US4510149A
Expired / Lapsed
US
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N-Imidazolyl derivatives containing naphthalene or indene nucleus
Assignee: Pfizer Italia SRL
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Filing: 1983-07-01
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Granted: 1985-04-09
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Expires: 2003-07-01
Abstract
Abstract Compounds of the formula (I) <IMAGE> (I) wherein the symbol represents a single or a double bond; Z completes a single bond or is a -CH2- group; each of R1, R2, R3 and R4, which may be the same or different is (a) hydrogen; hydroxy; halogen; cyano; C1-C6 alkyl; C1-C6 alkoxy; a C2-C4 acyl or C2-C4 acylamino group; -SR', -N(R') (R''), -CH2OR', -COR or -CH2COR, wherein R is OR' or -N(R') (R'') and each of R' and R'', being the same or different, is hydrogen or C1-C6 alkyl; or (b) one of R1, R2, R3 and R4 is 5- tetrazolyl or a group selected from -COCH2OR', -CH=C(R')-COR and -X-C(R') (R'')-COR, wherein R, R' and R'' are as defined above, and X is -O-, -S-, or -NH-, and the others are as defined above under (a); one of R5 and R6 is hydrogen and the other is hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl, or a phenyl or pyridyl ring, wherein the phenyl or pyridyl ring is unsubstituted or substituted by one to three substituents chosen from hydroxy and C1-C4 alkoxy; or pharmaceutically acceptable salts thereof exhibit pharmaceutical activity as vasodilators or blood platelet aggregation inhibitors. Additionally, these compounds and their pharmaceutically acceptable salts are useful in the treatment of migraine, diabetic microangeopathy, rheumatoid arthritis, hypertension, peptic ulcers, osteoporosis, angina pectoris, atherosclerosis and dislipidaemies.
Inventors
- 👤 Paolo Cozzi
- 👤 Germano Carganico
- 👤 Antonio Pillan
- 👤 Umberto Branzoli
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-25 08:05
CPC Classifications
C; C07; C07D; C07D231/00; C07D231/02; C07D231/10; C07D231/12; A; A61; A61P; A61P1/00; A61P1/04; A61P25/00; A61P25/04; A61P25/06; A61P29/00; A61P3/00; A61P3/06; A61P7/00; A61P7/02; A61P9/00; A61P9/10; A61P9/12; C07D233/00; C07D233/54; C07D233/56; C07D249/00; C07D249/02; C07D249/08
Claims Analysis
Total Claims: 45
Claim 1
Independent Claim
224 words
A compound of formula (I) ##STR57## wherein the symbol represents a single or a double bond; Z completes a single bond or is a --CH 2 -- group; each of R 1 , R 2 , R 3 and R 4 , which may be the same or different, is (a) hydrogen; hydroxy; halogen; cyano; C 1 -C 6 alkyl; C 1 -C 6 alkoxy; a C 2 -C 4 acyl or C 2 -C 4 acylamino group; --SR', ##STR58## --CH 2 OR', --COR or --CH 2 COR, wherein R is --OR' or ##STR59## and each of R'0 and R", being the same or different, is hydrogen or C 1 -C 6 alkyl; or (b) one of R 1 , R 2 , R 3 and R 4 is 5-tetrazolyl or a group selected from --COCH 2 OR', ##STR60## wherein R, R' and R" are as defined above, and X is --O--, --S-- or --NH--, and the others are as defined above under (a); one of R 5 and R 6 is hydrogen and the other is hydrogen, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, or a phenyl or pyridyl ring, wherein the phenyl or pyridyl ring is unsubstituted or substituted by one to three substituents chosen from hydroxy and C 1 -C 4 alkoxy; or a pharmaceutically acceptable salt thereof.
