Bicyclic [3.1.0] derivatives as glycine transporter inhibitors

1. A compound of formula I, wherein

Y is H or (R 100 ) k —R 1 —(R 6 ) m ;

k is 0 or 1;

l=0, 1, 2 or 3;

m=1, 2 or 3;

n is 0, 1, 2, 3 or 4;

o is 0 or 1;

p is 0, 1, 2, or 3;

q is 0, 1, 2, 3 or 4;

r is 1 or 2;

s is 0, 1, 2, 3 or 4;

t is 0 or 1;

u is 1, 2, or 3;

v is 1, 2, or 3;

R 100 is —CH 2 —, —CH(C 1 -C 3 )alkyl-, —C(═O)— or —SO 2 —;

R 1 is —(C 1 -C 6 )alkyl, —(C 3 -C 8 )cycloalkyl, -(4 to 7 membered) heterocycloalkyl, —(CH 2 ) l —(C 6 -C 10 aryl) or -(5 to 10 membered) heteroaryl, or -(5 to 10 membered) tetrahydro-heteroaryl;

each R 6 can be same or different and is independently selected from H, halo, —(C 1 -C 6 )alkyl-B, (C 1 -C 7 ) alkoxy-D, (C 2 -C 4 )alkenoxy, (C 1 -C 6 )alkyl-OH, —OH, CN, —NO 2 , —CR 7 R 8 R 9 ,

—NR 20 R 21 , —NHCOalkyl(C 1 -C 3 ), NHSO 2 alkyl(C 1 -C 3 ), C(═O)OR 22 , —R 23 —C(═O)OR 22 , —C(═O)NH 2 , phenyl-E, phenoxy-F, morpholine, —NR 20 R 21 , aryl, heteroaryl, —S—R 24 , and —SO 2 —R 25 ;

B and D are each independently H, OH, phenyl, diphenyl or trifluro;

E and F are each independently H, alkyl, or halo;

R 7 , R 8 and R 9 are each independently H, (C 1 -C 4 ) alkyl, —OH, —O—(C 1 -C 4 )alkyl, —CN,

—NR 26 R 27 and —NHC(═O) (C 1 -C 3 )alkyl, wherein said alkyl groups are optionally substituted with OH, OCH 3 , NH 2 , NHC(═O) (C 1 -C 3 )alkyl, or R 7 and R 8 together with the carbon atom to which they are attached optionally form a (C 3 -C 7 )cycloalkyl ring, or a (C 4 -C 7 )heterocycloalkyl ring which contains 1-3 heteroatoms selected from N, O, S and optionally contains a C═O group;

R 20 and R 21 are each independently H or (C 1 -C 6 ) alkyl;

or R 20 and R 21 can be connected by 4 to 7 carbon atoms wherein from one to three of said carbon atoms can optionally be replaced with O, N or S, to form a heterocycloalkyl ring;

or R 20 and R 21 can be connected by 3 to 7 atoms selected from C, N, O or S to form a 5 to 10 membered heteroaryl ring;

R 22 , R 23 and R 24 are each independently H, or (C 1 -C 5 )alkyl;

R 25 is (C 1 -C 5 )alkyl;

R 26 and R 27 are each independently H or (C 1 -C 3 )alkyl;

or R 26 and R 27 can be connected by 4 to 7 carbon atoms to form a heterocycloalkyl ring;

R 2 and R 3 are each independently H or (C 1 -C 3 )alkyl;

R 4 and R 5 are each independently H or (C 1 -C 3 ) alkyl;

or R 4 and R 5 can be taken together form a double bond to an oxygen to form (C═O), or R 4 and R 5 are connected with 2 to 4 carbon atoms to form a 3-5 member carbocyclic ring;

A is H or (C 1 -C 3 )alkyl-(R 28 ) n ;

R 28 is independently (C 1 -C 3 )alkoxy, —OH, —NR 12 R 13 or —NHC(═O)(C 1 -C 4 )alkyl;

R 12 and R 13 are each independently H or —(C 1 -C 4 )alkyl; or

R 12 and R 13 can be connected by 4 to 7 carbon atoms to form a heterocycloalkyl ring;

X is a bond, —CH 2 —(R 29 ) p , —C(═O) or —SO 2 ;

R 29 is —(C 1 -C 3 )alkyl;

W is alkyl, —(C 3 -C 8 ) cycloalkyl, -(3 to 7 membered) heterocyclcoalkyl, -(3 to 7 membered) heterocyclcoalkyl with 1 or 2 C═O groups, phenyl, or -(5 to 7 member) heteroaryl or heterocyclic;

R 30 is —(C 1 -C 4 )alkyl, —(C 1 -C 3 )alkoxy, CN, —F, —Cl, —Br, —I, —NR 18 R 19 , —NHC(═O)R 18 ,

—SCH 3 or —C(═O)CH 3 ;

R 18 and R 19 are each independently H or —(C 1 -C 3 )alkyl;

Q is a bond, —CH—(R 31 ) r , —C(═O) or —SO 2 ;

R 31 is independently H or —(C 1 -C 3 )alkyl;

Z is phenyl;

R 14 is F, Cl, Br, I, V, H, —NR 16 R 17 , —OR 16 , —C(═O)NR 16 R 17 ,

—(SO 2 )NR 16 R 17 , or —NR 32 —C═O—R 33 ,

R 15 is —(C 1 -C 3 )alkyl, —(C 1 -C 3 )alkoxy, —F, —Br, —Cl, —I —OH or —CN;

V is —(C 3 -C 8 )cycloalkyl, —(C 1 -C 5 )alkyl, (5 to 7 membered) heterocycloalkyl, (5 to 7 membered)heterocycloalkyl substituted with 1 or 2 C═O groups or 1, 2, or 3 (C 1 -C 5 )alkyl groups;

R 16 and R 17 are each independently H, —(C 1 -C 6 )alkyl-(R 34 ) u , or (C 3 -C 8 )cycloalkyl-(R 35 ) v ;

or R 16 and R 17 together with the nitrogen atom to which they are attached form a 4 to 7 membered heterocycloalkyl ring optionally containing from 1 to 3 additional heteroatoms independently selected from N, S and O, and contain C═O, wherein said heterocycloalkyl ring is optionally and independently substituted with 1 to 3 substituents independently selected from (C 1 -C 4 )alkyl, OH, (C 1 -C 4 )alkoxy, NH 2 ,

—NH(C═O)alkyl, —N(C 1 -C 3 )alkyl) 2 , —C(═O)CH 3 , CONH 2 , CO 2 H, CH 2 OH, CH 2 Oalkyl(C 2 -C 4 ), and (5 to 7 membered) heterocycloalkyl;

R 32 and R 33 are each independently H or (C 1 -C 5 )alkyl;

or R 32 and R 33 can be taken together to form a 3-7 membered cycloalky ring, a 3-7 membered heterocycloalkyl ring with 1 to 3 heteroatoms, or a 5-7 membered heteroaryl ring with 1 to 3 heteroatoms;

R 34 and R 35 are each independently H, OH, (C 1 -C 5 )alkyl, (C 2 -C 4 )alkoxy, NH 2 , NH(C═O)(C 1 -C 3 )alkyl, or a 5 to 7 membered heterocycloalkyl;

or R 34 and R 35 can be taken together to form a bridge containing 1-2 carbon atoms;

or pharmaceutically acceptable salts thereof.

2. A compound as in claim 1 , wherein the stereochemistry is as in formula II

3. A compound as in claim 1 , wherein the stereochemistry is as in formula III

4. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carriers.