Claims
- 1. A composition for treating pain comprising an analgesic dose of a First Compound selected from the group consisting of: ##STR40## wherein W is oxygen or sulphur;
- R is hydrogen, amino, halogen, NHR.sup.6, NR.sup.6 R.sup.7, R.sup.4, --OR.sup.4, --SR.sup.4, --SOR.sup.4, --SO.sub.2 R.sup.4, C.sub.3-10 -cycloalkyl, C.sub.4-12 -(cycloalkylalkyl), --Z--C.sub.3-10 -cycloalkyl and --Z--C.sub.4-12 -(cycloalkylalkyl) wherein
- R.sup.4 is C.sub.1-15 -alkyl, C.sub.2-15 -alkenyl, C.sub.2-15 -alkynyl, each of which is optionally substituted with one or more halogen(s), --CF.sub.3, --CN, Y, phenyl or phenoxy wherein phenyl or phenoxy is optionally substituted with halogen, --CN, C.sub.1-4 -alkyl, C.sub.1-4 -alkoxy, --OCF.sub.3, --CF.sub.3, --CONH.sub.2 or --CSNH.sub.2 ; or
- R is phenyl or benzyloxycarbonyl, each of which is optionally substituted with halogen, --CN, C.sub.1-4 -alkyl, C.sub.1-4 -alkoxy, --OCF.sub.3, --CF.sub.3, --CONH.sub.2 or --CSNH.sub.2 ; or
- R is --OR.sup.5 Y, --SR.sup.5 Y, OR.sup.5 --Z--Y, --SR.sup.5 ZY, --O--R.sup.5 --Z--R.sup.4 or --S--R.sup.5 --Z--R.sup.4 wherein Z is oxygen or sulphur, R.sup.5 is C.sub.1-15 -alkyl, C.sub.2-15 -alkenyl, C.sub.2-15 -alkynyl, and Y is a 5 or 6 membered heterocyclic group; and
- G is selected from one of the following azacyclic or azabicyclic ring systems: ##STR41## or G can optionally be substituted C.sub.3 -C.sub.8 cycloalkyl or optionally substituted C.sub.1-6 -alkyl wherein the substitution is --NR.sup.6 R.sup.7 ;
- R.sup.6 and R.sup.7 independently are hydrogen, C.sub.1-6 -alkyl; or
- R.sup.6 and R.sup.7 together with the nitrogen atom optionally form a 4- to 6-member ring;
- R.sup.1 and R.sup.2 independently are hydrogen, C.sub.1-15 -alkyl, C.sub.2-5 -alkenyl, C.sub.2-5 -alkynyl, C.sub.1-10 -alkoxy, C.sub.1-5 -alkyl substituted with --OH, --COR.sup.6', CH.sub.2 --OH, halogen, --NH.sub.2, carboxy, or phenyl;
- R.sup.3 is hydrogen, C.sub.1-5 -alkyl, C.sub.2-5 -alkenyl or C.sub.2-5 -alkynyl;
- R.sup.6' is hydrogen, C.sub.1-6 -alkyl;
- n is 0, 1 or 2;
- m is 0, 1 or 2;
- p is 0, 1 or 2;
- q is 1 or 2;
- r is 0, 1 or 2;
- ....... is a single or double bond; and ##STR42## wherein W' is oxygen or sulfur;
- R' is hydrogen, amino, halogen, NHR.sup.6', NR.sup.6' R.sup.7', R.sup.4', --OR.sup.4', --SR.sup.4', --SOR.sup.4', --SO.sub.2 R.sup.4', C.sub.3-10 -cycloalkyl, C.sub.4-12 -(cycloalkylalkyl), --Z'--C.sub.3-10 -cycloalkyl and --Z'--C.sub.4-12 -(cycloalkylalkyl) wherein R.sup.4' is C.sub.1-15 -alkyl, C.sub.2-15 -alkenyl, C.sub.2-15 -alkynyl, each of which is optionally substituted with one or more halogen(s), --CF.sub.3, --CN, Y', phenyl or phenoxy wherein phenyl or phenoxy is optionally substituted with halogen, --CN, C.sub.1-4 -alkyl, C.sub.1-4 -alkoxy, --OCF.sub.3, --CF.sub.3, --CONH.sub.2 or --CSNH.sub.2 ; or
- R' is phenyl or benzyloxycarbonyl, each of which is optionally substituted with halogen, --CN, C.sub.1-4 -alkyl, C.sub.1-4 -alkoxy, --OCF.sub.3, --CF.sub.3, --CONH.sub.2 or --CSNH.sub.2 ; or
- R' is --OR.sup.5' Y', --SR.sup.5' Y', OR.sup.5' --Z'--Y', --SR.sup.5' Z'Y', --O--R.sup.5' --Z--R.sup.4' or --S--R.sup.5' --Z'--R.sup.4' wherein Z' is oxygen or sulphur, R.sup.5' is C.sub.1-15 -alkyl, C.sub.2-15 -alkenyl, C.sub.2-15 -alkynyl, and Y' is a 5 or 6 membered heterocyclic group; and
- G' is selected from one of the following azacyclic or azabicyclic ring systems: ##STR43## or G' can optionally be substituted C.sub.3 -C.sub.8 cycloalkyl or optionally substituted C.sub.1-6 -alkyl wherein the substitution is --NR.sup.6' R.sup.7' ;
- R.sup.6' and R.sup.7' independently are hydrogen, C.sub.1-6 -alkyl; or
- R.sup.6' and R.sup.7' together with the nitrogen atom optionally form a 4- to 6-member ring;
- R.sup.1 and R.sup.2 independently are hydrogen, C.sub.1-15 -alkyl, C.sub.2-5 -alkenyl, C.sub.2-5 -alkynyl, C.sub.1-10 -alkoxy, C.sub.1-5 -alkyl substituted with --OH, --COR.sup.6", CH.sub.2 --OH, halogen, --NH.sub.2, carboxy, or phenyl;
- R.sup.3 is hydrogen, C.sub.1-5 -alkyl, C.sub.2-5 -alkenyl or C.sub.2-5 -alkynyl;
- R.sup.6" is hydrogen, C.sub.1-15 -alkyl
- n is 0, 1 or 2;
- m is 0, 1 or 2;
- p is 0, 1 or 2;
- q is 1 or 2;
- r is 0, 1 or 2;
- ....... is a single or double bond; or
- a pharmaceutically acceptable salt or solvate thereof;
- and one or more Synergistic Analgesics in a weight ratio of First Compound to Synergistic Analgesic of from about 1 to about 1000.
- 2. A composition as claimed by claim 1 wherein the First Compound is selected from the group consisting of Formula I.sup.1' and Formula I; or a pharmaceutically acceptable salt or solvate thereof.
- 3. A composition as claimed by claim 1 wherein the Synergistic Analgesic is a nonsteroidal anti-inflammatory drug.
- 4. A composition as claimed by claim 3 wherein the nonsteroidal anti-inflammatory drug is selected from the group consisting of indomethacin, ibuprofen, naproxen, fenoprofen, tolmetin, sulindac, meclofenamate, keoprofen, piroxicam, flurbiprofen, and diclofenac.
- 5. A composition as claimed by claim 3 wherein the nonsteroidal anti-inflammatory drug is ibuprofen.
- 6. A composition as claimed by claim 3 wherein the First Compound is selected from the group consisting of Formula I and Formula I.sup.1', or a pharmaceutically acceptable salt or solvate thereof.
