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Claims for Patent: 5,719,147

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Claims for Patent: 5,719,147

Title: Morpholine and thiomorpholine tachykinin receptor antagonists
Abstract:Substituted heterocycles of the general structural formula: ##STR1## are tachykinin receptor antagonists useful in the treatment of inflammatory diseases, pain or migraine, asthma and emesis, and calcium channel blockers useful in the treatment of cardiovascular conditions such as angina, hypertension or ischemia.
Inventor(s): Dorn; Conrad P. (Plainfield, NJ), Finke; Paul E. (Milltown, NJ), Hale; Jeffrey J. (Westfield, NJ), MacCoss; Malcolm (Freehold, NJ), Mills; Sander G. (Woodbridge, NJ), Shah; Shrenik K. (Metuchen, NJ), Chambers; Mark Stuart (North Bushey, GB2), Harrison; Timothy (Great Dunmow, GB2), Ladduwahetty; Tamara (Buckhurst Hill, GB2), Williams; Brian John (Great Dunnow, GB2)
Assignee: Merck & Co., Inc. (Rahway, NJ)
Application Number:08/525,259
Patent Claims: 1. A compound of the structural formula: ##STR19## or a pharmaceutically acceptable salt thereof, wherein: R.sup.1 is selected from the group consisting of:

(1) hydrogen;

(2) C.sub.1-6 alkyl, unsubstituted or substituted with one or more of the substituents selected from:

(a) hydroxy,

(b) OXO,

(c) C.sub.1-6 alkoxy,

(d) phenyl-C.sub.1-3 alkoxy,

(e) phenyl,

(f) --CN,

(g) halo, wherein halo is fluoro, chloro, bromo or iodo,

(h) --NR.sup.9 R.sup.10, wherein R.sup.9 and R.sup.10 are independently selected from:

(i) hydrogen,

(ii) C.sub.1-6 alkyl,

(iii) hydroxy-C.sub.1-6 alkyl, and

(iv) phenyl,

(i) --NR.sup.9 COR.sup.10,

(j) --NR.sup.9 CO.sub.2 R.sup.10,

(j) --NR.sup.9 CO.sub.2 R.sup.10,

(k) --CONR.sup.9 R.sup.10,

(l) --COR.sup.9,

(m) --CO.sub.2 R.sup.9,

(n) heterocycle, wherein the heterocycle is selected from the group consisting of:

(A) benzimidazolyl,

(B) benzofuranyl,

(C) benzothiophenyl,

(D) benzoxazolyl,

(E) furanyl,

(F) imidazolyl,

(G) indolyl,

(H) isooxazolyl,

(I) isothiazolyl,

(J) oxadiazolyl,

(K) oxazolyl,

(L) pyrazinyl,

(M) pyrazolyl,

(N) pyridyl,

(O) pyrimidyl,

(P) pyrrolyl,

(Q) quinolyl,

(R) tetrazolyl,

(S) thiadiazolyl,

(T) thiazolyl,

(U) thienyl,

(V) triazolyl,

(W) azetidinyl,

(X) 1,4-dioxanyl,

(Y) hexahydroazepinyl,

(Z) piperazinyl,

(AA) piperidinyl,

(AB) pyrrolidinyl,

(AC) tetrahydrofuranyl, and

(AD) tetrahydrothienyl, and wherein the heterocycle is unsubstituted or substituted with one or more substituent(s) selected from:

(i) C.sub.1-6 alkyl, unsubstituted or substituted with halo, --CF.sub.3, --OCH.sub.3, or phenyl,

(ii) C.sub.1-6 alkoxy,

(iii) oxo,

(iv) hydroxy,

(v) thioxo,

(vi) --SR.sup.9,

(vii) halo,

(viii) cyano,

(ix) phenyl,

(x) trifluoromethyl,

(xi) --(CH.sub.2).sub.m --NR.sup.9 R.sup.10, wherein m is 0, 1 or 2,

(xii) --NR.sup.9 COR.sup.10,

(xiii) --CONR.sup.9 R.sup.10,

(xiv) --CO.sub.2 R.sup.9, and

(xv) --(CH.sub.2).sub.m --OR.sup.9 ;

(3) C.sub.2-6 alkenyl, unsubstituted or substituted with one or more of the substituent(s) selected from:

(a) hydroxy,

(b) oxo,

(c) C.sub.1-6 alkoxy,

(d) phenyl-C.sub.1-3 alkoxy,

(e) phenyl,

(f) --CN,

(g) halo,

(h) --CONR.sup.9 R.sup.10,

(i) --COR.sup.9,

(j) --CO.sub.2 R.sup.9,

(k) heterocycle;

(4) C.sub.2-6 alkynyl;

(5) phenyl, unsubstituted or substituted with one or more of the substituent(s) selected from:

(a) hydroxy,

(b) C.sub.1-6 alkoxy,

(c) C.sub.1-6 alkyl,

(d) C.sub.2-5 alkenyl,

(e) halo,

(f) --CN,

(g) --NO.sub.2,

(h) --CF.sub.3,

(i) --(CH.sub.2).sub.m --NR.sup.9 R.sup.10,

(j) --NR.sup.9 COR.sup.10,

(k) --NR.sup.9 CO.sub.2 R.sup.10,

(l) --CONR.sup.9 R.sup.10,

(m) --CO.sub.2 NR.sup.9 R.sup.10,

(n) --COR.sup.9, and

(o) --CO.sub.2 R.sup.9 ;

R.sup.2 and R.sup.3 are independently selected from the group consisting of:

(1) hydrogen,

(2) C.sub.1-6 alkyl, unsubstituted or substituted with one or more of the substituents selected from:

(a) hydroxy,

(b) oxo,

(c) C.sub.1-6 alkoxy,

(d) phenyl-C.sub.1-3 alkoxy,

(e) phenyl,

(f) --CN,

(g) halo,

(h) --NR.sup.9 R.sup.10,

(i) --NR.sup.9 COR.sup.10,

(j) --NR.sup.9 CO.sub.2 R.sup.10,

(k) --CONR.sup.9 R.sup.10,

(l) --COR.sup.9, and

(m) --CO.sub.2 R.sup.9 ;

(3) C.sub.2-6 alkenyl, unsubstituted or substituted with one or more of the substituent(s) selected from:

(a) hydroxy,

(b) oxo,

(c) C.sub.1-6 alkoxy,

(d) phenyl-C.sub.1-3 alkoxy,

(e) phenyl,

(f) --CN,

(g) halo,

(h) --CONR.sup.9 R.sup.10,

(i) --COR.sup.9, and

(j) --CO.sub.2 R.sup.9 ;

(4) C.sub.2-6 alkynyl;

(5) phenyl, unsubstituted or substituted with one or more of the substituent(s) selected from:

(a) hydroxy,

(b) C.sub.1-6 alkoxy,

(c) C.sub.1-6 alkyl,

(d) C.sub.2-5 alkenyl,

(e) halo,

(f) --CN,

(g) --NO.sub.2,

(h) --CF.sub.3,

(i) --(CH.sub.2).sub.m --NR.sup.9 R.sup.10,

(j) --NR.sup.9 COR.sup.10,

(k) --NR.sup.9 CO.sub.2 R.sup.10,

(l) --CONR.sup.9 R.sup.10,

(m) --CO.sub.2 NR.sup.9 R.sup.10,

(n) --COR.sup.9, and

(o) --CO.sub.2 R.sup.9 ;

R.sup.6, R.sup.7 and R.sup.8 are independently selected from the group consisting of:

(1) hydrogen;

(2) C.sub.1-6 alkyl, unsubstituted or substituted with one or more of the substituents selected from:

(a) hydroxy,

(b) oxo,

(c) C.sub.1-6 alkoxy,

(d) phenyl-C.sub.1-3 alkoxy,

(e) phenyl,

(f) --CN,

(g) halo,

(h) --NR.sup.9 R.sup.10,

(i) --NR.sup.9 COR.sup.10,

(j) --NR.sup.9 CO.sub.2 R.sup.10,

(k) --CONR.sup.9 R.sup.10,

(l) --COR.sup.9, and

(m) --CO.sub.2 R.sup.9 ;

(3) C.sub.2-6 alkenyl, unsubstituted or substituted with one or more of the substituent(s) selected from:

(a) hydroxy,

(b) oxo,

(c) C.sub.1-6 alkoxy,

(d) phenyl-C.sub.1-3 alkoxy,

(e) phenyl,

(f) --CN,

(g) halo,

(h) --CONR.sup.9 R.sup.10,

(i) --COR.sup.9, and

(j) --CO.sub.2 R.sup.9 ;

(4) C.sub.2-6 alkynyl;

(5) phenyl, unsubstituted or substituted with one or more of the substituent(s) selected from:

(a) hydroxy,

(b) C.sub.1-6 alkoxy,

(c) C.sub.1-6 alkyl,

(d) C.sub.2-5 alkenyl,

(e) halo,

(f) --CN,

(g) --NO.sub.2,

(h) --CF.sub.3,

(i) --(CH.sub.2).sub.m --NR.sup.9 R.sup.10,

(j) --NR.sup.9 COR.sup.10,

(k) --NR.sup.9 CO.sub.2 R.sup.10,

(l) --CONR.sup.9 R.sup.10,

(m) --CO.sub.2 NR.sup.9 R.sup.10,

(n) --COR.sup.9, and

(o) --CO.sub.2 R.sup.9 ;

(6) halo,

(7) --CN,

(8) --CF.sub.3,

(9) --NO.sub.2,

(10) --SR.sup.14, wherein R.sup.14 is hydrogen or C.sub.1-5 alkyl,

(11) --SOR.sup.14,

(12) --SO.sub.2 R.sup.14,

(13) NR.sup.9 COR.sup.10,

(14) CONR.sup.9 COR.sup.10,

(15) NR.sup.9 R.sup.10,

(16) NR.sup.9 CO.sub.2 R.sup.10,

(17) hydroxy,

(18) C.sub.1-6 alkoxy,

(19) COR.sup.9,

(20) CO.sub.2 R.sup.9,

(21) 2-pyridyl,

(22) 3-pyridyl,

(23) 4-pyridyl,

(24) 5-tetrazolyl,

(25) 2-oxazolyl, and

(26) 2-thiazolyl;

R.sup.11, R.sup.12 and R.sup.13 are independently selected from the definitions of R.sup.6, R.sup.7 and R.sup.8 ;

X is selected from the group consisting of:

(1) --O--,

(2) --S--,

(3) --SO--, and

(4) --SO.sub.2 --;

Y is selected from the group consisting of:

(1) a single bond,

(2) --O--,

(3) --S--,

(4) --CO--,

(5) --CH.sub.2 --,

(6) --CHR.sup.15 --, and

(7) --CR.sup.15 R.sup.16 --, wherein R.sup.15 and R.sup.16 are independently selected from the group consisting of:

(a) C.sub.1-6 alkyl, unsubstituted or substituted with one or more of the substituents selected from:

(i) hydroxy,

(ii) oxo,

(iii) C.sub.1-6 alkoxy,

(iv) phenyl-C.sub.1-3 alkoxy,

(v) phenyl,

(vi) --CN,

(vii) halo,

(viii) --NR.sup.9 R.sup.10,

(ix) --NR.sup.9 COR.sup.10,

(x) --NR.sup.9 CO.sub.2 R.sup.10,

(xi) --CONR.sup.9 R.sup.10,

(xii) --COR.sup.9, and

(xiii) --CO.sub.2 R.sup.9 ;

(b) phenyl, unsubstituted or substituted with one or more of the substituent(s) selected from:

(i) hydroxy,

(ii) C.sub.1-6 alkoxy,

(iii) C.sub.1-6 alkyl,

(iv) C.sub.2-5 alkenyl,

(v) halo,

(vi) --CN,

(vii) --NO.sub.2,

(viii) --CF.sub.3,

(ix) --(CH.sub.2).sub.m --NR.sup.9 R.sup.10,

(x) --NR.sup.9 COR.sup.10,

(xi) --NR.sup.9 CO.sub.2 R.sup.10,

(xii) --CONR.sup.9 R.sup.10,

(xiii) --CO.sub.2 NR.sup.9 R.sup.10,

(xiv) --COR.sup.9, and

(xv) --CO.sub.2 R.sup.9 ;

Z is C.sub.1-6 alkyl.

