US5304658A
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Quinone derivatives, their production and use
Assignee: Takeda Pharmaceutical Co Ltd
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Filing: 1992-08-03
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Granted: 1994-04-19
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Expires: 2012-08-03
Abstract
Abstract Quinone derivatives of the general formula: ##STR1## (wherein R 1 and R 2 are the same or different, and independently are a hydrogen atom or a methyl or methoxy group, or R 1 and R 2 combine with each other to represent --CH═CH--CH═CH--; R 3 is a hydrogen atom or a methyl group; R 4 is an aliphatic, aromatic or heterocyclic group which may be substituted; R 5 is a methyl or methoxy group, a hydroxymethyl group which may be substituted or a carboxyl group which may be esterified or amidated; Z is a group represented by --C.tbd.C--, --CH═CH--, ##STR2## n is an integer of 0 to 10; m is an integer of 0 to 3; k is an integer of 0 to 5, provided, however, that in the case of m being 2 or 3, Z and k can vary arbitrarily within the bracketed repeating units) are novel compounds, possess metabolism ameliorating action for polyunsaturate fatty acids, particularly production inhibitory activity of lipid peroxides (antioxidant activity), thromboxane A 2 receptor antagonism, or production inhibitory activity of 5-lipoxygenase metabolites in mammals, and of use as drugs, such as antiasthmatic, antiallergic agent and cerebral-circulatory metabolism ameliorating agent.
Inventors
- 👤 Shinji Terao
- 👤 Yoshitaka Maki
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 14:47
CPC Classifications
A; A61; A61C; A61C15/00; A61C15/02
Claims Analysis
Total Claims: 16
Claim 1
Independent Claim
241 words
A compound of the formula ##STR280## wherein R 1 and R 2 are the same or different, and independently are methyl or methoxy, or R 1 and R 2 together represent --CH═CH--CH═CH--, R 4 is (a) a phenyl, (b) a naphthyl, (c) a thienyl or (d) a furyl, each of (a), (b), (c) or (d) being unsubstituted or substituted by 1 to 5 substituents selected from the group consisting of hydroxyl, a halogen, an alkyl having 1 to 3 carbon atoms, an alkoxy having 1 to 3 carbon atoms, acetyl, phenyl, p-tolyl, m-tolyl, a pyridyl, 3-pyridlmethyl, benzoyl, methylenedioxy, trimethylene, 1-imidazolyl and 1-imidazolylmethyl, R 5 is methoxy, hydroxymethyl, nitroxymethyl, aminocarbonyloxymethyl, methylaminocarbonyloxymethyl, ethylaminocarbonyloxymethyl, dimethylaminocarbonyloxymethyl, phenylaminocarbonyloxymethyl, morpholinocarbonyloxymethyl, piperidinocarbonyloxymethyl, aminocarbonyl, a mono- or di-alkylaminocarbonyl having 2 to 4 carbon atoms, benzylaminocarbonyl, α- or β-phenethylaminocarbonyl, 1-(α-naphthyl)ethylaminocarbonyl, aminocarbonyl substituted by phenyl or naphthyl, whose phenyl or naphthyl may be further substituted by hydroxy, amino, nitro, halogen, methyl or methoxy, hydroxyaminocarbonyl, N-hydroxy-N-methylaminocarbonyl, N-hydroxy-N-phenylaminocarbonyl, an amino acid residue-carbonyl whose amino acid is one selected from the group consisting of glycine, arginine, histidine, aspartic acid, proline, phenylalanine, methionine, alanine, and leucine, or a cyclic aminocarbonyl, selected from the group consisting of morpholinocarbonyl, piperidinocarbonyl, piperazinocarbonyl and pyrrolidinocarbonyl, the cyclic aminocarbonyl being unsubstituted or substituted by methyl, ethyl, propyl, pyrrolidinecarbonylmethyl, 4-fluorophenylcarbonylpropyl, phenyl, naphthyl, 2-methoxyphenyl, 4-methylphenyl, 4-bromophenyl, benzyl, 2-phenylethyl, 4-fluorophenylmethyl, 4-methoxyphenylmethyl, 3,4,5-trimethoxyphenylmethyl, diphenylmethyl, aminocarbonyl, 6-(9-β-D-ribofuranoside)adenyl or 4-amino-6,7-dimethoxyquinazolinyl, and n is an integer of 2 to 10, or the hydroquinone form of said compound.
