US4400381A
Expired / Lapsed
US
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Piperazine derivatives of theophylline
Assignee: Laroche Navarron SA
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Filing: 1981-07-31
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Granted: 1983-08-23
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Expires: 2001-07-31
Abstract
Abstract New compounds of the formula <IMAGE> (I) <IMAGE> and the pharmaceutically acceptable acid addition salts thereof, wherein M is selected from the group consisting of hydrogen, morpholino, benzylamino, di-n-lower alkylamine, n-lower alkylamine, and aryl piperazino; Z1 and Z2 are each independently selected from the group consisting of CH2, CHOB and C=O, wherein B is selected from the group consisting of hydrogen and alkanoyl; Y is oxygen or sulfur; n is an integer from 0-4 but cannot be zero when Z1 is CHOB; m is an integer from 0-4 but cannot be zero when Z2 is CHOB, or when m is hydrogen; R1, R2 and R3 are each independently hydrogen, halogen, hydroxy, trifluoromethyl, alkyl or alkoxy; and R4 and R5 are each independently lower alkyl, with the proviso that both R4 and R5 cannot be methyl when M is hydrogen; are antihistamines and are therefore useful in the treatment of respiratory diseases including asthma, hay fever, allergies and the common cold. They are also vasodilators.
Inventors
- 👤 Colette Favier
- 👤 Henri Pinhas
- 👤 Serge Beranger
- 👤 Jean-Claude Pascal
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-27 09:35
CPC Classifications
C; C07; C07C; C07C321/00; C07D; C07D473/00; C07D473/02; C07D473/04; C07D473/06; C07D473/08
Claims Analysis
Total Claims: 18
Claim 1
Independent Claim
156 words
A compound of the formula ##STR10## and the pharmaceutically acceptable acid addition salts thereof, wherein M is selected from the group consisting of hydrogen, morpholino, benzylamino, di-n-lower alkylamino, n-lower alkylamino, and ##STR11## wherein Ar is optionally substituted phenyl; Z 1 and Z 2 are each independently selected from the group consisting of CH 2 , CHOB and C═O, wherein B is selected from the group consisting of hydrogen and alkanoyl; Y is oxygen or sulfur; n is an integer from 0-4 but cannot be zero when Z 1 is CHOB; m is an integer from 0-4 but cannot be zero when Z 2 is CHOB, or when M is hydrogen; R 1 , R 2 and R 3 are each independently hydrogen, halogen, hydroxy, trifluoromethyl, alkyl or alkoxy; and R 4 and R 5 are each independently lower alkyl, with the proviso that both R 4 and R 5 cannot be methyl when M is hydrogen.
Claim 2
Dependent Claim
156 words
A compound of the formula ##STR10## and the pharmaceutically acceptable acid addition salts thereof, wherein M is selected from the group consisting of hydrogen, morpholino, benzylamino, di-n-lower alkylamino, n-lower alkylamino, and ##STR11## wherein Ar is optionally substituted phenyl; Z 1 and Z 2 are each independently selected from the group consisting of CH 2 , CHOB and C═O, wherein B is selected from the group consisting of hydrogen and alkanoyl; Y is oxygen or sulfur; n is an integer from 0-4 but cannot be zero when Z 1 is CHOB; m is an integer from 0-4 but cannot be zero when Z 2 is CHOB, or when M is hydrogen; R 1 , R 2 and R 3 are each independently hydrogen, halogen, hydroxy, trifluoromethyl, alkyl or alkoxy; and R 4 and R 5 are each independently lower alkyl, with the proviso that both R 4 and R 5 cannot be methyl when M is hydrogen.
Claim 3
Dependent Claim
47 words
The compound of claim 1 and the pharmaceutically acceptable acid addition salts thereof wherein Z 1 and Z 2 are each independently CH 2 or CHOH; m and n are both 1; and at least one of R 1 , R 2 and R 3 is hydrogen.
Claim 4
Dependent Claim
58 words
The compound of claim 2 and the pharmaceutically acceptable acid addition salts thereof wherein either at least one of R 4 and R 5 is methyl, or both R 4 and R 5 are identical; and either at least two of R 1 , R 2 and R 3 are hydrogen or two of these are otherwise identical.
Claim 5
Dependent Claim
16 words
The compound of claim 3 and the pharmaceutically acceptable acid addition salts thereof which is 1-[3-(3-i-butyl-1-methyl-3,7-dihydro-1H-purine-2,6-dion-7-yl)-2-hydroxypropyl]-4-(3-phenylthiopropyl)-piperazine.
