US4446113A
Expired / Lapsed
US
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Benzopyrans
Assignee: Beecham Group PLC
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Filing: 1982-09-24
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Granted: 1984-05-01
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Expires: 2002-09-24
Abstract
Abstract Compounds of formula (I): <IMAGE> (I) wherein: one of R1 and R2 is hydrogen and the other is selected from the class of alkylcarbonyl, alkoxycarbonyl, alkylcarbonyloxy, alkylhydroxymethyl, nitro, cyano, chloro, trifluoromethyl, alkylsulphinyl, alkylsulphonyl, alkoxysulphinyl, alkoxysulphonyl, alkylcarbonylamino, alkoxycarbonylamino, or aminosulphinyl, aminosulphonyl or aminocarbonyl, the amino moiety being optionally substituted by one or two alkyl groups, or alkylsulphinylamino, alkylsulphonylamino, alkoxysulphinylamino or alkoxysulphonylamino, or ethylenyl terminally substituted by alkylcarbonyl, nitro or cyano or -C(alkyl)NOH or -C(alkyl)NNH2, the alkyl groups or alkyl moieties of alkyl-containing groups having from 1 to 6 carbon atoms; one of R3 and R4 is hydrogen or alkyl having from 1 to 4 carbon atoms and the other is alkyl having from 1 to 4 carbon atoms, or R3 and R4 together with the carbon atom to which they are attached are spiroalkyl having from 3 to 6 carbon atoms; R5 is hydrogen, alkyl having from 1 to 3 carbon atoms or acyl having from 1 to 8 carbon atoms; and n is 1 or 2; the lactam group being trans to the OR5 group; have anti-hypertensive activity and are of use in the treatment of high blood pressure.
Inventors
- 👤 John M. Evans
- 👤 Robin E. Buckingham
- 👤 Kenneth Willcocks
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-30 22:09
CPC Classifications
C; C07; C07D; C07D405/00; C07D405/02; C07D405/04; A; A61; A61P; A61P9/00; A61P9/12; C07D311/00; C07D311/02; C07D311/04; C07D311/58; C07D311/68; C07D311/70
Claims Analysis
Total Claims: 31
Claim 1
Independent Claim
186 words
A compound of formula (I): ##STR29## wherein: one of R 1 and R 2 is hydrogen and the other is selected from the class of alkylcarbonyl, alkoxycarbonyl, alkylcarbonyloxy, alkylhydroxymethyl, nitro, cyano, chloro, trifluoromethyl, alkylsulphinyl, alkylsulphonyl, alkoxysulphinyl, alkoxysulphonyl, alkylcarbonylamino, alkoxycarbonylamino, or aminosulphinyl, aminosulphonyl or aminocarbonyl, the amino moiety being optionally substituted by one or two alkyl groups, or alkylsulphinylamino, alkylsulphonylamino, alkoxysulphinylamino or alkoxysulphonylamino, or ethylenyl terminally substituted by alkylcarbonyl, nitro or cyano or --C(alkyl)NOH or --C(alkyl)NNH 2 , the alkyl groups or alkyl moieties of alkyl-containing groups having from 1 to 6 carbon atoms; one of R 3 and R 4 is hydrogen or alkyl having from 1 to 4 carbon atoms and the other is alkyl having from 1 to 4 carbon atoms, or R 3 and R 4 together with the carbon atom to which they are attached are spiroalkyl having from 3 to 6 carbon atoms; R 5 is hydrogen, alkyl having from 1 to 3 carbon atoms or carboxylic acyl having from 1 to 8 carbon atoms; and n is 1 or 2; the lactam group being trans to the OR 5 group.
Claim 2
Dependent Claim
186 words
A compound of formula (I): ##STR29## wherein: one of R 1 and R 2 is hydrogen and the other is selected from the class of alkylcarbonyl, alkoxycarbonyl, alkylcarbonyloxy, alkylhydroxymethyl, nitro, cyano, chloro, trifluoromethyl, alkylsulphinyl, alkylsulphonyl, alkoxysulphinyl, alkoxysulphonyl, alkylcarbonylamino, alkoxycarbonylamino, or aminosulphinyl, aminosulphonyl or aminocarbonyl, the amino moiety being optionally substituted by one or two alkyl groups, or alkylsulphinylamino, alkylsulphonylamino, alkoxysulphinylamino or alkoxysulphonylamino, or ethylenyl terminally substituted by alkylcarbonyl, nitro or cyano or --C(alkyl)NOH or --C(alkyl)NNH 2 , the alkyl groups or alkyl moieties of alkyl-containing groups having from 1 to 6 carbon atoms; one of R 3 and R 4 is hydrogen or alkyl having from 1 to 4 carbon atoms and the other is alkyl having from 1 to 4 carbon atoms, or R 3 and R 4 together with the carbon atom to which they are attached are spiroalkyl having from 3 to 6 carbon atoms; R 5 is hydrogen, alkyl having from 1 to 3 carbon atoms or carboxylic acyl having from 1 to 8 carbon atoms; and n is 1 or 2; the lactam group being trans to the OR 5 group.
