US5468746A
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Compounds active on the cardiovascular system
Assignee: Zambon Group SpA
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Filing: 1991-06-21
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Granted: 1995-11-21
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Expires: 2011-06-21
Abstract
Abstract Compounds of the formula ##STR1## (wherein Ar, R, R 1 , R 2 , R 3 , R 4 , R 5 , m and n have the meanings given in the description), their preparation and pharmaceutical compositions containing them. The compounds of formula I are active on the cardiovascular system as antivasospastics, antiangina agents, antihypertensives and vasodilators.
Inventors
- 👤 Cesare Casagrande
- 👤 Stefania Montanari
- 👤 Francesco Santangelo
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 12:43
CPC Classifications
C; C07; C07D; C07D405/00; C07D405/02; C07D405/06; C07D211/00; C07D211/04; C07D211/80; C07D211/84; C07D211/90; C07F; C07F7/00; C07F7/02; C07F7/08; C07F7/18; C07F7/1804
Claims Analysis
Total Claims: 21
Claim 1
Independent Claim
341 words
A compound of the formula ##STR15## wherein Ar is an optionally substituted mono- or dicyclo aromatic or heteroaromatic ring system, having at most 10 ring atoms, any heteroaromatic ring having at least 5 ring atoms, any substituent of a substituted ring system being a member selected from the group consisting of halogen, hydroxy, C 1 -C 5 alkyl, C 2 -C 5 alkenyl, C 1 -C 3 alkoxy, allyloxy, alkoxyalkyl having from 1 to 5 carbon atoms in each of the alkyl and alkoxy moieties and optional unsaturation in the chain, phenoxy, phenylalkoxy, aminocarbonylalkyl having from 1 to 3 carbon atoms in the alkyl moiety, cyano, carboxy, carbamoylalkyl, aminocarboxy, amino, mono-alkylamino and dialkylamino wherein the nitrogen atom is optionally a ring member; each of R and R 1 is, independently, hydrogen or C 1 -C 3 alkyl; R 2 is a straight-chain or branched unsubstituted or aryl-substituted C 1 -C 7 alkyl, straight-chain or branched unsubstituted or aryl-substituted C 2 -C 7 alkenyl, or X--R 7 , where X is CO, CS or SO 2 , and R 7 is alkyl or alkoxyalkyl having from 1 to 5 carbon atoms in each of the alkyl and alkoxy moieties, hydroxy, C 1 -C 3 alkoxy, phenyl, mono-alkylamino or di-alkylamino having from 1 to 5 carbon atoms in each alkyl moiety or C 1 -C 5 alkylthio; R 3 is cyano, amino or optionally-fluoro-substituted C 1 -C 3 alkyl; each of R 4 and R 6 is, independently, alkyl or alkoxyalkyl having from 1 to 5 carbon atoms in each alkyl and alkoxy moiety; R 5 is an optionally-substituted ring selected from the group consisting of phenyl, napthyl, tetrahydronaphthyl and indanyl, wherein any ring substituent is a member selected from the group consisting of halogen, hydroxy, alkyl, alkenyl, alkoxy, alkenyloxy, alkoxyalkyl, alkanoyl, trifluoromethyl, amino, nitro, carbamoyl, cyano, alkylthio, carbamoylalkyl and alkanoylamino having up to six carbon atoms in the alkyl moiety; each of m and n is, independently, 1, 2 or 3; or a salt thereof with an organic or inorganic pharmaceutically-acceptable acid.
