US 2009/0264433 A1Published application

Compounds, Compositions and Methods Comprising Triazine Derivatives

AssigneeInstitute for OneWorld Health

InventorsMichael Geoffrey Neil Russell, Joanne Peach, Jacqueline Anne Macritchie, Sebastian Bruckner, Kevin James Doyle

Life of this patent

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Abstract

The present invention relates to compositions and methods for treating a disease in an animal, which disease is responsive to inhibiting of functional cystic fibrosis transmembrane conductance regulator (CFTR) polypeptide by administering to a mammal in need thereof an effective amount of a compound defined herein (including those compounds set forth in Table 1 or encompassed by formulas I-II) or compositions thereof, thereby treating the disease. The present invention particularly, relates to a method of treating diarrhea and polycystic kidney disease.

Claims36

Dependent claims

A compound of formula I:

wherein:
Z is O, NR7, S, or absent, wherein R7 is selected from the group consisting of hydrogen, alkyl and substituted alkyl;
R1 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heterocyclic and substituted heterocyclic;
R3 and R4 are each independently halo;
and
R5 is selected from the group consisting of hydrogen and hydroxyl;
R6 is selected from the group consisting of hydrogen, alkyl and substituted alkyl;
and
alk is selected from the group consisting of a direct bond, alkylene and substituted alkylene;
or a pharmaceutically acceptable salt, isomer, or tautomer thereof;
wherein said compound exhibits at least one of the following:
a) an IC50 of less than 30 μM in the T84 assay;
b) a greater than 30% inhibition at 20 μM in the FRT assay;
or
c) a greater than 35% inhibition at 50 μM in a T84 assay, provided that the compound does not have an IC50 greater than 30 μM.

12 more elements

A compound selected from the group consisting of:

2,6-dibromo-4-(3-(2-(naphthalen-1-yl)ethoxy)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-(4-bromophenethoxy)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-(3,4-difluorobenzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-(2,4-difluorobenzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-(5-chloro-2-methoxybenzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-(2-bromobenzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-(3-chlorobenzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-(naphthalen-2-ylmethoxy)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-(2-chloro-4-fluorobenzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-(2,4-dichlorophenethoxy)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-(1-(4-chlorophenyl)ethoxy)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-(1-(3-chlorophenyl)ethoxy)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-(naphthalen-1-ylmethoxy)-1,2,4-triazin-6-yl)phenol;
4-(3-(biphenyl-4-ylmethoxy)-1,2,4-triazin-6-yl)-2,6-dibromophenol;
2,6-dibromo-4-(3-(2,4-dichlorobenzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-(4-(trifluoromethyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-(3-(dimethylamino)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-(2-chlorobenzyloxy)-1,2,4-triazin-6-yl)phenol;
4-(3-(benzyloxy)-1,2,4-triazin-6-yl)-2,6-dibromophenol;
2,6-dibromo-4-(3-(4-chlorobenzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-(3,4-dichlorophenoxy)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-(2,4,6-trichlorobenzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-(2,3-dichlorobenzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-(4-bromobenzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-(3-bromobenzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-(3,5-dichlorobenzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-(3-phenoxybenzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-(4-(trifluoromethoxy)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-(4-chloro-2-methylbenzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-((2,3-dichlorophenoxy)methyl)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-(hydroxydiphenylmethyl)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-((naphthalen-1-yloxy)methyl)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-((2-chloro-5-methylphenoxy)methyl)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-((4-(2-phenylpropan-2-yl)phenoxy)methyl)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(hydroxydiphenylmethyl)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-((2,3-dichlorophenoxy)methyl)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-((4-chloro-2-methylphenoxy)methyl)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-((4-chloro-2-methylphenoxy)methyl)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-((7-methyl-2,3-dihydro-1H-inden-4-yloxy)methyl)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-((2,4-dichlorophenoxy)methyl)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-((2,5-dichlorophenoxy)methyl)-1,2,4-triazin-6-yl)phenol;
4-(3-((2-allylphenoxy)methyl)-1,2,4-triazin-6-yl)-2,6-dibromophenol;
2,6-dibromo-4-(3-((7-methyl-2,3-dihydro-1H-inden-4-yloxy)methyl)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-((5-bromo-7-methyl-2,3-dihydro-1H-inden-4-yloxy)methyl)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-((4-chloro-3,5-dimethyl phenoxy)methyl)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-((2,3-dihydro-1H-inden-5-yloxy)methyl)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-((4-bromophenoxy)methyl)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-((2,2-dimethyl-2,3-dihydrobenzofuran-7-yloxy)methyl)-1,2,4-triazin-6-yl)phenol;
4-(3-((4-(1,3-dithiolan-2-yl)phenoxy)methyl)-1,2,4-triazin-6-yl)-2,6-dibromophenol;
2,6-dibromo-4-(3-((2,5-dimethylphenoxy)methyl)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-((5-isopropyl-2-methylphenoxy)methyl)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-((4-bromo-3,5-dimethylphenoxy)methyl)-1,2,4-triazin-6-yl)phenol;
4-(3-((biphenyl-4-yloxy)methyl)-1,2,4-triazin-6-yl)-2,6-dibromophenol;
2,6-dibromo-4-(3-((2,4-difluorophenoxy)methyl)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-((2-isopropyl-5-methylphenoxy)methyl)-1,2,4-triazin-6-yl)phenol;
4-(3-(3-(benzyloxy)benzyloxy)-1,2,4-triazin-6-yl)-2,6-dibromophenol;
2,6-dibromo-4-(3-(4-chlorophenethoxy)-1,2,4-triazin-6-yl)phenol;
4-(3-(9H-xanthen-9-yloxy)-1,2,4-triazin-6-yl)-2,6-dibromophenol;
tert-butyl 4-(5-chloro-2-((6-(3,5-dibromo-4-hydroxyphenyl)-1,2,4-triazin-3-yl)methoxy)benzyl)piperazine-1-carboxylate;
2,6-dibromo-4-(3-(4-tert-butylphenethoxy)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-(2-chlorophenethoxy)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-(3-(4-chlorophenyl)propoxy)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-phenethoxy-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-(4-methoxyphenethoxy)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-(4-methylphenethoxy)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-(3,4-dichlorophenethoxy)-1,2,4-triazin-6-yl)phenol;
4-(3-(bis(4-chlorophenyl)(hydroxy)methyl)-1,2,4-triazin-6-yl)-2,6-dibromophenol;
4-((6-(3,5-dibromo-4-hydroxyphenyl)-1,2,4-triazin-3-yloxy)methyl)benzonitrile;
2,6-dibromo-4-(3-(pyridin-2-ylmethoxy)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-(pyridin-4-ylmethoxy)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-((4-bromothiophen-2-yl)methoxy)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-(1,2,3,4-tetrahydronaphthalen-2-yloxy)-1,2,4-triazin-6-yl)phenol;
4-(3-(bis(3-(trifluoromethyl)phenyl)methoxy)-1,2,4-triazin-6-yl)-2,6-dibromophenol;
2,6-dibromo-4-(3-(4-(morpholinomethyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(1,2-diphenylethoxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(4-chlorophenethoxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(4-chlorobenzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(2,3-dichlorobenzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(2-(naphthalen-1-yl)ethoxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(naphthalen-1-ylmethoxy)-1,2,4-triazin-6-yl)phenol;
4-(3-(4-bromophenethoxy)-1,2,4-triazin-6-yl)-2,6-dichlorophenol;
2,6-dibromo-4-(3-((2-bromothiazol-5-yl)methoxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(3-(dimethylamino)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(2,3-dichlorobenzylamino)-1,2,4-triazin-6-yl)phenol;
4-(3-(2-(benzylamino)ethoxy)-1,2,4-triazin-6-yl)-2,6-dichlorophenol;
2,6-dichloro-4-(3-(2-(phenylamino)ethoxy)-1,2,4-triazin-6-yl)phenol;
(4-(5-chloro-2-((6-(3,5-dibromo-4-hydroxyphenyl)-1,2,4-triazin-3-yl)methoxy)benzyl)piperazin-1-yl)(3-(trifluoromethyl)phenyl)methanone;
and
2,6-dichloro-4-(3-(2-fluorobenzyloxy)-1,2,4-triazin-6-yl)phenol;
or a pharmaceutically acceptable salt, isomer, or tautomer thereof.