2. The compound of claim 1 wherein:

R.sup.1 is C.sub.1-6 alkyl, substituted with one or more of the substituents selected from:

heterocycle, wherein the heterocycle is selected from the group consisting of:

(A) benzimidazolyl,

(B) imidazolyl,

(C) isooxazolyl,

(D) isothiazolyl,

(E) oxadiazolyl,

(F) pyrazinyl,

(G) pyrazolyl,

(H) pyridyl,

(I) pyrrolyl,

(J) tetrazolyl,

(K) thiadiazolyl,

(L) triazolyl, and

(M) piperidinyl,

and wherein the heterocycle is unsubstituted or substituted with one or more substituent(s) selected from:

(i) C.sub.1-6 alkyl, unsubstituted or substituted with halo, --CF.sub.3, --OCH.sub.3, or phenyl,

(ii) C.sub.1-6 alkoxy,

(iii) oxo,

(iv) thioxo,

(v) cyano,

(vi) --SCH.sub.3,

(vii) phenyl,

(viii) hydroxy,

(ix) trifluoromethyl,

(x) --(CH.sub.2).sub.m --NR.sup.9 R.sup.10, wherein m is 0, 1 or 2, and wherein R.sup.9 and R.sup.10 are independently selected from:

(I) hydrogen,

(II) C.sub.1-6 alkyl,

(III) hydroxy-C.sub.1-6 alkyl, and

(IV) phenyl,

(xi) --NR.sup.9 COR.sup.10, and

(xii) --CONR.sup.9 R.sup.10.

3. The compound of claim 1 wherein:

R.sup.2 and R.sup.3 are independently selected from the group consisting of:

(1) hydrogen,

(2) C.sub.1-6 alkyl,

(3) C.sub.2-6 alkenyl, and

(4) phenyl;

R.sup.6, R.sup.7 and R.sup.8 are independently selected from the group consisting of:

(1) hydrogen,

(2) C.sub.1-6 alkyl,

(3) fluoro,

(4) chloro,

(5) bromo,

(6) iodo, and

(7) --CF.sub.3 ;

R.sup.11, R.sup.12 and R.sup.13 are independently selected from the group consisting of:

(1) hydrogen,

(2) C.sub.1-6 alkyl,

(3) fluoro,

(4) chloro,

(5) bromo,

(6) iodo, and

(7) --CF.sub.3 ;

X is --O--;

Y is --O--; and

Z is C.sub.1-4 alkyl.

4. The compound of claim 1 wherein Z is C.sub.1-4 alkyl.

5. The compound of claim 1 wherein Z is --CH.sub.3.

6. The compound of claim 1 wherein R.sup.1 is selected from the group consisting of: ##STR20##

7. The compound of claim 1 wherein R.sup.1 is selected from the group consisting of:

(1,2,4-triazolo)methyl; and

(5-oxo-1H,4H-1,2,4-triazolo)methyl.

8. The compound of claim 1 wherein R.sup.1 is selected from the group consisting of:

(1,3-imidazolo)methyl; and

(2-oxo-1,3-imidazolo)methyl.

9. The compound of claim 1 of the structural formula: ##STR21## or a pharmaceutically acceptable salt thereof, wherein R.sup.1, R.sup.2, R.sup.3, R.sup.6, R.sup.7, R.sup.8, R.sup.11, R.sub.12, R.sub.13, Y and Z are as defined in claim 1.

10. The compound of claim 1 of the structural formula II: ##STR22## or a pharmaceutically acceptable salt thereof, wherein R.sup.1, R.sup.2, R.sup.3, R.sup.6, R.sup.7, R.sup.8, R.sup.11, R.sup.12, R.sup.13 and Z are as defined in claim 1.

11. The compound of claim 1 of the structural formula III: ##STR23## or a pharmaceutically acceptable salt thereof, wherein R.sup.1, R.sup.2, R.sup.3, R.sup.6, R.sup.7, R.sup.8, R.sup.11, R.sup.12, R.sup.13 and Z are as defined in claim 1.

12. The compound of claim 1 of the structural formula: ##STR24## or a pharmaceutically acceptable salt thereof, wherein R.sup.1, R.sup.2, R.sup.3, R.sup.6, R.sup.7, R.sup.8, R.sup.11, R.sup.12, R.sup.13, Y and Z are as defined in claim 1.

13. The compound of claim 1 of the structural formula: ##STR25## or a pharmaceutically acceptable salt thereof, wherein R.sup.1, R.sup.2, R.sup.3, R.sup.6, R.sup.7, R.sup.8, R.sup.11, R.sup.12, R.sup.13, Y and Z are as defined in claim 1.

14. The compound of claim 1 of the structural formula: ##STR26## or a pharmaceutically acceptable salt thereof, wherein R.sup.1, R.sup.7, R.sup.8, R.sup.11, R.sub.12, R.sub.13, Y and Z are as defined in claim 1.

15. A compound which is selected from the group consisting of:

1) (+/-)-2-(3,5-bis(trifluoromethyl)benzyloxy)-3-phenyl-morpholine;

2) (2R,S)-(3,5-bis(trifluoromethyl)benzyloxy)-(3R)-phenyl-(6R)-methyl-morphol ine;

3) (2R,S)-(3,5-bis(trifluoromethyl)benzyloxy)-(3S)-phenyl-(6R)-methyl-morphol ine;

4) (+/-)-2-(3,5-bis(trifluoromethyl)benzyloxy)-3-phenyl-4-methylcarboxamido-m orpholine;

5) (+/-)-2-(3,5-bis(trifluoromethyl)benzyloxy)-3-phenyl-4-methoxycarbonylmeth yl-morpholine;

6) 2-(2-(3,5-bis(trifluoromethyl)phenyl)ethenyl)-3-phenyl-5-oxo-morpholine;

7) 3-phenyl-2-(2-(3,5-bis(trifluoromethyl)phenyl)-ethyl)-morpholine;

8) 2-(R)-(3,5-bis(trifluoromethyl)benzyloxy)-3-(R)-phenyl-6-(S)-methyl-morpho line;

9) 2-(R)-(3,5-bis(trifluoromethyl)benzyloxy)-3-(S)-phenyl-6-(S)-methyl-morpho line;

10) 2-(S)-(3,5-bis(trifluoromethyl)benzyloxy)-3-(R)-phenyl-6-(S)-methyl-morpho line;

11) 2-(S)-(3,5-bis(trifluoromethyl)benzyloxy)-3-(S)-phenyl-6-(S)-methyl-morpho line;

12) 2-(R)-(3,5-bis(trifluoromethyl)benzyloxy)-3-(R)-phenyl-5-(R)-methyl-morpho line;

13) 2-(R)-(3,5-bis(trifluoromethyl)benzyl oxy)-3-(S)-phenyl-5-(R)-methyl-morpholine;

14) 2-(S)-(3,5-bis(trifluoromethyl)benzyloxy)-3-(R)-phenyl-5-(R)-methyl-morpho line;

15) 2-(S)-(3,5-bis(trifluoromethyl)benzyloxy)-3-(S)-phenyl-5-(R)-methyl-morpho line;

16) 2-(S)-(3,5-bis(trifluoromethyl)benzyloxy)-3-(S)-phenyl-morpholine;

17) 4-(3-(1,2,4-triazolo)methyl)-2-(S)-(3,5-bis(trifluoromethyl)benzyloxy)-3-( S)-phenyl-morpholine;

18) 4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methyl)-2-(S)-(3,5-bis-(trifluoromethyl)b enzyloxy)-3-(S)-phenyl-morpholine;

19) 2-(R)-(3,5-bis(trifluoromethyl)benzyloxy)-3-(R)-phenyl-6-(R)-methyl-morpho line;

20) 2-(S)-(3,5-bis(trifluoromethyl)benzyloxy)-3-(R)-phenyl-6-(R)-methyl-morpho line;

21) 2-(R)-(3,5-bis(trifluoromethyl)benzyloxy)-3-(S)-phenyl-6-(R)-methyl-morpho line;

22) 2-(S)-(3,5-bis(trifluoromethyl)benzyloxy)-3-(S)-phenyl-6-(R)-methyl-morpho line;

23) 2-(R)-(3,5-bis(trifluoromethyl)-benzyl oxy)-3-(S)-phenyl-5-(S)-methyl-morpholine;

24) 2-(S)-(3,5-bis(trifluoromethyl)benzyloxy)-3-(S)-phenyl-5-(S)-methyl-morpho line;

25) 2-(R)-(3,5-bis(trifluoromethyl)benzyloxy)-3-(R)-phenyl-5-(S)-methyl-morpho line;

26) 2-(R)-(3,5-bis(trifluoromethyl)benzyloxy)-3-(S)-phenyl-5-(R)-phenyl-morpho line;

27) 2-(S)-(3,5-bis(trifluoromethyl)benzyloxy)-3-(S)-phenyl-5-(R)-phenyl-morpho line;

28) 2-(S)-(3,5-bis(trifluoromethyl)benzyloxy)-3-(R)-phenyl-5-(S)-phenyl-morpho line;

29) 2-(R)-(3,5-bis(trifluoromethyl)benzyloxy)-3-(R)-phenyl-5-(S)-phenyl-morpho line;

30) 2-(S)-(3,5-bis(trifluoromethyl)benzyloxy)-6-(R)-methyl-3-(S)-phenyl-4-(3-( 1,2,4-triazolo)methyl)-morpholine;

31) 2-(S)-(3,5-bis(trifluoromethyl)benzyloxy)-6-(R)-methyl-4-(3-(5-oxo-1H ,4H-1,2,4-triazolo)methyl)-3-(S)-phenyl-morpholine;

32) 2-(S)-(3,5-bis(trifluoromethyl)benzyloxy)-3-(R)-phenyl-morpholine;

33) 4-(3-(1,2,4-triazolo)methyl)-2-(S)-(3,5-bis(trifluoromethyl)benzyloxy)-3-( R)-phenyl-morpholine;

34) 4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methyl)-2-(S)-(3,5-bis-(trifluoromethyl)b enzyloxy)-3-(R)-phenyl-morpholine;

35) 4-(2-(imidazolo)methyl)-2-(S)-(3,5-bis(trifluoro-methyl)benzyloxy)-3-(R)-p henyl-morpholine;

36) 4-(4-(imidazolo)methyl)-2-(S)-(3,5-bis(trifluoromethyl)benzyloxy)-3-(R)-ph enyl-morpholine;

37) 4-(aminocarbonylmethyl)-2-(S)-(3,5-bis(trifluoromethyl)benzyloxy)-3-(R)-ph enyl-morpholine;

38) 4-(2-(imidazolo)methyl)-2-(S)-(3,5-bis(trifluoromethyl)benzyloxy)-3-(S)-ph enyl-morpholine;

39) 4-(4-(imidazolo)methyl)-2-(S)-(3,5-bis(trifluoromethyl)benzyloxy)-3-(S)-ph enyl-morpholine;

40) 4-(2-(imidazolo)methyl)-2-(S)-(3,5-bis(trifluoromethyl)benzyloxy)-3-(S)-ph enyl-6-(R)-methyl-morpholine;

41) 4-(4-(imidazolo)methyl)-2-(S)-(3,5-bis(trifluoromethyl)benzyloxy)-3-(S)-ph enyl-6(R)-methyl-morpholine;

42) 2-(S)-(3,5-bis(trifluoromethyl)benzyloxy)-4-((6-hydroxy)-hexyl)-3-(R)-phen yl-morpholine;

43) 2-(S)-(3,5-bis(trifluoromethyl)benzyloxy)-4-(5-(methylaminocarbonyl)pentyl )-3-(R)-phenyl-morpholine;

44) 4-(3-(1,2,4-triazolo)methyl)-2-(3,5-dimethylbenzyloxy)-3-phenylmorpholine;

45) 4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methyl)-2-(3,5-dimethyl)-benzyloxy)-3-phe nyl-morpholine;

46) 4-(3-(1,2,4-triazolo)methyl)-2-(3,5-di(tert-butyl)-benzyloxy)-3-phenylmorp holine;

47) 4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methyl)-2-(3,5-di(tert-butyl)-benzyloxy)- 3-phenyl-morpholine;

48) 4-(3-(1,2,4-triazolo)methyl)-2-(3-(tert-butyl)-5-methyl-benzyloxy)-3-pheny l-morpholine;

49) 4-(3-(5-oxo-1H ,4H-1,2,4-triazolo)methyl)-2-(3-(tert-butyl)-5-methylbenzyloxy)-3-phenyl-m orpholine;

50) 4-(3-(1,2,4-triazolo)methyl)-2-(3-(trifluoro-methyl)-5-methyl-benzyloxy)-3 -phenyl-morpholine;

51) 4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methyl)-2-(3-(trifluoro-methyl)-5-methylb enzyloxy)-3-phenyl-morpholine;

52) 4-(3-(1,2,4-triazolo)methyl)-2-(3-(tert-butyl)-5-(trifluoro-methyl)benzylo xy)-3-phenyl-morpholine;

53) 4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methyl)-2-(3-(tert-butyl)-5-(trifluoromet hyl)benzyloxy)-3-phenyl-morpholine;

54) 4-(2-(imidazolo)methyl)-2-(3,5-dimethyl-benzyloxy)-3-phenyl-morpholine;

