Pharmacokinetically improved compounds

The compound of the formula I, having the formula IV,

• or pharmaceutically acceptable salt or hydrate thereof, wherein:
• R13 and R14 are independently selected from the group consisting of H, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR16R17, —(C1-C6 alkyl)-C(═)NR16R17, aryl, aralkyl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C3-C7 cycloalkyl, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• or R13 and R14 may be taken together form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, C3-C7 cycloalkyl, oxo, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• X is selected from a covalent bond, O, NH, and C1-C6 alkyl;
• and R17 independently selected from the group consisting of H, C1-C8 alkyl, C2-C8 alkenyl, C1-C8 alkynyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), aryl, aralkyl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• or R16 and R17 may be taken together form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, oxo, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• each R2 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl;
• each R3 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl;
• n is selected from 0 to 4;
• and
• m is selected from 0 to 3.

The compound of the formula I, having the formula IVa:

• or pharmaceutically acceptable salt or hydrate thereof, wherein:
• R13 and R14 are independently selected from the group consisting of H, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR16R17, —(C1-C6 alkyl)-C(═O)NR16R17, aryl, aralkyl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C3-C7 cycloalkyl, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• or R13 and R14 may be taken together form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, oxo, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• R16 and R17 independently selected from the group consisting of H, C1-C8 alkyl, C2-C8 alkenyl, C1-C8 alkynyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), aryl, aralkyl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• or R16 and R17 may be taken together form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, oxo, hydroxy, amino, cyano and C1-C3 perfluoro alkyl.

The compound of the formula I, having the formula V:

• or pharmaceutically acceptable salt or hydrate thereof, wherein:
• R12 is selected from the group consisting of C1-C6 alkyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR16R17, —(C1-C6 alkyl)-C(═O)NR16R17, —(C1-C6 alkyl)-O—(C1-C6 alkyl)-O—(C1-C6 alkyl), aryl, aralkyl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted at one or more carbon atoms by from 1 to 3 substituents independently selected from halo, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• each R2 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl;
• each R3 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl;
• it is selected from 0 to 4;
• and
• in is selected from 0 to 3.

The compound of the formula I, having the formula VI:

• or pharmaceutically acceptable salt or hydrate thereof, wherein:
• R13 and R14 are independently selected from the group consisting of H, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR16R17, —(C1-C6 alkyl)-C(═O)NR16R17, aryl, aralkyl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C3-C7 cycloalkyl, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• or R13 and R14 may be taken together form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, C3-C7 cycloalkyl, oxo, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• R16 and R17 independently selected from the group consisting of H, C1-C8 alkyl, C2-C8 alkenyl, C1-C8 alkynyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), aryl, aralkyl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• or R16 and R17 may be taken together form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, oxo, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• each R2 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl;
• each R3 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl;
• n is selected from 0 to 4;
• and
• m is selected from 0 to 3.

The compound of the formula I, having the formula VIa:

• or pharmaceutically acceptable salt or hydrate thereof, wherein:
• R13 and R14 are independently selected from the group consisting of H, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR16R17, —(C1-C6 alkyl)-C(═O)NR16R17, aryl, aralkyl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C3-C7 cycloalkyl, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• or R13 and R14 may be taken together form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, C3-C7 cycloalkyl, oxo, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• R16 and R17 independently selected from the group consisting of H, C1-C8 alkyl, C2-C8 alkenyl, C1-C8 alkynyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), aryl, aralkyl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• or R16 and R17 may be taken together form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, oxo, hydroxy, amino, cyano and C1-C3 perfluoro alkyl.

The compound of the formula I, having the formula VII:

• or pharmaceutically acceptable salt or hydrate thereof, wherein:
• R13 and R14 are independently selected from the group consisting of H, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR16R17, —(C1-C6 alkyl)-C(═O)NR16R17, aryl, aralkyl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C3-C7 cycloalkyl, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• or R13 and R14 may be taken together form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, oxo, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• R16 it and R17 independently selected from the group consisting of H, C1-C8 alkyl, C2-C8 alkenyl, C1-C8 alkynyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), aryl, aralkyl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• or R16 and R17 may be taken together form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, oxo, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• each R2 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl;
• each R3 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl;
• n is selected from 0 to 4;
• and
• m is selected from 0 to 3.

