Mmp-12 inhibitors
AssigneeShionogi & Co., Ltd.
InventorsYozo Hori, Fumihiko Watanabe, Hiroshige Tsuzuki, Shingo Furue, Yoshinori Tamura
Life of this patent
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Abstract
A compound of the formula (1): 1 wherein R1 is hydroxy and the like; R2 is optionally substituted lower alkyl and the like; R3 is hydrogen atom and the like; R4 is optionally substituted arylene and the like; R5 is —C≡C— and the like; R6 is optionally substituted naphtyl and the like its optically active substance, its prodrug, their pharmaceutically acceptable salt, or solvate thereof.
Claims33
A compound of the formula (I):
- 80
- wherein R1 is NHOH, hydroxy, or lower alkyloxy;
- R2 is hydrogen atom, optionally substituted lower alkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, or optionally substituted heteroarylalkyl;
- R3 is hydrogen atom, optionally substituted lower alkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, or optionally substituted heteroarylalkyl;
- R4 is optionally substituted arylene, or optionally substituted heteroarylene;
- R5 is a bond, —(CH2)p—, —CH═CH—, —C≡C—, —CO—, CO—NH—, —N═N—, —N(RA)—, —NH—CO—NH—, —NH—CO—, —O—, —S—, —SO2—, —SO2NH—, —SO2—NH—N═CH—, or
- a group represented by the formula:
- 81
- wherein RA is hydrogen atom or lower alkyl, p is 1 or 2
- R6 is optionally substituted naphtyl, optionally substituted isoquinolyl, optionally substituted quinolyl, optionally substituted 1,3-benzodioxolyl, optionally substituted benzofuranyl, or optionally substituted benzothienyl, its optically active substance, its prodrug, their pharmaceutically acceptable salt, or solvate thereof.
A compound of the formula (IV):
- 85
- wherein R9 is hydrogen atom, methyl, isopropyl, isobutyl, aminocarbonylmethyl, 2-methylthioethyl, 4-hydroxyphenyl, benzyl, 4-hydroxybenzyl, indol-3-ylmethyl, or (5-hydroxy-indol-3-yl)methyl;
- R10 is 1,4-phenylene or 2,5-thiophen-diyl;
- R11 is —C≡C—, —CO—NH—, —NH—CO—, —O—, or
- a group represented by a formula:
- 86
- R12 is each independently hydrogen atom, halogen, lower alkyl, lower alkyloxy, halo(lower)alkyl, nitro, cyano, optionally substituted amino, or hydroxy;
- m is 0, 1, 2, or 3,
- its optically active substance, its prodrug, their pharmaceutically acceptable salt, or solvate thereof.
A pharmaceutical composition containing as an active ingredient a compound having an inhibitory activity against matrix metalloproteinase-12.
A composition for treating or preventing chronic obstructive pulmonary disease containing as an active ingredient a compound having an inhibitory activity against matrix metalloproteinase-12.
A method for treating a mammal, including a human, to alleviate the pathological effects of chronic obstructive pulmonary disease, which comprises administration to said mammal of a compound having an inhibitory activity against matrix metalloproteinase-12.
Use of a compound having an inhibitory activity against matrix metalloproteinase-12 for preparation of a pharmaceutical composition for treating chronic obstructive pulmonary disease.
A method of inhibiting matrix metalloproteinase-12, which is characterized by contacting a compound having an inhibitory activity against matrix metalloproteinase-12 with matrix metalloproteinase-12.
(Addition) A compound of the formula (II):
- 87
- wherein R1 is NHOH, hydroxy, or lower alkyloxy;
- R2 is optionally substituted lower alkyl, (hydroxy, carboxy, lower alkylthio, or aminocarbonyl as a substituent), optionally substituted aryl, optionally substituted aralkyl;
- R3 is hydrogen atom, optionally substituted lower alkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, or optionally substituted heteroarylalkyl;
- R4 is 1,4-phenylene or 2,5-thiophen-diyl;
- R5 is —C≡C—, —CO—NH—, —NH—CO—, —O—, or
- a group represented by a formula:
- 88
- R7 is each independently hydrogen atom, halogen, lower alkyl, cycloalkyl, lower alkenyl, lower alkynyl, lower alkyloxy, lower alkenyloxy, lower alkylthio, halo(lower)alkyl, hydroxy, carboxy, lower alkyloxycarbonyl, aminocarbonyl, acyl, nitro, cyano, or optionally substituted amino;
- m is 0, 1, 2, or 3
- its optically active substance, its prodrug, their pharmaceutically acceptable salt, or solvate thereof.
(Addition) A compound of the formula (IV):
- 89
- wherein R9 is methyl, isopropyl, isobutyl, aminocarbonylmethyl, 2-methylthioethyl, 4-hydroxyphenyl, benzyl, 4-hydroxybenzyl;
- R10 is ,4-phenylene or 2,5-thiophen-diyl;
- R11 is —C≡C—, —CO—NH—, —NH—CO—, —O—, or
- a group represented by a formula:
- 90
- R12 is each independently hydrogen atom, halogen, lower alkyl, lower alkyloxy, halo(lower)alkyl, nitro, cyano, optionally substituted amino, or hydroxy;
- m is 0, 1, 2, or 3
- its optically active substance, its prodrug, their pharmaceutically acceptable salt, or solvate thereof.
Dependencies are inferred from the claim text.