Claims
- 1. A compound, or a solvate or salt thereof, of formula (I): ##STR18## in which, R.sub.1 is hydrogen, linear or branched C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkenyl, C.sub.4-6 cycloalkylalkyl, C.sub.3-5 alkenyl, aryl, aralkyl or furan-2 or 3-yl alkyl or (CH.sub.2).sub.m COR wherein m is 1 to 5 and R represents hydroxy, OC.sub.1-5 alkyl, OC.sub.3-6 alkenyl, aryl or aralkyl or R.sub.1 is a group A-B wherein A represents C.sub.1-10 alkylene and B represents substituted or unsubstituted aryl or heteroaryl;
- R.sub.2 is hydrogen, hydroxy or C.sub.1-5 alkoxy, halogen, nitro, NR.sub.7 R.sub.8, SR.sub.7, where R.sub.7 and R.sub.8, which may be the same or different, are each hydrogen, linear or branched C.sub.1-6 alkyl, aryl, aralkyl, or COR.sub.1 ;
- R.sub.3 and R.sub.4, which can be the same or different, are each hydrogen, hydroxy, C.sub.1-3 alkoxy, haloalkyl, halogen, SH, C.sub.1-4 -alkylthio, NHR.sub.7, NR.sub.7 R.sub.8, NHCOR.sub.7, NHSO.sub.2 R.sub.7, wherein R.sub.7 and R.sub.8 have the same meaning described above;
- R.sub.5 and R.sub.6 which may be the same or different are hydrogen or a group ##STR19## in which n is 0 or 1 and when n=1, Z is CHR.sub.14, oxygen, sulphur, NR.sub.14, where R.sub.14 has the same meaning described below, or ethylene, ethenylene, ethynylene, provided that R.sub.5 and R.sub.6 are not simultaneously hydrogen;
- R.sub.9 is hydrogen, hydroxy, C.sub.1-5 alkoxy, halogen, SR.sub.11, nitro, cyano, NHR.sub.11, NR.sub.11 R.sub.12, NHCOR.sub.11, NHSO.sub.2 R.sub.11, where R.sub.11 and R.sub.12, which may be the same or different, are each hydrogen or C.sub.1-6 alkyl, where p is 1-3;
- R.sub.10 is hydrogen, cyano or is a group C(T)R.sub.13, in which T is oxygen or sulphur, R.sub.13 is C.sub.1-18 alkyl, C.sub.1-18 alkoxy or NR.sub.14 R.sub.15, where R.sub.14 and R.sub.15, which may be the same or different, are hydrogen, linear or branched C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, C.sub.4-6 cycloalkylalkyl, C.sub.3-6 alkenyl, aryl, aralkyl or an optionally substituted heterocyclic ring or may form together a C.sub.3-6 alkyl ring which may be interrupted by an oxygen or a NR.sub.14 in which R.sub.14 has the same meaning described above;
- X and Y, which may be the same or different, are each hydrogen, hydroxy, C.sub.1-5 alkoxy, COR.sub.1 or together may form a double bond, or;
- X or Y may form together with R.sub.5 and R.sub.6 respectively, an exocyclic double bond, forming a group ##STR20## where R.sub.9, R.sub.10 and R.sub.14 have the same meaning described above, or may form an exocyclic double bond, forming a group ##STR21## where R.sub.10 and R.sub.14 have the same meaning described above, with the proviso that when R.sub.10 is hydrogen, R.sub.14 is not hydrogen or methyl, or;
- X forms together with R.sub.5 a C.dbd.O group with the proviso that Y and/or R.sub.6 may not be hydrogen, hydroxy, lower alkyl or lower alkoxy, or;
- Y forms together with R.sub.6 a C.dbd.O group with the proviso that X and/or R.sub.5 may not be hydrogen, hydroxy, lower alkyl or lower alkoxy, and;
- Q and W which may be the same or different, are each hydrogen or form a double bond with Y and X respectively.
- 2. A compound according to claim 1 in which R.sub.1 is methyl, ethyl, phenyl or phenyl-C.sub.1-6 alkyl.
- 3. A compound according to claim 1 in which R.sub.2 is hydrogen, and R.sub.3 and R.sub.4 are each independently hydrogen, hydroxy or methoxy.
- 4. A compound according to claim 1 in which R.sub.9 is hydrogen or bromine, and R.sub.10 is hydrogen.
- 5. A compound according to claim 1 in which W and Q are each hydrogen.
