Antirheumatic agent

An osteoclast formation inhibiting agent comprising as an active ingredient a compound of formula I:

• 22
• wherein
• R1 is hydrogen, lower alkyl, lower alkoxy, hydroxy lower alkyl, or carboxy lower alkyl and R4 is hydroxy;
• or
• R1 and R4 taken together form —CR5R6—(CH2)m—O— or —CR5R6—(CH2)pCH(OH)—O—
• wherein m is an integer of 1 to 3;
• p is an integer of 0 to 2;
• and
• R5 and R6 are each independently hydrogen, lower alkyl, lower alkoxy, or hydroxy lower alkyl;
• R2 is hydrogen, lower alkyl, lower alkoxy, hydroxy lower alkyl, or carboxy lower alkyl;
• and
• R3 is hydrogen, lower alkyl, cycloalkyl, lower alkoxy, arylalkyloxy, heteroarylalkyloxy, lower alkylcarbonyl, arylcarbonyl, substituted or unsubstituted carbamoyl or a group represented by the formula:
• —(CH2)n-Q
• wherein Q is hydroxy, substituted or unsubstituted amino, aryl, heteroaryl, hydroxycarbonyl or lower alkyloxycarbonyl;
• and
• n is an integer of 0 to 3
• or a pharmaceutically acceptable salt or hydrate thereof.

A nitrogen monoxide production inhibiting agent comprising as an active ingredient a compound of formula I:

• 23
• wherein
• R1 is hydrogen, lower alkyl, lower alkoxy, hydroxy lower alkyl, or carboxy lower alkyl and R4 is hydroxy;
• or
• R1 and R4 taken together form —CR5R6—(CH2)m—O— or —CR5R6—(CH2)pCH(OH)—O—
• wherein m is an integer of 1 to 3;
• p is an integer of 0 to 2;
• and
• R5 and R6 are each independently hydrogen, lower alkyl, lower alkoxy, or hydroxy lower alkyl;
• R2 is hydrogen, lower alkyl, lower alkoxy, hydroxy lower alkyl, or carboxy lower alkyl;
• and
• R3 is hydrogen, lower alkyl, cycloalkyl, lower alkoxy, arylalkyloxy, heteroarylalkyloxy, lower alkylcarbonyl, arylcarbonyl, substituted or unsubstituted carbamoyl or a group represented by the formula:
• —(CH2)n-Q
• wherein Q is hydroxy, substituted or unsubstituted amino, aryl, heteroaryl, hydroxycarbonyl or lower alkyloxycarbonyl;
• and
• n is an integer of 0 to 3
• or a pharmaceutically acceptable salt or hydrate thereof.

A transcription factor NFκB suppressing agent comprising as an active ingredient a compound of formula I:

• 24
• wherein
• R1 is hydrogen, lower alkyl, lower alkoxy, hydroxy lower alkyl, or carboxy lower alkyl and R4 is hydroxy;
• or
• R1 and R4 taken together form —CR5R6—(CH2)m—O— or —CR5R6—(CH2)pCH(OH)—O—
• wherein m is an integer of 1 to 3;
• p is an integer of 0 to 2;
• and
• R5 and R6 are each independently hydrogen, lower alkyl, lower alkoxy, or hydroxy lower alkyl;
• R2 is hydrogen, lower alkyl, lower alkoxy, hydroxy lower alkyl, or carboxy lower alkyl;
• and
• R3 is hydrogen, lower alkyl, cycloalkyl, lower alkoxy, arylalkyloxy, heteroarylalkyloxy, lower alkylcarbonyl, arylcarbonyl, substituted or unsubstituted carbamoyl or a group represented by the formula:
• —(CH2)n-Q
• wherein Q is hydroxy, substituted or unsubstituted amino, aryl, heteroaryl, hydroxycarbonyl or lower alkyloxycarbonyl;
• and
• n is an integer of 0 to 3
• or a pharmaceutically acceptable salt or hydrate thereof.

A compound of formula I′:

• 25
• wherein
• R1′ is hydroxy lower alkyl or carboxy lower alkyl and R4 is hydroxy;
• or
• R1′ and R4′ taken together form —CR5R6—(CH2)m—O— or —CR5R6 (CH2)pCH(OH)—O—
• wherein m is an integer of 1 to 3;
• p is an integer of 0 to 2;
• and
• R5 and R6 are each independently hydrogen, lower alkyl, lower alkoxy, or hydroxy lower alkyl;
• R2′ is hydrogen, lower alkyl, lower alkoxy, hydroxy lower alkyl, or carboxy lower alkyl;
• and
• R3′ is hydrogen, lower alkyl, cycloalkyl, lower alkoxy, arylalkyloxy, heteroarylalkyloxy, lower alkylcarbonyl, arylcarbonyl, substituted or unsubstituted carbamoyl or a group represented by the formula:
• —(CH2)n-Q
• wherein Q is hydroxy, substituted or unsubstituted amino, aryl, heteroaryl, hydroxycarbonyl or lower alkyloxycarbonyl;
• and
• n is an integer of 0 to 3
• or a pharmaceutically acceptable salt or hydrate thereof.