US4048317A
Expired / Lapsed
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Chroman derivatives
Assignee: Beecham Group PLC
•
Filing: 1975-05-14
•
Granted: 1977-09-13
•
Expires: 1995-05-14
Abstract
Abstract Anti-hypertensive derivatives of trans-3-hydroxy-4-amino-chroman, their preparation from amines and chroman epoxide derivatives, and pharmaceutical compositions containing such anti-hypertensive derivatives for reducing blood pressure in mammals including humans.
Inventors
- 👤 Eric Alfred Watts
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-31 03:50
CPC Classifications
A; A61; A61K; A61K31/00; A61K31/33; A61K31/395; A61P; A61P9/00; A61P9/08; A61P9/12; C; C07; C07D; C07D311/00; C07D311/02; C07D311/04; C07D311/58; C07D311/68; C07D311/70; C07D311/78; C07D311/92
Claims Analysis
Total Claims: 58
Claim 1
Independent Claim
124 words
A compound of the formula (I): ##STR11## or a pharmaceutically acceptable acid addition salt thereof wherein NR 1 R 2 is a 3- to 8-membered heterocycle wherein the nitrogen atom is the only heteroatom, unsubstituted or substituted by 1 or 2 methyl groups; R 3 is hydrogen, halogen, alkyl of 1 to 6 carbon atoms, amino, alkylamino of 1 to 6 carbon atoms in the alkyl moiety, dialkylamino of 1 to 6 carbon atoms in each alkyl moiety, nitro, trifluoromethyl or lower alkanoylamino of 2 to 7 carbon atoms; R 4 is hydrogen, halogen, methyl or methoxy; R 5 is hydrogen, alkyl of 1 to 6 carbon atoms or phenyl; and R 6 is hydrogen, alkyl of 1 to 6 carbon atoms or phenyl.
Claim 2
Dependent Claim
124 words
A compound of the formula (I): ##STR11## or a pharmaceutically acceptable acid addition salt thereof wherein NR 1 R 2 is a 3- to 8-membered heterocycle wherein the nitrogen atom is the only heteroatom, unsubstituted or substituted by 1 or 2 methyl groups; R 3 is hydrogen, halogen, alkyl of 1 to 6 carbon atoms, amino, alkylamino of 1 to 6 carbon atoms in the alkyl moiety, dialkylamino of 1 to 6 carbon atoms in each alkyl moiety, nitro, trifluoromethyl or lower alkanoylamino of 2 to 7 carbon atoms; R 4 is hydrogen, halogen, methyl or methoxy; R 5 is hydrogen, alkyl of 1 to 6 carbon atoms or phenyl; and R 6 is hydrogen, alkyl of 1 to 6 carbon atoms or phenyl.
Claim 3
Dependent Claim
15 words
A compound according to claim 1 wherein R 5 and R 6 are methyl groups.
Claim 4
Dependent Claim
19 words
A compound according to claim 1 wherein NR 1 R 2 is a pyrrolidyl, piperidyl, methylpyrrolidyl or hexamethyleneimino moiety.
Claim 5
Dependent Claim
17 words
A compound according to claim 1 wherein R 5 and R 6 are each methyl or ethyl.
Claim 6
Dependent Claim
13 words
A compound according to claim 1 wherein R 4 is hydrogen or chlorine.
Claim 7
Dependent Claim
42 words
A compound according to claim 1 in the form of an acid addition salt wherein said salt is selected from the group consisting of the hydrochloride, hydrobromide, sulphate, phosphate, methane sulfonate, p-toluene sulfonate, acetate, propionate, succinate, citrate, tartrate, mandelate, lactate or gluconate.
Claim 8
Dependent Claim
129 words
A compound according to claim 1 of the formula (II): ##STR12## or a pharmaceutically acceptable acid addition salt thereof wherein NR 1 R 2 is a moiety of the formula ##STR13## wherein X is a bond joining the two carbon atoms, CH 2 , CH 2 --CH 2 , CH 2 --CH 2 --CH 2 , or CH═CH, R 13 is hydrogen or methyl; R 14 is hydrogen or methyl; R 3 is hydrogen, halogen, alkyl of 1 to 6 carbon atoms, amino, alkylamino of 1 to 6 carbon atoms in the alkyl moiety, dialkylamino of 1 to 6 carbon atoms in each alkyl moiety, nitro, trifluoromethyl or lower alkanoylamino of 2 to 7 carbon atoms; R 9 is methyl or ethyl; and R 10 is methyl or ethyl.
