Tricyclic-bridged piperidinylidene derivatives as delta opioid modulators

Abstract

Disclosed are compounds, compositions and methods for treating various diseases and conditions, including pain. Such compounds are represented by Formula I as follows: wherein A, G, Y, R3, R4, and R5 are defined herein.

1 . A compound of Formula (I): 
     
       
         
         
             
             
         
       
     
     wherein:
 G is —C(Z)NR 1 R 2 , C 6-10 aryl, C 6-10 arylthio, or a heterocycle selected from the group consisting of imidazolyl, triazolyl, tetrazolyl, oxadiazolyl, thiadiazolyl, oxathiadiazolyl, imidazolinyl, tetrahydropyrimidinyl, thienyl, pyrazolyl, pyrimidinyl, triazinyl, furyl, indazolyl, indolyl, indolinyl, isothiazolyl, isoxazolyl, oxazolyl, isoxadiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl, and pyridinyl; wherein the C 6-10 aryl group in the C 6-10 aryl-containing substituents of G and the heterocycles of G are optionally substituted with one to three substituents independently selected from the group consisting of C 1-8 alkanyl, C 2-8 alkenyl, C 2-8 alkynyl, C 1-8 alkanyloxy, hydroxy(C 1-6 )alkanyl, carboxy(C 1-6 )alkanyl, C 1-6 alkanylcarbonylamino, halogen, hydroxy, cyano, nitro, oxo, thioxo, amino, C 1-6 alkanylamino, di(C 1-6 alkanyl)amino, C 1-8 alkanylthio, C 1-8 alkanylsulfonyl, C 1-8 alkanylsulfonylamino, aminocarbonyl, aminothiocarbonyl, aminocarbonylamino, aminothiocarbonylamino, C 1-8 alkanylaminocarbonyl, di(C 1-8 alkanyl)aminocarbonyl, and C 1-6 alkanyloxycarbonylamino; 
 R 1  is a substituent selected from the group consisting of hydrogen, C 1-8 alkanyl, C 2-8 alkenyl, and C 2-8 alkynyl; 
 R 2  is a substituent selected from the group consisting of hydrogen; C 1-8 alkanyl; C 2-8 alkenyl; C 2-8 alkynyl; C 6-10 aryl; and C 3-8 cycloalkanyl; provided that when Z is O or S, R 2  is other than hydrogen or unsubstituted C 1-8 alkanyl; and, wherein C 1-8 alkanyl of R 2  is optionally substituted with one to three substituents independently selected from the group consisting of phenyl, amino, C 1-6 alkanylamino, di(C 1-6 alkanyl)amino, C 1-6 alkanyloxy, C 1-6 alkanylthio, hydroxy, fluoro, chloro, cyano, aminocarbonyl, C 1-8 alkanylaminocarbonyl, di(C 1-8 alkanyl)aminocarbonyl, C 1-6 alkanyloxycarbonyl, and aryloxy; wherein the phenyl and aryloxy substituents of C 1-8 alkanyl are further substituted with, and the C 6-10 aryl and C 3-8 cycloalkanyl substituents of R 2  are optionally substituted with, one to three substituents independently selected from the group consisting of C 1-8 alkanyl, C 2-8 alkenyl, C 2-8 alkynyl, C 1-8 alkanyloxy, trifluoromethyl, trifluoromethoxy, phenyl, halogen, cyano, hydroxy, C 1-8 alkanylthio, C 1-8 alkanylsulfonyl, and C 1-8 alkanylsulfonylamino; 
 or R 1  and R 2  taken together with the nitrogen to which they are attached form a 5-7 membered cycloheteroalkyl optionally substituted with phenyl (wherein phenyl is optionally substituted with one to three C 1-4 alkanyl or C 1-4 alkanyloxy substituents) and one to two additional substituents independently selected from the group consisting of C 1-8 alkanyl, hydroxy(C 1-8 )alkanyl, hydroxy, amino, C 1-6 alkanylamino, di(C 1-6 alkanyl)amino, and halogen; 
 or, R 1  and R 2  taken together with the nitrogen to which they are attached form a 5-7 membered cycloheteroalkyl optionally substituted with one to three substituents independently selected from the group consisting of C 1-8 alkanyl, hydroxy(C 1-8 )alkanyl, hydroxy, amino, C 1-6 alkanylamino, di(C 1-6 alkanyl)amino, and halogen; 
 R 3  is a substituent selected from the group consisting of hydrogen, C 1-8 alkanyl, halo 1-3 (C 1-8 )alkanyl, C 2-8 alkenyl, C 2-8 alkynyl, C 3-8 cycloalkanyl, cycloalkanyl(C 1-8 )alkanyl, C 1-8 alkanyloxy(C 1-8 )alkanyl, C 1-8 alkanylthio(C 1-8 )alkanyl, hydroxyC 1-8 alkanyl, C 1-8 alkanyloxycarbonyl, halo 1-3 (C 1-8 )alkanylcarbonyl, formyl, thioformyl, carbamimidoyl, phenylimino(C 1-8 )alkanyl, phenyl(C 1-8 )alkanyl, phenyl(C 1-8 )alkenyl, phenyl(C 1-8 )alkynyl, naphthyl(C 1-8 )alkanyl and heteroaryl(C 1-8 )alkanyl wherein the heteroaryl is selected from the group consisting of benzo[1,3]dioxolyl, imidazolyl, furanyl, pyridinyl, thienyl, indazolyl, indolyl, indolinyl, isoindolinyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyrimidinyl, pyrrolyl, quinolinyl, isoquinolinyl, tetrazolyl, thiazolyl; wherein phenyl, naphthyl, and heteroaryl are optionally substituted with one to three substituents independently selected from the group consisting of C 1-6 alkanyl, C 2-6 alkenyl, C 1-6 alkanyloxy, amino, C 1-6 alkanylamino, di(C 1-6 alkanyl)amino, C 1-6 alkanylcarbonyl, C 1-6 alkanylcarbonyloxy, C 1-6 alkanylcarbonylamino, C 1-6 alkanylthio, C 1-6 alkanylsulfonyl, halogen, hydroxy, cyano, fluoro(C 1-6 )alkanyl, thioureido, and fluoro(C 1-6 )alkanyloxy; alternatively, when phenyl and heteroaryl are optionally substituted with alkanyl or alkanyloxy substituents attached to adjacent carbon atoms, the two substituents can together form a fused cyclic alkanyl or cycloheteroalkanyl selected from the group consisting of —(CH 2 ) 3-5 —, —O(CH 2 ) 2-4 —, —(CH 2 ) 2-4 O—, and —O(CH 2 ) 1-3 O—; 
 R 4  is one to three substituents independently selected from the group consisting of hydrogen, C 1-6 alkanyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl(C 2-6 )alkynyl, C 1-6 alkanyloxy, amino, C 1-6 alkanylamino, di(C 1-6 alkanyl)amino, C 1-6 alkanylcarbonyl, C 1-6 alkanylcarbonyloxy, C 1-6 alkanyloxycarbonyl, aminocarbonyl, C 1-6 alkanylaminocarbonyl, di(C 1-6 alkanyl)aminocarbonyl, C 1-6 alkanylcarbonylamino, C 1-6 alkanylthio, C 1-6 alkanylsulfonyl, halogen, hydroxy, mercapto, aminothiocarbonyl, amidino, hydroxyamidino, phenylcarbonyl, —C(═NOH)phenyl, aminomethyl, hydroxymethyl, methanesulfonylamino, C 6-10 arylamino (wherein C 6-10 aryl is optionally substituted with one to three substitutents independently selected from the group consisting of C 1-6 alkanyl, C 1-6 alkoxy, halogen, and hydroxy), dihydroimidazolyl, formylamino, thioformylamino, pyridinylamino, cyano, hydroxycarbonyl, C 6-10 aryl, chromanyl, chromenyl, furanyl, imidazolyl, indazolyl, indolyl, indolinyl, isoindolinyl, isoquinolinyl, isothiazolyl, isoxazolyl, naphthyridinyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinolizinyl, quinoxalinyl, tetrazolyl, thiazolyl, thienyl, fluoroalkanyl and fluoroalkanyloxy; or optionally, when R 4  is two substituents attached to adjacent carbon atoms, the two substituents together form a single fused moiety; wherein the fused moiety is selected from the group consisting of —(CH 2 ) 3-5 —, —O(CH 2 ) 2-4 —, —(CH 2 ) 2-4 O—, —O(CH 2 ) 1-3 O— and —S—C(NH 2 )═N—; 
 R 5  is one to two substituents independently selected from the group consisting of hydrogen, C 1-6 alkanyl, C 2-6 alkenyl, C 1-6 alkanyloxy, amino, C 1-6 alkanylamino, di(C 1-6 alkanyl)amino, C 1-6 alkanylcarbonyl, C 1-6 alkanylcarbonyloxy, C 1-6 alkanyloxycarbonyl, C 1-6 alkanylaminocarbonyl, C 1-6 alkanylcarbonylamino, C 1-6 alkanylthio, C 1-6 alkanylsulfonyl, halogen, hydroxy, cyano, fluoro(C 1-6 )alkanyl and fluoro(C 1-6 )alkanyloxy; 
 A is (CH 2 ) 2 ; 
 Y is S; 
 X is O or S 
 n is 0 or 1; 
 Z is O, S, NH, N(C 1-6 alkanyl), N(OH), N(OC 1-6 alkanyl), or N(phenyl); 
 and enantiomers, diastereomers, tautomers, solvates, or pharmaceutically acceptable salts thereof. 
 
