Spiro compounds as modulators of muscarinic receptors

1. A compound formula (XX)

or pharmaceutically acceptable salts thereof, wherein

Each of R 1 , R 2 , R 3 is independently Q 1 or Q 2 ;

Z 1 is —N(Q 1 )— or —N(Q 2 );

Z 2 is N;

L is a bond or —CH 2 —;

G is

G 1 is —N—;

G 2 is absent or a C 1-3 alkyl;

G 3 is an aryl or heteroaryl, each optionally substituted with 1-3 substituents independently selected from Q 2 and Q 3 ; and

G 5 is 0 or 1 when G 2 is absent or 0 when G 2 is a C 1-3 alkyl;

Each Q 1 is independently halo, —CN, —NO 2 , —OQ 2 , —S(O) z Q 2 , —S(O) z N(Q 2 ) 2 , —N(Q 2 ) 2 , —C(O)OQ 2 , —C(O)-Q 2 , —C(O)N(Q 2 ) 2 , —C(O)N(Q 2 )(OQ 2 ), —N(Q 2 )C(O)-Q 2 , —N(Q 2 )C(O)N(Q 2 ) 2 , —N(Q 2 )C(O)O-Q 2 , —N(Q 2 )S(O) z -Q 2 or aliphatic optionally including 1-3 substituents independently selected from Q 2 or Q 3 ;

Each Q 2 is independently H, aliphatic, cycloaliphatic, aryl, arylalkyl, heterocyclic, or heteroaryl ring, each optionally including 1-3 substituents independently selected from Q 3 ;

Each Q 3 is halo, oxo, —CN, —NO 2 , —CF 3 , —OCF 3 , —OH, —S(O) z Q 4 , —N(Q 4 ) 2 , —COOQ 4 , —C(O)Q 4 , —OQ 4 , or C 1-4 alkyl optionally substituted with halo, oxo, —CN, —NO 2 , —CF 3 , —OCF 3 , —OH, —SH, —S(O) z H, —NH 2 , or —COOH;

Each Q 4 is aliphatic, cycloaliphatic, aryl, aralkyl, heterocycloaliphatic, heteroaralky, or heteroaryl, each optionally including 1-3 substituents selected from halo, oxo, —CN, —NO 2 , —CF 3 , —OCF 3 , —OH, —SH, —S(O) z H, —NH 2 , or —COOH;

Each Q 5 is a heterocyclic ring optionally including 1-3 substituents selected from halo, C 1-4 alkyl, oxo, —CN, —NO 2 , —CF 3 , —OCF 3 , —OH, —SH, —S(O) z H, —NH 2 , —COOH;

Each i is independently 1, 2, or 3;

Each m and n is independently 2;

Each p is 0 or 1;

Each y is independently 0 or 1;

Each t is 1 to 4; and

Each z is independently 0, 1, or 2.

2. The compound of claim 1 , wherein G 2 is absent.

3. The compound of claim 2 , wherein G 3 is a heteroaryl optionally substituted with 1-3 of halo, cyano, C 1-4 alkoxy, C 1-4 alkyl, cyclopropyl or phenyl optionally substituted with 1-3 of halo, cyano, hydroxy, C 1-4 alkoxy, or C 1-4 alkyl.

4. The compound of claim 2 , wherein G5 is 1.

5. The compound of claim 1 , wherein G is one selected from

6. The compound of claim 1 , wherein Z 1 is —NH—, or —N(Q 1 )-.

7. The compound of claim 6 , wherein Z 1 is —N(Q 1 )- and Q 1 is alkylcarbonylamino, alkylsulfonylamino, alkoxycarbonylamino, aminocarbonyl, alkylcarbonylalkyl, alkoxyalkoxycarbonyl, alkoxyalkyl, alkylaminocarbonyl, alkoxycarbonyl, haloarylcarbonyl, haloarylsulfonyl, alkylheteroarylcarbonyl, heteroarylcarbonyl, heterocycloalkylcarbonyl, haloarylaminocarbonyl, alkylheteroarylsulfonyl, cyanoalkylarylcarbonyl, heterocycloalkoxycarbonyl, alkynyloxycarbonyl, cycloalkoxycarbonyl, heterobicycloarylcarbonyl, alkylheteroarylaminocarbonyl, alkylsulfonyl, alkylcarbonylalkyl, alkoxyarylcarbonyl, haloalkoxycarbonyl, alkylarylcarbonyl, haloalkoxyarylcarbonyl, alkylaminocarbonyl, alkylcarbonyl, or arylaminocarbonyl.

