Patent US4492707A successfully refreshed from Google Patents.
US4492707A
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N-Imidazolyl derivatives of 1,2,3,4-tetrahydro-naphthalene and indan
Assignee: Pfizer Italia SRL
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Filing: 1982-07-15
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Granted: 1985-01-08
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Expires: 2002-07-15
Abstract
Abstract Compounds of the formula <IMAGE> where Z completes a bond or is a <IMAGE> group; one of R1 and R2 is hydroxy and the other is hydrogen or alkyl, or R1 and R2, taken together, form an oxo group; and the remaining substituents are as defined in the specification. These compounds possess hypolipaemic properties.
Inventors
- 👤 Paolo Cozzi
- 👤 Antonio Pillan
- 👤 Pier P. Lovisolo
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-26 19:37
CPC Classifications
C; C07; C07D; C07D231/00; C07D231/02; C07D231/10; C07D231/12; C07D233/00; C07D233/54; C07D233/56; C07D249/00; C07D249/02; C07D249/08
Claims Analysis
Total Claims: 14
Claim 1
Independent Claim
502 words
A pharmaceutical composition having hypolipaemic activity containing a suitable carrier and/or diluent and a therapeutically effective amount of a compound of formula (I) ##STR114## wherein: Z completes a bond or is a ##STR115## group, wherein each of R 5 and R 6 , being the same or different, is hydrogen or C 1 -C 4 alkyl; one of R 1 and R 2 is hydroxy and the other is hydrogen or C 1 -C 6 alkyl, or R 1 and R 2 , taken together, form an oxo group; one of R 3 and R 4 is hydrogen or C 1 -C 4 alkyl and the other represents hydrogen or: (a) C 1 -C 8 alkyl, unsubstituted or substituted by one or more substituents chosen from halogen; hydroxy, cyano; --COOR', wherein R' is hydrogen or C 1 -C 6 alkyl; ##STR116## wherein each of R' and R", being the same or different, represents hydrogen or C 1 -C 6 alkyl; (b) straight or branched C 1 -C 4 alkyl or C 2 -C 4 alkenyl, each substituted by a C 1 -C 4 alkyl, or a C 3 -C 7 monocycloalkyl; (c) cyano; ##STR117## wherein R' and R" are as defined above; each of X 1 , X 2 , X 3 , and X 4 , which may be the same or different, is hydrogen; halogen; hydroxy; nitro; cyano, C 1 -C 6 alkyl; C 2 -C 6 alkenyl; C 1 -C 6 alkoxy; trihalo-C 1 -C 6 alkyl; ##STR118## R' and R" being as defined above; or a C 2 -C 4 acylamino group; or one of X 1 , X 2 , X 3 and X 4 is phenyl, phenylthio, phenoxy or benzyl, the phenyl, phenylthio, phenoxy or benzyl groups being unsubstituted or substituted by one or more substituents chosen from halogen, C 1 -C 6 alkyl, hydroxy, C 1 -C 6 alkoxy,--SR' or --S--S--R', wherein R' is as defined above, and the others are as defined above; or any two adjacent X 1 , X 2 , X 3 and X 4 groups, taken together, complete a saturated or unsaturated 6-membered carbocyclic ring fused to the benzene ring shown in formula (I), the carbocyclic ring being unsubstituted or substituted by one or more substituents selected from halogen, C 1 -C 6 alkyl, halo-C 1 -C 6 alkyl, C 1 -C 6 alkoxy, --SR' or --S--S--R', wherein R' is as defined above, and any groups X 1 to X 4 not participating in the completion of such a fused ring are as defined above; provided that: when Z is a group ##STR119## and, at the same time, at least one of R 3 and R 4 is different from hydrogen, then R 5 and R 6 are both hydrogen; and when Z is a group ##STR120## and, at the same time, at least one of R 5 and R 6 is different from hydrogen, then R 3 and R 4 are both hydrogen, or a pharmaceutically acceptable salt thereof.
