Claims
- 1. A compound of the formula III or a pharmaceutically acceptable salt thereof ##STR156## wherein n=1-3;
- R.sub.1 and R.sub.2 are independently .dbd.CH.sub.3 ; --(CH.sub.2).sub.m, where m=4-8, --CH.sub.2 CH(OH)(CH.sub.2).sub.2 --; --CH.sub.2 CH(F)(CH.sub.2).sub.2 --;
- --(CH.sub.2).sub.2 O(CH.sub.2).sub.2 --; or --(CH.sub.2).sub.2 CH.dbd.CHCH.sub.2 --;
- Ar=unsubstituted or mono-, or di-substituted phenyl wherein said substituents are selected from the group consisting of halogen, OCH.sub.3, SO.sub.2 CH.sub.3, CF.sub.3, amino, alkyl, and 3,4-dichloro; benzothiophenyl; benzofuranyl; naphthyl; diphenyl methyl; or 9-fluorene; or Ar=heteroaromatic groups having 1-3 heteroatoms selected from the group consisting N, O and S and bearing 1-4 substituents selected from the group consisting of chlorobenzoyl, Br, Cl, F, alkyl, alkoxy, carboxy, carboxamided, amine, amide and sulfonamide;
- X.sub.7 is
- --NHSO.sub.2 CH.sub.3 ; --NHP(O)(OBn).sub.2 ; --NHP(O)(OH).sub.2 ; --(CH.sub.2).sub.u NHSO.sub.2 CH.sub.3 ; --(CH.sub.2).sub.u NHC(S)NHCH(CO.sub.2 H)(CH.sub.2).sub.u CO.sub.2 H; --CONHOH; or --(CH.sub.2).sub.u CONHOH;
- wherein
- u=1-5;
- or X.sub.7 is ##STR157## R.sub.6 =--H or -Ac; X.sub.8 =--CO.sub.2 H; --NHSO.sub.2 CH.sub.3 ; --NHP(O)(OBn).sub.2 ;
- --NHP(O)(OH).sub.2 ; --OP(O)(OBn).sub.2 ; or
- --OP(O)(OH).sub.2 ;
- R.sub.7 =--NH(CH.sub.2).sub.v CO.sub.2 H; --NH(CH.sub.2).sub.v CH(NH.sub.2)(CO.sub.2 H);
- --NHCH(CO.sub.2 H)(CH.sub.2).sub.v NH.sub.2 ; --NH(CH.sub.2).sub.v SO.sub.3 H;
- --NH(CH.sub.2).sub.v PO.sub.3 H.sub.2 ; --NH(CH.sub.2).sub.v NHC(NH)NH.sub.2 ; or
- --NHCH(CO.sub.2 H)(CH.sub.2).sub.v CO.sub.2 H; and
- v=1-20.
- 2. The compound according to claim 1 selected from the group consisting of: 2-(3,4-dichlorophenyl)-N-methyl-N-{1-�3-(N-2-acetic acid)carboxamido!phenyl-2-(1-pyrrolidinyl)ethyl}acetamide; 2-(3,4-dichlorophenyl)-N-methyl-N-{1-�3-(N-methanesulfonamido)aminomethyl!phenyl-2-(1-pyrrolidinyl)ethyl}acetamide; 2-(3,4-dichlorophenyl)-N-methyl-N-{1-�3-(N-succinic acid-2S-thioureido)aminomethyl!phenyl-2-(1-pyrrolidinyl)ethyl}acetamide; and 2-(3,4-dichlorophenyl)-N-methyl-N-{1-�3-(N-2-acetic acid)sulfonamido!phenyl-2-(1-pyrrolidinyl)ethyl}acetamide.