The compound of the formula I, having the formula VIIa:

• or pharmaceutically acceptable salt or hydrate thereof, wherein:
• R13 and R14 are independently selected from the group consisting of H, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR16R17, —(C1-C6 alkyl)-C(═O)NR16R17, aryl, aralkyl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C3-C7 cycloalkyl, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• or R13 and R14 may be taken together form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, oxo, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• R16 and R17 independently selected from the group consisting of H, C1-C8 alkyl, C2-C8 alkenyl, C1-C8 alkynyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), aryl, aralkyl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• or R16 and R17 may be taken together form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, oxo, hydroxy, amino, cyano and Cl-C3 perfluoro alkyl.

The compound of the formula I, having the formula VIII:

• or pharmaceutically acceptable salt or hydrate thereof, wherein:
• X is selected from a covalent bond, O, NH, and C1-C6 alkyl;
• R15 is selected from the group consisting of H, aryl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl,
• or R15 is selected from —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR16R17, —CO2R18, —O—(CH2)x—CO2R18, and —C(═O)NR16R17;
• R16 and R17 independently selected from the group consisting of H, C1-C8 alkyl, C2-C8 alkenyl, C1-C8 alkynyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), aryl, aralkyl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• or R16 and R17 may be taken together form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, oxo, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• R18 is selected from the group consisting of H, aryl, aralkyl, heteroaryl, C1-C6 alkyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR16R17, —(C1-C6 alkyl)-O—(C1-C6 alkyl)-O—(C1-C6 alkyl), each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoroalkyl;
• x is selected from 0 to 6,
• each R2 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl;
• each R3 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl;
• n is selected from 0 to 4;
• and
• m is selected from 0 to 3.

The compound of the formula I, having the formula VIII.:

• or pharmaceutically acceptable salt or hydrate thereof, wherein:
• X is selected from a covalent bond, O, NH, and C1-C6 alkyl;
• R15 is selected from the group consisting of H, aryl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl,
• or R15 is selected from —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR16R17, —CO2R18, —O—(CH2)x—CO2R18, and —C(═O)NR16R17;
• R16 and R17 independently selected from the group consisting of H, C1-C8 alkyl, C2-C8 alkenyl, C1-C8 alkynyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), aryl, aralkyl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• or R16 and R17 may be taken together form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, oxo, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• R18 is selected from the group consisting of H, aryl, aralkyl, heteroaryl, C1-C6 alkyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR16R17, —(C1-C6 alkyl)-O—(C1-C6 alkyl)-O—(C1-C6 alkyl), each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoroalkyl;
• and
• x is selected from 0 to 6.

The compound of the formula I, having the formula IX:

• or pharmaceutically acceptable salt or hydrate thereof, wherein:
• R1 is selected from the group consisting of aryl, —(CH2)y—NR13R14, —O—(CH2)y—CO2R12, —O—(CH2)y—C(═O)NR13R14, —O—(CH2)y-heteroaryl, —O—(CH2)y-cycloalkyl, —O—C(═O)—(CH2)y—NR13R14, —O—(CH2)z—NR13R14, —NH—C(═O)—(CH2)y—NR13R14, —NH—C(═O)—X—R15, —NH—(CH2)y—NR13R14;
• R12 is selected from the group consisting of C1-C6 alkyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR16R17, —(C1-C6 alkyl)-C(═O)NR16R17, —(C1-C6 alkyl)-O—(C1C6 alkyl)-O—(C1-C6 alkyl), aryl, aralkyl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted at one or more carbon atoms by from 1 to 3 substituents independently selected from halo, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• R13 and R14 are independently selected from the group consisting of H, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR16R17, —(C1-C6 alkyl)-C(═O)NR16R17, aryl, aralkyl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C3-C7 cycloalkyl, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• or R13 and R14 may be taken together form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, oxo, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• X is selected from a covalent bond, O, NH, and C1-C6 alkyl;
• R15 is selected from the group consisting of H, aryl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl,
• or R15 is selected from —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR16R17, —CO2R18, —O—(CH2)x—CO2R18, and —C(═O)NR16R17;
• R16 and R17 independently selected from the group consisting of H, C1-C8 alkyl, C2-C8 alkenyl, C1-C8 alkynyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), aryl, aralkyl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C5, alkenyl, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• or R16 and R17 may be taken together form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, oxo, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• R18 is selected from the group consisting of H, aryl, aralkyl, heteroaryl, C1-C6 alkyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR16R17, —(C1-C6 alkyl)-O—(C1-C6 alkyl)-O—(C1-C6 alkyl), each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoroalkyl;
• x is selected from 0 to 6;
• y is selected from 0 to 6;
• z is selected from 2 to 6;
• each R2 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl;
• each R3 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl;
• R43 and R44 are independently selected from the group consisting of H, C1-C8 alkyl, C2-C8 alkenyl, C1-C8 alkynyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR46R47, —(C1-C6 alkyl)-C(═O)NR46R47, aryl, aralkyl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C3-C7 cycloalkyl, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• or R43 and R44 may be taken together form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, oxo, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• R46 and R47 independently selected from the group consisting of H, C1-C8 alkyl, C2-C8 alkenyl, C1-C8 alkynyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), aryl, aralkyl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• or R46 and R47 may be taken together form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, oxo, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• R48 is selected from the group consisting of H, aryl, aralkyl, heteroaryl, C1-C6 alkyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR46R47, —(C1-C6 alkyl)-O—(C1-C6 alkyl)-O—(C1-C6 alkyl), each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoroalkyl;
• c is selected from 2 to 6;
• n is selected from 0 to 4;
• and
• in is selected from 0 to 3.