- 7. A composition as claimed by claim 3 wherein the First Compound is selected from the group consisting of
- (.+-.)-3-Methoxy-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-3-Ethoxy-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-3-Propyloxy-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-3-Butyloxy-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-3-Pentyloxy-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-3-Hexyloxy-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-3-(4-Methylpentyloxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-3-Chloro-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-3-Propylthio-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-3-Butylthio-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-3-Pentylthio-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (S)-3-Pentylthio-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-3-Hexylthio-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-3-(3,3-Dimethylbutylthio)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-3-(2-(2-Thienylthio)ethylthio)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-3-(2,2,3,3,3-Pentafluoropropylthio)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-3-(3-(2-Thienyl)propylthio)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-3-Butylthio-4-((1-azabicyclo[2.2.2]octan-3-yl)methoxy)-1,2,5-thiadiazole,
- (.+-.)-Exo-3-pentylthio-4-(1-azabicyclo[3.2.1)octyl-6-oxy)-1,2,5-thiadiazole,
- (.+-.)-Endo-3-pentylthio-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole,
- (.+-.)-Endo-3-butyloxy-4-(1-azabicyclo[2.2.1]heptyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-Exo-3-butyloxy-4-(1-azabicyclo[2.2.1]heptyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-Butyloxy-4-(3-pyrrolidinyloxy)-1,2,5-thiadiazole,
- (.+-.)-3-Butyloxy-4-(1-methyl-3-pyrrolidinyloxy)-1,2,5-thiadiazole,
- (.+-.)-3-Butylthio-4-(1-methyl-3-piperidyloxy)-1,2,5-thiadiazole,
- 3-Butylthio-4-(1-methyl-4-piperidyloxy)-1,2,5-thiadiazole,
- (S)-3-Butyloxy-4-(1-methyl-2-pyrrolidinylmethoxy)-1,2,5-thiadiazole,
- (S)-3-Butyloxy-4-(2-pyrrolidinylmethoxy)-1,2,5-thiadiazole,
- 3-Butyloxy-4-(2-(dimethylamino)ethoxy)-1,2,5-thiadiazole,
- 3-Butylthio-4-(2-(diethylamino)ethoxy)-1,2,5-thiadiazole,
- 3-Butyloxy-4-(2-(trimethylamino)ethoxy)-1,2,5-thiadiazole iodide,
- (R)-3-Pentylthio-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-3-(4-Methylpentylthio)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-3-(3-Phenylpropylthio)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-3-(4-Cyanobenzylthio)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-3-(4-Fluorobenzylthio)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5- thiadiazole,
- (.+-.)-3-(2-Phenylethylthio)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-3-(2-Phenyloxyethylthio)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- Endo-3-butyloxy-4-(N-methyl-8-azabicyclo[3.2.1]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-Exo-3-butyloxy-4-(6-(N-methyl-8-azabicyclo[3.2.1]octan-3-onoxy))-1,2,5-thiadiazole,
- (.+-.)-Exo-3-chloro-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole,
- (.+-.)-Endo-3-chloro-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole,
- (.+-.)-Endo-3-(4-cyanobenzylthio)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole,
- 3-Butyloxy-4-(3-azetidinyloxy)-1,2,5-thiadiazole,
- 3-Butylthio-4-(3-azetidinyloxy)-1,2,5-thiadiazole,
- (.+-.)-Trans-3-butyloxy-4-(2-dimethylaminocyclopentyloxy)-1,2,5-thiadiazole
- (.+-.)-3-Butylthio-4-(3-pyrrolidinyloxy)-1,2,5-thiadiazole,
- (.+-.)-3-(2-(2-(5-(2-Thienyl)thienyl)thio)ethylthio)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-3-(2-(5-(2-Thienyl)thienyl)thio)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-3-(3-N-(2-Thiazolidonyl)propylthio)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)3-Butylthio-4-(exo-2-azabicyclo[2.2.2]oct-6-yloxy)-1,2,5-thiadiazole,
- (.+-.)3-(2,2,3,3,4,4,4-heptafluorobutyloxy)-4-[-3-(1-azabicyclo[2.2.2]octyloxy)]-1,2,5-thiadiazole,
- (.+-.)3-(1-butylthio)-4-[endo-6-(1-azabicyclo[3.2.1]octyloxy)]-1,2,5-thiadiazole,
- (.+-.)3-(3-phenylpropylthio)-4-[endo-6-(1-azabicyclo-[3.2.1]octyloxy)]-1,2,5-thiadiazole
- (.+-.)3-[3-(4-fluorophenyl)propylthio]-4-[-3-(1-azabicyclo-[2.2.2]octyloxy)]-1,2,5-thiadiazole
- (.+-.)3-(3-[4-(trifluoromethyl)phenyl]propylthio)-4-[-3-(1-azabicyclo[2.2.2]octyloxy)]-1,2,5-thiadiazole; and
- (.+-.).sup.3 -(1-Butylamino)-4-[-3-(1-azabicyclo[2.2.2]octyloxy)]-1,2,5-thiadiazole; and
- (.+-.)-3-(2-Methylthioethyl)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(1-Azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-Hexyl-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-Butylsulfonyl-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-Propylsulfonyl-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(4,4,4-Trifluorobutyloxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(2-Butynyloxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(Cyclopropylmethoxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-3-(3-Phenylpropynyloxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(3-Butenyloxy)-4-(1-azabicyclo[2.2.2)octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(trans-2-Butenyloxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-.sup.3 -(cis-2-Butenyloxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(2-Methoxyethoxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(2-Phenoxyethoxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(3-Butynoxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(2-Cyclopropylethoxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(2-(Methylthio)ethoxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(3-Chloropropoxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(4-Fluorobutyloxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(2-[4-Chlorophenoxy]ethoxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(3-[2-methoxy-5-pyridyl]propyloxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(trans-3-Chloro-2-propenyloxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(2-[4-Fluorophenoxy]ethoxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(4-Pentenyloxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(3-Fluoropropyloxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(Cyclobutylmethoxy)-.sup.4 -(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(3,3,3,2,2-Pentafluoropropyloxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(2-[Phenylthio]ethoxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(2-[1-napthyloxy]ethoxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(2-[4-Bromophenoxy]ethoxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(2-Hydroxyethoxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- 3-Butylthio-4-hydroxy-1,2,5-thiadiazole
- (.+-.)Exo-3-Butylthio-4-(1-azabicyclo[2.2.1]heptyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(2-[3-{1,2,5-Thiadiazoyloxy}]ethoxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-exo-3-Butyloxy-4-(7-azabicyclo[2.2.1]heptyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-Butyloxy-4-(3-piperidinyloxy)-1,2,5-thiadiazole
- 3-Butyloxy-4-(cis-1R-.sup.2 -aminocyclopentanoxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-Hexyloxy-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2, 5-thiadiazole
- (5S,6S)-endo-3-Butylthio-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (5R, 6R) -endo-3-Butylthio-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-trans-3-Butylthio-4-(1-azabicyclo[4.3.0]nonyl-5-oxy)-1,2,5-thiadiazole
- (.+-.)-cis-3-Butylthio-4-(1-azabicyclo[4.3.0]nonyl-5-oxy)-1,2,5-thiadiazole
- (.+-.)-trans-3-Butylthio-4-(2-dimethylaminocyclopentyloxy)-1,2,5-thiadiazole
- 3-Butylthio-4-(2-dimethylaminoethoxy)-1,2,5-thiadiazole
- (.+-.)-trans-3-Butylthio-4-(N-tert-butylcarboxy-4-hydroxy-pyrollidin-3-oxy)-1,2,5-thiadiazole
