Claims
- 1. A compound of formula (I): ##STR27## wherein: R.sub.1 represents linear or branched (C.sub.1 -C.sub.6)alkyl which is unsubstituted or substituted by amino, (3,5-di-tert-butyl-4-hydroxy)benzylcarbonylamino, (3,5-di-tert-butyl-4-hydroxy)phenylthio or 3-[(3,5-di-tert-butyl-4-hydroxy)phenylthio]propylcarbonylamino,
- R.sub.2 represents linear or branched (C.sub.1 -C.sub.6)alkyl,
- A represents, with the nitrogen and carbon atoms to which it is attached, a 2-azabicyclo[2.2.2]octane, 2-azabicyclo[2.2.1]heptane, perhydroindole, perhydroisoindole, indoline, isoindoline, perhydroquinoline, perhydroisoquinoline, 1,2,3,4-tetra-hydroquinoline, cyclopenta[b]pyrrolidine or 1,3-thiazolidine ring,
- B represents any one of the following radicals: ##STR28## wherein: R.sub.3 represents hydrogen or linear or branched (C.sub.1 -C.sub.6)alkyl which is unsubstituted or substituted by phenyl,
- X, Y, which are different, represent CO or SO.sub.2,
- Z represents
- linear or branched (C.sub.1 -C.sub.6)alkyl which is substituted by one or two, identical or different, (C.sub.3 -C.sub.7)cycloalkyl or (C.sub.1 -C.sub.4)trihaloalkyl,
- adamant-1-yl,
- phenyl which is unsubstituted or substituted by one or a number of, identical or different, halogen or linear or branched (C.sub.1 -C.sub.6)alkyl, hydroxyl, linear or branched (C.sub.1 -C.sub.6)alkoxy, (C.sub.1 C.sub.4)trihaloalkyl, cyano, 1,4-dihydropyrid-4-yl (unsubstituted or substituted by one or a number of, identical or different, linear or branched (C.sub.1 -C.sub.6)alkyl or linear or branched (C.sub.1 -C.sub.6)-alkoxycarbonyl radicals), (3,5-di-tert-butyl-4-hydroxy)benzylcarbonylaminosulfonyl, (3,5-di-tert-butyl-4-hydroxy)benzoyloxy, (3-ethoxy-2-hydroxy)propoxy or [3,5-di-tert-butyl-4-(ethoxymethoxy)]benzyloxy,
- or, (C.sub.1 -C.sub.4)alkenyl substituted by [3,5-di-tert-butyl-4-(ethoxy-methoxy)]phenyl or (3,5-di-tert-butyl-4-hydroxy)phenyl, ##STR29## wherein: R.sub.4 and R.sub.5, which are identical or different, represent: hydrogen or linear or branched (C.sub.1 -C.sub.6)alkyl (unsubstituted or substituted by phenyl), phenyl (unsubstituted or substituted by one or a number of halogen or linear or branched (C.sub.1 -C.sub.6)alkyl, linear or branched (C.sub.1 -C.sub.6)alkoxy or (C.sub.1 -C.sub.4)trihaloalkyl radicals), 3-azabicyclo[3.3.0]oct-3-yl, 4-(2,3,4-trimethoxybenzyl)piperazino, morpholino, pyrrolidino, piperidino, azetidino or 1-oxa-3,8-diaza-2-oxospiro[4.5]dec-8-yl (unsubstituted or substituted by linear or branched (C.sub.1 -C.sub.6)alkyl or linear or branched (C.sub.1 -C.sub.6)phenylalkyl), or
- form, with the nitrogen atom to which they are attached, any one of the following rings:
