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US5075321A
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Methods of treating diseases characterized by interactions of IgG-containing immune complexes with macrophage Fc receptors using antiestrogenic benzothiophenes
Assignee: University of Pennsylvania
•
Filing: 1988-02-24
•
Granted: 1991-12-24
•
Expires: 2008-02-24
Abstract
Abstract Clearance of antibody-coated cells from the circulation is modulated by administering an effective amount of certain benzothiophene derivatives, or the physiologically acceptable acid addition salts thereof. The compounds are useful in treating mammalian diseases characterized by interactions between IgG containing immune complexes and macrophage Fc receptors.
Inventors
- 👤 Alan D. Schreiber
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 06:51
CPC Classifications
A; A61; A61K; A61K31/00; A61K31/56; A61K31/57
Claims Analysis
Total Claims: 60
Claim 1
Independent Claim
136 words
A method of modulating the clearance of antibody-coated cells from the circulation of mammals comprising administering to said mammal an effective amount of a compound of the formula ##STR5## wherein X and Y are independently OR 1 or COR 4 ; R 1 is hydrogen, COR 2 or R 3 ; R 2 is hydrogen, C 1 -C 14 alkyl, C 1 -C 3 chloroalkyl, C 1 -C 3 fluoroalkyl, C 5 -C 7 cycloalkyl, C 1 -C 4 alkoxy, phenyl, or phenyl mono- or disubstituted with C 1 -C 4 alkyl, C 1 -C 4 alkoxy, hydroxy, nitro, chloro, fluoro or tri(chloro or fluoro) methyl; R 3 is C 1 -C 4 alkyl, C 5 -C 7 cycloalkyl or benzyl; and R 4 is C 1 -C 6 alkyl; or a physiologically acceptable salt thereof.
Claim 2
Independent Claim
136 words
A method of modulating the clearance of antibody-coated cells from the circulation of mammals comprising administering to said mammal an effective amount of a compound of the formula ##STR5## wherein X and Y are independently OR 1 or COR 4 ; R 1 is hydrogen, COR 2 or R 3 ; R 2 is hydrogen, C 1 -C 14 alkyl, C 1 -C 3 chloroalkyl, C 1 -C 3 fluoroalkyl, C 5 -C 7 cycloalkyl, C 1 -C 4 alkoxy, phenyl, or phenyl mono- or disubstituted with C 1 -C 4 alkyl, C 1 -C 4 alkoxy, hydroxy, nitro, chloro, fluoro or tri(chloro or fluoro) methyl; R 3 is C 1 -C 4 alkyl, C 5 -C 7 cycloalkyl or benzyl; and R 4 is C 1 -C 6 alkyl; or a physiologically acceptable salt thereof.
Claim 3
Dependent Claim
12 words
The method of claim 1 wherein said modulation is inhibition of clearance.
Claim 4
Dependent Claim
12 words
The method of claim 1 wherein said antibody-coated cells are IgG-coated cells.
Claim 5
Dependent Claim
12 words
The method of claim 1 wherein said antibody-coated cells are antibody-coated erythrocytes.
Claim 6
Dependent Claim
12 words
The method of claim 3 wherein said IgG-coated cells are IgG-coated erythrocytes.
Claim 7
Dependent Claim
13 words
The method of claim 1 wherein X and Y are COR 4 .
Claim 8
Dependent Claim
10 words
The method of claim 6 wherein R 4 is tert-butyl.
Claim 9
Dependent Claim
14 words
The method of claim 1 wherein X and Y are independently OR 1 .
Claim 10
Dependent Claim
12 words
The method of claim 8 wherein X and Y are independently hydroxyl.
Claim 11
Dependent Claim
26 words
The method according to claim 1 wherein said amount is provided in doses of from about 0.05 mg/kg/day to about 50 mg/kg/day of mammal body weight.
Claim 12
Dependent Claim
25 words
The method according to claim 1 wherein said amount is provided in doses of from about 1.0 mg/kg/day to 20 mg/kg/day of mammal body weight.
