Retinoic acid agonists as preventive and therapeutic agents for nephritis
First Claim
1. A method of treating nephritis or lupus nephritis comprising administering to a subject in need of same an effective a compound of the following formula or a pharmacologically acceptable salt thereof or a hydrate of the salt:
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where R1, R2, R3, R4 and R8 each represents hydrogen, halogeno, optionally substituted lower alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted lower alkoxy, optionally substituted aryloxy, optionally substituted heteroaryloxy, optionally substituted cycloalkylalkyl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted cycloalkyloxy, optionally substituted cycloalkylalkyloxy, optionally substituted arylalkyloxy, optionally substituted heteroarylalkyloxy, optionally substituted alkenyl or optionally substituted alkynyl, or alternatively two of R1, R2, R3, R4 and R8 adjacent to each other together with the carbon atoms to which they are bonded respectively may form a ring which may contain a heteroatom or be substituted;
A represents an optionally substituted pyrrole ring, B represents an optionally substituted aromatic hydrocarbon ring or an optionally substituted unsaturated heterocycle; and
D represents an optionally protected carboxyl.
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Accused Products
Abstract
The present invention provides a therapeutic or prophylactic agent as a substitute for conventional steroids or immunosuppressive agents to treat or prevent systemic erythematosus, glomerulonephritis, lupus nephritis, idiopathic thrombocytopenic purpura or autoimmune anemia. The agent comprises a retinoic acid receptor agonist, specifically a retinoic acid receptor subtype α (RARα) agonist, including for example:
(1) carboxylic acid compounds having condensed rings represented by the following formula:
(wherein the rings L and M are condensed, are the same as or different from each other, and represent an aromatic hydrocarbon which may have a substituent group or a heterocycle which may have a substituent group; the rings A and B are independent of each other and represent an aromatic hydrocarbon ring or heterocycle which may have a substituent group; and D represents a carboxyl group which may have a protective group),
(2) 4-{[(3,5-bistrimethylsilylphenyl)carbonyl]amino}benzoic acid, 4-{2-[5-(3-methoxymethyl-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene-2-yl)pyrrolyl]}benzoic acid, etc.
46 Citations
7 Claims
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1. A method of treating nephritis or lupus nephritis comprising administering to a subject in need of same an effective a compound of the following formula or a pharmacologically acceptable salt thereof or a hydrate of the salt:
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where R1, R2, R3, R4 and R8 each represents hydrogen, halogeno, optionally substituted lower alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted lower alkoxy, optionally substituted aryloxy, optionally substituted heteroaryloxy, optionally substituted cycloalkylalkyl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted cycloalkyloxy, optionally substituted cycloalkylalkyloxy, optionally substituted arylalkyloxy, optionally substituted heteroarylalkyloxy, optionally substituted alkenyl or optionally substituted alkynyl, or alternatively two of R1, R2, R3, R4 and R8 adjacent to each other together with the carbon atoms to which they are bonded respectively may form a ring which may contain a heteroatom or be substituted;
A represents an optionally substituted pyrrole ring, B represents an optionally substituted aromatic hydrocarbon ring or an optionally substituted unsaturated heterocycle; and
D represents an optionally protected carboxyl.- View Dependent Claims (2, 3, 4, 5, 6)
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7. A method of treating nephritis or lupus nephritis comprising administering to a subject in need of same an effective amount of a compound selected from the group consisting of 4-{2-[5-(4,7-dimethylbenzofuran-2-yl)pyrrolyl]}benzoic acid;
- 4-{2-[5-(7-fluoro-4-trifluoromethylbenzofuran-2-yl)pyrrolyl]}benzoic acid;
4-{2-[5-(3-fluoro-4,7-dimethylbenzofuran-2-yl)pyrrolyl]}benzoic acid; and
4-{2-[5-(7-ethyl-4-methylbenzofuran-2-yl)pyrrolyl]}benzoic acid.
- 4-{2-[5-(7-fluoro-4-trifluoromethylbenzofuran-2-yl)pyrrolyl]}benzoic acid;
Specification
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- Resources
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Current AssigneeEisai R & D Management Company Limited (Eisai Medical Research Incorporated)
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Original AssigneeEisai Company Limited (Eisai Medical Research Incorporated)
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InventorsIshibashi, Akira, Yamauchi, Toshihiko, Nagai, Mitsuo, Tokuhara, Naoki
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Primary Examiner(s)Raymond, Richard L.
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Assistant Examiner(s)Patel, Sudhaker B.
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Application NumberUS09/529,675Time in Patent Office693 DaysField of Search514/427, 514/429, 514/469, 548/517, 548/529, 549/469, 549/491US Class Current514/427CPC Class CodesA61K 31/00 Medicinal preparations cont...A61K 31/40 having five-membered rings ...A61K 31/4025 not condensed and containin...A61K 31/4155 non condensed and containin...A61K 31/498 Pyrazines or piperazines or...A61K 31/55 having seven-membered rings...A61K 31/695 Silicon compounds