- 3-azabicyclo[3.3.0]octane,
- 4-(2,3,4-trimethoxybenzyl)piperazine,
- morpholine,
- pyrrolidine,
- azetidine,
- 3,8-diaza-1-oxa-2-oxospiro[4.5]decane which is unsubstituted or substituted by a linear or branched (C.sub.1 -C.sub.6)alkyl or linear or branched (C.sub.1 -C.sub.6)phenylalkyl radical, ##STR30## wherein: R.sub.3 is as defined above and
- R.sub.6 represents hydrogen or halogen or linear or branched (C.sub.1 -C.sub.6)alkyl, linear or branched (C.sub.1 -C.sub.6)alkoxy, (C.sub.1 -C.sub.4)trihaloalkyl or cyano, ##STR31## wherein: R.sub.3 is as defined above,
- T represents any one of the following groups:
- --(CH.sub.2)m--,
- --SO.sub.2 --NH--CO--,
- --CO--NH--SO.sub.2 --, ##STR32## such that m is an integer between 1 and 4, inclusive ##STR33## wherein: X is as defined above,
- n is equal to 0, 1, 2 or 3,
- n' is equal to 0 or 1,
- R.sub.7 represents:
- 3. 5-di-tert-butyl-4-hydroxyphenyl,
- 3,5-di-tert-butyl-4-hydroxyphenoxy,
- or 3,5-di-tert-butyl-4-hydroxyphenylthio, ##STR34## wherein p is equal to 1 or 2, ##STR35## wherein R.sub.3 is as defined above, ##STR36## wherein A is as defined above, which compound of formula (I) comprises the corresponding hydrates of the COCF.sub.3 ketone functional group, its enantiomers, diastereoisomers and epimers, and its addition salts with a pharmaceutically acceptable acid or base.
- 2. The compound of formula (I) as claimed in claim 1, wherein B represents ##STR37## wherein: R.sub.3 represents hydrogen or linear or branched (C.sub.1 -C.sub.6)alkyl which is unsubstituted or substituted by phenyl,
- X, Y, which are different, represent CO or SO.sub.2,
- Z represents
- linear or branched (C.sub.1 -C.sub.6)alkyl which is substituted by one or two, identical or different, (C.sub.3 -C.sub.7)cycloalkyl or (C.sub.1 -C.sub.4)trihaloalkyl,
- adamant-1-yl,
- phenyl which is unsubstituted or substituted by one or a number of, identical or different, halogen or linear or branched (C.sub.1 -C.sub.6)alkyl, hydroxyl, linear or branched (C.sub.1 -C.sub.6)alkoxy, (C.sub.1 -C.sub.4)trihaloalkyl, cyano, 1,4-dihydropyrid-4-yl (unsubstituted or substituted by one or a number of, identical or different, linear or branched (C.sub.1 -C.sub.6)alkyl or linear or branched (C.sub.1 -C.sub.6)alkoxycarbonyl), (3,5-di-tert-butyl-4-hydroxy)benzylcarbonyl-aminosulfonyl, (3,5-di-tert-butyl-4-hydroxy)benzoyloxy, (3-ethoxy-2-hydroxy)propoxy or [3,5-di-tert-butyl-4-(ethoxymethoxy)]benzyloxy,
- or, (C.sub.1 -C.sub.4)alkenyl substituted by [3,5-di-tert-butyl-4-(ethoxymethoxy)]phenyl or (3,5-di-tert-butyl-4-hydroxy)phenyl,
- its hydrates, enantiomers, diastereoisomers and epimers, and its addition salts with a pharmaceutically acceptable acid or base.