Claim 3
Dependent Claim
32 words
A compound according to claim 1, wherein one of R 1 and R 2 is hydrogen and the other is selected from the class of alkylcarbonyl, alkoxycarbonyl, alkylcarbonyloxy, alkylhydroxymethyl, nitro or cyano.
Claim 4
Dependent Claim
32 words
A compound according to claim 1, wherein the alkyl groups or alkyl moieties of alkyl-containing groups, in respect of the other of R 1 and R 2 , are methyl or ethyl.
Claim 5
Dependent Claim
22 words
A compound according to claim 1, wherein R 3 and R 4 are both alkyl having from 1 to 4 carbon atoms.
Claim 6
Dependent Claim
11 words
A compound according to claim 1, wherein R 5 is hydrogen.
Claim 7
Dependent Claim
61 words
A compound of formula (II): ##STR30## wherein one of R 1 and R 2 is hydrogen and the other is selected from the class of alkylcarbonyl, alkoxycarbonyl, alkylcarbonyloxy, alkylhydroxymethyl, nitro or cyano, the alkyl groups or alkyl moieties of alkyl containing groups being methyl or ethyl, and n is 1 or 2; the lactam group being trans to the OH group.
Claim 8
Dependent Claim
61 words
A compound of formula (II): ##STR30## wherein one of R 1 and R 2 is hydrogen and the other is selected from the class of alkylcarbonyl, alkoxycarbonyl, alkylcarbonyloxy, alkylhydroxymethyl, nitro or cyano, the alkyl groups or alkyl moieties of alkyl containing groups being methyl or ethyl, and n is 1 or 2; the lactam group being trans to the OH group.
Claim 9
Dependent Claim
23 words
A compound according to claim 1, wherein one of R 1 and R 2 is hydrogen and the other is nitro or cyano.
Claim 10
Dependent Claim
11 words
A compound according to claim 1 wherein R 2 is hydrogen.
Claim 11
Dependent Claim
11 words
6-Cyano-3,4-dihydro-2,2-dimethyl-trans-4-(2-oxo-1-piperidinyl)-2H-benzo[b]pyran-3-ol; 7-nitro-3,4-dihydro-2,2-dimethyl-trans-4-(2-oxo-1-pyrrolidinyl)-2H-benzo[b]pyran-3-ol; 6-cyano-3,4-dihydro-2,2-dimethyl-trans-4-(2-oxo-1-pyrrolidinyl)-2H-benzo[b]-pyran-3-yl acetate; 6-nitro-3,4-dihydro-2-methyl-trans-4-(2-oxo-1-pyrrolidinyl-2H-benzo[b]pyran-3-ol; 6-carbomethoxy-3,4-dihydro-2,2-dimethyl-trans-4-(2-oxo-1-pyrrolidinyl)-2H-benzo[b]pyran-3-ol; 6-carbomethoxy-3,4-dihydro-2,2-dimethyl-trans-4-(2-oxo-1-piperidinyl)-2H-benzo[b]pyran-3-ol; 6-chloro-3,4-dihydro-2,2-dimethyl-trans-4-(2-oxo-1-pyrrolidinyl)-2H-benzo[b]-pyran-3-ol; 6-acetyl-3,4-dihydro-2,2-dimethyl-trans-4-(2-oxo-1-pyrrolidinyl)-2H-benzo[b]pyran-3-ol; and 6-acetyl-3,4-dihydro-2,2-dimethyl-trans-4-(2-oxo-1-piperidinyl)-2H-benzo[b]pyran-3-ol.