Claim 2
Dependent Claim
241 words
A compound of the formula ##STR280## wherein R 1 and R 2 are the same or different, and independently are methyl or methoxy, or R 1 and R 2 together represent --CH═CH--CH═CH--, R 4 is (a) a phenyl, (b) a naphthyl, (c) a thienyl or (d) a furyl, each of (a), (b), (c) or (d) being unsubstituted or substituted by 1 to 5 substituents selected from the group consisting of hydroxyl, a halogen, an alkyl having 1 to 3 carbon atoms, an alkoxy having 1 to 3 carbon atoms, acetyl, phenyl, p-tolyl, m-tolyl, a pyridyl, 3-pyridlmethyl, benzoyl, methylenedioxy, trimethylene, 1-imidazolyl and 1-imidazolylmethyl, R 5 is methoxy, hydroxymethyl, nitroxymethyl, aminocarbonyloxymethyl, methylaminocarbonyloxymethyl, ethylaminocarbonyloxymethyl, dimethylaminocarbonyloxymethyl, phenylaminocarbonyloxymethyl, morpholinocarbonyloxymethyl, piperidinocarbonyloxymethyl, aminocarbonyl, a mono- or di-alkylaminocarbonyl having 2 to 4 carbon atoms, benzylaminocarbonyl, α- or β-phenethylaminocarbonyl, 1-(α-naphthyl)ethylaminocarbonyl, aminocarbonyl substituted by phenyl or naphthyl, whose phenyl or naphthyl may be further substituted by hydroxy, amino, nitro, halogen, methyl or methoxy, hydroxyaminocarbonyl, N-hydroxy-N-methylaminocarbonyl, N-hydroxy-N-phenylaminocarbonyl, an amino acid residue-carbonyl whose amino acid is one selected from the group consisting of glycine, arginine, histidine, aspartic acid, proline, phenylalanine, methionine, alanine, and leucine, or a cyclic aminocarbonyl, selected from the group consisting of morpholinocarbonyl, piperidinocarbonyl, piperazinocarbonyl and pyrrolidinocarbonyl, the cyclic aminocarbonyl being unsubstituted or substituted by methyl, ethyl, propyl, pyrrolidinecarbonylmethyl, 4-fluorophenylcarbonylpropyl, phenyl, naphthyl, 2-methoxyphenyl, 4-methylphenyl, 4-bromophenyl, benzyl, 2-phenylethyl, 4-fluorophenylmethyl, 4-methoxyphenylmethyl, 3,4,5-trimethoxyphenylmethyl, diphenylmethyl, aminocarbonyl, 6-(9-β-D-ribofuranoside)adenyl or 4-amino-6,7-dimethoxyquinazolinyl, and n is an integer of 2 to 10, or the hydroquinone form of said compound.
Claim 3
Dependent Claim
27 words
A compound as claimed in claim 1, wherein R 4 is phenyl or a phenyl having an halogen at meta or para p-position on the phenyl ring.
Claim 4
Dependent Claim
70 words
A compound as claimed in claim 1, wherein R 4 is (a) a phenyl or (b) a naphthyl, each of (a) or (b) being unsubstituted or substituted by 1 to 5 substituents selected from the group consisting of hydroxyl, a halogen, an alkyl having 1 to 3 carbon atoms, an alkoxy having 1 to 3 carbon atoms, acetyl, phenyl, p-tolyl, m-tolyl, a pyridyl, 3-pyridylmethyl, benzoyl, methylenedioxy, trimethylene, 1-imidazolyl and 1-imidazolylmethyl.
Claim 5
Dependent Claim
121 words
A compound as claimed in claim 1, wherein R 5 is aminocarbonyl, a mono- or di-alkylaminocarbonyl having 2 to 4 carbon atoms, benzylaminocarbonyl, α- or β-phenethylaminocarbonyl, 1-(α-naphthyl)ethylaminocarbonyl, aminocarbonyl substituted by phenyl or naphthyl, whose phenyl or naphthyl may be further substituted by hydroxy, amino, nitro, halogen, methyl or methoxy, hydroxyaminocarbonyl, N-hydroxy-N-methylaminocarbonyl, N-hydroxy-N-phenylaminocarbonyl, an amino acid residue-carbonyl whose amino acid is one selected from the group consisting of glycine, arginine, histidine, aspartic acid, proline, phenylalanine methionine, alanine, and leucine, or a cyclic aminocarbonyl selected from a group consisting of morpholinocarbonyl, piperidinocarbonyl, piperazinocarbonyl and pyrrolidinocarbonyl, the cyclic aminocarbonyl being unsubstituted or substituted by methyl, ethyl, propyl, pyrrolidinecarbonylmethyl, 4-fluorophenylcarbonylpropyl, phenyl, naphthyl, 2-methoxyphenyl, 4-methylphenyl, 4-bromophenyl, benzyl, 2-phenylethyl, 4-fluorophenylmethyl, 4-methoxyphenylmethyl, 3,4,5-trimethoxyphenylmethyl, diphenylmethyl, aminocarbonyl, 6-(9-β-D-ribofuranoside)adenyl or 4-amino-6,7-dimethoxyquinazolinyl.
