US4755524A
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Novel phenolic thioethers as inhibitors of 5-lipoxygenase
Assignee: GD Searle LLC
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Filing: 1987-01-15
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Granted: 1988-07-05
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Expires: 2007-01-15
Abstract
Abstract The compounds of the present invention comprise substituted phenolic thioethers represented by the formula: ##STR1## wherein: R 1 and R 2 are the same or different and independently represent tert-alkyl or phenyl; A represents methylene or methylene substituted by alkyl, dialkyl or hydroxy, provided that when A includes hydroxymethylene, the hydroxymethylene group is not adjacent to a heteroatom; B represents sulfur, sulfoxide, sulfone, oxygen, --NH-- or nitrogen substituted by alkyl, phenyl, benzyl, substituted phenyl or substituted benzyl; C represents methylene or methylene substituted by alkyl; R 3 represents CO 2 H, CO 2 -alkyl or a tetrazole group; m is 0 or 1, n is 2, 3 or 4 and p is 1, 2 or 3; and the pharmaceutically acceptable salts thereof. The compounds of the present invention are specific inhibitors of 5-lipoxygenase and, therefore, are useful in the treatment of local and systemic inflammation, allergy and hypersensitivity reactions and other disorders in which agents formed in the 5-lipoxygenase metabolic pathway are involved.
Inventors
- 👤 Richard A. Mueller
- 👤 Richard A. Partis
- 👤 James R. Deason
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-03 13:02
CPC Classifications
C; C07; C07D; C07D257/00; C07D257/02; C07D257/04; A; A61; A61P; A61P11/00; A61P29/00; A61P37/00; A61P37/08; A61P43/00; C07C; C07C317/00; C07C317/44; C07C323/00; C07C323/10; C07C323/18; C07C323/20; C07C323/22; C07C323/23; C07C323/24; C07C323/25; C07C323/50; C07C323/51; C07C323/52; C07C323/64; C07C323/65; C07C327/00; C07C327/20; C07C327/22; C07C327/36; C07C331/00; C07C331/02; C07C331/10
Claims Analysis
Total Claims: 41
Claim 1
Independent Claim
206 words
A compound of the formula: ##STR77## or a pharmaceutically acceptable salt thereof wherein R 1 and R 2 are the same or different and independently represent tert-alkyl or phenyl; A represents methylene or methylene substituted by alkyl, dialkyl or hydroxy, provided that when A includes hydroxymethylene, the hydroxymethylene group is not adjacent to a heteroatom; B represents sulfur, sulfone, oxygen, --NH-- or nitrogen substituted by alkyl, phenyl, benzyl, phenyl substituted by one or two substituents which may be the same or different and are independently selected from the group consisting of halogen, C 1 -C 6 alkyl, hydroxy, C 1 -C 6 -alkoxy, acetoxy, carboxylic acid and C 1 -C 6 alkyl esters thereof, nitro or phenyl or benzyl substituted by one or two substituents which may be the same or different and are independently selected from the group consisting of halogen, C 1 -C 6 alkyl, hydroxy, C 1 -C 6 alkoxy, acetoxy, carboxylic acid and C 1 -C 6 alkyl esters thereof, nitro or phenyl; C represents methylene or methylene substituted by alkyl; R 3 represents CO 2 H, CO 2 -alkyl, or a tetrazole group; m is 0 or 1, n is 2, 3, or 4 and p is 1, 2 or 3.
Claim 2
Dependent Claim
206 words
A compound of the formula: ##STR77## or a pharmaceutically acceptable salt thereof wherein R 1 and R 2 are the same or different and independently represent tert-alkyl or phenyl; A represents methylene or methylene substituted by alkyl, dialkyl or hydroxy, provided that when A includes hydroxymethylene, the hydroxymethylene group is not adjacent to a heteroatom; B represents sulfur, sulfone, oxygen, --NH-- or nitrogen substituted by alkyl, phenyl, benzyl, phenyl substituted by one or two substituents which may be the same or different and are independently selected from the group consisting of halogen, C 1 -C 6 alkyl, hydroxy, C 1 -C 6 -alkoxy, acetoxy, carboxylic acid and C 1 -C 6 alkyl esters thereof, nitro or phenyl or benzyl substituted by one or two substituents which may be the same or different and are independently selected from the group consisting of halogen, C 1 -C 6 alkyl, hydroxy, C 1 -C 6 alkoxy, acetoxy, carboxylic acid and C 1 -C 6 alkyl esters thereof, nitro or phenyl; C represents methylene or methylene substituted by alkyl; R 3 represents CO 2 H, CO 2 -alkyl, or a tetrazole group; m is 0 or 1, n is 2, 3, or 4 and p is 1, 2 or 3.
Claim 3
Dependent Claim
15 words
A compound according to claim 1 wherein R 1 and R 2 are both tert-alkyl.
Claim 4
Dependent Claim
11 words
A compound according to claim 2 wherein said tert-alkyl is tert-butyl.
Claim 5
Dependent Claim
15 words
A compound according to claim 1 wherein R 1 and R 2 are both phenyl.
Claim 6
Dependent Claim
21 words
A compound according to claim 2 wherein (A) n is --CH 2 --CH 2 -- or --CH 2 --CH(OH)--CH 2 --.
Claim 7
Dependent Claim
12 words
A compound according to claim 2 wherein B is sulfur or sulfone.
Claim 8
Dependent Claim
23 words
A compound according to claim 2 wherein B is oxygen, --NH-- or nitrogen substituted by alkyl, phenyl, benzyl, substituted phenyl or substituted benzyl.
Claim 9
Dependent Claim
12 words
A compound according to claim 2 wherein C is --CH 2 --.
