Upgrade to enjoy subscriber-only features like email alerts and data export. See the Plans and Pricing

Serving leading biopharmaceutical companies globally:

Boehringer Ingelheim
Baxter
US Army
Argus Health
QuintilesIMS
Cantor Fitzgerald
Queensland Health
Novartis
UBS
US Department of Justice

Generated: December 12, 2017

DrugPatentWatch Database Preview

Claims for Patent: 5,721,244

« Back to Dashboard

Claims for Patent: 5,721,244

Title: Combination of angiotensin-converting enzyme inhibitors with calcium antagonists as well as their use in drugs
Abstract:The invention relates to combinations of angiotensin-converting enzyme inhibitors with calcium antagonists, processes for their preparation and their use as medicaments.
Inventor(s): Becker; Reinhard (Wiesbaden, DE), Henning; Rainer (Hattersheim am Main, DE), Ruger; Wolfgang (Kelkheim, DE), Teetz; Volker (Hofheim am Taunus, DE), Urbach; Hans Jorg (Kronberg/Taunus, DE)
Assignee: Hoechst Aktiengesellschaft (Frankfurt an Main, DE)
Application Number:08/483,961
Patent Claims: 1. A pharmaceutical composition comprising:

(a) an angiotensin-converting enzyme inhibitor (ACE inhibitor) of the formula I ##STR14## in which n=1 or 2,

R=hydrogen,

an aliphatic radical with 1-8 carbon atoms,

an alicyclic radical with 3-9 carbon atoms, or

an aromatic radical with 6-12 carbon atoms,

an araliphatic radical with 7-14 carbon atoms,

an alicyclic-aliphatic radical with 7-14 carbon atoms,

a radical OR.sup.a or SR.sup.a, wherein

R.sup.a represents an aliphatic radical with 1-4 carbon atoms or an aromatic radical with 6-12 carbon atoms,

R.sup.1 is hydrogen,

an aliphatic radical with 1-6 carbon atoms,

an alicyclic radical with 3-9 carbon atoms,

an alicyclic-aliphatic radical with 4-12 carbon atoms,

an aromatic radical with 6-12 carbon atoms,

an araliphatic radical with 7-16 carbon atoms or

the side chain, protected if necessary, of a naturally occurring .alpha.-amino acid,

R.sup.2 and R.sup.3 are the same or different and are

hydrogen,

an aliphatic radical with 1-6 carbon atoms,

an alicyclic radical with 3-9 carbon atoms,

an aromatic radical with 6-12 carbon atoms,

an araliphatic radical with 7-16 carbon atoms and

R.sup.4 and R.sup.5 together with the atoms carrying them form a heterocyclic bicyclic or tricyclic ring system selected from tetrahydroisoquinoline, decahydroisoquinoline, octahydroindole, 2-azaspiro[4,5]decane, 2-azaspiro[4,4]nonane, spiro[(bicyclo[2,2,1]heptane)-2,3'-pyrrolidine], spiro [(bicyclo[2,2,2]octane)-2,3'-pyrrolidine], 2-azatricyclo[4,3,0,1.sup.6.9 ]decane, decahydrocyclophepta[b]pyrrole, octahydroisoindole, octahydrocyclocopenta[c]pyrrole, 2,2,3a,4,5,7a-hexahydroindole, 2-azabicyclo[3,1,0]-hexane, hexahydrocyclopenta[b]pyrrole,

or a physiologically acceptable salt thereof, and

(b) a calcium antagonist or a physiologically acceptable salt thereof;

wherein said ACE inhibitor and said calcium antagonist are present in said composition in amounts effective for treating hypertension;

and with the proviso that when said calcium antagonist is 4-(2,3-dichlorophenyl)-2,6-dimethyl-3-methoxycarbonyl-5-ethoxycarbonyl-1,4 -dihydropyridine (felodipine), said angiotensin-converting enzyme inhibitor is not 1-(2S,3aR,7aS)-octahydro[1H]indole-2-S-carboxylic acid (trandolapril).