   
   
       2 . The compound according to  claim 1  wherein G is —C(Z)NR 1 R 2 , phenyl, or a heterocycle selected from the group consisting of imidazolyl, triazolyl, tetrazolyl, oxadiazolyl, thiadiazolyl, oxathiadiazolyl, imidazolinyl, tetrahydropyrimidinyl, thienyl, pyrazolyl, pyrimidinyl, triazinyl, furyl, isothiazolyl, isoxazolyl, oxazolyl, isoxadiazolyl, quinolinyl, and pyridinyl; wherein phenyl and the heterocycles of G are optionally substituted with one to three substituents independently selected from the group consisting of C 1-8 alkanyl, C 1-8 alkanyloxy, hydroxy(C 1-8 )alkanyl, carboxy(C 1-8 )alkanyl, C 1-8 alkanylcarbonylamino, halogen, hydroxy, cyano, oxo, thioxo, amino, C 1-6 alkanylamino, di(C 1-6 alkanyl)amino, C 1-8 alkanylthio, aminocarbonyl, aminothiocarbonyl, C 1-8 alkanylaminocarbonyl, di(C 1-8 alkanyl)aminocarbonyl, and C 1-6 alkanyloxycarbonylamino. 
   
   
       3 . The compound according to  claim 1  wherein G is —C(Z)NR 1 R 2 , phenyl, or a heterocycle selected from the group consisting of imidazolyl, tetrazolyl, oxadiazolyl, thiadiazolyl, oxathiadiazolyl, imidazolinyl, thienyl, pyrazolyl, pyrimidinyl, triazinyl, furyl, isothiazolyl, isoxazolyl, oxazolyl, isoxadiazolyl, quinolinyl, and pyridinyl; wherein phenyl and the heterocycles of G are optionally substituted with one to three substituents independently selected from the group consisting of C 1-4 alkanyl, C 1-4 alkanyloxy, hydroxy(C 1-4 )alkanyl, carboxy(C 1-4 )alkanyl, C 1-4 alkanylcarbonylamino, hydroxy, cyano, oxo, thioxo, amino, C 1-6 alkanylamino, di(C 1-6 alkanyl)amino, C 1-8 alkanylthio, aminocarbonyl, aminothiocarbonyl, C 1-8 alkanylaminocarbonyl, and di(C 1-8 alkanyl)aminocarbonyl. 
   
   
       4 . The compound according to  claim 1  wherein G is —C(Z)NR 1 R 2 , phenyl, or a heterocycle selected from the group consisting of imidazolyl, tetrazolyl, oxadiazolyl, thiadiazolyl, oxathiadiazolyl, thiophenyl, isothiazolyl, isoxazolyl, isoxadiazolyl, and pyridinyl; wherein phenyl and the heterocycles of G are optionally substituted with one to three substituents independently selected from the group consisting of C 1-4 alkanyl, C 1-4 alkanyloxy, hydroxy(C 1-4 )alkanyl, C 1-4 alkanylcarbonylamino, hydroxy, cyano, oxo, thioxo, and aminocarbonyl. 
   
   
       5 . The compound according to  claim 1  wherein R 1  is a substituent selected from the group consisting of hydrogen and C 1-4 alkanyl. 
   
   
       6 . The compound according to  claim 1  wherein R 1  is selected from the group consisting of hydrogen, methyl, ethyl, and propyl. 
   
   
       7 . The compound according to  claim 1  wherein R 1  is selected from the group consisting of hydrogen, methyl, and ethyl. 
   
   
       8 . The compound according to  claim 1  wherein R 2  is selected from the group consisting of hydrogen; C 1-4 alkanyl; phenyl; and C 3-6 cycloalkanyl; provided that when Z is O or S, R 2  is other than hydrogen or unsubstituted C 1-4 alkanyl; and, wherein C 1-4 alkanyl is optionally substituted with one to three substituents independently selected from the group consisting of phenyl, amino, C 1-6 alkanylamino, di(C 1-6 alkanyl)amino, C 1-4 alkanyloxy, hydroxy, fluoro, chloro, cyano, aminocarbonyl, C 1-8 alkanylaminocarbonyl, di(C 1-8 alkanyl)aminocarbonyl, and phenoxy; wherein the phenyl and phenoxy substituents of C 1-4 alkanyl are optionally further substituted with, and the phenyl and C 3-6 cycloalkanyl substituents of R 2  are optionally substituted with, one to three substituents independently selected from the group consisting of C 1-8 alkanyl, C 1-8 alkanyloxy, trifluoromethyl, phenyl, fluoro, hydroxy, C 1-8 alkanylthio, C 1-8 alkanylsulfonyl, and C 1-8 alkanylsulfonylamino; or R 1  and R 2  taken together with the nitrogen to which they are attached form a 5-7 membered cycloheteroalkyl optionally substituted with phenyl (wherein phenyl is optionally substituted with C 1-4 alkanyloxy or hydroxy), C 1-4 alkanyl, or hydroxy. 
   
