# US 4,399,138 A · Alkanolamine derivatives

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- Number: US 4,399,138 A
- Document ID: US4399138A
- Status: Granted
- Kind: A
- Application number: 06/344,969
- Filed: 1982-02-02
- Granted: 1983-08-16
- Earliest claimed: 1981-02-02
- Assignees: Imperial Chemical Industries PLC
- Inventors: Jeffrey J. Barlow; Leslie H. Smith
- Web page: https://patentgrep.com/patent/US4399138A

## CPC

- C07D 403/12: linked by a chain containing hetero atoms as chain links
- A61P 7/10: Antioedematous agents; Diuretics
- A61P 25/02: for peripheral neuropathies
- C07D 241/26: with nitrogen atoms directly attached to ring carbon atoms
- C07D 405/12: linked by a chain containing hetero atoms as chain links
- C07D 409/12: linked by a chain containing hetero atoms as chain links
- 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

Novel alkanolamine derivatives of the formula: ##STR1## wherein Ar is phenyl or naphthyl which is unsubstituted or which bears one or two substituents selected from halogen, trifluoromethyl, hydroxy, amino, nitro, carbamoyl, carbamoylmethyl and cyano, and alkyl, alkenyl, alkoxy, alkenyloxy, alkylthio, alkanoyl and alkanoylamino each of up to 6 carbon atoms, or Ar is 4-indolyl, 4-benzo[b]thienyl, 5-benzo[1,4]dioxanyl, 4- or 5-indanyl, 5- or 6- 1,2,3,4-tetrahydronaphthyl), 2,3-dihydroxy-1,2,3,4-tetrahydronaphth-5-yl or 4- morpholino-1,2,5-thiadiazol-3-yl; wherein R is halogen; wherein A.sup.1 is alkylene of 2 to 6 carbon atoms; and wherein A.sup.2 is alkylene of 1 to 7 carbon atoms which in unsubstituted or bears a phenyl, hydroxy or carbamoyl substituent, or A.sup.2 is cycloalkylene of 3 to 6 carbon atoms; or acid-addition salts thereof. The compounds possess either .beta.-adrenergic blocking activity or diuretic activity or both such activities and may be used in the treatment of heart disease or hypertension. Also disclosed are processes for the manufacture of the compounds and pharmaceutical compositions containing them.

## Claims

### Claim 1

An alkanolamine compound of the formula: ##STR9## wherein Ar is phenyl or naphthyl which is unsubstituted or which bears one or two substituents selected from halogen, trifluoromethyl, hydroxy, amino, nitro, carbamoyl, carbamoylmethyl and cyano, and alkyl, alkenyl, alkoxy, alkenyloxy, alkylthio, alkanoyl and alkanoylamino each of up to 6 carbon atoms, or Ar is 4-indolyl, 4-benzo[b]thienyl, 5-benzo[1,4]dioxanyl, 4- or 5-indanyl, 5- or 6-(1,2,3,4-tetrahydronaphthyl), 2,3-dihydroxy-1,2,3,4-tetrahydronaphth-5yl or 4-morpholino-1,2,5-thiadiazol-3-yl;
wherein R is halogen;
wherein A.sup.1 is alkylene of 2 to 6 carbon atoms; and
wherein A.sup.2 is alkylene of 1 to 7 carbon atoms which is unsubstituted or bears a phenyl, hydroxy or carbamoyl substituent, or A.sup.2 is cycloalkylene of 3 to 6 carbon atoms;
or an acid-addition salt thereof.

### Claim 2 (depends on 1)

An alkanolamine derivative as claimed in claim 1
wherein
Ar is unsubstituted naphthyl, or Ar is phenyl which is unsubstituted or which bears one halogen, carbamoyl, carbamoylmethyl, cyano, alkyl, alkoxy, alkenyl, alkenyloxy, alkanoyl or alkanoylamino substituent, or Ar is 4-indolyl, 4-benzo[b]thienyl, 5-benzo[1,4]dioxanyl, 4-indanyl, 5-(1,2,3,4-tetrahydronaphthyl), 2,3-dihydroxy-1,2,3,4-tetrahydronaphth-5-yl or 4-morpholino-1,2,5-thiadiazol-3-yl;
wherein R is chlorine;
wherein A.sup.1 is ethylene or 1,1-dimethylethylene[--C(CH.sub.3).sub.2--CH.sub.2 --];
and wherein A.sup.2 is methylene, ethylene, ethylidene[--CH(CH.sub.3)--] or 1-methylethylidene [--C(CH.sub.3).sub.2 --];
or an acid-addition salt thereof.

### Claim 3 (depends on 1)

An alkanolamine derivative as claimed in claim 1 wherein Ar and A.sup.1 have the meanings stated in claim 1, wherein R is chlorine and wherein A.sup.2 is --CR.sup.1 R.sup.2 --, wherein R.sup.1 is hydrogen or alkyl of up to 3 carbon atoms and R.sup.2 is alkyl of up to 3 carbon atoms which is unsubstituted or which bears a phenyl, hydroxy or carbamoyl substituent, or R.sup.1 and R.sup.2 are joined to form alkylene of 2 to 5 carbon atoms, or an acid-addition salt thereof.

### Claim 4

The compound 3,5-diamino-6-chloro-N-{1-[N-.beta.-(2-hydroxy-3-.alpha.-naphthoxypropylam ino)ethylcarbamoyl]-1-methylethyl}pyrazine-2-carboxamide or an acid-addition salt thereof.

### Claim 5 (depends on 1)

An acid-addition salt as claimed in claim 1 which is hydrochloride, hydrobromide, phosphate, sulphate, oxalate, lactate, succinate, tartrate, acetate, salicylate, citrate, benzoate, .beta.-naphthoate, adipate or 1,1-methylene-bis-(2-hydroxy-3-naphthoate), or a salt derived from a sulphonated polystyrene resin.

### Claim 6 (depends on 1)

A pharmaceutical composition comprising as active ingredient at least one alkanolamine derivative or an acid-addition salt thereof, claimed in claim 1 in association with a pharmaceutically-acceptable diluent or carrier therefor.

### Claim 7 (depends on 1)

A method for the treatment of heart disease or hypertension in a warm-blooded animal which comprises administering to said animal an effective amount of at least one compound claimed in claim 1.