2. A composition according to claim 1, wherein:

n=1 or 2,

R is (C.sub.1 -C.sub.6)-alkyl, (C.sub.2 -C.sub.6)-alkenyl, (C.sub.3 -C.sub.9)-cycloalkyl, or (C.sub.6 -C.sub.12)-aryl,

R.sup.1 is hydrogen, (C.sub.1 -C.sub.6)-alkyl, (C.sub.2 -C.sub.6)-alkenyl, (C.sub.3 -C.sub.9)-cycloalkyl, (C.sub.5 -C.sub.9)-cycloalkenyl, (C.sub.3 -C.sub.7)-cycloalkyl-(C.sub.1 -C.sub.4)-alkyl, (C.sub.6 -C.sub.12)-aryl or partially hydrogenated aryl,

or a side chain of a naturally occurring, optionally protected .alpha.-amino acid,

R.sup.2 and R.sup.3 are the same or different and are hydrogen, (C.sub.1 -C.sub.6)-alkyl, or (C.sub.2 -C.sub.6)-alkenyl, and

R.sup.4 and R.sup.5 are as defined in claim 1.

3. A composition according to claim 1, wherein said ACE inhibitor is 1-[N-(1-S-ethoxycarbonyl-3-phenylpropyl)-S-alanyl]-(2S,3aR,7aS)-octahydro[ 1H]indole-2-carboxylic acid (trandolapril) or a physiologically acceptable salt thereof, or 2-[N-(1-S-ethoxycarbonyl-3-phenylpropyl)-S-alanyl]-1,2,3,4-tetrahydroisoqu inoline-3-S-carboxylic acid (quinapril) or a physiologically acceptable salt thereof.

4. A composition according to claim 1, wherein the amounts of ACE inhibitor, or salt thereof, and calcium antagonist, or salt thereof, in combination are effective for simultaneous, separate or periodic regulated use in the treatment of high blood pressure.

5. A composition according to claim 1, wherein the amounts of ACE inhibitor, or salt thereof, and calcium antagonist, or salt thereof, in said composition are effective as a medicament in the treatment of cardiac insufficiency.

6. A composition according to claim 1, wherein the amounts of ACE inhibitor, or salt thereof, and calcium antagonist, or salt thereof, in said composition are effective as a medicament in the treatment of coronary head disease.

7. A method for the treatment of high blood pressure, comprising administering to a host in recognized need thereof a pharmaceutical composition according to claim 1.

8. A method for the treatment of cardiac insufficiency, comprising administering to a host in recognized need thereof a pharmaceutical composition according to claim 1.

9. A method for the treatment of coronary head disease, comprising administering to a host in recognized need thereof a pharmaceutical composition according to claim 1.

10. A pharmaceutical composition according to claim 1, wherein said composition further comprises a physiologically acceptable carrier.

11. A pharmaceutical composition comprising:

(a) an angiotensin-converting enzyme inhibitor (ACE inhibitor) of the formula I ##STR15## in which n=1 or 2,

R=

hydrogen,

an aliphatic radical with 1-8 carbon atoms,

an alicyclic radical with 3-9 carbon atoms, or

an aromatic radical with 6-12 carbon atoms,

an araliphatic radical with 7-14 carbon atoms,

an alicyclic-aliphatic radical with 7-14 carbon atoms,

a radical OR.sup.a or SR.sup.a, wherein

R.sup.a represents an aliphatic radical with 1-4 carbon atoms or an aromatic radical with 6-12 carbon atoms,

R.sup.1 is hydrogen,

an aliphatic radical with 1-6 carbon atoms,

an alicyclic radical with 3-9 carbon atoms,

an alicyclic-aliphatic radical with 4-12 carbon atoms,

an aromatic radical with 6-12 carbon atoms,

an araliphatic radical with 7-16 carbon atoms or

the side chain, protected if necessary, of a naturally occurring .alpha.-amino acid,

R.sup.2 and R.sup.3 are the same or different and are

hydrogen,

an aliphatic radical with 1-6 carbon atoms,

an alicyclic radical with 3-9 carbon atoms,

an aromatic radical with 6-12 carbon atoms,

an araliphatic radical with 7-16 carbon atoms and

R.sup.4 and R.sup.5 together with the atoms carrying them form a heterocyclic bicyclic or tricyclic ring system selected from tetrahydroisoquinoline, decahydroisoquinoline, octahydroindole, 2-azaspiro[4,5]decane, 2-azaspiro[4,4]nonane, spiro[(bicyclo[2,2,1]heptane)-2,3'-pyrrolidine], spiro [(bicyclo[2,2,2]octane)-2,3'-pyrrolidine], 2-azatricyclo[4,3,0,1.sup.6.9 ]decane, decahydrocyclophepta[b]pyrrole, octahydroisoindole, octahydrocyclocopenta[c]pyrrole, 2,2,3a,4,5,7a-hexahydroindole, 2-azabicyclo[3,1,0]-hexane, hexahydrocyclopenta[b]pyrrole,

