Claims for Patent: 7,094,781

Summary for Patent: 7,094,781

Title:	Sulfamides and their use as endothelin receptor antagonists
Abstract:	The invention relates to novel sulfamides and their use as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of the compounds, pharmaceutical compositions containing one or more of those compounds and especially their use as endothelin receptor antagonists.
Inventor(s):	Bolli; Martin (Allschwil, CH), Boss; Christoph (Allschwil, CH), Fischli; Walter (Allschwil, CH), Clozel; Martine (Saint-Louis, FR), Weller; Thomas (Binningen, CH)
Assignee:	Actelion Pharmaceuticals Ltd. (CH)
Application Number:	10/433,041
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 7,094,781
Patent Claims:	1. A compound of general formula I ##STR00561## or an optically pure enantiomer or diastereomer, a mixture of enantiomers or diastereomers, a diastereomeric racemate, a mixture of diastereomeric racemates or a meso-form or a pharmaceutically acceptable salt thereof; wherein R.sup.1 represents aryl; aryl-lower alkyl; heteroaryl; heteroaryl-lower alkyl; cycloalkyl; cycloalkyl-lower alkyl; heterocyclyl; heterocyclyl-lower alkyl; lower alkyl; or hydrogen; R.sup.2 represents --CH.sub.3; --(CH.sub.2).sub.n--Y--R.sup.a; --(CH.sub.2).sub.m--C.ident.C--(CH.sub.2).sub.p-Z-R.sup.a; --(CH.sub.2).sub.k--C(R.sup.b).dbd.CR.sup.cR.sup.d; or --CH.sub.2-tetrahydrofuran-2-yl; R.sup.3 represents aryl; or heteroaryl; R.sup.4 represents hydrogen; trifluoromethyl; lower alkyl; lower alkyl-amino; lower alkyloxy; lower alkyloxy-lower alkyloxy; hydroxy-lower alkoxy; lower alkyl-sulfinyl; lower alkylthio; lower alkylthio-lower alkyl; hydroxy-lower alkyl; lower alkyl-oxylower alkyl; hydroxy-lower alkyl-oxy-lower alkyl; hydroxy-lower alkyl-amino; lower alkyl-amino-lower alkyl; amino; di-lower alkyl-amino; [N-(hydroxy-lower alkyl)-N(lower alkyl)]-amino; aryl; aryl-amino; aryl-lower alkyl-amino; aryl-thio; aryl-lower alkyl-thio; aryloxy; aryl-lower alkyl-oxy; aryl-lower alkyl; aryl-sulfinyl; heteroaryl; heteroaryl-oxy; heteroaryl-lower alkyl-oxy; heteroaryl-amino; heteroaryl-lower alkyl-amino; heteroaryl-thio; heteroaryl-lower alkyl-thio; heteroaryl-lower alkyl; heteroaryl-sulfinyl; heterocyclyl; heterocyclyl-lower alkyl-oxy; heterocyclyl-oxy; heterocyclyl-amino; heterocyclyl-lower alkyl-amino; heterocyclyl-thio; heterocyclyl-lower alkyl-thio; heterocyclyl-lower alkyl; heterocyclyl-sulfinyl; cycloalkyl; cycloalkyl-oxy; cycloalkyl-lower alkyl-oxy; cycloalkyl-amino; cycloalkyl-lower alkyl-amino; cycloalkyl-thio; cycloalkyl-lower alkyl-thio; cycloalkyl-lower alkyl; or cycloalkylsulfinyl; R.sup.6 represents hydrogen; or lower alkyl; X represents oxygen; sulfur; --CH.sub.2-- or a bond; Y represents a bond, --O--; --NH--; --NH--SO.sub.2--; --NH--SO.sub.2--NH--; O--CO--; --CO--O--; --O--CO--NH--; --NH--CO--O--; or --NH--CO--NH--; Z represents oxygen or a bond; k represents 1, 2, 3, 4, 5 or 6; n represents 2, 3, 4, 5 or 6; m represents 1, 2, 3, 4 or 5; p represents 0 (zero), 1, 2 or 3 and if p represents 0 (zero), Z cannot represent oxygen; R.sup.a represents aryl; heteroaryl; lower alkyl; cycloalkyl; or hydrogen; R.sup.b and R.sup.c independently represent hydrogen or lower alkyl; and R.sup.d represents hydrogen; lower alkyl; aryl; or heteroaryl. 