IP Library Granted Patent US 9,073,891
Granted Patent B2
US 9,073,891 · App. 13/617,630 · Granted Jul 7, 2015

Inhibitors of Jun N-terminal kinase

Inventors: Hing L. Sham (Palo Alto, CA); Roy K. Hom (San Francisco, CA); Andrei W. Konradi (Burlingame, CA); Gary D. Probst (San Francisco, CA); Simeon Bowers (Oakland, CA); Anh Truong (Burlingame, CA); R. Jeffrey Neitz (San Francisco, CA); Jennifer Sealy (Oakland, CA); Gergely Toth (Palo Alto, CA)
Assignee: Imago Pharmaceuticals, Inc.
C07D409/04A61K31/381A61K31/433C07D409/14C07D413/04C07D413/14C07D417/04C07D417/14C07D471/04C07D487/04A61K31/401A61K31/4196A61K31/4245A61K31/4709A61K31/4725A61K31/498A61K31/4985A61K31/519
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 9,073,891
App. No.
13/617,630
Granted
Jul 7, 2015
Kind
B2
Abstract

The present disclosure provides inhibitors of c-Jun N-terminal kinases (JNK) having a structure according to the following formula: or a salt or solvate thereof, wherein ring A, C a , C b , Z, R 5 , W and Cy are defined herein. The disclosure further provides pharmaceutical compositions including the compounds of the present disclosure and methods of making and using the compounds and compositions of the present disclosure, e.g., in the treatment and prevention of various disorders, such as Alzheimer's disease.

Claims (364)

1. A method of treating a neurodegenerative disease, the method comprising:

administering to a mammalian subject in need thereof a pharmaceutically effective amount of a compound having a structure according to Formula (I):

or a salt thereof,

wherein:

ring A is 5-membered heteroaryl comprising a sulfur atom, wherein the heteroaryl is optionally substituted with 1or 2 substituents independently selected from alkyl, alkenyl, alkynyl, haloalkyl, heteroalkyl, C 3 -C 10 -cycloalkyl, 3- to 8-membered heterocycloalkyl, aryl, 5- or 6-membered heteroaryl, CN, halogen, OR 12 , SR 12 , NR 12 R 13 , C(O)R 14 , C(O)NR 12 R 13 , OC(O)NR 12 R 13 , C(O)OR 12 , NR 15 C(O)R 14 , NR 15 C(O)OR 12 , NR 15 C(O)NR 12 R 13 , NR 15 C(S)NR 12 R 13 , NR 15 S(O) 2 R 14 , S(O) 2 NR 12 R 13 , S(O)R 14 and S(O) 2 R 14 ;

wherein:

R 12 , R 13 , and R 15 are each independently selected from H, acyl, C 1 -C 6 -alkyl, 2- to 6-membered heteroalkyl, aryl, 5- or 6-membered heteroaryl, C 3 -C 8 cycloalkyl and 3- to 8-membered heterocycloalkyl, or R 12 and R 13 , together with the nitrogen atom to which they are bound form a 5- to 7-membered heterocyclic ring; and

R 14 is acyl, C 1 -C 6 -alkyl, 2- to 6-membered heteroalkyl, aryl, 5- or 6-membered heteroaryl, C 3 -C 8 cycloalkyl and 3- to 8-membered heterocycloalkyl;

C a and C b are carbon atoms, which are adjacent to each other and are part of ring A;

Z is 5- or 6-membered heteroaryl selected from the group consisting of optionally substituted pyrazole, optionally substituted imidazole, optionally substituted triazole, optionally substituted oxazole, optionally substituted thiazole, optionally substituted oxadiazole, optionally substituted pyridine and optionally substituted pyrazine, with the proviso that when ring A is optionally substituted thiophene, then Z is not methyl-substituted thiazole or oxadiazole substituted with optionally substituted phenyl;

R 5 is selected from H, acyl, optionally substituted C 1 -C 6 alkyl, and C 3 -C 6 cycloalkyl;

W is selected from C 1 -C 4 alkylene, wherein the alkylene is optionally substituted with 1-4 substituents independently selected from alkyl, alkenyl, alkynyl, haloalkyl, heteroalkyl, C 3 -C 6 -cycloalkyl, 3- to 8-membered heterocycloalkyl, aryl, 5- or 6-membered heteroaryl, CN, halogen, OR 42 , SR 42 , NR 42 R 43 , C(O)R 44 , C(O)NR 42 R 43 , OC(O)NR 42 R 43 , C(O)OR 42 , NR 45 C(O)R 44 , C(O)OR 42 , NR 45 C(O)NR 42 R 43 , NR 45 C(S)NR 42 R 43 , NR 45 S(O) 2 R 44 S(O) 2 NR 42 R 43 , S(O)R 44 , and S(O) 2 R 44 ,

wherein:

R 42 , R 43 , and R 45 are independently selected from H, acyl, C 1 -C 6 -alkyl, 2- to 6-membered heteroalkyl, aryl, 5- or 6-membered heteroaryl, C 3 -C 8 cycloalkyl and 3- to 8-membered heterocycloalkyl, wherein R 42 and R 43 , together with the nitrogen atom to which they are bound are optionally joined to form a 5- to 7-membered heterocyclic ring; and

R 44 is independently selected from acyl, C 1 -C 6 -alkyl, 2- to 6-membered heteroalkyl, aryl, 5- or 6-membered heteroaryl, C 3 -C 8 cycloalkyl and 3- to 8-membered heterocycloalkyl;

Cy is selected from cycloalkyl, heterocycloalkyl, aryl, and heteroaryl, wherein the cycloalkyl, heterocycloalkyl, aryl or heteroaryl is optionally substituted with 1-6 substituents independently selected from substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, haloalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, ═O, CN, halogen, OR 52 , SR 52 , NR 52 R 53 , C(O)R 54 , C(O)NR 52 R 53 , OC(O)NR 52 R 53 , C(O)OR 52 , NR 55 C(O)R 54 , NR 55 C(O)OR 52 , NR 55 C(O)NR 52 R 53 , NR 55 C(S)NR 52 R 53 , NR 55 S(O) 2 R 54 , S(O) 2 NR 52 R 53 , S(O)R 54 and S(O) 2 R 54 ,

wherein:

R 52 , R 53 and R 55 are independently selected from H, acyl, C 1 -C 6 -alkyl, 2- to 6-membered heteroalkyl, aryl, 5- or 6-membered heteroaryl, C 3 -C 8 cycloalkyl and 3- to 8-membered heterocycloalkyl, wherein R 52 and R 53 , together with the nitrogen atom to which they are bound are optionally joined to form a 5- to 7-membered heterocyclic ring, wherein C 1 -C 6 -alkyl is optionally substituted with one or more substituents independently selected from halogen, 3 to 10 membered heterocycloalkyl, and heteroaryl; and

R 54 is independently selected from acyl, C 1 -C 6 -alkyl, 2- to 6-membered heteroalkyl, aryl, 5- or 6-membered heteroaryl, C 3 -C 8 cycloalkyl and 3- to 8-membered heterocycloalkyl, and

wherein the compound according to Formula (I) exhibits the ability to inhibit c-Jun N-terminal kinase 3 (JNK3) in vitro, wherein said neurodegenerative disease is Alzheimer's disease, diffuse Lewy body type of Alzheimer's disease, or mild cognitive impairment (MCI), and the mammalian subject is a human.

2. The method of claim 1 , wherein said compound is at least one selected from the group consisting of:

N-(4-methyl-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydroquinolin -1(2H)-yl)acetamide;

N-(4-methyl-3-(3-methyl-1H-1,2,4-triazol-5-thiophen-2-yl)-2-(2-oxo-3,4-dihydroquinolin-1(2H)-yl)acetamide;

N-(4-chloro-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydroquinolin-1-(2H)-yl)acetamide;

N-(4-chloro-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(isoquinolin-5-yl)acetamide;

N-(4-chloro-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(quinolin-5-yl)acetamide;

N-(4-methyl-3-(3-methyl-1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(quinolin-5-yl) acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(isoquinolin-5-yl)acetamide ;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(quinolin-5-yl)acetamide ;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydroquinolin -1(2H)-yl)acetamide;

N-(4-cyano-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(isoquinolin-5-yl)acetamide;

N-(4-cyano-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydroquinolin -1(2H)-yl)acetamide;

N-(4-cyano-3-(4H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(quinolin-5-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-7-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(6-fluoro-2-oxo-3,4-dihydroquinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(7-fluoro-2-oxoquinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(7-chloro-2-oxo-3,4-dihydroquinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(6,7-difluoro-2-oxoquinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(6-fluoro-2-oxoquinolin-1(2H)-yl)acetamide; N-(4,4′-bithiazol-5yl)-2(isoquinolin-5yl)acetamide;

N-(4-bromo-3-(4H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(quinolin-4-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(8-fluoroisoquinolin-5-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-1,6-naphthyridin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(8-fluoroquinolin-5-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-1,5-naphthyridin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydro-1,6-naphthyridin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydro-1,5-naphthyridin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(6-chloro-2-oxoquinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(5-fluoro-2-oxoquinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethoxy)quinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(4H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(isoquinolin-4-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(3-fluoroquinolin-5-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-7-(trifluoromethoxy)quinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(7-cyano-2-oxoquinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(isoquinolin-8-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(6-cyano-2-oxoquinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-5-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)-3,4-dihydroquinolin-1(2H)-yl)acetamide;