Claim 2
Dependent Claim
341 words
A compound of the formula ##STR15## wherein Ar is an optionally substituted mono- or dicyclo aromatic or heteroaromatic ring system, having at most 10 ring atoms, any heteroaromatic ring having at least 5 ring atoms, any substituent of a substituted ring system being a member selected from the group consisting of halogen, hydroxy, C 1 -C 5 alkyl, C 2 -C 5 alkenyl, C 1 -C 3 alkoxy, allyloxy, alkoxyalkyl having from 1 to 5 carbon atoms in each of the alkyl and alkoxy moieties and optional unsaturation in the chain, phenoxy, phenylalkoxy, aminocarbonylalkyl having from 1 to 3 carbon atoms in the alkyl moiety, cyano, carboxy, carbamoylalkyl, aminocarboxy, amino, mono-alkylamino and dialkylamino wherein the nitrogen atom is optionally a ring member; each of R and R 1 is, independently, hydrogen or C 1 -C 3 alkyl; R 2 is a straight-chain or branched unsubstituted or aryl-substituted C 1 -C 7 alkyl, straight-chain or branched unsubstituted or aryl-substituted C 2 -C 7 alkenyl, or X--R 7 , where X is CO, CS or SO 2 , and R 7 is alkyl or alkoxyalkyl having from 1 to 5 carbon atoms in each of the alkyl and alkoxy moieties, hydroxy, C 1 -C 3 alkoxy, phenyl, mono-alkylamino or di-alkylamino having from 1 to 5 carbon atoms in each alkyl moiety or C 1 -C 5 alkylthio; R 3 is cyano, amino or optionally-fluoro-substituted C 1 -C 3 alkyl; each of R 4 and R 6 is, independently, alkyl or alkoxyalkyl having from 1 to 5 carbon atoms in each alkyl and alkoxy moiety; R 5 is an optionally-substituted ring selected from the group consisting of phenyl, napthyl, tetrahydronaphthyl and indanyl, wherein any ring substituent is a member selected from the group consisting of halogen, hydroxy, alkyl, alkenyl, alkoxy, alkenyloxy, alkoxyalkyl, alkanoyl, trifluoromethyl, amino, nitro, carbamoyl, cyano, alkylthio, carbamoylalkyl and alkanoylamino having up to six carbon atoms in the alkyl moiety; each of m and n is, independently, 1, 2 or 3; or a salt thereof with an organic or inorganic pharmaceutically-acceptable acid.
Claim 3
Dependent Claim
68 words
A compound according to claim 1, wherein Ar is an optionally-substituted monocyclic or bicyclic ring selected from the group consisting of phenyl, naphthyl, isobenzofuranyl, benzofuranyl, 3,4-dihydrocarbostyryl, benzopyranyl, tetrahydronaphthyl, carbazolyl, indenyl, indolyl and 1,2,5-thiadiazolyl, and any ring substituent is a member selected from the group consisting of fluorine, chlorine, bromine, acetyl, allyl, carbamoylmethyl, butyroylamino, cyclohexyl, cyano, hydroxy, butyroyl, acetylamino, methoxycarbonyl, methoxyethyl, methoxy, allyloxy, cyclopentyl, cyclopropyl, morpholine, ethyl and isobutyroyl.
Claim 4
Dependent Claim
92 words
A compound according to claim 1, wherein Ar is a member selected from the group consisting of 2-methoxyphenyl, 2-allyloxyphenyl, 2-cyanophenyl, 2-methylphenyl, 2-allylphenyl, 4-carbamoylmethylphenyl, 4-hydroxyphenyl, 4-morpholino-1,2,5-thiadiazol-3-yl,indol-4-yl and 3,4-dihydro-1(H)-carbostyryl-5-yl; each of R and R 1 is, independently, hydrogen or methyl; R 2 has its previously-ascribed meaning; R 3 is methyl or trifluoromethyl; R 5 is substituted phenyl, any substituent of which is a member selected from the group consisting of nitro, trifluoromethyl and halogen; X is a carbonyl or sulfonic group; and R 7 is methyl, ethyl, isopropyl, phenyl, dimethylamino, diethylamino, methoxy or ethoxy.
Claim 5
Dependent Claim
10 words
A compound of claim 1 wherein R 3 is cyano.
Claim 6
Dependent Claim
10 words
A compound of claim 1 wherein R 3 is amino.
Claim 7
Dependent Claim
14 words
A compound of claim 1 wherein R 3 is C 1 -C 3 alkyl.
Claim 8
Dependent Claim
15 words
A compound of claim 1 wherein R 3 is fluoro-substituted C 1 -C 3 alkyl.