Claim 6
Dependent Claim
22 words
A compound as claimed in claim 1, wherein R 5 is methoxy, hydroxymethyl, nitroxymethyl, aminocarbonyloxymethyl, methylaminocarbonyloxymethyl, ethylaminocarbonyloxymethyl, dimethylaminocarbonyloxymethyl, phenylaminocarbonyloxymethyl, morpholinocarbonyloxymethyl, or piperidinocarbonyloxymethyl.
Claim 7
Dependent Claim
183 words
A compound as claimed in claim 1, wherein R 4 is (a) a phenyl or (b) a naphthyl, each of (a) or (b) being unsubstituted or substituted by 1 to 5 substituents selected from the group consisting of hydroxyl, a halogen, an alkyl having 1 to 3 carbon atoms, an alkxoy having 1 to 3 carbon atoms, acetyl, phenyl, p-tolyl, m-tolyl, pyridyl, 3-pyridylmethyl, benzoyl, methylenedioxy, trimethylene, 1-imidazolyl and 1-imidazolylmethyl, and R 5 is aminocarbonyl, a mono- or di-alkylaminocarbonyl having 2 to 4 carbon atoms, benzylaminocarbonyl, α- or β-phenethylaminocarbonyl, 1-(α-naphthyl)ethylaminocarbonyl, aminocarbonyl substituted by phenyl or naphthyl, whose phenyl or naphthyl may be further substituted by hydroxy, amino, nitro, halogen, methyl or methoxy, hydroxyaminocarbonyl, N-hydroxy-N-methylaminocarbonyl, N-hydroxy-N-phenylaminocarbonyl, an amino acid residue-carbonyl whose amino acid is one selected from the group consisting of glycine, arginine, histidine, aspartic acid, proline, phenylalanine methionine, alanine, and leucine, or a cyclic aminocarbonyl selected from a group consisting of morpholinocarbonyl, piperidinocarbonyl, piperazinocarbonyl and pyrrolidinocarbonyl, the cyclic aminocarbonyl being unsubstituted or substituted by methyl, ethyl, propyl, pyrrolidinecarbonylmethyl, 4-fluorophenylcarbonylpropyl, phenyl, naphthyl, 2-methoxyphenyl, 4-methylphenyl, 4-bromophenyl, benzyl, 2-phenylethyl, 4-fluorophenylmethyl, 4-methoxyphenylmethyl, 3,4,5-trimethoxyphenylmethyl, diphenylmethyl, aminocarbonyl, 6-(9-β-D-ribofuranoside)adenyl or 4-amino-6,7-dimethoxyquinazolinyl.
Claim 8
Dependent Claim
84 words
A compound as claimed in claim 1, wherein R 4 is (a) a phenyl or (b) a naphthyl, each of (a) or (b) being unsubstituted or substituted by 1 to 5 substituents selected from the group consisting of hydroxyl, a halogen, an alkyl having 1 to 3 carbon atoms, an alkxoy having 1 to 3 carbon atoms, acetyl, phenyl, p-tolyl, m-tolyl, pyridyl, 3-pyridylmethyl, benzoyl, methylenedioxy, trimethylene, 1-imidazolyl and 1-imidazolylmethyl, and R 5 is methoxy, hydroxymethyl, nitroxymethyl, aminocarbonyloxymethyl, methylaminocarbonyloxymethyl, ethylaminocarbonyloxymethyl, dimethylaminocarbonyloxymethyl, phenylaminocarbonyloxymethyl, morpholinocarbonyloxymethyl, or piperidinocarbonyloxymethyl.
Claim 9
Dependent Claim
66 words
A compound as claimed in claim 1, wherein R 4 is a thienyl or a furyl, each of which is unsubstituted or substituted by 1 to 5 substituents selected from the group consisting of hydroxyl, a halogen, an alkyl having 1 to 3 carbon atoms, an alkoxy having 1 to 3 carbon atoms, acetyl, phenyl, p-tolyl, m-tolyl, a pyridyl, 3-pyridylmethyl, benzoyl, methylenedioxy, trimethylene, 1-imidazolyl and 1-imidazolylmethyl.