Claim 9
Dependent Claim
14 words
Compound according to claim 7 wherein R 9 and R 10 are each methyl.
Claim 10
Dependent Claim
24 words
A compound according to claim 7 wherein X is a bond joining the two carbon atoms, CH 2 or CH 2 --CH 2 .
Claim 11
Dependent Claim
15 words
A compound according to claim 7 wherein R 9 and R 10 are each methyl.
Claim 12
Dependent Claim
10 words
The compound according to claim 1 which is trans-4-pyrrolidino-3,4-dihydro-2,2-diethyl-2H-benzo[b]pyran-3-ol hydrochloride.
Claim 13
Dependent Claim
66 words
A compound according to claim 1 of the formula (VI): ##STR14## wherein NR 1 R 2 is a 3- to 8-membered heterocycle wherein the nitrogen atom is the only heteroatom, unsubstituted or substituted by 1 or 2 methyl groups; R 5 is hydrogen, alkyl of 1 to 6 carbon atoms or phenyl; and R 6 is hydrogen, alkyl of 1 to 6 carbon atoms or phenyl.
Claim 14
Dependent Claim
14 words
Compound according to claim 12 wherein R 5 and R 6 are each methyl.
Claim 15
Dependent Claim
10 words
The compound according to claim 1 which is trans-4-pyrrolidino-3,4-dihydro-2,2-dimethyl-6-nitro-2H-benzo[b]pyran-3-ol hydrochloride.
Claim 16
Dependent Claim
10 words
The compound according to claim 1 which is trans-4-[4-methylpiperidino]-3,4-dihydro-2,2-dimethyl-6-nitro-2H-benzo[b]pyran-3-ol hydrochloride.
Claim 17
Dependent Claim
10 words
The compound according to claim 1 which is trans-4-hexamethylenimino-3,4-dihydro-2,2-dimethyl-6-nitro-2H-benzo[b]pyran-3-ol hydrochloride.
Claim 18
Dependent Claim
10 words
The compound according to claim 1 which is trans-4-heptamethylenimino-3,4-dihydro-2,2-dimethyl-6-nitro-2H-benzo[b]pyran-3-ol hydrochloride.
Claim 19
Dependent Claim
10 words
The compound according to claim 1 which is trans-4-[2,4-dimethylpyrrolidino]-3,4-dihydro-2,2-dimethyl-6-nitro-2H-benzo[b]pyran-3-ol hydrochloride.
Claim 20
Dependent Claim
10 words
The compound according to claim 1 which is trans-4-piperidino-3,4-dihydro-2,2-dimethyl-6-nitro-2H-benzo(b)pyran-3-ol hydrochloride.
Claim 21
Dependent Claim
149 words
A pharmaceutical composition useful for treating hypertension in humans and animals which comprises an antihypertensively effective amount of a compound of the formula (I) ##STR15## or a pharmaceutically acceptable acid addition salt thereof wherein NR 1 R 2 is a 3- to 8-membered heterocycle wherein the nitrogen atom is the only heteroatom, unsubstituted or substituted by 1 or 2 methyl groups; R 3 is hydrogen, halogen, alkyl of 1 to 6 carbon atoms, amino, alkylamino of 1 to 6 carbon atoms in the alkyl moiety, dialkylamino of 1 to 6 carbon atoms in each alkyl moiety, nitro, trifluoromethyl or lower alkanoylamino of 2 to 7 carbon atoms; R 4 is hydrogen, halogen, methyl or methoxy; R 5 is hydrogen, alkyl of 1 to 6 carbon atoms or phenyl; and R 6 is hydrogen, alkyl of 1 to 6 carbon atoms or phenyl; in combination with a pharmaceutically acceptable carrier.