The compound of the formula I, having the formula X:

• or pharmaceutically acceptable salt or hydrate thereof, wherein:
• R1 is selected from the group consisting of aryl, —(CH2)y—NR13R14, —X—R12, —O—(CH2)y—CO2R12, —O—(CH2)y—C(═O)NR13R14, —O—(CH2)y-heteroaryl, —O—(CH2)y-cycloalkyl, —O—C(═O)—(CH2)y—NR13R14, —O—(CH2)z—NR13R14, —NH—C(═O)—(CH2)y—NR13R14, —NH—C(═O)—X—R15, —NH—(CH2)y—NR13R14;
• R12 is selected from the group consisting of C1-C6 alkyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR16R17, —(C1-C6 alkyl)-C(═O)NR16R17, —(C1-C6 alkyl)-O—(C1-C6 alkyl)-O—(C1-C6 alkyl), aryl, aralkyl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted at one or more carbon atoms by from 1 to 3 substituents independently selected from halo, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• R13 and R14 are independently selected from the group consisting of H, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR16R17, —(C1-C5 alkyl)-C(═O)NR16R17, aryl, aralkyl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C3-C7 cycloalkyl, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• or R13 and R14 may be taken together form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, oxo, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• X is selected from a covalent bond, O, NH, and C1-C6 alkyl;
• R15 is selected from the group consisting of H, aryl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl,
• or R15 is selected from —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR16R17, —CO2R18, —O—(CH2)x—CO2R18, and —C(═O)NR16R17;
• R16 and R17 independently selected from the group consisting of H, C1-C8 alkyl, C2-C8 alkenyl, C1-C8 alkynyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), aryl, aralkyl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• or R16 and R17 may be taken together form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, oxo, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• R18 is selected from the group consisting of H, aryl, aralkyl, heteroaryl, C1-C6 alkyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR16R17, —(C1-C6 alkyl)-O—(C1-C6 alkyl)-O—(C1-C6 alkyl), each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoroalkyl;
• x is selected from 0 to 6;
• y is selected from 0 to 6;
• z is selected from 2 to 6;
• each R2 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl;
• each R3 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl;
• R42 is selected from the group consisting of C1-C6 alkyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR46R47, —(C1-C6 alkyl)-C(═O)NR46R47, —(C1-C6 alkyl)-O—(C1-C6 alkyl)-O—(C1-C6 alkyl), each of which may be optionally substituted at one or more carbon atoms by from 1 to 3 substituents independently selected from halo, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• R46 and R47 independently selected from the group consisting of H, C1-C8 alkyl, C2-C8 alkenyl, C1-C8 alkynyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), aryl, aralkyl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• or R46 and R47 may be taken together form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, oxo, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• n is selected from 0 to 4;
• and
• m is selected from 0 to 3.