55) 4-(4-(imidazolo)methyl)-2-(3,5-dimethyl-benzyloxy)-3-phenyl-morpholine;

56) 4-(2-(imidazolo)methyl)-2-(3,5-di(tert-butyl)-benzyloxy)-3-phenyl-morpholi ne;

57) 4-(4-(imidazolo)methyl)-2-(3,5-di(tert-butyl)-benzyloxy)-3-phenyl-morpholi ne;

58) 4-(2-(imidazolo)methyl)-2-(3-(tert-butyl)-5-methylbenzyloxy)-3-phenyl-morp holine;

59) 4-(4-(imidazolo)methyl)-2-(3-(tert-butyl)-5-methylbenzyloxy)-3-phenyl-morp holine;

60) 4-(2-(imidazolo)methyl)-2-(3-(trifluoro-methyl)-5-methylbenzyloxy)-3-pheny l-morpholine;

61) 4-(4-(imidazolo)methyl)-2-(3-(trifluoro-methyl)-5-methylbenzyloxy)-3-pheny l-morpholine;

62) 4-(2-(imidazolo)methyl)-2-(3-(tert-butyl)-5-(trifluoromethyl)benzyloxy)-3- phenyl-morpholine;

63) 2-(S)-(3,5-dichlorobenzyloxy)-3-(S)-phenyl-morpholine;

64) 2-(S)-(3,5-dichlorobenzyloxy)-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methyl)-3-( S)-phenylmorpholine;

65) 2-(S)-(3,5-bis(trifluoromethyl)benzyloxy)-4-(methoxycarbonylmethyl)-3-(S)- phenyl-morpholine;

66) 2-(S)-(3,5-bis(trifluoromethyl)benzyloxy)-4-(carboxymethyl)-3-(S)-phenyl-m orpholine;

67) 2-(S)-(3,5-bis(trifluoromethyl)benzyloxy)-4-((2-aminoethyl)aminocarbonylme thyl)-3-(S)-phenyl-morpholine;

68) 2-(S)-(3,5-bis(trifluoromethyl)benzyloxy)-4-((3-aminopropyl)amino carbonylmethyl)-3-(S)-phenylmorpholine;

69) 4-benzyl-5-(S),6-(R)-dimethyl-3-(S)-phenylmorpholinone and 4-benzyl-5-(R), 6-(S)-dimethyl-3-(S)-phenyl-morpholinone;

70) 2-(R)-(3,5-bis(trifluoromethyl)benzyloxy)-[5-(S),6-(R) or 5-(R),6-(S)-dimethyl]-3-(S)-phenyl-morpholinone;

71) 2-(S)-(3,5-bis(trifluoromethyl)benzyloxy)-[5-(R),6-(S) or 5-(S),6-(R)-dimethyl]-3-(S)-phenyl-morpholinone;

72) 2-(R)-(3,5-bis(trifluoromethyl)benzyloxy)-4-(3-(1,2,4-triazolo)methyl)-[5- (S),6-(R) or 5-(R),6-(S)-dimethyl]-3-(S)-phenyl-morpholinone;

73) 2-(R)-(3,5-bis(trifluoromethyl)benzyloxy)-4-(3-(5-oxo-1H,4H-1,2,4-triazolo )methyl)-[5-(S),6-(R) or 5-(R),6-(S)-dimethyl]-3-(S)-phenyl-morpholinone;

74) 2-(S)-(3,5-bis(trifluoromethyl)benzyloxy)-4-(3-(1,2,4-triazolo)methyl)-[5- (R),6-(S) or 5-(S),6-(R)-dimethyl]-3-(S)-phenyl-morpholinone;

75) 2-(S)-(3,5-bis(trifluoromethyl)benzyloxy)-4-(3-(5-oxo-1H,4H-1,2,4-triazolo )methyl)-[5-(R),6-(S) or 5-(S),6-(R)-dimethyl]-3-(S)-phenyl-morpholinone;

76) 2-(S)-(3,5-bis(trifluoromethyl)benzyloxy)-4-(2-(1-(4-benzyl)piperidino)eth yl)-3-(S)-phenyl-morpholine;

77) 3-(S)-(4-fluorophenyl)-4-benzyl-2-morpholinone;

78) 2-(S)-(3,5-bis(trifluoromethyl)benzyloxy)-3-(S)-(4-fluorophenyl)-4-benzyl- morpholine;

79) 2-(S)-(3,5-Bis(trifluoromethyl)benzyloxy)-3-(S)-(4-fluorophenyl)morpholine ;

80) 2-(S)-(3,5-bis(trifluoromethyl)benzyloxy)-3-(S)-(4-fluorophenyl)-4-(3-(5-o xo-1H,4H-1,2,4-triazolo)methyl-morpholine;

81) 2-(S)-(3,5-bis(trifluoromethyl)benzyloxy)-4-((3-pyridyl)methyl carbonyl)-3-(R)-phenyl-morpholine;

83) 2-(S)-(3,5-bis(trifluoromethyl)benzyloxy)-4-(methoxycarbonylpentyl)-3-(R)- phenyl-morpholine;

83) 2-(S)-(3,5-bis(trifluoromethyl)benzyloxy)-4-(carboxypentyl)-3-(R)-phenyl-m orpholine;

84) 2-(S)-(3,5-bis(trifluoromethyl)benzyloxy)-4-(methylaminocarbonylpentyl)-6- oxo-hexyl)-3-(R)-phenyl-morpholine;

85) 2-(R)-(3,5-bis(trifluoromethyl)benzoyloxy)-3-(S)-phenyl-4-benzyl-morpholin e;

86) 2-(R)-(1-(3,5-bis(trifluoromethyl)phenyl)ethenyloxy)-3-(S)-phenyl-4-benzyl -morpholine;

87) 2-(R)-(1-(S)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-phenyl-morpholi ne;

88) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-phenyl-morpholi ne;

89) 2-(R)-(1-(S)-(3,5-Bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-phenyl-4-(3-(5- oxo-1H,4H-1,2,4-triazolo)methyl-morpholine;

90) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-phenyl-4-(3-(5- oxo-1H,4H-1,2,4-triazolo)methyl-morpholine;

93) 2-(R)-(1-(S)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-(4-fluoro)pheny l-morpholine;

94) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-(4-fluoro)pheny l-morpholine;

95) 2-(R)-(1-(S)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-(4-fluoro)pheny l-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methyl-morpholine;

96) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-(4-fluoro)pheny l-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methyl-morpholine;

98) 2-(R)-(1-(R)-(1-(3-(methyl)naphthyl))ethoxy)-3-(S)-phenyl-4-(4-(2-oxo-1,3- imidazolo)methyl-morpholine;

99) 2-(R)-(1-(R)-(3-(fluoro)-5-(trifluoromethyl)phenyl)ethoxy)-3-(S)-phenyl-mo rpholine;

100) 2-(R)-(1-(R)-(3-(fluoro)-5-(trifluoromethyl)phenyl)ethoxy)-3-(S)-phenyl-4- (3-(5-oxo-1H,4H-1,2,4-triazolo)methyl)-morpholine;

101) 2-(R)-(1-(R)-(3-(chloro)-5-(trifluoromethyl)phenyl)ethoxy)-3-(S)-phenyl-mo rpholine;

102) 2-(R)-(1-(R)-(3-(chloro)-5-(trifluoromethyl)phenyl)ethoxy)-3-(S)-phenyl-4- (3-(5-oxo-1H,4H-1,2,4-triazolo)methyl)-morpholine;

103) 2-(R)-(1-(R)-(3,5-(dimethyl)phenyl)ethoxy)-3-(S)-phenyl-morpholine;

104) 2-(R)-(1-(R)-(3,5-(dimethyl)phenyl)ethoxy)-3-(S)-phenyl-4-(3-(5-oxo-1H,4H- 1,2,4-triazolo)methyl)-morpholine;

105) 2-(R)-(1-(R)-(3-(fluoro)-5-(methyl)phenyl)ethoxy)-3-(S)-phenyl-morpholine;

106) 2-(R)-(1-(R)-(3-(fluoro)-5-(methyl)phenyl)ethoxy)-3-(S)-phenyl-4-(3-(5-oxo -1H,4H-1,2,4-triazolo)methyl)-morpholine;

107) 2-(R)-(1-(R)-(3-(chloro)-5-(methyl)phenyl)ethoxy)-3-(S)-phenyl-morpholine;

108) 2-(R)-(1-(R)-(3-(chloro)-5-(methyl)phenyl)ethoxy)-3-(S)-phenyl-4-(3-(5-oxo -1H,4H-1,2,4-triazolo)methyl)-morpholine;

109) 2-(R)-(1-(R)-(3-(bromo)-5-(methyl)phenyl)ethoxy)-3-(S)-phenyl-morpholine;

110) 2-(R)-(1-(R)-(3-(bromo)-5-(methyl)phenyl)ethoxy)-3-(S)-phenyl-4-(3-(5-oxo- 1H,4H-1,2,4-triazolo)methyl)-morpholine;

111) 2-(R)-(1-(R)-(3-(isopropoxy)phenyl)ethoxy)-3-(S)-phenyl-morpholine;

112) 2-(R)-(1-(R)-(3-(isopropoxy)phenyl)ethoxy)-3-(S)-phenyl-4-(3-(5-oxo-1H,4H- 1,2,4-triazolo)methyl)-morpholine;

113) 2-(R)-(1-(R)-(3-(isopropoxy)-5-trifluoromethyl)phenyl)ethoxy)-3-(S)-phenyl -morpholine;

114) 2-(R)-(1-(R)-(3-(isopropoxy)-5-trifluoromethyl)phenyl)ethoxy)-3-(S)-phenyl -4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methyl)-morpholine;

115) 2-(R)-(1-(R)-(3-(chloro)-5-(isopropoxy)phenyl)ethoxy)-3-(S)-phenyl-morphol ine;

116) 2-(R)-(1-(R)-(3-(chloro)-5-(isopropoxy)phenyl)ethoxy)-3-(S)-phenyl-4-(3-(5 -oxo-1H,4H-1,2,4-triazolo)methyl)-morpholine;

117) 2-(R)-(1-(R)-(3-(fluoro)-5-(isopropoxy)phenyl)ethoxy)-3-(S)-phenyl-morphol ine;

118) 2-(R)-(1-(R)-(3-(fluoro)-5-(isopropoxy)phenyl)ethoxy)-3-(S)-phenyl-4-(3-(5 -oxo-1H,4H-1,2,4-triazolo)methyl)-morpholine;

121) 2-(R)-(1-(R)-(3-(t-butyl)-5-(chloro)phenyl)ethoxy)-3-(S)-phenyl-morpholine ;

122) 2-(R)-(1-(R)-(3-(t-butyl)-5-(chloro)phenyl)ethoxy)-3-(S)-phenyl-4-(3-(5-ox o-1H,4H-1,2,4-triazolo)methyl)-morpholine;

123) 2-(R)-(1-(R)-(3-(t-butyl)-5-(trifluoromethyl)phenyl)ethoxy)-3-(S)-phenyl-m orpholine;

124) 2-(R)-(1-(R)-(3-(t-butyl)-5-(trifluoromethyl)phenyl)ethoxy)-3-(S)-phenyl-4 -(3-(5-oxo-1H,4H-1,2,4-triazolo)methyl)-morpholine;

125) 2-(R)-(1-(R)-(3,5-(dimethyl)-4-(fluoro)phenyl)ethoxy)-3-(S)-phenyl-morphol ine;

126) 2-(R)-(1-(R)-(3,5-(dimethyl)-4-(fluoro)phenyl)ethoxy)-3-(S)-phenyl-4-(3-(5 -oxo-1H,4H-1,2,4-triazolo)methyl)-morpholine;

127) 2-(R)-(1-(R)-(3,5-(dimethyl)-4-(chloro)phenyl)ethoxy)-3-(S)-phenyl-morphol ine;

128) 2-(R)-(1-(R)-(3,5-(dimethyl)-4-(chloro)phenyl)ethoxy)-3-(S)-phenyl-4-(3-(5 -oxo-1H,4H-1,2,4-triazolo)methyl)-morpholine;

129) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)-4-(fluoro)phenyl)ethoxy)-3-(S)-phen yl-morpholine;

130) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)-4-(fluoro)phenyl)ethoxy)-3-(S)-phen yl-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methyl)-morpholine;

131) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)-4-chloro)phenyl)ethoxy)-3-(S)-pheny l-morpholine;

132) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)-4-chloro)phenyl)ethoxy)-3-(S)-pheny l-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methyl)-morpholine;

133) 2-(R)-(1-(R)-(3,5-(dichloro)phenyl)ethoxy)-3-(S)-phenyl-morpholine;

134) 2-(R)-(1-(R)-(3,5-(dichloro)phenyl)ethoxy)-3-(S)-phenyl-4-(3-(5-oxo-1H,4H- 1,2,4-triazolo)methyl)-morpholine;