Claim 2
Dependent Claim
224 words
A compound of formula (I) ##STR57## wherein the symbol represents a single or a double bond; Z completes a single bond or is a --CH 2 -- group; each of R 1 , R 2 , R 3 and R 4 , which may be the same or different, is (a) hydrogen; hydroxy; halogen; cyano; C 1 -C 6 alkyl; C 1 -C 6 alkoxy; a C 2 -C 4 acyl or C 2 -C 4 acylamino group; --SR', ##STR58## --CH 2 OR', --COR or --CH 2 COR, wherein R is --OR' or ##STR59## and each of R'0 and R", being the same or different, is hydrogen or C 1 -C 6 alkyl; or (b) one of R 1 , R 2 , R 3 and R 4 is 5-tetrazolyl or a group selected from --COCH 2 OR', ##STR60## wherein R, R' and R" are as defined above, and X is --O--, --S-- or --NH--, and the others are as defined above under (a); one of R 5 and R 6 is hydrogen and the other is hydrogen, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, or a phenyl or pyridyl ring, wherein the phenyl or pyridyl ring is unsubstituted or substituted by one to three substituents chosen from hydroxy and C 1 -C 4 alkoxy; or a pharmaceutically acceptable salt thereof.
Claim 3
Dependent Claim
173 words
A compound of formula (I) according to claim 1 wherein the symbol represents a double bond; Z is as defined in claim 1; each of R 1 , R 2 , R 3 and R 4 , which may be the same or different, is (a') hydrogen, hydroxy, halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, --CH 2 OH, --COOR a or ##STR61## wherein each of R a and R b is independently hydrogen, or C 1 -C 4 alkyl; or (b') one of R 1 , R 2 , R 3 and R 4 is C 2 -C 4 acyl, ##STR62## wherein R a and R b are as defined above, and the others are as defined above under (a'); one of R 5 and R 6 is hydrogen and the other is hydrogen, C 1 -C 3 alkyl, cyclopropyl, or a phenyl or pyridyl ring unsubstituted or substituted by one to three substituents chosen from hydroxy and C 1 -C 2 alkoxy; or a pharmaceutically acceptable salt thereof.
Claim 4
Dependent Claim
106 words
A compound of formula (I) according to claim 1 wherein the symbol represents a double bond; Z is a --CH 2 -- group; one of R 1 , R 2 , R 3 and R 4 is --COOR a , wherein R a is as defined in claim 2, and the others are independently chosen from hydrogen and hydroxy; or one of R 1 , R 2 , R 3 and R 4 is ##STR63## wherein R a and R b are as defined in claim 2, and the others are hydrogen; R 5 and R 6 are both hydrogen; or a pharmaceutically acceptable salt thereof.
Claim 5
Dependent Claim
78 words
A compound of formula (I) according to claim 1 wherein the symbol represents a double bond; Z is a --CH 2 -- group; one of R 1 , R 2 , R 3 and R 4 is ##STR64## wherein R g is is --NH 2 or --OR a and R a and R b are as defined in claim 2, and the others are hydrogen; R 5 and R 6 are hydrogen; or a pharmaceutically acceptable salt thereof.
Claim 6
Dependent Claim
87 words
A compound of formula (I) according to claim 1 wherein the symbol represents a double bond; Z is a --CH 2 -- group; one of R 1 , R 2 , R 3 and R 4 is --COR g , --CH 2 --COOR a or ##STR65## wherein R a is as defined in claim 2, and R g is as defined in claim 4, and the others are independently chosen from hydrogen and hydroxy; R 5 and R 6 are hydrogen, or a pharmaceutically acceptable salt thereof.
Claim 7
Dependent Claim
67 words
A compound of formula (I) according to claim 1 wherein the symbol represents a double bond; Z is a --CH 2 -- group; one of R 1 , R 2 , R 3 and R 4 is --COR g , wherein R g is as defined in claim 4, and the others are hydrogen; R 5 and R 6 are hydrogen, or a pharmaceutically acceptable salt thereof.
Claim 8
Dependent Claim
14 words
1,2-dihydro-3-(1-imidazolyl)-6-carboxynaphthalene, the C 1 -C 4 alkyl esters or a pharmaceutically acceptable salt thereof.