   
       9 . The compound according to  claim 1  wherein R 2  is selected from the group consisting of C 1-4 alkanyl, phenyl, and C 3-6 cycloalkanyl; provided that when Z is O or S, R 2  is other than unsubstituted C 1-4 alkanyl; and, wherein C 1-4 alkanyl is optionally substituted with one to three substituents independently selected from the group consisting of phenyl, C 1-4 alkanyloxy, hydroxy, fluoro, aminocarbonyl, C 1-8 alkanylaminocarbonyl, di(C 1-8 alkanyl)aminocarbonyl, and phenoxy; wherein the phenyl and phenoxy substituents of C 1-4 alkanyl are optionally further substituted with, and the phenyl of R 2  is optionally substituted with, one to three substituents independently selected from the group consisting of C 1-6 alkanyl, C 1-6 alkanyloxy, fluoro, hydroxy, and C 1-6 alkanylthio; or R 1  and R 2  taken together with the nitrogen to which they are attached form a pyrrolidinyl or piperidinyl ring wherein said pyrrolidinyl or piperidinyl is optionally substituted with a substituent selected from the group consisting of C 1-4 alkanyl and hydroxy. 
   
   
       10 . The compound according to  claim 1  wherein R 2  is selected from the group consisting of C 1-4 alkanyl and phenyl; provided that when Z is O or S, R 2  is other than unsubstituted C 1-4 alkanyl; and, wherein C 1-4 alkanyl is optionally substituted with one to three substituents independently selected from the group consisting of phenyl, C 1-4 alkanyloxy, hydroxy, fluoro, and phenoxy; wherein the phenyl and phenoxy substituents of C 1-4 alkanyl are optionally further substituted with, and the phenyl of R 2  is optionally substituted with, one to three substituents independently selected from the group consisting of C 1-6 alkanyl, C 1-6 alkanyloxy, fluoro, and hydroxy; or R 1  and R 2  taken together with the nitrogen to which they are attached form a pyrrolidinyl or piperidinyl ring wherein said pyrrolidinyl or piperidinyl is optionally substituted with a substituent selected from the group consisting of C 1-3 alkanyl and hydroxy. 
   
   
       11 . The compound according to  claim 1  wherein R 3  is selected from the group consisting of hydrogen, C 1-8 alkanyl, C 2-8 alkenyl, C 2-8 alkynyl, C 1-8 alkanyloxy(C 1-8 )alkanyl, C 1-8 alkanylthio(C 1-8 )alkanyl, hydroxyC 1-8 alkanyl, thioformyl, phenylimino(C 1-8 )alkanyl, phenyl(C 1-8 )alkanyl, and heteroaryl(C 1-8 )alkanyl wherein heteroaryl is selected from the group consisting of benzo[1,3]dioxolyl, imidazolyl, furanyl, pyridinyl, thienyl, indolyl, indolinyl, isoquinolinyl, pyrazinyl, pyrazolyl, pyridazinyl, pyrimidinyl, pyrrolyl, quinolinyl, isoquinolinyl, tetrazolyl; wherein phenyl and heteroaryl are optionally substituted with one to three substituents independently selected from the group consisting of C 1-6 alkanyloxy and hydroxy; or optionally, when phenyl and heteroaryl are optionally substituted with two substituents attached to adjacent carbon atoms, the two substituents together form a single fused moiety; wherein the moiety is selected from —O(CH 2 ) 1-3 O—. 
   
   
       12 . The compound according to  claim 1  wherein R 3  is selected from the group consisting of hydrogen, methyl, allyl, 2-methyl-allyl, propynyl, hydroxyethyl, methylthioethyl, methoxyethyl, thioformyl, phenyliminomethyl, phenethyl, and heteroaryl(C 1-8 )alkanyl wherein the heteroaryl is selected from the group consisting of benzo[1,3]dioxolyl, imidazolyl, furanyl, pyridinyl, thienyl, pyrimidinyl, pyrrolyl, quinolinyl, isoquinolinyl, tetrazolyl; wherein the phenyl in any phenyl-containing substituent is optionally substituted with one hydroxyl group. 
   
   
       13 . The compound according to  claim 1  wherein R 3  is hydrogen, methyl, allyl, or heteroarylmethyl wherein heteroaryl is selected from the group consisting of benzo[1,3]dioxolyl, imidazolyl, furanyl, pyridinyl, and thienyl. 
   
   
       14 . The compound according to  claim 1  wherein R 4  is one to three substituents independently selected from the group consisting of hydrogen, C 1-6 alkanyl, C 1-6 alkanyloxy, aminocarbonyl, aminothiocarbonyl, hydroxyamidino, formylamino, C 1-6 alkanylaminocarbonyl, C 1-6 alkanylcarbonylamino, halogen, hydroxy, C 6-10 aryl, chromanyl, chromenyl, furanyl, imidazolyl, indazolyl, indolyl, indolinyl, isoindolinyl, isoquinolinyl, isothiazolyl, isoxazolyl, naphthyridinyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinolizinyl, quinoxalinyl, tetrazolyl, thiazolyl, and thienyl. 
   
   
       15 . The compound according to  claim 1  wherein R 4  is one to two substituents independently selected from the group consisting of hydrogen, C 1-4 alkanyl, C 1-4 alkanyloxy, halogen, phenyl, furanyl, imidazolyl, indazolyl, indolyl, indolinyl, isoindolinyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, quinolinyl, tetrazolyl, thiazolyl, thienyl, hydroxy, and aminocarbonyl. 
   
   
       16 . The compound according to  claim 1  wherein R 4  is one to two substituents independently selected from the group consisting of hydrogen, methyl, methoxy, bromo, fluoro, 5- or 6-phenyl, 5- or 6-pyridinyl, 5- or 6-furanyl, and hydroxy. 
   
   
       17 . The compound according to  claim 1  wherein R 5  is one to two substituents independently selected from the group consisting of hydrogen and halogen. 
   
   
       18 . The compound according to  claim 1  wherein R 5  is hydrogen. 
   
   
       19 . (canceled) 
   
   
       20 . (canceled) 
   
   
       21 . The compound according to  claim 1  wherein X is O or S. 
   
   
       22 . (canceled) 
   
   
       23 . The compound according to  claim 1  wherein Z is O, NH, N(C 1-6 alkanyl), N(OH), N(OC 1-6 alkanyl), or N(phenyl). 
   
   
       24 . The compound according to  claim 1  wherein Z is O, NH, or N(OH). 
   
   
       25 . The compound according to  claim 1  wherein Z is O or NH. 
   
   
       26 . A compound of Formula (I): 
     
       
         
         
             
             
         
       
     