135) 2-(R)-(1-(R)-(3,5-(difluoro)phenyl)ethoxy)-3-(S)-phenyl-morpholine;

136) 2-(R)-(1-(R)-(3,5-(difluoro)phenyl)ethoxy)-3-(S)-phenyl-4-(3-(5-oxo-1H,4H- 1,2,4-triazolo)methyl)-morpholine;

153) 2-(R)-(1-(R)-(2-fluoro-5-trifluoromethyl)phenylethoxy)-3-(S)-phenyl-morpho line;

154) 2-(R)-(1-(R)-(2-fluoro-5-trifluoromethyl)phenylethoxy)-3-(S)-(4-fluoro)phe nyl-morpholine;

157) 2-(R)-(1-(R)-(2-fluoro-5-trifluoromethyl)phenyl)ethoxy)-3-(S)-phenyl-4-(3- (1,2,4-triazolo)methyl)-morpholine;

158) 2-(R)-(1-(R)-(2-fluoro-5-trifluoromethyl)phenylethoxy)-3-(S)-(4-fluoro)phe nyl-4-(3-(1,2,4-triazolo)methyl)-morpholine;

161) 2-(R)-(1-(R)-(2-fluoro-5-trifluoromethyl)phenylethoxy)-3-(S)-phenyl-4-(3-( 5-oxo-1H,4H-1,2,4-triazolo)methyl)-morpholine;

162) 2-(R)-(1-(R)-(2-fluoro-5-trifluoromethyl)phenylethoxy)-3-(S)-(4-fluoro)phe nyl-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methyl)-morpholine;

165) 2-(R)-(1-(R)-(2-fluoro-5-trifluoromethyl)phenylethoxy)-3-(S)-phenyl-4-(4-( 2-oxo-1,3-imidazolo)methyl)-morpholine;

166) 2-(R)-(1-(R)-(2-fluoro-5-trifluoromethyl)phenylethoxy)-3-(S)-(4-fluoro)phe nyl-4-(4-(2-oxo-1,3-imidazolo)methyl)-morpholine;

169) 2-(R)-(1-(R)-(2-fluoro-5-trifluoromethyl)phenylethoxy)-3-(S)-phenyl-4-(2-i midazolo)methyl-morpholine;

170) 2-(R)-(1-(R)-(2-fluoro-5-trifluoromethyl)phenylethoxy)-3-(S)-(4-fluoro)phe nyl-4-(2-imidazolo)methyl-morpholine;

173) 2-(R)-(1-(R)-(2-fluoro-5-trifluoromethyl)phenylethoxy)-3-(S)-phenyl-4-(4-i midazolo)methyl-morpholine;

174) 2-(R)-(1-(R)-(2-fluoro-5-trifluoromethyl)phenylethoxy)-3-(S)-(4-fluoro)phe nyl-4-(4-imidazolo)methyl-morpholine;

177) 2-(R)-(1-(R)-(2-fluoro-5-trifluoromethyl)phenylethoxy)-3-(S)-phenyl-4-(5-t etrazolo)methyl-morpholine;

178) 2-(R)-(1-(R)-(2-fluoro-5-trifluoromethyl)phenylethoxy)-3-(S)-(4-fluoro)phe nyl-4-(5-tetrazolo)methyl-morpholine;

181) 2-(R)-(1-(R)-(2-fluoro-5-trifluoromethyl)phenylethoxy)-3-(S)-phenyl-4-(2-o xo-5H-pyrrol-4-yl)methyl-morpholine;

182) 2-(R)-(1-(R)-(2-fluoro-5-trifluoromethyl)phenylethoxy)-3-(S)-(4-fluoro)phe nyl-4-(2-oxo-5H-pyrrol-4-yl)methyl-morpholine;

185) 2-(R)-(1-(R)-(2-chloro-5-trifluoromethyl)phenylethoxy)-3-(S)-phenyl-morpho line;

186) 2-(R)-(1-(R)-(2-chloro-5-trifluoromethyl)phenylethoxy)-3-(S)-(4-fluoro)phe nyl-morpholine;

189) 2-(R)-(1-(R)-(2-chloro-5-trifluoromethyl)phenylethoxy)-3-(S)-phenyl-4-(3-( 1,2,4-triazolo)methyl)-morpholine;

190) 2-(R)-(1-(R)-(2-chloro-5-trifluoromethyl)phenylethoxy)-3-(S)-(4-fluoro)phe nyl-4-(3-(1,2,4-triazolo)methyl)-morpholine;

193) 2-(R)-(1-(R)-(2-chloro-5-trifluoromethyl)phenylethoxy)-3-(S)-phenyl-4-(3-( 5-oxo-1H,4H-1,2,4-triazolo)methyl)-morpholine;

194) 2-(R)-(1-(R)-(2-chloro-5-trifluoromethyl)phenylethoxy)-3-(S)-(4-fluoro)phe nyl-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methyl)-morpholine;

197) 2-(R)-(1-(R)-(2-chloro-5-trifluoromethyl)phenylethoxy)-3-(S)-phenyl-4-(4-( 2-oxo-1,3-imidazolo)methyl)-morpholine;

198) 2-(R)-(1-(R)-(2-chloro-5-trifluoromethyl)phenylethoxy)-3-(S)-(4-fluoro)phe nyl-4-(4-(2-oxo-1,3-imidazolo)methyl)-morpholine;

201) 2-(R)-(1-(R)-(2-chloro-5-trifluoromethyl)phenylethoxy)-3-(S)-phenyl-4-(2-i midazolo)methyl)-morpholine;

202) 2-(R)-(1-(R)-(2-chloro-5-trifluoromethyl)phenylethoxy)-3-(S)-(4-fluoro)phe nyl-4-(2-imidazolo)methyl)-morpholine;

205) 2-(R)-(1-(R)-(2-chloro-5-trifluoromethyl)phenylethoxy)-3-(S)-phenyl-4-(4-i midazolo)methyl-morpholine;

206) 2-(R)-(1-(R)-(2-chloro-5-trifluoromethyl)phenylethoxy)-3-(S)-(4-fluoro)phe nyl-4-(4-imidazolo)methyl-morpholine;

209) 2-(R)-(1-(R)-(2-chloro-5-trifluoromethyl)phenylethoxy)-3-(S)-phenyl-4-(5-t etrazolo)methyl-morpholine;

210) 2-(R)-(1-(R)-(2-chloro-5-trifluoromethyl)phenylethoxy)-3-(S)-(4-fluoro)phe nyl-4-(5-tetrazolo)methyl-morpholine;

213) 2-(R)-(1-(R)-(2-chloro-5-trifluoromethyl)phenylethoxy)-3-(S)-phenyl-4-(2-o xo-5H-pyrrol-4-yl)methyl-morpholine;

214) 2-(R)-(1-(R)-(2-Chloro-5-trifluoromethyl)phenylethoxy)-3-(S)-(4-fluoro)phe nyl-4-(2-oxo-5H-pyrrol-4-yl)methyl-morpholine;

217) 2-(R)-(1-(R)-(3-methyl)phenylethoxy)-3-(S)-phenyl-morpholine;

218) 2-(R)-(1-(R)-(3-methyl)phenylethoxy)-3-(S)-(4-fluoro)phenyl-morpholine;

221) 2-(R)-(1-(R)-(3-methyl)phenylethoxy)-3-(S)-phenyl-4-(3-(1,2,4-triazolo)met hyl)-morpholine;

222) 2-(R)-(1-(R)-(3-methyl)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(1,2,4-tr iazolo)methyl)-morpholine;

225) 2-(R)-(1-(R)-(3-methyl)phenylethoxy)-3-(S)-phenyl-4-(3-(5-oxo-1,2,4-triazo lo)methyl)-morpholine;

226) 2-(R)-(1-(R)-(3-methyl)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(5-oxo-1H ,4H-1,2,4-triazolo)methyl)-morpholine;

229) 2-(R)-(1-(R)-(3-methyl)phenylethoxy)-3-(S)-phenyl-4-(4-(2-oxo-1,3-imidazol o)methyl)-morpholine;

230) 2-(R)-(1-(R)-(3-methyl)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4-(4-(2-oxo-1, 3-imidazolo)methyl)-morpholine;

233) 2-(R)-(1-(R)-(3-methyl)phenylethoxy)-3-(S)-phenyl-4-(2-imidazolo)methyl-mo rpholine;

234) 2-(R)-(1-(R)-(3-methyl)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4-(2-imidazolo )methyl-morpholine;

237) 2-(R)-(1-(R)-(3-methyl)phenylethoxy)-3-(S)-phenyl-4-(4-imidazolo)methyl-mo rpholine;

238) 2-(R)-(1-(R)-(3-methyl)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4-(4-imidazolo )methyl-morpholine;

241) 2-(R)-(1-(R)-(3-methyl)phenylethoxy)-3-(S)-phenyl-4-(5-tetrazolo)methyl-mo rpholine;

242) 2-(R)-(1-(R)-(3-methyl)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4-(5-tetrazolo )methyl-morpholine;

245) 2-(R)-(1-(R)-(3-methyl)phenylethoxy)-3-(S)-phenyl-4-(2-oxo-5H-pyrrol-4-yl) methyl-morpholine;

246) 2-(R)-(1-(R)-(3-methyl)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4-(2-oxo-5H-py rrol-4-yl)methyl-morpholine;

249) 2-(R)-(1-(R)-(3-bromo)phenylethoxy)-3-(S)-phenyl-morpholine;

250) 2-(R)-(1-(R)-(3-bromo)phenylethoxy)-3-(S)-(4-fluoro)phenyl-morpholine;

253) 2-(R)-(1-(R)-(3-bromo)phenylethoxy)-3-(S)-phenyl-4-(3-(1,2,4-triazolo)meth yl-morpholine;

254) 2-(R)-(1-(R)-(3-bromo)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(1,2,4-tri azolo)methyl-morpholine;

257) 2-(R)-(1-(R)-(3-bromo)phenylethoxy)-3-(S)-phenyl-4-(3-(5-oxo-1H ,4H-1,2,4-triazolo)methyl)-morpholine;

258) 2-(R)-(1-(R)-(3-bromo)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(5-oxo-1H, 4H-1,2,4-triazolo)methyl)-morpholine;

261) 2-(R)-(1-(R)-(3-bromo)phenylethoxy)-3-(S)-phenyl-4-(4-(2-oxo-1,3-imidazolo )methyl)-morpholine;

262) 2-(R)-(1-(R)-(3-bromo)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4-(4-(2-oxo-1,3 -imidazolo)methyl)-morpholine;

265) 2-(R)-(1-(R)-(3-bromo)phenylethoxy)-3-(S)-phenyl-4-(2-imidazolo)methyl-mor pholine;

266) 2-(R)-(1-(R)-(3-bromo)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4-(2-imidazolo) methyl-morpholine;

269) 2-(R)-(1-(R)-(3-bromo)phenylethoxy)-3-(S)-phenyl-4-(4-imidazolo)methyl-mor pholine;

270) 2-(R)-(1-(R)-(3-bromo)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4-(4-imidazolo) methyl-morpholine;

273) 2-(R)-(1-(R)-(3-bromo)phenylethoxy)-3-(S)-phenyl-4-(5-tetrazolo)methyl-mor pholine;

274) 2-(R)-(1-(R)-(3-bromo)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4-(5-tetrazolo) methyl-morpholine;

277) 2-(R)-(1-(R)-(3-bromo)phenylethoxy)-3-(S)-phenyl-4-(2-oxo-5H-pyrrol-4-yl)m ethyl-morpholine;

278) 2-(R)-(1-(R)-(3-bromo)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4-(2-oxo-5H-pyr rol-4-yl)methyl-morpholine;

281) 2-(R)-(1-(R)-(3-chloro)phenylethoxy)-3-(S)-phenyl-morpholine;

282) 2-(R)-(1-(R)-(3-chloro)phenylethoxy)-3-(S)-(4-fluoro)phenyl-morpholine;

285) 2-(R)-(1-(R)-(3-chloro)phenylethoxy)-3-(S)-phenyl-4-(3-(1,2,4-triazolo)met hyl)-morpholine;

286) 2-(R)-(1-(R)-(3-chloro)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(1,2,4-tr iazolo)methyl)-morpholine;

289) 2-(R)-(1-(R)-(3-chloro)phenylethoxy)-3-(S)-phenyl-4-(3-(5-oxo-1H,4H-1,2,4- triazolo)methyl)-morpholine;

290) 2-(R)-(1-(R)-(3-chloro)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(5-oxo-1H ,4H-1,2,4-triazolo)methyl)-morpholine;

293) 2-(R)-(1-(R)-(3-chloro)phenylethoxy)-3-(S)-phenyl-4-(4-(2-oxo-1,3-imidazol o)methyl)-morpholine;