Claim 9
Dependent Claim
14 words
1,2-dihydro-3-(1-imidazolyl)-6-carboxynaphthalene, the C 1 -C 4 alkyl esters or a pharmaceutically acceptable salt thereof.
Claim 10
Dependent Claim
14 words
1,2-dihydro-3-(1-imidazolyl)-6-(2-carboxyisopropoxy)-naphthalene, the C 1 -C 4 alkyl esters or a pharmaceutically acceptable salt thereof.
Claim 11
Dependent Claim
14 words
1,2-dihydro-3-(1-imidazolyl)-6-(2-carboxyisopropoxy)-naphthalene, the C 1 -C 4 alkyl esters or a pharmaceutically acceptable salt thereof.
Claim 12
Dependent Claim
7 words
1,2-dihydro-3-(1-imidazolyl)-6-carbamoylnaphthalene or a pharmaceutically acceptable salt thereof.
Claim 13
Dependent Claim
7 words
1,2-dihydro-3-(1-imidazolyl)-6-carbamoylnaphthalene or a pharmaceutically acceptable salt thereof.
Claim 14
Dependent Claim
8 words
A compound selected from the group consisting of:
Claim 15
Dependent Claim
8 words
A compound selected from the group consisting of:
Claim 16
Dependent Claim
13 words
2-dihydro-3-(1-imidazolyl)-naphthalene; 1,2-dihydro-3-(1-imidazolyl)-6-methoxynaphthalene; 1,2-dihydro-3-(1-imidazolyl)-7-methoxynaphthalene; 1,2-dihydro-3-(1-imidazolyl)-6-methoxy-7-bromonaphthalene; 1,2-dihydro-3-(1-imidazolyl)-8-methoxynaphthalene; 1,2-dihydro-3-(1-imidazolyl)-6-ethoxycarbonylnaphthalene; 1,2-dihydro-3-(1-imidazolyl)-6-hydroxymethylnaphthalene; 1,2-dihydro-3-(1-imidazolyl)-7-carboxynaphthalene; 1,2-adihydro-3-(1-imidazolyl)-5-carboxynaphthalene; 1,2-dihydro-3-(1-imidazolyl)-5-carbamoylnaphthalene; 1,2-dihydro-3-(1-imidazolyl)-6-ethoxycarbonylmethyloxynaphthalene; 1,2-dihydro-3-(1-imidazolyl)-6-(2-ethoxycarbonylisopropoxy)-naphthalene; 1,2-dihydro-3-(1-imidazolyl)-6-carboxymethyloxynaphthalene;
Claim 17
Dependent Claim
13 words
2-dihydro-3-(1-imidazolyl)-naphthalene; 1,2-dihydro-3-(1-imidazolyl)-6-methoxynaphthalene; 1,2-dihydro-3-(1-imidazolyl)-7-methoxynaphthalene; 1,2-dihydro-3-(1-imidazolyl)-6-methoxy-7-bromonaphthalene; 1,2-dihydro-3-(1-imidazolyl)-8-methoxynaphthalene; 1,2-dihydro-3-(1-imidazolyl)-6-ethoxycarbonylnaphthalene; 1,2-dihydro-3-(1-imidazolyl)-6-hydroxymethylnaphthalene; 1,2-dihydro-3-(1-imidazolyl)-7-carboxynaphthalene; 1,2-adihydro-3-(1-imidazolyl)-5-carboxynaphthalene; 1,2-dihydro-3-(1-imidazolyl)-5-carbamoylnaphthalene; 1,2-dihydro-3-(1-imidazolyl)-6-ethoxycarbonylmethyloxynaphthalene; 1,2-dihydro-3-(1-imidazolyl)-6-(2-ethoxycarbonylisopropoxy)-naphthalene; 1,2-dihydro-3-(1-imidazolyl)-6-carboxymethyloxynaphthalene;
Claim 18
Dependent Claim
30 words