Claim 2
Dependent Claim
502 words
A pharmaceutical composition having hypolipaemic activity containing a suitable carrier and/or diluent and a therapeutically effective amount of a compound of formula (I) ##STR114## wherein: Z completes a bond or is a ##STR115## group, wherein each of R 5 and R 6 , being the same or different, is hydrogen or C 1 -C 4 alkyl; one of R 1 and R 2 is hydroxy and the other is hydrogen or C 1 -C 6 alkyl, or R 1 and R 2 , taken together, form an oxo group; one of R 3 and R 4 is hydrogen or C 1 -C 4 alkyl and the other represents hydrogen or: (a) C 1 -C 8 alkyl, unsubstituted or substituted by one or more substituents chosen from halogen; hydroxy, cyano; --COOR', wherein R' is hydrogen or C 1 -C 6 alkyl; ##STR116## wherein each of R' and R", being the same or different, represents hydrogen or C 1 -C 6 alkyl; (b) straight or branched C 1 -C 4 alkyl or C 2 -C 4 alkenyl, each substituted by a C 1 -C 4 alkyl, or a C 3 -C 7 monocycloalkyl; (c) cyano; ##STR117## wherein R' and R" are as defined above; each of X 1 , X 2 , X 3 , and X 4 , which may be the same or different, is hydrogen; halogen; hydroxy; nitro; cyano, C 1 -C 6 alkyl; C 2 -C 6 alkenyl; C 1 -C 6 alkoxy; trihalo-C 1 -C 6 alkyl; ##STR118## R' and R" being as defined above; or a C 2 -C 4 acylamino group; or one of X 1 , X 2 , X 3 and X 4 is phenyl, phenylthio, phenoxy or benzyl, the phenyl, phenylthio, phenoxy or benzyl groups being unsubstituted or substituted by one or more substituents chosen from halogen, C 1 -C 6 alkyl, hydroxy, C 1 -C 6 alkoxy,--SR' or --S--S--R', wherein R' is as defined above, and the others are as defined above; or any two adjacent X 1 , X 2 , X 3 and X 4 groups, taken together, complete a saturated or unsaturated 6-membered carbocyclic ring fused to the benzene ring shown in formula (I), the carbocyclic ring being unsubstituted or substituted by one or more substituents selected from halogen, C 1 -C 6 alkyl, halo-C 1 -C 6 alkyl, C 1 -C 6 alkoxy, --SR' or --S--S--R', wherein R' is as defined above, and any groups X 1 to X 4 not participating in the completion of such a fused ring are as defined above; provided that: when Z is a group ##STR119## and, at the same time, at least one of R 3 and R 4 is different from hydrogen, then R 5 and R 6 are both hydrogen; and when Z is a group ##STR120## and, at the same time, at least one of R 5 and R 6 is different from hydrogen, then R 3 and R 4 are both hydrogen, or a pharmaceutically acceptable salt thereof.
Claim 3
Independent Claim
512 words
A method of producing a hypolipaemic effect in a patient in need of such effect, said method comprising administering to said patient a therapeutically effective amount of a compound of formula (I) ##STR121## wherein: Z completes a bond or is a ##STR122## group, wherein each of R 5 and R 6 , being the same or different, is hydrogen or C 1 -C 4 alkyl; one of R 1 and R 2 is hydroxy and the other is hydrogen or C 1 -C 6 alkyl, or R 1 and R 2 , taken together, form an oxo group; one of R 3 and R 4 is hydrogen or C 1 -C 4 alkyl and the other represents hydrogen or: (a) C 1 -C 8 alkyl, unsubstituted or substituted by one or more substituents chosen from halogen; hydroxy, cyano; --COOR', wherein R' is hydrogen or C 1 -C 6 alkyl; ##STR123## wherein each of R' and R", being the same or different, represents hydrogen or C 1 -C 6 alkyl; (b) straight or branched C 1 -C 4 alkyl or C 2 -C 4 alkenyl, each substituted by a C 1 -C 4 alkyl, or a C 3 -C 7 monocycloalkyl; (c) cyano; ##STR124## wherein R' and R" are as defined above; each of X 1 , X 2 , X 3 , and X 4 , which may be the same or different, is hydrogen; halogen; hydroxy; nitro; cyano, C 1 -C 6 alkyl; C 2 -C 6 alkenyl; C 1 -C 6 alkoxy; trihalo-C 1 -C 6 alkyl; ##STR125## R' and R" being