Isoxazolo [4,5-d] pyrimidines as CRF antagonists

A compound of formula (I):

• 9
• or a stereoisomer or pharmaceutically acceptable salt form thereof, wherein:
• R is selected from phenyl, naphthyl, pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzthiazolyl, isoxazolyl and pyrazolyl, and is substituted with 0-5 R3 groups;
• R1 is selected from H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, halo, —CN, C1-4 haloalkyl, NR6R7, NR8COR9, —OR10, SH and —S(O)nR11;
• R2 is selected from NR6aR7a and OR10a;
• R3 is independently selected at each occurrence from C1-10 alkyl substituted with 0-2 Ra, C2-10 alkenyl substituted with 0-2 Ra, C2-10 alkynyl substituted with 0-2 Ra, C3-6 cycloalkyl substituted with 0-2 Ra, (C3-6 cycloalkyl)C1-4 alkyl substituted with 0-2 Ra, —NO2, halo, —CN, C1-4 haloalkyl, —NR6R7, —NR8COR13a, —NR8C(O)OR13a, —COR13, —OR10a, —CONR6R7, —NR8CONR6R7, C(O)OR10a, SH, and —S(O)nR12;
• Ra is independently selected at each occurrence from C1-4 alkyl, —NO2, halo, —CN, —NR6R7, —NR8COR13a, —NR8C(O)OR13a, —COR13, —OR10a, —CONR6R7, —NR8CONR6R7, C(O)OR10a, SH, and —S(O)nR12;
• R6 is independently at each occurrence selected from H, C1-4 alkyl, C3-6 cycloalkyl and (C3-6 cycloalkyl)methyl;
• R6a is independently selected at each occurrence from H, C1-6 alkyl substituted with 0-2 Rb, C2-6 alkenyl substituted with 0-2 Rb, C2-6 alkynyl substituted with 0-2 Rb, C1-4 haloalkyl, C3-6 cycloalkyl substituted with 0-2 Rb, (C3-6 cycloalkyl)C1-4 alkyl substituted with 0-2 Rb, aryl substituted with 0-2 Rb, (aryl)C1-4 alkyl substituted with 0-2 Rb, heteroaryl substituted with 0-2 Rb, (heteroaryl)C1-4 alkyl substituted with 0-2 Rb, heterocyclyl substituted with 0-2 Rb, and (heterocyclyl)C1-4 alkyl substituted with 0-2 Rb;
• Rb is independently selected at each occurrence from C1-4 alkyl, —NO2, halo, —CN, —NR6bR7a, —NR8COR13a, —NR8C(O)OR13a, —COR13, OR10a, ONR6bR7a, —NR8CONR6bR7a, C(O)OR10a, SH, and —S(O)nR12;
• R6b is independently at each occurrence selected from H, C1-4 alkyl, C3-6 cycloalkyl and (C3-6 cycloalkyl)methyl;
• R7 is independently at each occurrence selected from H, C1-4 alkyl, C3-6 cycloalkyl and (C3-6 cycloalkyl)methyl;
• R7a is independently selected at each occurrence from H, C1-6 alkyl, phenyl, benzyl, C3-6 cycloalkyl, (C3-6 cycloalkyl)methyl, and C1-4 haloalkyl;
• alternatively, NR6aR7a is selected from piperidine, pyrrolidine, morpholine, thiomorpholine, thiomorpholine-oxide, and thiomorpholine-dioxide, and is substituted with 0-1 Re;
• Re is C1-4 alkyl;
• alternatively, NR6aR7a is piperazine or N-methylpiperazine, and is substituted with 0-1 Rf;
• Rf is selected from C1-4 alkyl, C(O)C1-4 alkyl, C(O)benzyl, C(O)OC1-4 alkyl, C(O)O-benzyl, SO2-C1-4 alkyl, SO2-benzyl, and SO2-phenyl;
• R8 is independently at each occurrence selected from H, C1-4 alkyl, C3-6 cycloalkyl and (C3-6 cycloalkyl)C1-14 alkyl;
• R9 is independently at each occurrence selected from H, C1-4 alkyl, C3-6 cycloalkyl and (C3-6 cycloalkyl)C1-14 alkyl;