2-dihydro-3-(1-imidazolyl)-6-(2-carboxyvinyl)-naphthalene; 1,2-dihydro-3-(1-imidazolyl)-6-(2-ethoxycarbonylvinyl)-naphthalene; 1,2-dihydro-3-(1-imidazolyl)-6-hydroxy-7-acetylnaphthalene; 1,2-dihydro-3-(1-imidazolyl)-6-hydroxy-7-carboxynaphthalene; 1,2-dihydro-3-(1-imidazolyl)-6-tert-butyl-7-hydroxynaphthalene; 1,2-dihydro-3-(1-imidazolyl)-6-carboxymethylnaphthalene; 1,2-dihydro-3-(1-imidazolyl)-8-carboxynaphthalene; 1,2,3,4-tetrahydro-2-(1-imidazolyl)-7-carboxynaphthalene; 1,2,3,4-tetrahydro-2-(1-imidazolyl)-6-carboxynaphthalene; 1,2,3,4-tetrahydro-2-(1-imidazolyl)-7-(2-carboxyvinyl)-naphthalene; 2-(1-imidazolyl)-5-carboxyindene, and 2-(1-imidazolyl)-5-(2-carboxyvinyl)indene, or a pharmaceutically acceptable salt thereof, or, when appropriate, the C 1 -C 4 alkyl ester thereof.
Claim 19
Dependent Claim
30 words
2-dihydro-3-(1-imidazolyl)-6-(2-carboxyvinyl)-naphthalene; 1,2-dihydro-3-(1-imidazolyl)-6-(2-ethoxycarbonylvinyl)-naphthalene; 1,2-dihydro-3-(1-imidazolyl)-6-hydroxy-7-acetylnaphthalene; 1,2-dihydro-3-(1-imidazolyl)-6-hydroxy-7-carboxynaphthalene; 1,2-dihydro-3-(1-imidazolyl)-6-tert-butyl-7-hydroxynaphthalene; 1,2-dihydro-3-(1-imidazolyl)-6-carboxymethylnaphthalene; 1,2-dihydro-3-(1-imidazolyl)-8-carboxynaphthalene; 1,2,3,4-tetrahydro-2-(1-imidazolyl)-7-carboxynaphthalene; 1,2,3,4-tetrahydro-2-(1-imidazolyl)-6-carboxynaphthalene; 1,2,3,4-tetrahydro-2-(1-imidazolyl)-7-(2-carboxyvinyl)-naphthalene; 2-(1-imidazolyl)-5-carboxyindene, and 2-(1-imidazolyl)-5-(2-carboxyvinyl)indene, or a pharmaceutically acceptable salt thereof, or, when appropriate, the C 1 -C 4 alkyl ester thereof.
Claim 20
Dependent Claim
225 words
A compound of the formula (I) ##STR66## wherein the symbol represents a single or a double bond; Z completes a single bond or is a --CH 2 -- group; each of R 1 , R 2 , R 3 and R 4 , which may be the same or different, is (a) hydrogen; hydroxy; halogen; cyano; C 1 -C 6 alkyl; C 1 -C 6 alkoxy; C 2 -C 4 acyl or C 2 -C 4 acylamino; --SR', --N(R')(R"), --CH 2 OR', --COR or --CH 2 COR, wherein R is --OR' or --N(R')(R"), and each of R' and R", being the same or different, is hydrogen or C 1 -C 6 alkyl; or (b) one of R 1 , R 2 , R 3 and R 4 is 5-tetrazolyl or a group selected from --COCH 2 OR', --CH═C(R')--COR and --X--C(R') (R") --COR, wherein R,R' and R" are as defined above, and X is --S-- or --NH--, and the others are as defined above under (a); one of R 5 and R 6 is hydrogen and the other is hydrogen, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, or a phenyl or pyridyl ring, wherein the phenyl or pyridyl ring is unsubstituted or substituted by one to three substituents chosen from hydroxy and C 1 -C 4 alkoxy; or a pharmaceutically acceptable salt thereof.