2. The compound according to claim 1 or a pharmaceutically acceptable salt thereof; wherein R.sup.1, R.sup.2 and R.sup.4 are as above; X represents oxygen; and R.sup.3 represents phenyl or mono-substituted phenyl substituted with halogen, lower alkyl, lower alkoxy or lower alkanoyl. 3. The compound according to claim 1 or a pharmaceutically acceptable salt thereof wherein R.sup.1 and R.sup.4 are as above; X represents oxygen; R.sup.3 represents phenyl or monosubstituted phenyl substituted with lower alkoxy; R.sup.2 represents --(CH.sub.2).sub.n--Y--R.sup.a; and n, Y and R.sup.a are as defined in general formula I. 4. The compound according to claim 1 or a pharmaceutically acceptable salt thereof wherein R.sup.1 and R.sup.4 are as above; X represents oxygen; R.sup.3 represents phenyl or monosubstituted phenyl substituted with lower alkoxy; and R.sup.2 represents --(CH.sub.2).sub.2--O--R.sup.a, wherein R.sup.a is as defined in general formula I in claim 1. 5. A compound of formula II ##STR00562## or an optically pure enantiomer or diastereomer, a mixture of enantiomers or diastereomers, a diastereomeric racemate, a mixture of diastereomeric racemates or a meso-form or a pharmaceutically acceptable salt thereof; wherein R.sup.1 represents aryl; aryl-lower alkyl; heteroaryl; heteroaryl-lower alkyl; cycloalkyl; cycloalkyl-lower alkyl; heterocyclyl; heterocyclyl-lower alkyl; lower alkyl; or hydrogen; R.sup.2 represents --CH.sub.3; --(CH.sub.2).sub.n--Y--R.sup.a; --(CH.sub.2).sub.m--C.ident.C--(CH.sub.2).sub.p-Z-R.sup.a; --(CH.sub.2).sub.k--C(R.sup.b).dbd.CR.sup.cR.sup.d; or --CH.sub.2-tetrahydrofuran-2-yl; Y represents a bond, --O--; --NH--; --NH--SO.sub.2--; --NH--SO.sub.2--NH--; O--CO--; --CO--O--; --O--CO--NH--; --NH--CO--O--; or --NH--CO--NH--; R.sup.a represents aryl; heteroaryl; lower alkyl; cycloalkyl; or hydrogen; Z represents oxygen or a bond; k represents 1, 2, 3, 4, 5 or 6; R.sup.b and R.sup.c independently represent hydrogen or lower alkyl; and R.sup.d represents hydrogen; lower alkyl; aryl; or heteroaryl; n represents 2, 3, 4, 5 or 6; m represents 1, 2, 3, 4 or 5; p represents 0 (zero), 1, 2 or 3 and if p represents 0 (zero), Z cannot represent oxygen; R.sup.3 represents aryl; or heteroaryl; and R.sup.4 represents hydrogen; trifluoromethyl; lower alkyl; lower alkyl-amino; lower alkyloxy; lower alkyloxy-lower alkyloxy; hydroxy-lower alkoxy; lower alkyl-sulfinyl; lower alkylthio; lower alkylthio-lower alkyl; hydroxy-lower alkyl; lower alkyl-oxylower alkyl; hydroxy-lower alkyl-oxy-lower alkyl; hydroxy-lower alkyl-amino; lower alkyl-amino-lower alkyl; amino; di-lower alkyl-amino; [N-(hydroxy-lower alkyl)-N(lower alkyl)]-amino; aryl; aryl-amino; aryl-lower alkyl-amino; aryl-thio; aryl-lower alkyl-thio; aryloxy; aryl-lower alkyl-oxy; aryl-lower alkyl; aryl-sulfinyl; heteroaryl; heteroaryl-oxy; heteroaryl-lower alkyl-oxy; heteroaryl-amino; heteroaryl-lower alkyl-amino; heteroaryl-thio; heteroaryl-lower alkyl-thio; heteroaryl-lower alkyl; heteroaryl-sulfinyl; heterocyclyl; heterocyclyl-lower alkyl-oxy; heterocyclyl-oxy; heterocyclyl-amino; heterocyclyl-lower alkyl-amino; heterocyclyl-thio; heterocyclyl-lower alkyl-thio; heterocyclyl-lower alkyl; heterocyclyl-sulfinyl; cycloalkyl; cycloalkyl-oxy; cycloalkyl-lower alkyl-oxy; cycloalkyl-amino; cycloalkyl-lower alkyl-amino; cycloalkyl-thio; cycloalkyl-lower alkyl-thio; cycloalkyl-lower alkyl; or cycloalkylsulfinyl. 