Imidazolylphenyl amidines, pharmaceutical compositions containing same and use thereof

• US 4,386,099 A
• Filed: 11/19/1981
• Issued: 05/31/1983
• Est. Priority Date: 11/28/1980
• Status: Expired due to Fees

• Current Assignee: Istituto de Angeli SPA
• Original Assignee: Istituto de Angeli SPA
• Inventors: Cereda, Enzo, del Soldato, Piero, Donetti, Arturo, Bergamaschi, Mario
• Primary Examiner(s): Ramsuer, Robert W.
• Application Number:
  US06/322,903
• Time in Patent Office: 558 Days
• Field of Search: 548/336, 548/346, 548/245, 424/273 R, 424/272
• US Class Current: 514/397
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: C07D 233/64 with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine

Abstract

This invention relates to imidazolylphenyl amidines, the preparation thereof, and pharmaceutical compositions containing them. More particularly, this invention relates to compounds of the general formula ##STR1## in which R, R₁, R₃, which may be the same or different, each represent a hydrogen atom or a lower alkyl group, and R₂ represents a linear or branched alkyl, alkenyl, or alkynyl group, a cyano group, a hydroxyl group, a substituted or unsubstituted cycloalkyl or cycloaliphatic alkyl group, a bicyclic group, an aralkyl or aryl group optionally substituted by halogen, methyl, methoxy, or methylenedioxy groups, or a substituted or unsubstituted heterocyclylalkyl or heterocyclic group which may also contain a further hetero atom, or a non-toxic, pharmacologically acceptable acid addition salt thereof. These compounds are useful in treating disorders of the gastrointestinal tract.

Claims

1. A compound of the formula ##STR14## in which R, R₁, and R₃, which may be the same or different, each represent a hydrogen atom or a lower alkyl group, and R₂ represents a linear or branched alkyl, alkenyl, or alkynyl group, a cyano group, a hydroxyl group, a substituted or unsubstituted cycloalkyl or cycloaliphatic alkynyl group, a bicyclic group, an aralkyl or aryl group optionally substituted by halogen, methyl, methoxy, or methylenedioxy groups, or a substituted or unsubstituted heterocyclicalkyl or heterocyclic group which may also contain a further hetero atom, or a non-toxic, pharmacologically acceptable acid addition salt thereof.

2. A compound of claim 1, wherein the acid addition salt is formed with hydrochloric acid, fumaric acid, methanesulfonic acid, or maleic acid.

3. A compound of claim 1, wherein R, R₁, and R₃ each represent a hydrogen atom.

4. A compound of claim 1 or 3, wherein the amidine radical is in the para position of the benzene ring.

5. A compound of claim 1, wherein R₂ represents a hydroxyl, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, t-butyl, neopentyl, hexyl, heptyl, octyl, allyl, α

-methylallyl, prenyl, propargyl, α

-methylpropargyl, cyano, norbornyl, benzyl, cyclopropyl, cyclopropylmethyl, dimethylcyclopropylmethyl, menthyl, cyclohexyl, cyclohexylmethyl, phenyl, p-chlorophenyl, p-methylphenyl, p-methoxyphenyl, methylenedioxyphenyl, or 2-furylmethyl group.

6. The compound of claim 1 which is N-ethyl-N'"'"'-[4-(imidazol-4-yl)-phenyl]-formamidine or a non-toxic, pharmacologically acceptable acid addition salt thereof.

7. The compound of claim 1 which is N-isopropyl-N'"'"'-[4-(imidazol-4-yl)-phenyl]-formamidine or a non-toxic, pharmacologically acceptable acid addition salt thereof.

8. The compound of claim 1 which is N-allyl-N'"'"'-[4-(imidazol-4-yl)-phenyl]-formamidine or a non-toxic, pharmacologically acceptable acid addition salt thereof.

9. The compound of claim 1 which is N-n-propyl-N'"'"'-[4-(imidazol-4-yl)-phenyl]-formamidine or a non-toxic, pharmacologically acceptable acid addition salt thereof.

10. The compound of claim 1 which is N-sec-butyl-N'"'"'-[4-(imidazol-4-yl)-phenyl]-formamidine or a non-toxic, pharmacologically acceptable acid addition salt thereof.

11. The compound of claim 1 which is N-isobutyl-N'"'"'-[4-(imidazol-4-yl)-phenyl]-formamidine or a non-toxic, pharmacologically acceptable acid addition salt thereof.

12. The compound of claim 1 which is N-prenyl-N'"'"'-[4-(imidazol-4-yl)-phenyl]-formamidine or a non-toxic, pharmacologically acceptable acid addition salt thereof.

13. The compound of claim 1 which is N-cyclopropylmethyl-N'"'"'-[4-(imidazol-4-yl)-phenyl]-formamidine or a non-toxic, pharmacologically acceptable acid addition salt thereof.

14. The compound of claim 1 which is N-cyclopropyl-N'"'"'-[4-(imidazol-4-yl)-phenyl]-formamidine or a non-toxic, pharmacologically acceptable acid addition salt thereof.

15. The compound of claim 1 which is N-(α

-methylallyl)-N'"'"'-[4-(imidazol-4-yl)-phenyl]-formamidine or a non-toxic, pharmacologically acceptable acid addition salt thereof.

16. The compound of claim 1 which is N-neopentyl-N'"'"'-[4-(imidazol-4-yl)-phenyl]-formamidine or a non-toxic, pharmacologically acceptable acid addition salt thereof.

17. The compound of claim 1 which is N-(2,2-dimethyl)cyclopropylmethyl-N'"'"'-[4-(imidazol-4-yl)-phenyl]-formamidine or a non-toxic, pharmacologically acceptable acid addition salt thereof.

18. A pharmaceutical composition for the treatment of disorders of the gastrointestinal tract which consists essentially of inert, pharmacologically acceptable carrier and an effective amount of a compound of claim 1.

19. A method for the treatment of disorders of the gastrointestinal tract which comprises perorally, parenterally, rectally, or topically administering to a warm-blooded animal or person in need of such treatment an effective amount of a compound of claim 1.

20. The method of claim 19 which is a method for treating ulcers.