- (.+-.)-trans-3-Butylthio-4-(4-hydroxy-pyrollidin-3-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-Butyloxy-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(4-Phenylbutylthio)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(3-Phenyl-2-propenylthio)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(3-[4-Fluorophenyl]propan-3-onethio)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(3-[N-Phenothiazinyl]propylthio)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(3-[4-Fluorophenyl]-3-[4-fluorophenoxy]propylthio)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(3-Phenyl-3-[4-trifluoromethylphenoxy]propylthio)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(4,4,4-Trifluorobutylthio)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(3-[3-Pyridyl]propylthio)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(2-Phenoxyethylthio)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-exo-3-Propythio-4-(2-methoxycarbonyl-2-azabicyclo[2.2.2]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-exo-3-Propylsulfonyl-4-(2-methoxycarbonyl-2-azabicyclo[2.2.2]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-exo-3-(4,4,4-Trifluorobutyloxy)-4-(2-methoxycarbonyl-2-azabicyclo[2.2.2)octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-exo-3-(4,4,4-Trifluorobutyloxy)-4-(2-azabicyclo[2.2.2]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-exo-3-(Hexyloxy)-4-(2-azabicyclo[2.2.2]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(4,4,4-Trifluorobutyloxy)-4-(2-azabicyclo[2.2.2]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-exo-3-(2-[Fluorophenoxy]ethylthio)-4-(2-methoxycarbonyl-2-azabicyclo[2.2.2]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-exo-3-(2-[Fluorophenoxy]ethylthio)-4-(2-azabicyclo[2.2.2]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-Propylthio-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-Propylsulfonyl-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(4,4,4-Trifluorobutoxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(2-Butynyloxy)-4-(1-azabicyclo [3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(trans-2-Butenyloxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(2-Methylthioethoxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(2-(4-Methyl-1,3-thiazol-5-yl)ethoxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(4-Methylthiobenzyloxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(2-Thienylmethoxy)-4-(1-azabicyclo [3.2.1) octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(2-cyclohexenyloxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(3-Pentynyloxy)-4-(1-azabicyclo[3 .2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(3-Hexynyloxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(3-Chloropropoxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-[2-(2-Napthalyl)ethoxy]-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(4-Chloro-.alpha.-cyclopropyl-benzyloxy)-4-(1-azabicyclo [3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(4-Methyl-3-pentenyloxy)-4-(1-azabicyclo [3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(cis-2-Butenyloxy)-4-(1-azabicyclo[3 .2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(Cyclopropylmethoxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(2-Methoxyethoxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(3-Butenyloxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(2-cyclopropylethoxy)-4-(1-azabicyclo [3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(3-Butynyloxy)-4-(1-azabicyclo [3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(4,4,4,3,3,2,2-Heptafluorobutoxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-[2-(3-Trifluoromethylphenyl)ethoxy]-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-[2-(2-Thienyl)ethoxy]-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(3,3,3,2,2,Pentafluoropropoxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(2-Phenoxyethoxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(4-n-Butylbenzyloxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-[3-(4-Methoxyphenyl)propoxy]-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(4-Fluorobenzyloxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(2,4-Difluorobenzyloxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-[4-(Trifluoromethoxy)benzyloxy]-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(4-Fluorobutoxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(4-tert-Butylbenzyloxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(1-Cyclopropylethoxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(2-Cyclohexylethoxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(3-Methyl-2-butenyloxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(4-Cyclohexylbutoxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(3-Butyn-2-oxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(3-Methyl-3-phenylbutoxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(3-Fluoropropoxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-[3-(2-Thienyl)propoxy]-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(2-[4-Fluorophenoxy]ethylthio)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(2-Methylthioethyl)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(1-Azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-Hexyl-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- 3-Butylthio-4-hydroxy-1,2,5-thiadiazole
- (.+-.)-3-(2- [3-{1, 2, 5-Thiadiazoyloxy}]ethoxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (+/-)-3-butylthio-4-(azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-oxadiazole, (+/-)-3-(2-butyloxy)-4-[(+/-)-3-azabicyclo[2.2.2]octyloxy)-1,2,5-oxadiazole, (+/-)-3-butyloxy-4-[endo-(+/-)-6-[1-azabicyclo[3.2.1]octyloxy)]-1,2,5-oxadiazole, 3-(2,2,3,3,4,4,4-heptaflurorobutyloxy)-4-[(+/-)-3-(1-azabicyclo[2.2.2]octyloxy)]-1,2,5-oxadiazole, 3-methoxy-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-oxadiazole, 3-pentylthio-4-(1-azabicyclo[2.2.2]ocytl-3-oxy)-1,2,5-oxadiazole, trans-3-butyloxy-4-(2-dimethylaminocyclopentyloxy)-1,2,5-oxadiazole, 3-butylthio-4-(3-azetidinyloxy)-1,2,5-oxadiazole, 3-(3-N-(2-thiazolidonyl)propylthio)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-oxadiazole, 3-chloro-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-oxadiazole, 3-(2-2-thio-5-trifluoromethylthienyl)ethylthio)-4-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-oxadiazole, 3-butylthio-4-[3-.+-.-endo-(1-azabicyclo[2.2.1]heptyloxy)]-1,2,5-oxadiazole, 3-hexyloxy-4-[6-.+-.-endo-(2-azabicyclo[2.2.2]ocyloxy)]-1,2,5-oxadiazole,3-(4,4,4-trifluorobutylthio)-4-[2-.+-.-exo-(7-azabicyclo[2.2.1]heptyloxy)]-1,2,5-oxadiazole, 3-(2-phenoxyethylthio)-4-[3-.+-.-endo-(1-azabicyclo[3.2.1]octyloxy)]-1,2,5-oxadiazole, 3-(5-hexenyloxy)-4-[7-.+-.-endo-(2-azabicyclo[2.2.1]heptyloxy)]-1,2,5-oxadiazole, 3-butyl-4-[5-(1-azabicyclo[3.2.1]octyloxy)]-1,2,5-oxadiazole, 3-cyclobutylmethyl-4-[2-i-endo-(8-azabicyclo[3.2.1]octyloxy)]-1,2,5-oxadiazole, (+/-)-3-butylthio-4-(azabicyclo[2.2.2]octyl-3-oxy)-pyrazine, (+/-)-3-(2-butyloxy)-4-[(+/-)-3-azabicyclo[2.2.2]octyloxy)-pyrazine, (+/-)-3-butyloxy-4-[endo-(+/-)-6-[1-azabicyclo[3.2.1]octyloxy)]-pyrazine, 3-(2,2,3,3,4,4,4-heptaflurorobutyloxy)-4-[(+/-)-3-(1-azabicyclo[2.2.2]octyloxy)]-pyrazine, 3-methoxy-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-pyrazine, 3-pentylthio-4-(1-azabicyclo[2.2.2]ocytl-3-oxy)-pyrazine, trans-3-butyloxy-4-(2-dimethylaminocyclopentyloxy)-pyrazine, 3-butylthio-4-(3-azetidinyloxy)-pyrazine, 3-(3-N-(2-thiazolidonyl)propylthio)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-pyrazine, 3-chloro-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-pyrazine, 3-(2-2-thio-5-trifluoromethylthienyl)ethylthio)-4-azabicyclo[2.2.2]octyl-3-oxy)-pyrazine, 3-butylthio-4-[3-+-endo-(1-azabicyclo[2.2.1]heptyloxy)]-pyrazine, 3-hexyloxy-4-[6-.+-.-endo-(2-azabicyclo[2.2.2]ocyloxy)]-pyrazine, 3-(4,4,4-trifluorobutylthio)-4-[2-.+-.-exo-(7-azabicyclo[2.2.1]heptyloxy)]-pyrazine, 3-(2-phenoxyethylthio)-4-[3-.+-.-endo-(1-azabicyclo[3.2.1]octyloxy)]-pyrazine, 3-(5-hexenyloxy)-4-[7-.+-.-endo-(2-azabicyclo[2.2.1]heptyloxy)]-pyrazine, 3-butyl-4-[5-(1-azabicyclo[3.2.1]octyloxy)]-pyrazine, and 3-cyclobutylmethyl-4-[2-.+-.-endo-(8-azabicyclo[3.2.1]octyloxy)]-pyrazine, 2-[exo-(+/-)-3-[1-azabicyclo[3.2.1]octyloxy)]pyrazine, 3-butylthio-2-(1-azabicyclo[2.2.2]ocytl-3-oxy)]pyrazine, 3-butyloxy-2-[3-.+-.-endo-(1-azabicyclo[2.2.1]heptyloxy)]pyrazine, 3-(2-butynyloxy)-2-[6-.+-.-endo-(1-azabicyclo[3.2.1]octyloxy)pyrazine, 3-hexylthio-2-[6-.+-.-exo-(2-azabicyclo[2.2.1]heptyloxy)]pyrazine, 3-(3-phenylpropynylthio)-2-[2-.+-.-exo-(7-azabicyclo[2.2.1]heptyloxy)]pyrazine, 3-(2-methylthioethoxy)-2-[3-.+-.-exo-(1-azabicyclo[3.2.1]octyloxy)]pyrazine, 3-propargyl-2-[4-(1-azabicyclo[2.2.1]heptyloxy)]pyrazine, and 3-cyclopropylmethylthio-2-[2-.+-.-exo-(8-azabicyclo[3.2.1loctyloxy)]pyrazine; or a pharmaceutically acceptable salt or solvate thereof.
