# US 5,348,965 A · N-substituted azaheterocyclic carboxylic acids

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- Number: US 5,348,965 A
- Document ID: US5348965A
- Status: Granted
- Kind: A
- Application number: 07/882,788
- Filed: 1992-05-14
- Granted: 1994-09-20
- Earliest claimed: 1991-05-17
- Assignees: Novo Nordisk A/S
- Inventors: Knud E. Andersen; Lars J. S. Knutsen; Per O. Sorensen; Behrend F. Lundt; Jesper Lau; Hans Petersen
- Web page: https://patentgrep.com/patent/US5348965A

## CPC

- C07D 401/12: linked by a chain containing hetero atoms as chain links
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- A61P 25/08: Antiepileptics; Anticonvulsants
- A61P 25/20: Hypnotics; Sedatives
- A61P 25/24: Antidepressants
- A61P 25/26: Psychostimulants, e.g. nicotine, cocaine
- C07D 211/60: Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D 403/12: linked by a chain containing hetero atoms as chain links
- C07D 413/10: linked by a carbon chain containing aromatic rings
- C07D 417/12: linked by a chain containing hetero atoms as chain links
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The invention relates to therapeutically active azaheterocyclic compounds and to pharmaceutical compositions comprising the compounds. The novel compounds are useful in treating a central nervous system ailment related to the GABA uptake.

## Claims

### Claim 1

A compound of formula I ##STR4## wherein R.sup.1 and R.sup.2 independently are hydrogen, halogen, trifluoromethyl, C.sub.1-6 -alkyl or C.sub.1-6 -alkoxy;
Y is >CH--CH.sub.2 -- or >C.dbd.CH-- when s is 0, 1 or 2 or Y is >CH--CH.dbd.NH-- or >C.dbd.N-- when s is 0, wherein the underscored atom is part of the ring system;
X is --O--;
Z is --CH.sub.2 --, --CH.sub.2 --CH.sub.2 --, CH.dbd.CH--CH.sub.2 --, --CH.sub.2 --CH.dbd.CH--, --CH.sub.2 --CH.sub.2 --CH.sub.2 -- or --CH.dbd.CH--;
R.sup.4 and R.sup.5 independently are hydrogen or together represent a bond;
R.sup.6 is OH or C.sub.1-8 -alkoxy;
p is 0 or 1;
q is 0 or 1;
s is 0, 1 or 2;
r is 2, 3 or 4;
m is 2; and
n is 0; or
a pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

A compound according to claim 1 wherein Z is --CH.sub.2 --CH.sub.2 --.

### Claim 3 (depends on 1)

A compound according to claim 1, wherein s is 1.

### Claim 4 (depends on 1)

A compound according to claim 1, wherein Y is >CH--CH.dbd.N-- and s is 0.

### Claim 5 (depends on 1)

A compound according to claim 1, wherein p and q are 0.

### Claim 6 (depends on 1)

A compound according to claim 1, wherein r is 2.

### Claim 7 (depends on 1)

A compound according to claim 1, wherein Z is --CH.sub.2 --CH.sub.2 --, p and q are 0 and r is 2.

### Claim 8 (depends on 7)

A compound according to claim 7, wherein s is 1.

### Claim 9 (depends on 7)

A compound according to claim 7 wherein Y is >CH--CH.dbd.N-- and s is 1.

### Claim 10 (depends on 1)

A compound according to claim 1 which is:
(R)-N-(2-(2-(10,11-Dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)ethoxy)ethy l)-3-piperidinecarboxylic acid;
(R)-N-(2-(2-(10,11-Dihydro-5H-dibenzo[a,d]cyclohepten-5-yl)ethoxy)ethyl)-3- piperidinecarboxylic acid;
(R)-N-(3-(2-(10,11-Dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)ethoxy)-1-p ropyl)-3-piperidinecarboxylic acid;
(R)-N-(3-(2-(10,11-Dihydro-5H-dibenzo[a,d]cyclohepten-5-yl)ethoxy)-1-propyl )-3-piperidinecarboxylic acid;
(R)-N-(2-(((10,11-Dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)amino)oxy)et hyl)-3-piperidinecarboxylic acid;
(R)-N-(2-((10,11-Dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)methoxy)ethyl )-3-piperidinecarboxylic acid;
(R)-N-(2-(2-(10,11-Dihydro-5H-dibenzo[a,d]cyclohepten-5-yl)ethoxy)ethyl)-1, 2,5,6-tetrahydro-3-pyridinecarboxylic acid;
(R)-N-(2-((((10,11-Dihydro-5H-dibenzo[a,d]cyclohepten-5-yl)methylene)amino) oxy)ethyl)-3-piperidinecarboxylic acid;
(R)-N-(2-(3-(2-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)ethoxy)-1-propyl)-3-pi peridinecarboxylic acid; or
a pharmaceutically acceptable salt thereof.

### Claim 11 (depends on 1)

A pharmaceutical composition comprising a compound according to claim 1 together with a pharmaceutically acceptable carrier or diluent.

### Claim 12 (depends on 1)

A pharmaceutical composition suitable for treating a central nervous system ailment related to the GABA uptake comprising an effective amount of a compound according to claim 1 together with a pharmaceutically acceptable carrier or diluent.

### Claim 13 (depends on 11)

The pharmaceutical composition according to claim 11 comprising between 0.5 mg and 1000 mg of the compound per unit dose.

### Claim 14 (depends on 12)

The pharmaceutical composition according to claim 12 comprising between 0.5 mg and 1000 mg of the compound per unit dose.

### Claim 15 (depends on 1)

A method of treating a central nervous system ailment related to the GABA uptake in a subject in need thereof comprising administering to said subject an effective amount of a compound according to claim 1.

### Claim 16 (depends on 12)

A method of treating a central nervous system ailment related to the GABA uptake in a subject in need thereof comprising administering to said subject a pharmaceutical composition according to claim 12.