• R10 is independently at each occurrence selected from H, C1-4 alkyl, C1-4 haloalkyl, C3-6 cycloalkyl, and (C3-6 cycloalkyl)C1-4 alkyl;
• R10a is independently selected at each occurrence from H, C1-6 alkyl, phenyl, benzyl, C3-6 cycloalkyl, (C3-6 cycloalkyl)C1-4 alkyl, (C1-4 alkoxy)C1-4 alkyl, and C1-4 haloalkyl;
• R10b is independently selected at each occurrence from H, C1-6 alkyl, C2-4 alkenyl, phenyl, benzyl, C3-6 cycloalkyl, (C3-6 cycloalkyl)C1-4 alkyl, (C1-4 alkoxy)C1-4 alkyl, and C1-4 haloalkyl;
• R11 is independently at each occurrence selected from C1-4 alkyl, C1-4 haloalkyl, and C3-6 cycloalkyl;
• R12 is independently at each occurrence selected from C1-4 alkyl, C1-4 haloalkyl, (C1-4 alkoxy)C1-4 alkyl, C3-6 cycloalkyl, (C3-6 cycloalkyl)C1-14 alkyl, aryl, and (aryl) C1-4 alkyl;
• R13 is independently at each occurrence selected from H, C1-6 alkyl, phenyl, benzyl, C3-6 cycloalkyl, and (C3-6 cycloalkyl)C1-4 alkyl;
• R13a is independently at each occurrence selected from C1-6 alkyl, phenyl, benzyl, C3-6 cycloalkyl, and (C3-6 cycloalkyl)C1-4 alkyl;
• aryl is independently at each occurrence selected from phenyl and naphthyl, and is substituted with 0-3 Rg;
• Rg is independently at each occurrence selected from C1-6 alkyl, C3-6 cycloalkyl, halo, C1-4 haloalkyl, cyano, nitro, —OR10a, SH, —S(O)nR15, —COR16, —C(O)OR16, —OC(O)R17, —NR8COR16a, NR8CONR6aR7a, NR8C(O)OR16a, NR6aR7a, and —CONR6aR7a;
• R15 is independently at each occurrence selected from C1-4 alkyl, C1-4 haloalkyl, (C1-4 alkoxy)C1-4 alkyl, C3-6 cycloalkyl, (C3-6 cycloalkyl)C1-4 alkyl, phenyl, benzyl, (phenyl)C1-4 alkyl and (naphthyl)C1-4 alkyl;
• R16 is independently at each occurrence selected from H, C1-6 alkyl, phenyl, benzyl, C3-6 cycloalkyl, and (C3-6 cycloalkyl)C1-4 alkyl;
• R16a is independently at each occurrence selected from C1-6 alkyl, phenyl, benzyl, C3-6 cycloalkyl, and (C3-6 cycloalkyl)C1-4 alkyl;
• R17 is independently at each occurrence selected from C1-4 alkyl, C1-4 haloalkyl, (C1-4 alkoxy)C1-4 alkyl, C3-6 cycloalkyl, (C3-6 cycloalkyl)C1-4 alkyl, phenyl, benzyl, (phenyl)C1-4 alkyl, (naphthyl)C1-4 alkyl, heteroaryl and (heteroaryl)C1-4 alkyl;
• heteroaryl is independently at each occurrence selected from pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzthiazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, and indazolyl, and is substituted with 0-3 Rh;
• heterocyclyl is saturated or partially saturated heteroaryl, substituted with 0-3 Rh;
• and
• Rh is independently at each occurrence selected from C1-6 alkyl, C3-6 cycloalkyl, halo, C1-4 haloalkyl, cyano, nitro, —OR10a, SH, —S(O)nR15, —COR16, —C(O)OR16, —OC(O)R18, NR8COR16a, —NR8CONR6aR7a, —NR8CO2R16a, —NR6aR7a, and CONR6aR7a;
• R18 is independently selected at each occurrence from C1-6 alkyl, C3-6 cycloalkyl, phenyl and benzyl;
• and
• n is independently at each occurrence selected from 0, 1 and 2.