- 8. A composition as claimed by claim 1 wherein the Synergistic Analgesic is an opioid.
- 9. A composition as claimed by claim 8 wherein the First Compound is selected from the group consisting of Formula I and Formula I.sup.1' or a pharmaceutically acceptable salt or solvate thereof.
- 10. A composition as claimed by claim 8 wherein the First Compound is Formula I' or a pharmaceutically acceptable salt or solvate thereof.
- 11. A composition as claimed by claim 8 wherein the First Compound is selected from the group consisting of
- (.+-.)-3-Ethoxy-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-3-Propyloxy-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-3-Butyloxy-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-3-Pentyloxy-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-3-Hexyloxy-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-3-(4-Methylpentyloxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-3-Chloro-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-3-Propylthio-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-3-Butylthio-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-3-Pentylthio-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (S)-3-Pentylthio-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-3-Hexylthio-4-(I-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-3-(3,3-Dimethylbutylthio)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-3-(2-(2-Thienylthio)ethylthio)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-3-(2,2,3,3,3-Pentafluoropropylthio)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-3-(3-(2-Thienyl)propylthio)-4-(1-azabicyclo[2.2.2)octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-3-Butylthio-4-((1-azabicyclo[2.2.2]octan-3-yl)methoxy)-1,2,5-thiadiazole,
- (.+-.)-Exo-3-pentylthio-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole,
- (.+-.)-Endo-3-pentylthio-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole,
- (.+-.)-Endo-3-butyloxy-4-(1-azabicyclo[2.2.1]heptyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-Exo-3-butyloxy-4-(1-azabicyclo[2.2.1)heptyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-Butyloxy-4-(3-pyrrolidinyloxy)-1,2,5-thiadiazole,
- (.+-.)-3-Butyloxy-4-(1-methyl-3-pyrrolidinyloxy)-1,2,5-thiadiazole,
- (.+-.)-3-Butylthio-4-(1-methyl-3-piperidyloxy)-1,2,5-thiadiazole,
- 3-Butylthio-4-(1-methyl-4-piperidyloxy)-1,2,5-thiadiazole,
- (S)-3-Butyloxy-4-(1-methyl-2-pyrrolidinylmethoxy)-1,2,5-thiadiazole,
- (S)-3-Butyloxy-4-(2-pyrrolidinylmethoxy)-1,2,5-thiadiazole,
- 3-Butyloxy-4-(2-(dimethylamino)ethoxy)-1,2,5-thiadiazole,
- 3-Butylthio-4-(2-(diethylamino)ethoxy)-1,2,5-thiadiazole,
- 3-Butyloxy-4-(2-(trimethylamino)ethoxy)-1,2,5-thiadiazole iodide,
- (R)-3-Pentylthio-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-3-(4-Methylpentylthio)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-3-(3-Phenylpropylthio)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-3-(4-Cyanobenzylthio)-4-(1-azabicyclo[2.2.2)octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-3-(4-Fluorobenzylthio)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5- thiadiazole,
- (.+-.)-3-(2-Phenylethylthio)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-3-(2-Phenyloxyethylthio)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- Endo-3-butyloxy-4-(N-methyl-8-azabicyclo[3.2.1]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-Exo-3-butyloxy-4-(6-(N-methyl-8-azabicyclo [3.2.1]octan-3-onoxy))-1,2,5-thiadiazole,
- (.+-.)-Exo-3-chloro-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole,
- (.+-.)-Endo-3-chloro-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole,
- (.+-.)-Endo-3-(4-cyanobenzylthio)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole,
- 3-Butyloxy-4-(3-azetidinyloxy)-1,2,5-thiadiazole,
- 3-Butylthio-4-(3-azetidinyloxy)-1,2,5-thiadiazole,
- (.+-.)-Trans-3-butyloxy-4-(2-dimethylaminocyclopentyloxy)-1,2,5-thiadiazole
- (.+-.)-3-Butylthio-4-(3-pyrrolidinyloxy)-1,2,5-thiadiazole,
- (.+-.)-3-(2-(2-(5-(2-Thienyl) thienyl) thio) ethylthio)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-3-(2-(5-(2-Thienyl)thienyl)thio)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)-3-(3-N-(2-Thiazolidonyl)propylthio)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole,
- (.+-.)3-Butylthio-4-(exo-2-azabicyclo[2.2.2]oct-6-yloxy)-1,2,5-thiadiazole,
- (.+-.)3-(2,2,3,3,4,4,4-heptafluorobutyloxy)-4- [-3-(1-azabicyclo[2.2.2]octyloxy) ]-1,2,5-thiadiazole,
- (.+-.)3-(1-butylthio)-4-[endo-6-(1-azabicyclo[3.2.1]octyloxy)]-1,2,5-thiadiazole,
- (.+-.)3-(3-phenylpropylthio)-4-[endo-6-(1-azabicyclo-[3.2.1]octyloxy)]-1,2,5-thiadiazole
- (.+-.)3-[3-(4-fluorophenyl)propylthio]-4-[-3-(1-azabicyclo-[2.2.2]octyloxy)]-1,2,5-thiadiazole
- (.+-.)3-{3-[4-(trifluoromethyl)phenyl]propylthio}-4-[-3-(1-azabicyclo[2.2.2]octyloxy)]-1,2,5-thiadiazole; and
- (.+-.)3-(1-Butylamino)-4-[-3-(1-azabicyclo[2.2.2]octyloxy)]-1,2,5-thiadiazole; and
- (.+-.)-3-(2-Methylthioethyl)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(1-Azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-Hexyl-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-Butylsulfonyl-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-Propylsulfonyl-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(4,4,4-Trifluorobutyloxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(2-Butynyloxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(Cyclopropylmethoxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(3-Phenylpropynyloxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(3-Butenyloxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(trans-2-Butenyloxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(cis-2-Butenyloxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(2-Methoxyethoxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(2-Phenoxyethoxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(3-Butynoxy)-4-(1-azabicyclo[2.2.2)octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(2-Cyclopropylethoxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(2-(Methylthio)ethoxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(3-Chloropropoxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(4-Fluorobutyloxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(2-[4-Chlorophenoxy]ethoxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(3-[2-methoxy-5-pyridyl]propyloxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(trans-3-Chloro-2-propenyloxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(2-[4-Fluorophenoxy]ethoxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(4-Pentenyloxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(3-Fluoropropyloxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(Cyclobutylmethoxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(3,3,3,2,2-Pentafluoropropyloxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(2-[Phenylthio]ethoxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(2-[1-napthyloxy]ethoxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(2-[4-Bromophenoxy]ethoxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(2-Hydroxyethoxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- 