US4191759A
Expired / Lapsed
US
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N-substituted-17β-carbamoylandrost-4-en-3-one 5α reductase inhibitors
Assignee: Merck and Co Inc
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Filing: 1978-04-13
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Granted: 1980-03-04
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Expires: 1998-04-13
Abstract
Abstract Amides of 17 beta -carboxy-4-androsten-3-one having the formula: <IMAGE> where R1 and R2 are hydrogen (only one may be hydrogen), C1-4 alkyl, cyclo C5-6 alkyl, phenyl, or together with the nitrogen are a 5 or 6 membered heterocycle with up to one other heteroatom selected from oxygen and nitrogen; R3, R4, R5, and R6 are hydrogen or C1-3 alkyl; R7 is hydrogen or cyano; Z is oxygen, N-R8 where R8 is C1-3 alkyl, or CH-R9 where R9 is hydrogen, alpha -fluoro, or alpha -C1-3 alkyl, active as testosterone 5 alpha -reductase inhibitors, and thus useful topically for treatment of acne, seborrhea, female hirsutism and male pattern baldness.
Inventors
- 👤 David B. R. Johnston
- 👤 Glen E. Arth, deceased
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-08 10:54
CPC Classifications
C; C07; C07J; C07J41/00; C07J41/0033; C07J41/0066; C07J43/00; C07J43/003
Claims Analysis
Total Claims: 15
Claim 1
Independent Claim
157 words
A compound of the formula: ##STR15## wherein R 1 and R 2 are the same or different and each represents: (1) hydrogen, provided that only one of R 1 and R 2 may be hydrogen (2) lower alkyl, (3) lower cycloalkyl, (4) phenyl, or R 1 and R 2 taken together with the nitrogen to which they are attached represents a 5-6 membered saturated ring comprising up to one other heteroatom selected from oxygen and nitrogen; R 3 , R 4 , R 5 , and R 6 are the same or different and each represents: (1) hydrogen, or (2) lower alkyl; R 7 represents: (1) hydrogen or (2) cyano; Z represents: CH--R 9 where R 9 is (a) hydrogen, (b) α-fluoro, or (c) α-lower alkyl; and the dotted line between positions 1 and 2 represents the possibility of a single bond when Z is CH--R 9 and a double bond when Z is C--R 9 .
Claim 2
Dependent Claim
157 words
A compound of the formula: ##STR15## wherein R 1 and R 2 are the same or different and each represents: (1) hydrogen, provided that only one of R 1 and R 2 may be hydrogen (2) lower alkyl, (3) lower cycloalkyl, (4) phenyl, or R 1 and R 2 taken together with the nitrogen to which they are attached represents a 5-6 membered saturated ring comprising up to one other heteroatom selected from oxygen and nitrogen; R 3 , R 4 , R 5 , and R 6 are the same or different and each represents: (1) hydrogen, or (2) lower alkyl; R 7 represents: (1) hydrogen or (2) cyano; Z represents: CH--R 9 where R 9 is (a) hydrogen, (b) α-fluoro, or (c) α-lower alkyl; and the dotted line between positions 1 and 2 represents the possibility of a single bond when Z is CH--R 9 and a double bond when Z is C--R 9 .
Claim 3
Dependent Claim
19 words
A compound of claim 1 of the formula: ##STR16## where R 1 and R 2 are as previously defined.
Claim 4
Dependent Claim
14 words
A compound of claim 2 wherein R 1 and R 2 are lower alkyl.
Claim 5
Dependent Claim
10 words
A compound of claim 2 wherein the compound is N,N-diethyl-17β-carbamoylandrost-4-en-3-one.
Claim 6
Independent Claim
192 words
A method of treating the hyperandrogenic conditions of acne vulgaris, seborrhea, male pattern baldness and female hirsuitism comprising topical administration to a patient in need of such treatment of a therapeutically effective amount of a compound of the formula: ##STR17## wherein R 1 and R 2 are the same or different and each represents: (1) hydrogen, provided that only one of R 1 and R 2 may be hydrogen, (2) lower alkyl, (3) lower cycloalkyl, (4) phenyl, or R 1 and R 2 taken together with the nitrogen to which they are attached represents a 5-6 membered saturated ring comprising up to one other heteroatom selected from oxygen and nitrogen; R 3 , R 4 , R 5 , and R 6 are the same or different and each represents: (1) hydrogen, or (2) lower alkyl; R 7 represents: (1) hydrogen or (2) cyano; Z represents: CH--R 9 , where R 9 is (a) hydrogen, (b) α-fluoro, or (c) α-lower alkyl; and the dotted line between positions 1 and 2 represents the possibility of a single bond when Z is CH--R 9 and a double bond when Z is C--R 9 .
Claim 7
Independent Claim
192 words
A method of treating the hyperandrogenic conditions of acne vulgaris, seborrhea, male pattern baldness and female hirsuitism comprising topical administration to a patient in need of such treatment of a therapeutically effective amount of a compound of the formula: ##STR17## wherein R 1 and R 2 are the same or different and each represents: (1) hydrogen, provided that only one of R 1 and R 2 may be hydrogen, (2) lower alkyl, (3) lower cycloalkyl, (4) phenyl, or R 1 and R 2 taken together with the nitrogen to which they are attached represents a 5-6 membered saturated ring comprising up to one other heteroatom selected from oxygen and nitrogen; R 3 , R 4 , R 5 , and R 6 are the same or different and each represents: (1) hydrogen, or (2) lower alkyl; R 7 represents: (1) hydrogen or (2) cyano; Z represents: CH--R 9 , where R 9 is (a) hydrogen, (b) α-fluoro, or (c) α-lower alkyl; and the dotted line between positions 1 and 2 represents the possibility of a single bond when Z is CH--R 9 and a double bond when Z is C--R 9 .
