US 6,294,674 B1 · Dibenzofuran sulfonamide matrix metalloproteinase inhibitors

Abstract

The present invention relates to compounds of Formula I that inhibit matrix metalloproteinases and to a method of inhibiting matrix metalloproteinases using the compounds. wherein Q is an un-natural amino acid. More particurlarly, the present invention relates to a method of treating diseases in which matrix metalloproteinases are involved such as multiple sclerosis, atherosclerotic plaque rupture, restenosis, aortic aneurism, heart failure, periodontal disease, corneal ulceration, burns, decubital ulcers, chronic ulcers or wounds, cancer metastasis, tumor angiogenesis, arthiritis, or other autoimmune or inflammatory diseases dependent upon tissue invasion by leukocytes.

The compounds:

6-[2-(4-Chloro-phenoxy)-2-methyl-propionylamino]-2-(dibenzofuran-2-sulfonylamino)-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-6-[2-(pyridin-4-ylsulfanyl)-acetylamino]-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-6-[2-(2,4-dichloro-phenoxy)-acetylamino]-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-6-[2-(2-trifluoromethyl-phenyl)-acetylamino]-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-6-(2-thiophen-2-yl-acetylamino)-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-6-(2-phenoxy-butyrylamino)-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-6-(phenylsulfanyl-acetylamino)-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-6-(2-phenoxy-acetylamino)-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-6-[2-(3,4-dimethoxy-phenyl)-acetylamino]-hexanoic acid;
6-[2-(4-tert-Butyl-phenoxy)-acetylamino]-2-(dibenzofuran-2-sulfonylamino)-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-6-[3-(3,4-dimethoxy-phenyl)-propionylamino]-hexanoic acid;
6-(2-(Cyclopent-1-enyl-acetylamino)-2-(dibenzofuran-2-sulfonylamino)-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-6-[2-(4-methoxy-phenoxy)-acetylamino]-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-6-[2-(naphthalen-1-yloxy)-acetylamino]-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-6-[2-(4-nitro-phenoxy)-acetylamino]-hexanoic acid;
6-[4-(4Chloro-3-methyl-phenoxy)-butyrylamino]-2-(dibenzofuran-2-sulfonylamino)-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-6-[3-(4-methoxy-phenyl)-propionylamino]-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-6-(2-pyridin-3-yl-acetylamino)-hexanoic acid;
6-(2-Benzo[1,3]dioxol-5-yl-acetylamino)-2-(dibenzofuran-2-sulfonylamino)-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-6-(2-pyridin-2-yl-acetylamino)-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-6-[4-(4-nitro-phenyl)-butyrylamino]-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-6-(3-pyridin-4-yl-propionylamino)-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-6-(2-phenylamino-acetylamino)-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-6-(2-indol-1-yl-acetylamino)-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-6-[3-(2-methoxy-phenyl)-propionylamino]-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-6-(4-phenyl-butyrylamino)-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-6-(3-p-tolyl-propionylamino)-hexanoic acid;
6-[3-(4-Chloro-phenyl)-propionylamino]-2-(dibenzofuran-2-sulfonylamino)-hexanoic acid;
6-[2-(2-Benzyloxy-phenyl)-acetylamino]-2-(dibenzofuran-2-sulfonylamino)-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-6-[2-naphthalen-2-yl-acetylamino)-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-6-(4-1H-indol-3-yl-butyrylamino)-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-6-(2-naphthalen-1-yl-acetylamino)-hexanoic acid;
6-[3-(4-Chloro-phenoxy)-propionylamino]-2-(dibenzofuran-2-2-sulfonylamino)-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-6-(6-phenyl-hexanoylamino)-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-6-[4-thiophen-2-yl-butyrylamino)-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-6-[3,3,3-triphenyl-propionylamino)-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-6-(3-diethylamino-propionylamino)-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-6-(1-phenyl-cyclopropane carbonylamino)-hexanoic acid;
6-(3-Benzo[1,3]dioxol-5-yl-propionylamino)-2-(dibenzofuran-2-sulfonylamino)-hexanoic acid;
6-[(Cyclopentyl-phenyl-acetyl)-amino]-2-(dibenzofuran-2-sulfonylamino)-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-6-[3-(4-methoxy-phenyl)-ureido]-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-6-[3-(3,4-dichloro-phenyl)-ureido]-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-6-(3-pyridin-3-yl-thioureido)-hexanoic acid;