- 6. A compound selected from:
- (.+-.)-trans-1,2,3,4,4a,5,6,7,8,8a-Decahydro-4a-(3-methoxyphenyl)-2-methyl-6-phenyl-6-isoquinolinol;
- (.+-.)-trans-4a-(3-Methoxyphenyl)-2-methyl-6-phenyl-1,2,3,4,4a,5,8,8a-octahydroisoquinoline;
- (.+-.)-trans-4a-(3-Hydroxyphenyl)-2-methyl-6-phenyl-1 ,2,3,4,4a,5,8,8a-octahydroisoquinoline;
- (.+-.)-trans-7-Benzylidene-1 ,2,3,4,4a,5,6,7,8,8a-decahydro-4a-(3-methoxyphenyl)-2-methyl-6-isoquinolinone;
- (.+-.)-trans-7-Benzylidene-1 ,2,3,4,4a,5,6,7,8,8a-decahydro-4a-(3-hydroxyphenyl)-2-methyl-6-isoquinolinone hydrochloride;
- (.+-.)-trans-1,2,3,4,4a,5,6,7,8,8a-Decahydro-2-methyl-4a-(3-methoxyphenyl)-6-phenylamino isoquinoline;
- (.+-.)-trans-1,2,3,4,4a,5,6,7,8,8a-Decahydro-4a-(3-hydroxyphenyl)-2-methyl-6-phenylamino isoquinoline;
- (.+-.)-trans-6-(3-Bromophenyl)-1 ,2,3,4,4a,5,6,7,8,8a-decahydro-2-ethyl-4a-(3-methoxyphenyl)-6-isoquinolinol;
- (.+-.)-trans-6-(3-Bromophenyl)-2-ethyl-4a-(3-methoxyphenyl)-1,2,3,4,4a,5,8,8a-octahydroisoquinoline;
- (.+-.)-trans-6-(3-Bromophenyl)-2-ethyl-4a-(3-hydroxyphenyl)-1,2,3,4,4a,5,8,8a-octahydroisoquinoline;
- (.+-.)-trans-1,2,3,4,4a,5,6,7,8,8a-Decahydro-2-ethyl-4a-(3-methoxyphenyl)-6-phenyl-6-isoquinolinol:
- (.+-.)-trans-2-Ethyl-4a-(3-methoxyphenyl)-6-phenyl-1,2,3,4,4a,5,8,8a-octahydroisoquinoline;
- (.+-.)-trans-2-Ethyl-4a-(3-hydroxyphenyl)-6-phenyl-1,2,3,4,4a,5,8,8a-octahydroisoquinoline;
- (.+-.)-trans-6-Benzylidene-1,2,3,4,4a,5,6,7,8,8a-decahydro-2-ethyl-4a-(3-methoxyphenyl)isoquinoline;
- (.+-.)-trans-6-Benzyl-2-ethyl-4a-(3-hydroxyphenyl)-1,2,3,4,4a,5,8,8a-octahydroisoquinoline;
- (.+-.)-trans-2-Ethyl-1,2,3,4,4a,5,6,7,8,8a-decahydro-4a-(3-methoxyphenyl)-6-phehylethynyl-6-isoquinolinol;
- (.+-.)-trans-2-Ethyl-4a-(3-methoxyphenyl)-1,2,3,4,4a,7,8,8a-octahydro-6-phenylethynylisoquinoline hydrochloride, and;
- (.+-.)-trans-2-Ethyl-4a-(3-methoxyphenyl)-1,2,3,4,4a,5,8,8a-octahydro-6-phenylethynylisoquinoline hydrochloride.
- 7. A method for treating a pathological condition mediated by a delta opioid receptor, which comprises administering a compound according to claim 1.
- 8. A method according to claim 7 for the treatment or prophylaxis of pain, allergy or inflammation, brain cell degeneration, drug or alcohol abuse, gastritis, diarrhoea, cardiovascular or respiratory diseases, cough, mental illness, or neurological disorders, which comprises administering a compound according to claim 1.
- 9. A method for treating organ transplant or skin graft rejection which comprises administering a compound according to claim 1.
- 10. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier.
Priority Claims (1)
Number |
Date |
Country |
Kind |
MI95A1900 |
Sep 1995 |
ITX |
|
Parent Case Info
This application is a 371 of PCT/EP96/04036, filed Sep. 12, 1996.
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
102e Date |
371c Date |
PCT/EP96/04036 |
9/12/1996 |
|
|
5/29/1998 |
5/29/1998 |
Publishing Document |
Publishing Date |
Country |
Kind |
WO97/10216 |
3/20/1997 |
|
|
US Referenced Citations (2)
Foreign Referenced Citations (1)
Number |
Date |
Country |
2193600 |
Jan 1974 |
FRX |
Non-Patent Literature Citations (1)
Entry |
Judd et al., Journal of Medicinal Chemistry, 35(1), pp. 48-56 (1992). |