6. A compound of formula III ##STR00563## or an optically pure enantiomer or diastereomer, a mixture of enantiomers or diastereomers, a diastereomeric racemate, a mixture of diastereomeric racemates or a meso-form or a pharmaceutically acceptable salt thereof; wherein R.sup.1 represents aryl; aryl-lower alkyl; heteroaryl; heteroaryl-lower alkyl; cycloalkyl; cycloalkyl-lower alkyl; heterocyclyl; heterocydyl-lower alkyl; lower alkyl; or hydrogen; R.sup.2 represents --CH.sub.3; --(CH.sub.2).sub.n--Y--R.sup.a; --(CH.sub.2).sub.m--C.ident.C--(CH.sub.2).sub.p-Z-R.sup.a; --(CH.sub.2).sub.k--C(R.sup.b).dbd.CR.sup.cR.sup.d; --CH.sub.2-tetrahydrofuran-2-yl; k represents 1, 2, 3, 4, 5 or 6; p represents 0 (zero), 1, 2 or 3 and if p represents 0 (zero), Z cannot represent oxygen; m represents 1, 2, 3, 4 or 5; n represents 2, 3, 4, 5 or 6; Y represents a bond, --O--; --NH--; --NH--SO.sub.2--; --NH--SO.sub.2--NH--; O--CO--; --CO--O--; --O--CO--NH--; --NH--CO--O--; or --NH--CO--NH--; R.sup.a represents aryl; heteroaryl; lower alkyl; cycloalkyl; or hydrogen; Z represents oxygen or a bond; R.sup.b and R.sup.c independently represent hydrogen or lower alkyl; R.sup.d represents hydrogen; lower alkyl; aryl; or heteroaryl; R.sup.4 represents hydrogen; trifluoromethyl; lower alkyl; lower alkyl-amino; lower alkyloxy; lower alkyloxy-lower alkyloxy; hydroxy-lower alkoxy; lower alkyl-sulfinyl; lower alkylthio; lower alkylthio-lower alkyl; hydroxy-lower alkyl; lower alkyl-oxylower alkyl; hydroxy-lower alkyl-oxy-lower alkyl; hydroxy-lower alkyl-amino; lower alkyl-amino-lower alkyl; amino; di-lower alkyl-amino; [N-(hydroxy-lower alkyl)-N(lower alkyl)]-amino; aryl; aryl-amino; aryl-lower alkyl-amino; aryl-thio; aryl-lower alkyl-thio; aryloxy; aryl-lower alkyl-oxy; aryl-lower alkyl; aryl-sulfinyl; heteroaryl; heteroaryl-oxy; heteroaryl-lower alkyl-oxy; heteroaryl-amino; heteroaryl-lower alkyl-amino; heteroaryl-thio; heteroaryl-lower alkyl-thio; heteroaryl-lower alkyl; heteroaryl-sulfinyl; heterocyclyl; heterocyclyl-lower alkyl-oxy; heterocyclyl-oxy; heterocyclyl-amino; heterocyclyl-lower alkyl-amino; heterocyclyl-thio; heterocyclyl-lower alkyl-thio; heterocyclyl-lower alkyl; heterocyclyl-sulfinyl; cycloalkyl; cycloalkyl-oxy; cycloalkyl-lower alkyl-oxy; cycloalkyl-amino; cycloalkyl-lower alkyl-amino; cycloalkyl-thio; cycloalkyl-lower alkyl-thio; cycloalkyl-lower alkyl; or cycloalkylsulfinyl; and A represents hydrogen, methyl, ethyl, chlorine, bromine, fluorine, trifluoromethyl or methoxy. 7. A compound of formula IV ##STR00564## or an optically pure enantiomer or diastereomer, a mixture of enantiomers or diastereomers, a diastereomeric racemate, a mixture of diastereomeric racemates or a meso-form or a pharmaceutically acceptable salt thereof; wherein R.sup.1 represents aryl; aryl-lower alkyl; heteroaryl; heteroaryl-lower alkyl; cycloalkyl; cycloalkyl-lower alkyl; heterocyclyl; heterocyclyl-lower alkyl; lower alkyl; or hydrogen; R.sup.4 represents hydrogen; trifluoromethyl; lower alkyl; lower alkyl-amino; lower alkyloxy; lower alkyloxy-lower alkyloxy; hydroxy-lower alkoxy; lower alkyl-sulfinyl; lower alkylthio; lower alkylthio-lower alkyl; hydroxy-lower alkyl; lower alkyl-oxylower alkyl; hydroxy-lower alkyl-oxy-lower alkyl; hydroxy-lower alkyl-amino; lower alkyl-amino-lower alkyl; amino; di-lower alkyl-amino; [N-(hydroxy-lower alkyl)-N(lower alkyl)]-amino; aryl; aryl-amino; aryl-lower alkyl-amino; aryl-thio; aryl-lower alkyl-thio; aryloxy; aryl-lower alkyl-oxy; aryl-lower