Claim 12
Dependent Claim
11 words
6-Cyano-3,4-dihydro-2,2-dimethyl-trans-4-(2-oxo-1-piperidinyl)-2H-benzo[b]pyran-3-ol; 7-nitro-3,4-dihydro-2,2-dimethyl-trans-4-(2-oxo-1-pyrrolidinyl)-2H-benzo[b]pyran-3-ol; 6-cyano-3,4-dihydro-2,2-dimethyl-trans-4-(2-oxo-1-pyrrolidinyl)-2H-benzo[b]-pyran-3-yl acetate; 6-nitro-3,4-dihydro-2-methyl-trans-4-(2-oxo-1-pyrrolidinyl-2H-benzo[b]pyran-3-ol; 6-carbomethoxy-3,4-dihydro-2,2-dimethyl-trans-4-(2-oxo-1-pyrrolidinyl)-2H-benzo[b]pyran-3-ol; 6-carbomethoxy-3,4-dihydro-2,2-dimethyl-trans-4-(2-oxo-1-piperidinyl)-2H-benzo[b]pyran-3-ol; 6-chloro-3,4-dihydro-2,2-dimethyl-trans-4-(2-oxo-1-pyrrolidinyl)-2H-benzo[b]-pyran-3-ol; 6-acetyl-3,4-dihydro-2,2-dimethyl-trans-4-(2-oxo-1-pyrrolidinyl)-2H-benzo[b]pyran-3-ol; and 6-acetyl-3,4-dihydro-2,2-dimethyl-trans-4-(2-oxo-1-piperidinyl)-2H-benzo[b]pyran-3-ol.
Claim 13
Dependent Claim
1 words
6-Cyano-3,4-dihydro-2,2-dimethyl-trans-4-(2-oxo-1-pyrrolidinyl)-2H-benzo[b]-pyran-3-ol.
Claim 14
Dependent Claim
1 words
6-Cyano-3,4-dihydro-2,2-dimethyl-trans-4-(2-oxo-1-pyrrolidinyl)-2H-benzo[b]-pyran-3-ol.
Claim 15
Dependent Claim
14 words
A compound according to claim 1 wherein it is in a substantially pure form.
Claim 16
Dependent Claim
30 words
A pharmaceutical composition for treatment of hypertension in mammals, which comprises an anti-hypertensive effective amount of a compound of formula (I) according to claim 1, and a pharmaceutically acceptable carrier.
Claim 17
Dependent Claim
31 words
A method of treatment of hypertension in mammals, which comprises administering an anti-hypertensive effective amount of a compound of formuls (I) according to claim 1 to a mammal in need thereof.
Claim 18
Dependent Claim
11 words
The compound of claim 10, in the form of a solid.
Claim 19
Dependent Claim
12 words
The compound of claim 14, in the form of a crystalline solid.
Claim 20
Dependent Claim
14 words
The compound of claim 14, having a melting point from 226° to 231° C.
Claim 21
Dependent Claim
14 words
The compound of claim 16, having a melting point from 230° to 231° C.
Claim 22
Dependent Claim
9 words
The compound of claim 10 in pharmaceutically acceptable form.
Claim 23
Dependent Claim
20 words
A compound according to claim 8, wherein R 1 is cyano and R 3 and R 4 are both methyl.
Claim 24
Dependent Claim
27 words
A compound according to claim 1, wherein one of R 1 and R 2 is hydrogen, and the other is cyano, nitro, chloro, alkoxycarbonyl, alkylcarbonyloxy or alkylhydroxymethyl.
Claim 25
Dependent Claim
190 words
A compound of formula (XIV): ##STR31## wherein: one of R 1 and R 2 is hydrogen and the other is selected from the class of alkylcarbonyl, alkoxycarbonyl, alkylcarbonyloxy, alkylhydroxymethyl, nitro, cyano, chloro, trifluoromethyl, alkylsulphinyl, alkylsulphonyl, alkoxysulphinyl, alkoxysulphonyl, alkylcarbonylamino, alkoxycarbonylamino, or aminosulphinyl, aminosulphonyl or aminocarbonyl, the amino moiety being optionally substituted by one or two alkyl groups, or alkylsulphinylamino, alkylsulphonylamino, alkoxysulphinylamino or alkoxysulphonylamino, or ethylenyl terminally substituted by alkylcarbonyl, nitro or cyano or --C(alkyl)NOH or --C(alkyl)NNH 2 , the alkyl groups or alkyl moieties of alkyl-containing groups having from 1 to 6 carbon atoms; one of R 3 and R 4 is hydrogen or alkyl having from 1 to 4 carbon atoms and the other is alkyl having from 1 to 4 carbon atoms, or R 3 and R 4 together with the carbon atom to which they are attached are spiroalkyl having from 3 to 6 carbon atoms; R 5 is hydrogen, alkyl having from 1 to 3 carbon atoms or acyl having from 1 to 8 carbon atoms; n is 1 or 2; and L 3 is chloro, the substituted amino group being trans to the OR 5 group.