or a physiologically acceptable salt thereof, and

(b) a calcium antagonist or a physiologically acceptable salt thereof;

wherein said ACE inhibitor and said calcium antagonist are present in said composition in amounts effective for treating cardiac insufficiency;

and with the proviso that when said calcium antagonist is 4-(2,3-dichlorophenyl)-2,6-dimethyl-3-methoxycarbonyl-5-ethoxycarbonyl-1,4 -dihydropyridine (felodipine), said angiotensin-converting enzyme inhibitor is not 1-[N-(1-S-ethoxycarbonyl-3-phenylpropyl)-S-alanyl]-(2S,3aR,7aS)-octahydro[ 1H]indole-2-S-carboxylic acid (trandolapril).

12. A pharmaceutical composition comprising:

(a) an angiotensin-converting enzyme inhibitor (ACE inhibitor) of the formula I ##STR16## in which n=1 or 2,

R=

hydrogen,

an aliphatic radical with 1-8 carbon atoms,

an alicyclic radical with 3-9 carbon atoms, or

an aromatic radical with 6-12 carbon atoms,

an araliphatic radical with 7-14 carbon atoms,

an alicyclic-aliphatic radical with 7-14 carbon atoms,

a radical OR.sup.a or SR.sup.a, wherein

R.sup.a represents an aliphatic radical with 1-4 carbon atoms or an aromatic radical with 6-12 carbon atoms,

R.sup.1 is hydrogen,

an aliphatic radical with 1-6 carbon atoms,

an alicyclic radical with 3-9 carbon atoms,

an alicyclic-aliphatic radical with 4-12 carbon atoms,

an aromatic radical with 6-12 carbon atoms,

an araliphatic radical with 7-16 carbon atoms or

the side chain, protected if necessary, of a naturally occurring .alpha.-amino acid,

R.sup.2 and R.sup.3 are the same or different and are

hydrogen,

an aliphatic radical with 1-6 carbon atoms,

an alicyclic radical with 3-9 carbon atoms,

an aromatic radical with 6-12 carbon atoms,

an araliphatic radical with 7-16 carbon atoms and

R.sup.4 and R.sup.5 together with the atoms carrying them form a heterocyclic bicyclic or tricyclic ring system selected from tetrahydroisoquinoline, decahydroisoquinoline, octahydroindole, 2-azaspiro[4,5]decane, 2-azaspiro[4,4]nonane, spiro[(bicyclo[2,2,1]heptane)-2,3'-pyrrolidine], spiro [(bicyclo[2,2,2]octane)-2,3'-pyrrolidine], 2-azatricyclo[4,3,0,1.sup.6.9 ]decane, decahydrocyclophepta[b]pyrrole, octahydroisoindole, octahydrocyclocopenta[c]pyrrole, 2,2,3a,4,5,7a-hexahydroindole, 2-azabicyclo[3,1,0]-hexane, hexahydrocyclopenta[b]pyrrole,

or a physiologically acceptable salt thereof, and

(b) a calcium antagonist or a physiologically acceptable salt thereof;

wherein said ACE inhibitor and said calcium antagonist are present in said composition in amounts effective for treating coronary heart disease;

and with the proviso that when said calcium antagonist is 4-(2,3-dichlorophenyl)-2,6-dimethyl-3-methoxycarbonyl-5-ethoxycarbonyl-1,4 -dihydropyridine (felodipine), said angiotensin-converting enzyme inhibitor is not 1-[N-(1-S-ethoxycarbonyl-3-phenylpropyl)-S-alanyl]-(2S,3aR,7aS)-octahydro[ 1H]indole-2-S-carboxylic acid (trandolapril).
« Back to Dashboard

For more information try a trial or see the database preview and plans and pricing

Serving leading biopharmaceutical companies globally:

US Department of Justice
Teva
Queensland Health
Colorcon
Boehringer Ingelheim
Julphar
Mallinckrodt
Daiichi Sankyo
Cipla
Fuji

Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verifification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.

Copyright 2002-2017 thinkBiotech LLC
ISSN: 2162-2639

Secure SSL Encrypted
Privacy and Cookies
Terms & Conditions

Follow DrugPatentWatch:

botpot