294) 2-(R)-(1-(R)-(3-chloro)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4-(4-(2-oxo-1, 3-imidazolo)methyl)-morpholine;

297) 2-(R)-(1-(R)-(3-chloro)phenylethoxy)-3-(S)-phenyl-4-(2-imidazolo)methyl-mo rpholine;

298) 2-(R)-(1-(R)-(3-chloro)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4-(2-imidazolo )methyl-morpholine;

301) 2-(R)-(1-(R)-(3-chloro)phenylethoxy)-3-(S)-phenyl-4-(4-imidazolo)methyl-mo rpholine;

302) 2-(R)-(1-(R)-(3-chloro)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4-(4-imidazolo )methyl-morpholine;

305) 2-(R)-(1-(R)-(3-chloro)phenylethoxy)-3-(S)-phenyl-4-(5-tetrazolo)methyl-mo rpholine;

306) 2-(R)-(1-(R)-(3-chloro)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4-(5-tetrazolo )methyl-morpholine;

309) 2-(R)-(1-(R)-(3-chloro)phenylethoxy)-3-(S)-phenyl-4-(2-oxo-5H-pyrrol-4-yl) methyl-morpholine;

310) 2-(R)-(1-(R)-(3-chloro)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4-(2-oxo-5H-py rrol-4-yl)methyl-morpholine;

313) 2-(R)-(1-(R)-(3-trifluoromethyl)phenylethoxy)-3-(S)-phenyl-morpholine;

314) 2-(R)-(1-(R)-(3-trifluoromethyl)phenylethoxy)-3-(S)-(4-fluoro)phenyl-morph oline;

317) 2-(R)-(1-(R)-(3-trifluoromethyl)phenylethoxy)-3-(S)-phenyl-4-(3-1H,4H-1,2, 4-triazolo)methyl-morpholine;

318) 2-(R)-(1-(R)-(3-trifluoromethyl)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4-(3- (1,2,4-triazolo)methyl-morpholine;

321) 2-(R)-(1-(R)-(3-trifluoromethyl)phenylethoxy)-3-(S)-phenyl-4-(3-(5-oxo-1H ,4H-1,2,4-triazolo)methyl)-morpholine;

322) 2-(R)-(1-(R)-(3-trifluoromethyl)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4-(3- (5-oxo-1H,4H-1,2,4-triazolo)methyl)-morpholine;

325) 2-(R)-(1-(R)-(3-trifluoromethyl)phenylethoxy)-3-(S)-phenyl-4-(4-(2-oxo-1,3 -imidazolo)methyl)-morpholine;

326) 2-(R)-(1-(R)-(3-trifluoromethyl)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4-(4- (2-oxo-1,3-imidazolo)methyl)-morpholine;

329) 2-(R)-(1-(R)-(3-trifluoromethyl)phenylethoxy)-3-(S)-phenyl-4-(2-imidazolo) methyl-morpholine;

330) 2-(R)-(1-(R)-(3-trifluoromethyl)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4-(2- imidazolo)methyl-morpholine;

333) 2-(R)-(1-(R)-(3-trifluoromethyl)phenylethoxy)-3-(S)-phenyl-4-(4-imidazolo) methyl-morpholine;

334) 2-(R)-(1-(R)-(3-trifluoromethyl)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4-(4- imidazolo)methyl-morpholine;

337) 2-(R)-(1-(R)-(3-trifluoromethyl)phenylethoxy)-3-(S)-phenyl-4-(5-tetrazolo) methyl-morpholine;

338) 2-(R)-(1-(R)-(3-trifluoromethyl)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4-(5- tetrazolo)methyl-morpholine;

341) 2-(R)-(1-(R)-(3-trifluoromethyl)phenylethoxy)-3-(S)-phenyl-4-(2-oxo-5H-pyr rol-4-yl)methyl-morpholine;

342) 2-(R)-(1-(R)-(3-trifluoromethyl)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4-(2- oxo-5H-pyrrol-4-yl)methyl-morpholine;

345) 2-(R)-(1-(R)-(3-t-butyl)phenylethoxy)-3-(S)-phenyl-morpholine;

346) 2-(R)-(1-(R)-(3-t-butyl)phenylethoxy)-3-(S)-(4-fluoro)phenyl-morpholine;

349) 2-(R)-(1-(R)-(3-t-butyl)phenylethoxy)-3-(S)-phenyl-4-(3-(1,2,4-triazolo)me thyl)-morpholine;

350) 2-(R)-(1-(R)-(3-t-butyl)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(1,2,4-t riazolo)methyl)-morpholine;

353) 2-(R)-(1-(R)-(3-t-butyl)phenylethoxy)-3-(S)-phenyl-4-(3-(5-oxo-1H,4H-1,2,4 -triazolo)methyl)-morpholine;

354) 2-(R)-(1-(R)-(3-t-butyl)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(5-oxo-1 H,4H-1,2,4-triazolo)methyl)-morpholine;

357) 2-(R)-(1-(R)-(3-t-butyl)phenylethoxy)-3-(S)-phenyl-4-(4-(2-oxo-1,3-imidazo lo)methyl-morpholine;

358) 2-(R)-(1-(R)-(3-t-butyl)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4-(4-(2-oxo-1 ,3-imidazolo)methyl)-morpholine;

361) 2-(R)-(1-(R)-(3-t-butyl)phenylethoxy)-3-(S)-phenyl-4-(2-imidazolo)methyl-m orpholine;

362) 2-(R)-(1-(R)-(3-t-butyl)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4-(2-imidazol o)methyl-morpholine;

365) 2-(R)-(1-(R)-(3-t-butyl)phenylethoxy)-3-(S)-phenyl-4-(4-imidazolo)methyl-m orpholine;

366) 2-(R)-(1-(R)-(3-(t-butyl)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(4-imidaz olo)methyl-morpholine;

369) 2-(R)-(1-(R)-(3-(t-butyl)phenyl)ethoxy)-3-(S)-phenyl-4-(5-tetrazolo)methyl -morpholine;

370) 2-(R)-(1-(R)-(3-(t-butyl)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(5-tetraz olo)methyl-morpholine;

373) 2-(R)-(1-(R)-(3-(t-butyl)phenyl)ethoxy)-3-(S)-phenyl-4-(2-oxo-5H-pyrrol-4- yl)methyl-morpholine;

374) 2-(R)-(1-(R)-(3-(t-butyl)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(2-oxo-5H -pyrrol-4-yl)methyl-morpholine;

378) 2-(R)-(1-(R)-(2,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-(4-fluorophenyl )-morpholine;

379) 2-(R)-(1-(R)-(2,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-(4-fluorophenyl )-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methyl)-morpholine;

380) 2-(R)-(1-(R)-(2,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-(4-fluorophenyl )-4-(3-(1,2,4-triazolo)methyl)-morpholine;

381) 2-(R)-(1-(R)-(2,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-(4-fluorophenyl )-4-(4-(2-oxo-1,3-imidazolo)methyl)-morpholine;

382) 2-(R)-(1-(R)-(3-(thiomethyl)phenyl)ethoxy)-3-(S)-phenyl-morpholine;

383) 2-(R)-(1-(R)-(3-(thiomethylphenyl)ethoxy)-3-(S)-phenyl-4-(3-(5-oxo-1H,4H-1 ,2,4-triazolo)methyl)-morpholine;

384) 2-(R)-(1-(R)-(3-(thiomethylphenyl)ethoxy)-3-(S)-phenyl-4-(3-(1,2,4-triazol o)methyl)-morpholine;

385) 2-(R)-(1-(R)-(3-(thiomethylphenyl)ethoxy)-3-(S)-phenyl-4-(4-(2-oxo-1,3-imi dazolo)methyl)-morpholine;

386) 2-(R)-(1-(R)-(3-(thiomethyl)-5-(trifluoromethyl)phenyl)ethoxy)-3-(S)-pheny l-morpholine;

387) 2-(R)-(1-(R)-(3-(thiomethyl-5-(trifluoromethyl)phenyl)ethoxy)-3-(S)-phenyl -4-(3-(5-oxo-1H ,4H-1,2,4-triazolo)methyl)-morpholine;

388) 2-(R)-(1-(R)-(3-(thiomethyl-5-(trifluoromethyl)phenyl)ethoxy)-3-(S)-phenyl -4-(3-(1,2,4-triazolo)methyl)-morpholine;

389) 2-(R)-(1-(R)-(3-(thiomethyl-5-(trifluoromethyl)phenyl)ethoxy)-3-(S)-phenyl -4-(4-(2-oxo-1,3-imidazolo)methyl)-morpholine;

394) 2-(R)-(1-(R)-(3,5-(dimethoxy)phenyl)ethoxy)-3-(S)-phenyl-morpholine;

395) 2-(R)-(1-(R)-(3,5-(dimethoxy)phenyl)ethoxy)-3-(S)-phenyl-4-(3-(5-oxo-1H,4H -1,2,4-triazolo)methyl)-morpholine;

396) 2-(R)-(1-(R)-(3,5-(dimethoxy)phenyl)ethoxy)-3-(S)-phenyl-4-(3-(1,2,4-triaz olo)methyl)-morpholine;

397) 2-(R)-(1-(R)-(3,5-(dimethoxy)phenyl)ethoxy)-3-(S)-phenyl-4-(4-(2-oxo-1,3-i midazolo)methyl)-morpholine;

398) 2-(R)-(1-(R)-(3-(fluoro)-5-(trifluoromethyl)phenyl)-ethoxy)-3-(S)-(4-fluor ophenyl)-morpholine;

399) 2-(R)-(1-(R)-(3-(fluorophenyl)-5-(trifluoromethyl)ethoxy)-3-(S)-(4-fluoro) phenyl-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methyl)-morpholine;

400) 2-(R)-(1-(R)-(3-(fluorophenyl)-5-(trifluoromethyl)ethoxy)-3-(S)-(4-fluoro) phenyl-4-(3-(1,2,4-triazolo)methyl)-morpholine;

401) 2-(R)-(1-(R)-(3-(fluorophenyl)-5-(trifluoromethyl)ethoxy)-3-(S)-(4-fluoro) phenyl-4-(4-(2-oxo-1,3-imidazolo)methyl)-morpholine;

402) 2-(R)-(1-(R)-(3-(chloro)-5-(trifluoromethyl)phenyl)-ethoxy)-3-(S)-(4-fluor o)phenyl-morpholine;

403) 2-(R)-(1-(R)-(3-(chlorophenyl)-5-(trifluoromethyl)ethoxy)-3-(S)-(4-fluoro) phenyl-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methyl)-morpholine;

404) 2-(R)-(1-(R)-(3-(chlorophenyl)-5-(trifluoromethyl)ethoxy)-3-(S)-(4-fluoro) phenyl-4-(3-(1,2,4-triazolo)methyl)-morpholine;

405) 2-(R)-(1-(R)-(3-(chlorophenyl)-5-(trifluoromethyl)ethoxy)-3-(S)-(4-fluoro) phenyl-4-(4-(2-oxo-1,3-imidazolo)methyl)-morpholine;

406) 2-(R)-(1-(R)-(3,5-(dimethyl)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-morpholi ne;

407) 2-(R)-(1-(R)-(3,5-(dimethyl)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(5- oxo-1H ,4H-1,2,4-triazolo)methyl)-morpholine;

408) 2-(R)-(1-(R)-(3,5-(dimethyl)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(1, 2,4-triazolo)methyl)-morpholine;

409) 2-(R)-(1-(R)-(3,5-(dimethyl)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(4-(2- oxo-1,3-imidazolo)methyl)-morpholine;

410) 2-(R)-(1-(R)-(3-(fluoro)-5-(methyl)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-m orpholine;

411) 2-(R)-(1-(R)-(3-(fluoro)-5-(methyl)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4 -(3-(5-oxo-1H,4H-1,2,4-triazolo)methyl)-morpholine;

412) 2-(R)-(1-(R)-(3-(fluoro)-5-(methyl)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4 -(3-(1,2,4-triazolo)methyl)-morpholine;

413) 2-(R)-(1-(R)-(3-(fluoro)-5-(methyl)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4 -(4-(2-oxo-1,3-imidazolo)methyl)-morpholine;

414) 2-(R)-(1-(R)-(3-(chloro)-5-(methyl)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-m orpholine;

415) 2-(R)-(1-(R)-(3-(chloro)-5-(methyl)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4 -(3-(5-oxo-1H,4H-1,2,4-triazolo)methyl)-morpholine;

416) 2-(R)-(1-(R)-(3-(chloro)-5-(methyl)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4 -(3-(1,2,4-triazolo)methyl)-morpholine;

417) 2-(R)-(1-(R)-(3-(chloro)-5-(methyl)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4 -(4-(2-oxo-1,3-imidazolo)methyl)-morpholine;

