US 11,964,944 B2
Compounds and methods for treating, detecting, and identifying compounds to treat apicomplexan parasitic diseases
Rima McLeod, Chicago, IL (US); Martin McPhillie, Leeds (GB); Colin W. G. Fishwick, Leeds (GB); Hernan Alejandro Lorenzi, Rockville, MD (US); Kai Wang, Seattle, WA (US); Taek-Kyun Kim, Seattle, WA (US); Yong Zhou, Seattle, WA (US); Leroy E. Hood, Seattle, WA (US); Ying Zhou, Chicago, IL (US); Kamal El Bissati, Chicago, IL (US); Mark Hickman, Silver Spring, MD (US); QiGui Li, Silver Spring, MD (US); and Craig Roberts, Glasgow (GB)
Assigned to The University of Chicago, Chicago, IL (US); J. Craig Venter Institute, Inc., Ajolla, CA (US); The University of Sheffield, (GB); Institute for Systems Biology, Seattle, WA (US); The University of Leeds, (GB); The University of Strathclyde, (GB); and The Government of the United States, Fort Detrick, MD (US)
Filed by The University of Chicago, Chicago, IL (US); University of Leeds, Leeds (GB); The J. Craig Venter Institute, Rockville, MD (US); Institute For Systems Biology, Seattle, WA (US); U.S. Government, as represented by The Secretary of The Army Medical Command (MEDCOM), Fort Detrick, MD (US); and The University of Strathclyde, Glasgow (GB)
Filed on Jun. 2, 2022, as Appl. No. 17/831,049.
Application 17/831,049 is a division of application No. 16/063,877, granted, now 11,414,385, previously published as PCT/US2016/067795, filed on Dec. 20, 2016.
Claims priority of provisional application 62/306,385, filed on Mar. 10, 2016.
Claims priority of provisional application 62/270,264, filed on Dec. 21, 2015.
Prior Publication US 2023/0140413 A1, May 4, 2023
Int. Cl. C07D 215/233 (2006.01); A61P 33/06 (2006.01); C07D 401/12 (2006.01); C07D 405/12 (2006.01); C07D 471/04 (2006.01); C07D 487/04 (2006.01)
CPC C07D 215/233 (2013.01) [A61P 33/06 (2018.01); C07D 401/12 (2013.01); C07D 405/12 (2013.01); C07D 471/04 (2013.01); C07D 487/04 (2013.01)] 17 Claims
 
1. A compound of the structure of
(a) Formula (I):

OG Complex Work Unit Chemistry
or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof,
wherein
ring A combines with Y1 and Y2 to form a C3-7cycloalkenyl or heteroaryl ring,
wherein the C3-7cycloalkenyl or heteroaryl is optionally substituted by halogen, C1-3alkyl, C1-3alkoxy, C1-3haloalkyl, —O—C1-3haloalkyl, —S—C1-3haloalkyl, —C(O)OR, cyano or phenyl;
Y1 is N;
Y2 is C or N;
X1 is C(Rx1) or N,
wherein Rx1 is hydrogen, halogen, C1-3alkyl, C1-3alkoxy or C1-3haloalkyl;
X2 is C(Rx2) or N,
wherein Rx2 is hydrogen, halogen, C1-3alkyl, C1-3alkoxy or C1-3haloalkyl;
X3 is O, N(R), S or C1-3alkyl;
X4 is C or N;
X5 is C or N;
R1 is hydrogen or C1-3alkyl;
R2 is hydrogen, C1-3alkyl, C1-3haloalkyl, —CH2OH, —CH2OR or —C(O)OR;
n is 0, 1, 2, 3 or 4;
each R3 is independently halogen, C1-3alkyl, C1-3alkoxy, C1-3haloalkyl, —O—C1-3haloalkyl, —S—C1-3haloalkyl, —C(O)OR or SF5;
or two R3 groups, together with the carbons to which they are attached, form a 1,3-dioxolane; and
each R is independently hydrogen or C1-3alkyl; or
(b) Formula (I-p):