Claim 6
Dependent Claim
16 words
The compound of claim 3 and the pharmaceutically acceptable acid addition salts thereof which is 1-(3-(8-morpholino-3-i-butyl-1-methyl-3,7-dihydro-1H-purine-2,6-dion-7-yl)-2-hydroxypropyl]-4-(3-phenylthiopropyl)piperazine.
Claim 7
Dependent Claim
16 words
The compound of claim 3 and the pharmaceutically acceptable acid addition salts thereof which is 1-[3-(3-i-butyl-1-methyl-3,7-dihydro-1H-purine-2,6-dion-7-yl)-2-hydroxypropyl]-4-(3-phenoxypropyl)piperazine.
Claim 8
Dependent Claim
16 words
The compound of claim 3 and the pharmaceutically acceptable acid addition salts thereof which is 1-[3-(3-i-butyl-1-methyl-3,7-dihydro-1H-purine-2,6-dion-7-yl)-2-hydroxypropyl]-4-(3-phenylthio-2-hydroxypropyl)piperazine.
Claim 9
Dependent Claim
16 words
The compound of claim 3 and the pharmaceutically acceptable acid addition salts thereof which is 1-[3-(3-i-butyl-1-methyl-3,7-dihydro-1H-purine-2,6-dion-7-yl)-2-hydroxypropyl]-4-[3-(4-methylphenylthio)-propyl]piperazine.
Claim 10
Dependent Claim
16 words
The compound of claim 3 and the pharmaceutically acceptable acid addition salts thereof which is 1-[3-(3-n-butyl-1-methyl-3,7-dihydro-1H-purine-2,6-dion-7-yl)-2-hydroxypropyl]-4-(3-phenylthiopropyl)-piperazine.
Claim 11
Dependent Claim
16 words
The compound of claim 3 and the pharmaceutically acceptable acid addition salts thereof which is 1-[3-(3-i-butyl-1-methyl-3,7-dihydro-1H-purine-2,6-dion-7-yl)propyl]-4-(3-phenoxypropyl)piperazine.
Claim 12
Dependent Claim
16 words
The compounds of claim 3 and the pharmaceutically acceptable acid addition salts thereof which is 1-[3-(8-morpholino-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dion-7-yl)-2-hydroxypropyl]-4-(3-phenylthiopropyl)piperazine.
Claim 13
Dependent Claim
16 words
The compound of claim 3 and the pharmaceutically acceptable acid addition salts thereof which is 1-[3-(8-morpholino-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dion-7-yl)-2-hydroxypropyl]-4-[3-(4-methylphenylthiopropyl]piperazine;
Claim 14
Dependent Claim
16 words
The compound of claim 3 and the pharmaceutically acceptable acid addition salts thereof which is 1-[3-(8-n-butylamino-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dion-7-yl)-2-hydroxypropyl]-4-[3-(2,6-dimethylphenoxy)-propyl]piperazine.
Claim 15
Dependent Claim
16 words
The compound of claim 3 and the pharmaceutically acceptable acid addition salts thereof which is 1-[3-(8-morpholino-3-n-butyl-1-methyl-3,7-dihydro-1H-purine-2,6-dion-7-yl)-2-hydroxypropyl]-4-(3-phenylthiopropyl)piperazine.
Claim 16
Dependent Claim
42 words
A pharmaceutical composition for treating respiratory diseases or effecting vasodilation in mammals, which comprises a therapeutically effective amount of the compound of claim 1 or a pharmaceutically acceptable acid addition salt thereof, in admixture with at least one pharmaceutically acceptable, non-toxic excipient.
Claim 17
Dependent Claim
46 words
A method for treating respiratory diseases in mammals, which method comprises administering to a subject in need of such treatment, an effective amount of, or a pharmaceutical composition containing an effective amount of a compound of claim 1 or a pharmaceutically acceptable acid addition salt thereof.
Claim 18
Dependent Claim
48 words
A method for effecting vasodilation in human beings which method comprises administering to a subject in need of such treatment a therapeutically effective amount of, or a pharmaceutical composition containing a therapeutically effective amount of, the compound of claim 1 or a pharmaceutically acceptable acid addition salt thereof.
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) | 1986-08-22 | 1987-02-21 | 1987-08-23 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1990-08-22 | 1991-02-21 | 1991-08-23 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1994-08-22 | 1995-02-21 | 1995-08-23 | $7700.00 | Window Closed / Lapsed |