- 3. The compound of formula (I) as claimed in claim 1, wherein B represents ##STR38## wherein: R.sub.4 and R.sub.5, which are identical or different, represent: hydrogen or linear or branched (C.sub.1 -C.sub.6)alkyl, phenyl (unsubstituted or substituted by one or a number of halogen or linear or branched (C.sub.1 -C.sub.6)alkyl, linear or branched (C.sub.1 -C.sub.6)alkoxy or (C.sub.1 -C.sub.4)trihaloalkyl), 3-azabicyclo[3.3.0]oct-3-yl, 4-(2,3,4-trimethoxybenzyl)piperazino, morpholino, pyrrolidino, piperidino, azetidino or 1-oxa-3,8-diaza-2-oxospiro[4,5]dec-8-yl (unsubstituted or substituted by linear or branched (C.sub.1 -C.sub.6)alkyl or linear or branched (C.sub.1 -C.sub.6)phenylalkyl radical), or
- form, with the nitrogen atom to which they are attached, any one of the following rings:
- 3-azabicyclo[3.3.0]octane,
- 4-(2,3,4-trimethoxybenzyl)piperazine,
- morpholine,
- pyrrolidine,
- azetidine,
- 3,8-diaza-1-oxa-2-oxospiro[4.5]decane which is unsubstituted or substituted by a linear or ranched (C.sub.1 -C.sub.6)alkyl or linear or branched (C.sub.1 -C.sub.6)phenylalkyl,
- its hydrates, enantiomers, diastereoisomers and epimers, and its addition salts with a pharmaceutically acceptable acid or base.
- 4. The compound of formula (I) as claimed in claim 1, wherein B represents ##STR39## wherein: R.sub.3 is as defined above and
- R.sub.6 represents hydrogen or halogen or linear or branched (C.sub.1 -C.sub.6)alkyl, linear or branched (C.sub.1 -C.sub.6)alkoxy, (C.sub.1 -C.sub.4)trihaloalkyl or cyano,
- its hydrates, enantiomers, diastereoisomers and epimers, and its addition salts with a pharmaceutically acceptable acid or base.
- 5. The compound of formula (I) as claimed in claim 1, wherein B represents: ##STR40## in which: R.sub.3 is as defined above,
- T represents any one of the following groups:
- --(CH.sub.2)m--,
- --SO.sub.2 --NH--CO--,
- --CO--NH--SO.sub.2 --, ##STR41## such that m is an integer between 1 and 4, inclusive its hydrates, enantiomers, diastereoisomers and epimers, and its addition salts with a pharmaceutically acceptable acid or base.
- 6. The compound of formula (I) as claimed in claim 1, wherein B represents: ##STR42## in which: X is as defined above,
- n is equal to 0, 1, 2 or 3,
- n' is equal to 0 or 1,
- R.sub.7 represents:
- 3. 5-di-tert-butyl-4-hydroxyphenyl,
- 3,5-di-tert-butyl-4-hydroxyphenoxy,
- or 3,5-ditert-butyl-4-hydroxyphenylthio
- its hydrates, enantiomers, diastereoisomers and epimers, and its addition salts with a pharmaceutically acceptable acid or base.
- 7. The compound of formula (I) as claimed in claim 1, wherein A represents, with the nitrogen and carbon atoms to which it is attached, a 2-azabicyclo[2.2.2]octane ring, its hydrates, enantiomers, diastereoisomers and epimers, and its addition salts with a pharmaceutically acceptable acid or base.
- 8. The compound of formula (I) as claimed in claim 1, wherein A represents, with the nitrogen and carbon atoms to which it is attached, a perhydroindole ring, its hydrates, enantiomers, diastereoisomers and epimers, and its addition salts with a pharmaceutically acceptable acid or base.
- 9. The compound of formula (I) as claimed in either of claims 7 or 8, wherein B represents 4-chlorobenzoyl-aminosulfonyl, its hydrates, enantiomers, diastereoisomers and epimers, and its addition salts with a pharmaceutically acceptable acid or base.
- 10. The compound of formula (I) as claimed in either of claims 7 or 8, wherein B represents 4-chlorophenylsulfonylaminocarbonyl, its hydrates, enantiomers, diastereoisomers and epimers, and its additional salts with a pharmaceutically acceptable acid or base.
- 11. The compound of formula (I) as claimed in claim 1, which is 4-(4-chlorophenylsulfonylaminocarbonyl)-benzoyl-(S)-Val-(2S,3aS,7aS)-Phi-(R,S)-Val-CF.sub.3, Phi representing a perhydroindole-2-carbonyl residue and Val a valyl residue, its hydrates and isomers, and its addition salts with a pharmaceutically acceptable acid or base.