- 3. The compound according to claim 1 selected from the group consisting of:
- 2-(3,4-Dichlorophenyl)-N-methyl-N-{�1S!-1-�N-(S-aspartic acid-a-amide-S-aspartic acid-a-amido)-3-aminophenyl!-2-�1-pyrrolidinyl!ethyl}acetamide;
- 2-(3,4-Dichlorophenyl)-N-methyl-N-{�1S!-1-�N-(bis-methylsulfonamido)-3-aminophenyl!-2-!1-pyrrolidinyl!ethyl}acetamide;
- 2-(2-Nitrophenyl)-N-methyl-N-�(1S)-1-(3-nitrophenyl)-2-(1-pyrrolidinyl)ethyl!acetamide;
- 2-(2-Aminophenyl)-N-methyl-N-�(1S)-1-(3-aminophenyl)-2-(1-pyrrolidinyl)ethyl!acetamide;
- 2-(N-Diethyl phosphoramidate-2-aminophenyl)-N-methyl-N-�(1S)-1-(N-diethyl phosphoramidate-3-aminophenyl)-2-(1-pyrrolidinyl)ethyl!acetamide;
- 2-(N-Bis-sulfonamido-2-aminophenyl)-N-methyl-N-�(1S)-1-(N-bis-sulfonamido-3-aminophenyl)-2-(1-pyrrolidinyl)ethyl!acetamide;
- 2-(2-Nitro-4,5-dichlorophenyl)-N-methyl-N-�(1S)-1-(3-nitrophenyl)-2-(1-pyrrolidinyl)ethyl!acetamide;
- 2-(4-Methylsulfonylphenyl)-N-methyl-N-�(1S)-1-(3-nitrophenyl)-2-(1-pyrrolidinyl)ethyl!acetamide;
- 2-(N-Butyloxycarbonyl-4-aminophenyl)-N-methyl-N-�(1S)-1-(3-nitrophenyl)-2-(1-pyrrolidinyl)ethyl!acetamide;
- 2-(4-Aminophenyl)-N-methyl-N-�(1S)-1-(3-nitrophenyl)-2-(1-pyrrolidinyl)ethyl!acetamide;
- 2-(N-Bis-sulfonamido-4-aminophenyl)-N-methyl-N-�(1S)-1-(3-nitrophenyl)-2-(1-pyrrolidinyl)ethyl!acetamide;
- 2-(N-B is-sulfonamido-4-aminophenyl)-N-methyl-N-�(1S)-1-(3-aminophenyl)-2-(1-pyrrolidinyl)ethyl!acetamide;
- 2-(N-Bis-sulfonamido-4-aminophenyl)-N-methyl-N-�(1S)-1-(N-diethyl phosphoramidate-3-aminophenyl)-2-(1-pyrrolidinyl)ethyl!acetamide;
- 2-(2-Nitrophenyl)-N-methyl-N-{�1S!-1-phenyl-2-�1-(3S)-(3-hydroxypyrrolidinyl)!ethyl}acetamide;
- 2-(2-Nitro-4,5 -dichlorophenyl)-N-methyl-N-{�1S!-1-phenyl-2-�1-(3S)-(3-hydroxypyrrolidinyl)!ethyl}acetamide;
- 2-(4-Methylsulfonylphenyl)-N-methyl-N-{�1S!-1-phenyl-2-�1-(3S)-(3-hydroxypyrrolidinyl)!ethyl}acetamide;
- 2-(2-Nitro-4-trifluoromethylphenyl)-N-methyl-N-{�1S!-1-phenyl-2-�1-(3S)-(3-hydroxypyrrolidinyl)!ethyl}acetamide;
- 2-(2-Amino-4-trifluoromethylphenyl)-N-methyl-N-{�1S!-1-phenyl-2-�1-(3S)-(3-hydroxypyrrolidinyl)!ethyl}acetamide;
- 2,2-Diphenyl-N-methyl-N-�(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl!acetamide;
- N',N'-Diphenyl-N-methyl-N-�(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl!urea;
- 2-(2-Nitrophenyl)-N-methyl-N-�(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl!acetamide;
- 2-(2-Nitro-4,5-dichlorophenyl)-N-methyl-N-�(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl!acetamide;
- 2-(4-Methylsulfonylphenyl)-N-methyl-N-�(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl!acetamide;
- 2-(2-Methoxyphenyl)-N-methyl-N-�(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl!acetamide;
- 2-(3-Indolyl)-N-methyl-N-�(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl!acetamide;
- 2-(.alpha.,.alpha.,.alpha.-Trifluoro-p-tolyl)-N-methyl-N-�(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl!acetamide;
- 2-(2-Nitro-.alpha.,.alpha.,.alpha.-Trifluro-4-tolyl)-N-methyl-N-�(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl!acetamide;
- 2-(1-�4-Chlorobenzoyl)-5-methoxy-2-methyl indole)-N-�(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl!acetamide;
- 2-(4-Nitrophenyl)-N-methyl-N-�(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl!acetamide;
- 2-(3-Nitrophenyl)-N-methyl-N-�(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl!acetamide;
- 2-(2-Pyridyl)-N-methyl-N-�(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl!acetamide;
- 2-(3-Pyridyl)-N-methyl-N-�(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl!acetamide;
- 2-((+)-6-Methoxy-a-methyl-2-napthalene)-N-�(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl!acetamide;
- 2-(.alpha.,.alpha.,.alpha.-Trifluoro-3-tolyl)-N-methyl-N-�(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl!acetamide;
- 2-(4-Pyridyl)-N-methyl-N-�(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl!acetamide;
- 2-(.alpha.,.alpha.,.alpha.-Trifluoro-2-tolyl)-N-methyl-N-�(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl!acetamide;
- 2-((S)-(+)-4-Isobutyl-a-methylphenyl)-N-methyl-N-�(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl!acetamide;