N-(4-cyano-3-(1-methyl-1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(quinolin-5-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(7-fluoroquinolin-5-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(3-(trifluoromethyl)quinolin-5-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(6-fluoroquinolin-5-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(6-ethynyl-2-oxoquinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-7-(trifluoromethyl)-1,6-naphthyridin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(5-oxopyrazolo[1,5-a]pyrimidin-4(5H)-yl)acetamide;

2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)-N-(2-(thiazol-4-yl)thiophen-3-yl)acetamide;

N-(4- cyano-3-(pyrazin-2-yl)thiophen-2-yl)-2-(quinolin-5-yl)acetamide;

2-(benzo[d]thiazol-7-yl)-N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)acetamide;

N-(4-chloro-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-cyano-3-(oxazol-2-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)-1,5-naphthyridin-1(2H)-yl)acetamide;

N-(4-cyano-3-(thiazol-2-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(5-oxo-2-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-4(5H)-yl)acetamide;

N-(4-cyano-3-(thiazol-4-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(7-fluoro-2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1-methyl-1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydro-1,5-naphthyridin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(6-fluoroisoquinolin-5-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(6-fluoroisoquinolin-7-yl)acetamide;

N-(4-cyano-3-(2H-1,2,3-triazol-2-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-chloro-3-(1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydro-1,5-naphthyridin-1(2H)-yl)acetamide;

N-(4-cyano-3-(thiazol-2-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydro-1,5-naphthyridin-1(2H)-yl)acetamide;

N-(4-chloro-3-(1-methyl-1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydro -1,5-naphthyridin-1(2H)-yl)acetamide;

N-(4-chloro-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(5-oxopyrazolo[1,5-a]pyrimidin-4(5H)-yl)acetamide;

N-(4-bromo-3-(oxazol-2-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydro-1,5-naphthyridin-1(2H)-yl)acetamide;

N-(4-bromo-3-(thiazol-2-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydro-1,5-naphthyridin-1(2H)-yl)acetamide;

N-(4-chloro-3-(thiazol-2-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydro-1,5-naphthyridin-1(2H)-yl)acetamide;

N-(4-chloro-3-(3-methyl-1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydro-1,5-naphthyridin-1(2H)-yl)acetamide;

N-(4-chloro-3-(1-(3-(dimethylamino)propyl)-1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-chloro-3-(1-(3-(4-methylpiperazin-1-yl)propyl)-1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-chloro-3-(3-ethyl-1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydro-1,5-naphthyridin-1(2H)-yl)acetamide;

N-(4-chloro-3-(1-(2-(dimethylamino)ethyl)-1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-cyano-3-(1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydro-1,5-naphthyridin-1(2H)-yl)acetamide;

N-(4-chloro-3-(1-methyl-1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(5-oxopyrazolo[1,5-a]pyrimidin-4(5H)-yl)acetamide;

N-(4-chloro-3-(1-(3-morpholinopropyl)-1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-chloro-3-(1-(3-(pyrrolidin-1-yl)propyl)-1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-chloro-3-(1-methyl-1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)-1,5-naphthyridin-1(2H)-yl)acetamide;

N-(4-bromo-3-(2H-1,2,3-triazol-2-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-chloro-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)-1,5-naphthyridin-1(2H)-yl)acetamide;

2-(6-bromo-2-oxoquinolin-1(2H)-yl)-N-(4-bromo-3-(1H-1,2,4-triazol-3-yl)thiophen-2-yl)acetamide;

N-(4-cyano-3-(1-methyl-1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydro-1,5-naphthyridin-1(2H)-yl)acetamide;

2-(6-bromo-2-oxoquinolin-1(2H)-yl)-N-(4-chloro-3-(1H-1,2,4-triazol-3-yl)thiophen-2-yl)acetamide;

N-(4-chloro-3-(1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(6-cyano-2-oxoquinolin-1(2H)-yl)acetamide;

N-(4-chloro-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(5-oxo-2-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-4(5H)-yl)acetamide;

N-(4-chloro-3-(1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(2-oxo-7-(trifluoromethyl)-1,6-naphthyridin-1(2H)-yl)acetamide;

N-(4-chloro-3-(1-methyl-1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(5-oxo-2-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-4(5H)-yl)acetamide; and

N-(4-chloro-3-(1-methyl-1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(2-oxo-7-(trifluoromethyl)-1,6-naphthyridin-1(2H)-yl)acetamide,

or a pharmaceutically acceptable salt thereof.