6-(3-Benzhydryl-thioureido)-2-(dibenzofuran-2-sulfonylamino)-hexanoic acid;
6-(3-Benzyl-thioureido)-2-(dibenzofuran-2-sulfonylamino)-hexanoic acid;
6-(3-Adamantan-1-yl-thioureido)-2-(dibenzofuran-2-sulfonylamino)-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-6-(3-naphthalen-2-yl-thioureido)-hexanoic acid;
6-(3-Allyl-ureido)-2-(dibenzofuran-2-sulfonylamino)-hexanoic acid;
6-(3-Benzyl-ureido)-2-(dibenzofuran-2-sulfonylamino)-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-6-(3-phenyl-ureido)-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-6-(3-phenyl-acryloylamino)-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-6-phenylacetylamino-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-6-(3-phenyl-propionylamino)-hexanoic acid;
6-[2-(4-Chloro-phenoxy)-acetylamino]-2-(dibenzofuran-2-sulfonylamino)-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-6-[2-(2,4,6-triisopropyl-phenyl)-acetylamino]-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-6-(2-phenyl-butyrylamino)-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-6-(4fluoro-benzenesulfonylamino)-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-6-(4-methoxy-benzenesulfonylamino)-hexanoic acid;
6-(4-Bromo-benzenesulfonylamino)-2-(dibenzofuran-2-sulfonylamino)-hexanoic acid;
6-(2-Acetylaminothiazole-5-sulfonylamino)-2-(dibenzofuran-2-sulfonylamino)-hexanoic acid;
6-(4-Acetylamino-benzensulfonylamino)-2-(dibenzofuran-2-sulfonylamino)-hexanoic acid;
6-Benzenesulfonylamino-2-(dibenzofuran-2-sulfonylamino)-hexanoic acid;
6-(Butane-1-sulfonylamino)-2-(dibenzofuran-2-sulfonylamino)-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-6-(naphthalene-2-sulfonylamino)-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-6-(naphthalene-1-sulfonylamino)-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-6-(2-phenyl-ethenesulfonylamino)-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-6-isobutoxycarbonylamino-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-6-(9H-fluoren-9-ylmethoxycarbonylamino)-hexanoic acid;
6-(Adamantan-1-yloxycarbonylamino)-2-(dibenzofuran-2-sulfonylamino)-hexanoic acid;
6-Allyloxycarbonylamino-2-(dibenzofuran-2-sulfonylamino)-hexanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-4-(2-pyridin-4-yl-ethylcarbamoyl)-butyric acid;
2-(Dibenzofuran-2-sulfonylamino)-4-(2-methyl-butylcarbamoyl)-butyric acid;
2-(Dibenzofuran-2-sulfonylamino)-4-(2-hydroxy-propylcarbamoyl)-butyric acid;
2-(Dibenzofuran-2-sulfonylamino)-4-(4-propyl-phenylcarbamoyl)-butyric acid;
2-(Dibenzofuran-2-sulfonylamino)-4-(2,2-diphenyl-ethylcarbamoyl)-butyric acid;
4-Cyclopropylcarbamoyl-2-(dibenzofuran-2-sulfonylamino)-butyric acid;
2-(Dibenzofuran-2-sulfonylamino)-4-[(thiophen-2-ylmethyl)-carbamoyl]-butyric acid;
2-(Dibenzofuran-2-sulfonylamino)-4-(1,3-dimethyl-butylcarbamoyl)-butyric acid;
2-(Dibenzofuran-2-sulfonylamino)-4-(2-dimethylamino-ethylcarbamoyl)-butyric acid;
4-Benzylcarbamoyl-2-(dibenzofuran-2-sulfonylamino)-butyric acid;
2-(Dibenzofuran-2-sulfonylamino)-4-(2-thiophen-2-yl-ethylcarbamoyl)-butyric acid;
4-(4-Chloro-phenylcarbamoyl)-2-(dibenzofuran-2-sulfonylamino)-butyric acid;
2-(Dibenzofuran-2-sulfonylamino)-4-(4-phenyl-butylcarbamoyl)-butyric acid;
2-(Dibenzofuran-2-sulfonylamino)-4-[2-(1-methyl-1H-pyrrol-2-yl)-ethylcarbamoyl]-butyric acid;
2-(Dibenzofuran-2-sulfonylamino)-4-(2-methoxy-benzylcarbamoyl)-butyric acid;
2-(Dibenzofuran-2-sulfonylamino)-4-(naphthalen-1-ylmethyl)-carbamoyl]-butyric acid;
2-(Dibenzofuran-2-sulfonylamino)-pentanedioic acid 1-tert-butyl ester;
2-(Dibenzofuran-2-sulfonylamino)-4-phenethylcarbamoyl-butyric acid;
2-Dibenzofuran-2-sulfonylamino)-4-oxo-4-(4-propyl-phenyl)-butyric acid;
3-(4-tert-Butoxy-phenyl)-2-(dibenzofuran-2-sulfonylamino)-propionic acid;
3-Benzyloxy-2-(dibenzofiuran-2-sulfonylamino)-propionic acid;
2-(Dibenzofuran-2-sulfonylamino)-5-(toluene-4-sulfonylamino)-pentanoic acid;
5-Benzyloxycarbonylamino-2-(dibenzofuran-2-sulfonylamino)-pentanoic acid;
2-(Dibenzofuran-2-sulfonylamino)-butyric acid;
3-tert-Butoxy-2-(dibenzofuran-2-sulfonylamino)-propionic acid;
(Dibenzofuran-2-sulfonylamino)-phenyl-acetic acid;
and
2-(Dibenzofuran-2-sulfonylamino)-3-(4-fluorophenyl)-propionic acid.

95 more elements

Dibenzofuran sulfonamide matrix metalloproteinase inhibitors

Life of this patent

Dibenzofuran sulfonamide matrix metalloproteinase inhibitors

Life of this patent

Abstract

Claims1