as defined above; or a C 2 -C 4 acylamino group; or one of X 1 , X 2 , X 3 and X 4 is phenyl, phenylthio, phenoxy or benzyl, the phenyl, phenylthio, phenoxy or benzyl groups being unsubstituted or substituted by one or more substituents chosen from halogen, C 1 -C 6 alkyl, hydroxy, C 1 -C 6 alkoxy, --SR' or --S--S--R', wherein R' is as defined above, and the others are as defined above; or any two adjacent X 1 , X 2 , X 3 and X 4 groups, taken together, complete a saturated or unsaturated 6-membered carbocyclic ring fused to the benzene ring shown in formula (I), the carbocyclic ring being unsubstituted or substituted by one or more substituents selected from halogen, C 1 -C 6 alkyl, halo-C 1 -C 6 alkyl, C 1 -C 6 alkoxy, --SR' or --S--S--R', wherein R' is as defined above, and any groups X 1 to X.sub. 4 not participating in the completion of such a fused ring are as defined above; provided that: when Z is a group ##STR126## and, at the same time, at least one of R 3 and R 4 is different from hydrogen, then R 5 and R 6 are both hydrogen; and when Z is a group ##STR127## and, at the same time, at least one of R 5 and R 6 is different from hydrogen, then R 3 and R 4 are both hydrogen, or a pharmaceutically acceptable salt thereof.
Claim 4
Independent Claim
512 words
A method of producing a hypolipaemic effect in a patient in need of such effect, said method comprising administering to said patient a therapeutically effective amount of a compound of formula (I) ##STR121## wherein: Z completes a bond or is a ##STR122## group, wherein each of R 5 and R 6 , being the same or different, is hydrogen or C 1 -C 4 alkyl; one of R 1 and R 2 is hydroxy and the other is hydrogen or C 1 -C 6 alkyl, or R 1 and R 2 , taken together, form an oxo group; one of R 3 and R 4 is hydrogen or C 1 -C 4 alkyl and the other represents hydrogen or: (a) C 1 -C 8 alkyl, unsubstituted or substituted by one or more substituents chosen from halogen; hydroxy, cyano; --COOR', wherein R' is hydrogen or C 1 -C 6 alkyl; ##STR123## wherein each of R' and R", being the same or different, represents hydrogen or C 1 -C 6 alkyl; (b) straight or branched C 1 -C 4 alkyl or C 2 -C 4 alkenyl, each substituted by a C 1 -C 4 alkyl, or a C 3 -C 7 monocycloalkyl; (c) cyano; ##STR124## wherein R' and R" are as defined above; each of X 1 , X 2 , X 3 , and X 4 , which may be the same or different, is hydrogen; halogen; hydroxy; nitro; cyano, C 1 -C 6 alkyl; C 2 -C 6 alkenyl; C 1 -C 6 alkoxy; trihalo-C 1 -C 6 alkyl; ##STR125## R' and R" being as defined above; or a C 2 -C 4 acylamino group; or one of X 1 , X 2 , X 3 and X 4 is phenyl, phenylthio, phenoxy or benzyl, the phenyl, phenylthio, phenoxy or benzyl groups being unsubstituted or substituted by one or more substituents chosen from halogen, C 1 -C 6 alkyl, hydroxy, C 1 -C 6 alkoxy, --SR' or --S--S--R', wherein R' is as defined above, and the others are as defined above; or any two adjacent X 1 , X 2 , X 3 and X 4 groups, taken together, complete a saturated or unsaturated 6-membered carbocyclic ring fused to the benzene ring shown in formula (I), the carbocyclic ring being unsubstituted or substituted by one or more substituents selected from halogen, C 1 -C 6 alkyl, halo-C 1 -C 6 alkyl, C 1 -C 6 alkoxy, --SR' or --S--S--R', wherein R' is as defined above, and any groups X 1 to X.sub. 4 not participating in the completion of such a fused ring are as defined above; provided that: when Z is a group ##STR126## and, at the same time, at least one of R 3 and R 4 is different from hydrogen, then R 5 and R 6 are both hydrogen; and when Z is a group ##STR127## and, at the same time, at least one of R 5 and R 6 is different from hydrogen, then R 3 and R 4 are both hydrogen, or a pharmaceutically acceptable salt thereof.