8. The compound of claim 6 , wherein Z 1 is one selected from —NH—,

9. The compound of claim 1 , wherein R 1 is selected from hydrogen, halo, or optionally substituted alkyl, heteroaryl, alkoxy, alkenyl, cycloalkyl, cyanoalkylaryl, alkylaryl, alkylsulfonylaryl, alkylcarbonylaryl, aryl, aminocarbonylaryl, alkylcarbonylaminoaryl, cycloalkenyl, and alkoxyaryl.

10. The compound of claim 9 , wherein R 1 is selected from hydrogen, halo, methyl, —OCH 3

11. The compound of claim 1 , wherein R 2 and R 3 are independently hydrogen or alkyl.

12. The compound of claim 11 , wherein R 2 and R 3 are both hydrogen.

13. The compound of claim 1 , wherein p is 0.

14. The compound of claim 1 , wherein L is a bond.

15. A compound selected from

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16. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutical carrier.

17. A pharmaceutical composition comprising a compound according to claim 15 and a pharmaceutical carrier.

18. The compound of claim 1 , wherein L is —CH 2 —.

19. A compound formula (XX)

or pharmaceutically acceptable salts thereof, wherein

Each of R 1 , R 2 , R 3 is independently Q 1 or Q 2 ;

Z 1 is —N(Q 1 )- or —N(Q 2 )-;

Z 2 is N;

L is a bond or —CH 2 —;

G is

G 1 is —N—;

G 2 is absent or a C 1-3 alkyl;

G 3 is an aryl or heteroaryl, each optionally substituted with 1-3 substituents independently selected from Q 2 and Q 3 ; and

G5 is 0 or 1 when G 2 is absent or 0 when G 2 is a C 1-3 alkyl;

Each Q 1 is independently halo, —CN, —NO 2 , —OQ 2 , —S(O) z Q 2 , —S(O) z N(Q 2 ) 2 , —N(Q 2 ) 2 , —C(O)OQ 2 , —C(O)-Q 2 , —C(O)N(Q 2 ) 2 , —C(O)N(Q 2 )(OQ 2 ), —N(Q 2 )C(O)-Q 2 , —N(Q 2 )C(O)N(Q 2 ) 2 , —N(Q 2 )C(O)O-Q 2 , —N(Q 2 )S(O) z -Q 2 or aliphatic optionally including 1-3 substituents independently selected from Q 2 or Q 3 ;

Each Q 2 is independently H, aliphatic, cycloaliphatic, aryl, arylalkyl, heterocyclic, or heteroaryl ring, each optionally including 1-3 substituents independently selected from Q 3 ;

Each Q 3 is halo, oxo, —CN, —NO 2 , —CF 3 , —OCF 3 , —OH, —S(O) z Q 4 , —N(Q 4 ) 2 , —COOQ 4 , —C(O)Q 4 , —OQ 4 , or C 1-4 alkyl optionally substituted with halo, oxo, —CN, —NO 2 , —CF 3 , —OCF 3 , —OH, —SH, —S(O) z H, —NH 2 , or —COOH;

Each Q 4 is aliphatic, cycloaliphatic, aryl, aralkyl, heterocycloaliphatic, heteroaralky, or heteroaryl, each optionally including 1-3 substituents selected from halo, oxo, —CN, —NO 2 , —CF 3 , —OCF 3 , —OH, —SH, —S(O) z H, —NH 2 , or —COOH;

Each Q5 is a heterocyclic ring optionally including 1-3 substituents selected from halo, C 1-4 alkyl, oxo, —CN, —NO 2 , —CF 3 , —OCF 3 , —OH, —SH, —S(O) z H, —NH 2 , —COOH;

Each i is independently 1, 2, or 3;

Each m and n is independently 2;

Each p is 1;

Each y is independently 0 or 1;

Each t is 1 to 4; and

Each z is independently 0, 1, or 2.