Claim 13
Dependent Claim
21 words
The method according to claim 1 wherein said amount is provided in doses of about 10 mg/kg/day of mammal body weight.
Claim 14
Independent Claim
155 words
A method of treating a mammalian autoimmune disease characterized by interactions of IgG-containing immune complexes with macrophage Fc receptors comprising administering to an individual suspected of having the disease a compound having the formula: ##STR6## wherein X and Y are independent OR 1 or COR 4 ; R 1 is hydrogen, COR 2 or R 3 ; R 2 is hydrogen, C 1 -C 14 alkyl, C 1 -C 3 chloroalkyl, C 1 -C 3 fluoroalkyl, C 5 -C 7 cycloalkyl, C 1 -C 4 alkoxy, phenyl, or phenyl mono- or disubstituted with C 1 -C 4 alkoxy, hydroxy, nitro, chloro, fluoro or tri(chloro or fluoro) methyl; R 3 is C 1 -C 4 alkyl, C 5 -C 7 cycloalkyl or benzyl; and R 4 is C 1 -C 6 alkyl; or physiologically acceptable salt thereof in an amount effective to modulate the clearance by macrophages of antibody-coated cells from the circulation of said mammal.
Claim 15
Independent Claim
155 words
A method of treating a mammalian autoimmune disease characterized by interactions of IgG-containing immune complexes with macrophage Fc receptors comprising administering to an individual suspected of having the disease a compound having the formula: ##STR6## wherein X and Y are independent OR 1 or COR 4 ; R 1 is hydrogen, COR 2 or R 3 ; R 2 is hydrogen, C 1 -C 14 alkyl, C 1 -C 3 chloroalkyl, C 1 -C 3 fluoroalkyl, C 5 -C 7 cycloalkyl, C 1 -C 4 alkoxy, phenyl, or phenyl mono- or disubstituted with C 1 -C 4 alkoxy, hydroxy, nitro, chloro, fluoro or tri(chloro or fluoro) methyl; R 3 is C 1 -C 4 alkyl, C 5 -C 7 cycloalkyl or benzyl; and R 4 is C 1 -C 6 alkyl; or physiologically acceptable salt thereof in an amount effective to modulate the clearance by macrophages of antibody-coated cells from the circulation of said mammal.
Claim 16
Dependent Claim
26 words
The method of claim 13 wherein said modulation is inhibition of clearance and the amount is an amount effective to inhibit clearance of the antibody-coated cells.
Claim 17
Dependent Claim
12 words
The method of claim 13 wherein said antibody-coated cells are IgG-coated cells.
Claim 18
Dependent Claim
12 words
The method of claim 13 wherein said antibody-coated cells are antibody-coated erythrocytes.
Claim 19
Dependent Claim
11 words
The method of claim 15 wherein said IgG-coated are IgG-coated erythrocytes.
Claim 20
Dependent Claim
13 words
The method of claim 13 wherein X and Y are COR 4 .
Claim 21
Dependent Claim
10 words
The method of claim 18 wherein R 4 is tert-butyl.
Claim 22
Dependent Claim
14 words
The method of claim 13 wherein X and Y are independently OR 1 .
Claim 23
Dependent Claim
12 words
The method of claim 20 wherein X and Y are independently hydroxyl.
Claim 24
Dependent Claim
26 words
The method according to claim 13 wherein said amount is provided in doses of from about 0.05 mg/kg/day to about 50 mg/kg/day of mammal body weight.
Claim 25
Dependent Claim
25 words
The method according to claim 13 wherein said amount is provided in doses of from about 1.0 mg/kg/day to 20 mg/kg/day of mammal body weight.
Claim 26
Dependent Claim
21 words
The method according to claim 13 wherein said amount is provided in doses of about 10 mg/kg/day of mammal body weight.
Claim 27
Dependent Claim
13 words
A method according to claim 13 wherein the disease is immune thrombocytopenic purpura.