Claim 5
Dependent Claim
40 words
A composition according to claim 1, wherein said compound is selected from the group consisting of: 2-(1-imidazolyl)-3,4-dihydro-7-amino-1(2H)-naphthalenone; 2-(1-imidazolyl)-3,4-dihydro-7-dimethylamino-1(2H)-naphthalenone; 2-(1-imidazolyl)-3,4-dihydro-7-acetylamino-1(2H)-naphthalenone; 2-(1-imidazolyl)-3,4-dihydro-7-methoxy-1(2H)-naphthalenone; 2-(1-imidazolyl)-3,4-dihydro-8-methoxy-1(2H)-naphthalenone; 2-(1-imidazolyl)-3,4-dihydro-5-bromo-6-hydroxy-1-(2H)-naphthalenone; 2-(1-imidazolyl)-3,4-dihydro-5-bromo-6-methoxy-1(2H)-naphthalenone; 2-(1-imidazolyl)-3,4-dihydro-6-hydroxy-7-tert.butyl-1(2H)-naphthalenone; 2-(1-imidazolyl)-3,4-dihydro-5,7-dibromo-6-hydroxy-1(2H)-naphthalenone; 2-(1-imidazolyl)-3,4-dihydro-7-carboxy-1(2H)-naphthalenone; 2-(1-imidazolyl)-3,4-dihydro-5-bromo-7-carboxy-1(2H)-naphthalenone; 2-(1-imidazolyl)-3,4-dihydro-8-carboxy-1(2H)-naphthalenone; 2-(1-imidazolyl)-3,4-dihydro-7-methoxy-8-bromo-1(2H)-naphthalenone; 2-(1-imidazolyl)-3,4-dihydro-7-hydroxy-8-bromo-1(2H)-naphthalenone; 2-(1-imidazolyl)-3,4-dihydro-5-allyl-6-hydroxy-1(2H)-naphthalenone; 2-(1-imidazolyl)-3,4-dihydro-7-phenyl-1(2H)-naphthalenone; 2-(1-imidazolyl)-3,4-dihydro-3-methyl-1(2H)-naphthalenone; 2-(1-imidazolyl)-3,4-dihydro-3-carboxy-1(2H)-naphthalenone; and the pharmaceutically acceptable salts thereof.
Claim 6
Dependent Claim
40 words
A composition according to claim 1, wherein said compound is selected from the group consisting of: 2-(1-imidazolyl)-1,2,3,4-tetrahydro-7-methoxy-1-naphthalenol; 2-(1-imidazolyl)-1,2,3,4-tetrahydro-7-carboxy-1-naphthalenol; 2-(1-imidazolyl)-1,2,3,4-tetrahydro-6-hydroxy-7-tert.butyl-1-naphthalenol; 2-(1-imidazolyl)-1,2,3,4-tetrahydro-5-bromo-6-hydroxy-1-naphthalenol; 2-(1-imidazolyl)-1,2,3,4-tetrahydro-8-carboxy-1-naphthalenol, both in the form of cis or trans isomer and of their mixture, and the pharmaceutically acceptable salts thereof.
Claim 7
Dependent Claim
24 words
A composition according to claim 1, wherein said compound is selected from the group consisting of: 2-(1-imidazolyl)-5-methoxy-1-indanone; 2-(1-imidazolyl)-6-carboxy-1-indanone, and the pharmaceutically acceptable salts thereof.
Claim 8
Dependent Claim
30 words
A composition according to claim 1, wherein said compound is 2-(1-imidazolyl)-3-methyl-1-indanone both in the form of cis or trans isomer and of their mixture, and the pharmaceutically acceptable salts thereof.
Claim 9
Dependent Claim
17 words
A composition according to claim 1, wherein said compound is 2-(1-imidazolyl)-3,4-dihydro-5-bromo-6-hydroxy-1(2H)-naphthalenone, and the pharmaceutically acceptable salts thereof.