3. The method of claim 1 , wherein the compound according to Formula (I) exhibits an IC 50 <10 μM.

4. The method of claim 3 , wherein the compound according to Formula (I) exhibits an IC 50 <0.1 μM.

5. A method of treating Alzheimer's disease, diffuse Lewy body type of Alzheimer's disease, or mild cognitive impairment (MCI), the method comprising:

administering to a mammalian subject in need thereof a pharmaceutically effective amount of a compound selected from the group consisting of:

N-(2-(1H-1,2,4-triazol-5-yl)thiophen-3-yl)-2-(naphthalen-1-yl)acetamide;

N-(2-(3-methyl-1H-1,2,4-triazol-5-yl)thiophen-3-yl)-2-(naphthal en-1-yl)acetamide;

2-(4-methoxyphenyl)-N-(2-(3-methyl-1H-1,2,4-triazol-5-yl)thiophen-3-yl)acetamide;

2-(4-methoxyphenyl)-N-(4-methyl-3-(3-methyl-1H-1,2,4-triazol-5-yl)thiophen-2-yl)acetamide;

N-(2-(2H-1,2,3-triazol-2-yl)thiophen-3-yl)-2-(4-methoxyphenyl)acetamide;

N-(2-(3-cyclopropyl-1H-1,2,4-triazol-5-yl)thiophen-3-yl)-2-(4-methoxyphenyl)acetamide;

N-(2-(3-ethyl-1H-1,2,4-triazol-5-yl)thiophen-3-yl)-2-(4-methoxyphenyl)acetamide;

N-(2-(3-tert-butyl-1H-1,2,4-triazol-5-yl)thiophen-3-yl)-2-(4-methoxyphenyl)acetamide;

2-(4-methoxyphenyl)-N-(2(3-(tetrahydrofuran-2-yl)-1H-1,2,4-triazol-5-yl)thiophen-3-yl)acetamide;

N-(4-methyl-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydroquinolin-1(2H)-yl)acetamide;

N-(4-methyl-3-(3-methyl-1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydroquinolin-1(2H )-yl)acetamide;

N-(2-(3-amino-1H-1,2,4-triazol-5-yl)thiophen-3-yl)-2-(4-methoxyphenyl)acetamide;

N-(4-chloro-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydroquinolin-1-(2H)-yl)acetamide;

N-(3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydroquinolin-1(2H)-yl)acetamide;

N-(4-chloro-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(isoquinolin-5-yl)acetamide;

N-(4-chloro-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(quinolin-5-yl)acetamide;

N-(2-(1H-1,2,4-triazol-5-yl)thiophen-3-yl)-2-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)acetamide;

N-(4-methyl-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(quinolin-5-yl)acetamide 2-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-N-(2-(3-methyl-1H-1,2,4-triazol-5-yl)thiophen-3-yl)acetamide;

N-(2-(1H-1,2,4-triazol-5-yl)thiophen-3-yl)-2-(quinolin-5-yl)acetamide;

N-(4-methyl-3-(3-methyl-1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(quinolin-5-yl)acetamide;

N-(4-methyl-3-(1H-1,2 ,4-triazol-5-yl)thiophen-2-yl)-2-(quinoxalin-5-yl)acetamide;

N-(4-methyl-3-(3-methyl-1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(quinoxalin-5-yl)acetamide;

N-(4-methyl-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(4-(3-(piperidin-1-yl)propoxy)phenyl)acetamide;

N-(4-methyl-3-(3-methyl-1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(4-(3-(piperidin-1-yl)propoxy)phenyl)acetamide;

2-(4-(2-(1H-imidazol-1-yl)ethoxy)phenyl)-N-(4-methyl-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(isoquinolin-5-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(quinolin-5-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydroquinolin-1(2H)-yl)acetamide;

N-(4-cyano-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(isoquinolin-5-yl)acetamide;

N-(4-cyano-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydroquinolin-1(2H)-yl)acetamide;

N-(2-(3-methyl-1H-1,2,4-triazol-5-yl)thiophen-3-yl)-2-(4-(2-oxopyrrolidin-1-yl)phenyl)acetamide;

N-(4-methyl-3-(5-methyl-4H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(4-(pyridin-4-yl)phenyl)acetamide;

N-(4-cyano-3-(4H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(quinolin-5-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-7-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(6-fluoro-2-oxo-3,4-dihydroquinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(7-fluoro-2-oxoquinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(7-chloro-2-oxo-3,4-dihydroquinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(6,7-difluoro-2-oxoquinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(6-fluoro-2-oxoquinolin-1(2H)-yl)acetamide;

2-(isoquinolin-5-yl)-N-(2-(4-methylthiazol-2-yl)thiophen-3-yl)acetamide;

2-(isoquinolin-5-yl)-N-(2-(thiazol-4-yl)thiophen-3-yl)acetamide;

2-(2-oxo-3,4-dihydro-1,6-naphthyridin-1(2H)-yl)-N-(2-(thiazol-4-yl)thiophen-3-yl)acetamide;