Claim 8
Dependent Claim
14 words
The method of claim 5 wherein there is employed a compound of formula: ##STR18##
Claim 9
Dependent Claim
10 words
The method of claim 5 wherein there is employed N,N-diethyl-17β-carbamoylandrost-4-en-3-one.
Claim 10
Independent Claim
184 words
A method of inhibiting testosterone-5α-reductase in a patient in need of such inhibiting treatment, comprising administration to such a patient of a therapeutically effective amount of a compound of the formula: ##STR19## wherein R 1 and R 2 are the same or different and each represents: (1) hydrogen, provided that only one of R 1 and R 2 may be hydrogen, (2) lower alkyl, (3) lower cycloalkyl, (4) phenyl or R 1 and R 2 taken together with the nitrogen to which they are attached represents a 5-6 membered saturated ring comprising up to one other heteroatom selected from oxygen and nitrogen; R 3 , R 4 , R 5 , and R 6 are the same or different and each represents: (1) hydrogen, or (2) lower alkyl; R 7 represents: (1) hydrogen or (2) cyano; Z represents: CH--R 9 , where R 9 is (a) hydrogen, (b) α-fluoro, or (c) α-lower alkyl; and the dotted line between positions 1 and 2 represents the possibility of a single bond when Z is CH--R 9 and a double bond when Z is C--R 9 .
Claim 11
Independent Claim
184 words
A method of inhibiting testosterone-5α-reductase in a patient in need of such inhibiting treatment, comprising administration to such a patient of a therapeutically effective amount of a compound of the formula: ##STR19## wherein R 1 and R 2 are the same or different and each represents: (1) hydrogen, provided that only one of R 1 and R 2 may be hydrogen, (2) lower alkyl, (3) lower cycloalkyl, (4) phenyl or R 1 and R 2 taken together with the nitrogen to which they are attached represents a 5-6 membered saturated ring comprising up to one other heteroatom selected from oxygen and nitrogen; R 3 , R 4 , R 5 , and R 6 are the same or different and each represents: (1) hydrogen, or (2) lower alkyl; R 7 represents: (1) hydrogen or (2) cyano; Z represents: CH--R 9 , where R 9 is (a) hydrogen, (b) α-fluoro, or (c) α-lower alkyl; and the dotted line between positions 1 and 2 represents the possibility of a single bond when Z is CH--R 9 and a double bond when Z is C--R 9 .
Claim 12
Dependent Claim
167 words
A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of the formula: ##STR20## wherein R 1 and R 2 are the same or different and each represents: (1) hydrogen, provided that only one of R 1 and R 2 may be hydrogen, (2) lower alkyl, (3) lower cycloalkyl, (4) phenyl, or R 1 and R 2 taken together with the nitrogen to which they are attached represents a 5-6 membered saturated ring comprising up to one other heteroatom selected from oxygen and nitrogen; R 3 , R 4 , R 5 , and R 6 are the same or different and each represents: (1) hydrogen, or (2) lower alkyl; R 7 represents: (1) hydrogen or (2) cyano; Z represents: CH--R 9 , where R 9 is (a) hydrogen, (b) α-fluoro, or (c) α-lower alkyl; and the dotted line between positions 1 and 2 represents the possibility of a single bond when Z is CH--R 9 and a double bond when Z is C--R 9 .
Claim 13
Dependent Claim
167 words
A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of the formula: ##STR20## wherein R 1 and R 2 are the same or different and each represents: (1) hydrogen, provided that only one of R 1 and R 2 may be hydrogen, (2) lower alkyl, (3) lower cycloalkyl, (4) phenyl, or R 1 and R 2 taken together with the nitrogen to which they are attached represents a 5-6 membered saturated ring comprising up to one other heteroatom selected from oxygen and nitrogen; R 3 , R 4 , R 5 , and R 6 are the same or different and each represents: (1) hydrogen, or (2) lower alkyl; R 7 represents: (1) hydrogen or (2) cyano; Z represents: CH--R 9 , where R 9 is (a) hydrogen, (b) α-fluoro, or (c) α-lower alkyl; and the dotted line between positions 1 and 2 represents the possibility of a single bond when Z is CH--R 9 and a double bond when Z is C--R 9 .
Claim 14
Dependent Claim
14 words
The composition of claim 9 wherein there is employed a compound of formula: ##STR21##
Claim 15
Dependent Claim
10 words
The composition of claim 9 wherein there is employed N,N-diethyl-17β-carbamoylandrost-4-en-3-one.
References Cited (Backward Citations)
US3917829A
Cited
US4088760A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1983-03-04 | 1983-09-03 | 1984-03-04 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1987-03-04 | 1987-09-03 | 1988-03-04 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1991-03-04 | 1991-09-03 | 1992-03-04 | $7700.00 | Window Closed / Lapsed |