Sulfonated amino acid derivatives and metalloproteinase inhibitors containing the same

A composition for inhibiting metalloproteinase which comprises a compound of formula I:

• wherein R1 is optionally substituted heteroarylalkyl;
• R2 is hydrogen atom or optionally substituted lower alkyl;
• R3 is optionally substituted arylene;
• R4 is a bond, —(CH2)m—, —CH═CH— or —C≡C—;
• R5 is optionally substituted aryl;
• Y is —NHOH or —OH;
• and m is 1 or 2;
• provided R2 is hydrogen atom when Y is —NHOH,
• R5 is aryl substituted by lower alkyl or optionally substituted aryl when R4 is a bond,
• with the proviso that R5 and R3 together do not form a biphenyl group, and
• its optically active substance, pharmaceutically acceptable salt, or hydrate thereof.

A compound of the formula I:

• wherein R1 is optionally substituted heteroarylalkyl;
• R2 is hydrogen atom or optionally substituted lower alkyl;
• R3 is optionally substituted arylene;
• R4 is a bond, —(CH2)m—, —CH═CH— or —C≡C—;
• R5 is optionally substituted aryl;
• Y is —NHOH or —OH;
• and m is 1 or 2;
• provided R2 is hydrogen atom when Y is —NHOH,
• R5 is aryl substituted with lower alkyl or optionally substituted aryl when R4 is a bond,
• and R3 is not 1,2-phenylene,
• and its optically active substance, pharmaceutically acceptable salt, or hydrate thereof.

A compound of formula II:

• wherein R6 is —CH═CH— or —C≡C—;
• R7 is optionally substituted aryl;
• R8 and R9 are each independently hydrogen atom, lower alkoxy, or nitro;
• R1 is optionally substituted heteroarylalkyl;[,]
• R2 is hydrogen atom or optionally substituted lower alkyl;
• Y is—NHOH or —OH;
• and
• its optically active substance, pharmaceutically acceptable salt, or hydrate thereof.

A compound of formula III:

• wherein R10 is —(CH2)m—;
• m is 1 or 2;
• R1 is optionally substituted heteroarylalkyl;
• R2 is hydrogen atom or optionally substituted lower alkyl;
• R7 is optionally substituted aryl;
• R8 and R9 are each independently hydrogen atom, lower alkoxy, or nitro;
• Y is—NHOH or —OH;
• and
• its optically active substance, pharmaceutically acceptable salt, or hydrate thereof.

A compound of formula V:

• wherein R12 is —CH═CH— or —C≡C—;
• R1 is optionally substituted heteroarylalkyl;
• R1 is hydrogen atom or optionally substituted lower alkyl;
• R7 is optionally substituted aryl;
• R8 and R9 are each independently hydrogen atom, lower alkoxy or nitro;
• and
• its optically active substance, pharmaceutically acceptable salt, or hydrate thereof.

A compound of formula X:

• wherein R12 is —CH═CH— or —C≡C—;
• R1 is optionally substituted heteroarylalkyl;
• R7 is optionally substituted aryl;
• R8 and R9 are each independently hydrogen atom, lower alkoxy or nitro;
• and
• its optically active substance, pharmaceutically acceptable salt, or hydrate thereof.

A method of inhibiting the activity of a metalloproteinase, comprising administering to a subject in need thereof an effective amount of a compound of formula I:

• wherein R1 is optionally substituted heteroarylalkyl;
• R1 is hydrogen atom or optionally substituted lower alkyl;
• R3 is optionally substituted arylene;
• R4 is a bond, —(CH2)m—, —CH═CH— or —C≡C—;
• R5 is optionally substituted aryl;
• Y is —NHOH or —OH;
• and m is 1 or 2;
• provided R2 is hydrogen atom when Y is —NHOH,
• with the proviso that R5 and R3 together do not form a biphenyl group, and
• its optically active substance, pharmaceutically acceptable salt, or hydrate thereof.

A method of inhibiting the activity of a type-IV collagenase, comprising administering to a subject in need thereof an effective amount of a compound of formula I:

• wherein R1 is or optionally substituted heteroarylalkyl;
• R2 is hydrogen atom or optionally substituted lower alkyl;
• R3 is optionally substituted arylene;
• R4 is a bond, —(CH2)m—, —CH═CH— or —C≡C—;
• R5 is optionally substituted aryl;
• Y is —NHOH or —OH;
• and m is 1 or 2;
• provided R2 is hydrogen atom when Y is —NHOH,
• with the proviso that R5 and R3 together do not form a biphenyl group, and
• its optically active substance, pharmaceutically acceptable salt, or hydrate thereof.