US4537903A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Substituted cinnamyl-2,3-dihydrobenzofuran and analogs useful as anti-inflammatory agents
Assignee: Merck and Co Inc
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Filing: 1983-10-12
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Granted: 1985-08-27
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Expires: 2003-10-12
Abstract
Abstract Substituted cinnamyl-2,3-dihydrobenzofurans and analogs were prepared from the nucleophilic substitution of a cinnamylhalide with a 2,3-dihydrobenzofuran anion or an analog thereof. These compounds were found to be potent topical anti-inflammatory agents.
Inventors
- 👤 Michael N. Chang
- 👤 Milton L. Hammond
- 👤 Norman P. Jensen
- 👤 John McDonald
- 👤 Robert A. Zambias
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-06 04:47
CPC Classifications
C; C07; C07D; C07D307/00; C07D307/77; C07D307/78; C07D307/79; A; A61; A61P; A61P29/00; C07C; C07C255/00; C07C43/00; C07C43/02; C07C43/20; C07C43/225; C07C43/23; C07C47/00; C07C47/52; C07C47/575; C07C49/00; C07C49/20; C07C49/24; C07C49/245; C07C49/248; C07C49/76; C07C49/82; C07C49/835; C07C49/84; C07D311/00; C07D311/02; C07D311/04; C07D311/58
Claims Analysis
Total Claims: 15
Claim 1
Independent Claim
167 words
A compound of formula (I) or (II) ##STR4## or a pharmaceutically acceptable salt thereof wherein n is 2 or 3 A is (a) phenyl substituted with (R 1 ) q wherein when q is 2 to 5 R 1 can be the same or different from each other and R 1 is (1) hydrogen; (2) halo; (3) loweralykoxy; (4) lower alkylthio; (5) lower alkyl sulfinyl; (6) lower alkyl sulfonyl; (7) unsubstituted or substituted phenyl loweralkoxy; (8) loweralkyl; (9) loweralkenyl; (10) lower alkanoyl; (11) haloloweralkyl; (12) --COOH; (13) aryl; (14) aryloxy; (15) cyano; (16) hydroxyloweralkyl; (17) halo loweralkanoyl; (18) heteroaryl as defined below; or (19) loweralkanoyloxy; q is 0 to 5; (b) unsubstituted or substituted heteroaryl selected from a group consisting of: (1) thienyl; (2) benzothienyl; (3) furyl; (4) benzofuryl; (5) pyrryl; (6) indolyl; (7) thiazolyl; (8) benzothiazolyl; (9) thiadiazolyl; (10) benzothiadiazolyl; (11) quinolyl; (12) isoquinolyl; (13) pyridyl; (14) pyrazinyl; (15) tetrazolyl; or (16) triazolyl, the heteroaryl above being substituted with one or more of R 1 .
Claim 2
Dependent Claim
167 words
A compound of formula (I) or (II) ##STR4## or a pharmaceutically acceptable salt thereof wherein n is 2 or 3 A is (a) phenyl substituted with (R 1 ) q wherein when q is 2 to 5 R 1 can be the same or different from each other and R 1 is (1) hydrogen; (2) halo; (3) loweralykoxy; (4) lower alkylthio; (5) lower alkyl sulfinyl; (6) lower alkyl sulfonyl; (7) unsubstituted or substituted phenyl loweralkoxy; (8) loweralkyl; (9) loweralkenyl; (10) lower alkanoyl; (11) haloloweralkyl; (12) --COOH; (13) aryl; (14) aryloxy; (15) cyano; (16) hydroxyloweralkyl; (17) halo loweralkanoyl; (18) heteroaryl as defined below; or (19) loweralkanoyloxy; q is 0 to 5; (b) unsubstituted or substituted heteroaryl selected from a group consisting of: (1) thienyl; (2) benzothienyl; (3) furyl; (4) benzofuryl; (5) pyrryl; (6) indolyl; (7) thiazolyl; (8) benzothiazolyl; (9) thiadiazolyl; (10) benzothiadiazolyl; (11) quinolyl; (12) isoquinolyl; (13) pyridyl; (14) pyrazinyl; (15) tetrazolyl; or (16) triazolyl, the heteroaryl above being substituted with one or more of R 1 .
Claim 3
Dependent Claim
43 words
The compound of formula (I) according to claim 1 wherein: A is phenyl substituted with (R 1 ) q wherein R 1 is (a) hydrogen; (b) loweralkoxy; (c) halo; (d) lowerhaloalkyl, (e) loweralkanoyl; (f) hydroxyloweralkyl; or (g) CN; q is 1 or 2.