Claim 9
Dependent Claim
259 words
A compound of the formula ##STR16## wherein Ar is a member selected from the group consisting of phenyl, naphthyl, isobenzofuranyl, benzofuranyl, 3,4-dihydrocarbostyryl, benzopyranyl, tetrahydronaphthyl, carbazolyl, indenyl, indolyl and 1,2,5-thiadiazolyl optionally substituted by fluorine, chlorine, bromine, acetyl, allyl, carbamoylmethyl, butyroylamino, cyclohexyl, cyano, hydroxy, butyroyl, acetylamino, methoxycarbonyl, methoxyethyl, methoxy, allyloxy, cyclopentyl, cyclopropyl, morpholine, ethyl or isobutyroyl; each of R and R 1 is, independently, hydrogen or C 1 -C 3 alkyl; R 2 is optionally-aryl-substituted straight or branched C 1 -C 7 alkyl, optionally-aryl-substituted straight or branched C 2 -C 7 alkenyl, or X--R 7 , where X is CO, CS or SO 2 , and R 7 is alkyl or alkoxyalkyl having from 1 to 5 carbon atoms in each alkyl and alkoxy moiety, hydroxy, C 1 --C 3 alkoxy, mono- or di-alkylamino having from 1 to 5 carbon atoms in each alkyl moiety, or C 1 -C 5 alkylthio; R 3 is cyano, amino or optionally-fluoro-substituted C 1 -C 3 alkyl; each of R 4 and R 6 is, independently, alkyl or alkoxyalkyl having from 1 to 5 carbon atoms in each of the alkyl and alkoxy moieties; R 5 is optionally-ring-substituted phenyl, naphthyl, tetrahydronaphthyl or indanyl, wherein any ring substituent is a member selected from the group consisting of halogen, hydroxy, alkyl, alkenyl, alkoxy, alkenyloxy, alkoxyalkyl, alkanoyl, trifluoromethyl, amino, nitro, carbamoyl, cyano, alkylthio, carbamoylalkyl and alkanoylamino having up to 6 carbon atoms in the alkyl moiety; each of m and n is, independently, 1, 2 or 3; or a salt thereof with an organic or inorganic pharmaceutically-acceptable acid.
Claim 10
Dependent Claim
259 words
A compound of the formula ##STR16## wherein Ar is a member selected from the group consisting of phenyl, naphthyl, isobenzofuranyl, benzofuranyl, 3,4-dihydrocarbostyryl, benzopyranyl, tetrahydronaphthyl, carbazolyl, indenyl, indolyl and 1,2,5-thiadiazolyl optionally substituted by fluorine, chlorine, bromine, acetyl, allyl, carbamoylmethyl, butyroylamino, cyclohexyl, cyano, hydroxy, butyroyl, acetylamino, methoxycarbonyl, methoxyethyl, methoxy, allyloxy, cyclopentyl, cyclopropyl, morpholine, ethyl or isobutyroyl; each of R and R 1 is, independently, hydrogen or C 1 -C 3 alkyl; R 2 is optionally-aryl-substituted straight or branched C 1 -C 7 alkyl, optionally-aryl-substituted straight or branched C 2 -C 7 alkenyl, or X--R 7 , where X is CO, CS or SO 2 , and R 7 is alkyl or alkoxyalkyl having from 1 to 5 carbon atoms in each alkyl and alkoxy moiety, hydroxy, C 1 --C 3 alkoxy, mono- or di-alkylamino having from 1 to 5 carbon atoms in each alkyl moiety, or C 1 -C 5 alkylthio; R 3 is cyano, amino or optionally-fluoro-substituted C 1 -C 3 alkyl; each of R 4 and R 6 is, independently, alkyl or alkoxyalkyl having from 1 to 5 carbon atoms in each of the alkyl and alkoxy moieties; R 5 is optionally-ring-substituted phenyl, naphthyl, tetrahydronaphthyl or indanyl, wherein any ring substituent is a member selected from the group consisting of halogen, hydroxy, alkyl, alkenyl, alkoxy, alkenyloxy, alkoxyalkyl, alkanoyl, trifluoromethyl, amino, nitro, carbamoyl, cyano, alkylthio, carbamoylalkyl and alkanoylamino having up to 6 carbon atoms in the alkyl moiety; each of m and n is, independently, 1, 2 or 3; or a salt thereof with an organic or inorganic pharmaceutically-acceptable acid.
Claim 11
Dependent Claim
115 words
A compound according to claim 1, wherein Ar is a member selected from the group consisting of 2-methoxyphenyl, 2-allyloxyphenyl, 2-cyanophenyl, 2-methylphenyl, 2-allylphenyl, 4-carbamoylmethylphenyl, 4-hydroxyphenyl, 4-morpholino-1,2,5-thiadiazol-3-yl, indol-4-yl and 3,4-dihydro-1(H)-carbostyryl-5-yl; each of R and R 1 is, independently, hydrogen or methyl; R 2 is optionally-aryl-substituted straight or branched C 1 -C 7 alkyl, optionally-aryl-substituted straight or branched C 2 -C 7 alkenyl, or X--R 7 , where X is a carbonyl or a sulfonic group, and R 7 is methyl, ethyl, isopropyl, phenyl, dimethylamino, diethylamino, methoxy or ethoxy; R 3 is methyl or trifluoromethyl; and R 5 is a substituted phenyl where any substituent is a member selected from the group consisting of nitro, trifluoromethyl and halogen.