Claim 26
Dependent Claim
190 words
A compound of formula (XIV): ##STR31## wherein: one of R 1 and R 2 is hydrogen and the other is selected from the class of alkylcarbonyl, alkoxycarbonyl, alkylcarbonyloxy, alkylhydroxymethyl, nitro, cyano, chloro, trifluoromethyl, alkylsulphinyl, alkylsulphonyl, alkoxysulphinyl, alkoxysulphonyl, alkylcarbonylamino, alkoxycarbonylamino, or aminosulphinyl, aminosulphonyl or aminocarbonyl, the amino moiety being optionally substituted by one or two alkyl groups, or alkylsulphinylamino, alkylsulphonylamino, alkoxysulphinylamino or alkoxysulphonylamino, or ethylenyl terminally substituted by alkylcarbonyl, nitro or cyano or --C(alkyl)NOH or --C(alkyl)NNH 2 , the alkyl groups or alkyl moieties of alkyl-containing groups having from 1 to 6 carbon atoms; one of R 3 and R 4 is hydrogen or alkyl having from 1 to 4 carbon atoms and the other is alkyl having from 1 to 4 carbon atoms, or R 3 and R 4 together with the carbon atom to which they are attached are spiroalkyl having from 3 to 6 carbon atoms; R 5 is hydrogen, alkyl having from 1 to 3 carbon atoms or acyl having from 1 to 8 carbon atoms; n is 1 or 2; and L 3 is chloro, the substituted amino group being trans to the OR 5 group.
Claim 27
Dependent Claim
40 words
A compound of formula (III): ##STR32## wherein R 1 to R 5 and n are as defined in claim 1 and L 1 is hydroxy or C 1-4 alkoxy, the substituted amino group being trans to the OR 5 group.
Claim 28
Dependent Claim
27 words
A compound of formula (IX): ##STR33## wherein R 1 to R 4 are as defined in claim 1, the azide group being trans to the hydroxy group.
Claim 29
Dependent Claim
31 words
A compound of formula (XI): ##STR34## wherein R 1 to R 5 and n are as defined in claim 1, the substituted amino group being trans to the OR 5 group.
Claim 30
Dependent Claim
13 words
A compound which is: 6-Cyano-3,4-dihydro-2,2-dimethyl-trans-4-amino-2H-benzo[b]pyran-3-ol, 6-Cyano-3,4-dihydro-2,2-dimethyl-trans-4-(1-keto-4-chlorobutylamino)-2H-benzo[b]pyran-3-ol, 6-Cyano-3,4-dihydro-2,2-dimethyl-trans-4-(4,4-diethoxybutylamino)-2H-benzo[b]pyran-3-ol, 6-Nitro-3,4-dihydro-2-methyl-3,4-epoxy-2H-benzo[b]-pyran, 6-Nitro-3,4-dihydro-2-methyl-trans-4-(ethoxycarbonylpropylamino)-2H-benzo[b]pyran-3-ol, 7-Nitro-3,4-dihydro-2,2-dimethyl-trans-4-(3-carbethoxypropylamino)-2H-benzo[b]pyran-3-ol, 6-Chloro-3,4-dihydro-2,2-dimethyl-trans-3-bromo-4-hydroxy-2H-benzo[b]pyran, or 6-Chloro-3,4-dihydro-2,2-dimethyl-3,4-epoxy-2H-benzo[b]pyran.
Claim 31
Dependent Claim
13 words
A compound which is: 6-Cyano-3,4-dihydro-2,2-dimethyl-trans-4-amino-2H-benzo[b]pyran-3-ol, 6-Cyano-3,4-dihydro-2,2-dimethyl-trans-4-(1-keto-4-chlorobutylamino)-2H-benzo[b]pyran-3-ol, 6-Cyano-3,4-dihydro-2,2-dimethyl-trans-4-(4,4-diethoxybutylamino)-2H-benzo[b]pyran-3-ol, 6-Nitro-3,4-dihydro-2-methyl-3,4-epoxy-2H-benzo[b]-pyran, 6-Nitro-3,4-dihydro-2-methyl-trans-4-(ethoxycarbonylpropylamino)-2H-benzo[b]pyran-3-ol, 7-Nitro-3,4-dihydro-2,2-dimethyl-trans-4-(3-carbethoxypropylamino)-2H-benzo[b]pyran-3-ol, 6-Chloro-3,4-dihydro-2,2-dimethyl-trans-3-bromo-4-hydroxy-2H-benzo[b]pyran, or 6-Chloro-3,4-dihydro-2,2-dimethyl-3,4-epoxy-2H-benzo[b]pyran.
References Cited (Backward Citations)
EP0009912A1
Cited
US4366163A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1987-05-01 | 1987-10-31 | 1988-05-01 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1991-05-01 | 1991-10-31 | 1992-05-01 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1995-05-01 | 1995-10-31 | 1996-05-01 | $7700.00 | Window Closed / Lapsed |