The compound of the formula 1, having the formula XI:

• or pharmaceutically acceptable salt or hydrate thereof, wherein:
• R1 is selected from the group consisting of aryl, —(CH2)y—NR13R14, —X—R12, —O—(CH2)y—CO2R12, —O—(CH2)y—C(═O)NR13R14, —O—(CH2)y-heteroaryl, —O—(CH2)y-cycloalkyl, —O—C(═O)—(CH2)y—NR13R14, —O—(CH2)z—NR13R14, —NH—C(═O)—(CH2)y—NR13R14, —NH—C(═O)—X—R15, —NH—(CH2)y—NR13R14;
• R12 is selected from the group consisting of C1-C6 alkyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR16R17, —(C1-C6 alkyl)-C(═O)NR16R17, —(C1-C6 alkyl)-O—(C1-C6 alkyl)-O—(C1-C6 alkyl), aryl, aralkyl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted at one or more carbon atoms by from 1 to 3 substituents independently selected from halo, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• R13 and R14 are independently selected from the group consisting of H, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl-NR16R17, —(C1-C6 alkyl)-C(═O)NR16R17, aryl, aralkyl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C3-C7 cycloalkyl, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• or R13 and R14 may be taken together form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, oxo, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• X is selected from a covalent bond, O, NH, and C1-C6 alkyl;
• R15 is selected from the group consisting of H, aryl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl,
• or R15 is selected from —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR16R17, —CO2R18, —O—(CH2)x—CO2R18, and —C(═O)NR16R17;
• R16 and R17 independently selected from the group consisting of H, C1-C8 alkyl, C2-C8 alkenyl, C1-C8 alkynyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), aryl, aralkyl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• or R16 and R17 may be taken together form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, alkenyl, C1-C6 alkoxy, oxo, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• R18 is selected from the group consisting of H, aryl, aralkyl, heteroaryl, C1-C6 alkyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR16R17, —(C1-C6 alkyl)-O—(C1-C6 alkyl)-O—(C1-C6 alkyl), each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoroalkyl;
• x is selected from 0 to 6;
• y is selected from 0 to 6;
• z is selected from 2 to 6;
• each R2 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl;
• each R3 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl;
• R43 and R44 are independently selected from the group consisting of H, C1-C8 alkyl, C2-C8 alkenyl, C1-C8 alkynyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR46R47, —(C1-C6 alkyl)-C(═O)NR46R47, aryl, aralkyl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C3-C7 cycloalkyl, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• or R43 and R44 may be taken together form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, oxo, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• R46 and R47 independently selected from the group consisting of H, C1-C6 alkyl, C2-C8 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• or R46 and R47 may be taken together form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, oxo, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• R48 is selected from the group consisting of H, aryl, aralkyl, heteroaryl, C1-C6 alkyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR46R47, —(C1-C6 alkyl)-O—(C1-C6 alkyl)-O—(C1-C6 alkyl), each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoroalkyl;
• n is selected from 0 to 4;
• and
• m is selected from 0 to 3.

The compound of the formula I, having the formula XII:

• or pharmaceutically acceptable salt or hydrate thereof, wherein:
• R1 is selected from the group consisting of aryl, —(CH2)y—NR13R14, —X—R12, —O—(CH2)y—CO2R12, —O—(CH2)y—C(═O)NR13R14, —O—(CH2)4-heteroaryl, —O—(CH2)y-cycloalkyl, —O—C(═O)—(CH2)y—NR13R14, —O—(CH2)z—NR13R14, —NH—C(═O)—(CH2)y—NR13R14, —NH—C(═O)—X—R15, —NH—(CH2)y—NR13R14;
• R12 is selected from the group consisting of C1-C6 alkyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR16R17, —(C1-C6 alkyl)-C(═O)NR16R17, —(C1-C6 alkyl)-O—(C1-C6 alkyl)-O—(C1-C6 alkyl), aryl, aralkyl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted at one or more carbon atoms by from 1 to 3 substituents independently selected from halo, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• R13 and R14 are independently selected from the group consisting of H, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR16R17, —(C1-C6 alkyl)-C(═O)NR16R17, aryl, aralkyl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C3-C7 cycloalkyl, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• or R13 and R14 may be taken together form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, C3-C7 cycloalkyl, oxo, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• X is selected from a covalent bond, O, NH, and C1-C6 alkyl;
• R15 is selected from the group consisting of H, aryl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl,
• or R15 is selected from —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR16R17, —CO2R18, —O—(CH2)x—CO2R18, and —C(═O)NR16R17;
• R16 and R17 independently selected from the group consisting of H, C1-C8 alkyl, C2-C8 alkenyl, C1-C8 alkynyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), aryl, aralkyl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• or R16 and R17 may be taken together form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, oxo, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• R18 is selected from the group consisting of H, aryl, aralkyl, heteroaryl, C1-C6 alkyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR16R17, —(C1-C6 alkyl)-O—(C1-C6 alkyl)-O—(C1-C6 alkyl), each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoroalkyl;
• x is selected from 0 to 6;
• y is selected from 0 to 6;
• z is selected from 2 to 6;
• each R2 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl;
• each R3 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl;
• R4 is selected from —(CH2)a—NR43R44, —Y—R42, —O—(CH2)a—CO2R42, —O—(CH2)a—C(═O)NR43R44, —O—(CH2)a-heteroaryl, —O—(CH2)a-cycloalkyl, —O—C(═O)—(CH2)a—NR43R44, —O—(CH2)c—NR43R44, —NH—C(═O)—(CH2)a—NR43R44, —NH—C(═O)—Y—R45, —NH—C(═O)—(CH2)a—NR43R44;
• R42 is selected from the group consisting of C1-C6 alkyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR46R47, —(C1-C6 alkyl)-C(═O)NR46R47, —(C1-C6 alkyl)-O—(C1-C6 alkyl)-O—(C1-C6 alkyl), each of which may be optionally substituted at one or more carbon atoms by from 1 to 3 substituents independently selected from halo, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• R43 and R44 are independently selected from the group consisting of H, C1-C8 alkyl, C2-C8 alkenyl, C1-C8 alkynyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR46R47, —(C1-C6 alkyl)-C(═O)NR46R47, aryl, aralkyl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C3-C7 cycloalkyl, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• or R43 and R44 may be taken together form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, oxo, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• Y is selected from a covalent bond, O, NH, and C1-C6 alkyl;
• R45 is selected from the group consisting of H, aryl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR46R47, —CO2R48, —O—(CH2)b—CO2R48, and —C(═O)NR46R47,
• R46 and R47 independently selected from the group consisting of H, C1-C8 alkyl, C2-C8 alkenyl, C1-C8 alkynyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), aryl, aralkyl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• or R46 and R47 may be taken together form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, oxo, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• R48 is selected from the group consisting of H, aryl, aralkyl, heteroaryl, C1-C6 alkyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR46R47, —(C1-C6 alkyl)-O—(C1-C6 alkyl)-O—(C1-C6 alkyl), each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoroalkyl;
• a is selected from 0 to 6;
• b is selected from 0 to 6;
• c is selected from 2 to 6;
• R5 is selected from the group consisting of H, C1-C6 alkyl, —(CH2)d—C(═O)—NR53R54, —C(═O)—(CH2)d—NR53R54, —C(═O)—X—R55, and —C(═O)—(CH2)d—NR53R54;
• R53 and R54 are independently selected from the group consisting of H, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR56R57, —(C1-C6 alkyl)-C(═O)R56R57, aryl, aralkyl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C3-C7 cycloalkyl, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• or R53 and R54 may be taken together form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, C3-C7 cycloalkyl, oxo, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• R55 is selected from the group consisting of H, aryl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR56R57, —CO2R58, —O—(CH2)e—CO2R58, and —C(═O)NR56R57,
• R56 and R57 independently selected from the group consisting of H, C1-C8 alkyl, C2-C8 alkenyl, C1-C8 alkynyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), aryl, aralkyl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• or R56 and R57 may be taken together form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, oxo, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• R58 is selected from the group consisting of H, aryl, aralkyl, heteroaryl, C1-C6 alkyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR56R57, —(C1-C6 alkyl)-O—(C1-C6 alkyl)-O—(C1-C6 alkyl), each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoroalkyl;
• d is selected from 0 to 6;
• e is selected from 0 to 6;
• R6 is selected from the group consisting of H, C1-C6 alkyl, —(CH2)r—C(═O)—NR63R64, —C(═O)—(CH2)r—NR63R64, —C(═O)—X—R65, and —C(═O)—(CH2)r—NR63R64;
• R63 and R64 are independently selected from the group consisting of H, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR66R67, —(C1-C6 alkyl)-C(═O)NR66R67, aryl, aralkyl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C3-C7 cycloalkyl, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• or R63 and R64 may be taken together form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, C3-C7 cycloalkyl, oxo, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• R65 is selected from the group consisting of H, aryl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR66R67, —CO2R68, —O—(CH2)s—CO2R68, and —C(═O)NR66R67,
• R66 and R67 independently selected from the group consisting of H, C1-C8 alkyl, C2-C8 alkenyl, C1-C8 alkynyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), aryl, aralkyl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• or R66 and R67 may be taken together form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, oxo, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• R68 is selected from the group consisting of H, aryl, aralkyl, heteroaryl, C1-C6 alkyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR66R67, —(C1-C6 alkyl)-O—(C1-C6 alkyl)-O—(C1-C6 alkyl), each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoroalkyl;
• r is selected from 0 to 6;
• s is selected from 0 to 6;
• n is selected from 0 to 4;
• m is selected from 0 to 3;
• and
• p is selected from 0 and 1.