418) 2-(R)-(1-(R)-(3-(bromo)-5-(methyl)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-mo rpholine;

419) 2-(R)-(1-(R)-(3-(bromo)-5-(methyl)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4- (3-(5-oxo-1H,4H-1,2,4-triazolo)methyl)-morpholine;

420) 2-(R)-(1-(R)-(3-(bromo)-5-(methyl)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4- (3-(1,2,4-triazolo)methyl)-morpholine;

421) 2-(R)-(1-(R)-(3-(bromo)-5-(methyl)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4- (4-(2-oxo-1,3-imidazolo)methyl)-morpholine;

422) 2-(R)-(1-(R)-(3-(isopropoxy)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-morpholi ne;

423) 2-(R)-(1-(R)-(3-(isopropoxy)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(5- oxo-1H,4H-1,2,4-triazolo)methyl)-morpholine;

424) 2-(R)-(1-(R)-(3-(isopropoxy)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(1, 2,4-triazolo)methyl)-morpholine;

425) 2-(R)-(1-(R)-(3-(isopropoxy)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(4-(2- oxo-1,3-imidazolo)methyl)-morpholine;

426) 2-(R)-(1-(R)-(3-(isopropoxy)-5-(trifluoromethyl)phenyl)ethoxy)-3-(S)-(4-fl uoro)phenyl-morpholine;

427) 2-(R)-(1-(R)-(3-(isopropoxy)-5-(trifluoromethyl)phenyl)ethoxy)-3-(S)-(4-fl uoro)phenyl-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methyl)-morpholine;

428) 2-(R)-(1-(R)-(3-(isopropoxy)-5-(trifluoromethyl)phenyl)ethoxy)-3-(S)-(4-fl uoro)phenyl-4-(3-(1,2,4-triazolo)methyl)-morpholine;

429) 2-(R)-(1-(R)-(3-(isopropoxy)-5-(trifluoromethyl)phenyl)ethoxy)-3-(S)-(4-fl uoro)phenyl-4-(4-(2-oxo-1,3-imidazolo)methyl)-morpholine;

430) 2-(R)-(1-(R)-(3-(chloro)-5-(isopropoxy)phenyl)ethoxy)-3-(S)-(4-fluoro)phen yl-morpholine;

431) 2-(R)-(1-(R)-(3-(chloro)-5-(isopropoxy)phenyl)ethoxy)-3-(S)-(4-fluoro)phen yl-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methyl)-morpholine;

432) 2-(R)-(1-(R)-(3-(chloro)-5-(isopropoxy)phenyl)ethoxy)-3-(S)-(4-fluoro)phen yl-4-(3-(1,2,4-triazolo)methyl)-morpholine;

433) 2-(R)-(1-(R)-(3-(chloro)-5-(isopropoxy)phenyl)ethoxy)-3-(S)-(4-fluoro)phen yl-4-(4-(2-oxo-1,3-imidazolo)methyl)-morpholine;

434) 2-(R)-(1-(R)-(3-(fluoro)-5-(isopropoxy)phenyl)ethoxy)-3-(S)-(4-fluoro)phen yl-morpholine;

435) 2-(R)-(1-(R)-(3-(fluoro)-5-(isopropoxy)phenyl)ethoxy)-3-(S)-(4-fluoro)phen yl-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methyl)-morpholine;

436) 2-(R)-(1-(R)-(3-(fluoro)-5-(isopropoxy)phenyl)ethoxy)-3-(S)-(4-fluoro)phen yl-4-(3-(1,2,4-triazolo)methyl)-morpholine;

437) 2-(R)-(1-(R)-(3-(fluoro)-5-(isopropoxy)phenyl)ethoxy)-3-(S)-(4-fluoro)phen yl-4-(4-(2-oxo-1,3-imidazolo)methyl)-morpholine;

438) 2-(R)-(1-(R)-(3-(t-butyl)-5-(chloro)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl- morpholine;

439) 2-(R)-(1-(R)-(3-(t-butyl)-5-(chloro)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl- 4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methyl)-morpholine;

440) 2-(R)-(1-(R)-(3-(t-butyl)-5-(chloro)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl- 4-(3-(1,2,4-triazolo)methyl)-morpholine;

441) 2-(R)-(1-(R)-(3-(t-butyl)-5-(chloro)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl- 4-(4-(2-oxo-1,3-imidazolo)methyl)-morpholine;

442) 2-(R)-(1-(R)-(3-(t-butyl)-5-(trifluoromethyl)phenyl)ethoxy)-3-(S)-(4-fluor o)phenyl-morpholine;

443) 2-(R)-(1-(R)-(3-(t-butyl)-5-(trifluoromethyl)phenyl)ethoxy)-3-(S)-(4-fluor o)phenyl-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methyl)-morpholine;

444) 2-(R)-(1-(R)-(3-(t-butyl)-5-(trifluoromethyl)phenyl)ethoxy)-3-(S)-(4-fluor o)phenyl-4-(3-(1,2,4-triazolo)methyl)-morpholine;

445) 2-(R)-(1-(R)-(3-(t-butyl)-5-(trifluoromethyl)phenyl)ethoxy)-3-(S)-(4-fluor o)phenyl-4-(4-(2-oxo-1,3-imidazolo)methyl)-morpholine;

446) 2-(R)-(1-(R)-(3,5-(dimethyl)-4-(fluoro)phenyl)ethoxy)-3-(S)-(4-fluoro)phen yl-morpholine;

447) 2-(R)-(1-(R)-(3,5-(dimethyl)-4-(fluoro)phenyl)ethoxy)-3-(S)-(4-fluoro)phen yl-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methyl)-morpholine;

448) 2-(R)-(1-(R)-(3,5-(dimethyl)-4-(fluoro)phenyl)ethoxy)-3-(S)-(4-fluoro)phen yl-4-(3-(1,2,4-triazolo)methyl)-morpholine;

449) 2-(R)-(1-(R)-(3,5-(dimethyl)-4-(fluoro)phenyl)ethoxy)-3-(S)-(4-fluoro)phen yl-4-(4-(2-oxo-1,3-imidazolo)methyl)-morpholine;

450) 2-(R)-(1-(R)-(3,5-(dimethyl)-4-(chloro)phenyl)ethoxy)-3-(S)-(4-fluoro)phen yl-morpholine;

451) 2-(R)-(1-(R)-(3,5-(dimethyl)-4-(chloro)phenyl)ethoxy)-3-(S)-(4-fluoro)phen yl-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methyl)-morpholine;

452) 2-(R)-(1-(R)-(3,5-(dimethyl)-4-(chloro)phenyl)ethoxy)-3-(S)-(4-fluoro)phen yl-4-(3-(1,2,4-triazolo)methyl)-morpholine;

453) 2-(R)-(1-(R)-(3,5-(dimethyl)-4-(chloro)phenyl)ethoxy)-3-(S)-(4-fluoro)phen yl-4-(4-(2-oxo-1,3-imidazolo)methyl)-morpholine;

454) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)-4-(fluoro)phenyl)ethoxy)-3-(S)-(4-f luoro)phenyl-morpholine;

455) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)-4-(fluoro)phenyl)ethoxy)-3-(S)-(4-f luoro)phenyl-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methyl)-morpholine;

456) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)-4-(fluoro)phenyl)ethoxy)-3-(S)-(4-f luoro)phenyl-4-(3-(1,2,4-triazolo)methyl)-morpholine;

457) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)-4-(fluoro)phenyl)ethoxy)-3-(S)-(4-f luoro)phenyl-4-(4-(2-oxo-1,3-imidazolo)methyl)-morpholine;

458) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)-4-(chloro)phenyl)ethoxy)-3-(S)-(4-f luoro)phenyl-morpholine;

459) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)-4-(chloro)phenyl)ethoxy)-3-(S)-(4-f luoro)phenyl-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methyl)-morpholine;

460) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)-4-(chloro)phenyl)ethoxy)-3-(S)-(4-f luoro)phenyl-4-(3-(1,2,4-triazolo)methyl)-morpholine;

461) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)-4-(chloro)phenyl)ethoxy)-3-(S)-(4-f luoro)phenyl-4-(4-(2-oxo-1,3-imidazolo)methyl)-morpholine;

462) 2-(R)-(1-(R)-(3,5-(dichloro)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-morpholi ne;

463) 2-(R)-(1-(R)-(3,5-(dichloro)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(5- oxo-1H,4H-1,2,4-triazolo)methyl)-morpholine;

464) 2-(R)-(1-(R)-(3,5-(dichloro)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(1, 2,4-triazolo)methyl)-morpholine;

465) 2-(R)-(1-(R)-(3,5-(dichloro)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(4-(2- oxo-1,3-imidazolo)methyl)-morpholine;

466) 2-(R)-(1-(R)-(3,5-(difluoro)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-morpholi ne;

467) 2-(R)-(1-(R)-(3,5-(difluoro)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(5- oxo-1H ,4H-1,2,4-triazolo)methyl)-morpholine;

468) 2-(R)-(1-(R)-(3,5-(difluoro)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(1, 2,4-triazolo)methyl)-morpholine;

469) 2-(R)-(1-(R)-(3,5-(difluoro)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(4-(2- oxo-1,3-imidazolo)methyl)-morpholine;

494) 2-(R)-(1-(R)-(3-(thiomethyl)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-morpholi ne;

495) 2-(R)-(1-(R)-(3-(thiomethylphenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(5-o xo-1H ,4H-1,2,4-triazolo)methyl)-morpholine;

496) 2-(R)-(1-(R)-(3-(thiomethylphenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(1,2 ,4-triazolo)methyl)-morpholine;

497) 2-(R)-(1-(R)-(3-(thiomethylphenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(4-(2-o xo-1,3-imidazolo)methyl)-morpholine;

498) 2-(R)-(1-(R)-(3-(thiomethyl)-5-(trifluoromethyl)phenyl)ethoxy)-3-(S)-(4-fl uoro)phenyl-morpholine;

499) 2-(R)-(1-(R)-(3-(thiomethyl-5-(trifluoromethyl)phenyl)ethoxy)-3-(S)-(4-flu oro)phenyl-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methyl)-morpholine;

500) 2-(R)-(1-(R)-(3-(thiomethyl-5-(trifluoromethyl)phenyl)ethoxy)-3-(S)-(4-flu oro)phenyl-4-(3-(1,2,4-triazolo)methyl)-morpholine;

501) 2-(R)-(1-(R)-(3-(thiomethyl-5-(trifluoromethyl)phenyl)ethoxy)-3-(S)-(4-flu oro)phenyl-4-(4-(2-oxo-1,3-imidazolo)methyl)-morpholine;

506) 2-(R)-(1-(R)-(3,5-(dimethoxy)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-morphol ine;

507) 2-(R)-(1-(R)-(3,5-(dimethoxy)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(5 -oxo-1H,4H-1,2,4-triazolo)methyl)-morpholine;

508) 2-(R)-(1-(R)-(3,5-(dimethoxy)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(1 ,2,4-triazolo)methyl)-morpholine;

509) 2-(R)-(1-(R)-(3,5-(dimethoxy)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(4-(2 -oxo-1,3-imidazolo)methyl)-morpholine;

510) 2-(R)-(1-(R)-(phenyl)ethoxy)-3-(S)-phenyl-morpholine;

511) 2-(R)-(1-(R)-(phenyl)ethoxy)-3-(S)-phenyl-4-(3-(5-oxo-1H,4H-1,2,4-triazolo )methyl)-morpholine;

512) 2-(R)-(1-(R)-(phenyl)ethoxy)-3-(S)-phenyl-4-(3-(1,2,4-triazolo)methyl)-mor pholine;

513) 2-(R)-(1-(R)-(phenyl)ethoxy)-3-(S)-phenyl-4-(4-(2-oxo-1,3-imidazolo)methyl )-morpholine;

514) 2-(R)-(1-(R)-(phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl morpholine;

515) 2-(R)-(1-(R)-(phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(5-oxo-1H,4H-1,2, 4-triazolo)methyl)-morpholine;

516) 2-(R)-(1-(R)-(phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(1,2,4-triazolo)m ethyl)-morpholine;

517) 2-(R)-(1-(R)-(phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(4-(2-oxo-1,3-imidaz olo)methyl)-morpholine;

518) 2-(R)-(1-(R)-(3-(fluoro)phenyl)ethoxy)-3-(S)-phenyl-morpholine;

519) 2-(R)-(1-(R)-(3-(fluoro)phenyl)ethoxy)-3-(S)-phenyl-4-(3-(5-oxo-1H,4H-1,2, 4-triazolo)methyl)-morpholine;

520) 2-(R)-(1-(R)-(3-(fluoro)phenyl)ethoxy)-3-(S)-phenyl-4-(3-(1,2,4-triazolo)m ethyl)-morpholine;