Claim 12
Dependent Claim
10 words
A compound of claim 8 wherein R 3 is cyano.
Claim 13
Dependent Claim
10 words
A compound of claim 8 wherein R 3 is amino.
Claim 14
Dependent Claim
14 words
A compound of claim 8 wherein R 3 is C 1 -C 3 alkyl.
Claim 15
Dependent Claim
15 words
A compound of claim 8 wherein R 3 is fluoro-substituted C 1 -C 3 alkyl.
Claim 16
Dependent Claim
242 words
A compound of claim 1 wherein Ar is a member selected from the group consisting of 2-methoxyphenyl, 2-allyloxyphenyl, 2-cyanophenyl, 2-methylphenyl, 2-allylphenyl, 4-carbamoylmethylphenyl, 4-hydroxyphenyl, 4-morpholino-1,2,5-thiadiazol-3-yl, indol-4-yl and 3,4-dihydro-2(H)-carbostyryl-5-yl; each of R and R 1 is, independently, hydrogen or C 1 -C 3 alkyl; R 2 is optionally-aryl-substituted straight or branched C 1 -C 7 alkyl, optionally-aryl-substituted straight or branched C 2 -C 7 alkenyl, or X--R 7 , where X is CO, CS or SO 2 , and R 7 is alkyl or alkoxyalkyl having from 1 to 5 carbon atoms in each of the alkyl and alkoxy moieties, hydroxy, C 1 -C 3 alkoxy, monoalkylamino or dialkylamino having from 1 to 5 carbon atoms in each alkyl moiety, or C 1 -C 5 alkylthio; R 3 is cyano, amino or optionally-fluoro-substituted C 1 -C 3 alkyl; each of R 4 and R 6 is, independently, alkyl or alkoxyalkyl having from 1 to 5 carbon atoms in each alkyl and alkoxy moiety; R 5 is optionally-substituted ring selected from the group consisting of phenyl, naphthyl, tetrahydronaphthyl and indanyl, wherein any substituent of a substituted ring is a member selected from the group consisting of halogen, hydroxy, alkyl, alkenyl, alkoxy, alkenyloxy, alkoxyalkyl, alkanoyl, trifluoromethyl, amino, nitro, carbamoyl, cyano, alkylthio, carbamoylalkyl and alkanoylamino having up to 6 carbon atoms in the alkyl moiety; each of m and n is, independently, 1, 2 or 3; or a salt thereof with an organic or inorganic pharmaceutically-acceptable acid.
Claim 17
Dependent Claim
82 words
A compound of claim 14, wherein each of R and R 1 is, independently, hydrogen or methyl; R 2 is optionally-aryl-substituted straight or branched C 1 -C 7 alkyl, optionally-aryl-substituted straight or branched C 2 -C 7 alkenyl, or X--R 7 , where X is a carbonyl or a sulfonic group, and R 7 is methyl, ethyl, isopropyl, phenyl, dimethylamino, diethylamino, methoxy or ethoxy; R 3 is methyl or trifluoromethyl; and R 5 is phenyl optionally substituted by nitro, trifluoromethyl or halogen.
Claim 18
Dependent Claim
27 words
A pharmaceutical composition useful for treating vasospastic, angina, hypertension and vasoconstriction pathologies, containing an effective amount of a compound of claim 1 together with a pharmaceutical excipient.
Claim 19
Dependent Claim
27 words
A pharmaceutical composition useful for treating vasospastic, angina, hypertension and vasoconstriction pathologies, containing an effective amount of a compound of claim 8 together with a pharmaceutical excipient.
Claim 20
Dependent Claim
27 words
A pharmaceutical composition useful for treating vasospastic, angina, hypertension and vasoconstriction pathologies, containing an effective amount of a compound of claim 14 together with a pharmaceutical excipient.
Claim 21
Dependent Claim
29 words
A compound of claim 1 wherein Ar is an optionally-substituted member selected from the group consisting of phenyl, naphthyl, isobenzofuranyl, benzofuranyl, 3,4-dihydrocarbostyryl, benzopyranyl, tetrahydronaphthyl, carbazolyl, indenyl, indolyl and 1,2,5-thiadazolyl.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1998-11-20 | 1999-05-22 | 1999-11-21 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2002-11-20 | 2003-05-22 | 2003-11-21 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2006-11-20 | 2007-05-22 | 2007-11-21 | $7700.00 | Window Closed / Lapsed |