Claim 10
Dependent Claim
39 words
A method according to claim 2, wherein said compound is selected from the group consisting of: 2-(1-imidazolyl)-3,4-dihydro-7-amino-1(2H)-naphthalenone; 2-(1-imidazolyl)-3,4-dihydro-7-dimethylamino-1(2H)-naphthalenone; 2-(1-imidazolyl)-3,4-dihydro-7-acetylamino-1(2H)-naphthalenone; 2-(1-imidazolyl)-3,4-dihydro-7-methoxy-1(2H)-naphthalenone; 2-(1-imidazolyl)-3,4-dihydro-8-methoxy-1(2H)-naphthalenone; 2-(1-imidazolyl)-3,4-dihydro-5-bromo-6-methoxy-1(2H)-naphthalenone; 2-(1-imidazolyl)-3,4-dihydro-6-hydroxy-7-tert.butyl-1(2H)-naphthalenone; 2-(1-imidazolyl)-3,4-dihydro-5,7-dibromo-6-hydroxy-1(2H)-naphthalenone; 2-(1-imidazolyl)-3,4-dihydro-7-carboxy-1(2H)-naphthalenone; 2-(1-imidazolyl)-3,4-dihydro-5-bromo-7-carboxy-1(2H)-naphthalenone; 2-(1-imidazolyl)-3,4-dihydro-8-carboxy-1(2H)-naphthalenone; 2-(1-imidazolyl)-3,4-dihydro-7-methoxy-8-bromo-1(2H)-naphthalenone; 2-(1-imidazolyl)-3,4-dihydro-7-hydroxy-8-bromo-1(2H)-naphthalenone; 2-(1-imidazolyl)-3,4-dihydro-5-allyl-6-hydroxy-1(2H)-naphthalenone; 2-(1-imidazolyl)-3,4-dihydro-7-phenyl-1(2H)-naphthalenone; 2-(1-imidazolyl)-3,4-dihydro-3-methyl-1(2H)-naphthalenone; 2-(1-imidazolyl)-3,4-dihydro-3-carboxy-1(2H)-naphthalenone; and the pharmaceutically acceptable salts thereof.
Claim 11
Dependent Claim
40 words
A method according to claim 2, wherein said compound is selected from the group consisting of: 2-(1-imidazolyl)-1,2,3,4-tetrahydro-7-methoxy-1-naphthalenol; 2-(1-imidazolyl)-1,2,3,4-tetrahydro-7-carboxy-1-naphthalenol; 2-(1-imidazolyl)-1,2,3,4-tetrahydro-6-hydroxy-7-tert.butyl-1-naphthalenol; 2-(1-imidazolyl)-1,2,3,4-tetrahydro-5-bromo-6-hydroxy-1-naphthalenol; 2-(1-imidazolyl)-1,2,3,4-tetrahydro-8-carboxy-1-naphthalenol, both in the form of cis or trans isomer and of their mixture, and the pharmaceutically acceptable salts thereof.
Claim 12
Dependent Claim
24 words
A method according to claim 2, wherein said compound is selected from the group consisting of: 2-(1-imidazolyl)-5-methoxy-1-indanone; 2-(1-imidazolyl)-6-carboxy-1-indanone, and the pharmaceutically acceptable salts thereof.
Claim 13
Dependent Claim
30 words
A method according to claim 2, wherein said compound is 2-(1-imidazolyl)-3-methyl-1-indanone both in the form of cis or trans isomer and of their mixture, and the pharmaceutically acceptable salts thereof.
Claim 14
Dependent Claim
17 words
A method according to claim 2, wherein said compound is 2-(1-imidazolyl)-3,4-dihydro-5-bromo-6-hydroxy-1(2H)-naphthalenone, and the pharmaceutically acceptable salts thereof.
References Cited (Backward Citations)
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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) | 1988-01-08 | 1988-07-09 | 1989-01-08 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1992-01-08 | 1992-07-09 | 1993-01-08 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1996-01-08 | 1996-07-09 | 1997-01-08 | $7700.00 | Window Closed / Lapsed |