Claim 28
Dependent Claim
13 words
A method according to claim 13 wherein the disease is immune hemolytic anemia.
Claim 29
Dependent Claim
13 words
A method according to claim 13 wherein the disease is systemic lupus erythematosus.
Claim 30
Dependent Claim
12 words
A method according to claim 13 wherein the disease is rheumatoid arthritis.
Claim 31
Dependent Claim
128 words
The use in the manufacture of a medicament for treating an autoimmune disease of a composition in accordance with the formula: ##STR7## wherein X and Y are independent OR 1 or COR 4 ; R 1 is hydrogen, COR 2 or R 3 ; R 2 is hydrogen, C 1 -C 14 alkyl, C 1 -C 3 chloroalkyl, C 1 -C 3 fluoroalkyl, C 5 -C 7 cycloalkyl, C 1 -C 4 alkoxy, phenyl, or phenyl mono- or disubstituted with C 1 -C 4 alkyl, C 1 -C 4 alkoxy, hydroxy, nitro, chloro, fluoro or tri(chloro or fluoro) methyl; R 3 is C 1 -C 4 alkyl, C 5 -C 7 cycloalkyl or benzyl; and R 4 is C 1 -C 6 alkyl; or physiologically acceptable salt thereof.
Claim 32
Dependent Claim
128 words
The use in the manufacture of a medicament for treating an autoimmune disease of a composition in accordance with the formula: ##STR7## wherein X and Y are independent OR 1 or COR 4 ; R 1 is hydrogen, COR 2 or R 3 ; R 2 is hydrogen, C 1 -C 14 alkyl, C 1 -C 3 chloroalkyl, C 1 -C 3 fluoroalkyl, C 5 -C 7 cycloalkyl, C 1 -C 4 alkoxy, phenyl, or phenyl mono- or disubstituted with C 1 -C 4 alkyl, C 1 -C 4 alkoxy, hydroxy, nitro, chloro, fluoro or tri(chloro or fluoro) methyl; R 3 is C 1 -C 4 alkyl, C 5 -C 7 cycloalkyl or benzyl; and R 4 is C 1 -C 6 alkyl; or physiologically acceptable salt thereof.
Claim 33
Dependent Claim
13 words
The method of claim 29 wherein X and Y are COR 4 .
Claim 34
Dependent Claim
10 words
The method of claim 30 wherein R 4 is tert-butyl.
Claim 35
Dependent Claim
14 words
The method of claim 29 wherein X and Y are independently OR 1 .
Claim 36
Dependent Claim
12 words
The method of claim 32 wherein X and Y are independently hydroxyl.
Claim 37
Dependent Claim
128 words
The use in the manufacture of a medicament for treating immune thrombocytopenic purpurea of a composition in accordance with the formula: ##STR8## wherein X and Y are independent OR 1 or COR 4 ; R 1 is hydrogen, COR 2 or R 3 ; R 2 is hydrogen, C 1 -C 14 alkyl, C 1 -C 3 chloroalkyl, C 1 -C 3 fluoroalkyl, C 5 -C 7 cycloalkyl, C 1 -C 4 alkoxy, phenyl, or phenyl mono- or disubstituted with C 1 -C 4 alkyl, C 1 -C 4 alkoxy, hydroxy, nitro, chloro, fluoro or tri(chloro or fluoro) methyl; R 3 is C 1 -C 4 alkyl, C 5 -C 7 cycloalkyl or benzyl; and R 4 is C 1 -C 6 alkyl; or physiologically acceptable salt thereof.
Claim 38
Dependent Claim
128 words
The use in the manufacture of a medicament for treating immune thrombocytopenic purpurea of a composition in accordance with the formula: ##STR8## wherein X and Y are independent OR 1 or COR 4 ; R 1 is hydrogen, COR 2 or R 3 ; R 2 is hydrogen, C 1 -C 14 alkyl, C 1 -C 3 chloroalkyl, C 1 -C 3 fluoroalkyl, C 5 -C 7 cycloalkyl, C 1 -C 4 alkoxy, phenyl, or phenyl mono- or disubstituted with C 1 -C 4 alkyl, C 1 -C 4 alkoxy, hydroxy, nitro, chloro, fluoro or tri(chloro or fluoro) methyl; R 3 is C 1 -C 4 alkyl, C 5 -C 7 cycloalkyl or benzyl; and R 4 is C 1 -C 6 alkyl; or physiologically acceptable salt thereof.