2-(2-oxo-3,4-dihydroquinolin-1(2H)-yl)-N-(2-(thiazol-4-yl)thiophen-3-yl)acetamide;

2-(isoquinolin-5-yl)-N-(2-(2-methoxythiazol-4-yl)thiophen-3-yl)acetamide;

N-(2-(2-chlorothiazol-4-yl)thiophen-3-yl)-2-(isoquinolin-5-yl)acetamide;

2-(isoquinolin-5-yl)-N-(2-(thiazol-2-yl)thiophen-3-yl)acetamide;

2-(isoquinolin-5-yl)-N-(2-(5-methylthiazol-2-yl)thiophen-3-yl)acetamide;

2-(4-(3-(piperidin-1-yl)propoxy)phenyl)-N-(2-(thiazol-4-yl)thiophen-3-yl)acetamide;

N-(3-(benzo[d]thiazol-2-yl)-4-methylthiophen-2-yl)-2-(isoquinolin-5-yl)acetamide;

2-(4-methoxyphenyl)-N-(2-(oxazol-2-yl)thiophen-3-yl)acetamide;

2-(isoquinolin-5-yl)-N-(2-(oxazol-2-yl)thiophen-3-yl)acetamide;

2-(4-methoxyphenyl)-N-(3-(5-methyl-1,2,4-oxadiazol-3-yl)thiophen-2-yl)acetamide;

N-(2-(1,3,4-oxadiazol-2-yl)thiophen-3-yl)-2-(naphthalen-1-yl)acetamide;

2-(4-methoxyphenyl)-N-(2-(5-methyl-1,3,4-oxadiazol-2-yl)thiophen-3-yl)acetamide;

N-(2-(5-isopropyl-1,3,4-oxadiazol-2-yl)thiophen-3-yl)-2-(4-methoxyphenyl)acetamide;

N-(2-(5-methyl-1,3,4-oxadiazol-2-yl)thiophen-3-yl)-2-(naphthalen-1-yl)acetamide;

N-(4-methyl-3-(3-methyl-1,2,4-oxadiazol-5-yl)thiophen-2-yl)-2-(naphthalen-1-yl)acetamide;

N-(4-methyl-3-(3-methyl-1,2,4-oxadiazol-5-yl)thiophen-2-yl)-2-(4-(pyridin-4-yl)phenyl)acetamide;

N-(2-(3-methyl-1,2,4-oxadiazol-5-yl)thiophen-3-yl)-2-(naphthalen-1-yl)acetamide;

N-(4-(1H-1,2,4-triazol-5-yl)thiazol-5-yl)-2-(isoquinolin-5-yl)acetamide;

2-(isoquinolin-5-yl)-N-(4-(1-methyl-1H-1,2,4-triazol-5-yl)thiazol-5-yl)acetamide;

2-(2-pyridyl)-3-(1-naphthylacetylamino)thiophene;

N-(2-(1H-pyrazol-3-yl)thiophen-3-yl)-2-(naphthalen-1-yl)acetamide;

N-(2-(5-methyl-1H-pyrazol-3-yl)thiophen-3-yl)-2-(naphthalen-1-yl)acetamide;

N-(3-(2H-tetrazol-5-yl)thiophen-2-yl)-2-(4-methoxyphenyl)-acetamide;

2-(4-methoxyphenyl)-N-(3-(2-methyl-2H-tetrazol-5-yl)thiophen-2-yl)acetamide;

N-(3-(1-(methoxymethyl)-1H-tetrazol-5-yl)thiophen-2-yl)-2-(4-methoxyphenyl)acetamide;

N-(2-(1H-imidazol-4-yl)thiophen-3-yl)-2-(2-oxo-3,4-dihydroquinolin-1(2H)-yl)acetamide;

N-(2-(1H-imidazol-1-yl)thiophen-3-yl)2-(naphthalen-1-yl)acetamide;

2-(4-methoxyphenyl)-N-(2-(pyrazin-2-yl)thiophen-3-yl)acetamide;

2-(isoquinolin-5-yl)-N-(4-(pyrazin-2-yl)thiazol-5-yl)acetamide;

N-(4,4’-bithiazol-5-yl)-2-(isoquinolin-5-yl)acetamide;

2-(7-bromo-2-oxo-3,4-dihydroquinolin-1(2H)-yl)-N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)acetamide;

N-(4-bromo-3-(4H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(quinolin-4-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(8-fluoroisoquinolin-5-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-1,6-naphthyridin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(8-fluoroquinolin-5-yl)acetamide;

N-(4-bromo-3-(4H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(7-(trifluoromethyl)quinolin-5yl)acetamide;