Claim 21
Dependent Claim
225 words
A compound of the formula (I) ##STR66## wherein the symbol represents a single or a double bond; Z completes a single bond or is a --CH 2 -- group; each of R 1 , R 2 , R 3 and R 4 , which may be the same or different, is (a) hydrogen; hydroxy; halogen; cyano; C 1 -C 6 alkyl; C 1 -C 6 alkoxy; C 2 -C 4 acyl or C 2 -C 4 acylamino; --SR', --N(R')(R"), --CH 2 OR', --COR or --CH 2 COR, wherein R is --OR' or --N(R')(R"), and each of R' and R", being the same or different, is hydrogen or C 1 -C 6 alkyl; or (b) one of R 1 , R 2 , R 3 and R 4 is 5-tetrazolyl or a group selected from --COCH 2 OR', --CH═C(R')--COR and --X--C(R') (R") --COR, wherein R,R' and R" are as defined above, and X is --S-- or --NH--, and the others are as defined above under (a); one of R 5 and R 6 is hydrogen and the other is hydrogen, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, or a phenyl or pyridyl ring, wherein the phenyl or pyridyl ring is unsubstituted or substituted by one to three substituents chosen from hydroxy and C 1 -C 4 alkoxy; or a pharmaceutically acceptable salt thereof.
Claim 22
Dependent Claim
175 words
A compound of formula (I) ##STR67## wherein the symbol represents a single bond or a double bond; Z completes a single bond or is a --CH 2 -- group; one of R 1 , R 2 , R 3 and R 4 is --O--C(R')(R")--COR and the remainder, which may be the same or different, are hydrogen; hydroxy, halogen; cyano; C 1 -C 6 alkyl; C 1 -C 6 alkoxy; C 2 -C 4 acyl or C 2 -C 4 acylamino; --SR', --N(R')(R"), --CH 2 OR', --COR or --CH 2 COR; wherein R is --OR' or --N(R')(R") and each of R' and R", being the same or different, is hydroge or C 1 -C 6 alkyl; one of R 5 and R 6 is hydrogen and the other is hydrogen, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, or a phenyl or pyridyl ring, wherein the phenyl or pyridyl ring is unsubstituted or substituted by one to three substituents chosen from hydroxy and C 1 -C 4 alkoxy; or a pharmaceutically acceptable salt thereof.
Claim 23
Dependent Claim
175 words
A compound of formula (I) ##STR67## wherein the symbol represents a single bond or a double bond; Z completes a single bond or is a --CH 2 -- group; one of R 1 , R 2 , R 3 and R 4 is --O--C(R')(R")--COR and the remainder, which may be the same or different, are hydrogen; hydroxy, halogen; cyano; C 1 -C 6 alkyl; C 1 -C 6 alkoxy; C 2 -C 4 acyl or C 2 -C 4 acylamino; --SR', --N(R')(R"), --CH 2 OR', --COR or --CH 2 COR; wherein R is --OR' or --N(R')(R") and each of R' and R", being the same or different, is hydroge or C 1 -C 6 alkyl; one of R 5 and R 6 is hydrogen and the other is hydrogen, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, or a phenyl or pyridyl ring, wherein the phenyl or pyridyl ring is unsubstituted or substituted by one to three substituents chosen from hydroxy and C 1 -C 4 alkoxy; or a pharmaceutically acceptable salt thereof.
Claim 24
Dependent Claim
25 words
A pharmaceutical composition for inducing vasodilation comprising a suitable carrier or diluent and a vasodilatory effective amount of the compound as claimed in claim 11.
Claim 25
Dependent Claim
29 words
A pharmaceutical composition for inhibiting blood platelet aggregation comprising a suitable carrier or diluent and a blood platelet antiaggregatory effective amount of the compound as claimed in claim 11.
Claim 26
Dependent Claim
27 words
A pharmaceutical composition for the treatment of migraine comprising a suitable carrier or diluent and a therapeutically effective amount of the compound as claimed in claim 11.
Claim 27
Dependent Claim
28 words
A pharmaceutical composition for the treatment of diabetic microangiopathy comprising a suitable carrier or diluent and a therapeutically effective amount of the compound as claimed in claim 11.
