1-(4-Acylamino-phenyl)-2-amino-ethanols and salts thereof

• US 4,214,001 A
• Filed: 03/06/1978
• Issued: 07/22/1980
• Est. Priority Date: 03/14/1977
• Status: Expired due to Term

• Current Assignee: Boehringer Ingelheim GmbH (C.H. Boehringer Sohn AG & Co. KG)
• Original Assignee: Boehringer Ingelheim GmbH (C.H. Boehringer Sohn AG & Co. KG)
• Inventors: Pieper, Helmut, Noll, Klaus, Engelhardt, Gunther, Keck, Johannes, Kruger
• Primary Examiner(s): Torrence, Dolph H.
• Application Number:
  US05/883,814
• Time in Patent Office: 869 Days
• Field of Search: 560/21, 260/465 D, 260/553 A, 560/29, 424/304, 424/300, 424/322
• US Class Current: 514/482
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: C07C 275/40 being further substituted by nitrogen atoms not being part of nitro or nitroso groups

Abstract

Compounds of the formula ##STR1## wherein R₁ is hydrogen, halogen or cyano;

R₂ is fluorine, cyano, trifluoromethyl, nitro or alkyl of 1 to 4 carbon atoms;

R₃ is alkoxy of 1 to 5 carbon atoms, alkenyloxy of 2 to 5 carbon atoms, aryloxy of 6 to 10 carbon atoms, aralkoxy of 7 to 11 carbon atoms, or --NR₅ R₆, where R₅ and R₆ are each hydrogen, alkyl of 1 to 5 carbon atoms, alkenyl of 2 to 5 carbon atoms, aryl of 6 to 10 carbon atoms or aralkyl of 7 to 11 carbon atoms; and

R₄ is cycloalkyl of 3 to 5 carbon atoms or alkyl of 3 to 5 carbon atoms;

and non-toxic, pharmacologically acceptable acid addition salt thereof. The compounds as well as the salts are useful as analgesics, uterospasmolytics and antiasthmatics.

Claims

1. A compound of the formula ##STR7## wherein R₁ is hydrogen, halogen or cyano;

R₂ is fluorine, cyano, trifluoromethyl, nitro or alkyl of 1 to 4 carbon atoms;

R₃ is alkoxy of 1 to 5 carbon atoms, alkenyloxy of 2 to 5 carbon atoms, aryloxy of 6 to 10 carbon atoms, aralkoxy of 7 to 11 carbon atoms, or

--NR₅ R₆, where R₅ and R₆ are each hydrogen, alkyl of 1 to 5 carbon atoms, alkenyl of 2 to 5 carbon atoms, aryl of 6 to 10 carbon atoms or aralkyl of 7 to 11 carbon atoms; and

R₄ is cycloalkyl of 3 to 5 carbon atoms or alkyl of 3 to 5 carbon atoms;

or a non-toxic, pharmacologically acceptable acid addition salt thereof.

2. A compound of claim 1,

where

R₁ is hydrogen, halogen or cyano;

R₂ is fluorine, cyano, trifluoromethyl, nitro or alkyl of 1 to 4 carbon atoms;

R₃ is alkoxy of 1 to 5 carbon atoms, alkenyloxy of 2 to 5 carbon atoms, aralkoxy of 7 to 11 carbon atoms or, when R₁ is hydrogen or halogen and R₂ is fluorine, trifluoromethyl or nitro, also

--NHR₆, where R₆ is hydrogen, alkyl of 1 to 5 carbon atoms, alkenyl of 2 to 5 carbon atoms, aryl of 6 to 10 carbon atoms or aralkyl of 7 to 11 carbon atoms; and

R₄ is cycloalkyl of 3 to 5 carbon atoms or alkyl of 3 to 5 carbon atoms;

or a non-toxic, pharmacologically acceptable acid addition salt thereof.

3. A compound of claim 1,

where

R₁ is hydrogen, halogen or cyano;

R₂ is fluorine, cyano, trifluoromethyl, nitro or alkyl of 1 to 4 carbon atoms;

R₃ is alkoxy of 1 to 4 carbon atoms or, when R₁ is hydrogen or halogen and R₂ is fluorine, trifluoromethyl or nitro, also --HNR₆ where R₆ is hydrogen or alkyl of 1 to 4 carbon atoms; and

R₄ is isopropyl or tert. butyl;

or a non-toxic, pharmacologically acceptable acid addition salt thereof.

4. A compound of claim 1,

where

R₁ is hydrogen, halogen or cyano;

R₂ is fluorine, cyano, trifluoromethyl or nitro;

R₃ is alkoxy of 1 to 4 carbon atoms; and

R₄ is isopropyl or tert. butyl;

or a non-toxic, pharmacologically acceptable acid addition salt thereof.

5. A compound according to claim 1 having bronchospasmolytic activity selected from the group consisting of:

1-(4'"'"'-ethoxycarbonylamino-3'"'"'-cyano-5'"'"'-fluoro-phenyl)-2-tert.butylamino ethanol;

1-(4'"'"'-ethoxycarbonylamino-3'"'"'-cyano-phenyl)-2-tert.butyl-amino-ethanol;

1-(4'"'"'-ethoxycarbonylamino-3'"'"'-cyano-phenyl)-2-isopropylamino-ethanol

and their non-toxic, pharmacologically acceptable acid addition salts.

6. A compound of claim 1 having bronchospasmolytic activity selected from the group consisting of:

1-(4'"'"'-ethoxycarbonylamino-3'"'"'-chloro-5'"'"'-fluoro-phenyl)-2-tert.butylamino ethanol;

1-(4'"'"'-ethoxycarbonylamino-3'"'"'-cyano-5'"'"'-fluoro-phenyl)-2-tert.butylamino ethanol;

1-(4'"'"'-ethoxycarbonylamino-3'"'"'-cyano-phenyl)-2-tert.butylamino-ethanol;

1-(4'"'"'-ethoxycarbonylamino-3'"'"'-3'"'"'-cyano-phenyl)-2-isopropylamino-ethanol

and their non-toxic, pharmacologically acceptable acid addition salts.

7. A compound of claim 6, which is 1-(4'"'"'-ethoxycarbonyllamino-3'"'"'-chloro-5'"'"'-fluoro-phenyl)-2-tert.-butylaminoethanol or a non-toxic, pharmacologically acceptable acid addition salt thereof.

8. A compound of claim 6, which is 1-(4'"'"'-ethoxycarbonylamino-3'"'"'-cyano-5'"'"'-fluoro-phenyl)-2-tert.-butylamino-ethanol or a non-toxic, pharmacologically acceptable acid addition salt thereof.

9. A compound of claim 6, which is 1-(4'"'"'-ethoxycarbonylamino-3'"'"'-cyano-phenyl)-2-tert. butylamino-ethanol or a non-toxic, pharmacologically acceptable acid addition salt thereof.

10. A compound of claim 6, which is 1-(4'"'"'-ethoxycarbonylamino-3'"'"'-cyano-phenyl)-2-isopropylamino-ethanol or a non-toxic, pharmacologically acceptable acid addition salt thereof.

11. A bronchospasmolytic pharmaceutical dosage unit composition consisting essentially of an inert pharmaceutical carrier and an effective bronchospasmolytic amount of a compound of claim 6.

12. The method of antagonizing bronchospasm in a warm-blooded animal in need thereof, which comprises perorally, parenterally or rectally administering to said animal an effective bronchospasmolytic amount of a compound of claim 6.