Patent ID: 6890925

Claim:
A method of treating a condition caused by endothelial dysfunction, chosen from insulin resistance syndrome, hypertension, angina, ischemia, ischemic stroke, renal disease and Raynaud's disease, said method comprising administering to a patient in need thereof a therapeutically effective amount of a compound of Formula I: wherein: R 1 and R 3 are the same or different and each is CF 3 , halogen, CN, C 1-8 alkyl or branched alkyl, C 2-8 alkenyl or C 3-8 branched alkenyl, C 2-8 alkynyl or C 3-8 branched alkynyl, C 3-8 cycloalkyl optionally substituted with OH, CN or methoxy, C 1-8 alkyloxy, C 1-4 alkyloxyC 1-4 alkyl, C 1-8 alkylthio, C 1-4 alkylthioC 1-4 alkyl, C 1-8 dialkylamino, C 1-4 dialkylaminoalkyl, CO 2 R 5 where R 5 is C 1-4 alkyl or C 2-4 alkenyl optionally substituted with carbocyclyl or heterocyclyl, aryl or R 1 , is heterocyclyl connected to the pyrazole in any position that makes a stable bond optionally substituted with halogen, C 1-4 alkyl, C 2-4 alkenyl, CN, (CH 3 ) 2 N, CO 2 CH 3 , alkyloxy, aryl, heterocyclyl or R 5 ; R 2 is H, halogen or methyl; L is —NHC(O)—, —NHC(O)O—or —NHC(O)C(O)—, R 4 is C 1-8 alkyl, C 1-8 alkyloxy, C 1-8 alkylthio, C 1-8 alkylamino, C 1-4 alkyloxyalkyl, C 1-4 alkylthioalkyl, C 1-4 alkylaminoalkyl, C 1-4 dialkylaminoalkyl, carbocyclyl or heterocyclyl each optionally substituted with one or more halogen, —CN, —NO 2 , SO 2 NH 2 alkylthio, alkylsulfinyl, alkylsulfonyl or R 7 where R 7 is phenyl, heterocyclyl, C 3-6 cycloalkyl, C 1-6 alkyl, C 2-6 alkenyl, C 1-6 alkyloxyalkyl, C 1-4 alkyloxy, C 1-5 alkylamino, C 1-6 alkylthioalkyl, C 1-6 alkylsulfmylalkyl or C 1-6 alkylsulfonylalkyl, each R 7 in turn is optionally substituted with halogen, OH, alkyloxy, CN, COO-lower alkyl, —CONH-lower alkyl, —CON(lower alkyl) 2 , dialkylamino, phenyl or heterocylcyl; R 8 is H; or the pharmaceutically acceptable salts thereof; with the proviso that when R 3 is alkyl or CF 3 and R 4 is pyridyl, then the pyridyl is substituted except that the substituents on the pyridyl cannot be halogen; and with the proviso that the following compounds are excluded: N-[4-(5-ethyl-3-pyridin-3-yl-pyrazol-1-yl)-phenly]nicotinamide; N-[4-(5-Ethyl-3-pyridin-3-yl-pyrazol- 1yl)phenyl]-1-methylindole-2-carboxamide; 4-(3-Cyanopropoxy)-N-[4-(5-cyano-3-pyridin-3-yl-pyrazol-1-yl)phenyl]benzamide; and N-[4-(5-cyano-3-pyridin-3-yl-pyrazol-1yl)phenyl]-4-(3-[1,3]dioxolan-2-yl-propoxy)benzamide.