87 more elements

A compound selected from the group consisting of:

2,6-dibromo-4-(3-((2,2-dimethyl-2,3-dihydrobenzofuran-7-yloxy)methyl)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-(3-phenoxyphenyl)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-(naphthalen-1-ylmethyl)-1,2,4-triazin-6-yl)phenol;
2,6-dibromo-4-(3-((2-nitrophenylthio)methyl)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(4-methoxybenzylamino)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(3,4-dichlorobenzylamino)-1,2,4-triazin-6-yl)phenol, formate salt;
2,6-dichloro-4-(3-(2,4-dichlorobenzylamino)-1,2,4-triazin-6-yl)phenol, formate salt;
2,6-dichloro-4-(3-(4-chlorobenzylamino)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(4-(4-dioxothiomorphilinomethyl)benzylamino)-1,2,4-triazin-6-yl)phenol, formate salt;
2,6-dichloro-4-(3-(4-(4-methylpiperazin-1-yl)benzylamino)-1,2,4-triazin-6-yl)phenol, formate salt;
4-(3-(2-(benzyl(methyl)amino)ethoxy)-1,2,4-triazin-6-yl)-2,6-dichlorophenol;
tert-butyl 4-((6-(3,5-dichloro-4-hydroxyphenyl)-1,2,4-triazin-3-yloxy)methyl)-4-phenylpiperidine-1-carboxylate;
2,6-dichloro-4-(3-(2-(dimethylamino)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(4-((2,3-dichlorobenzylamino)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
4-((6-(3,5-dichloro-4-hydroxyphenyl)-1,2,4-triazin-3-yloxy)methyl)benzaldehyde;
2,6-dichloro-4-(3-(4-((4-phenylpiperazin-1-yl)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2-(4-(4-((6-(3,5-dichloro-4-hydroxyphenyl)-1,2,4-triazin-3-yloxy)methyl)benzyl)piperazin-1-yl)benzic acid;
tert-butyl 4-(4-((6-(3,5-dichloro-4-hydroxyphenyl)-1,2,4-triazin-3-yloxy)methyl)benzyl)piperazine-1-carboxylate, ammonium salt;
2,6-dichloro-4-(3-(4-fluorobenzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(3,4-difluorobenzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(2,4-difluorobenzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(4-((naphthalen-1-ylmethylamino)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(4-((4-(2,4-dichlorophenyl)piperazin-1-yl)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(4-((4-(2,4-difluorophenyl)piperazin-1-yl)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(4-((4-phenethylpiperazin-1-yl)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(3-(trifluoromethoxy)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(4-(trifluoromethoxy)benzyloxy)-1,2,4-triazin-6-yl)phenol;
1-(4-(4-((6-(3,5-dichloro-4-hydroxyphenyl)-1,2,4-triazin-3-yloxy)methyl)benzyl)piperazin-1-yl)-2-phenoxyethanone;
2,6-dichloro-4-(3-(4-((pyridin-4-ylmethylamino)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(4-((2-morpholino-1-phenylethylamino)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(4-((4-(pyridin-3-ylmethyl)piperazin-1-yl)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
4-(3-(4-((benzyl(2-hydroxyethyl)amino)methyl)benzyloxy)-1,2,4-triazin-6-yl)-2,6-dichlorophenol;
2,6-dichloro-4-(3-((2-hydroxyethyl)(pyridin-3-ylmethyl)amino)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(4-(((2-hydroxy-2-phenylethyl)(methyl)amino)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol, formate salt;
2,6-dichloro-4-(3-(4-(isoindolin-2-ylmethyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
4-(3-(4-((benzyl(methyl)amino)methyl)benzyloxy)-1,2,4-triazin-6-yl)-2,6-dichlorophenol;
2,6-dichloro-4-(3-(4-((4-fluorobenzylamino)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(4-(((4-fluorobenzyl)(methyl)amino)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(dihydroisoquinolin-2(1H)-yl)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(4-((dibenzylamino)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
4-(3-(4-((4-benzylpiperidin-1-yl)methyl)benzyloxy)-1,2,4-triazin-6-yl)-2,6-dichlorophenol;
2,6-dichloro-4-(3-(4-(((6-(trifluoromethyl)pyridin-3-yl)methylamino)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
4-(3-(4-((((5-bromopyridin-3-yl)methyl)(methyl)amino)methyl)benzyloxy)-1,2,4-triazin-6-yl)-2,6-dichlorophenol;
4-(3-(4-((benzhydryl(methyl)amino)methyl)benzyloxy)-1,2,4-triazin-6-yl)-2,6-dichlorophenol;
2,6-dichloro-4-(3-(4-(((2-chlorobenzyl)(2-hydroxyethyl)amino)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
1-(4-((6-(3,5-dichloro-4-hydroxyphenyl)-1,2,4-triazin-3-yloxy)methyl)benzyl)-4-phenylpiperidin-4-ol;
2,6-dichloro-4-(3-(4-((4-(hydroxydiphenylmethyl)piperidin-1-yl)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol, formate salt;
2,6-dichloro-4-(3-(4-((methyl(pyridin-4-ylmethyl)amino)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(4-((methyl(4-(pyridin-2-yloxy)benzyl)amino)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(4-((methyl(3-(pyridin-4-yl)benzyl)amino)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(4-((5-fluoroisoindolin-2-yl)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(4-fluorophenethoxy)-1,2,4-triazin-6-yl)phenol;
4-(3-(bromo-3,4-dihydroisoquinolin-2(1H)-yl)methyl)benzyloxy)-1,2,4-triazin-6-yl)-2,6-dichlorophenol;
