ZA200506460B - Aminoheteroaryl compounds as protein kinase inhibitors - Google Patents

Aminoheteroaryl compounds as protein kinase inhibitors Download PDF

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ZA200506460B
ZA200506460B ZA200506460A ZA200506460A ZA200506460B ZA 200506460 B ZA200506460 B ZA 200506460B ZA 200506460 A ZA200506460 A ZA 200506460A ZA 200506460 A ZA200506460 A ZA 200506460A ZA 200506460 B ZA200506460 B ZA 200506460B
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South Africa
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phenyl
amino
pyridin
benzyloxy
dichloro
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ZA200506460A
Inventor
Jingjong-Jean Cui
Dilip Bhumralkar
Iriny Botrous
Lee A Funk
Ji Y Chu
Harris Jr G Davis
Lei Jia
Joanne Johnson
Stephen A Kolodziej
Pei-Pei Kung
Xiaoyuan Li
Jason Lin
Jerry J Meng
Mitchell D Nambu
Cathleen E Hanau
Christopher G Nelson
Mason A Pairish
Hong Shen
Michelle Tram-Dube
Allison Walter
Fang-Jie Zhang
Jennifer Zhang
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Sugen Inc
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Description

¢ AMINOHETEROARYL COMPOUNDS AS PROTEIN KINASE INHIBITORS v FIELD OF THE INVENTION
The present invention relates generally to novel chemical compounds and methods. More particularly, the invention provides novel aminoheteroaryl compounds, particularly aminopyridines and aminopyrazines, having protein tyrosine kinase activity, and methods of synthesizing and using such compounds.
BACKGROUND
Protein kinases ("PKs") are enzymes that catalyze the phosphorylation of hydroxy groups on tyrosine, serine and threonine residues of proteins. The consequences of this seemingly simple activity are staggering; cell growth, differentiation and proliferation, i.e., virtually all aspects of cell iife in one way or another depend on PK activity. Furthermore, abnormal PK activity has been related to a host of disorders, ranging from relatively non-life threatening diseases such as psoriasis to extremely virulent diseases such as glioblastoma (brain cancer).
The PKs can be conveniently broken down inte two classes, the protein tyrosine kinases (PTKs) and the serine-threonine kinases (STKs).
One of the prime aspects of PTK activity is their involvement with growth factor receptors.
Growth factor receptors are cell-surface proteins. When bound by a growth factor ligand, growth factor receptors are converted to an active form which interacts with proteins on the inner surface of a cell membrane. This leads to phosphorylation on tyrosine residues of the receptor and other proteins and to the formation inside the cell of complexes with a variety of cytoplasmic signaling molecules that, in tum, effect numerous celluler rzsponsss such 2s czll division (proliferation), czlt difiereniiziion, cell growth, expression of metabolic efiecis io the extracellular microsnvironmani, efc. For a more complete discussion, see Schlessinger and Ullrich, Neuron 9:303-391 (1922), which is incorporated by reference, including any drawings, as if fully set forth herein.
Growth factor receptors with PTK activity are known as receptor tyrosine kinases ("“RTKs").
They comprise a large family of transmembrane receptors with diverse biological activity. At present, at least nineteen (19) distinct subfamilies of RTKs have been identified. An example of these is the subfamily designated the “HER” RTKs, which include EGFR (epithelial growth factor receptor), HERZ,
HER3 and HER4. These RTKs consist of an extracellular glycosylated ligand binding domain, a transmembrane domain and an intracellular cytoplasmic catalytic domain that can phosphorylate tyrosine residues on proteins. ! Another RTK subfamily consists of insulin receptor (IR), insulin-like growth factor | receptor (IGF-1R) and insulin receptor related receptor (IRR). IR and IGF-1R interact with insulin, IGF-I and IGF- ; I to form a heterotetramer of two entirely extracellular glycosylated a subunits and two 8 subunits which cross the cell membrane and which contain the tyrosine kinase domain.
A third RTK subfamily is referred to as the platelet derived growth factor receptor (*PDGFR”) group, which includes PDGFRa, PDGFRB, CSFIR, c-kit and c-fms. These receptors consist of glycosylated extracellular domains composed of variable numbers of immunoglobin-like loops and an
¢ intracellular domain wherein the tyrosine kinase domain is interrupted by unrelated amino acid sequences. ’ Another group which, because of its similarity to the PDGFR subfamily, is sometimes subsumed into the later group is the fetus liver kinase (“lk”) receptor subfamily. This group is believed to be made up of kinase insert domain-receptor fetal liver kinase-1 (KDR/FLK-1), fik-1R, flk-4 and fms-like tyrosine kinase 1 (fit-1).
A further member of the tyrosine kinase growth factor receptor family is the fibroblast growth factor (“FGF”) receptor subgroup. This group consists of four receptors, FGFR1-4, and seven ligands,
FGF1-7. While not yet well defined, it appears that the receptors consist of a glycosylated extracellular domain containing a variable number of immunogilobin-like loops and an intracellular domain in which the tyrosine kinase sequence is interrupted by regions of unrelated amino acid sequences.