N-(4-bromo-3-(4H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(5-(trifluoromethyl)quinolin-7-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-1,5-naphthyridin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydro-1,6-naphthyridin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydro-1,5-naphthyridin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(6-chloro-2-oxoquinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(5-fluoro-2-oxoquinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(3-fluoroquinolin-8-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethoxy)quinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(4H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(isoquinolin-4-yl)acetamide;

N-(5-chloro-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(3-fluoroquinolin-5-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-7-(trifluoromethoxy)quinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(7-cyano-2-oxoquinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(isoquinolin-8-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(6-cyano-2-oxoquinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(quinolin-8-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-5-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)-3,4-dihydroquinolin-1(2H)-yl)acetamide;

N-(4-cyano-3-(1-methyl-1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(quinolin-5-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(2-(trifluoromethyl)quinolin-7-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(7-fluoroquinolin-5-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(3-(trifluoromethyl)quinolin-5-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(6-fluoroquinolin-5-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(6-fluoroquinolin-7-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(6-ethynyl-2-oxoquinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-7-(trifluoromethyl)-1,6-naphthyridin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(5-oxopyrazolo[1,5-a]pyrimidin-4(5H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(3-(trifluoromethyl)quinolin-8-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(6-methylimidazo[2,1-b]thiazol-3-yl)acetamide;

2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)-N-(2-(thiazol-4-yl)thiophen-3-yl)acetamide;

N-(4-cyano-3-(pyrazin-2-yl)thiophen-2-yl)-2-(quinolin-5-yl)acetamide;

2-(2-oxo-1,6-naphthyridin-1(2H)-yl)-N-(2-(thiazol-4-yl)thiophen-3-yl)acetamide;

N-(4-bromo-3-(4H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(3,3-difluoro-2-oxoindolin-1-yl)acetamide;

2-(benzo[d]thiazol-7-yl)-N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)acetamide;

N-(4-chloro-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-cyano-3-(oxazol-2-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)-1,5-naphthyridin-1(2H)-yl)acetamide;

N-(3-(1,2,4-oxadiazol-3-yl)thiophen-2-yl)-2-(6,7-difluoro-2-oxoquinolin-1(2H)-yl)acetamide ;

N-(4-cyano-3-(thiazol-2-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(5-oxo-2-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-4(5H)-yl)acetamide;

N-(4-cyano-3-(thiazol-4-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(imidazo[1,2-a]pyridin-5-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(7-fluoro-2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide ;

N-(4-bromo-3-(1-methyl-1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydro-1,5-naphthyridin-1(2H)-yl)acetamide;

N-(4-cyano-3-(thiazol-5-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide ;

N-(4-cyano-3-(1H-1,2,3-triazol-1-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(3-(1H-benzo[d][1,2,3]triazol-1-yl)-4-cyanothiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(6-fluoroisoquinolin-5-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(6-fluoroisoquinolin-7-yl)acetamide;

N-(4-cyano-3-(2H-1,2,3-triazol-2-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-chloro-3-(1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydro-1,5-naphthyridin-1(2H)-yl)acetamide;

N-(4-cyano-3-(thiazol-2-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydro-1,5-naphthyridin-1(2H)-yl)acetamide;

N-(4-chloro-3-(1-methyl-1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydro-1,5-naphthyridin-1(2H)-yl)acetamide;

N-(4-chloro-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(5-oxopyrazolo[1,5-a]pyrimidin-4(5H)-yl)acetamide;

N-(4-bromo-3-(oxazol-2-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydro-1,5-naphthyridin-1(2H)-yl)acetamide;

N-(4-bromo-3-(thiazol-2-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydro-1,5-naphthyridin-1(2H)-yl)acetamide;

N-(4-chloro-3-(thiazol-2-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydro-1,5-naphthyridin-1(2H)-yl)acetamide;

N-(3-(benzo[d]thiazol-2-yl)-4-cyanothiophen-2-yl)-2-(2-oxo-3,4-dihydro-1,5-naphthyridin-1(2H)-yl)acetamide;

N-(4-chloro-3-(3-methyl-1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydro-1,5-naphthyridin-1(2H)-yl)acetamide;

N-(4-chloro-3-(1-(3-(dimethylamino)propyl)-1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-chloro-3-(1-(3-(4-methylpiperazin-1-yl)propyl)-1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-chloro-3-(3-ethyl-1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydro-1,5-naphthyridin-1(2H)-yl)acetamide;

N-(4-chloro-3-(1-(2-(dimethylamino)ethyl)-1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-chloro-3-(1H-1,2,4-triazol-3-yl)thiophen-2-yl)-N-(2-(dimethylamino)ethyl)-2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-cyano-3-(1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydro-1,5-naphthyridin-1(2H)-yl)acetamide;