Claim 10
Dependent Claim
13 words
A compound according to claim 2 wherein R 3 is --CO 2 H.
Claim 11
Dependent Claim
28 words
A pharmaceutical composition for the treatment of inflammation and allergy conditions comprising a therapeutically effective amount of a compound according to claim 1 and a pharmaceutically acceptable carrier.
Claim 12
Dependent Claim
11 words
A pharmaceutical composition according to claim 10 adapted for oral administration.
Claim 13
Dependent Claim
11 words
A pharmaceutical composition according to claim 10 adapted for aerosol administration.
Claim 14
Dependent Claim
11 words
A pharmaceutical composition according to claim 10 adapted for parenteral administration.
Claim 15
Dependent Claim
14 words
A pharmaceutical composition according to claim 13 wherein said parenteral administration is intravenous administration.
Claim 16
Dependent Claim
29 words
A method of eliciting an anti-inflammatory or anti-allergic effect in a mammal in need thereof comprising administering thereto a therapeutically effective amount of a compound according to claim 1.
Claim 17
Dependent Claim
25 words
A method of treating asthma in a mammal in need thereof comprising administering thereto a therapeutically effective amount of a compound according to claim 1.
Claim 18
Dependent Claim
27 words
A method of treating proliferative skin disorders in a mammal in need thereof comprising administering thereto a therapeutically effective amount of a compound according to claim 1.
Claim 19
Dependent Claim
12 words
A method according to claim 14 wherein said compound is administered topically.
Claim 20
Dependent Claim
25 words
A method of inhibiting 5-lipoxygenase in a mammal in need thereof comprising administering thereto a therapeutically effective amount of a compound according to claim 1.
Claim 21
Dependent Claim
10 words
A compound according to claim 1 which is [[2-[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]thio]-1-methylpropyl]thio]acetic acid.
Claim 22
Dependent Claim
10 words
A compound according to claim 1 which is [2-[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]thio]ethoxy]acetic acid.
Claim 23
Dependent Claim
10 words
A compound according to claim 1 which is [2S*-[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]thio]-1R*-methylpropoxy]acetic acid.
Claim 24
Dependent Claim
10 words
A compound according to claim 1 which is [2R*-[[3,5-bis-(1,1-dimethylethyl)-4-hydroxyphenyl]thio]-1R*-methylpropoxy]acetic acid.
Claim 25
Dependent Claim
28 words
A pharmaceutical composition for the treatment of inflammation and allergy conditions comprising a therapeutically effective amount of a compound according to claim 10 and a pharmaceutically acceptable carrier.
Claim 26
Dependent Claim
28 words
A pharmaceutical composition for the treatment of inflammation and allergy conditions comprising a therapeutically effective amount of a compound according to claim 20 and a pharmaceutically acceptable carrier.
Claim 27
Dependent Claim
28 words
A pharmaceutical composition for the treatment of inflammation and allergy conditions comprising a therapeutically effective amount of a compound according to claim 21 and a pharmaceutically acceptable carrier.
Claim 28
Dependent Claim
28 words
A pharmaceutical composition for the treatment of inflammation and allergy conditions comprising a therapeutically effective amount of a compound according to claim 22 and a pharmaceutically acceptable carrier.
Claim 29
Dependent Claim
29 words
A method of eliciting an anti-inflammatory or anti-allergic effect in a mammal in need thereof comprising administering thereto a therapeutically effective amount of a compound according to claim 10.
Claim 30
Dependent Claim
29 words
A method of eliciting an anti-inflammatory or anti-allergic effect in a mammal in need thereof comprising administering thereto a therapeutically effective amount of a compound according to claim 20.
Claim 31
Dependent Claim
29 words
A method of eliciting an anti-inflammatory or anti-allergic effect in a mammal in need thereof comprising administering thereto a therapeutically effective amount of a compound according to claim 21.
Claim 32
Dependent Claim
29 words
A method of eliciting an anti-inflammatory or anti-allergic effect in a mammal in need thereof comprising administering thereto a therapeutically effective amount of a compound according to claim 23.
Claim 33
Dependent Claim
10 words
A compound according to claim 1 which is ethyl [2R*-[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]thio-]1R*-methylpropoxy]acetate.
Claim 34
Dependent Claim
10 words
A compound according to claim 1 which is ethyl 4-[[2-[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]thio]ethyl]thio]butanoate.
Claim 35
Dependent Claim
10 words
A compound according to claim 1 which is ethyl [[2-[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]thio]ethyl]thio]acetate.
Claim 36
Dependent Claim
9 words
A compound according to claim 1 which is 1,1-dimethylethyl[[2-[[3,5-bis-(1,1-dimethylethyl)-4-hydroxyphenyl]thio]ethyl]thio]acetate.
Claim 37
Dependent Claim
9 words
A compound according to claim 1 which is ethyl[[2-[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]sulfinyl]ethyl]thio]acetate.
Claim 38
Dependent Claim
10 words
A compound according to claim 1 which is methyl [[3-[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]thio]propyl](phenylmethyl)amino]acetate.
Claim 39
Dependent Claim
11 words
A compound according to claim 1 which is [[3-[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]thio]propyl](phenylmethyl)amino]acetic acid hydrochloride.
Claim 40
Dependent Claim
10 words
A compound according to claim 1 which is ethyl [2S*-[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]thio]-1R*-methylpropoxy]acetate.
Claim 41
Dependent Claim
10 words
A compound according to claim 1 which is [[4-[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]thio]butyl]thio]acetic acid.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1991-07-05 | 1992-01-04 | 1992-07-05 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1995-07-05 | 1996-01-04 | 1996-07-05 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1999-07-05 | 2000-01-04 | 2000-07-05 | $7700.00 | Window Closed / Lapsed |