Claim 28
Dependent Claim
28 words
A pharmaceutical composition for the treatment of rheumatoid arthritis comprising a suitable carrier or diluent and a therapeutically effective amount of the compound as claimed in claim 11.
Claim 29
Dependent Claim
27 words
A pharmaceutical composition for the treatment of hypertension comprising a suitable carrier or diluent and a therapeutically effective amount of the compound as claimed in claim 11.
Claim 30
Dependent Claim
28 words
A pharmaceutical composition for the treatment of peptic ulcers comprising a suitable carrier or diluent and a therapeutically effective amount of the compound as claimed in claim 11.
Claim 31
Dependent Claim
27 words
A pharmaceutical composition for the treatment of osteoporosis comprising a suitable carrier or diluent and a therapeutically effective amount of the compound as claimed in claim 11.
Claim 32
Dependent Claim
28 words
A pharmaceutical composition for the treatment of angina pectoris comprising a suitable carrier or diluent and a therapeutically effective amount of the compound as claimed in claim 11.
Claim 33
Dependent Claim
27 words
A pharmaceutical composition for the treatment of atherosclerosis comprising a suitable carrier or diluent and a therapeutically effective amount of the compound as claimed in claim 12.
Claim 34
Dependent Claim
27 words
A pharmaceutical composition for the treatment of dislipidaemies comprising a suitable carrier or diluent and a therapeutically effective amount of the compound as claimed in claim 12.
Claim 35
Dependent Claim
25 words
A method of inducing vasodilation in a patient comprising administering to the patient a vasodilatory effective amount of the compound as claimed in claim 11.
Claim 36
Dependent Claim
29 words
A method of inhibiting blood platelet aggregation in a patient comprising administering to the patient a blood platelet antiaggregatory affective amount of the compound as claimed in claim 11.
Claim 37
Dependent Claim
25 words
A method of treating migraine in a patient comprising administering to the patient a therapeutically effective amount of the compound as claimed in claim 11.
Claim 38
Dependent Claim
26 words
A method of treating diabetic microangiopathy in a patient comprising administering to the patient a therapeutically effective amount of the compound as claimed in claim 11.
Claim 39
Dependent Claim
26 words
A method of treating rheumatoid arthritis in a patient comprising administering to the patient a therapeutically effective amount of the compound as claimed in claim 11.
Claim 40
Dependent Claim
25 words
A method of treating hypertension in a patient comprising administering to the patient a therapeutically effective amount of the compound as claimed in claim 11.
Claim 41
Dependent Claim
26 words
A method of treating peptic ulcers in a patient comprising administering to the patient a therapeutically effective amount of the compound as claimed in claim 11.
Claim 42
Dependent Claim
25 words
A method of treating osteoporosis in a patient comprising administering to the patient a therapeutically effective amount of the compound as claimed in claim 11.
Claim 43
Dependent Claim
26 words
A method of treating angina pectoris in a patient comprising administering to the patient a therapeutically effective amount of the compound as claimed in claim 11.
Claim 44
Dependent Claim
25 words
A method of treating atherosclerosis in a patient comprising administering to the patient a therapeutically effective amount of the compound as claimed in claim 12.
Claim 45
Dependent Claim
25 words
A method of treating dislipidaemies in a patient comprising administering to the patient a therapeutically effective amount of the compound as claimed in claim 12.
References Cited (Backward Citations)
NL6705095A
Cited
US3485917A
Cited
US3541109A
Cited
US3637731A
Cited
BE827870A
Cited
US4006243A
Cited
EP0000951A1
Cited
BE887766A
Cited
US4342775A
Cited
BE893917A
Cited
EP0073663A2
Cited
JPS6081566A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1988-04-08 | 1988-10-08 | 1989-04-09 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1992-04-08 | 1992-10-08 | 1993-04-09 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1996-04-08 | 1996-10-08 | 1997-04-09 | $7700.00 | Window Closed / Lapsed |