Claim 10
Dependent Claim
180 words
A compound as claimed in claim 1, wherein R 4 is a thienyl or a furyl, each of which is unsubstituted or substituted by 1 to 5 substituents selected from the group consisting of hydroxyl, a halogen, an alkyl having 1 to 3 carbon atoms, an alkoxy having 1 to 3 carbon atoms, acetyl, phenyl, p-tolyl, m-tolyl, a pyridyl, 3-pyridylmethyl, benzoyl, methylenedioxy, trimethylene, 1-imidazolyl and 1-imidazolylmethyl, and R 5 is aminocarbonyl, a mono- or di-alkylaminocarbonyl having 2 to 4 carbon atoms, benzylaminocarbonyl, α- or β-phenethylaminocarbonyl, 1-(α-naphthyl)ethylaminocarbonyl, aminocarbonyl substituted by phenyl or naphthyl, whose phenyl or naphthyl may be further substituted by hydroxy, amino, nitro, halogen, methyl or methoxy, hydroxyaminocarbonyl, N-hydroxy-N-methylaminocarbonyl, N-hydroxy-N-phenylaminocarbonyl, an amino acid residue-carbonyl whose amino acid is one selected from the group consisting of glycine, arginine, histidine, aspartic acid, proline, phenylalanine methionine, alanine, and leucine, or a cyclic aminocarbonyl selected from a group consisting of morpholinocarbonyl, piperidinocarbonyl, piperazinocarbonyl and pyrrolidinocarbonyl, the cyclic aminocarbonyl being unsubstituted or substituted by methyl, ethyl, propyl, pyrrolidinecarbonylmethyl, 4-fluorophenylcarbonylpropyl, phenyl, naphthyl, 2-methoxyphenyl, 4-methylphenyl, 4-bromophenyl, benzyl, 2-phenylethyl, 4-fluorophenylmethyl, 4-methoxyphenylmethyl, 3,4,5-trimethoxyphenylmethyl, diphenylmethyl, aminocarbonyl, 6-(9-β-D-ribofuranoside)adenyl or 4-amino-6,7-dimethoxyquinazolinyl.
Claim 11
Dependent Claim
80 words
A compound as claimed in claim 1, wherein R 4 is a thienyl or a furyl, each of which is unsubstituted or substituted by 1 to 5 substituents selected from the group consisting of hydroxyl, a halogen, an alkyl having 1 to 3 carbon atoms, an alkoxy having 1 to 3 carbon atoms, acetyl, phenyl, p-tolyl, m-tolyl, a pyridyl, 3-pyridylmethyl, benzoyl, methylenedioxy, trimethylene, 1-imidazolyl and 1-imidazolylmethyl, R 5 is methoxy, hydroxymethyl, nitroxymethyl, aminocarbonyloxymethyl, methylaminocarbonyloxymethyl, ethylaminocarbonyloxymethyl, dimethylaminocarbonyloxymethyl, phenylaminocarbonyloxymethyl, morpholinocarbonyloxymethyl, or piperidinocarbonyloxymethyl.
Claim 12
Dependent Claim
12 words
A compound as claimed in claim 1, wherein the compound is 7-(3,5,6-trimethyl-1,4-benzoquinon-2-yl)-7-phenylheptanol.
Claim 13
Dependent Claim
12 words
A compound as claimed in claim 1, wherein the compound is 7-(3,5,6-trimethyl-1,4-benzoquinon-2-yl)-7-phenylheptanamide.
Claim 14
Dependent Claim
12 words
A compound as claimed in claim 1, wherein the compound is 7-(3,5,6-trimethyl-1,4-benzoquinon-2-yl)-7-phenylheptanoglycine.
Claim 15
Dependent Claim
13 words
A compound as claimed in claim 1, wherein the compound is 1-[7-(3,5,6-trimethyl-1,4-benzoquinon-2-yl)-7-phenylheptanoyl] 4-(2-phenylethyl)piperadine.
Claim 16
Dependent Claim
29 words
A pharmaceutical composition which comprises a pharmaceutically effective amount of a compound as claimed in claim 1 or its hydroquinone form in association with a pharmaceutically acceptable carrier therefor.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1997-04-18 | 1997-10-18 | 1998-04-19 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2001-04-18 | 2001-10-18 | 2002-04-19 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2005-04-18 | 2005-10-18 | 2006-04-19 | $7700.00 | Window Closed / Lapsed |