521) 2-(R)-(1-(R)-(3-(fluoro)phenyl)ethoxy)-3-(S)-phenyl-4-(4-(2-oxo-1,3-imidaz olo)methyl)-morpholine;

522) 2-(R)-(1-(R)-(3-(fluoro)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-morpholine;

523) 2-(R)-(1-(R)-(3-(fluoro)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(5-oxo- 1H,4H-1,2,4-triazolo)methyl)-morpholine;

524) 2-(R)-(1-(R)-(3-(fluoro)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(1,2,4- triazolo)methyl)-morpholine;

525) 2-(R)-(1-(R)-(3-(fluoro)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(4-(2-oxo- 1,3-imidazolo)methyl)-morpholine;

526) 2-(R)-(1-(R)-(4-(fluoro)phenyl)ethoxy)-3-(S)-phenyl-morpholine;

527) 2-(R)-(1-(R)-(4-(fluoro)phenyl)ethoxy)-3-(S)-phenyl-4-(3-(5-oxo-1H ,4H-1,2,4-triazolo)methyl)-morpholine;

528) 2-(R)-(1-(R)-(4-(fluoro)phenyl)ethoxy)-3-(S)-phenyl-4-(3-(1,2,4-triazolo)m ethyl)-morpholine;

529) 2-(R)-(1-(R)-(4-(fluoro)phenyl)ethoxy)-3-(S)-phenyl-4-(4-(2-oxo-1,3-imidaz olo)methyl)-morpholine;

530) 2-(R)-(1-(R)-(4-(fluoro)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-morpholine;

531) 2-(R)-(1-(R)-(4-(fluoro)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(5-oxo- 1H,4H-1,2,4-triazolo)methyl)-morpholine;

532) 2-(R)-(1-(R)-(4-(fluoro)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(1,2,4- triazolo)methyl)-morpholine;

533) 2-(R)-(1-(R)-(4-(fluoro)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(4-(2-oxo- 1,3-imidazolo)methyl)-morpholine;

534) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-(3-fluoro)pheny l-morpholine;

535) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-(3-fluoro)pheny l-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methyl)-morpholine;

536) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-(3-fluoro)pheny l-4-(3-(1,2,4-triazolo)methyl)-morpholine;

537) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-(3-fluoro)pheny l-4-(4-(2-oxo-1,3-imidazolo)methyl)-morpholine;

538) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-(3,4-difluoro)p henyl-morpholine;

539) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-(3,4-difluoro)p henyl-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methyl)-morpholine;

540) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-(3,4-difluoro)p henyl-4-(3-(1,2,4-triazolo)methyl)-morpholine;

541) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-(3,4-difluoro)p henyl-4-(4-(2-oxo-1,3-imidazolo)methyl)-morpholine;

542) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-(3,4-dichloro)p henyl-morpholine;

543) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-(3,4-dichloro)p henyl-4-(3-(5-oxo-1H,4Ho 1,2,4-triazolo)methyl)-morpholine;

544) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-(3,4-dichloro)p henyl-4-(3-(1,2,4-triazolo)methyl)-morpholine;

545) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-(3,4-dichloro)p henyl-4-(4-(2-oxo-1,3-imidazolo)methyl)-morpholine;

546) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-(3,4-dimethyl)p henyl-morpholine;

547) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-(3,4-dimethyl)p henyl-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methyl)-morpholine;

548) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-(3,4-dimethyl)p henyl-4-(3-(1,2,4-triazolo)methyl)-morpholine;

549) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-(3,4-dimethyl)p henyl-4-(4-(2-oxo-1,3-imidazolo)methyl)-morpholine;

550) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-3,4-methylenedi oxyphenyl-morpholine;

551) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-3,4-methylenedi oxyphenyl-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methyl)-morpholine;

552) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-3,4-methylenedi oxyphenyl-4-(3-(1,2,4-triazolo)methyl)-morpholine;

553) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-3,4-methylenedi oxyphenyl-4-(4-(2-oxo-1,3-imidazolo)methyl)-morpholine;

554) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-(2-naphthyl)-mo rpholine;

555) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-(2-naphthyl)-4- (3-(5-oxo-1H,4H-1,2,4-triazolo)methyl)-morpholine;

556) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-(2-naphthyl)-4- (3-(1,2,4-triazolo)methyl)-morpholine;

557) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-(2-naphthyl)-4- (4-(2-oxo-1,3-imidazolo)methyl)-morpholine;

558) 2-(R)-(1-(R)-(3-(fluorophenyl)-5-(trifluoromethyl)ethoxy)-3-(S)-phenyl-4-( 3-(1,2,4-triazolo)methyl)-morpholine;

559) 2-(R)-(1-(R)-(3-(fluorophenyl)-5-(trifluoromethyl)ethoxy)-3-(S)-phenyl-4-( 4-(2-oxo-1,3-imidazolo)methyl)-morpholine;

560) 2-(R)-(1-(R)-(3-(chlorophenyl)-5-(trifluoromethyl)ethoxy)-3-(S)-phenyl-4-( 3-(1,2,4-triazolo)methyl)-morpholine;

561) 2-(R)-(1-(R)-(3-(chlorophenyl)-5-(trifluoromethyl)ethoxy)-3-(S)-phenyl-4-( 4-(2-oxo-1,3-imidazolo)methyl)-morpholine;

562) 2-(R)-(1-(R)-(3,5-(dimethyl)phenyl)ethoxy)-3-(S)-phenyl-4-(3-(1,2,4-triazo lo)methyl)-morpholine;

563) 2-(R)-(1-(R)-(3,5-(dimethyl)phenyl)ethoxy)-3-(S)-phenyl-4-(4-(2-oxo-1,3-im idazolo)methyl)-morpholine;

564) 2-(R)-(1-(R)-(3-(fluoro)-5-(methyl)phenyl)ethoxy)-3-(S)-phenyl-4-(3-(1,2,4 -triazolo)methyl)-morpholine;

565) 2-(R)-(1-(R)-(3-(fluoro)-5-(methyl)phenyl)ethoxy)-3-(S)-phenyl-4-(4-(2-oxo -1,3-imidazolo)methyl)-morpholine;

566) 2-(R)-(1-(R)-(3-(chloro)-5-(methyl)phenyl)ethoxy)-3-(S)-phenyl-4-(3-(-1H,4 H-1,2,4-triazolo)methyl)-morpholine;

567) 2-(R)-(1-(R)-(3-(chloro)-5-(methyl)phenyl)ethoxy)-3-(S)-phenyl-4-(4-(2-oxo -1,3-imidazolo)methyl)-morpholine;

568) 2-(R)-(1-(R)-(3-(bromo)-5-(methyl)phenyl)ethoxy)-3-(S)-phenyl-4-(3-(1,2,4- triazolo)methyl)-morpholine;

569) 2-(R)-(1-(R)-(3-(bromo)-5-(methyl)phenyl)ethoxy)-3-(S)-phenyl-4-(4-(2-oxo- 1,3-imidazolo)methyl)-morpholine;

570) 2-(R)-(1-(R)-(3-(isopropoxy)phenyl)ethoxy)-3-(S)-phenyl-4-(3-(1,2,4-triazo lo)methyl)-morpholine;

571) 2-(R)-(1-(R)-(3-(isopropoxy)phenyl)ethoxy)-3-(S)-phenyl-4-(4-(2-oxo-1,3-im idazolo)methyl)-morpholine;

572) 2-(R)-(1-(R)-(3-(isopropoxy)-5-(trifluoromethyl)phenyl)ethoxy)-3-(S)-pheny l-4-(3-(-1H ,4H-1,2,4-triazolo)methyl)-morpholine;

573) 2-(R)-(1-(R)-(3-(isopropoxy)-5-(trifluoromethyl)phenyl)ethoxy)-3-(S)-pheny l-4-(4-(2-oxo-1,3-imidazolo)methyl)-morpholine;

574) 2-(R)-(1-(R)-(3-(chloro)-5-(isopropoxy)phenyl)ethoxy)-3-(S)-phenyl-4-(3-(- 1H,4H-1,2,4-triazolo)methyl)-morpholine;

575) 2-(R)-(1-(R)-(3-(chloro)-5-(isopropoxy)phenyl)ethoxy)-3-(S)-phenyl-4-(4-(2 -oxo-1,3-imidazolo)methyl)-morpholine;

576) 2-(R)-(1-(R)-(3-(fluoro)-5-(isopropoxy)phenyl)ethoxy)-3-(S)-phenyl-4-(3-(- 1H,4H-1,2,4-triazolo)methyl)-morpholine;

577) 2-(R)-(1-(R)-(3-(fluoro)-5-(isopropoxy)phenyl)ethoxy)-3-(S)-phenyl-4-(4-(2 -oxo-1,3-imidazolo)methyl)-morpholine;

578) 2-(R)-(1-(R)-(3-(t-butyl)-5-(chloro)phenyl)ethoxy)-3-(S)-phenyl-4-(3-(-1H ,4H-1,2,4-triazolo)methyl)-morpholine;

579) 2-(R)-(1-(R)-(3-(t-butyl)-5-(chloro)phenyl)ethoxy)-3-(S)-phenyl-4-(4-(2-ox o-1,3-imidazolo)methyl)-morpholine;

580) 2-(R)-(1-(R)-(3-(t-butyl)-5-(trifluoromethyl)phenyl)ethoxy)-3-(S)-phenyl-4 -(3-(-1H,4H-1,2,4-triazolo)methyl)-morpholine;

581) 2-(R)-(1-(R)-(3-(t-butyl)-5-(trifluoro methyl)phenyl)ethoxy)-3-(S)-phenyl-4-(4-(2-oxo-1,3-imidazolo)methyl)-morph oline;

582) 2-(R)-(1-(R)-(3,5-(dimethyl)-4-(fluoro)phenyl)ethoxy)-3-(S)-phenyl-4-(3-(1 ,2,4-triazolo)methyl)-morpholine;

583) 2-(R)-(1-(R)-(3,5-(dimethyl)-4-(fluoro)phenyl)ethoxy)-3-(S)-phenyl-4-(4-(2 -oxo-1,3-imidazolo)methyl)-morpholine;

584) 2-(R)-(1-(R)-(3,5-(dimethyl)-4-(chloro)phenyl)ethoxy)-3-(S)-phenyl-4-(3-(- 1H,4H-1,2,4-triazolo)methyl)-morpholine;

585) 2-(R)-(1-(R)-(3,5-(dimethyl)-4-(chloro)phenyl)ethoxy)-3-(S)-phenyl-4-(4-(2 -oxo-1,3-imidazolo)methyl)-morpholine;

586) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)-4-(fluoro)phenyl)ethoxy)-3-(S)-phen yl-4-(3-(-1H,4H-1,2,4-triazolo)methyl)-morpholine;

587) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)-4-(fluoro)phenyl)ethoxy)-3-(S)-phen yl-4-(4-(2-oxo-1,3-imidazolo)methyl)-morpholine;

588) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)-4-(chloro)phenyl)ethoxy)-3-(S)-phen yl-4-(3-(-1H,4H-1,2,4-triazolo)methyl)-morpholine;

589) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)-4-(chloro)phenyl)ethoxy)-3-(S)-phen yl-4-(4-(2-oxo-1,3-imidazolo)methyl)-morpholine;

590) 2-(R)-(1-(R)-(3,5-(dichloro)phenyl)ethoxy)-3-(S)-phenyl-4-(3-(-1H,4H-1,2,4 -triazolo)methyl)-morpholine;

591) 2-(R)-(1-(R)-(3,5-(dichloro)phenyl)ethoxy)-3-(S)-phenyl-4-(4-(2-oxo-1,3-im idazolo)methyl)-morpholine;

592) 2-(R)-(1-(R)-(3,5-(difluoro)phenyl)ethoxy)-3-(S)-phenyl-4-(3-(1,2,4-triazo lo)methyl)-morpholine;

593) 2-(R)-(1-(R)-(3,5-(difluoro)phenyl)ethoxy)-3-(S)-phenyl-4-(4-(2-oxo-1,3-im idazolo)methyl)-morpholine;

or a pharmaceutically acceptable salt thereof.

16. A compound which is:

2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl -4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methyl-morpholine;

or a pharmaceutically acceptable salt thereof.

17. A compound which is: ##STR27## or a pharmaceutically acceptable salt thereof.

18. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and an effective amount of the compound of claim 1.

19. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and an effective amount of the compound of a compound which is: ##STR28## or a pharmaceutically acceptable salt thereof.

20. A method for antagonizing the effect of substance P at its receptor site or for the blockade of neurokinin-1 receptors in a mammal which comprises the administration to the mammal of the compound of claim 1 in an amount that is effective for antagonizing the effect of substance P at its receptor site in the mammal.