3-Butylthio-4-hydroxy-1,2,5-thiadiazole
- (.+-.)Exo-3-Butylthio-4-(1-azabicyclo[2.2.1]heptyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(2- [3-{1, 2, 5-Thiadiazoyloxy}]ethoxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-exo-3-Butyloxy-4-(7-azabicyclo[2.2.1]heptyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-Butyloxy-4-(3-piperidinyloxy)-1,2,5-thiadiazole
- 3-Butyloxy-4-(cis-lR-2-aminocyclopentanoxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-Hexyloxy-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (5S,6S)-endo-3-Butylthio-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (5R, 6R)-endo-3-Butylthio-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-trans-3-Butylthio-4-(1-azabicyclo[4.3.0]nonyl-5-oxy)-1,2,5-thiadiazole
- (.+-.)-cis-3-Butylthio-4-(1-azabicyclo[4.3.0]nonyl-5-oxy)-1,2,5-thiadiazole
- (.+-.)-trans-3-Butylthio-4-(2-dimethylaminocyclopentyloxy)-1,2,5-thiadiazole
- 3-Butylthio-4-(2-dimethylaminoethoxy)-1,2,5-thiadiazole
- (.+-.)-trans-3-Butylthio-4-(N-tert-butylcarboxy-4-hydroxy-pyrollidin-3-oxy)-1,2,5-thiadiazole
- (.+-.)-trans-3-Butylthio-4-(4-hydroxy-pyrollidin-3-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-Butyloxy-4-(1-azabicyclo [3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(4-Phenylbutylthio)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(3-Phenyl-2-propenylthio)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(3-[4-Fluorophenyl]propan-3-onethio)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(3-[N-Phenothiazinyl]propylthio)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(3-[4-Fluorophenyl]-3-[4-fluorophenoxy]propylthio)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(3-Phenyl-3-[4-trifluoromethylphenoxy]propylthio)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(4,4,4-Trifluorobutylthio)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(3-[3-Pyridyl]propylthio)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(2-Phenoxyethylthio)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-exo-3-Propythio-4-(2-methoxycarbonyl-2-azabicyclo[2.2.2]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-exo-3-Propylsulfonyl-4-(2-methoxycarbonyl-2-azabicyclo[2.2.2]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-exo-3-(4,4,4-Trifluorobutyloxy)-4-(2-methoxycarbonyl-2-azabicyclo[2.2.2]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-exo-3-(4,4,4-Trifluorobutyloxy)-4-(2-azabicyclo[2.2.2]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-exo-3-(Hexyloxy)-4-(2-azabicyclo[2.2.2]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(4,4,4-Trifluorobutyloxy)-4-(2-azabicyclo[2.2.2]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-exo-3-(2-[Fluorophenoxy]ethylthio)-4-(2-methoxycarbonyl-2-azabicyclo[2.2.2]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-exo-3-(2-[Fluorophenoxy]ethylthio)-4-(2-azabicyclo[2.2.2]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-Propylthio-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-Propylsulfonyl-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(4,4,4-Trifluorobutoxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(2-Butynyloxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(trans-2-Butenyloxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(2-Methylthioethoxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(2-(4-Methyl-1,3-thiazol-5-yl)ethoxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(4-Methylthiobenzyloxy)-4-(1-azabicyclo[3.2.]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(2-Thienylmethoxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(2-Cyclohexenyloxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(3-Pentynyloxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(3-Hexynyloxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(3-Chloropropoxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-[2-(2-Napthalyl)ethoxy]-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(4-Chloro-.alpha.-cyclopropyl-benzyloxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(4-Methyl-3-pentenyloxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(cis-2-Butenyloxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(Cyclopropylmethoxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(2-Methoxyethoxy)-4-(1-azabicyclo[3 .2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(3-Butenyloxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(2-cyclopropylethoxy)-4-(1-azabicyclo [3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(3-Butynyloxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(4,4,4,3,3,2,2-Heptafluorobutoxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-[2-(3-Trifluoromethylphenyl)ethoxy]-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-[2-(2-Thienyl)ethoxy]-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(3,3,3,2,2,Pentafluoropropoxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(2-Phenoxyethoxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(4-n-Butylbenzyloxy)-4-(1-azabicyclo [3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3- [3-(4-Methoxyphenyl)propoxy]-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(4-Fluorobenzyloxy)-4-(1-azabicyclo [3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(2,4-Difluorobenzyloxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-[4-(Trifluoromethoxy)benzyloxy]-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(4-Fluorobutoxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(4-tert-Butylbenzyloxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(1-Cyclopropylethoxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(2-Cyclohexylethoxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(3-Methyl-2-butenyloxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(4-Cyclohexylbutoxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(3-Butyn-2-oxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(3-Methyl-3-phenylbutoxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-(3-Fluoropropoxy)-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-endo-3-[3-(2-Thienyl)propoxy]-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(2-[4-Fluorophenoxy]ethylthio)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(2-Methylthioethyl)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-(1-Azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (.+-.)-3-Hexyl-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- 3-Butylthio-4-hydroxy-1,2,5-thiadiazole
- (.+-.)-3-(2-[3-{1,2,5-Thiadiazoyloxy}]ethoxy)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-thiadiazole
- (+/-)-3-butylthio-4-(azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-oxadiazole, (+/-)-3-(2-butyloxy)-4-[(+/-)-3-azabicyclo[2.2.2]octyloxy)-1,2,5-oxadiazole, (+/-)-3-butyloxy-4-[endo-(+/-)-6-[1-azabicyclo[3.2.1)octyloxy)]-1,2,5-oxadiazole, 3-(2,2,3,3,4,4,4-heptaflurorobutyloxy)-4-[(+/-)-3-(1-azabicyclo[2.2.2]octyloxy)]-1,2,5-oxadiazole, 3-methoxy-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-oxadiazole, 3-pentylthio-4-(1-azabicyclo[2.2.2]ocytl-3-oxy)-1,2,5-oxadiazole, trans-3-butyloxy-4-(2-dimethylaminocyclopentyloxy)-1,2,5-oxadiazole, 3-butylthio-4-(3-azetidinyloxy)-1,2,5-oxadiazole, 3-(3-N-(2-thiazolidonyl)propylthio)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-oxadiazole, 3-chloro-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-1,2,5-oxadiazole, 3-(2-2-thio-5-trifluoromethylthienyl)ethylthio)-4-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-oxadiazole, 3-butylthio-4-[3-.+-.-endo-(1-azabicyclo[2.2.1]heptyloxy)]-1,2,5-oxadiazole, 3-hexyloxy-4-[6-.+-.-endo-(2-azabicyclo[2.2.2]ocyloxy)]-1,2,5-oxadiazole,3-(4,4,4-trifluorobutylthio)-4-[2-+-exo-(7-azabicyclo[2.2.1]heptyloxy)]-1,2,5-oxadiazole, 3-(2-phenoxyethylthio)-4-[3-.+-.-endo-(1-azabicyclo[3.2.1]octyloxy)]-1,2,5-oxadiazole, 3-(5-hexenyloxy)-4-[7-+-endo-(2-azabicyclo[2.2.1]heptyloxy)]-1,2,5-oxadiazole, 3-butyl-4-[5-(1-azabicyclo[3.2.1]octyloxy)]-1,2,5-oxadiazole, 3-cyclobutylmethyl-4-[2-.+-.-endo-(8-azabicyclo[3.2.1]octyloxy)]-1,2,5-oxadiazole, (+/-)-3-butylthio-4-(azabicyclo[2.2.2]octyl-3-oxy)-pyrazine, (+/-)-3-(2-butyloxy)-4-[(+/-)-3-azabicyclo[2.2.2]octyloxy)pyrazine, (+/-)-3-butyloxy-4-[endo-(+/-)-6-[1-azabicyclo[3.2.1]octyloxy)]-pyrazine, 3-(2,2,3,3,4,4,4-heptaflurorobutyloxy)-4-[(+/-)-3-(1-azabicyclo[2.2.2]octyloxy)]-pyrazine, 3-methoxy-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-pyrazine, 3-pentylthio-4-(1-azabicyclo[2.2.2]ocytl-3-oxy)-pyrazine, trans-3-butyloxy-4-(2-dimethylaminocyclopentyloxy)-pyrazine, 3-butylthio-4-(3-azetidinyloxy)-pyrazine, 3-(3-N-(2-thiazolidonyl)propylthio)-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-pyrazine, 3-chloro-4-(1-azabicyclo[3.2.1]octyl-6-oxy)-pyrazine, 3-(2-2-thio-5-trifluoromethylthienyl)ethylthio)-4-azabicyclo[2.2.2]octyl-3-oxy)-pyrazine, 3-butylthio-4-[3-.+-.-endo-(1-azabicyclo[2.2.1]heptyloxy)]-pyrazine, 3-hexyloxy-4-[6-.+-.-endo-(2-azabicyclo[2.2.2)ocyloxy)]-pyrazine, 3-(4,4,4-trifluorobutylthio)-4-[2-.+-.-exo-(7-azabicyclo[2.2.1]heptyloxy)]-pyrazine, 3-(2-phenoxyethylthio)-4-[3-.+-.-endo-(1-azabicyclo[3.2.1]octyloxy)]-pyrazine, 3-(5-hexenyloxy)-4-[7-.+-.-endo-(2-azabicyclo[2.2.1]heptyloxy)]-pyrazine, 3-butyl-4-[5-(1-azabicyclo[3.2.1]octyloxy)]-pyrazine, and 3-cyclobutylmethyl-4-[2-+-endo-(8-azabicyclo[3.2.1]octyloxy)]-pyrazine, 2-[exo-(+/-)-3-[1-azabicyclo[3.2.1]octyloxy)]pyrazine, 3-butylthio-2-(1-azabicyclo[2.2.2]ocytl-3-oxy)]pyrazine, 3-butyloxy-2-[3-.+-.-endo-(1-azabicyclo[2.2.1]heptyloxy)]pyrazine, 3-(2-butynyloxy)-2-[6-.+-.-endo-(1-azabicyclo[3.2.1]octyloxy)]pyrazine, 3-hexylthio-2-[6-.+-.-exo-(2-azabicyclo[2.2.1]heptyloxy)]pyrazine, 3-(3-phenylpropynylthio)-2-[2-+-exo-(7-azabicyclo[2.2.1]heptyloxy)]pyrazine, 3-(2-methylthioethoxy)-2-[3-+-exo-(1-azabicyclo[3.2.1]octyloxy)]pyrazine,3-propargyl-2-[4-(1-azabicyclo[2.2.1]heptyloxy)]pyrazine, and 3-cyclopropylmethylthio-2-[2-.+-.-exo-(8-azabicyclo[3.2.1]octyloxy)]pyrazine; or a pharmaceutically acceptable salt thereof.
- 12. A composition as claimed by claim 8 wherein the opioid is selected from the group consisting of morphine, codeine, meperidine, methadone, propoxyphene, levorphanol, hydromorphone, oxymorphone, oxycodone, brompton's cocktail, naloxone, naltrexone, pentazocine, butorphanol, nabuphine, and buprenorphine.
- 13. A composition as claimed by claim 8 wherein the opioid is selected from the group consisting of hydromorphone, hydrocodone, meperidone, buprenorphine, butorphenol, nalbuphine, pentazocine, oxymorphine, oxycodone, levorphanol, fentanyl, and alphaprodine.
- 14. A composition as claimed by claim 8 wherein the opioid is selected from the group consisting of propoxyphene, methadone, hydrocodone, hydromorphine, and codeine.
- 15. A composition as claimed by claim 1 wherein the Synergistic Analgesic is acetaminophen.
- 16. A composition as claimed by claim 15 wherein the First Compound is selected from the group consisting of Formula I and Formula I.sup.1' ; or a pharmaceutically acceptable salt or solvate thereof.
- 17. A composition as claimed by claim 15 wherein the First Compound is Formula II; or a pharmaceutically acceptable salt thereof.
- 18. A composition as claimed by claim 1 wherein the Synergistic Analgesic is an alpha-adrenergic compound.
- 19. A composition as claimed by claim 18 wherein the First Compound is selected from the group consisting of Formula I and Formula I.sup.1' ; or a pharmaceutically acceptable salt or solvate thereof.
- 20. A composition as claimed by claim 19 wherein the First Compound is Formula I'; or a pharmaceutically acceptable salt thereof.