Claim 4
Dependent Claim
16 words
The compound of claim 1 having the formula: ##STR5## wherein R 1 is loweralkanoyl or hydroxyloweralkyl.
Claim 5
Dependent Claim
13 words
The compounds of claim 1 which is (a) 2,3-dihydro-5-hydroxy-6-(o-hydroxymethyl-cinnamyl) benzofuran; or (b) 6-(p-acetylcinnamyl)-2,3-dihydro-5-hydroxybenzofuran.
Claim 6
Dependent Claim
183 words
A pharmaceutical composition for treating topical inflammation comprising a pharmaceutical carrier and an effective amount of a compound of formula (I) or (II) ##STR6## or a pharmaceutically acceptable salt thereof wherein n is 2 or 3 A is (a) phenyl substituted with (R 1 ) q wherein when q is 2 to 5 R 1 can be the same or different from each other and R 1 is (1) hydrogen; (2) halo; (3) loweralkoxy; (4) lower alkylthio; (5) lower alkyl sulfinyl; (6) lower alkyl sulfonyl; (7) unsubstituted or substituted phenyl loweralkoxy; (8) loweralkyl; (9) loweralkenyl; (10) lower alkanoyl; (11) haloloweralkyl; (12) --COOH; (13) aryl; (14) aryloxy; (15) cyano; (16) hydroxyloweralkyl; (17) halo loweralkanoyl; (18) heteroaryl as defined below; or (19) loweralkanoyloxy; q is 0 to 5; (b) unsubstituted or substituted heteroaryl, selected from a group consisting of: (1) thienyl; (2) benzothienyl; (3) furyl; (4) benzofuryl; (5) pyrryl; (6) indolyl; (7) thiazolyl; (8) benzothiazolyl; (9) thiadiazolyl; (10) benzothiadiazolyl; (11) quinolyl; (12) isoquinolyl; (13) pyridyl; (14) pyrazinyl; (15) tetrazolyl; or (16) triazolyl, the heteroaryl above being substituted with one or more of R 1 .
Claim 7
Dependent Claim
183 words
A pharmaceutical composition for treating topical inflammation comprising a pharmaceutical carrier and an effective amount of a compound of formula (I) or (II) ##STR6## or a pharmaceutically acceptable salt thereof wherein n is 2 or 3 A is (a) phenyl substituted with (R 1 ) q wherein when q is 2 to 5 R 1 can be the same or different from each other and R 1 is (1) hydrogen; (2) halo; (3) loweralkoxy; (4) lower alkylthio; (5) lower alkyl sulfinyl; (6) lower alkyl sulfonyl; (7) unsubstituted or substituted phenyl loweralkoxy; (8) loweralkyl; (9) loweralkenyl; (10) lower alkanoyl; (11) haloloweralkyl; (12) --COOH; (13) aryl; (14) aryloxy; (15) cyano; (16) hydroxyloweralkyl; (17) halo loweralkanoyl; (18) heteroaryl as defined below; or (19) loweralkanoyloxy; q is 0 to 5; (b) unsubstituted or substituted heteroaryl, selected from a group consisting of: (1) thienyl; (2) benzothienyl; (3) furyl; (4) benzofuryl; (5) pyrryl; (6) indolyl; (7) thiazolyl; (8) benzothiazolyl; (9) thiadiazolyl; (10) benzothiadiazolyl; (11) quinolyl; (12) isoquinolyl; (13) pyridyl; (14) pyrazinyl; (15) tetrazolyl; or (16) triazolyl, the heteroaryl above being substituted with one or more of R 1 .
Claim 8
Dependent Claim
40 words
The pharmaceutical composition of claim 5 wherein: A is phenyl substituted with (R 1 ) q wherein R 1 is (a) hydrogen; (b) loweralkoxy; (c) halo; (d) loweraloalkyl, (e) loweralkanoyl; (f) hydroxyloweralkyl; or (g) CN; q is 1 or 2.
Claim 9
Dependent Claim
21 words
The pharmaceutical composition of claim 5 wherein the active compound is of formula: ##STR7## wherein R 1 is loweralkanoyl or hydroxyloweralkyl.
