US4418068A
Expired / Lapsed
US
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Antiestrogenic and antiandrugenic benzothiophenes
Assignee: Eli Lilly and Co
•
Filing: 1981-12-16
•
Granted: 1983-11-29
•
Expires: 2001-12-16
Abstract
Abstract 6-Hydroxy-2-(4-hydroxyphenyl)-3-[4-(2-piperidinoethoxy)benzoyl]benzo[b ]thiophene, its ethers and esters, and the physiologically acceptable acid addition salts thereof, are valuable antiestrogens and antiendrogens.
Inventors
- 👤 Charles D. Jones
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 16:17
CPC Classifications
C; C07; C07D; C07D333/00; C07D333/50; C07D333/52; C07D333/54; C07D333/56
Claims Analysis
Total Claims: 65
Claim 1
Independent Claim
21 words
A compound of the formula ##STR5## a physiologically acceptable ester or ether thereof, or a physiologically acceptable acid addition salt thereof.
Claim 2
Dependent Claim
21 words
A compound of the formula ##STR5## a physiologically acceptable ester or ether thereof, or a physiologically acceptable acid addition salt thereof.
Claim 3
Dependent Claim
100 words
A compound of claim 1 of the formula ##STR6## wherein R and R 1 independently are 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; or a physiologically acceptable acid addition salt thereof.
Claim 4
Dependent Claim
16 words
The compound of claim 2 which is 6-hydroxy-2-(4-hydroxyphenyl)-3-[4-(2-piperidinoethoxy)benzoyl]benzo[b]thiophene, or a physiologically acceptable acid addition salt thereof.
Claim 5
Dependent Claim
20 words
A compound of claim 2 wherein R and R 1 are the same, and are a group other than hydrogen.
Claim 6
Dependent Claim
14 words
A compound of claim 2 wherein one of R and R 1 is hydrogen.
Claim 7
Dependent Claim
18 words
A compound of claim 2 wherein one or both of R and R 1 is --COR 2 .
Claim 8
Dependent Claim
18 words
A compound of claim 2 wherein one or both of R and R 1 is R 3 .
Claim 9
Dependent Claim
20 words
A compound of any one of claims 2, 4 or 6 wherein R 2 is C 1 -C 14 alkyl.
Claim 10
Dependent Claim
26 words
A compound of any one of claims 2, 4 or 6 wherein R 2 is C 1 -C 3 chloroalkyl or C 1 -C 3 fluoroalkyl.
Claim 11
Dependent Claim
20 words
A compound of any one of claims 2, 4 or 6 wherein R 2 is C 5 -C 7 cycloalkyl.
Claim 12
Dependent Claim
20 words
A compound of any one of claims 2, 4 or 6 wherein R 2 is C 1 -C 4 alkoxy.
Claim 13
Dependent Claim
16 words
A compound of any one of claims 2, 4 or 6 wherein R 2 is phenyl.
Claim 14
Dependent Claim
17 words
A compound of any one of claims 2, 4 or 6 wherein R 2 is substituted phenyl.
Claim 15
Dependent Claim
21 words
A compound of any one of claims 2, 4, 5 or 7 wherein R 3 is C 1 -C 4 alkyl.
Claim 16
Dependent Claim
21 words
A compound of any one of claims 2, 4, 5 or 7 wherein R 3 is C 5 -C 7 cycloalkyl.
Claim 17
Dependent Claim
17 words
A compound of any one of claims 2, 4, 5 or 7 wherein R 3 is benzyl.
Claim 18
Dependent Claim
13 words
A compound of any one of claims 1-7 which is a free base.
Claim 19
Dependent Claim
16 words
A compound of any one of claims 1-7 which is a physiologically acceptable acid addition salt.
Claim 20
Dependent Claim
12 words
A compound of any one of claims 1-7 which is a hydrochloride.
Claim 21
Dependent Claim
16 words
The compound of claim 1 which is 6-acetoxy-2-(4-acetoxyphenyl)-3-[4-(2-piperidinoethoxy)benzoyl]benzo[b]thiophene, or a physiologically acceptable acid addition salt thereof.
Claim 22
Dependent Claim
16 words
The compound of claim 1 which is 6-benzoyloxy-2-(4-benzoyloxyphenyl)-3-[4-(2-piperidinoethoxy)benzoyl]benzo[b]thiophene, or a physiologically acceptable acid addition salt thereof.
Claim 23
Dependent Claim
16 words
The compound of claim 1 which is 6-ethoxycarbonyloxy-2-(4-ethoxycarbonyloxyphenyl)-3-[4-(2-piperidinoethoxy)benzoyl]benzo[b]thiophene, or a physiologically acceptable acid addition salt thereof.