Claim 39
Dependent Claim
13 words
The use of claim 34 wherein X and Y are COR 4 .
Claim 40
Dependent Claim
10 words
The use of claim 35 wherein R 4 is tert-butyl.
Claim 41
Dependent Claim
14 words
The use of claim 34 wherein X and Y are independently OR 1 .
Claim 42
Dependent Claim
12 words
The use of claim 37 wherein X and Y are independently hydroxyl.
Claim 43
Dependent Claim
128 words
The use in the manufacture of a medicament for treating immune hemolytic anemia of a composition in accordance with the formula: ##STR9## wherein X and Y are independent OR 1 or COR 4 ; R 1 is hydrogen, COR 2 or R 3 ; R 2 is hydrogen, C 1 -C 14 alkyl, C 1 -C 3 chloroalkyl, C 1 -C 3 fluoroalkyl, C 5 -C 7 cycloalkyl, C 1 -C 4 alkoxy, phenyl, or phenyl mono- or disubstituted with C 1 -C 4 alkyl, C 1 -C 4 alkoxy, hydroxy, nitro, chloro, fluoro or tri(chloro or fluoro) methyl; R 3 is C 1 -C 4 alkyl, C 5 -C 7 cycloalkyl or benzyl; and R 4 is C 1 -C 6 alkyl; or physiologically acceptable salt thereof.
Claim 44
Dependent Claim
128 words
The use in the manufacture of a medicament for treating immune hemolytic anemia of a composition in accordance with the formula: ##STR9## wherein X and Y are independent OR 1 or COR 4 ; R 1 is hydrogen, COR 2 or R 3 ; R 2 is hydrogen, C 1 -C 14 alkyl, C 1 -C 3 chloroalkyl, C 1 -C 3 fluoroalkyl, C 5 -C 7 cycloalkyl, C 1 -C 4 alkoxy, phenyl, or phenyl mono- or disubstituted with C 1 -C 4 alkyl, C 1 -C 4 alkoxy, hydroxy, nitro, chloro, fluoro or tri(chloro or fluoro) methyl; R 3 is C 1 -C 4 alkyl, C 5 -C 7 cycloalkyl or benzyl; and R 4 is C 1 -C 6 alkyl; or physiologically acceptable salt thereof.
Claim 45
Dependent Claim
13 words
The use of claim 39 wherein X and Y are COR 4 .
Claim 46
Dependent Claim
10 words
The use of claim 40 wherein R 4 is tert-butyl.
Claim 47
Dependent Claim
14 words
The use of claim 39 wherein X and Y are independently OR 1 .
Claim 48
Dependent Claim
12 words
The use of claim 42 wherein X and Y are independently hydroxyl.
Claim 49
Dependent Claim
128 words
The use in the manufacture of a medicament for treating systemic lupus erythematosus of a composition in accordance with the formula: ##STR10## wherein X and Y are independent OR 1 or COR 4 ; R 1 is hydrogen, COR 2 or R 3 ; R 2 is hydrogen, C 1 -C 14 alkyl, C 1 -C 3 chloroalkyl, C 1 -C 3 fluoroalkyl, C 5 -C 7 cycloalkyl, C 1 -C 4 alkoxy, phenyl, or phenyl mono- or disubstituted with C 1 -C 4 alkyl, C 1 -C 4 alkoxy, hydroxy, nitro, chloro, fluoro or tri(chloro or fluoro) methyl; R 3 is C 1 -C 4 alkyl, C 5 -C 7 cycloalkyl or benzyl; and R 4 is C 1 -C 6 alkyl; or physiologically acceptable salt thereof.
