Pyrimido-diazepinone compounds and methods of treating disorders

1. A compound of formula I:

or a pharmaceutically acceptable salt thereof, wherein,

A is a single bond or double bond;

R′ is H or alkyl;

L is absent, S, SO, SO 2 , or CO;

X is hydrogen;

R 1 is alkyl or alkenyl, each of which may be interrupted by 1 N atom, wherein R 1 may be optionally substituted; or R 1 is aryl, arylalkyl, heteroaryl, or carbocyclic, wherein R 1 may be optionally substituted;

R 2 is hydrogen, optionally substituted alkyl, or optionally substituted cycloalkyl; and

R 6 is hydrogen or optionally substituted alkyl.

2. The compound of claim 1 , wherein R 1 is phenyl or pyridyl, each of which may be optionally substituted

3. The compound of claim 1 ,

wherein R 2 is H, methyl, or ethyl;

wherein R 6 is H;

wherein X is H;

wherein R′ is H;

wherein L is absent; and

wherein A is a single bond.

4. The compound of claim 1 , wherein the compound is

5. A compound of formula V:

or a pharmaceutically acceptable salt thereof,

wherein,

X is hydrogen;

R′ is hydrogen;

R 2 is hydrogen or optionally substituted alkyl;

R 3 is —OH or O-(optionally substituted alkyl);

R 4 is hydrogen or optionally substituted alkyl; and

R 6 is hydrogen or optionally substituted alkyl;

wherein optional substituents are selected from the group consisting of:

—F, —Cl, —Br, —I,

—OH, protected hydroxy,

—NO 2 , —CN,

—NH 2 , protected amino, —NH—C 1 -C 12 -alkyl, —NH—C 2 -C 12 -alkenyl, —NH—C 2 -C 12 -alkenyl, —NH—C 3 -C 12 -cycloalkyl, —NH-aryl, —NH-heteroaryl, —NH-heterocycloalkyl, -dialkylamino, -diarylamino, -diheteroarylamino, —O-C 1 -C 12 -alkyl, -O-C 2 -C 12 -alkenyl, -O-C 2 -C 12 -alkenyl, -O-C 3 -C 12 -cycloalkyl, —O-aryl, —O-heteroaryl, -O-heterocycloalkyl,