Claim 10
Dependent Claim
16 words
The pharmaceutical composition of claim 5 wherein the active compound is (a) 2,3-dihydro-5-hydroxy-6-(o-hydroxymethylcinnamyl)benzofuran; or (b) 6-(p-acetylcinnamyl)-2,3-dihydro-5-hydroxy-benzofuran.
Claim 11
Independent Claim
192 words
A method of treating or decreasing topical inflammation comprising the administration to a mammalian species in need of such treatment a therapeutically effective amount of a compound of formula I or II ##STR8## or a pharmaceutically acceptable salt thereof wherein n is 2 or 3 A is (a) phenyl substituted with (R 1 ) q wherein when q is 2 to 5 R 1 can be the same or different from each other and R 1 is (1) hydrogen; (2) halo; (3) loweralkoxy; (4) lower alkylthio; (5) lower alkyl sulfinyl; (6) lower alkyl sulfonyl; (7) unsubstituted or substituted phenyl loweralkoxy; (8) loweralkyl; (9) loweralkenyl; (10) lower alkanoyl; (11) haloloweralkyl; (12) --COOH; (13) aryl; (14) aryloxy; (15) cyano; (16) hydroxyloweralkyl; (17) halo loweralkanoyl; (18) heteroaryl as defined below; or (19) loweralkanoyloxy; q is 0 to 5; (b) unsubstituted or substituted heteroaryl, selected from a group consisting of: (1) thienyl; (2) benzothienyl; (3) furyl; (4) benzofuryl; (5) pyrryl; (6) indolyl; (7) thiazolyl; (8) benzothiazolyl; (9) thiadiazolyl; (10) benzothiadiazolyl; (11) quinolyl; (12) isoquinolyl; (13) pyridyl; (14) pyrazinyl; (15) tetrazolyl; or (16) triazolyl, the heteroaryl above being substituted with one or more of R 1 .
Claim 12
Independent Claim
192 words
A method of treating or decreasing topical inflammation comprising the administration to a mammalian species in need of such treatment a therapeutically effective amount of a compound of formula I or II ##STR8## or a pharmaceutically acceptable salt thereof wherein n is 2 or 3 A is (a) phenyl substituted with (R 1 ) q wherein when q is 2 to 5 R 1 can be the same or different from each other and R 1 is (1) hydrogen; (2) halo; (3) loweralkoxy; (4) lower alkylthio; (5) lower alkyl sulfinyl; (6) lower alkyl sulfonyl; (7) unsubstituted or substituted phenyl loweralkoxy; (8) loweralkyl; (9) loweralkenyl; (10) lower alkanoyl; (11) haloloweralkyl; (12) --COOH; (13) aryl; (14) aryloxy; (15) cyano; (16) hydroxyloweralkyl; (17) halo loweralkanoyl; (18) heteroaryl as defined below; or (19) loweralkanoyloxy; q is 0 to 5; (b) unsubstituted or substituted heteroaryl, selected from a group consisting of: (1) thienyl; (2) benzothienyl; (3) furyl; (4) benzofuryl; (5) pyrryl; (6) indolyl; (7) thiazolyl; (8) benzothiazolyl; (9) thiadiazolyl; (10) benzothiadiazolyl; (11) quinolyl; (12) isoquinolyl; (13) pyridyl; (14) pyrazinyl; (15) tetrazolyl; or (16) triazolyl, the heteroaryl above being substituted with one or more of R 1 .
Claim 13
Dependent Claim
39 words
The method of claim 9 wherein: A is phenyl substituted with (R 1 ) q wherein R 1 is (a) hydrogen; (b) loweralkoxy; (c) halo; (d) lowerhaloalkyl, (e) loweralkanoyl; (f) hydroxyloweralkyl; or (g) CN; q is 1 or 2.
Claim 14
Dependent Claim
20 words
The method of claim 9 wherein the active amount is of formula: ##STR9## wherein R 1 is loweralkanoyl or hydroxyloweralkyl.
Claim 15
Dependent Claim
14 words
The method of claim 9 wherein the compound is: (a) 2,3-dihydro-5-hydroxy-6-(o-hydroxymethylcinnamyl)benzofuran; or (b) 6-(p-acetylcinnamyl)-2,3-dihydro-5-hydroxybenzofuran.
References Cited (Backward Citations)
US3865748A
Cited
US4105698A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1988-08-26 | 1989-02-25 | 1989-08-27 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1992-08-26 | 1993-02-25 | 1993-08-27 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1996-08-26 | 1997-02-25 | 1997-08-27 | $7700.00 | Window Closed / Lapsed |