     wherein:
 G is —C(Z)NR 1 R 2 , phenyl, or a heterocycle selected from the group consisting of imidazolyl, triazolyl, tetrazolyl, oxadiazolyl, thiadiazolyl, oxathiadiazolyl, imidazolinyl, tetrahydropyrimidinyl, thienyl, pyrazolyl, pyrimidinyl, triazinyl, furyl, isothiazolyl, isoxazolyl, oxazolyl, isoxadiazolyl, quinolinyl, and pyridinyl; wherein phenyl and the heterocycles of G are optionally substituted with one to three substituents independently selected from the group consisting of C 1-8 alkanyl, C 1-8 alkanyloxy, hydroxy(C 1-8 )alkanyl, carboxy(C 1-8 )alkanyl, C 1-8 alkanylcarbonylamino, halogen, hydroxy, cyano, oxo, thioxo, amino, C 1-6 alkanylamino, di(C 1-6 alkanyl)amino, C 1-8 alkanylthio, aminocarbonyl, aminothiocarbonyl, C 1-8 alkanylaminocarbonyl, di(C 1-8 alkanyl)aminocarbonyl, and C 1-6 alkanyloxycarbonylamino; 
 R 1  is hydrogen or C 1-4 alkanyl; 
 R 2  is selected from the group consisting of hydrogen; C 1-4 alkanyl; phenyl; and C 3-6 cycloalkanyl; provided that when Z is O or S, R 2  is other than hydrogen or unsubstituted C 1-4 alkanyl; and, wherein C 1-4 alkanyl is optionally substituted with one to three substituents independently selected from the group consisting of phenyl, amino, C 1-6 alkanylamino, di(C 1-6 alkanyl)amino, C 1-4 alkanyloxy, hydroxy, fluoro, chloro, cyano, aminocarbonyl, C 1-8 alkanylaminocarbonyl, di(C 1-8 alkanyl)aminocarbonyl, and phenoxy; wherein the phenyl and phenoxy substituents of C 1-4 alkanyl are optionally further substituted with, and the phenyl and C 3-6 cycloalkanyl substituents of R 2  are optionally substituted with, one to three substituents independently selected from the group consisting of C 1-8 alkanyl, C 1-8 alkanyloxy, trifluoromethyl, phenyl, fluoro, hydroxy, C 1-8 alkanylthio, C 1-8 alkanylsulfonyl, and C 1-8 alkanylsulfonylamino; 
 or R 1  and R 2  taken together with the nitrogen to which they are attached form a 5-7 membered cycloheteroalkyl optionally substituted with phenyl (wherein phenyl is optionally substituted with C 1-4 alkanyloxy or hydroxy), C 1-4 alkanyl, or hydroxy; 
 R 3  is selected from the group consisting of hydrogen, C 1-8 alkanyl, C 2-8 alkenyl, C 2-8 alkynyl, C 1-8 alkanyloxy(C 1-8 )alkanyl, C 1-8 alkanylthio(C 1-8 )alkanyl, hydroxyC 1-8 alkanyl, thioformyl, phenylimino(C 1-8 )alkanyl, phenyl(C 1-8 )alkanyl, and heteroaryl(C 1-8 )alkanyl wherein heteroaryl is selected from the group consisting of benzo[1,3]dioxolyl, imidazolyl, furanyl, pyridinyl, thienyl, indolyl, indolinyl, isoquinolinyl, pyrazinyl, pyrazolyl, pyridazinyl, pyrimidinyl, pyrrolyl, quinolinyl, isoquinolinyl, tetrazolyl; wherein phenyl and heteroaryl are optionally substituted with one to three substituents independently selected from the group consisting of C 1-6 alkanyloxy and hydroxy; or optionally, when phenyl and heteroaryl are optionally substituted with two substituents attached to adjacent carbon atoms, the two substituents together form a single fused moiety; wherein the moiety is selected from —O(CH 2 ) 1-3 O—; 
 R 4  is one to three substituents independently selected from the group consisting of hydrogen, C 1-6 alkanyl, C 1-6 alkanyloxy, aminocarbonyl, aminothiocarbonyl, hydroxyamidino, formylamino, C 1-6 alkanylaminocarbonyl, C 1-6 alkanylcarbonylamino, halogen, hydroxy, C 6-10 aryl, chromanyl, chromenyl, furanyl, imidazolyl, indazolyl, indolyl, indolinyl, isoindolinyl, isoquinolinyl, isothiazolyl, isoxazolyl, naphthyridinyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinolizinyl, quinoxalinyl, tetrazolyl, thiazolyl, and thienyl; 
 R 5  is one to two substituents independently selected from the group consisting of hydrogen and halogen; 
 A is —(CH 2 ) 2 —; 
 Y is; 
 Z is O, NH, N(C 1-6 alkanyl), N(OH), N(OC 1-6 alkanyl), or N(phenyl); and 
 enantiomers, diastereomers, tautomers, solvates, and pharmaceutically acceptable salts thereof. 
 
   
   
       27 . A compound of Formula (I): 
     
       
         
         
             
             
         
       
     
     wherein:
 G is —C(Z)NR 1 R 2 , phenyl, or a heterocycle selected from the group consisting of imidazolyl, tetrazolyl, oxadiazolyl, thiadiazolyl, oxathiadiazolyl, imidazolinyl, thienyl, pyrazolyl, pyrimidinyl, triazinyl, furyl, isothiazolyl, isoxazolyl, oxazolyl, isoxadiazolyl, quinolinyl, and pyridinyl; wherein phenyl and the heterocycles of G are optionally substituted with one to three substituents independently selected from the group consisting of C 1-4 alkanyl, C 1-4 alkanyloxy, hydroxy(C 1-4 )alkanyl, carboxy(C 1-4 )alkanyl, C 1-4 alkanylcarbonylamino, hydroxy, cyano, oxo, thioxo, amino, C 1-6 alkanylamino, di(C 1-6 alkanyl)amino, C 1-8 alkanylthio, aminocarbonyl, aminothiocarbonyl, C 1-8 alkanylaminocarbonyl, and di(C 1-8 alkanyl)aminocarbonyl; 
 R 1  is selected from the group consisting of hydrogen, methyl, ethyl, and propyl; 
 R 2  is selected from the group consisting of C 1-4 alkanyl, phenyl, and C 3-6 cycloalkanyl; provided that when Z is O or S, R 2  is other than unsubstituted C 1-4 alkanyl; and, wherein C 1-4 alkanyl is optionally substituted with one to three substituents independently selected from the group consisting of phenyl, C 1-4 alkanyloxy, hydroxy, fluoro, aminocarbonyl, C 1-8 alkanylaminocarbonyl, di(C 1-8 alkanyl)aminocarbonyl, and phenoxy; wherein the phenyl and phenoxy substituents of C 1-4 alkanyl are optionally further substituted with, and the phenyl of R 2  is optionally substituted with, one to three substituents independently selected from the group consisting of C 1-6 alkanyl, C 1-6 alkanyloxy, fluoro, hydroxy, and C 1-6 alkanylthio; or R 1  and R 2  taken together with the nitrogen to which they are attached form pyrrolidinyl or piperidinyl ring wherein said pyrrolidinyl or piperidinyl is optionally substituted with a substituent selected from the group consisting of C 1-3 alkanyl and hydroxy; 
 R 3  is selected from the group consisting of hydrogen, methyl, allyl, 2-methyl-allyl, propynyl, hydroxyethyl, methylthioethyl, methoxyethyl, thioformyl, phenyliminomethyl, phenethyl, and heteroaryl(C 1-8 )alkanyl wherein the heteroaryl is selected from the group consisting of benzo[1,3]dioxolyl, imidazolyl, furanyl, pyridinyl, thienyl, pyrimidinyl, pyrrolyl, quinolinyl, isoquinolinyl, tetrazolyl; wherein the phenyl in any phenyl-containing substituent is optionally substituted with one hydroxyl group; 
 R 4  is one to two substituents independently selected from the group consisting of hydrogen, C 1-4 alkanyl, C 1-4 alkanyloxy, halogen, phenyl, furanyl, imidazolyl, indazolyl, indolyl, indolinyl, isoindolinyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, quinolinyl, tetrazolyl, thiazolyl, thienyl, hydroxy, and aminocarbonyl; 
 R 5  is hydrogen; 
 A is —(CH 2 ) 2 —; 
 Y is S; 
 Z is O, NH, or N(OH); and 
 enantiomers, diastereomers, tautomers, solvates, and pharmaceutically acceptable salts thereof. 
 