—C(O)—C 1 -C 12 -alkyl, —C(O)—C 2 -C 12 -alkenyl, —C(O)—C 2 -C 12 -alkenyl, —C(O)—C 3 -C 12 -cycloalkyl, —C(O)-aryl, —C(O)-heteroaryl, —C(O)-heterocycloalkyl, —CONH 2 , —CONH—C 1 -C 12 -alkyl, —CONH—C 2 -C 12 -alkenyl, —CONH—C 2 -C 12 -alkenyl, —CONH—C 3 -C 12 -cycloalkyl, —CONH-aryl, —CONH-heteroaryl, —CONH-heterocycloalkyl, —OCO 2 —C 1 -C 12 -alkyl, —OCO 2 —C 2 -C 12 -alkenyl, —OCO 2 —C 2 -C 12 -alkenyl, —OCO 2 -C 3 -C 12 -cycloalkyl, —OCO 2 -aryl, —OCO 2 -heteroaryl, —OCO 2 -heterocycloalkyl, —OCONH 2 , —OCONH—C 1 -C 12 -alkyl, —OCONH—C 2 -C 12 -alkenyl, —OCONH—C 2 -C 12 -alkenyl, —OCONH—C 3 -C 12 -cycloalkyl, —OCONH-aryl, —OCONH— heteroaryl, —OCONH— heterocycloalkyl, —NHC(O)—C 1 -C 12 -alkyl, —NHC(O)—C 2 -C 12 -alkenyl, —NHC(O)—C 2 -C 12 -alkenyl, —NHC(O)—C 3 -C 12 -cycloalkyl, —NHC(O)-aryl, —NHC(O)-heteroaryl, —NHC(O)-heterocycloalkyl, —NHCO 2 —C 1 -C 12 -alkyl, —NHCO 2 —C 2 -C 12 -alkenyl, —NHCO 2 —C 2 -C 12 -alkenyl, —NHCO 2 —C 3 -C 12 -cycloalkyl, —NHCO 2 -aryl, —NHCO 2 -heteroaryl, —NHCO 2 -heterocycloalkyl, —NHC(O)NH 2 , —NHC(O)NH—C 1 -C 12 -alkyl, —NHC(O)NH—C 2 -C 12 -alkenyl, —NHC(O)NH—C 2 -C 12 -alkenyl, —NHC(O)NH—C 3 -C 12 -cycloalkyl, —NHC(O)NH-aryl, —NHC(O)NH-heteroaryl, —NHC(O)NH-heterocycloalkyl, NHC(S)NH 2 , —NHC(S)NH—C 1 -C 12 -alkyl, —NHC(S)NH—C 2 -C 12 -alkenyl, —NHC(S)NH—C 2 -C 12 -alkenyl, —NHC(S)NH—C 3 -C 12 -cycloalkyl, —NHC(S)NH-aryl, —NHC(S)NH-heteroaryl, —NHC(S)NH-heterocycloalkyl, —NHC(NH)NH 2 , —NHC(NH)NH—C 1 -C 12 -alkyl, —NHC(NH)NH—C 2 -C 12 -alkenyl, —NHC(NH)NH—C 2 -C 12 -alkenyl, —NHC(NH)NH—C 3 -C 12 -cycloalkyl, —NHC(NH)NH-aryl, —NHC(NH)NH-heteroaryl, —NHC(NH)NH-heterocycloalkyl, —NHC(NH)—C 1 -C 12 -alkyl, —NHC(NH)—C 2 -C 12 -alkenyl, —NHC(NH)—C 2 -C 12 -alkenyl, —NHC(NH)—C 3 -C 12 -cycloalkyl, —NHC(NH)-aryl, —NHC(NH)-heteroaryl, —NHC(NH)-heterocycloalkyl, —C(NH)NH—C 1 -C 12 -alkyl, —C(NH)NH—C 2 -C 12 -alkenyl, —C(NH)NH—C 2 -C 12 -alkenyl, -C(NH)NH—C 3 -C 12 -cycloalkyl, —C(NH)NH-aryl, —C(NH)NH-heteroaryl, —C(NH)NH— heterocycloalkyl, —S(O)—C 1 -C 12 -alkyl, —S(O)—C 2 -C 12 -alkenyl, —S(O)—C 2 -C 12 -alkenyl, —S(O)—C 3 -C 12 -cycloalkyl, —S(O)-aryl, —S(O)-heteroaryl, —S(O)-heterocycloalkyl-SO 2 NH 2 , -SO 2 NH—C 1 -C 12 -alkyl, -SO 2 NH—C 2 -C 12 -alkenyl, -SO 2 NH—C 2 -C 12 -alkenyl, -SO 2 NH—C 3 -C 12 -cycloalkyl, -SO 2 NH-aryl, -SO 2 NH-heteroaryl, -SO 2 NH-heterocycloalkyl, —NHSO 2 -C 1 -C 12 -alkyl, —NHSO 2 -C 2 -C 12 -alkenyl, —NHSO 2 -C 2 -C 12 -alkenyl, —NHSO 2 -C 3 -C 12 -cycloalkyl, —NHSO 2 -aryl, —NHSO 2 -heteroaryl, —NHSO 2 -heterocycloalkyl, -CH 2 NH 2 , -CH 2 SO 2 CH 3 , -aryl, -arylalkyl, -heteroaryl, -heteroarylalkyl, -heterocycloalkyl, —C 3 -C 12 -cycloalkyl, polyalkoxyalkyl, polyalkoxy, -methoxymethoxy, -methoxyethoxy, -SH, -S-C 1 -C 12 -alkyl, -S-C 2 -C 12 -alkenyl, -S-C 2 -C 12 -alkenyl, -S-C 3 -C 12 -cycloalkyl, —S-aryl, —S-heteroaryl, —S-heterocycloalkyl, and methylthiomethyl.

6. The compound of claim 5 ,

wherein R 2 is H, methyl, or ethyl;

wherein R 6 is H;

wherein R 3 is —OCH 3 or —OCH 2 CH 3 ; and

wherein R 4 is methyl or ethyl.

7. The compound of claim 6 , wherein R 2 is methyl, R 6 is hydrogen, R 1 is hydrogen, R 3 is OCH 3 and R 4 is methyl.

8. The compound of claim 6 , wherein R 2 is methyl, R 6 is hydrogen, R 1 is hydrogen, R 3 is —OCH 2 CH 3 and R 4 is methyl.

9. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable carrier.

10. A pharmaceutical composition comprising a compound of claim 5 or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable carrier.

11. The compound of claim 2 , wherein R 1 is substituted with 0-4 substituents, selected from N(R A )(R A ), C(O)NH(R A ), alkoxy, alkylhalo,

each of which may be further substituted, wherein each R A is independently alkyl.

12. The compound of claim 11 , wherein R 1 is substituted with 0-4 substituents, selected from OMe, OEt, CF 3 ,