Animal and human anti-trypanosomonal and anti-leishmania agents
AssigneeCelgene Corporation
InventorsStacie S. Canan, Natalie Anne Hawryluk, Michael John Witty
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Abstract
Provided herein are Aminopurine compounds of Formula I: or pharmaceutically acceptable salts, tautomers, isotopologues, or stereoisomers thereof, wherein R1, R2, and R3 are as defined herein, compositions comprising an effective amount of an Aminopurine Compound, and methods for treating or preventing animal and human protozoal infections.
Claims35
A method for the treatment of trypanosomosis, trypanosomiasis, or leishmaniasis, the method comprising administering to a subject having trypanosomosis, trypanosomiasis, or leishmaniasis an effective amount of a compound of formula (I):
- or a pharmaceutically acceptable salt, tautomer, isotopologue, or stereoisomer thereof, wherein:
- R1 is CR1aR1bR1c, wherein each of R1a, R1b and R1c is independently (C1-4)alkyl, or (C1-4)alkyl(OR);
- or R1a and R1b and the carbon to which they are attached form a 3-6 membered cycloalkyl or 3-6 membered heterocyclyl, and R1c is (C1-4)alkyl;
- R2 is cycloalkyl or aryl, substituted with at least one NR2, OR, CN, NRC(O)R, CH2OR, CH2NR2, CH2NRCOR, CH2NRCOOR′, or heterocyclylalkyl;
- R3 is phenyl or pyridyl, optionally substituted with at least one halogen, CN, (C1-2)alkyl, or O(C1-2)alkyl, wherein the alkyl is optionally fluorinated;
- R is H or (C1-4) alkyl;
- and
- R′ is (C1-4)alkyl.
A method for the treatment of trypanosomosis, trypanosomiasis, or leishmaniasis, the method comprising administering to a subject having trypanosomosis, trypanosomiasis, or leishmaniasis an effective amount of a compound, wherein the compound is:
- 9-((1s,4s)-4-(aminomethyl)cyclohexyl)-N8-(3-chlorophenyl)-N2-(tetrahydro-2H-pyran-4-yl)-9H-purine-2,8-diamine,
- 9-((1r,4r)-4-aminocyclohexyl)-N8-(3-chlorophenyl)-N2-cyclopropyl-9H-purine-2,8-diamine,
- 9-((1r,4r)-4-aminocyclohexyl)-N8-(3-chlorophenyl)-N2-(cyclopropylmethyl)-9H-purine-2,8-diamine,
- 9-((1r,4r)-4-aminocyclohexyl)-N8-(3-chlorophenyl)-N2-(2,2,2-trifluoroethyl)-9H-purine-2,8-diamine,
- 9-((1s,4s)-4-(aminomethyl)cyclohexyl)-N8-(3-chlorophenyl)-N2-methyl-N2-(tetrahydro-2H-pyran-4-yl)-9H-purine-2,8-diamine,
- ((1s,4s)-4-(8-(3-chlorophenylamino)-2-(tetrahydro-2H-pyran-4-ylamino)-9H-purin-9-yl)cyclohexyl)methanol,
- 9-((1s,4s)-4-(aminomethyl)cyclohexyl)-N8-(3-chlorophenyl)-N2,N2-dimethyl-9H-purine-2,8-diamine,
- 9-((1s,4s)-4-(aminomethyl)cyclohexyl)-N8-(3-chlorophenyl)-N2-(2,2-dimethyltetrahydro-2H-pyran-4-yl)-9H-purine-2,8-diamine,
- 9-((1s,4s)-4-(aminomethyl)cyclohexyl)-N8-(3-chlorophenyl)-N2-methyl-9H-purine-2,8-diamine,
- 9-((1s,4s)-4-(aminomethyl)cyclohexyl)-N8-(3-chlorophenyl)-N2-(2,2,2-trifluoroethyl)-9H-purine-2,8-diamine,
- 4-(9-((1s,4s)-4-(aminomethyl)cyclohexyl)-8-(3-chlorophenylamino)-9H-purin-2-ylamino)-1-methylcyclohexanol,
- 9-((1s,4s)-4-(aminomethyl)cyclohexyl)-N8-(3-chloro-5-(trifluoromethyl)phenyl)-N2-(tetrahydro-2H-pyran-4-yl)-9H-purine-2,8-diamine,
- 9-((1s,4s)-4-(aminomethyl)cyclohexyl)-N8-(3-chloro-2-fluorophenyl)-N2-(tetrahydro-2H-pyran-4-yl)-9H-purine-2,8-diamine,
- 9-((1s,4s)-4-(aminomethyl)cyclohexyl)-N8-(2-fluoro-5-(trifluoromethyl)phenyl)-N2,N2-dimethyl-9H-purine-2,8-diamine,
- 9-((1s,4s)-4-(aminomethyl)cyclohexyl)-N-(2-fluoro-5-(trifluoromethyl)phenyl)-2-(pyrrolidin-1-yl)-9H-purin-8-amine,
- 9-((1s,4s)-4-(aminomethyl)cyclohexyl)-N8-(2-fluoro-5-(trifluoromethyl)phenyl)-N2-(tetrahydro-2H-pyran-4-yl)-9H-purine-2,8-diamine, or
- 9-((1s,4s)-4-(aminomethyl)cyclohexyl)-N8-(5-chloro-2-fluorophenyl)-N2-(tetrahydro-2H-pyran-4-yl)-9H-purine-2,8-diamine,
- or a pharmaceutically acceptable salt, tautomer, isotopologue, or stereoisomer thereof.
Dependencies are inferred from the claim text.