21. A method for antagonizing the effect of neurokinin A at its receptor site or for the blockade of neurokinin-2 receptors in a mammal which comprises the administration to the mammal of the compound of claim 1 in an amount that is effective for antagonizing the effect of neurokinin A at its receptor site in the mammal.

22. A method of treating or preventing pain or nociception attributable to or associated with migraine in a mammal in need thereof which comprises the administration to the mammmal of an effective amount of the compound of claim 1.

23. A method of treating or preventing a condition selected from the group consisting of: diabetic neuropathy; peripheral neuropathy; AIDS related neuropathy; chemotherapy-induced neuropathy; and neuralgia, in a mammal in need thereof which comprises the administration to the mammal of an effective amount of the compound of claim 1.

24. A method for the treatment or prevention of asthma in a mammal in need thereof which comprises the administration to the mammal of an effective amount of the compound of claim 1, either alone or in combination with a neurokinin-2 receptor antagonist or with a .beta..sub.2 -adrenergic receptor agonist.

25. A method for the treatment of cystic fibrosis in a mammal in need thereof which comprises the administration to the mammal of an effective amount of the compound of claim 1.

26. A method for the treatment or prevention of emesis in a mammal in need thereof which comprises the administration to the mammal of an effective amount of the compound of claim 1.

27. A process for the preparation of a compound of structural formula IV: ##STR29## or a pharmaceutically acceptable salt thereof, wherein: R.sup.1 is selected from the group consisting of:

(1) hydrogen;

(2) C.sub.1-6 alkyl, unsubstituted or substituted with one or more of the substituents selected from:

(a) hydroxy,

(b) oxo,

(c) C.sub.1-6 alkoxy,

(d) phenyl-C.sub.1-3 alkoxy,

(e) phenyl,

(f) --CN,

(g) halo, wherein halo is fluoro, chloro, bromo or iodo,

(h) --NR.sup.9 R.sup.10, wherein R.sup.9 and R.sup.10 are independently selected from:

(i) hydrogen,

(ii) C.sub.1-6 alkyl,

(iii) hydroxy-C.sub.1-6 alkyl, and

(iv) phenyl,

(i) --NR.sup.9 COR.sup.10,

(j) --NR.sup.9 CO.sub.2 R.sup.10,

(k) --CONR.sup.9 R.sup.10,

(l) --COR.sup.9,

(m) --CO.sub.2 R.sup.9,

(n) heterocycle, wherein the heterocycle is selected from the group consisting of:

(A) benzimidazolyl,

(B) benzofuranyl,

(C) benzothiophenyl,

(D) benzoxazolyl,

(E) furanyl,

(F) imidazolyl,

(G) indolyl,

(H) isooxazolyl,

(I) isothiazolyl,

(J) oxadiazolyl,

(K) oxazolyl,

(L) pyrazinyl,

(M) pyrazolyl,

(N) pyridyl,

(O) pyrimidyl,

(P) pyrrolyl,

(Q) quinolyl,

(R) tetrazolyl,

(S) thiadiazolyl,

(T) thiazolyl,

(U) thienyl,

(V) triazolyl,

(W) azetidinyl,

(X) 1,4-dioxanyl,

(Y) hexahydroazepinyl,

(Z) piperazinyl,

(AA) piperidinyl,

(AB) pyrrolidinyl,

(AC) tetrahydrofuranyl, and

(AD) tetrahydrothienyl, and wherein the heterocycle is unsubstituted or substituted with one or more substituent(s) selected from:

(i) C.sub.1-6 alkyl, unsubstituted or substituted with halo, --CF.sub.3, --OCH.sub.3, or phenyl,

(ii) C.sub.1-6 alkoxy,

(iii) oxo,

(iv) hydroxy,

(v) thioxo,

(vi) --SR.sup.9,

(vii) halo,

(viii) cyano,

(ix) phenyl,

(x) trifluoromethyl,

(xi) --(CH.sub.2).sub.m --NR.sup.9 R.sup.10, wherein m is 0, 1 or 2,

(xii) --NR.sup.9 COR.sup.10,

(xiii) --CONR.sup.9 R.sup.10,

(xiv) --CO.sub.2 R.sup.9, and

(xv) --(CH.sub.2).sub.m --OR.sup.9 ;

(3) C.sub.2-6 alkenyl, unsubstituted or substituted with one or more of the substituent(s) selected from:

(a) hydroxy,

(b) oxo,

(c) C.sub.1-6 alkoxy,

(d) phenyl-C.sub.1-3 alkoxy,

(e) phenyl,

(f) --CN,

(g) halo,

(h) --CONR.sup.9 R.sup.10,

(i) --COR.sup.9,

(j) --CO.sub.2 R.sup.9,

(k) heterocycle;

(4) C.sub.2-6 alkynyl;

(5) phenyl, unsubstituted or substituted with one or more of the substituent(s) selected from:

(a) hydroxy,

(b) C.sub.1-6 alkoxy,

(c) C.sub.1-6 alkyl,

(d) C.sub.2-5 alkenyl,

(e) halo,

(f) --CN,

(g) --NO.sub.2,

(h) --CF.sub.3,

(i) --(CH.sub.2).sub.m --NR.sup.9 R.sup.10,

(j) --NR.sup.9 COR.sup.10,

(k) --NR.sup.9 CO.sub.2 R.sup.10,

(l) --CONR.sup.9 R.sup.10,

(m) --CO.sub.2 NR.sup.9 R.sup.10,

(n) --COR.sup.9, and

(o) --CO.sub.2 R.sup.9 ;

R.sup.2 and R.sup.3 are independently selected from the group consisting of:

(1) hydrogen,

(2) C.sub.1-6 alkyl, unsubstituted or substituted with one or more of the substituents selected from:

(a) hydroxy,

(b) oxo,

(c) C.sub.1-6 alkoxy,

(d) phenyl-C.sub.1-3 alkoxy,

(e) phenyl,

(f) --CN,

(g) halo,

(h) --NR.sup.9 R.sup.10,

(i) --NR.sup.9 COR.sup.10,

(j) --NR.sup.9 CO.sub.2 R.sup.10,

(k) --CONR.sup.9 R.sup.10,

(l) --COR.sup.9, and

(m) --CO.sub.2 R.sup.9 ;

(3) C.sub.2-6 alkenyl, unsubstituted or substituted with one or more of the substituent(s) selected from:

(a) hydroxy,

(b) oxo,

(c) C.sub.1-6 alkoxy,

(d) phenyl-C.sub.1-3 alkoxy,

(e) phenyl,

(f) --CN,

(g) halo,

(h) --CONR.sup.9 R.sup.10,

(i) --COR.sup.9, and

(j) --CO.sub.2 R.sup.9 ;

(4) C.sub.2-6 alkynyl;

(5) phenyl, unsubstituted or substituted with one or more of the substituent(s) selected from:

(a) hydroxy,

(b) C.sub.1-6 alkoxy,

(c) C.sub.1-6 alkyl,

(d) C.sub.2-5 alkenyl,

(e) halo,

(f) --CN,

(g) --NO.sub.2,

(h) --CF.sub.3,

(i) --(CH.sub.2).sub.m --NR.sup.9 R.sup.10,

(j) --NR.sup.9 COR.sup.10,

(k) --NR.sup.9 CO.sub.2 R.sup.10,

(l) --CONR.sup.9 R.sup.10,

(m) --CO.sub.2 NR.sup.9 R.sup.10,

(n) --COR.sup.9, and

(o) --CO.sub.2 R.sup.9 ;

R.sup.6, R.sup.7 and R.sup.8 are independently selected from the group consisting of:

(1) hydrogen;

(2) C.sub.1-6 alkyl, unsubstituted or substituted with one or more of the substituents selected from:

(a) hydroxy,

(b) oxo,

(c) C.sub.1-6 alkoxy,

(d) phenyl-C.sub.1-3 alkoxy,

(e) phenyl,

(f) --CN,

(g) halo,

(h) --NR.sup.9 R.sup.10,

(i) --NR.sup.9 COR.sup.10,

(j) --NR.sup.9 CO.sub.2 R.sup.10,

(k) --CONR.sup.9 R.sup.10,

(l) --COR.sup.9, and

(m) --CO.sub.2 R.sup.9 ;

(3) C.sub.2-6 alkenyl, unsubstituted or substituted with one or more of the substituent(s) selected from:

(a) hydroxy,

(b) oxo,

(c) C.sub.1-6 alkoxy,

(d) phenyl-C.sub.1-3 alkoxy,

(e) phenyl,

(f) --CN,

(g) halo,

(h) --CONR.sup.9 R.sup.10,

(i) --COR.sup.9, and

(j) --CO.sub.2 R.sup.9 ;

(4) C.sub.2-6 alkynyl;

(5) phenyl, unsubstituted or substituted with one or more of the substituent(s) selected from:

(a) hydroxy,

(b) C.sub.1-6 alkoxy,

(c) C.sub.1-6 alkyl,

(d) C.sub.2-5 alkenyl,

(e) halo,

(f) --CN,

(g) --NO.sub.2,

(h) --CF.sub.3,

(i) --(CH.sub.2).sub.m --NR.sup.9 R.sup.10,

(j) --NR.sup.9 COR.sup.10,

(k) --NR.sup.9 CO.sub.2 R.sup.10,

(l) --CONR.sup.9 R.sup.10,

(m) --CO.sub.2 NR.sup.9 R.sup.10,

(n) --COR.sup.9, and

(o) --CO.sub.2 R.sup.9 ;

(6) halo,

(7) --CN,

(8) --CF.sub.3,

(9) --NO.sub.2,

(10) --SR.sup.14, wherein R.sup.14 is hydrogen or C.sub.1-5 alkyl,

(11) --SOR.sup.14,

(12) --SO.sub.2 R.sup.14,

(13) NR.sup.9 COR.sup.10,

(14) CONR.sup.9 COR.sup.10,

(15) NR.sup.9 R.sup.10,

(16) NR.sup.9 CO.sub.2 R.sup.10,

(17) hydroxy,

(18) C.sub.1-6 alkoxy,

(19) COR.sup.9,

(20) CO.sub.2 R.sup.9,

(21) 2-pyridyl,

(22) 3-pyridyl,

(23) 4-pyridyl,

(24) 5-tetrazolyl,

(25) 2-oxazolyl, and

(26) 2-thiazolyl;

R.sup.11, R.sup.12 and R.sup.13 are independently selected from the definitions of R.sup.6, R.sup.7 and R.sup.8 ;

Y is selected from the group consisting of:

(1) a single bond,

(2) --O--,

(3) --S--,

(4) --CO--,

(5) --CH.sub.2 --,

(6) --CHR.sup.15 --, and

(7) --CR.sup.15 R.sup.16 --, wherein R.sup.15 and R.sup.16 are independently selected from the group consisting of:

(a) C.sub.1-6 alkyl, unsubstituted or substituted with one or more of the substituents selected from:

(i) hydroxy,

(ii) oxo,

(iii) C.sub.1-6 alkoxy,

(iv) phenyl-C.sub.1-3 alkoxy,

(v) phenyl,

(vi) --CN,

(vii) halo,

(viii) --NR.sup.9 R.sup.10,

(ix) --NR.sup.9 COR.sup.10,

(x) --NR.sup.9 CO.sub.2 R.sup.10,

(xi) --CONR.sup.9 R.sup.10,

(xii) --COR.sup.9, and

(xiii) --CO.sub.2 R.sup.9 ;

(b) phenyl, unsubstituted or substituted with one or more of the substituent(s) selected from:

(i) hydroxy,

(ii) C.sub.1-6 alkoxy,

(iii) C.sub.1-6 alkyl,

(iv) C.sub.2-5 alkenyl,

(v) halo,

(vi) --CN,

(vii) --NO.sub.2,

(viii) --CF.sub.3,

(ix) --(CH.sub.2).sub.m --NR.sup.9 R.sup.10,

(x) --NR.sup.9 COR.sup.10,

(xi) --NR.sup.9 CO.sub.2 R.sup.10,

(xii) --CONR.sup.9 R.sup.10,

(xiii) --CO.sub.2 NR.sup.9 R.sup.10,

(xiv) --COR.sup.9, and

(xv) --CO.sub.2 R.sup.9 ;

Z is C.sub.1-6 alkyl;

which comprises contacting a compound of formula V: ##STR30## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.6, R.sup.7, R.sup.8, R.sup.11, R.sup.12 and R.sup.13 are as defined above;

with an inorganic or an organic acid selected from the group consisting of: toluenesulfonic acid, methanesulfonic acid, sulfuric acid, hydrochloric acid and mixtures thereof, in an aprotic solvent selected from the group consisting of: toluene, benzene, dimethylformamide, tetrahydrofuran, diethylether, dimethoxyethane, ethyl acetate, and mixtures thereof, at a temperature from 0.degree. C. to solvent reflux temperature for a sufficient time to produce a compound of structural formula IV.
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