N-(4-chloro-3-(1-methyl-1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(5-oxopyrazolo[1,5-a]pyrimidin-4(5H)-yl)acetamide;

N-(4-chloro-3-(1-(3-morpholinopropyl)-1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-chloro-3-(1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)-N-(3-(pyrrolidin-1-yl)propyl)acetamide;

N-(4-chloro-3-(1-(3-(pyrrolidin-1-yl)propyl)-1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-chloro-3-(1-methyl-1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)-1,5-naphthyridin-1(2H)-yl)acetamide;

N-(4-chloro-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(8-(trifluoromethyl)quinolin-5-yl)acetamide;

N-(4-bromo-3-(2H-1,2,3-triazol-2-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-chloro-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)-1,5-naphthyridin-1(2H)-yl)acetamide;

N-(4-chloro-3-(3-isopropyl-1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydro-1,5-naphthyridin-1(2H)-yl)acetamide;

2-(6-bromo-2-oxoquinolin-1(2H)-yl)-N-(4-bromo-3-(1H-1,2,4-triazol-3-yl)thiophen-2-yl)acetamide;

N-(4-cyano-3-(1-methyl-1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydro-1,5-naphthyridin-1(2H)-yl)acetamide;

2-(6-bromo-2-oxoquinolin-1(2H)-yl)-N-(4-chloro-3-(1H-1,2,4-triazol-3-yl)thiophen-2-yl)acetamide;

N-(4-chloro-3-(1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(6-cyano-2-oxoquinolin-1(2H)-yl)acetamide;

N-(4-chloro-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(5-oxo-2-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-4(5H)-yl)acetamide;

N-(4-chloro-3-(1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(2-oxo-7-(trifluoromethyl)-1,6-naphthyridin-1(2H)-yl)acetamide;

N-(4-chloro-3-(1-methyl-1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(5-oxo-2-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-4(5H)-yl)acetamide; and

N-(4-chloro-3-(1-methyl-1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(2-oxo-7-(trifluoromethyl)-1,6-naphthyridin-1(2H)-yl)acetamide,

or a pharmaceutically acceptable salt thereof.

6. The method of claim 5 , wherein said compound is at least one selected from the group consisting of:

N-(4-methyl-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydroquinolin-1(2H)-yl)acetamide;

N-(4-methyl-3-(3-methyl-1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydroquinolin-1(2H)-yl)acetamide;

N-(4-chloro-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydroquinolin-1-(2H)-yl)acetamide;

N-(4-chloro-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(isoquinolin-5-yl)acetamide;

N-(4-chloro-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(quinolin-5-yl)acetamide;

N-(4-methyl-3-(3-methyl-1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(quinolin-5-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(isoquinolin-5-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(quinolin-5-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydroquinolin-1(2H)-yl)acetamide;

N-(4-cyano-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(isoquinolin-5-yl)acetamide;

N-(4-cyano-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydroquinolin-1(2H)-yl)acetamide;

N-(4-cyano-3-(4H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(quinolin-5-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-7-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(6-fluoro-2-oxo-3,4-dihydroquinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(7-fluoro-2-oxoquinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(7-chloro-2-oxo-3,4-dihydroquinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(6,7-difluoro-2-oxoquinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(6-fluoro-2-oxoquinolin-1(2H)-yl)acetamide;

N-(4,4′-bithiazol-5-yl)-2-(isoquinolin-5-yl)acetamide;

N-(4-bromo-3-(4H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(quinolin-4-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(8-fluoroisoquinolin-5-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-1,6-naphthyridin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(8-fluoroquinolin-5-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-1,5-naphthyridin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydro-1,6-naphthyridin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydro-1,5-naphthyridin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(6-chloro-2-oxoquinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(5-fluoro-2-oxoquinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethoxy)quinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(4H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(isoquinolin-4-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(3-fluoroquinolin-5-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-7-(trifluoromethoxy)quinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(7-cyano-2-oxoquinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(isoquinolin-8-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(6-cyano-2-oxoquinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-5-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)-3,4-dihydroquinolin-1(2H)-yl)acetamide;

N-(4-cyano-3-(1-methyl-1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(quinolin-5-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(7-fluoroquinolin-5-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(3-(trifluoromethyl)quinolin-5-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(6-fluoroquinolin-5-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(6-ethynyl-2-oxoquinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-7-(trifluoromethyl)-1,6-naphthyridin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(5-oxopyrazolo[1,5-a]pyrimidin-4(5H)-yl)acetamide;

2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)-N-(2-(thiazol-4-yl)thiophen-3-yl)acetamide;

N-(4-cyano-3-(pyrazin-2-yl)thiophen-2-yl)-2-(quinolin-5-yl)acetamide;