   
   
       28 . The compound according to  claim 27  wherein G is —C(Z)NR 1 R 2 , phenyl, or a heterocycle selected from the group consisting of imidazolyl, tetrazolyl, oxadiazolyl, thiadiazolyl, oxathiadiazolyl, thienyl, isothiazolyl, isoxazolyl, isoxadiazolyl, quinolinyl, and pyridinyl; wherein phenyl and the heterocycles of G are optionally substituted with one to three substituents independently selected from the group consisting of C 1-4 alkanyl, C 1-4 alkanyloxy, hydroxy(C 1-4 )alkanyl, C 1-4 alkanylcarbonylamino, hydroxy, cyano, oxo, thioxo, and aminocarbonyl. 
   
   
       29 . The compound according to  claim 27  wherein G is —C(Z)NR 1 R 2 , 2-methylcarbonylaminophenyl, 2-aminocarbonyl-phenyl, 1H-tetrazol-5-yl, 2-methyl-tetrazol-5-yl, 4H-[1,2,4]-oxadiazol-5-oxo-3-yl, 4H-[1,2,4]-oxadiazol-5-thioxo-3-yl, 4H-[1,2,4]thiadiazol-5-oxo-3-yl, [1,2,3,5]oxathiadiazol-2-oxo-4-yl, or pyridin-3-yl. 
   
   
       30 . The compound according to  claim 27  wherein R 2  is selected from the group consisting of C 1-4 alkanyl and phenyl; provided that when Z is O or S, R 2  is other than unsubstituted C 1-4 alkanyl; and, wherein C 1-4 alkanyl is optionally substituted with one to three substituents independently selected from the group consisting of phenyl, C 1-4 alkanyloxy, hydroxy, fluoro, and phenoxy; wherein the phenyl and phenoxy substituents of C 1-4 alkanyl are optionally further substituted with, and the phenyl of R 2  is optionally substituted with, one to three substituents independently selected from the group consisting of C 1-6 alkanyl, C 1-6 alkanyloxy, fluoro, and hydroxy; or R 1  and R 2  taken together with the nitrogen to which they are attached form a pyrrolidinyl or piperidinyl ring wherein said pyrrolidinyl or piperidinyl is optionally substituted with a substituent selected from C 1-3 alkanyl or hydroxy; and R 3  is a substituent selected from the group consisting of benzo[1,3]dioxol-5-ylmethyl, carbamimidoyl, 1-H-imidazol-4-ylmethyl, phenyliminomethyl, 1-prop-2-ynyl, thioformyl, 2-hydroxyphenyl-methyl, hydroxy-ethyl, methoxy-ethyl, 2-methyl-allyl, 2-methyl-but-2-enyl, allyl, furan-3-ylmethyl, H, Me, methylthioethyl, phenethyl, pyridin-2-yl methyl, and thiophen-2-yl methyl. 
   
   
       31 . A compound of Formula (I): 
     
       
         
         
             
             
         
       
     
     wherein:
 G is selected from —C(Z)NR 1 R 2 , 2-methylcarbonylaminophenyl, 2-aminocarbonyl-phenyl, 1H-tetrazol-5-yl, 2-methyl-tetrazol-5-yl, 4H-[1,2,4]-oxadiazol-5-oxo-3-yl, 4H-[1,2,4]-oxadiazol-5-thioxo-3-yl, 4H-[1,2,4]thiadiazol-5-oxo-3-yl, [1,2,3,5]oxathiadiazol-2-oxo-4-yl, or pyridin-3-yl; 
 R 1  is hydrogen, methyl, or ethyl; 
 R 2  is selected from the group consisting of C 1-4 alkanyl and phenyl; provided that when Z is O or S, R 2  is other than unsubstituted C 1-4 alkanyl; and, wherein C 1-4 alkanyl is optionally substituted with one to three substituents independently selected from the group consisting of phenyl, C 1-4 alkanyloxy, hydroxy, fluoro, and phenoxy; wherein the phenyl and phenoxy substituents of C 1-4 alkanyl are optionally further substituted with, and the phenyl of R 2  is optionally substituted with, one to three substituents independently selected from the group consisting of C 1-6 alkanyl, C 1-6 alkanyloxy, fluoro, and hydroxy; or R 1  and R 2  taken together with the nitrogen to which they are attached form a pyrrolidinyl or piperidinyl ring wherein said pyrrolidinyl or piperidinyl is optionally substituted with a substituent selected from C 1-3 alkanyl or hydroxy; 
 R 3  is selected from the group consisting of hydrogen, methyl, allyl, 2-methyl-allyl, propynyl, hydroxyethyl, methylthioethyl, methoxyethyl, thioformyl, phenyliminomethyl, phenethyl, and heteroaryl(C 1-8 )alkanyl wherein the heteroaryl is selected from the group consisting of benzo[1,3]dioxolyl, imidazolyl, furanyl, pyridinyl, thienyl, pyrimidinyl, pyrrolyl, quinolinyl, isoquinolinyl, tetrazolyl; wherein the phenyl in any phenyl-containing substituent is optionally substituted with one hydroxyl group; 
 R 4  is one to three substituents independently selected from the group consisting of hydrogen, C 1-4 alkanyl, C 1-4 alkanyloxy, halogen, phenyl, furanyl, imidazolyl, indazolyl, indolyl, indolinyl, isoindolinyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, quinolinyl, tetrazolyl, thiazolyl, thienyl, hydroxy, and aminocarbonyl; 
 R 5  is hydrogen; 
 A is —(CH 2 ) 2 —; 
 Y is S; 
 Z is O or NH; and 
 
     enantiomers, diastereomers, tautomers, solvates, and pharmaceutically acceptable salts thereof. 
   
   
       32 . The compound according to  claim 31  wherein R 2  is a substituent selected from the group consisting of C 1-4 alkanyl and phenyl; provided that when Z is O or S, R 2  is other than unsubstituted C 1-4 alkanyl; and, wherein C 1-4 alkanyl is optionally substituted with one to three substituents independently selected from the group consisting of phenyl, C 1-4 alkanyloxy, hydroxy, and 2,6-dimethyl-phenoxy; one to three substituents independently selected from the group consisting of C 1-6 alkanyl, C 1-6 alkanyloxy, fluoro, and hydroxy; or R 1  and R 2  taken together with the nitrogen to which they are attached form a pyrrolidinyl or piperidinyl ring wherein said pyrrolidinyl or piperidinyl is optionally substituted with a substituent selected from C 1-3 alkanyl or hydroxy. 
   
   
       33 . The compound according to  claim 31  wherein R 3  is a substituent selected from the group consisting of benzo[1,3]dioxol-5-ylmethyl, carbamimidoyl, 1-H-imidazol-4-ylmethyl, phenyliminomethyl, 1-prop-2-ynyl, thioformyl, 2-hydroxyphenyl-methyl, hydroxy-ethyl, methoxy-ethyl, 2-methyl-allyl, 2-methyl-but-2-enyl, allyl, furan-3-ylmethyl, H, Me, methylthioethyl, phenethyl, pyridin-2-yl methyl, and thiophen-2-ylmethyl; and R 4  is one to two substituents independently selected from the group consisting of hydrogen, C 1-4 alkanyl, C 1-4 alkanyloxy, halogen, phenyl, furanyl, imidazolyl, indazolyl, indolyl, indolinyl, isoindolinyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, quinolinyl, tetrazolyl, thiazolyl, thienyl, and hydroxy. 
   