The compound of the formula I, having the formula MI,:

• or pharmaceutically acceptable salt or hydrate thereof, wherein:
• R1 is selected from the group consisting of aryl, —(CH2)y—NR13R14, —X—R12, —O—(CH2)y—CO2R12, —O—(CH2)y—C(═O)NR13R14, —O—(CH2)y-heteroaryl, —O—(CH2)y-cycloalkyl, —O—C(═O)—(CH2)y—NR13R14, —O—(CH2)z—NR13R14, —NH—C(═O)—(CH2)y—NR13R14, —NH—(CH2)y—NR13R14;
• R12 is selected from the group consisting of C1-C6 alkyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR16R17, —(C1-C6 alkyl)-C(═O)NR16R17, —(C1-C6 alkyl)-O—(C1-C6 alkyl)-O—(C1-C6 alkyl), aryl, aralkyl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted at one or more carbon atoms by from 1 to 3 substituents independently selected from halo, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• R13 and R14 are independently selected from the group consisting of H, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR16R17, —(C1-C6 alkyl)-C(═O)NR16R17, aryl, aralkyl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C3-C7 cycloalkyl, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• or R13 and R14 may be taken together form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, C3-C7 cycloalkyl, oxo, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• X is selected from a covalent bond, O, NH, and C1-C6 alkyl;
• R15 is selected from the group consisting of H, aryl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl,
• or R15 is selected from —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR16R17, —CO2R18, —O—(CH2)x—CO2R18, and —C(═O)NR16R17;
• R16 and R17 independently selected from the group consisting of H, C1-C8 alkyl, C2-C8 alkenyl, C1-C8 alkynyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), aryl, aralkyl heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• or R16 and R17 may be taken together form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, oxo, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• R18 is selected from the group consisting of H, aryl, aralkyl, heteroaryl, C1-C6 alkyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR16R17, —(C1-C6 alkyl)-O—(C1-C6 alkyl)-O—(C1-C6 alkyl), each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoroalkyl;
• x is selected from 0 to 6;
• y is selected from 0 to 6;
• z is selected from 2 to 6;
• each R2 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl;
• each R3 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl;
• n is selected from 0 to 4;
• and
• m is selected from 0 to 3.

The compound of the formula I, having the formula XIIb:

• or pharmaceutically acceptable salt or hydrate thereof, wherein:
• R7 is selected from the group consisting of —(CH2)y—NR13R14, and X—R15;
• R13 and R14 are independently selected from the group consisting of H, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR16R17, —(C1-C6 alkyl)-C(═O)NR16R17, aryl, aralkyl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C3-C7 cycloalkyl, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• or R13 and R14 may be taken together form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, C3-C7 cycloalkyl, oxo, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• X is selected from a covalent bond, O, NH, and C1-C6 alkyl;
• R15 is selected from the group consisting of H, aryl, heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl,
• or R15 is selected from —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR16R17, —CO2R18, —O—(CH2)x—CO2R18, and —C(═O)NR16R17;
• R16 and R17 independently selected from the group consisting of H, C1-C8 alkyl, C2-C8 alkenyl, C1-C8 alkynyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), aryl, aralkyl heteroaryl, C3-C7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• or R16 and R17 may be taken together form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6, alkenyl, C1-C6 alkoxy, oxo, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
• R18 is selected from the group consisting of H, aryl, aralkyl, heteroaryl, C1-C6 alkyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), —(C1-C6 alkyl)-NR16R17, —(C1-C6 alkyl)—O—(C1-C6 alkyl)-O—(C1-C6 alkyl), each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkoxy, hydroxy, amino, cyano and C1-C3 perfluoroalkyl;
• x is selected from 0 to 6;
• y is selected from 0 to 6;
• each R2 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl;
• each R3 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl;
• n is selected from 0 to 4;
• and
• in is selected from 0 to 3.