OG Complex Work Unit Chemistry
or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof,
wherein
ring A combines with Y1 and Y2 to form a C3-7cycloalkenyl or heteroaryl ring, wherein the C3-7cycloalkenyl or heteroaryl is optionally substituted by halogen, C1-3alkyl, C1-3alkoxy, C1-3haloalkyl, —O—C1-3haloalkyl, —S—C1-3haloalkyl, —C(O)OR, cyano or phenyl;
Y1 is N;
Y2 is C or N;
X1 is C(Rx1) or N,
wherein Rx1 is hydrogen, halogen, C1-3alkyl, C1-3alkoxy or C1-3haloalkyl;
X2 is C(Rx2) or N,
wherein Rx2 is hydrogen, halogen, C1-3alkyl, C1-3alkoxy or C1-3haloalkyl;
X3 is O, N(R), S or C1-3alkyl;
X5 is C or N;
P is —C(O)OR′, —C(O)R′, —C(O)NR′2, wherein R′ is hydrogen, C1-3alkyl or —CH2OR;
R2 is hydrogen, C1-3alkyl, C1-3haloalkyl, —CH2OH, —CH2OR, —C(O)OR or —CH2OP;
P is —C(O)OR′, —C(O)R′, —C(O)NR′2 or —OP(O)(OR′)OR′, wherein each R′ is independently hydrogen or C1-3alkyl;
n is 0, 1, 2, 3 or 4;
each R3 is independently halogen, C1-3alkyl, C1-3alkoxy, C1-3haloalkyl, —O—C1-3haloalkyl, —S—C1-3haloalkyl, —C(O)OR or SF5;
or two R3 groups, together with the carbons to which they are attached, form a 1,3-dioxolane; and
each R is independently hydrogen or C1-3alkyl.
 
14. A compound that is:
 
Structure Name
 
 

OG Complex Work Unit Chemistry
 5-methyl-6-(4-(4- (trifluoromethoxy)phenoxy)phenyl)- [1,2,4]triazolo[1,5-a] pyrimidin-7(4H)-one
 
 

OG Complex Work Unit Chemistry
 5-methyl-6-(4-(4- (trifluoromethoxy)phenoxy) phenyl)pyrazolo[1,5-a] pyrimidin-7(4H)-one
 
 

OG Complex Work Unit Chemistry
 2,5-dimethyl-6-(4-(4- (trifluoromethoxy)phenoxy) phenyl)pyrazolo[1,5-a] pyrimidin-7(4H)-one
 
 

OG Complex Work Unit Chemistry
 5-methyl-2-(methylthio)-6- (4-(4- (trifluoromethoxy)phenoxy) phenyl)- [l,2,4]triazolo[l,5-a] pyrimidin-7(4H)-one
 
 

OG Complex Work Unit Chemistry
 5-methyl-7-oxo-6-(4-(4- (trifluoromethoxy)phenoxy) phenyl)-4,7- dihydropyrazolo[l,5-a] pyrimidine-3-carbonitrile
 
 

OG Complex Work Unit Chemistry
 5-methyl-2-phenyl-6-(4-(4- (trifluoromethoxy)phenoxy) phenyl)pyrazolo[1,5-a] pyrimidin-7(4H)-one
 
5-methyl-6-(4-(4-(trifluoromethoxy)phenoxy)phenyl)-[1,2,4]triazolo[1,5-a]pyrimidin-7(4H)-one;
5-methyl-6-(4-(4-(trifluoromethoxy)phenoxy)phenyl)pyrazolo[1,5-a]pyrimidin-7(4H)-one;
2,5-dimethyl-6-(4-(4-(trifluoromethoxy)phenoxy)phenyl)pyrazolo[1,5-a]pyrimidin-7(4H)-one;
5-methyl-2-(methylthio)-6-(4-(4-(trifluoromethoxy)phenoxy)phenyl)-[1,2,4]triazolo [1,5-a]pyrimidin-7(4H)-one;
5-methyl-7-oxo-6-(4-(4-(trifluoromethoxy)phenoxy)phenyl)-4,7-dihydropyrazolo[1,5-a]pyrimidine-3-carbonitrile;
5-methyl-2-phenyl-6-(4-(4-(trifluoromethoxy)phenoxy)phenyl)pyrazolo[1,5-a]pyrimidin-7(4H)-one;
or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.