# US 5,334,601 A · Soft .beta.-adrenergic blocking agents

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- Number: US 5,334,601 A
- Document ID: US5334601A
- Status: Granted
- Kind: A
- Application number: 07/997,248
- Filed: 1992-12-28
- Granted: 1994-08-02
- Earliest claimed: 1984-03-14
- Inventors: Nicholas S. Bodor
- Web page: https://patentgrep.com/patent/US5334601A

## CPC

- C07C 217/36: by carbon atoms having at least two bonds to oxygen atoms
- C07C 69/732: of unsaturated hydroxy carboxylic acids
- C07C 235/06: having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07D 209/18: Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D 215/227: only one oxygen atom which is attached in position 2
- C07D 295/185: from aliphatic carboxylic acids
- C07D 307/54: Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07C 2601/14: The ring being saturated
- C07C 2601/18: with a ring being at least seven-membered
- C07C 2602/42: the bicyclo ring system containing seven carbon atoms
- C07C 2603/74: Adamantanes
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

New soft .beta.-adrenergic blocking agents, useful in the treatment or prevention of cardiovascular disorders and in the treatment of glaucoma, have the formula ##STR1## wherein n is an integer from 0 to 10; R is C.sub.6 -C.sub.12 cycloalkyl-C.sub.p H.sub.2p -, C.sub.6 -C.sub.18 polycycloalkyl-C.sub.p H.sub.2p -, C.sub.6 -C.sub.18 polycycloalkenyl-C.sub.p H.sub.2p - or C.sub.6 -C.sub.12 cycloalkenyl-C.sub.p H.sub.2p - (wherein p is 0, 1, 2 or 3), or together with the adjacent ##STR2## group represents a variety of other complex ester groupings; R.sub.1 is C.sub.1 -C.sub.7 alkyl; and Ar is a divalent radical containing at least one aromatic nucleus. The corresponding pharmaceutically acceptable acid addition salts are also described.

## Claims

### Claim 1

A compound of the formula ##STR301## or a pharmaceutically acceptable acid addition salt thereof, wherein: n is one;
R is C.sub.6 -C.sub.18 polycycloalkyl-C.sub.p H.sub.2p - consisting of a two or three ring bridged or fused saturated alicyclic hydrocarbon system bearing 0 to 3 methyl substituents and having a total of 6 to 18 carbon atoms in the polycycloalkyl portion and p is zero, one or two; or R is C.sub.6 -C.sub.18 polycycloalkenyl-C.sub.p H.sub.2p - consisting of a two or three ring bridged or fused unsaturated alicyclic hydrocarbon system bearing 0 to 3 methyl substituents and having a total of 6 to 18 carbon atoms in the polycycloalkenyl portion and p is zero, one or two;
R.sub.1 is C.sub.1 -C.sub.7 alkyl; and
Ar is a divalent fused ring system having two or three rings and at least one benzene nucleus, and optionally having one or two hetero ring atoms selected from the group consisting of N, O and S.

### Claim 2 (depends on 1)

A compound as defined by claim 1, wherein R is C.sub.6 -C.sub.18 polycycloalkyl-C.sub.p H.sub.2p - consisting of a two or three ring bridged saturated alicyclic hydrocarbon system bearing 0 to 3 methyl substituents and having a total of 6 to 18 carbon atoms in the polycycloalkyl portion and p is zero, one or two.

### Claim 3 (depends on 1)

A compound as defined by claim 1, wherein R is adamantyl, adamantylmethyl, adamantylethyl, norbornyl, norbornylmethyl, norbornylethyl, bornyl, norbornenyl, decahydronaphthyl, 6,6-dimethylbicyclo[3.1.1]hept-2-en-2-ethyl,1,3,3 -trimethyl-2-norbo or 5-norbornene-2-methyl.

### Claim 4 (depends on 1)

A compound as defined by claim 1, wherein R is adamantyl, (adamant-1-yl)ethyl, (adamant-1-yl)methyl or (norborn-2-yl)methyl.

### Claim 5 (depends on 1)

A compound as defined by claim 1, herein R.sub.1 is isopropyl or tert-butyl.

### Claim 6 (depends on 1)

An oxalate salt of a compound as defined by claim 1.

### Claim 7 (depends on 1)

A compound as defined by claim 1, wherein Ar is a radical of the formula ##STR302##

### Claim 8 (depends on 1)

A compound as defined by claim 1, wherein Ar is a radical of the formula ##STR303##

### Claim 9 (depends on 1)

The compound as defined by claim 1, said compound being a compound of the formula ##STR304## or a pharmaceutically acceptable acid addition salt thereof.

### Claim 10 (depends on 1)

The compound as defined by claim 1, having the formula ##STR305## or a pharmaceutically acceptable acid addition salt thereof.

### Claim 11 (depends on 1)

A method for eliciting a .beta.-adrenergic blocking response in a warm-blooded animal, which comprises administering to said animal an effective .beta.-adrenergic blocking amount of a compound of formula (I) as defined by claim 1, or a pharmaceutically acceptable acid addition salt thereof.

### Claim 12 (depends on 1)

A pharmaceutical composition of matter, in unit dosage form, for use in eliciting a .beta.-adrenergic blocking response in a warm-blooded animal, said composition comprising, per dosage unit, an effective unit .beta.-adrenergic blocking amount of a compound of formula (I) as defined by claim 1 or a pharmaceutically acceptable acid addition salt thereof, and a non-toxic pharmaceutically acceptable carrier therefor.

### Claim 13 (depends on 1)

A method for the treatment of glaucoma or for lowering intraocular pressure in a warm-blooded animal, which comprises administering to the eye or the eyes of said animal an effective intraocular pressure decreasing amount of a compound of formula (I) as defined by claim 1, or a pharmaceutically acceptable acid addition salt thereof.

### Claim 14 (depends on 1)

An ophthalmic composition of matter, in unit dosage form, for use in the treatment of glaucoma or in the lowering of intraocular pressure in a warm-blooded animal, said composition comprising, per dosage unit, an effective unit intraocular pressure decreasing amount of a compound of formula (I) as defined by claim 1 or a pharmaceutically acceptable acid addition salt thereof, and a non-toxic ophthalmically acceptable carrier therefor.