Claim 22
Dependent Claim
149 words
A pharmaceutical composition useful for treating hypertension in humans and animals which comprises an antihypertensively effective amount of a compound of the formula (I) ##STR15## or a pharmaceutically acceptable acid addition salt thereof wherein NR 1 R 2 is a 3- to 8-membered heterocycle wherein the nitrogen atom is the only heteroatom, unsubstituted or substituted by 1 or 2 methyl groups; R 3 is hydrogen, halogen, alkyl of 1 to 6 carbon atoms, amino, alkylamino of 1 to 6 carbon atoms in the alkyl moiety, dialkylamino of 1 to 6 carbon atoms in each alkyl moiety, nitro, trifluoromethyl or lower alkanoylamino of 2 to 7 carbon atoms; R 4 is hydrogen, halogen, methyl or methoxy; R 5 is hydrogen, alkyl of 1 to 6 carbon atoms or phenyl; and R 6 is hydrogen, alkyl of 1 to 6 carbon atoms or phenyl; in combination with a pharmaceutically acceptable carrier.
Claim 23
Dependent Claim
15 words
A composition according to claim 20 wherein R 5 and R 6 are methyl groups.
Claim 24
Dependent Claim
90 words
A composition according to claim 20 which comprises an antihypertensively effective amount of a compound of the formula (VI) ##STR16## or a pharmaceutically acceptable acid addition salt thereof wherein NR 1 R 2 is a 3- to 8-membered heterocycle wherein the nitrogen atom is the only heteroatom, unsubstituted or substituted by 1 or 2 methyl groups; R 5 is hydrogen, alkyl of 1 to 6 carbon atoms or phenyl; and R 6 is hydrogen, alkyl of 1 to 6 carbon atoms or phenyl; in combination with a pharmaceutically acceptable carrier.
Claim 25
Dependent Claim
145 words
A composition according to claim 20 which comprises an antihypertensively effective amount of a compound of the formula (II): ##STR17## or a pharmaceutically acceptable acid addition salt thereof wherein NR 1 R 2 is a moiety of the formula ##STR18## wherein X is a bond joining the two carbon atoms, CH 2 , CH 2 --CH 2 , CH 2 --CH 2 --CH 2 , or CH═CH; R 13 is hydrogen or methyl; R 14 is hydrogen or methyl; R 3 is hydrogen, halogen, alkyl of 1 to 6 carbon atoms, amino, alkylamino of 1 to 6 carbon atoms in the alkyl moiety, dialkylamino of 1 to 6 carbon atoms in each alkyl moiety, nitro, trifluoromethyl or lower alkanoylamino of 2 to 7 carbon atoms; R 9 is methyl or ethyl; and R 10 is methyl or ethyl; in combination with a pharmaceutically acceptable carrier.
Claim 26
Dependent Claim
15 words
A composition according to claim 23 wherein R 9 and R 10 are each methyl.
Claim 27
Dependent Claim
19 words
A composition according to claim 20 wherein NR 1 R 2 is a pyrrolidyl, piperidyl, methylpyrrolidyl or hexamethyleneimino moiety.
Claim 28
Dependent Claim
18 words
A composition according to claim 22 wherein wherein R 5 and R 6 are each methyl or ethyl.
Claim 29
Dependent Claim
24 words
A composition according to claim 23 wherein X is a bond joining the two carbon atoms, CH 2 or CH 2 --CH 2 .
Claim 30
Dependent Claim
13 words
A composition according to claim 20 wherein R 4 is hydrogen or chlorine.
Claim 31
Dependent Claim
46 words
A composition according to claim 20 wherein the compound is in the form of an acid addition salt wherein said salt is selected from the group consisting of the hydrochloride, hydrobromide, sulphate, phosphate, methane sulfonate, p-toluene sulfonate, acetate, propionate, succinate, citrate, tartrate, mandelate, lactate or gluconate.
Claim 32
Dependent Claim
12 words
A composition according to claim 20 wherein the compound is trans-4-pyrrolidino-3,4-dihydro-2,2-dimethyl-6-nitro-2H-benzo[b]pyran-3-ol hydrochloride.
Claim 33
Dependent Claim
12 words
A composition according to claim 20 wherein the compound is trans-4-[4-methylpiperidino]-3,4-dihydro-2,2-dimethyl-6-nitro-2H-benzo[b]pyran-3-ol hydrochloride.
