3-aryl substituted pyrazolo[4,3-D]pyrimidine derivatives; corticotropin-releasing factor receptor (CRF1) specific ligands

A compound of the formula:

• 28
• or the pharmaceutically acceptable salts thereof wherein
• Ra represents halogen, hydroxy, lower alkyl, or lower alkoxy;
• Rb, and Rc independently represent hydrogen halogen, hydroxy, lower alkyl, or lower alkoxy;
• R1 is lower alkyl;
• R2 is hydrogen or lower alkyl;
• and
• R3 and R4 are the same or different and represent hydrogen, lower alkyl, lower alkenyl, cycloalkyl, cycloalkyl lower alkyl, 2-hydroxyethyl or 3-hydroxypropyl;
• provided that not both R3 and R4 are hydrogen.

A compound of the formula:

• 29
• or the pharmaceutically acceptable salts thereof wherein
• Ra represents halogen, hydroxy, lower alkyl, or lower alkoxy;
• Rb, and Rc independently represent hydrogen, halogen, hydroxy, lower alkyl, or lower alkoxy;
• R1 is lower alkyl;
• R2 is hydrogen or lower alkyl;
• and
• R3 and R4 are the same or different and represent hydrogen, lower alkyl, cycloalkyl, cycloalkyl lower alkyl, or alkenyl;
• phenyl, 2-, 3-, or 4- pyridinyl, or 2-, 4- or 5-pyrimidinyl, each of which is optionally mono- or disubstituted with halogen, hydroxy, lower alkyl, or lower alkoxy;
• or
• phenyl-, 2-, 3-, or 4-pyridinyl-, or 2-, 4- or 5-pyrimidinyl-lower alkyl, each of which is optionally mono- or disubstituted with lower alkyl;
• provided that not both R3 and R4 are hydrogen.

A compound of the formula:

• 30
• or the pharmaceutically acceptable salts thereof wherein
• Ra represents halogen, hydroxy, lower alkyl, or lower alkoxy;
• Rb, and Rc independently represent hydrogen halogen, hydroxy, lower alky, or lower alkoxy;
• R1 is lower alkyl;
• R2 is hydrogen or lower alkyl;
• and
• R3 and R4 taken together represent with the nitrogen atom to which they are attached represent -(CH2)n-A-(CH2)m-where
• n is 2, or 3;
• A is methylene, 1,2-phenylene, oxygen, sulfur or NR6, wherein R6 is lower alkyl, phenyl, 2-, 3-, or 4-pyridinyl, 2-or 3-thienyl or 2-, 4- or 5-pyrimidinyl, or phenyl-, 2-, 3-or 4-pyridinyl-, 2-or 3-thienyl-, or 2-, 4- or 5-pyrimidinylalkyl;
• and
• m is 1,2 or 3.

A compound of the formula:

• 31
• or the pharmaceutically acceptable salts thereof wherein
• Ra, Rb, and Rc independently represent hydrogen, halogen, hydroxy, lower alkyl, or lower alkoxy, with the proviso that not both Ra and Rc are hydrogen;
• R1 is lower alkyl;
• R2 is hydrogen or lower alkyl;
• and
• R3 and R4 are the same or different and represent hydrogen, lower alkyl, cycloalkyl, cycloalkyl lower alkyl, alkenyl, 2-hydroxyethyl or 3-hydroxypropyl, provided that not both R3 and R4 are hydrogen.

A compound of the formula:

• 32
• or the pharmaceutically acceptable salts thereof wherein
• Ra, Rb, and Rc independently represent hydrogen, halogen, hydroxy, lower alkyl, or lower alkoxy, with the proviso that not both Ra and Rc are hydrogen;
• R1 is lower alkyl;
• R2 is hydrogen or lower alkyl;
• and
• R3 and R4 are the same or different and represent hydrogen, lower alkyl, cycloalkyl, cycloalkyl lower alkyl, alkenyl, 2-hydroxyethyl or 3-hydroxypropyl, provided that not both R3 and R4 are hydrogen.