Claims
- 1. A compound of the formula ##STR21## wherein R represents hydrogen, lower alkyl, halogen or lower alkoxy; R.sub.1 and R.sub.2 independently represent hydrogen, lower alkyl or aryl; Y represents a direct bond, lower aklylene, lower alkenylene, lower alkadienylene, (thio, sulfinyl or sulfonyl)-lower alkylene or oxy-lower alkylene; Z represents ##STR22## wherein R.sub.3 represents hydrogen or acyl; R.sub.4 represents lower alkyl, C.sub.3 -C.sub.7 -cycloalkyl, aryl or aryl-lower alkyl; or Z represents ##STR23## wherein R.sub.3 represents hydrogen or acyl; R.sub.5 represents lower alkyl, C.sub.3 -C.sub.7 -cycloalkyl, aryl, aryl-lower alkyl, amino or N-(mono- or di-lower alkyl)-amino; R.sub.6 and R.sub.7 represent hydrogen or lower alkyl; aryl in the above definitions represents phenyl of phenyl mono- or di-substituted by one or two radicals selected from lower alkyl, lower alkoxy, halogen, cyano and trifluoromethyl, or 1- 2-naphthyl; acyl represents lower alkanoyl or aroyl; and aroyl represents benzoyl or benzoyl mono- or di-substituted by one or two radicals selected from lower alkyl, lower alkoxy, halogen, cyano and trifluoromethyl, or 1- or 2-naphthoyl; or a pharmaceutically acceptable salt thereof provided that R.sub.3 represents hydrogen.
- 2. A compound according to claim 1 of the formula ##STR24## wherein R represents hydrogen, lower alkyl, halogen or lower alkoxy; R.sub.1 and R.sub.2 independently represent hydrogen, lower alkyl or aryl; R.sub.3 represents hydrogen or acyl; R.sub.4 represents lower alkyl, C.sub.3 -C.sub.7 -cycloalkyl, aryl or aryl-lower alkyl; Y represents a direct bond, lower alkylene, lower alkenylene, lower alkadienylene, (thio, sulfinyl or sulfonyl)-lower alkylene or oxy-lower alkylene; or a pharmaceutically acceptable salt of a said compound provided that wherein R.sub.3 represents hydrogen.
- 3. A compound according to claim 1 of the formula ##STR25## wherein R represents hydrogen, lower alkyl, halogen or lower alkoxy; R.sub.1 and R.sub.2 independently represent hydrogen, lower alkyl or aryl; Y represents a direct bond, lower alkylene, lower alkenylene, lower alkadienylene, (thio, sulfinyl or sulfonyl)-lower alkylene or oxy-lower alkylene; R.sub.3 represents hydrogen or acyl; R.sub.5 represents lower alkyl, C.sub.3 -C.sub.7 -cycloalkyl, aryl, aryl-lower alkyl, amino or N-(mono- or di-lower alkyl)-amino; R.sub.6 and R.sub.7 represent hydrogen or lower alkyl; or a pharmaceutically acceptable salt of a said compound provided that R.sub.3 represents hydrogen.
- 4. A compound according to claim 2 wherein Y is located meta or para to the pyrrolyl ring.
- 5. A compound according to claim 3 wherein Y is located meta or para to the pyrrolyl ring.
- 6. A compound according to claim 4 of formula II wherein Y represents lower alkenylene, lower alkadienylene, lower alkylene, thio-lower alkylene or oxy-lower alkylene; R represents hydrogen or halogen; R.sub.1 and R.sub.2 independently represent hydrogen or lower alkyl; R.sub.3 represents hydrogen or acyl; R.sub.4 represents lower alkyl; or a pharmaceutically acceptable salt of a said compound provided that R.sub.3 represents hydrogen.
- 7. A compound according to claim 4 of formula II wherein Y represents lower alkenylene, lower alkylene or oxy-lower alkylene; R represents hydrogen; R.sub.1 and R.sub.2 represent hydrogen or lower alkyl; R.sub.3 represents hydrogen, lower alkanoyl or aroyl; R.sub.4 represents lower alkyl; or a pharmaceutically acceptable salt thereof provided that R.sub.3 represents hydrogen.
- 8. A compound according to claim 7 of formula II wherein Y represents lower alkenylene; or a pharmaceutically acceptable salt thereof provided that R.sub.3 represents hydrogen.
- 9. A compound according to claim 8 of the formula ##STR26## wherein R.sub.1, R.sub.2 and R.sub.8 and R.sub.9 independently represent hydrogen, methyl or ethyl; R.sub.4 represents C.sub.1 -C.sub.3 -alkyl; R.sub.3 represents hydrogen; or a pharmaceutically acceptable salt thereof.
- 10. A compound according to claim 9 of the formula ##STR27## wherein R.sub.1, R.sub.2 and R.sub.8 and R.sub.9 independently represent hydrogen, methyl or ethyl; R.sub.4 represents C.sub.1 -C.sub.3 -alkyl; R.sub.3 represents hydrogen; or a pharmaceutically acceptable salt thereof.