- 12. The compound of formula (I) as claimed in claim 1, which is 4-(4-chlorophenylsulfonylaminocarbonyl)-benzoyl-(S)-Val-(S)-Abo-(R,S)-Val-CF.sub.3, Abo representing a 2-azabicyclo[2.2.2]octane-3-carbonyl residue and Val a valyl residue, its hydrates and isomers, and its addition salts with a pharmaceutically acceptable acid or base.
- 13. A method for treating a living animal body afflicted with emphysema comprising the step of administering to the living body an amount of a compound of claim 1 which is effective for alleviation of said condition.
- 14. A pharmaceutical composition useful in the treatment of emphysema comprising as active principle an effective amount of a compound as claimed in claim 1, together with one or more pharmaceutically acceptable excipients or vehicles.
- 15. A compound of claim 1 which is selected from 4-[(3,5-di-tert-butyl-4-hydroxybenzyl)carbonylaminosulfonyl]benzoyl-(S)-Val-(2S,3aS,7aS)-Phi(R,S)-Val-CF.sub.3, Phi representing a perhydroindole-2-carbonyl residue and Val a valyl residue, its hydrates and isomers, and its addition salts with a pharmaceutically-acceptable acid or base.
- 16. A compound of claim 1 which is selected from 4-{[4-chloro-3-[(3,5-di-tert-butyl-4-hydroxybenzyl)carbonylaminosulfonyl]benzoyl]aminosulfonyl}benzoyl-(S)-Val-(2S,3aS,7aS)-Phi-(R,S)-Val-CF.sub.3, Phi representing a perhydroindole-2-carbonyl residue and Val a valyl residue, its hydrates and isomers, and its addition salts with a pharmaceutically-acceptable acid or base.
- 17. A compound of claim 1 which is selected from 4-{[4-methoxy-3-(3-ethoxy-2-hydroxypropoxy)benzoyl]aminosulfonyl}benzoyl-(S)-Val-(2S,3aS,7aS)-Phi-(R,S)-Val-CF.sub.3, Phi representing a perhydro-indole-2-carbonyl residue and Val a valyl residue, its hydrates and isomers, and its addition salts with a pharmaceuticallyacceptable acid or base.
- 18. A compound of claim 1 which is selected from 4-[(3,5-di-tert-butyl-4-hydroxyphenylthio)acetylaminosulfonyl]benzoyl-(S)-Val-(2S,3aS,7aS)-Phi-(R,S)-Val-CF.sub.3, Phi representing a perhydro-indole-2-carbonyl residue and Val a valyl residue, its hydrates and isomers, and its addition salts with a pharmaceutically-acceptable acid or base.
- 19. A compound of claim 1 which is selected from 4-[(3,5-di-tert-butyl-4-hydroxybenzoyl)aminosulfonyl]benzoyl-(S)-Val-(2S,3aS,7aS)-Phi-(R,S)-Val-CF.sub.3, Phi representing a perhydro-indole-2-carbonyl residue and Val a valyl residue, its hydrates and isomers, and its addition salts with a pharmaceutically-acceptable acid or base.
Priority Claims (1)
Number |
Date |
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Kind |
92 09254 |
Jul 1992 |
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Parent Case Info
The present application is a continuation of our prior-filed U.S. application Ser. No. 08/099,915, filed Jul. 30, 1993, and now abandoned.
US Referenced Citations (1)
Number |
Name |
Date |
Kind |
4910190 |
Bergeson et al. |
Mar 1990 |
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Non-Patent Literature Citations (5)
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Skiles et al., J. Med. Chem., vol. 35 pp. 641-662 (1992). |
Trainor, Tips, vol. 8 pp. 303-307 (1987). |
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Continuations (1)
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99915 |
Jul 1993 |
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