- 2-(3,4,5-Trimethoxyphenyl)-N-methyl-N-�(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl!acetamide;
- 2-(2-Aminophenyl)-N-methyl-N-�(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl!acetamide;
- 2-(2-N,N-Dimethylsulfonamido-2-aminophenyl)-N-methyl-N-�(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl!acetamide;
- 2-(N-Methylsulfonamido-2-aminophenyl)-N-methyl-N-�(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl!acetamide;
- 2-(2-Amino4,5-dichlorophenyl)-N-methyl-N-�(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl!acetamide;
- 2-(N,N-Dimethysulfonamido-2-amino-4,5-dichlorophenyl)-N-methyl-N-�(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl!acetamide;
- 2-(2-Amino,.alpha.,.alpha.,.alpha.-Trifluoro-4-toly)-N-methyl-N-�(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl!acetamide;
- 2-(2-N,N-Dimethylsulfonamido-2-amino-.alpha.,.alpha.,.alpha.-trifluoro-4-tolyl)-N-methyl-N-�(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl!acetamide;
- 2-(N-Methylsulfonamido-2-amino-.alpha.,.alpha.,.alpha.-trifluro-4-tolyl)-N-methyl-N-�(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl!acetamide;
- 2-(2-Aminophenyl)-N-methyl-N-�(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl!acetamide;
- 2-(4-Aminophenyl)-N-methyl-N-�(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl!acetamide;
- 2-(N,N-Dimethylsulfonamido-2-aminophenyl)-N-methyl-N-�(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl!acetamide;
- 2-(N,N-Dimethylsulfonamido-2-aminophenyl)-N-methyl-N-�(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl!acetamide;
- 2-(2-Hydroxyphenyl)-N-methyl-N-methyl-N-�(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl!acetamide; and
- N-Methyl-N-�(1S)-1-phenyl-2-((3S)-3-hydroxypyrrolidine-1-yl)ethyl!-3,4,5-trimethoxyphenylacetamide.
- 4. A pharmaceutical composition comprising a compound of claim 1 in a pharmaceutically acceptable carrier.
- 5. A pharmaceutical composition comprising a compound of claim 2 in a pharmaceutically acceptable carrier.
- 6. A pharmaceutical composition comprising a compound of claim 3 in a pharmaceutically acceptable carrier.
- 7. A method of treating hyperalgesia in a patient comprising administering to said patient an effective amount of a compound of claim 1.
- 8. A method of treating hyperalgesia in a patient comprising administering to said patient an effective amount of a compound of claim 2.
- 9. A method of treating hyperalgesia in a patient comprising administering to said patient an effective amount of a compound of claim 3.
- 10. A method of treating hyperalgesia in a patient comprising administering to said patient an effective amount of the pharmaceutical composition of claim 4.
- 11. A method of treating hyperalgesia in a patient comprising administering to said patient an effective amount of the pharmaceutical composition of claim 5.
- 12. A method of treating hyperalgesia in a patient comprising administering to said patient an effective amount of the pharmaceutical composition of claim 6.
- 13. A pharmaceutical composition comprising a compound of claim 1 and an antibiotic, antiviral, antifungal, anti-inflammatory agent or a mixture thereof in a pharmaceutically acceptable carrier.
- 14. A pharmaceutical composition comprising a compound of claim 2 and an antibiotic, antiviral, antifungal, anti-inflammatory agent or a mixture thereof in a pharmaceutically acceptable carrier.
- 15. A pharmaceutical composition comprising a compound of claim 3 and an antibiotic, antiviral, antifungal, anti-inflammatory agent or a mixture thereof in a pharmaceutically acceptable carrier.
Parent Case Info
This application is a continuation-in-part of application Ser. No. 08/612,680, filed on Mar. 8, 1996.
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Continuation in Parts (1)
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Number |
Date |
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Parent |
612680 |
Mar 1996 |
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