- 21. A method for treating pain comprising administering an analgesic dose of a composition comprising a a First Compound selected from the group consisting of: ##STR44## wherein W is oxygen or sulphur;
- R is hydrogen, amino, halogen, NHR.sup.6, NR.sup.6 R.sup.7, R.sup.4, --OR.sup.4, --SR.sup.4, --SOR.sup.4, --SO.sub.2 R.sup.4, C.sub.3-10 -cycloalkyl, C.sub.4-12 -(cycloalkylalkyl) --Z--C.sub.3-10 -cycloalkyl and --Z--C.sub.4-12 -(cycloalkylalkyl) wherein R.sup.4 is C.sub.1-15 -alkyl, C.sub.2-15 -alkenyl, C.sub.2-15 -alkynyl, each of which is optionally substituted with one or more halogen(s), --CF.sub.3, --CN, Y, phenyl or phenoxy wherein phenyl or phenoxy is optionally substituted with halogen, --CN, C.sub.1-4 -alkyl, C.sub.1-4 -alkoxy, --OCF.sub.3, --CF.sub.3, --CONH.sub.2 or --CSNH.sub.2 ; or
- R is phenyl or benzyloxycarbonyl, each of which is optionally substituted with halogen, --CN, C.sub.1-4 -alkyl, C.sub.1-4 -alkoxy, --OCF.sub.3, --CF.sub.3, --CONH.sub.2 or --CSNH.sub.2 ; or
- R is --OR.sup.5 Y, --SR.sup.5 Y, OR.sup.5 --Z--Y, --SR.sup.5 ZY, --O--R.sup.5 --Z--R.sup.4 or --S--R.sup.5 --Z--R.sup.4 wherein Z is oxygen or sulphur, R.sup.5 is C.sub.1-15 -alkyl, C.sub.2-15 -alkenyl, C.sub.2-15 -alkynyl, and Y is a 5 or 6 membered heterocyclic group; and
- G is selected from one of the following azacyclic or azabicyclic ring systems: ##STR45## or G can optionally be substituted C.sub.3 -C.sub.8 cycloalkyl or optionally substituted C.sub.1-6 -alkyl wherein the substitution is --NR.sup.6 R.sup.7 ;
- R.sup.6 and R.sup.7 independently are hydrogen, C.sub.1-6 -alkyl; or
- R.sup.6 and R.sup.7 together with the nitrogen atom optionally form a 4- to 6-member ring;
- R.sup.1 and R.sup.2 independently are hydrogen, C.sub.1-15 -alkyl, C.sub.2-5 -alkenyl, C.sub.2-5 -alkynyl, C.sub.1-10 -alkoxy, C.sub.1-5 -alkyl substituted with --OH, --COR.sup.6', CH.sub.2 --OH, halogen, --NH.sub.2, carboxy, or phenyl;
- R.sup.3 is hydrogen, C.sub.1-5 -alkyl, C.sub.2-5 -alkenyl or C.sub.2-5 -alkynyl;
- R.sup.6' is hydrogen, C.sub.1-6 -alkyl;
- n is 0, 1 or 2;
- m is 0, 1 or 2;
- p is 0, 1 or 2;
- q is 1 or 2;
- r is 0, 1 or 2;
- ...... is a single or double bond; and ##STR46## wherein W' is oxygen or sulfur;
- R' is hydrogen, amino, halogen, NHR6', NR.sup.6' R.sup.7', R.sup.4', --OR.sup.4', --SR.sup.4', --SOR.sup.4", --SO.sub.2 R.sup.4', C.sub.3-10 -cycloalkyl, C.sub.4- 12 -(cycloalkylalkyl), --Z'-C.sub.3-10 -cycloalkyl and --Z'-C.sub.4-12 -(cycloalkylalkyl) wherein R.sup.4' is C.sub.1-5 -alkyl, C.sub.2-15 -alkenyl, C.sub.2-15 -alkynyl, each of which is optionally substituted with one or more halogen(s), --CF.sub.3, --CN, Y', phenyl or phenoxy wherein phenyl or phenoxy is optionally substituted with halogen, --CN, C.sub.1-4 -alkyl, C.sub.1-4 -alkoxy, --OCF.sub.3, --CF.sub.3, --CONH.sub.2 or --CSNH.sub.2 ; or
- R' is phenyl or benzyloxycarbonyl, each of which is optionally substituted with halogen, --CN, C.sub.1-4 -alkyl, C.sub.1-4 -alkoxy, --OCF.sub.3, --CF.sub.3, --CONH.sub.2 or --CSNH.sub.2 ; or
- R' is --OR.sup.5' Y', --SR.sup.5' Y', OR.sup.5' --Z'--Y', --SR.sup.5' Z'Y', --O--R.sup.5' --Z--R.sup.4' or --S--R.sup.5' --Z'--R.sup.4' wherein Z' is oxygen or sulphur, R.sup.5' is C.sub.1-15 -alkyl, C.sub.2-15 -alkenyl, C.sub.2-15 -alkynyl, and Y' is a 5 or 6 membered heterocyclic group; and
- G' is selected from one of the following azacyclic or azabicyclic ring systems: ##STR47## or G' can optionally be substituted C.sub.3 -C.sub.8 cycloalkyl or optionally substituted C.sub.16 -alkyl wherein the substitution is --NR.sup.6' R.sup.7' ;
- R.sup.6' and R.sup.7' independently are hydrogen, C.sub.1-6 -alkyl; or
- R.sup.6' and R.sup.7' together with the nitrogen atom optionally form a 4- to 6-member ring;
- R.sup.1 and R.sup.2 independently are hydrogen, C.sub.1-5 -alkyl, C.sub.2-5 -alkenyl, C.sub.2-5 -alkynyl, C.sub.1-10 -alkoxy, C.sub.1-5 -alkyl substituted with --OH, --COR.sup.6", CH.sub.2 --OH, halogen, --NH.sub.2, carboxy, or phenyl;
- R.sup.3 is hydrogen, C.sub.1-5 -alkyl, C.sub.2-5 -alkenyl or C.sub.2-5 -alkynyl;
- R.sup.6" is hydrogen, C.sub.1-15 -alkyl
- n is 0, 1 or 2;
- m is 0, 1 or 2;
- p is 0, 1 or 2;
- q is 1 or 2;
- r is 0, 1 or 2;
- ....... is a single or double bond; or
- a pharmaceutically acceptable salt or solvate thereof;
- and one or more Synergistic Analgesics in a weight ratio of First Compound to Synergistic Analgesic of from about 1 to about 1000.
- 22. A method as claimed by claim 21 wherein the First Compound is selected from the group consisting of Formula I and Formula I.sup.1' ; or a pharmaceutically acceptable salt or solvate thereof.
- 23. A method as claimed by claim 21 wherein the Synergistic Analgesic is a nonsteroidal anti-inflammatory drug.
- 24. A method as claimed by claim 23 wherein the nonsteroidal anti-inflammatory drug is selected from the group consisting of indomethacin, ibuprofen, naproxen, fenoprofen, tolmetin, sulindac, meclofenamate, keoprofen, piroxicam, flurbiprofen, and diclofenac.
- 25. A method as claimed by claim 23 wherein the nonsteroidal anti-inflammatory drug is ibuprofen.
- 26. A method as claimed by claim 23 wherein the First Compound is selected from the group consisting of Formula I and Formula I.sup.1' ; or a pharmaceutically acceptable salt or solvate thereof.
- 27. A method as claimed by claim 21 wherein the Synergistic Analgesic is an opioid.
- 28. A method as claimed by claim 27 wherein the First Compound is selected from the group consisting of Formula I and Formula I.sup.1' ; or a pharmaceutically acceptable salt or solvate thereof.
- 29. A method as claimed by claim 27 wherein the First Compound is Formula I'; or
- a pharmaceutically acceptable salt thereof.
- 30. A method as claimed by claim 27 wherein the opioid is selected from the group consisting of morphine, codeine, meperidine, methadone, propoxyphene, levorphanol, hydromorphone, oxymorphone, oxycodone, brompton's cocktail, naloxone, naltrexone, pentazocine, butorphanol, nabuphine, and buprenorphine.
- 31. A method as claimed by claim 27 wherein the opioid is selected from the group consisting of hydromorphone, hydrocodone, meperidone, buprenorphine, butorphenol, nalbuphine, pentazocine, oxymorphine, oxycodone, levorphanol, fentanyl, and alphaprodine.
- 32. A method as claimed by claim 27 wherein the opioid is selected from the group consisting of propoxyphene, methadone, hydrocodone, hydromorphine, and codeine.
- 33. A method as claimed by claim 21 wherein the Synergistic Analgesic is acetaminophen.
- 34. A method as claimed by claim 33 wherein the First Compound is selected from the group consisting of Formula I and Formula I.sup.1' ; or a pharmaceutically acceptable salt or solvate thereof.
- 35. A method as claimed by claim 21 wherein the Synergistic Analgesic is an alpha-adrenergic compound.
