Substituted triazolopyridines and analogs thereof

1. A compound of Formula I

or a pharmaceutically acceptable salt thereof, wherein

—X—Y— is —N═C(R 4 )—, —C(R 4 )═N—;

R 1 is H, halo, alkyl, alkoxy, —CF 3 , cycloalkyl, alkoxyalkoxy, OH, hydroxyalkyl, —OCF 3 , —O-cycloalkyl, benzyloxy, —C(O)Oalkyl, —O-alkyl-CO 2 H, —C(O)N(R 6 ) 2 , —N(R 6 ) 2 , -alkylN(R 6 ) 2 , —NR 6 —C(O)N(R 6 ) 2 , —N(R 6 )C(O)Oalkyl, —N(R 6 )SO 2 -alkyl, CN, —SF 5 , —OSF 5 , —SO 2 R 6 , —SR 6 , trimethylsilylphenyl, aryl, —C≡C—CH 2 OH, —C≡C-aryl, arylalkyl-, —C(O)NHCH 2 -aryl, heteroaryl, —C≡C-heteroaryl, heteroarylalkyl-, —C(O)NHCH 2 -heteroaryl,

R 1A is H, halo, alkyl, alkoxy, —CF 3 , cycloalkyl, alkoxyalkoxy, OH, hydroxyalkyl, —OCF 3 , —O-cycloalkyl, benzyloxy, —C(O)Oalkyl, —O-alkyl-CO 2 H, —C(O)N(R 6 ) 2 , —N(R 6 ) 2 , -alkylN(R 6 ) 2 , —NR 6 —C(O)N(R 6 ) 2 , —N(R 6 )C(O)Oalkyl, —N(R 6 )SO 2 -alkyl, CN, —SF 5 , —OSF 5 , —SO 2 R 6 , —SR 6 , trimethylsilylphenyl, —C≡C—CH 2 OH, —C≡C-aryl, or arylalkyl-;

Q is —O—, —N(R 10 )—, —S—, —SO—, —SO 2 — or —CH 2 —;

Z is:

—(CH(R 2 )) n —(CH(R 2A )) m —,

 optionally substituted by 1 or 2 alkyl groups, or

 optionally substituted by 1 or 2 alkyl groups, wherein G is —N(R 8 )—, —O— or —S—;

or —N(R 5 )— and —Z— together form a 4 to 7 membered ring

optionally substituted by 1 or 2 alkyl groups;

n is 1 or 2;

m is 0, 1 or 2;

p is 0, 1 or 2;

q is 0, 1, 2 or 3;

each R 2 is independently selected from the group consisting of H, alkyl or cycloalkyl;

each R 2A is independently selected from the group consisting of H, alkyl, cycloalkyl, fluoro, OH, alkoxy, —N(R 8 ) 2 or -alkyl-N(R 8 ) 2 ;

R 3 is selected from the group consisting of pyridine, pyrazine,

each R 4 is independently selected from the group consisting of H, alkyl, cycloalkyl, halo, —CF 3 , alkoxyalkyl, heteroaryl, —CN, hydroxyalkyl, aryl, arylalkyl-, heteroarylalkyl-, —OCF 3 , —SF 5 , —OSF 5 and —N(R 6 ) 2 ;

R 5 is H, alkyl or cycloalkyl;

each R 6 is independently selected from the group consisting of H, alkyl, cycloalkyl and arylalkyl;

R 7 is 1 or 2 substituents independently selected from the group consisting of H, halo, alkyl, alkoxy, —CF 3 , cycloalkyl, alkoxyalkoxy, OH, hydroxyalkyl, —OCF 3 , —O-cycloalkyl, benzyloxy, —C(O)Oalkyl, —O-alkyl-CO 2 H, —C(O)N(R 6 ) 2 , —N(R 6 ) 2 , -alkylN(R 6 ) 2 , —NR 6 —C(O)N(R 6 ) 2 , —N(R 6 )C(O)Oalkyl, —N(R 6 )SO 2 -alkyl, phenyl, CN, —SF 5 , —OSF 5 , —SO 2 R 6 , —SR 6 and trimethylsilyl;

each R 8 is independently selected from the group consisting of H and alkyl;

R 9 is 1 to 3 substituents independently selected from the group consisting of H and alkyl, and when Q is —CH 2 —, R 9 can also be halo, OH, alkoxy or —CF 3 ; and

R 10 is H, alkyl, —C(O)N(R 6 ) 2 , —C(O)Oalkyl, or —SO 2 -alkyl.

2. The compound of claim 1 wherein:

—X—Y— is —C(R 4 )═N— or —N═C(R 4 )—;

Z is —(CH(R 2 )) n —(CH(R 2A )) m —;

the sum of n and m is 1-3;

R 2 is H or alkyl;

R 2A is H or alkyl;

R 1 is H, halo, pyridyl, optionally substituted phenyl or —C≡C—CH 2 OH;

R 3 is

wherein R 7 is 1 or 2 substituents independently selected from H, halo, alkyl and alkoxy and R 6 is H or alkyl;

R 4 is alkyl, cycloalkyl, halo, —CF 3 or alkoxyalkyl; and

R 5 is H or alkyl

or a pharmaceutically acceptable salt thereof.

3. The compound of claim 2 wherein

—X—Y— is —C(R 4 )═N— or —N═C(R 4 )—;

Z is —(CH(R 2 )) n —(CH(R 2A )) m —;

the sum of n and m is 1-3;

R 2 is H or alkyl;

R 2A is H or alkyl;

R 1 is H, F, Br, pyridyl, OH-phenyl or —C≡C—CH 2 OH;

R 3 is

 wherein R 7 is one substituent selected from the group consisting of H, F, Br, Cl and —OCH 3 , or R 7 is two substituents independently selected from Cl and F, and wherein R 6 is H, methyl or ethyl;

R 4 is methyl, ethyl, propyl, isopropyl, t-butyl, cyclopropyl, cyclobutyl, Br, —CF 3 or methoxyethyl; and

R 5 is H or ethyl

or a pharmaceutically acceptable salt thereof.

4. The compound of claim 1 selected from the group consisting of Examples 1A, 1B, 1E, 1I, 1O, 1P, 1Q, 1R, 1S, 1T, 1AA, 1BB, 1DD, 1FF, 1GG, 1HH, 1II, 1LL, 1MM, 1NN, 1UU, 1XX, 1ZZ, 1BBB, 1DDD, 1FFF, 2B, 2D, 2F, 2G, 4A, 4D, 4E, 4F, 5B, 7A, 7D, 7E, 7K and 7O, or a pharmaceutically acceptable salt thereof.

5. A pharmaceutical composition, which comprises an effective amount of at least one compound of claim 1 or pharmaceutically acceptable salt thereof and a pharmaceutically acceptabale carrier.