Claim 34
Dependent Claim
11 words
A composition according to claim 20 wherein the compound is trans-4-hexamethylenimino-3,4-dihydro-2,2-dimethyl-6-nitro-2H-benzo[b]pyran-3-ol-hydrochloride.
Claim 35
Dependent Claim
12 words
A composition according to claim 20 wherein the compound is trans-4-heptamethylenimino-3,4-dihydro-2,2-dimethyl-6-nitro-2H-benzo[b]pyran-3-ol hydrochloride.
Claim 36
Dependent Claim
12 words
The composition according to claim 20 wherein the compound is trans-4-[2,4-dimethylpyrrolidino]-3,4-dihydro-2,2-dimethyl-6-nitro-2H-benzo[b]pyran-3-ol hydrochloride.
Claim 37
Dependent Claim
12 words
The composition according to claim 20 wherein the compound is trans-4-pyrrolidino-3,4-dihydro-2,2-diethyl-2H-benzo[b]pyran-3-ol hydrochloride.
Claim 38
Dependent Claim
12 words
The composition according to claim 20 wherein the compound is trans-4-piperidino-3,4-dihydro-2,2-dimethyl-6-nitro-2H-benzo[b]pyran-3-ol hydrochloride.
Claim 39
Dependent Claim
16 words
A composition according to claim 20 in unit dose form suitable for oral administration to humans.
Claim 40
Independent Claim
156 words
A method of treating hypertension in humans and animals which comprises administering to a human or animal in need thereof an antihypertensively effective amount of a compound of the formula (I) ##STR19## or a pharmaceutically acceptable acid addition salt thereof wherein NR 1 R 2 is a 3- to 8-membered heterocycle wherein the nitrogen atom is the only heteroatom, unsubstituted or substituted by 1 or 2 methyl groups; R 3 is hydrogen, halogen, alkyl of 1 to 6 carbon atoms, amino, alkylamino of 1 to 6 carbon atoms in the alkyl moiety, dialkylamino of 1 to 6 carbon atoms in each alkyl moiety, nitro, trifluoromethyl or lower alkanoylamino of 2 to 7 carbon atoms; R 4 is hydrogen, halogen, methyl or methoxy; R 5 is hydrogen, alkyl of 1 to 6 carbon atoms or phenyl; and R 6 is hydrogen, alkyl of 1 to 6 carbon atoms or phenyl; in combination with a pharmaceutically acceptable carrier.
Claim 41
Independent Claim
156 words
A method of treating hypertension in humans and animals which comprises administering to a human or animal in need thereof an antihypertensively effective amount of a compound of the formula (I) ##STR19## or a pharmaceutically acceptable acid addition salt thereof wherein NR 1 R 2 is a 3- to 8-membered heterocycle wherein the nitrogen atom is the only heteroatom, unsubstituted or substituted by 1 or 2 methyl groups; R 3 is hydrogen, halogen, alkyl of 1 to 6 carbon atoms, amino, alkylamino of 1 to 6 carbon atoms in the alkyl moiety, dialkylamino of 1 to 6 carbon atoms in each alkyl moiety, nitro, trifluoromethyl or lower alkanoylamino of 2 to 7 carbon atoms; R 4 is hydrogen, halogen, methyl or methoxy; R 5 is hydrogen, alkyl of 1 to 6 carbon atoms or phenyl; and R 6 is hydrogen, alkyl of 1 to 6 carbon atoms or phenyl; in combination with a pharmaceutically acceptable carrier.
Claim 42
Dependent Claim
15 words
A method according to claim 38 wherein R 5 and R 6 are methyl groups.
Claim 43
Dependent Claim
78 words
A method according to claim 38 wherein the compound is of the formula (VI) ##STR20## or a pharmaceutically acceptable acid addition salt thereof wherein NR 1 R 2 is a 3- to 8-membered heterocycle wherein the nitrogen atom is the only heteroatom, unsubstituted or substituted by 1 or 2 methyl groups; R 5 is hydrogen, alkyl of 1 to 6 carbon atoms or phenyl; and R 6 is hydrogen, alkyl of 1 to 6 carbon atoms or phenyl.