2,6-dichloro-4-(3-(4-((methyl(naphthalen-1-ylmethyl)amino)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(dihydroquinolin-1(2H)-yl)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(4-(((2,3-dichlorobenzyl)(methyl)amino)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(4-(((3,4-difluorobenzyl)(methyl)amino)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2-(4-((6-(3,5-dichloro-4-hydroxyphenyl)-1,2,4-triazin-3-yloxy)methyl)benzyl)-N-methyl-1,2,3,4-tetrahydroisoquinoline-3-carboxamide;
2,6-dichloro-4-(3-(4-((methyl(3-(pyridin-2-yloxy)benzyl)amino)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(4-((methyl(4-(pyridin-4-yl)benzyl)amino)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
1-(4-(4-((6-(3,5-dichloro-4-hydroxyphenyl)-1,2,4-triazin-3-yloxy)methyl)benzyl)piperazin-1-yl)-2,2-dimethylpropan-1-one;
2,6-dichloro-4-(3-(4-((methyl(quinolin-6-ylmethyl)amino)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(4-((2-(diethylamino)-1-phenylethylamino)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(4-(((2-hydroxyethyl)(pyridin-3-ylmethyl)amino)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
4-(3-(4-((benzyl(ethyl)amino)methyl)benzyloxy)-1,2,4-triazin-6-yl)-2,6-dichlorophenol;
2,6-dichloro-4-(3-(pyridin-4-yl)-3,4-dihydroisoquinolin-2(1H)-yl)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(4-((1-phenyl-2-(pyrrolidin-1-yl)ethylamino)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(4-((2-(4-methylpiperazin-1-yl)-1-phenylethylamino)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(4-((methyl(2-morpholino-1-phenylethyl)amino)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(4-((methyl(4-(pyridin-2-yl)benzyl)amino)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(4-(((4-(2-(dimethylamino)ethoxy)benzyl)(methyl)amino)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(4-(((4-(3-(dimethylamino)propoxy)benzyl)(methyl)amino)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(4-((methyl(3-(morpholinomethyl)benzyl)amino)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(4-((methyl(4-((4-methyl-1,4-diazepan-1-yl)methyl)benzyl)amino)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(4-((methyl(4-(pyrimidin-2-yl)benzyl)amino)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(4-((methyl(3-(6-methylpyrazin-2-yloxy)benzyl)amino)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(4-(((3-(3-(dimethylamino)propoxy)benzyl)(methyl)amino)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(4-((methyl(3-(pyrimidin-2-yl)benzyl)amino)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(4-((methyl(3-(pyrimidin-5-yl)benzyl)amino)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(4-((methyl(4-(pyrimidin-5-yl)benzyl)amino)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(4-((methyl(4-(piperidin-1-ylmethyl)benzyl)amino)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol, formate salt;
2,6-dichloro-4-(3-(4-((methyl(4-(6-methylpyrazin-2-yloxy)benzyl)amino)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(4-((methyl(4-(5-(trifluoromethyl)pyridin-2-yl)benzyl)amino)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(4-((methyl(4-(pyrrolidin-1-ylmethyl)benzyl)amino)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol, diformate salt;
2,6-dichloro-4-(3-(4-((methyl(3-(pyrrolidin-1-ylmethyl)benzyl)amino)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol, formate salt;
2,6-dichloro-4-(3-(4-((methyl(3-(pyridin-3-yl)benzyl)amino)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(4-((methyl(4-(2-morpholinoethoxy)benzyl)amino)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(4-(((2,3-dichlorobenzyl)(2-hydroxyethyl)amino)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
1-(4-(4-((6-(3,5-dichloro-4-hydroxyphenyl)-1,2,4-triazin-3-yloxy)methyl)benzyl)piperazin-1-yl)ethanone;
(4-(4-((6-(3,5-dichloro-4-hydroxyphenyl)-1,2,4-triazin-3-yloxy)methyl)benzyl)piperazin-1-yl)(furan-2-yl)methanone;
(4-(4-((6-(3,5-dichloro-4-hydroxyphenyl)-1,2,4-triazin-3-yloxy)methyl)benzyl)piperazin-1-yl)(phenyl)methanone;
cyclopropyl(4-(4-((6-(3,5-dichloro-4-hydroxyphenyl)-1,2,4-triazin-3-yloxy)methyl)benzyl)piperazin-1-yl)methanone;
(2-chlorophenyl)(4-(4-((6-(3,5-dichloro-4-hydroxyphenyl)-1,2,4-triazin-3-yloxy)methyl)benzyl)piperazin-1-yl)methanone;
1-(4-(4-((6-(3,5-dichloro-4-hydroxyphenyl)-1,2,4-triazin-3-yloxy)methyl)benzyl)piperazin-1-yl)propan-1-one;
2,6-dichloro-4-(3-(4-((methyl(pyridin-3-ylmethyl)amino)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
2,6-dichloro-4-(3-(4-(((3-(2-chlorobenzyloxy)benzyl)(2-hydroxyethyl)amino)methyl)benzyloxy)-1,2,4-triazin-6-yl)phenol;
(4-(4-((6-(3,5-dichloro-4-hydroxyphenyl)-1,2,4-triazin-3-yloxy)methyl)benzyl)piperazin-1-yl)(pyridin-3-yl)methanone;
and
1-(4-(4-((6-(3,5-dichloro-4-hydroxyphenyl)-1,2,4-triazin-3-yloxy)methyl)benzyl)piperazin-1-yl)-2-(4-methylthiazol-2-yl)ethanone;
or a pharmaceutically acceptable salt, isomer, or tautomer thereof.

