US4216216A
Expired / Lapsed
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Aromatic piperazinyl substituted dihydrouracils
Assignee: Hoechst AG
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Filing: 1978-06-15
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Granted: 1980-08-05
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Expires: 1998-06-15
Abstract
Abstract Compounds of general formula ##STR1## are disclosed wherein appropriate substituents for R 1 , R 2 to R 5 , R 6 , A, Q, X, and Z are defined for these novel hexahydropyrimidines. Procedures for the preparation of these compounds are also given. Because of the highly effective serotonin antagonistic activity in combination with a strong inhibiting effect on thrombocyte aggregation and good compatibility these compounds are effective in treating migraine. Additionally, the compounds also exhibit an anti-histamine activity, cause an increase in erythrocyte fluidity, a psychotropic activity, a weak bradykinin antagonism and hypotensive effects.
Inventors
- 👤 Rolf-Ortwin Weber
- 👤 Hiristo Anagnostopulos
- 👤 Ulrich Gebert
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-06 17:32
CPC Classifications
C; C07; C07D; C07D239/00; C07D239/02; C07D239/20; C07D239/22; A; A61; A61P; A61P25/00; A61P25/04; A61P43/00; C07D295/00; C07D295/04; C07D295/12; C07D295/125; C07D295/13
Claims Analysis
Total Claims: 9
Claim 1
Independent Claim
217 words
Compounds of formula ##STR29## wherein R 1 repreesnts a radical selected from the group consisting of hydrogen, phenyl, tolyl or alkyl having at most 2 carbon atoms; R 2 to R 5 each represent hydrogen or alkyl having at most 2 carbon atoms; R 6 represents a radical selected from the group consisting of hydrogen, anellated benzene nucleus, 1 to 3 identical or different substituents selected from the group consisting of alkoxy groups having from 1 to 3 carbon atoms, halogen atoms, nitro and hydroxy groups, alkyl groups having from 1 to 4 carbon atoms and such alkyl group being substituted by at least one halogen atom; A represents a single bond or a ##STR30## Q represents a radical selected from the group consisting of single bond, straight-chained or branched alkylene group of formula --C n H 2n -- in which n is from 2 to 6, at least two carbon atoms being between the two nitrogen atoms to which Q is attached and such an alkylene group; being substituted by not more than (n-2) hydroxy groups which are bound to a carbon atom not being linked to one of the nitrogen atoms to which Q is attached; X is oxygen or sulphur atom; and Z is nitrogen or the group ##STR31## and acid addition salts thereof.
Claim 2
Dependent Claim
217 words
Compounds of formula ##STR29## wherein R 1 repreesnts a radical selected from the group consisting of hydrogen, phenyl, tolyl or alkyl having at most 2 carbon atoms; R 2 to R 5 each represent hydrogen or alkyl having at most 2 carbon atoms; R 6 represents a radical selected from the group consisting of hydrogen, anellated benzene nucleus, 1 to 3 identical or different substituents selected from the group consisting of alkoxy groups having from 1 to 3 carbon atoms, halogen atoms, nitro and hydroxy groups, alkyl groups having from 1 to 4 carbon atoms and such alkyl group being substituted by at least one halogen atom; A represents a single bond or a ##STR30## Q represents a radical selected from the group consisting of single bond, straight-chained or branched alkylene group of formula --C n H 2n -- in which n is from 2 to 6, at least two carbon atoms being between the two nitrogen atoms to which Q is attached and such an alkylene group; being substituted by not more than (n-2) hydroxy groups which are bound to a carbon atom not being linked to one of the nitrogen atoms to which Q is attached; X is oxygen or sulphur atom; and Z is nitrogen or the group ##STR31## and acid addition salts thereof.
Claim 3
Dependent Claim
95 words
Compounds as claimed in claim 1 in which R 1 represents alkyl having at most 2 carbon atoms; R 2 and R 3 each represent hydrogen or alkyl having at most 2 carbon atoms; R 4 and R 5 each represent hydrogen atom; R 6 represents a radical selected from the group consisting of hydrogen, halogen, and halogenalkyl having at most 2 carbon atoms and up to 3 halogen atoms; A represents single bond; Q represents straight-chained alkylene group having 2 to 3 carbon atoms; X represents oxygen or sulphur; and Z represents nitrogen atom.
Claim 4
Dependent Claim
38 words
Compounds as claimed in claim 1 wherein R 1 represents methyl; one of R 2 and R 3 represents methyl group and the other hydrogen atom; and R 6 represents hydrogen atom or fluorine atom in the 4-position.
Claim 5
Dependent Claim
56 words
Compounds as claimed in claim 1 where in R 6 represents trifluoromethyl group in the 3-position, and one of R 1 to R 5 is other than hydrogen atom, A represents ##STR32## Q repreesnts single bond or is alkylene group having at least 4 carbon atoms, X represents sulphur atom, and Z represents the group ##STR33##
Claim 6
Dependent Claim
27 words
A compound selected from the group consisting of 3-{3-[4-(4-fluorophenyl)-1-piperazinyl]-propyl}-6,6-dimethyl-5,6-dihydrouracil hydrochloride hydrate; 3-[3-(4-phenyl-1-piperazinyl)-propyl]-6,6-dimethyl-5,6-dihydrouracil hydrochloride; 3-[3-(4-phenyl-1-piperazinyl)-propyl]-6,6-dimethyl-2-thio-5,6-dihydrouracil hydrochloride; 3-[3-(4-phenyl-1-piperazinyl)-propyl]-5,6-dimethyl-5,6-dihydrouracil hydrochloride; and 3-[2-(4-phenyl-1-piperazinyl)-ethyl]-6,6-dimethyl-2-thio-5,6-dihydrouracil hydrochloride and physiologically compatible acid addition salts thereof.
Claim 7
Dependent Claim
27 words
A compound selected from the group consisting of 3-{3-[4-(4-fluorophenyl)-1-piperazinyl]-propyl}-6,6-dimethyl-5,6-dihydrouracil hydrochloride hydrate; 3-[3-(4-phenyl-1-piperazinyl)-propyl]-6,6-dimethyl-5,6-dihydrouracil hydrochloride; 3-[3-(4-phenyl-1-piperazinyl)-propyl]-6,6-dimethyl-2-thio-5,6-dihydrouracil hydrochloride; 3-[3-(4-phenyl-1-piperazinyl)-propyl]-5,6-dimethyl-5,6-dihydrouracil hydrochloride; and 3-[2-(4-phenyl-1-piperazinyl)-ethyl]-6,6-dimethyl-2-thio-5,6-dihydrouracil hydrochloride and physiologically compatible acid addition salts thereof.
Claim 8
Dependent Claim
37 words
A pharmaceutical composition containing as active ingredients effective amounts for treating migraine at least one compound as claimed in claim 1 or a physiologically acceptable acid addition salt thereof in association with a pharmaceutical carrier or excipient.
Claim 9
Dependent Claim
26 words
A composition as claimed in claim 6 in the form of dosage units containing the active ingredient in an amount of from 0.1 to 50 mg.
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) | 1983-08-05 | 1984-02-04 | 1984-08-05 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1987-08-05 | 1988-02-04 | 1988-08-05 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1991-08-05 | 1992-02-04 | 1992-08-05 | $7700.00 | Window Closed / Lapsed |