Claim 50
Dependent Claim
128 words
The use in the manufacture of a medicament for treating systemic lupus erythematosus of a composition in accordance with the formula: ##STR10## wherein X and Y are independent OR 1 or COR 4 ; R 1 is hydrogen, COR 2 or R 3 ; R 2 is hydrogen, C 1 -C 14 alkyl, C 1 -C 3 chloroalkyl, C 1 -C 3 fluoroalkyl, C 5 -C 7 cycloalkyl, C 1 -C 4 alkoxy, phenyl, or phenyl mono- or disubstituted with C 1 -C 4 alkyl, C 1 -C 4 alkoxy, hydroxy, nitro, chloro, fluoro or tri(chloro or fluoro) methyl; R 3 is C 1 -C 4 alkyl, C 5 -C 7 cycloalkyl or benzyl; and R 4 is C 1 -C 6 alkyl; or physiologically acceptable salt thereof.
Claim 51
Dependent Claim
13 words
The use of claim 44 wherein X and Y are COR 4 .
Claim 52
Dependent Claim
10 words
The use of claim 45 wherein R 4 is tert-butyl.
Claim 53
Dependent Claim
14 words
The use of claim 44 wherein X and Y are independently OR 1 .
Claim 54
Dependent Claim
12 words
The use of claim 47 wherein X and Y are independently hydroxyl.
Claim 55
Dependent Claim
128 words
The use in the manufacture of a medicament for treating immune thrombocytopenic purpurea of a composition in accordance with the formula: ##STR11## wherein X and Y are independent OR 1 or COR 4 ; R 1 is hydrogen, COR 2 or R 3 ; R 2 is hydrogen, C 1 -C 14 alkyl, C 1 -C 3 chloroalkyl, C 1 -C 3 fluoroalkyl, C 5 -C 7 cycloalkyl, C 1 -C 4 alkoxy, phenyl, or phenyl mono- or disubstituted with C 1 -C 4 alkyl, C 1 -C 4 alkoxy, hydroxy, nitro, chloro, fluoro or tri(chloro or fluoro) methyl; R 3 is C 1 -C 4 alkyl, C 5 -C 7 cycloalkyl or benzyl; and R 4 is C 1 -C 6 alkyl; or physiologically acceptable salt thereof.
Claim 56
Dependent Claim
128 words
The use in the manufacture of a medicament for treating immune thrombocytopenic purpurea of a composition in accordance with the formula: ##STR11## wherein X and Y are independent OR 1 or COR 4 ; R 1 is hydrogen, COR 2 or R 3 ; R 2 is hydrogen, C 1 -C 14 alkyl, C 1 -C 3 chloroalkyl, C 1 -C 3 fluoroalkyl, C 5 -C 7 cycloalkyl, C 1 -C 4 alkoxy, phenyl, or phenyl mono- or disubstituted with C 1 -C 4 alkyl, C 1 -C 4 alkoxy, hydroxy, nitro, chloro, fluoro or tri(chloro or fluoro) methyl; R 3 is C 1 -C 4 alkyl, C 5 -C 7 cycloalkyl or benzyl; and R 4 is C 1 -C 6 alkyl; or physiologically acceptable salt thereof.
Claim 57
Dependent Claim
13 words
The use of claim 49 wherein X and Y are COR 4 .
Claim 58
Dependent Claim
10 words
The use of claim 50 wherein R 4 is tert-butyl.
Claim 59
Dependent Claim
14 words
The use of claim 49 wherein X and Y are independently OR 1 .
Claim 60
Dependent Claim
12 words
The use of claim 52 wherein X and Y are independently hydroxyl.
References Cited (Backward Citations)
US4418068A
Cited
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| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
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| 3.5 Years (Year 4) | 1994-12-23 | 1995-06-24 | 1995-12-24 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1998-12-23 | 1999-06-24 | 1999-12-24 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2002-12-23 | 2003-06-24 | 2003-12-24 | $7700.00 | Window Closed / Lapsed |