US 11,753,408 B2
Compounds and method for blocking transmission of malarial parasite
Wenwei Huang, Rockville, MD (US); Hao Li, Rockville, MD (US); Wei Sun, Germantown, MD (US); Xiuli Huang, Potomac, MD (US); Paresma R. Patel, Rockville, MD (US); Hangmao Sun, Germantown, MD (US); Wei Zheng, Potomac, MD (US); Xiao Lu, Rockville, MD (US); Philip E. Sanderson, Bethesda, MD (US); Myunghoon Kim, Olympia, WA (US); Meghan J. Orr, Nashville, IL (US); Gregory J. Tawa, Doylestown, PA (US); and Kim C. Williamson, Bethesda, MD (US)
Assigned to The United States of America, as represented by the Secretary, Department of Health and Human Services, Bethesda, MD (US); and Loyola University of Chicago, Chicago, IL (US)
Filed by The United States of America, as represented by the Secretary, Department of Health and Human Services, Bethesda, MD (US); and Loyola University of Chicago, Chicago, IL (US)
Filed on Apr. 22, 2021, as Appl. No. 17/237,351.
Application 17/237,351 is a continuation of application No. 16/341,000, granted, now 10,988,472, previously published as PCT/US2017/056619, filed on Oct. 13, 2017.
Claims priority of provisional application 62/407,861, filed on Oct. 13, 2016.
Prior Publication US 2021/0246137 A1, Aug. 12, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 471/14 (2006.01); A61K 31/4375 (2006.01); C07D 471/04 (2006.01); A61P 33/06 (2006.01); C07D 487/04 (2006.01); C07D 487/08 (2006.01); C07D 519/00 (2006.01)
CPC C07D 471/04 (2013.01) [A61P 33/06 (2018.01); C07D 487/04 (2013.01); C07D 487/08 (2013.01); C07D 519/00 (2013.01)] 8 Claims
 
1. A compound of formula (I):

OG Complex Work Unit Chemistry
wherein A is CR5 or N,
B is CR3═CR4,
R1 is C6-10 aryl or heteroaryl substituted with at least one substituent selected from —CN, cyanomethyl, —SO2R13, —SO2NHR15, and —CONR11R12, optionally further in combination with one or more substituents selected from halo, C1-12 alkyl, alkoxy, a heterocyclyl group selected from the group consisting of optionally substituted piperazinyl, morpholinyl, pyrrolinidyl, and diazepinyl, or an aryl bicyclic lactam of the formula:

OG Complex Work Unit Chemistry
wherein the aryl group of the aryl bicyclic lactam is optionally substituted with at least one substituent selected from —CN, cyanomethyl, —SO2R13, —SO2NH2, and —CONR11R12, optionally further in combination with one or more substituents selected from halo, C1-12 alkyl, alkoxy, 2-(dimethylamino)ethyl)amino, dimethylamino, a heterocyclyl group selected from the group consisting of optionally substituted piperazinyl, morpholinyl, pyrrolinidyl, azetidinyl, and diazepinyl,
R2 is selected from 4-pyridinyl, 2-amino-5-pyrimidinyl, 3-pyridyl, quinolin-3-yl, 5-pyrimidinyl, 2-acetylamino-5-pyridyl, 2-amino-4-methylpyrimidin-5-yl, 1-piperazinyl, indol-5-yl, 1H-imidazol-5-yl, 4-aminophenyl, 1,2,3,6-tetrahydropyridin yl, 1H-pyrazol-4-yl, N-methyl-pyrazol-4-yl, 1H-benzo[d]imidazol-5-yl, 4-sulfonylaminophenyl, 2-dimethylaminopyrimidin-5-yl, 3-trifluoromethylphenyl, bromo, 3-aminophenyl, vinyl, 4-aminocarbonylphenyl, 3-cyanophenyl, 3-hydroxyphenyl, 3-trifluoromethyl-5-pyridyl, tetrazolyl, 4-chlorophenyl, 4-fluorophenyl, 4-methoxyphenyl, 3-aminocarbonylphenyl, 3-acetylphenyl, 3-cyano-4-chlorophenyl, 3-cyano-5-methylphenyl, 3-hydroxy-4-chlorophenyl, 4-hydroxymethylphenyl, 3-amino-4-chlorophenyl, 2,3-dihydrobenzofuran-6-yl, 1-methyl-1H-indol-5-yl, benzo[d][1,3]dioxo-5-yl, 4-fluorophenyl, 4-hydroxyphenyl, morpholin-1-yl, benzo[b]thiophen-1-yl, 4-methyl sulfonylphenyl, benzo[c][1,2,5]oxadiazol-5-yl, 2-(piperidin-1-yl)-3-pyridinyl, 4-carboxyphenyl, 2-methyl-5-pyridyl, 4-methyl sulfonylphenyl, 4-dimethylaminocarbonylphenyl, 4-phenylphenyl, 4-methylphenyl, 3-chloro-5-pyridyl, (3-pyrrolidin-1-yl)phenyl, 4-([piperizin-1-yl]carbonyl)phenyl, 4-([morpholin-1-yl]carbonyl)phenyl, 2-hydroxypyrimidin-5-yl, 3-aminosulfonylphenyl, 2-oxo-1,2,3,4,tetrahydroisoquinolin-6-yl, 2-oxo-1,2,3,4,-tetrahydroquinolin-6-yl, 4-(methylaminocarbonyl)phenyl, 1-oxoindolin-5-yl, 2-oxoindolin-5-yl, 1-oxoisoindolin-5-yl, 2-amino-4-pyridyl, 4-aminomethylphenyl, 3-methoxy-4-chlorophenyl, 3-methylphenyl, 3-methoxyphenyl, phenyl, 5-indolinone, 5-isoindolinone, 2-hydroxy-4-chlorophenyl, 4-cyanophenyl, 4-azetidinylphenyl, 4-ethylphenyl, 3-fluorophenyl, 3-chlorophenyl, 3-dimethylaminomethylphenyl, 3-cyano-4-fluorophenyl, 3-amino-4-fluorophenyl, 4-(1-hydroxy-1-ethylphenyl, 3-methyl-5-pyridyl, 2-acetylamio-5-pyridyl, 2-oxoindolin-5-yl, benzimidazolin-5-yl, 3-dimethylamino-1-propargyl, 2-pyrrolyl, N-methyl-2-pyrrolyl, 2-thiopheneyl, 3-thiopheneyl, 3-furanyl, and 3-aminosulfonylphenyl,
R3 and R4 are independently selected from hydrogen, hydroxyl, OR5, halogen, optionally substituted C6-10 aryl, and optionally substituted C1-6 alkyl,
R5 is hydrogen, C1-12 alkyl, C6-10 aryl, halogen, hydroxyl, or OR16
R7-R10 are independently selected from hydrogen, C1-12 alkyl, C3-8 cycloalkyl, CH2COOR13, and H2N(CH2)n— wherein n is an integer of 2-6,
R11 and R12 selected from the group consisting of hydrogen, C1-12 alkyl and C3-10 cycloalkyl or, taken together with the N to which they are bound, form an optionally substituted 4-7 membered heterocyclyl ring containing O or N atoms, and
R13 is C1-12 alkyl,
R15 is hydrogen or C1-12 alkyl, and
R16 is C1-12 alkyl, C1-6 acyl, or C6-10 aryl,
or a pharmaceutically acceptable salt thereof.