   
       34 . The compound according to  claim 31  wherein R 3  is a substituent selected from the group consisting of benzo[1,3]dioxol-5-ylmethyl, carbamimidoyl, 1-H-imidazol-4-yl methyl, phenyliminomethyl, 1-prop-2-ynyl, thioformyl, 2-hydroxyphenyl-methyl, hydroxyethyl, methoxyethyl, allyl, furan-3-yl methyl, H, Me, methylthioethyl, and phenethyl; R 4  is one to two substituents independently selected from the group consisting of hydrogen, methyl, methoxy, bromo, fluoro, 5- or 6-phenyl, 5- or 6-pyridinyl, 5- or 6-furanyl, and hydroxy. 
   
   
       35 . The compound according to  claim 31  wherein R 3  is a substituent selected from the group consisting of H, benzo[1,3]dioxol-5-ylmethyl, 1-H-imidazol-4-yl methyl, furan-3-ylmethyl, pyridin-2-ylmethyl, and phenyliminomethyl; and R 4  is a substituent independently selected from the group consisting of hydrogen, methyl, methoxy, bromo, fluoro, 5- or 6-phenyl, 5- or 6-pyridinyl, 5- or 6-furanyl, and hydroxy. 
   
   
       36 . A compound of Formula (I): 
     
       
         
         
             
             
         
       
       selected from the group consisting of: 
       a compound of Formula (I) wherein G is phenylthio; R 3  is H; R 4  is H; R 5  is H; and Y is S; 
       a compound of Formula (I) wherein G is 1H-tetrazol-5-yl; R 3  is H; R 4  is H; R 5  is H; and Y is S; 
       a compound of Formula (I) wherein G is 1H-tetrazol-5-yl; R 3  is H; R 4  is H; R 5  is H; and Y is S; 
       a compound of Formula (I) wherein G is pyridin-3-yl; R 3  is H; R 4  is H; R 5  is H; and Y is S; 
       a compound of Formula (I) wherein G is 2-methylcarbonylamino-phenyl; R 3  is H; R 4  is H; R 5  is H; and Y is S; 
       a compound of Formula (I) wherein G is pyridin-3-yl; R 3  is methyl; R 4  is H; R 5  is H; and Y is S; 
       a compound of Formula (I) wherein G is pyridin-3-yl; R 3  is 1H-imidazol-2-ylmethyl; R 4  is H; R 5  is H; and Y is S; 
       a compound of Formula (I) wherein G is pyridin-3-yl; R 3  is fur-3-ylmethyl; R 4  is H; R 5  is H; and Y is S; 
       a compound of Formula (I) wherein G is pyridin-3-yl; R 3  is pyridin-2-ylmethyl; R 4  is H; R 5  is H; and Y is S; 
       a compound of Formula (I) wherein G is 2-methylcarbonylamino-phenyl; R 3  is methyl; R 4  is H; R 5  is H; and Y is S; 
       a compound of Formula (I) wherein G is 2-methylcarbonylamino-phenyl; R 3  is 1H-imidazol-2-ylmethyl; R 4  is H; R 5  is H; and Y is S; 
       a compound of Formula (I) wherein G is 2-methylcarbonylamino-phenyl; R 3  is fur-3-ylmethyl; R 4  is H; R 5  is H; and Y is S; and 
       a compound of Formula (I) wherein G is 2-methylcarbonylamino-phenyl; R 3  is pyridin-2-ylmethyl; R 4  is H; R 5  is H; and Y is S. 
     
   
   
       37 . A compound of Formula (I): 
     
       
         
         
             
             
         
       
       selected from the group consisting of: 
       a compound of Formula (I) wherein G is 1H-tetrazol-5-yl; R 3  is H; R 4  is H; R 5  is H; and Y is S; 
       a compound of Formula (I) wherein G is 1H-tetrazol-5-yl; R 3  is H; R 4  is H; R 5  is H; and Y is S; 
       a compound of Formula (I) wherein G is 2-methylcarbonylamino-phenyl; R 3  is H; R 4  is H; R 5  is H; and Y is S; 
       a compound of Formula (I) wherein G is pyridin-3-yl; R 3  is methyl; R 4  is H; R 5  is H; and Y is S; 
       a compound of Formula (I) wherein G is pyridin-3-yl; R 3  is 1H-imidazol-2-ylmethyl; R 4  is H; R 5  is H; and Y is S; 
       a compound of Formula (I) wherein G is pyridin-3-yl; R 3  is fur-3-ylmethyl; R 4  is H; R 5  is H; and Y is S; 
       a compound of Formula (I) wherein G is pyridin-3-yl; R 3  is pyridin-2-ylmethyl; R 4  is H; R 5  is H; and Y is S; 
       a compound of Formula (I) wherein G is 2-methylcarbonylamino-phenyl; R 3  is 1H-imidazol-2-ylmethyl; R 4  is H; R 5  is H; and Y is S; 
       a compound of Formula (I) wherein G is 2-methylcarbonylamino-phenyl; R 3  is fur-3-ylmethyl; R 4  is H; R 5  is H; and Y is S; and 
       a compound of Formula (I) wherein G is 2-methylcarbonylamino-phenyl; R 3  is pyridin-2-ylmethyl; R 4  is H; R 5  is H; and Y is S. 
     
   
   
       38 . A compound of Formula (I): 
     
       
         
         
             
             
         
       
       selected from the group consisting of: 
       a compound of Formula (I) wherein G is 1H-tetrazol-5-yl; R 3  is H; R 4  is H; R 5  is H; and Y is S; 
       a compound of Formula (I) wherein G is 1H-tetrazol-5-yl; R 3  is H; R 4  is H; R 5  is H; and Y is S; 
       a compound of Formula (I) wherein G is 2-methylcarbonylamino-phenyl; R 3  is H; R 4  is H; R 5  is H; and Y is S; 
       a compound of Formula (I) wherein G is pyridin-3-yl; R 3  is 1H-imidazol-2-ylmethyl; R 4  is H; R 5  is H; and Y is S; 
       a compound of Formula (I) wherein G is pyridin-3-yl; R 3  is fur-3-ylmethyl; R 4  is H; R 5  is H; and Y is S; 
       a compound of Formula (I) wherein G is pyridin-3-yl; R 3  is pyridin-2-ylmethyl; R 4  is H; R 5  is H; and Y is S; 
       a compound of Formula (I) wherein G is 2-methylcarbonylamino-phenyl; R 3  is fur-3-ylmethyl; R 4  is H; R 5  is H; and Y is S; and 
       a compound of Formula (I) wherein G is 2-methylcarbonylamino-phenyl; R 3  is pyridin-2-ylmethyl; R 4  is H; R 5  is H; and Y is S. 
     
   
   
       39 . A compound of Formula (I): 
     
       
         
         
             
             
         
       
       selected from the group consisting of: 
       a compound of Formula (I) wherein G is 1H-tetrazol-5-yl; R 3  is H; R 3  is H; R 5  is H; and Y is S; 
       a compound of Formula (I) wherein G is 1H-tetrazol-5-yl; R 3  is H; R 4  is H; R 5  is H; and Y is S; and 
       a compound of Formula (I) wherein G is 2-methylcarbonylamino-phenyl; R 3  is pyridin-2-ylmethyl; R 4  is H; R 5  is H; and Y is S. 
     
