (2-dimethylcarbamoyl-ethyl)-amide;

1-Methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (3-morpholin-4-yl-3-oxo-propyl)-amide;

1-Methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid methylcarbamoylmethyl-amide;

1-Methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid [2-((R)-3-hydroxy-pyrrolidin-1-yl)-2-oxo-ethyl]-amide;

2-(6-Chloro-benzothiazol-2-ylamino)-1-methyl-1H-benzoimidazole-5-carboxylic acid [2-((R)-3-methoxy-pyrrolidin-1-yl)-2-oxo-ethyl]-amide;

2-(6-Chloro-benzothiazol-2-ylamino)-1-methyl-1H-benzoimidazole-5-carboxylic acid [2-((S)-3-methoxy-pyrrolidin-1-yl)-2-oxo-ethyl]-amide;

1-Methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid [2-((S)-3-methoxy-pyrrolidin-1-yl)-2-oxo-ethyl]-amide;

1-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid [2-((R)-3-dimethylamino-pyrrolidin-1-yl)-2-oxo-ethyl]-amide;

1-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid [2-((S)-3-dimethylamino-pyrrolidin-1-yl)-2-oxo-ethyl]-amide;

1-Methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (2-morpholin-4-yl-2-oxo-ethyl)-amide;

1-Methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid [2-(4-methyl-piperazin-1-yl)-2-oxo-ethyl]-amide;

1-Methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid [2-((R)-3-hydroxy-piperidin-1-yl)-2-oxo-ethyl]-amide;

1-Methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid [2-((S)-3-hydroxy-piperidin-1-yl)-2-oxo-ethyl]-amide;

1-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid [2-(4-hydroxy-piperidin-1-yl)-2-oxo-ethyl]-amide;

2-(6-Chloro-benzothiazol-2-ylamino)-1-methyl-1H-benzoimidazole-5-carboxylic acid [2-(4-hydroxy-piperidin-1-yl)-2-oxo-ethyl]-amide;

2-(6-Chloro-benzothiazol-2-ylamino)-1-methyl-1H-benzoimidazole-5-carboxylic acid ((S)-1-dimethylcarbamoyl-ethyl)-amide;

1-Methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid ((S)-1-dimethylcarbamoyl-ethyl)-amide;

1-Methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid ((S)-1-methyl-2-morpholin-4-yl-2-oxo-ethyl)-amide;

1-Methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid ((R)-1-dimethylcarbamoyl-ethyl)-amide; and

1-Methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid [(R)-1-methyl-2-(4-methyl-piperazin-1-yl)-2-oxo-ethyl]-amide;

or a pharmaceutically acceptable salt thereof.

6. The method of claim 1 , wherein the Bach1 Inhibitor is a compound selected from the group consisting of

1-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid methyl amide;

1-Methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzimidazole-5-carboxylic acid dimethylcarbamoylmethyl-amide; and

1-Methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid [2-(2-hydroxy-ethoxy)-ethyl]-amide;

or a pharmaceutically acceptable salt thereof.

Assignments (3)
RELEASE OF SECURITY INTEREST Recorded Jan 27, 2021
From: HORIZON TECHNOLOGY FINANCE CORPORATION, AS COLLATERAL AGENT
To: VTV THERAPEUTICS LLC
Reel/Frame 055133/0214 →
SECURITY INTEREST Recorded Apr 18, 2018
From: VTV THERAPEUTICS LLC
To: HORIZON TECHNOLOGY FINANCE CORPORATION, AS COLLATERAL AGENT
Reel/Frame 045969/0774 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 10, 2017
From: ATTUCKS, OTIS CLINTON
To: VTV THERAPEUTICS LLC
Reel/Frame 042319/0681 →
Continuity (3)
Continuation PCTUS2015062096 · Nov 23, 2015
Provisional Application 62085875 · Dec 1, 2014
Related Publication 20170231967A1 · Aug 17, 2017