Ring fused pyrazole derivatives as CRF antagonists

A compound of Formula I or Formula II:

• wherein:
• R1 is —CRcRdRe or —C(O)NRaRb;
• R2 is C1-6alkyl;
• R3 and R4 are hydrogen;
• Ar is aryl or pyridine optionally substituted with one or more substituents independently selected from the group consisting of C1-6alkyl, C1-6 alkoxy, halogen and NRa′Rb′ wherein Ra′ and Rb′ are independently hydrogen or C1-6 alkyl;
• Ra and Rb taken together with the nitrogen to which they are attached form a heterocyclyl ring selected from the group consisting of pyrrolidine, piperidine, homopiperidine, 1,2,3,4-tetrahydroquinoline, 1,2,3,4-tetrahydroisoquinoline, hexahydropyrimidine, piperazine and morpholine, where each of said rings is optionally substituted with one or more substituents selected from the group consisting of hydroxy, oxo, alkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, aminoalkyl, acyl, acylamino, aminocarbonyl, aminocarbonylalkyl, aminocarbonylamino, aminosulfonyl, alkylsulfonylamino;
• Rc is hydrogen, hydroxy or —NRa″Rb″;
• Re is heterocyclyl or heteroaryl said heteroaryl groups optionally substituted with one or more substituents independently selected from the group consisting of C1-6 alkyl, haloalkyl, C1-6alkoxy, amino, alkylamino, dialkylamino, and halogen and Rd is hydrogen or C1-6alkyl;
• or
• Rc and Rd are taken are C1-6alkylidenyl;
• or
• Rd and Re are taken together with the carbon to which they are attached to form a heterocyclyl ring;
• Re″ and Rb″ are taken together with the nitrogen to which they are attached form an heterocyclyl or heteroaryl ring selected from the group consisting of pyrrolidine, piperidine, 1,2,3,4-tetrahydroquinoline, 1,2,3,4-tetrahydroisoquinoline, hexahydropyrimidine, piperazine, morpholine, imidazoline where each of said rings is optionally substituted with one or more substituents selected from the group consisting of hydroxy, oxo, alkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, aminoalkyl, acyl, acylamino, aminocarbonyl, aminocarbonylalkyl, aminocarbonylamino, aminosulfonyl, alkylsulfonylamino, aminosulfonylamino;
• n is 1;
• a is a single bond;
• or individual isomers, racemic or non-racemic mixtures of isomers, or pharmaceutically acceptable salts thereof.

A compound of formula I according to claim 2, which compounds are selected from the group consisting of:

• (3,4-Dihydro-1H-isoquinolin-2-yl)-[2-methyl-7-(2,4,6-trimethyl-phenyl)-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridin-3-yl]-methanone;
• 2-[2-Methyl-7-(2,4,6-trimethyl-phenyl)-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridin-3-ylmethyl]-1,2,3,4-tetrahydro-isoquinoline;
• hydrochloride salt;
• 2-Methyl-3-(1-thiophen-2-yl-butyl)-7-(2,4,6-trimethyl-phenyl)-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridine;
• 3-((Z)-1-Furan-2-yl-but-1-enyl)-2-methyl-7-(2,4,6-trimethyl-phenyl)-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridine;
• 2-Methyl-3-((Z)-1-thiophen-2-yl-but-1-enyl)-7-(2,4,6-trimethyl-phenyl)-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridine;
• 2-Methyl-3-((E)-1-thiazol-2-yl-but-1-enyl)-7-(2,4,6-trimethyl-phenyl)-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridine;
• 1-Furan-2-yl-1-[2-methyl-7-(2,4,6-trimethyl-phenyl)-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridin-3-yl]-butan-1-ol;
• 1-(1-Ethyl-1H-imidazol-2-yl)-1-[2-methyl-7-(2,4,6-trimethyl-phenyl)-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridin-3-yl]-butan-1-ol;
• 1-[2-Methyl-7-(2,4,6-trimethyl-phenyl)-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridin-3-yl]-1-thiazol-2-yl-butan-1-ol;
• 4-[2-Methyl-7-(2,4,6-trimethyl-phenyl)-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridin-3-yl]-tetrahydro-pyran-4-ol;
• Furan-2-yl-[2-methyl-7-(2,4,6-trimethyl-phenyl)-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridin-3-yl]-methanol;
• and,
• 1-[2-Methyl-7-(2,4,6-trimethyl-phenyl)-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridin-3-yl]-1-thiophen-2-yl-butan-1-ol.