Claim 44
Dependent Claim
15 words
A method according to claim 40 wherein R 5 and R 6 are each methyl.
Claim 45
Dependent Claim
132 words
A method according to claim 38 wherein the compound is of the formula (II) ##STR21## or a pharmaceutically acceptable acid addition salt thereof wherein NR 1 R 2 is a moiety of the formula ##STR22## wherein X is a bond joining the two carbon atoms, CH 2 , CH 2 --CH 2 , CH 2 --CH 2 --CH 2 , or CH═CH; R 13 is hydrogen or methyl; R 14 is hydrogen or methyl; R 3 is hydrogen, halogen, alkyl of 1 to 6 carbon atoms, amino, alkylamino of 1 to 6 carbon atoms in the alkyl moiety, dialkylamino of 1 to 6 carbon atoms in each alkyl moiety, nitro, trifluoromethyl, ower alkanoylamino of 2 to 7 carbon atoms; R 9 is methyl or ethyl; and R 10 is methyl or ethyl.
Claim 46
Dependent Claim
15 words
A method according to claim 42 wherein R 9 and R 10 are each methyl.
Claim 47
Dependent Claim
19 words
A method according to claim 38 wherein NR 1 R 2 is a pyrrolidyl, piperidyl, methylpyrrolidyl or hexamethyleneiamino moiety.
Claim 48
Dependent Claim
17 words
A method according to claim 40 wherein R 5 and R 6 are each methyl or ethyl.
Claim 49
Dependent Claim
24 words
A method according to claim 42 wherein X is a bond joining the two carbon atoms, CH 2 or CH 2 --CH 2 .
Claim 50
Dependent Claim
13 words
A method according to claim 38 wherein R 4 is hydrogen or chlorine.
Claim 51
Dependent Claim
46 words
A method according to claim 38 wherein the compound is in the form of an acid addition salt wherein said salt is selected from the group consisting of the hydrochloride, hydrobromide, sulphate, phosphate, methane sulfonate, p-toluene sulfonate, acetate, propionate, succinate, citrate, tartrate, mandelate, lactate or gluconate.
Claim 52
Dependent Claim
12 words
A method according to claim 38 wherein the compound is trans-4-pyrrolidino-3,4-dihydro-2,2-dimethyl-6-nitro-2H-benzo[b]pyran-3-ol hydrochloride.
Claim 53
Dependent Claim
12 words
A method according to claim 38 wherein the compound is trans-4-[4-methylpiperidino]-3,4-dihydro-2,2-dimethyl-6-nitro-2H-benzo[b]pyran-3-ol hydrochloride.
Claim 54
Dependent Claim
11 words
A method according to claim 38 wherein the compound is trans-4-hexamethylenimino-3,4-dihydro-2,2-dimethyl-6-nitro-2H-benzo[b]pyran-3-ol-hydrochloride.
Claim 55
Dependent Claim
12 words
A method according to claim 38 wherein the compound is trans-4-heptamethylenimino-3,4-dihydro-2,2-dimethyl-6-nitro-2H-benzo[b]pyran-3-ol hydrochloride.
Claim 56
Dependent Claim
12 words
A method according to claim 38 wherein the compound is trans-4-[2,5-dimethylpyrrolidino]-3,4-dihydro-2,2-dimethyl-6-nitro-2H-benzo[b]pyran-3-ol hydrochloride.
Claim 57
Dependent Claim
12 words
A method according to claim 38 wherein the compound is trans-4-pyrrolidino-3,4-dihydro-2,2-diethyl-2H-benzo[b]pyran-3-ol hydrochloride.
Claim 58
Dependent Claim
12 words
A method according to claim 38 wherein the compound is trans-4-piperidino-3,4-dihydro-2,2-dimethyl-6-nitro-2H-benzo[b]pyran-3-ol hydrochloride.
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) | 1980-09-12 | 1981-03-14 | 1981-09-13 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1984-09-12 | 1985-03-14 | 1985-09-13 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1988-09-12 | 1989-03-14 | 1989-09-13 | $7700.00 | Window Closed / Lapsed |