Spirocyclic compounds

1. A compound of formula:

or a pharmaceutically acceptable salt thereof;

wherein:

R 1 is absent or ═O;

X A1 is heteroarylene;

Y A is absent or selected from the group consisting of: —C(═O)—; —C(═O)—C(H,C 1-6 -alkyl)-; and —C(═O)—CH 2 —;

X 1 is selected from bond, NR 34 , CH 2 , CHR 34 , C(R 34 ) 2 , O, and S;

X 22 is selected from halo, —NH 2 , —NHR 34 , —N(R 34 ) 2 , hydroxyl, thiol, —B(OH) 2 , —Sn(R 36 ) 3 , —Si(R 36 ) 3 , —OS(O) 2 alkyl, —OS(O) 2 haloalkyl, alkenyl, alkynyl, ethynyl, ethenyl, —C(O)H, —NR 34 C(O)alkene, —NR 34 C(O)alkyne, cyano, —SC(O)alkyl, OC(O)alkyl, heterocycle, —C(O)OH, hydrogen, alkyl, aryl, heteroaryl, aliphatic, heteroaliphatic, and carbocyclic;

R 34 and R 34′ are independently selected at each occurrence from hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 3 -C 6 heterocycle, aryl, heteroaryl, —(CO)R 36 , —(CS)R 36 , —(C═NH)R 36 , —(SO)R 36 , and —(SO 2 )R 36 ;

R 36 is independently selected at each occurrence from hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 3 -C 6 heterocycle, aryl, heteroaryl, hydroxyl, C 1 -C 6 alkoxy, thio, C 1 -C 6 thioalkyl, —NH 2 , —NH(C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, C 3 -C 7 heterocycle, aryl, or heteroaryl), and —N(independently C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, C 3 -C 7 heterocycle, aryl, or heteroaryl) 2 ;

R 20 , R 21 , R 22 , R 23 and R 24 are independently selected from bond, alkyl, —C(O)—, —C(O)O—, —OC(O)—, —C(O)alkyl, —C(O)Oalkyl, —C(S)—, —SO 2 —, —S(O)—, —C(S)—, —C(O)NH—, —NHC(O)—, —N(alkyl)C(O)—, —C(O)N(alkyl)-, —O—, —S—, —NH—, —N(alkyl)-, —CH(—O—R 26 )—, —CH(—NR 34 R 34′ )—, —C(—O—R 26 )alkyl-, —C(—NR 34 R 34′ )alkyl-, —C(R 40 R 40 )—, -alkyl(R 27 )-alkyl(R 28 )—, —C(R 27 R 28 )—, —P(O)(OR 26 )O—, —P(O)(OR 26 )—, —NR 34 C(O)NR 34′ —, alkene, haloalkyl, alkoxy, alkyneheteroarylalkyl, aryl, arylalkyl, heterocycle, aliphatic, heteroaliphatic, heteroaryl, lactic acid, glycolic acid, carbocycle, -(ethylene glycol) 1-6 -, -(lactic-co-glycolic acid) 1-6 -, -(propylene glycol) 1-6 -, —O—(CH 2 ) 1-12 —O—, —NH—(CH 2 ) 1-12 —NH—, —NH—(CH 2 ) 1-12 —O—, —O—(CH 2 ) 1-12 —NH—, —S—(CH 2 ) 1-12 —O—, —O—(CH 2 ) 1-12 —S—, —S—(CH 2 ) 1-12 —S—, —S—(CH 2 ) 1-12 —NH—, and —NH—(CH 2 ) 1-12 —S—;

each of which R 20 , R 21 , R 22 , R 23 , and R 24 is optionally substituted with one or more substituents selected from R 101 ;

wherein at least one of R 20 , R 21 , R 22 , R 23 , and R 24 is not a bond;

R 101 is independently selected at each occurrence from hydrogen, alkyl, alkene, alkyne, haloalkyl, alkoxy, hydroxyl, aryl, heteroaryl, heterocycle, arylalkyl, heteroarylalkyl, heterocycloalkyl, aryloxy, heteroaryloxy, CN, —COOalkyl, COOH, NO 2 , F, Cl, Br, I, CF 3 , NH 2 , NHalkyl, N(alkyl) 2 , aliphatic, and heteroaliphatic;

R 26 is selected from hydrogen, alkyl, silane, arylalkyl, heteroarylalkyl, alkene, alkyne, aryl, heteroaryl, heterocyclic, aliphatic and heteroaliphatic;

R 27 and R 28 are independently selected from hydrogen, alkyl, amine, or together with the carbon atom to which they are attached, form C(O), C(S), C═CH 2 , a C 3 -C 6 spirocarbocycle, or a 4-, 5-, or 6-membered spiroheterocycle comprising 1 or 2 heteroatoms selected from N and O, or form a 1 or 2 carbon bridged ring; and

R 40 is selected at each instance from: hydrogen, alkyl, alkene, alkyne, halogen, hydroxyl, alkoxy, azide, amino, cyano, —NH(aliphatic), —N(aliphatic) 2 , —NHSO 2 (aliphatic), —N(aliphatic)SO 2 alkyl, —NHSO 2 (aryl, heteroaryl or heterocyclic), —N(alkyl)SO 2 (aryl, heteroaryl or heterocyclic) —NHSO 2 alkenyl, —N(alkyl)SO 2 alkenyl, —NHSO 2 alkynyl, —N(alkyl)SO 2 alkynyl, haloalkyl, aliphatic, heteroaliphatic, aryl, heteroaryl, heteroalkyl, heterocyclic, and carbocyclic.

2. The compound of claim 1 , wherein the compound is of the formula:

wherein

R 4 is selected from the group consisting of —C(═O)—O—C 1-6 -alkyl; C 1-6 alkyl; —NH 2 ; and —NH—C(═O)—C 1-6 -alkyl;

or a pharmaceutically acceptable salt thereof.

3. The compound of claim 1 , wherein the compound is of the formula:

wherein

R 4 is selected from the group consisting of —C(═O)—O—C 1-6 -alkyl; C 1-6 alkyl; —NH 2 ; and —NH—C(═O)—C 1-6 -alkyl;

or a pharmaceutically acceptable salt thereof.

4. The compound of claim 2 , wherein R 4 is —C(═O)—OCH 3 , —NHC(═O)CH 3 , or —C(═O)—OC(CH 3 ) 3 .

5. The compound of claim 2 , wherein R 4 is —NH 2 , or —C(═O)—O—C 1-6 -alkyl.

6. The compound of claim 2 , wherein R 4 is C 1-6 -alkyl or —NH—C(═O)—C 1-6 -alkyl.

7. The compound of claim 3 , wherein R 4 is —NH 2 , or —C(═O)—O—C 1-6 -alkyl.

8. The compound of claim 3 , wherein R 4 is C 1-6 -alkyl or —NH—C(═O)—C 1-6 -alkyl.

9. The compound of claim 1 selected from:

or a pharmaceutically acceptable salt thereof.

10. The compound of claim 1 , wherein the compound is selected from:

or a pharmaceutically acceptable salt thereof.

11. A pharmaceutical composition comprising an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, in a pharmaceutically acceptable carrier.