Claim 24
Dependent Claim
16 words
The compound of claim 1 which is 6-methoxy-2-(4-methoxyphenyl)-3-[4-(2-piperidinoethoxy)benzoyl]benzo[b]thiophene, or a physiologically acceptable acid addition salt thereof.
Claim 25
Dependent Claim
37 words
An antiestrogenic and antiandrogenic pharmaceutical composition comprising a pharmaceutically acceptable diluent and an effective amount of a compound of the formula ##STR7## a physiologically acceptable ester or ether thereof, or a physiologically acceptable acid addition salt thereof.
Claim 26
Dependent Claim
37 words
An antiestrogenic and antiandrogenic pharmaceutical composition comprising a pharmaceutically acceptable diluent and an effective amount of a compound of the formula ##STR7## a physiologically acceptable ester or ether thereof, or a physiologically acceptable acid addition salt thereof.
Claim 27
Dependent Claim
104 words
A composition of claim 24 wherein the compound is of the formula ##STR8## wherein R and R 1 independently are 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; or a physiologically acceptable acid addition salt thereof.
Claim 28
Dependent Claim
18 words
A composition of claim 25 wherein the compound is 6-hydroxy-2-(4-hydroxyphenyl)-3-[4-(2-piperidinoethoxy)benzoyl]benzo[b]thiophene, or a physiologically acceptable acid addition salt thereof.
Claim 29
Dependent Claim
11 words
A composition of claim 26 wherein the compound is the hydrochloride.
Claim 30
Dependent Claim
26 words
A composition of claim 25 wherein the compound is a compound wherein R and R 1 are the same, and are a group other than hydrogen.
Claim 31
Dependent Claim
20 words
A composition of claim 28 wherein the compound is a compound wherein R and R 1 are --COR 2 .
Claim 32
Dependent Claim
20 words
A composition of claim 29 wherein the compound is a compound wherein R 2 is C 1 -C 14 alkyl.
Claim 33
Dependent Claim
18 words
A composition of claim 30 wherein the compound is 6-acetoxy-2-(4-acetoxyphenyl)-3-[4-(2-piperidinoethoxy)benzoyl]benzo[b]thiophene, or a physiologically acceptable acid addition salt thereof.
Claim 34
Dependent Claim
16 words
A composition of claim 29 wherein the compound is a compound wherein R 2 is phenyl.
Claim 35
Dependent Claim
18 words
A composition of claim 32 wherein the compound is 6-benzoyloxy-2-(4-benzoyloxyphenyl)-3-[4-(2-piperidinoethoxy)benzoyl]benzo[b]thiophene, or a physiologically acceptable acid addition salt thereof.
Claim 36
Dependent Claim
20 words
A composition of claim 29 wherein the compound is a compound wherein R 2 is C 1 -C 4 alkoxy.
Claim 37
Dependent Claim
18 words
A composition of claim 34 wherein the compound is 6-ethoxycarbonyloxy-2-(4-ethoxycarbonyloxyphenyl)-3-[4-(2-piperidinoethoxy)benzoyl]benzo[b]thiophene, or a physiologically acceptable acid addition salt thereof.
Claim 38
Dependent Claim
14 words
A composition of claim 28 wherein R and R 1 and R 3 .
Claim 39
Dependent Claim
18 words
A composition of claim 36 wherein the compound is 6-methoxy-2-(4-methoxyphenyl)-3-[4-(2-piperidinoethoxy)benzoyl]benzo[b]thiophene, or a physiologically acceptable acid addition salt thereof.
Claim 40
Dependent Claim
20 words
A composition of claim 25 wherein the compound is a compound wherein one of R and R 1 is hydrogen.
Claim 41
Independent Claim
62 words
A method of alleviating a pathological condition of an endocrine target organ, which condition is dependent or partially dependent on an estrogen or on an androgen, which comprises administering to a subject suffering from such a condition an effective dose of a compound of the formula ##STR9## a physiologically acceptble ester or ether thereof, or a physiologically acceptable acid addition salt thereof.
Claim 42
Independent Claim
62 words
A method of alleviating a pathological condition of an endocrine target organ, which condition is dependent or partially dependent on an estrogen or on an androgen, which comprises administering to a subject suffering from such a condition an effective dose of a compound of the formula ##STR9## a physiologically acceptble ester or ether thereof, or a physiologically acceptable acid addition salt thereof.