alkyl; aryl-sulfinyl; heteroaryl; heteroaryl-oxy; heteroaryl-lower alkyl-oxy; heteroaryl-amino; heteroaryl-lower alkyl-amino; heteroaryl-thio; heteroaryl-lower alkyl-thio; heteroaryl-lower alkyl; heteroaryl-sulfinyl; heterocyclyl; heterocyclyl-lower alkyl-oxy; heterocyclyl-oxy; heterocyclyl-amino; heterocyclyl-lower alkyl-amino; heterocyclyl-thio; heterocyclyl-lower alkyl-thio; heterocyclyl-lower alkyl; heterocyclyl-sulfinyl; cycloalkyl; cycloalkyl-oxy; cycloalkyl-lower alkyl-oxy; cycloalkyl-amino; cycloalkyl-lower alkyl-amino; cycloalkyl-thio; cycloalkyl-lower alkyl-thio; cycloalkyl-lower alkyl; or cycloalkylsulfinyl n represents 2, 3, 4, 5 or 6; A represents hydrogen, methyl, ethyl, chlorine, bromine, fluorine, trifluoromethyl or methoxy; and R.sup.5 represents hydrogen, lower alkyl, aryl, heteroaryl or cycloalkyl. 8. A compound of formula V ##STR00565## or an optically pure enantiomer or diastereomer, a mixture of enantiomers or diastereomers, a diastereomeric racemate, a mixture of diastereomeric racemates or a meso-form or a pharmaceutically acceptable salt thereof; wherein R.sup.1 represents aryl; aryl-lower alkyl; heteroaryl; heteroaryl-lower alkyl; cycloalkyl; cycloalkyl-lower alkyl; heterocyclyl; heterocyclyl-lower alkyl; lower alkyl; or hydrogen; A represents hydrogen, methyl, ethyl, chlorine, bromine, fluorine, trifluoromethyl or methoxy; and R.sup.5 represents hydrogen, lower alkyl, aryl, heteroaryl or cycloalkyl. 9. The compound according to claim 8 or an optically pure enantiomer or diastereomer, a mixture of enantiomers or diastereomers, a diastereomeric racemate, a mixture of diastereomeric racemates or a meso-form or a pharmaceutically acceptable salt thereof; wherein R.sup.5 in Formula V represents heteroaryl. 10. The compound according to claim 1, being: Pyridin-2-yl-carbamic acid 2-[5-(2-methoxy-phenoxy)-6-(benzylsulfamic acid amido)-[2,2']bipyrimidinyl-4-yloxy]-ethyl ester; Pyridin-2-yl-carbamic acid 2-[5-(2-methoxy-phenoxy)-6-(4-methoxy-benzylsulfamic acid amido)-[2,2']bipyrimidinyl-4-yloxy]-ethyl ester; Benzylsulfamic acid [6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-5-(2-methoxy-phenoxy)-[2,2']bip- yrimidinyl-4-yl]-amide; Cyclopropylmethylsulfamic acid [6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-5-(2-methoxy-phenoxy)-[2,2']bip- yrimidinyl-4-yl]-amide; Furan-2-yl-methylsulfamic acid [6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-5-(2-methoxy-phenoxy)-[2,2']bip- yrimidinyl-4-yl]-amide; Cyclopropylsulfamic acid [6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-5-(2-methoxy-phenoxy)-[2,2']bip- yrimidinyl-4-yl]-amide; Benzylsulfamic acid-[6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-5-(2-methoxy-phenoxy)-pyri- midin-4-yl]-amide; Benzylsulfamic acid-[5-(2-chloro-5-methoxy-phenoxy)-6-[2-(5-methylsulfan-yl-pyrimidin-2-- yloxy)-ethoxy]-pyrimidin-4-yl]-amide; Furan-2-yl-methylsulfamic acid [6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-5-(4-chloro-phenyl)-pyrimidin-4- -yl]-amide; Cyclopropylmethylsulfamic acid [5-(4-chloro-phenyl)-6-[2-(5-methoxy-pyrimidin-2-yloxy)-ethoxy]-pyrimidin- -4-yl]-amide; Cyclopropylmethylsulfamic acid [6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-5-(4-chloro-phenyl)-pyrimidin-4- -yl]-amide; Cyclopropylmethylsulfamic acid [6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-5-p-tolyl-pyrimidin-4-yl]-amide- ; Benzylsulfamic acid [6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-2-pyridin-4-yl-5-p-tolyl-pyrimi- din-4-yl]-amide; Benzylsulfamic acid [6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-5-(4-chloro-phenyl)-2-pyridin-4- -yl-pyrimidin-4-yl]-amide; Ethylsulfamic acid [5-(4-chloro-phenyl)-6-[2-(5-methylsulfanyl-pyrimidin-2-yloxy)-ethoxy]-py- rimidin-4-yl]-amide; Ethylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-bromo-py(imidin-2-yloxy)-ethoxy]-pyrimidin-4-- yl]-amide; Ethylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-methylsulfanyl-pyrimidin-2-yloxy)-ethoxy]-pyr- imidin-4-yl]-amide; Benzylsulfamic acid [6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-5-(4-chloro-phenyl)-pyrimidin-4- -yl]-amide; Benzylsulfamic acid [6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-5-(4-bromo-phenyl)-pyrimidin-4-- yl]-amide; Pyridin-2-yl-methylsulfamic acid [6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-5-(4-chloro-phenyl)-pyrimidin-4- -yl]-amide; Thiophen-2-yl-methylsulfamic acid [6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-5-(4-chloro-phenyl)-pyrimidin-4- -yl]-amide; Benzylsulfamic acid [5-(2-chloro-5-methoxy-phenoxy)-6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-- pyrimidin-4-yl]-amide; Benzylsulfamic acid [6-[2-(5-methylsulfanyl-pyrimidin-2-yloxy)-ethoxy]-5-(4-bromo-phenyl)-pyr- imidin-4-yl]-amide; Ethylsulfamic acid [5-(4-chloro-phenyl)-6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-4- -yl]-amide; or a pharmaceutically acceptable salt thereof. 11. The compound according to claim 1, being: Pyridin-2-yl-methylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-pyrimid- in-4-yl]-amide; Pyridin-2-yl-methylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-methoxy-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-- 4-yl]-amide; Pyridin-2-yl-methylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-methylsulfanyl-pyrimidin-2-yloxy)-ethoxy]-pyr- imidin-4-yl]-amide; Pyridin-3-yl-methylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-4-- yl]-amide; Pyridin-3-yl-methylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-methoxy-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-- 4-yl]-amide; Pyridin-3-yl-methylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-methylsulfanyl-pyrimidin-2-yloxy)-ethoxy]-pyr- imidin-4-yl]-amide; Pyridin-4-yl-methylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-4-- yl]-amide; Pyridin-4-yl-methylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-methoxy-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-- 4-yl]-amide; Pyridin-4-yl-methylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-methylsulfanyl-pyrimidin-2-yloxy)-ethoxy]-pyr- imidin-4-yl]-amide; Pyridin-2-yl-methylsulfamic acid [5-(4-chloro-phenyl)-6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-4- -yl]-amide; Pyridin-2-yl-methylsulfamic acid [5-(4-chloro-phenyl)-6-[2-(5-methoxy-pyrimidin-2-yloxy)-ethoxy]-pyrimidin- -4-yl]-amide; Pyridin-2-yl-methylsulfamic acid [5-(4-chloro-phenyl)-6-[2-(5-methylsulfanyl-pyrimidin-2-yloxy)-ethoxy]-py- rimidin-4-yl]-amide; Pyridin-3-yl-methylsulfamic acid [5-(4-chloro-phenyl)-6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-4- -yl]-amide; Pyridin-3-yl-methylsulfamic acid [5-(4-chloro-phenyl)-6-[2-(5-methoxy-pyrimidin-2-yloxy)-ethoxy]-pyrimidin- -4-yl]-amide; Pyridin-3-yl-methylsulfamic acid [5-(4-chloro-phenyl)-6-[2-(5-methylsulfanyl-pyrimidin-2-yloxy)-ethoxy]-py- rimidin-4-yl]-amide; Pyridin-4-yl-methylsulfamic acid [5-(4-chloro-phenyl)-6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-4- -yl]-amide; Pyridin-4-yl-methylsulfamic acid [5-(4-chloro-phenyl)-6-[2-(5-methoxy-pyrimidin-2-yloxy)-ethoxy]-pyrimidin- -4-yl]-amide; Pyridin-4-yl-methylsulfamic acid [5-(4-chloro-phenyl)-6-[2-(5-methylsulfanyl-pyrimidin-2-yloxy)-ethoxy]-py- rimidin-4-yl]-amide; 4-Fluorobenzylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-4-- yl]-amide; 4-Fluorobenzylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-methoxy-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-- 4-yl]-amide; 4-Fluorobenzylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-methylsulfanyl-pyrimidin-2-yloxy)-ethoxy]-pyr- imidin-4-yl]-amide; 4-Fluorobenzylsulfamic acid [5-(4-chloro-phenyl)-6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-4- -yl]-amide; 4-Fluorobenzylsulfamic acid [5-(4-chloro-phenyl)-6-[2-(5-methoxy-pyrimidin-2-yloxy)-ethoxy]-pyrimidin- -4-yl]-amide; 4-Fluorobenzylsulfamic acid [5-(4-chloro-phenyl)-6-[2-(5-methylsulfanyl-pyrimidin-2-yloxy)-ethoxy]-py- rimidin-4-yl]-amide; Cyclopropylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-4-- yl]-amide; Cyclopropylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-methoxy-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-- 4-yl]-amide; Cyclopropylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-methylsulfanyl-pyrimidin-2-yloxy)-ethoxy]-pyr- imidin-4-yl]-amide; Thiophen-2-yl-methylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-4-- yl]-amide; Thiophen-2-yl-methylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-methoxy-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-- 4-yl]-amide; Thiophen-2-yl-methylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-methylsulfanyl-pyrimidin-2-yloxy)-ethoxy]-pyr- imidin-4-yl]-amide; Furan-2-yl-methylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-4-- yl]-amide; Furan-2-yl-methylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-methoxy-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-- 4-yl]-amide; Furan-2-yl-methylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-methylsulfanyl-pyrimidin-2-yloxy)-ethoxy]-pyr- imidin-4-yl]-amide; Furan-2-yl-methylsulfamic acid [5-(4-chloro-phenyl)-6-[2-(5-methylsulfanyl-pyrimidin-2-yloxy)-ethoxy]-py- rimidin-4-yl]-amide; Thiophen-2-yl-methylsulfamic acid [5-(4-chloro-phenyl)-6-[2-(5-methylsulfanyl-pyrimidin-2-yloxy)-ethoxy]-py- rimidin-4-yl]-amide; Methylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-4-- yl]-amide; Methylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-methoxy-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-- 4-yl]-amide; Methylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-methylsulfanyl-pyrimidin-2-yloxy)-ethoxy]-pyr- imidin-4-yl]-amide; Methylsulfamic acid [5-(4-chloro-phenyl)-6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-4- -yl]-amide; Methylsulfamic acid [5-(4-chloro-phenyl)-6-[2-(5-methoxy-pyrimidin-2-yloxy)-ethoxy]-pyrimidin- -4-yl]-amide; Methylsulfamic acid [5-(4-chloro-phenyl)-6-[2-(5-methylsulfanyl-pyrimidin-2-yloxy)-ethoxy]-py- rimidin-4-yl]-amide; Ethylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-4-- yl]-amide; Ethylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-methoxy-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-- 