- 11. A compound according to claim 10 of formula IV wherein R.sub.1, R.sub.2 and R.sub.4 represent methyl or ethyl; R.sub.3, R.sub.8 and R.sub.9 represent hydrogen; or a pharmaceutically acceptable salt thereof.
- 12. A compound according to claim 10 being (E)-3-[4-(2,5-dimethyl-1H-pyrrol-1-yl)-phenyl]-N-hydroxy-N-methyl-2-propenamide or a pharmaceutically acceptable salt thereof.
- 13. A compound according to claim 5 of formula V wherein Y represents a direct bond, thio-lower alkylene, oxy-lower alkylene, lower alkenylene or lower alkylene; R represents hydrogen; R.sub.1 and R.sub.2 independently represent hydrogen or lower alkyl; R.sub.3 represents hydrogen, lower alkanoyl or aroyl; R.sub.5 represents lower alkyl, aryl-lower alkyl, N-(mono- or di-lower alkyl)-amino or amino; R.sub.6 represents hydrogen; R.sub.7 represents hydrogen or lower alkyl; or a pharmaceutically acceptable salt thereof provided that R.sub.3 represents hydrogen.
- 14. A compound according to claim 13 wherein Y represents a direct bond, lower alkylene or lower alkenylene.
- 15. A compound according to claim 13 of the formula ##STR28## wherein R.sub.1 and R.sub.2 represents hydrogen or lower alkyl; Y represents a direct bond, methylene or ethylene; R.sub.3 represents hydrogen; R.sub.5 represents C.sub.1 -C.sub.3 -alkyl, N-(mono- or di-lower alkyl)-amino or amino; R.sub.7 represents hydrogen or C.sub.1 -C.sub.3 -alkyl; or a pharmaceutically acceptable salt thereof.
- 16. A compound according to claim 13 of formula VII ##STR29## wherein R.sub.1, R.sub.2, R.sub.7, R.sub.8 and R.sub.9 represent hydrogen, methyl or ethyl; R.sub.3 represents hydrogen; R.sub.5 represents C.sub.1 -C.sub.3 -alkyl, N-(mono- or di-lower alkyl)-amino or amino; or a pharmaceutically acceptable salt thereof.
- 17. A compound according to claim 15 being N-acetyl-N-hydroxy-1-[4-(2,5-dimethyl-1H-pyrrol-1-yl)-phenyl]-ethyl-amine or a pharmaceutically acceptable salt thereof.
- 18. A compound according to claim 13 being N-carba-moyl-N-hydroxy-4-(2,5-dimethyl-1H-pyrrol-1-yl)-cinnamyl-amine or a pharmaceutically acceptable salt thereof.
- 19. A compound according to claim 8 being (E)-3-[4-(2,5-dimethyl-1H-pyrrol-1-yl)-phenyl]-N-acetoxy-N-methyl-2-propenamide.
- 20. A pharmaceutical composition suitable for inhibiting 5-lipoxygenase activity in mammals comprising an effective 5-lipoxygenase inhibiting amount of a compound of claim 1 in combination with one or more pharmaceutically acceptable carriers.
- 21. A method of inhibiting lipoxygenase activity and of treating disorders in mammals which are responsive to such inhibition which comprises administering to a mammal in need thereof an effective lipoxygenase inhibiting amount of a compound of claim 1 or of a said compound in combination with one or more pharmaceutically acceptable carriers.
- 22. A method of inhibiting lipoxygenase activity and of treating disorders in mammals which are responsive to such inhibition which comprises administering to a mammal in need thereof an effective lipoxygenase inhibiting amount of a compound of claim 12 or of a said compound in combination with one or more pharmaceutically acceptable carriers.
CROSS REFERENCE TO RELATED APPLICATIONS
This is a continuation-in-part of application Ser. No. 293,908 filed Jan. 5, 1989 now abandoned.
The invention relates to the pyrrolylphenyl-substituted hydroxamic acid derivatives as defined herein which are particularly useful as selective lipoxygenase inhibitors, methods for preparation thereof, pharmaceutical compositions comprising said compounds, and a method of inhibiting lipoxygenase and of treating diseases in mammals which are responsive to lipoxygenase inhibition using said compounds or pharmaceutical compositions comprising said compounds of the invention.
The compounds of the invention are particularly useful for the treatment of various inflammatory and allergic conditions, e.g. bronchial allergies and inflammatory disorders such as asthma, ocular allergies and inflammation, and dermatological allergies and inflammation such as psoriasis; also for the treatment of rheumatic disorders such as rheumatoid arthritis; and also for the treatment of ischemic conditions such as myocardial infarction and cerebral ischemia.
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Continuation in Parts (1)
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Number |
Date |
Country |
| Parent |
293908 |
Jan 1989 |
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Patent Grant
5096919