- 36. A method as claimed by claim 35 wherein the First Compound is selected from the group consisting of Formula I and Formula I.sup.1' ; or a pharmaceutically acceptable salt or solvate thereof.
- 37. The use of a First Compound selected from the group consisting of: ##STR48## wherein W is oxygen or sulphur;
- R is hydrogen, amino, halogen, NHR.sup.6, NR.sup.6 R.sup.7, R.sup.4, --OR.sup.4, --SR.sup.4, --SOR.sup.4, --SO.sub.2 R.sup.4, C.sub.3-10 -cycloalkyl, C.sub.4-12 -(cycloalkylalkyl) --Z--C.sub.3-10 -cycloalkyl and --Z--C.sub.4-12 -(cycloalkylalkyl) wherein
- R.sup.4 is C.sub.1-15 -alkyl, C.sub.2-15 -alkenyl, C.sub.2-15 -alkynyl, each of which is optionally substituted with one or more halogen(s), --CF.sub.3, --CN, Y, phenyl or phenoxy wherein phenyl or phenoxy is optionally substituted with halogen, --CN, C.sub.1-4 -alkyl, C.sub.1-4 -alkoxy, --OCF.sub.3, --CF.sub.3, --CONH.sub.2 or --CSNH.sub.2 ; or
- R is phenyl or benzyloxycarbonyl, each of which is optionally substituted with halogen, --CN, C.sub.1-4 -alkyl, C.sub.1-4 -alkoxy, --OCF.sub.3, --CF.sub.3, --CONH.sub.2 or --CSNH.sub.2 ; or
- R is --OR.sup.5 Y, --SR.sup.5 Y, OR.sup.5 --Z--Y, --SR.sup.5 ZY, --O--R.sup.5 --Z--R.sup.4 or --S--R.sup.5 --Z--R.sup.4 wherein Z is oxygen or sulphur, R.sup.5 is C.sub.1-15 -alkyl, C.sub.2-15 -alkenyl, C.sub.2-15 -alkynyl, and Y is a 5 or 6 membered heterocyclic group; and
- G is selected from one of the following azacyclic or azabicyclic ring systems: ##STR49## or G can optionally be substituted C.sub.3 -C.sub.8 cycloalkyl or optionally substituted C.sub.1-6 -alkyl wherein the substitution is --NR.sup.6 R.sup.7 ;
- R.sup.6 and R.sup.7 independently are hydrogen, C.sub.1-6 -alkyl; or
- R.sup.6 and R.sup.7 together with the nitrogen atom optionally form a 4- to 6-member ring;
- R.sup.1 and R.sup.2 independently are hydrogen, C.sub.1-15 -alkyl, C.sub.2-5 -alkenyl, C.sub.2-5 -alkynyl, C.sub.1-10 -alkoxy, C.sub.1-5 -alkyl substituted with --OH, --COR.sup.6', CH.sub.2 --OH, halogen, --NH.sub.2, carboxy, or phenyl;
- R.sup.3 is hydrogen, C.sub.1-5 -alkyl, C.sub.2-5 -alkenyl or C.sub.2-5 -alkynyl;
- R.sup.6, is hydrogen, C.sub.1-6 -alkyl;
- n is 0, 1 or 2;
- m is 0, 1 or 2;
- p is 0, 1 or 2;
- q is 1 or 2;
- r is 0, 1 or 2;
- is a single or double bond; and ##STR50## wherein W' is oxygen or sulfur;
- R.sup.1 is hydrogen, amino, halogen, NHR6', NR.sup.6' R.sup.7", R.sup.4", --OR.sup.4', --SR.sup.4', --SOR.sup.4', --SO.sub.2 R.sup.4', C.sub.3-10 -cycloalkyl, C.sub.4-12 -(cycloalkylalkyl), --Z'--C.sub.3-10 -cycloalkyl and --Z'--C.sub.4-12 -(cycloalkylalkyl) wherein R.sup.4' is C.sub.1-15 -alkyl, C.sub.2-15 -alkenyl, C.sub.2-15 -alkynyl, each of which is optionally substituted with one or more halogen(s), --CF.sub.3, --CN, Y', phenyl or phenoxy wherein phenyl or phenoxy is optionally substituted with halogen, --CN, C.sub.1-4 -alkyl, C.sub.1-4 -alkoxy, --OCF.sub.3, --CF.sub.3, --CONH.sub.2 or --CSNH.sub.2 ; or
- R' is phenyl or benzyloxycarbonyl, each of which is optionally substituted with halogen, --CN, C.sub.14 -alkyl, C.sub.1-4 -alkoxy, --OCF.sub.3, --CF.sub.3, --CONH.sub.2 or --CSNH.sub.2 ; or
- R' is --OR.sup.5' Y', --SR.sup.5' Y', OR.sup.5' --Z'--Y', --SR.sup.5' Z'Y', --O--R.sup.5' --Z--R.sup.4' or --S--R.sup.5 --Z'--R.sup.4' wherein Z' is oxygen or sulphur, R.sup.5' is C.sub.1-15 -alkyl, C.sub.2-15 -alkenyl, C.sub.2-15 -alkynyl, and Y' is a 5 or 6 membered heterocyclic group; and
- G' is selected from one of the following azacyclic or azabicyclic ring systems: ##STR51## or G' can optionally be substituted C.sub.3 -C.sub.8 cycloalkyl or optionally substituted C.sub.1-6 -alkyl wherein the substitution is --NR.sup.6' R.sup.7' ;
- R.sup.6' and R.sup.7' independently are hydrogen, C.sub.1-6 -alkyl; or
- R.sup.6' and R.sup.7' together with the nitrogen atom optionally form a 4- to 6-member ring;
- R.sup.1 and R.sup.2 independently are hydrogen, C.sub.1-15 -alkyl, C.sub.2-5 -alkenyl, C.sub.2-5 -alkynyl, C.sub.1-10 -alkoxy, C.sub.1-5 -alkyl substituted with --OH, --COR.sup.6', CH.sub.2 --OH, halogen, --NH.sub.2, carboxy, or phenyl;
- R.sup.3 is hydrogen, C.sub.1-5 -alkyl, C.sub.2-5 -alkenyl or C.sub.2-5 -alkynyl;
- R.sup.6' is hydrogen, C.sub.1-15 -alkyl
- n is 0, 1 or 2;
- m is 0, 1 or 2;
- p is 0, 1 or 2;
- q is 1 or 2;
- r is 0, 1 or 2;
- ....... is a single or double bond; or
- a pharmaceutically acceptable salt or solvate thereof; and
- one or more Synergistic Analgesics in a weight ratio of Compound to Synergistic Analgesic of from about 1 to about 1000 for the manufacture of a medicament for therapeutic application in the treatment of pain.
- 38. A use as claimed by claim 37 wherein the Synergistic Analgesic is an opioid.
- 39. A use as claimed by claim 37 wherein the Synergistic Analgesic is acetaminophen.
- 40. A use as claimed by claim 37 wherein the Synergistic Analgesic is a nonsteroidal anti-inflammatory drug.
- 41. A use as claimed by claim 37 wherein the Synergistic Analgesic is an alpha-adrenergic compound.
Parent Case Info
This application is a continuation of provisional applications:
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
102e Date |
371c Date |
PCT/US96/19229 |
12/5/1996 |
|
|
6/4/1998 |
6/4/1998 |
Publishing Document |
Publishing Date |
Country |
Kind |
WO97/20819 |
6/12/1997 |
|
|
US Referenced Citations (6)