Patent NZ-525614-A (NZ)
Title: Novel sulfamides and their use as endothelin receptor antagonists
Inventor: BOLLI MARTIN
IPC: A61P31/10
Filed: 2001-12-04
Abstract: The disclosure relates to sulfamides of General Formula I, wherein R1 represents aryl; aryl-lower alkyl; heteroaryl; heteroaryl-lower alkyl; cycloalkyl; cycloalkyl-lower alkyl; heterocyclyl; heterocyclyl-lower alkyl; lower alkyl; hydrogen; or may form a heterocyclyl- or cycloalkyl-ring together with R6; R2 represents -CH3; -CH2)n-Y-Ra; -(CH2)m-Ca"C-(CH2)p-Z-Ra; -(CH2)k-C(Rb)-CRcRd; -CH2-tetrahydrofuran-2-yl; R3 represents aryl; heteroaryl; R4 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-oxy- lower 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 alkyloxy; 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; cycloalkyl-sulfinyl; R5 represents hydrogen; lower alkyl; or may form a heterocyclyl- or cycloalkyl-ring together with R1; X represents oxygen; sulfur; -CH2- or a bond; Y represents a bond, -O-; -NH-; -NH-SO2-; -NH-SO2-NH-; O-CO-; -CO-O-; -O-CO-NH-; -NH-CO-O-; -NH-CO-NH- Z represents oxygen or a bond; k represents the whole numbers 1, 2, 3, 4, 5 or 6; n represents the whole numbers 2, 3, 4, 5 or 6; m represents the whole numbers 1, 2, 3, 4 or 5; p represents the whole numbers 0 (zero), 1, 2 or 3 and if p represents the whole number 0 (zero), Z cannot represent oxygen; Ra represents aryl; heteroaryl; lower alkyl; cycloalkyl; hydrogen; Rs and Rc independently represent hydrogen or lower alkyl; Rd represents hydrogen; lower alkyl; aryl; heteroaryl; and optically pure enantiomers or diastereomers, mixtures of enantiomers or diastereomers, diastereomeric racemates, mixtures of diastereomeric racemates and the meso-forms and pharmaceutically acceptable salts thereof. Such compounds are useful as active ingredients in the preparation of pharmaceutical compositions suitable for the treatment of diseases associated with the role of endothelin, particularly circulatory disorders and proliferative diseases such as hypertension, ischemia, vasospasm, angina pectoris and cancer. Also disclosed are 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.