   
   
       40 . A compound of Formula (Ib): 
     
       
         
         
             
             
         
       
       selected from the group consisting of: 
       a compound of Formula (Ib) wherein G is methoxycarbonyl; R 3  is H; R 4  is H; R 5  is H; and Y is S; 
       a compound of Formula (Ib) wherein G is bromo; R 3  is H; R 4  is H; R 5  is H; and Y is S; and 
       a compound of Formula (Ib) wherein G is cyano; R 3  is H; R 4  is H; R 5  is H; and Y is S. 
     
   
   
       41 . A composition comprising the dextrorotatory enantiomer of a compound of formula (I) wherein said composition is substantially free from the levorotatory isomer of said compound. 
   
   
       42 . A composition comprising the levororotatory enantiomer of a compound of formula (I) wherein said composition is substantially free from the dextrorotatory isomer of said compound. 
   
   
       43 . A pharmaceutical composition comprising a compound, salt or solvate according to  claim 1  admixed with a pharmaceutically acceptable carrier, excipient or diluent. 
   
   
       44 . A veterinary composition comprising a compound, salt or solvate according to  claim 1  admixed with a veterinarily acceptable carrier, excipient or diluent. 
   
   
       45 . (canceled) 
   
   
       46 . (canceled) 
   
   
       47 . (canceled) 
   
   
       48 . (canceled) 
   
   
       49 . (canceled) 
   
   
       50 . (canceled) 
   
   
       51 . (canceled) 
   
   
       52 . (canceled) 
   
   
       53 . (canceled) 
   
   
       54 . (canceled) 
   
   
       55 . The method of  claim 49  wherein said therapeutically effective amount comprises a dose range of from about 100 mg to about 1000 mg. 
   
   
       56 . A kit comprising in one or more containers an amount of the composition of  claim 1  effective to treat or prevent mild to severe pain. 
   
   
       57 . (canceled) 
   
   
       58 . (canceled) 
   
   
       59 . (canceled) 
   
   
       60 . (canceled) 
   
   
       61 . (canceled) 
   
   
       62 . (canceled) 
   
   
       63 . (canceled) 
   
   
       64 . (canceled) 
   
   
       65 . (canceled) 
   
   
       66 . A kit comprising in one or more containers an amount of the composition of  claim 26  effective to treat or prevent mild to severe pain. 
   
   
       67 . (canceled) 
   
   
       68 . A veterinary composition comprising a compound, salt or solvate according to  claim 31  admixed with a veterinarily acceptable carrier, excipient or diluent. 
   
   
       69 . (canceled) 
   
   
       70 . (canceled) 
   
   
       71 . (canceled) 
   
   
       72 . (canceled) 
   
   
       73 . (canceled) 
   
   
       74 . (canceled) 
   
   
       75 . (canceled) 
   
   
       76 . A kit comprising in one or more containers an amount of the composition of  claim 31  effective to treat or prevent mild to severe pain. 
   
   
       77 . (canceled) 
   
   
       78 . A veterinary composition comprising a compound, salt or solvate according to  claim 36  admixed with a veterinarily acceptable carrier, excipient or diluent. 
   
   
       79 . (canceled) 
   
   
       80 . (canceled) 
   
   
       81 . (canceled) 
   
   
       82 . (canceled) 
   
   
       83 . (canceled) 
   
   
       84 . (canceled) 
   
   
       85 . (canceled) 
   
   
       86 . A kit comprising in one or more containers an amount of the composition of  claim 36  effective to treat or prevent mild to severe pain. 
   
   
       87 . (canceled) 
   
   
       88 . A veterinary composition comprising a compound, salt or solvate according to  claim 37  admixed with a veterinarily acceptable carrier, excipient or diluent. 
   
   
       89 . (canceled) 
   
   
       90 . (canceled) 
   
   
       91 . (canceled) 
   
   
       92 . (canceled) 
   
   
       93 . (canceled) 
   
   
       94 . (canceled) 
   
   
       95 . (canceled) 
   
   
       96 . A kit comprising in one or more containers an amount of the composition of  claim 37  effective to treat or prevent mild to severe pain. 
   
   
       97 . A pharmaceutical composition comprising a compound, salt or solvate according to  claim 38  admixed with a pharmaceutically acceptable carrier, excipient or diluent. 
   
   
       98 . A veterinary composition comprising a compound, salt or solvate according to  claim 38  admixed with a veterinarily acceptable carrier, excipient or diluent. 
   
   
       99 . (canceled) 
   
   
       100 . (canceled) 
   
   
       101 . (canceled) 
   
   
       102 . (canceled) 
   
   
       103 . (canceled) 
   
   
       104 . (canceled) 
   
   
       105 . (canceled) 
   
   
       106 . A kit comprising in one or more containers an amount of the composition of  claim 38  effective to treat or prevent mild to severe pain. 
   
   
       107 . A pharmaceutical composition comprising a compound, salt or solvate according to  claim 39  admixed with a pharmaceutically acceptable carrier, excipient or diluent. 
   
   
       108 . A veterinary composition comprising a compound, salt or solvate according to  claim 39  admixed with a veterinarily acceptable carrier, excipient or diluent. 
   
   
       109 . (canceled) 
   
   
       110 . (canceled) 
   
   
       111 . (canceled) 
   
   
       112 . (canceled) 
   
   
       113 . (canceled) 
   
   
       114 . (canceled) 
   
   
       115 . (canceled) 
   
   
       116 . A kit comprising in one or more containers an amount of the composition of  claim 39  effective to treat or prevent mild to severe pain. 
   
   
       117 . A compound of Formula (Ib): 
     
       
         
         
             
             
         
       
     