97 more elements

Dependencies are inferred from the claim text.

Facts

Application: 12/426,498Filed 20 Apr 2009
Priority: 21 Apr 2008
Published: 22 Oct 2009
Term ends: Not estimatedThe source records don’t support an estimate.

Classification8 codes

C07D 253/065
1,2,4-Triazines: having three double bonds between ring members or between ring members and non-ring members
A61P 1/12
Drugs for disorders of the alimentary tract or the digestive system: antidiarrhoeals
C07D 253/07
Having three double bonds between ring members or between ring members and non-ring members: with hetero atoms, or with carbon atoms having three…
C07D 405/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links

Family

Application61/046,783Us provisional application · filed 21 Apr 2008
Application61/098,539Us provisional application · filed 19 Sep 2008
US 2009/0264433 A1This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

Facts

Application

12/426,498Filed 20 Apr 2009

Priority

21 Apr 2008

Published

22 Oct 2009

Term ends

Not estimatedThe source records don’t support an estimate.

Classification8 codes

C07D 253/065
1,2,4-Triazines: having three double bonds between ring members or between ring members and non-ring members
A61P 1/12
Drugs for disorders of the alimentary tract or the digestive system: antidiarrhoeals
C07D 253/07
Having three double bonds between ring members or between ring members and non-ring members: with hetero atoms, or with carbon atoms having three…
C07D 405/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links