2-(benzo[d]thiazol-7-yl)-N-(4-bromo-3(1H-1,2,4-triazol-5-yl)thiophen-2-yl)acetamide;

N-(4-chloro-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-cyano-3-(oxazol-2-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)-1,5-naphthyridin-1(2H)-yl)acetamide;

N-(4-cyano-3-(thiazol-2-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(5-oxo-2-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-4(5H)-yl)acetamide;

N-(4-cyano-3-(thiazol-4-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(7-fluoro-2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1-methyl-1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydro-1,5-naphthyridin-1(2H)-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(6-fluoroisoquinolin-5-yl)acetamide;

N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(6-fluoroisoquinolin-7-yl)acetamide;

N-(4-cyano-3-(2H-1,2,3-triazol-2-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-chloro-3-(1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydro-1,5-naphthyridin-1(2H)-yl)acetamide;

N-(4-cyano-3-(thiazol-2-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydro-1,5-naphthyridin-1(2H)-yl)acetamide;

N-(4-chloro-3-(1-methyl-1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydro-1,5-naphthyridin-1(2H)-yl)acetamide;

N-(4-chloro-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(5-oxopyrazolo[1,5-a]pyrimidin-4(5H)-yl)acetamide;

N-(4-bromo-3-(oxazol-2-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydro-1,5-naphthyridin-1(2H)-yl)acetamide;

N-(4-bromo-3-(thiazol-2-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydro-1,5-naphthyridin-1(2H)-yl)acetamide;

N-(4-chloro-3-(thiazol-2-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydro-1,5-naphthyridin-1(2H)-yl)acetamide;

N-(4-chloro-3-(3-methyl-1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydro-1,5-naphthyridin-1(2H)-yl)acetamide;

N-(4-chloro-3-(1-(3-(dimethylamino)propyl)-1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-chloro-3-(1-(3-(4-methylpiperazin-1-yl)propyl)-1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-chloro-3-(3-ethyl-1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydro-1,5-naphthyridin-1(2H)-yl)acetamide;

N-(4-chloro-3-(1-(2-(dimethylamino)ethyl)-1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-cyano-3-(1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydro-1,5-naphthyridin-1(2H)-yl)acetamide;

N-(4-chloro-3-(1-methyl-1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(5-oxopyrazolo[1,5-a]pyrimidin-4(5H)-yl)acetamide;

N-(4-chloro-3-(1-(3-morpholinopropyl)-1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-chloro-3-(1-(3-(pyrrolidin-1-yl)propyl)-1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-chloro-3-(1-methyl-1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)-1,5-naphthyridin-1(2H)-yl)acetamide;

N-(4-bromo-3-(2H-1,2,3-triazol-2-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetamide;

N-(4-chloro-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-6-(trifluoromethyl)-1,5-naphthyridin-1(2H)-yl)acetamide;

2-(6-bromo-2-oxoquinolin-1(2H)-yl)-N-(4-bromo-3-(1H-1,2,4-triazol-3-yl)thiophen-2-yl)acetamide;

N-(4-cyano-3-(1-methyl-1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydro-1,5-naphthyridin-1(2H)-yl)acetamide;

2-(6-bromo-2-oxoquinolin-1(2H)-yl)-N-(4-chloro-3-(1H-1,2,4-triazol-3-yl)thiophen-2-yl)acetamide;

N-(4-chloro-3-(1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(6-cyano-2-oxoquinolin-1(2H)-yl)acetamide;

N-(4-chloro-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(5-oxo-2-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-4(5H)-yl)acetamide;

N-(4-chloro-3-(1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(2-oxo-7-(trifluoromethyl)-1,6-naphthyridin-1(2H)-yl)acetamide;

N-(4-chloro-3-(1-methyl-1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(5-oxo-2-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-4(5H)-yl)acetamide; and

N-(4-chloro-3-(1-methyl-1H-1,2,4-triazol-3-yl)thiophen-2-yl)-2-(2-oxo-7-(trifluoromethyl)-1,6-naphthyridin-1(2H)-yl)acetamide,

or a pharmaceutically acceptable salt thereof.

Assignments (2)
NUNC PRO TUNC ASSIGNMENT Recorded May 21, 2015
From: ELAN PHARMACEUTICALS, INC.
To: ELAN PHARMA INTERNATIONAL LTD.
Reel/Frame 035687/0576 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 21, 2015
From: ELAN PHARMA INTERNATIONAL LTD.
To: IMAGO PHARMACEUTICALS, INC.
Reel/Frame 035687/0629 →
Continuity (4)
Continuation 12701474 · Feb 5, 2010
Provisional Application 61207126 · Feb 6, 2009
Provisional Application 61244390 · Sep 21, 2009
Related Publication 20130072494A1 · Mar 21, 2013