     wherein:
 G is bromo, chloro, cyano, trifluoromethanesulfonyloxy, C 1-8 alkanyloxycarbonyl, carboxy, —C(Z)NR 1 R 2 , C 6-10 aryl, C 6-10 arylthio, or a heterocycle selected from the group consisting of imidazolyl, triazolyl, tetrazolyl, oxadiazolyl, thiadiazolyl, oxathiadiazolyl, imidazolinyl, tetrahydropyrimidinyl, thienyl, pyrazolyl, pyrimidinyl, triazinyl, furyl, indazolyl, indolyl, indolinyl, isothiazolyl, isoxazolyl, oxazolyl, isoxadiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl, and pyridinyl; wherein the C 6-10 aryl group in the C 6-10 aryl-containing substituents of G and the heterocycles of G are optionally substituted with one to three substituents independently selected from the group consisting of C 1-8 alkanyl, C 2-8 alkenyl, C 2-8 alkynyl, C 1-8 alkanyloxy, hydroxy(C 1-8 )alkanyl, carboxy(C 1-8 )alkanyl, C 1-8 alkanylcarbonylamino, halogen, hydroxy, cyano, nitro, oxo, thioxo, amino, C 1-6 alkanylamino, di(C 1-6 alkanyl)amino, C 1-8 alkanylthio, C 1-8 alkanylsulfonyl, C 1-8 alkanylsulfonylamino, aminocarbonyl, aminothiocarbonyl, aminocarbonylamino, aminothiocarbonylamino, C 1-8 alkanylaminocarbonyl, di(C 1-8 alkanyl)aminocarbonyl, and C 1-6 alkanyloxycarbonylamino; 
 R 1  is a substituent selected from the group consisting of hydrogen, C 1-8 alkanyl, C 2-8 alkenyl, and C 2-8 alkynyl; 
 R 2  is a substituent selected from the group consisting of hydrogen; C 1-8 alkanyl; C 2-8 alkenyl; C 2-8 alkynyl; C 6-10 aryl; and C 3-8 cycloalkanyl; provided that when Z is O or S, R 2  is other than hydrogen or unsubstituted C 1-8 alkanyl; and, wherein C 1-8 alkanyl of R 2  is optionally substituted with one to three substituents independently selected from the group consisting of phenyl, amino, C 1-6 alkanylamino, di(C 1-6 alkanyl)amino, C 1-6 alkanyloxy, C 1-6 alkanylthio, hydroxy, fluoro, chloro, cyano, aminocarbonyl, C 1-8 alkanylaminocarbonyl, di(C 1-8 alkanyl)aminocarbonyl, C 1-6 alkanyloxycarbonyl, and aryloxy; wherein the phenyl and aryloxy substituents of C 1-8 alkanyl are optionally further substituted with, and the C 6-10 aryl and C 3-8 cycloalkanyl substituents of R 2  are optionally substituted with, one to three substituents independently selected from the group consisting of C 1-8 alkanyl, C 2-8 alkenyl, C 2-8 alkynyl, C 1-8 alkanyloxy, trifluoromethyl, trifluoromethoxy, phenyl, halogen, cyano, hydroxy, C 1-8 alkanylthio, C 1-8 alkanylsulfonyl, and C 1-8 alkanylsulfonylamino; 
 or R 1  and R 2  taken together with the nitrogen to which they are attached form a 5-7 membered cycloheteroalkyl optionally substituted with phenyl (wherein phenyl is optionally substituted with one to three C 1-4 alkanyl or C 1-4 alkanyloxy substituents) and one to two additional substituents independently selected from the group consisting of C 1-8 alkanyl, hydroxy(C 1-8 )alkanyl, hydroxy, amino, C 1-6 alkanylamino, di(C 1-6 alkanyl)amino, and halogen; 
 or, R 1  and R 2  taken together with the nitrogen to which they are attached form a 5-7 membered cycloheteroalkyl optionally substituted with one to three substituents independently selected from the group consisting of C 1-8 alkanyl, hydroxy(C 1-8 )alkanyl, hydroxy, amino, C 1-6 alkanylamino, di(C 1-6 alkanyl)amino, and halogen; 
 R 3  is a substituent selected from the group consisting of hydrogen, C 1-8 alkanyl, halo 1-3 (C 1-8 )alkanyl, C 2-8 alkenyl, C 2-8 alkynyl, C 3-8 cycloalkanyl, cycloalkanyl(C 1-8 )alkanyl, C 1-8 alkanyloxy(C 1-8 )alkanyl, C 1-8 alkanylthio(C 1-8 )alkanyl, hydroxyC 1-8 alkanyl, C 1-8 alkanyloxycarbonyl, halo 1-3 (C 1-8 )alkanylcarbonyl, formyl, thioformyl, carbamimidoyl, phenylimino(C 1-8 )alkanyl, phenyl(C 1-8 )alkanyl, phenyl(C 1-8 )alkenyl, phenyl(C 1-8 )alkynyl, naphthyl(C 1-8 )alkanyl and heteroaryl(C 1-8 )alkanyl wherein the heteroaryl is selected from the group consisting of benzo[1,3]dioxolyl, imidazolyl, furanyl, pyridinyl, thienyl, indazolyl, indolyl, indolinyl, isoindolinyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyrimidinyl, pyrrolyl, quinolinyl, isoquinolinyl, tetrazolyl, thiazolyl; wherein phenyl, naphthyl and heteroaryl are optionally substituted with one to three substituents independently selected from the group consisting of C 1-6 alkanyl, C 2-6 alkenyl, C 1-6 alkanyloxy, amino, C 1-6 alkanylamino, di(C 1-6 alkanyl)amino, C 1-6 alkanylcarbonyl, C 1-6 alkanylcarbonyloxy, C 1-6 alkanylcarbonylamino, C 1-6 alkanylthio, C 1-6 alkanylsulfonyl, halogen, hydroxy, cyano, fluoro(C 1-6 )alkanyl, thioureido, and fluoro(C 1-6 )alkanyloxy; alternatively, when phenyl and heteroaryl are optionally substituted with alkanyl or alkanyloxy substituents attached to adjacent carbon atoms, the two substituents can together form a fused cyclic alkanyl or cycloheteroalkanyl selected from the group consisting of —(CH 2 ) 3-5 —, —O(CH 2 ) 2-4 —, —(CH 2 ) 2-4 O—, and —O(CH 2 ) 1-3 O—; 
 R 4  is one to three substituents independently selected from the group consisting of hydrogen, C 1-6 alkanyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl(C 2-6 )alkynyl, C 1-6 alkanyloxy, amino, C 1-6 alkanylamino, di(C 1-6 alkanyl)amino, C 1-6 alkanylcarbonyl, C 1-6 alkanylcarbonyloxy, C 1-6 alkanyloxycarbonyl, aminocarbonyl, C 1-6 alkanylaminocarbonyl, di(C 1-6 alkanyl)aminocarbonyl, C 1-6 alkanylcarbonylamino, C 1-6 alkanylthio, C 1-6 alkanylsulfonyl, halogen, hydroxy, mercapto, aminothiocarbonyl, amidino, hydroxyamidino, phenylcarbonyl, —C(═NOH)phenyl, aminomethyl, hydroxymethyl, methanesulfonylamino, C 6-10 arylamino (wherein C 6-10 aryl is optionally substituted with one to three substitutents independently selected from the group consisting of C 1-6 alkanyl, C 1-6 alkoxy, halogen, and hydroxy), dihydroimidazolyl, formylamino, thioformylamino, pyridinylamino, cyano, hydroxycarbonyl, C 6-10 aryl, chromanyl, chromenyl, furanyl, imidazolyl, indazolyl, indolyl, indolinyl, isoindolinyl, isoquinolinyl, isothiazolyl, isoxazolyl, naphthyridinyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinolizinyl, quinoxalinyl, tetrazolyl, thiazolyl, thienyl, fluoroalkanyl and fluoroalkanyloxy; or optionally, when R 4  is two substituents attached to adjacent carbon atoms, the two substituents together form a single fused moiety; wherein the fused moiety is selected from the group consisting of —(CH 2 ) 3-5 —, —O(CH 2 ) 2-4 —, —(CH 2 ) 2-4 O—, —O(CH 2 ) 1-3 O— and —S—C(NH 2 )═N—; 
 R 5  is one to two substituents independently selected from the group consisting of hydrogen, C 1-6 alkanyl, C 2-6 alkenyl, C 1-6 alkanyloxy, amino, C 1-6 alkanylamino, di(C 1-6 alkanyl)amino, C 1-6 alkanylcarbonyl, C 1-6 alkanylcarbonyloxy, C 1-6 alkanyloxycarbonyl, C 1-6 alkanylaminocarbonyl, C 1-6 alkanylcarbonylamino, C 1-6 alkanylthio, C 1-6 alkanylsulfonyl, halogen, hydroxy, cyano, fluoro(C 1-6 )alkanyl and fluoro(C 1-6 )alkanyloxy; 
 A (CH 2 ) 2 ; 
 Y is S; 
 X is O or S 
 n is 0 or 1; 
 Z is O, S, NH, N(C 1-6 alkanyl), N(OH), N(OC 1-6 alkanyl), or N(phenyl); 
 and enantiomers, diastereomers, tautomers, solvates, or pharmaceutically acceptable salts thereof. 
 
   
   
       118 . The compound according to  claim 117  wherein G is bromo or cyano