Claim 43
Dependent Claim
17 words
A method of claim 39 wherein the pathological condition is dependent or partially dependent on an estrogen.
Claim 44
Dependent Claim
20 words
A method of claim 40 wherein the dose of the compound is from about 0.05 mg./kg./day to about 50 mg./kg./day.
Claim 45
Dependent Claim
19 words
A method of claim 41 wherein the target organ is the breast, and the pathological condition is mammary cancer.
Claim 46
Dependent Claim
20 words
A method of claim 42 wherein the dose of the compound is from about 0.1 mg./kg./day to about 10 mg./kg./day.
Claim 47
Dependent Claim
19 words
A method of claim 41 wherein the target organ is the breast, and the pathological condition is fibrocystic disease.
Claim 48
Dependent Claim
20 words
A method of claim 44 wherein the dose of the compound is from about 0.1 mg./kg./day to about 10 mg./kg./day.
Claim 49
Dependent Claim
17 words
A method of claim 39 wherein the pathological condition is dependent or partially dependent on an androgen.
Claim 50
Dependent Claim
20 words
A method of claim 46 wherein the dose of the compound is from about 0.05 mg./kg./day to about 50 mg./kg./day.
Claim 51
Dependent Claim
19 words
A method of claim 47 wherein the target organ is the prostate, and the pathological condition is prostatic cancer.
Claim 52
Dependent Claim
20 words
A method of claim 48 wherein the dose of the compound is from about 0.1 mg./kg./day to about 10 mg./kg./day.
Claim 53
Dependent Claim
20 words
A method of claim 47 wherein the target organ is the prostate, and the pathological condition is benign prostatic hypertrophy.
Claim 54
Dependent Claim
17 words
A method of claim 50 wherein the dose is from about 0.1 mg./kg./day to about 10 mg./kg./day.
Claim 55
Independent Claim
107 words
A method of any one of claims 39-51 wherein the compound is of the formula ##STR10## wherein R and R 1 independently are 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; or a physiologically acceptable acid addition salt thereof.
Claim 56
Dependent Claim
18 words
A method of claim 52 wherein the compound is 6-hydroxy-2-(4-hydroxyphenyl)-3-[4-(2-piperidinoethoxy)benzoyl]benzo[b]thiophene, or a physiologically acceptable acid addition salt thereof.
Claim 57
Dependent Claim
11 words
A method of claim 53 wherein the compound is the hydrochloride.
Claim 58
Dependent Claim
26 words
A method of claim 52 wherein the compound is a compound wherein R and R 1 are the same, and are a group other than hydrogen.
Claim 59
Dependent Claim
20 words
A method of claim 55 wherein the compound is a compound wherein R and R 1 are --COR 2 .
Claim 60
Dependent Claim
18 words
A method or claim 56 wherein the compound is 6-acetoxy-2-(4-acetoxyphenyl)-3-[4-(2-piperidinoethoxy)benzoyl]benzo[b]thiophene, or a physiologically acceptable acid addition salt thereof.
Claim 61
Dependent Claim
18 words
A method of claim 56 wherein the compound is 6-benzoyloxy-2-(4-benzoyloxyphenyl)-3-[4-(2-piperidinoethoxy)benzoyl]benzo[b]thiophene, or a physiologically acceptable acid addition salt thereof.
Claim 62
Dependent Claim
18 words
A method of claim 56 wherein the compound is 6-ethoxycarbonyloxy-2-(4-ethoxycarbonyloxyphenyl)-3-[4-(2-piperidinoethoxy)benzoyl]benzo[b]thiophene, or a physiologically acceptable acid addition salt thereof.
Claim 63
Dependent Claim
20 words
A method of claim 55 wherein the compound is a compound wherein R and R 1 are R 3 .
Claim 64
Dependent Claim
18 words
A method of claim 60 wherein the compound is 6-methoxy-2-(4-methoxyphenyl)-3-[4-(2-piperidinoethoxy)benzoyl]benzo[b]thiophene, or a physiologically acceptable acid addition salt thereof.
Claim 65
Dependent Claim
20 words
A method of claim 52 wherein the compound is a compound wherein one of R and R 1 is hydrogen.
References Cited (Backward Citations)
US3920707A
Cited
BE819675A
Cited
US3947470A
Cited
US4001426A
Cited
US3983245A
Cited
US4075227A
Cited
US4133814A
Cited
US4230862A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1986-11-28 | 1987-05-30 | 1987-11-29 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1990-11-28 | 1991-05-30 | 1991-11-29 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1994-11-28 | 1995-05-30 | 1995-11-29 | $7700.00 | Window Closed / Lapsed |