4-yl]-amide; Ethylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-methylsulfanyl-pyrimidin-2-yloxy)-ethoxy]-pyr- imidin-4-yl]-amide; Ethylsulfamic acid [5-(4-chloro-phenyl)-6-[2-(5-methoxy-py(midin-2-yloxy-ethoxy]-pyrimidin-4- -yl]-amide; Propylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-4-- yl]-amide; Propylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-methoxy-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-- 4-yl]-amide; Propylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-methylsulfanyl-pyrimidin-2-yloxy)-ethoxy]-pyr- imidin-4-yl]-amide; Propylsulfamic acid [5-(4-chloro-phenyl)-6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-4- -yl]-amide; Propylsulfamic acid [5-(4-chloro-phenyl)-6-[2-(5-methoxy-pyrimidin-2-yloxy)-ethoxy]-pyrimidin- -4-yl]-amide; Propylsulfamic acid [5-(4-chloro-phenyl)-6-[2-(5-methylsulfanyl-pyrimidin-2-yloxy)-ethoxy]-py- rimidin-4-yl]-amide; Butylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-4-- yl]-amide; Butylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-methoxy-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-- 4-yl]-amide; Butylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-methylsulfanyl-pyrimidin-2-yloxy)-ethoxy]-pyr- imidin-4-yl]-amide; Butylsulfamic acid [5-(4-chloro-phenyl)-6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-4- -yl]-amide; Butylsulfamic acid [5-(4-chloro-phenyl)-6-[2-(5-methoxy-pyrimidin-2-yloxy)-ethoxy]-pyrimidin- -4-yl]-amide; Butylsulfamic acid [5-(4-chloro-phenyl)-6-[2-(5-methylsulfanyl-pyrimidin-2-yloxy)-ethoxy]-py- rimidin-4-yl]-amide; Cyclopropylsulfamic acid [5-(4-chloro-phenyl)-6-[2-(5-methoxy-pyrimidin-2-yloxy)-ethoxy]-pyrimidin- -4-yl]-amide; Cyclopropylsulfamic acid [5-(4-chloro-phenyl)-6-[2-(5-methylsulfanyl-pyrimidin-2-yloxy)-ethoxy]-py- rimidin-4-yl]-amide; Cyclopentylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-4-- yl]-amide; Cyclopentylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-methoxy-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-- 4-yl]-amide; Cyclopentylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-methylsulfanyl-pyrimidin-2-yloxy)-ethoxy]-pyr- imidin-4-yl]-amide; Cyclopentylsulfamic acid [5-(4-chloro-phenyl)-6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-4- -yl]-amide; Cyclopentylsulfamic acid [5-(4-chloro-phenyl)-6-[2-(5-methoxy-pyrimidin-2-yloxy)-ethoxy]-pyrimidin- -4-yl]-amide; Cyclopentylsulfamic acid [5-(4-chloro-phenyl)-6-[2-(5-methylsulfanyl-pyrimidin-2-yloxy)-ethoxy]-py- rimidin-4-yl]-amide; Cyclopropylmethylsulfamic acid [5-(4-chloro-phenyl)-6-[2-(5-methylsulfanyl-pyrimidin-2-yloxy)-ethoxy]-py- rimidin-4-yl]-amide; N-Benzylmethylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-4-- yl]-amide; N-Benzylmethylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-methoxy-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-- 4-yl]-amide; N-Benzylmethylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-methylsulfanyl-pyrimidin-2-yloxy)-ethoxy]-pyr- imidin-4-yl]-amide; N-Benzylmethylsulfamic acid [5-(4-chloro-phenyl)-6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-4- -yl]-amide; N-Benzylmethylsulfamic acid [5-(4-chloro-phenyl)-6-[2-(5-methoxy-pyrimidin-2-yloxy)-ethoxy]-pyrimidin- -4-yl]-amide; N-Benzylmethylsulfamic acid [5-(4-chloro-phenyl)-6-[2-(5-methylsulfanyl-pyrimidin-2-yloxy)-ethoxy]-py- rimidin-4-yl]-amide; or a pharmaceutically acceptable salt thereof.