Still another member of the tyrosine kinase growth factor receptor family is the vascular endothelial growth factor (“VEGF”) receptor subgroup. VEGF is a dimeric glycoprotein similar to PDGF but has different biological functions and target cell specificity in vivo. In particular, VEGF is presently thought fo play an essential role is vasculogenesis and angicgsnesis.
Still another member of the tyrosine kinase growth factor receptor family is MET, often referred to as c-Met, also known as human hepatocyte growth factor receptor tyrosine kinase (hHGFR). c-Met is thought to play 2 role in primary iumor growth and metastasis.
A more complete listing of the known RTK subfamilies is described in Plowman et al., DN&P, 7(6):334-339 (1994), which is incorporated by reference, including any drawings, as if fully set forth herein.
In addition fo the RTKs, there also exists a family of entirely intracellular FTKs called “non- receptor tyrosine Kinases” or “cellular tyrosine kinases.” This latter designation, abbreviated “CTK,” will be used herein. CTKs do not contain extracellular and transmembrane domains. At present, over 24
CTKs in 11 subfamilies (Src, Frk, Btk, Csk, Abl, Zap70, Fes, Fps, Fak, Jak and Ack) have been identified. The Src subfamily appear so far to be the largest group of CTKs and includes Src, Yes, Fyn,
Lyn, Lck, Blk, Hek, Fgr, AUR1, AUR2 and Yrk. For a more detailed discussion of CTKs, see Bolen,
Oncogene, 8:2025-2031 (1993), which is incorporated by reference, including any drawings, as if fully set forth herein.
The serine/threonine kinases, STKs, like the CTKs, are predominantly intracellular although there are a few receptor kinases of the STK type. STKs are the most common of the cytosolic kinases; . ie., kinases that perform their function in that part of the cytoplasm other than the cytoplasmic organelles and cytoskelton. The cytosol is the region within the cell where much of the cell's . intermediary metabolic and biosynthetic activity occurs; e.g., it is in the cytosol that proteins are synthesized on ribosomes. The STKs include CDk2, Raf, the ZC family of kinases, the NEK family of kinases, and BUBH1.
RTKs, CTKs and STKs have all been implicated in a host of pathogenic conditions including, significantly, cancer. Other pathogenic conditions which have been associated with PTKs include, without limitation, psoriasis, hepatic cirrhosis, diabetes, angiogenesis, restenosis, ocular diseases,
B rheumatoid arthritis and other inflammatory disorders, immunological disorders such as autoimmune disease, cardiovascular disease such as atherosclerosis and a variety of renal disorders. ) With regard to cancer, two of the major hypotheses advanced to explain the excessive cellular proliferation that drives tumor development relate to functions known to be PK regulated. That is, it has been suggested that malignant cell growth results from a breakdown in the mechanisms that control cell division and/or differentiation. It has been shown that the protein products of a number of proto- oncogenes are involved in the signal transduction pathways that regulate cell growth and differentiation.
These protein products of proto-oncogenes include the extracellular growth factors, transmembrane growth factor PTK receptors (RTKSs), cytoplasmic PTKs (CTKs) and cytosolic STKs, discussed above.
In view of the apparent link between PK-related cellular activities and wide variety of human disorders, it is no surprise that a great deal of effort is being expended in an attempt to identify ways to moduiate PK activity. Some of these have involved biomimetic approaches using large molecules patterned on those involved in the actual cellular processes (e.g., mutant ligands (U.S. Application Serial
No. 4,966,849); soluble receptors and antibodies (Application No. WO 94/10202, Kendall and Thomas,
Proc. Nat'l Acad. Sci,, @0:10705-10709 (1924), Kim, ef al., Nature, 362:841-844 (1993)); RNA ligands (Jelinek, et al., Biochemistry, 33:10450-56); Takano, et al., Mol. Bio. Cell, 4:358A (1993); Kinsella, et al.,
Exp. Cell Res., 192:56-62 (1992); Wright, et al., J. Cellular Phys., 152:448-57) and tyrosine kinase inhibitors (WO 94/03427; WO 92/21660; WO 91/15495; WO 94/14808; U.S. Patent No. 5,330,292;
Mariani, et al, Proc. Am. Assoc. Cancer Res., 35:2268 (1994)). : in addition to the above, attempts have been made to identify small molecules which act as PK inhibitors. For example, bis-monogylic, bicyclic and heterocyclic aryl compounds (PCT WO 92/20642), vinylene-azaindole derivatives (PCT WO 94/14808) and 1i-cyclopropyl-4-pyridylquinolonas (U.S. Paient
No. 5,330,992) have been described as tyrosine kinase inhibilors. Styryl compounds (U.S. Paient No. 5,217,899), styryl-substituted pyridy} compounds (U.S. Patent No. 5,302,606), quinazoline derivatives (EP Application No. 0 566 266 A1), selenaindoles and selenides (PCT WO 94/03427), tricyclic polyhydroxylic compounds (PCT WO 92/21660) and benzylphosphonic acid compounds (PCT WO 91/15495) have all been described as PTK inhibitors useful in the treatment of cancer.
SUMMARY
In one embodiment, the invention provides a compound of formula 4.
Rr! 2
A
1
Ny N
NH, wherein:
Yis Nor CR";
h R' is selected from Cs. aryl, 5-12 membered heteroaryl, Cs.12 cycloalkyl, 3-12 membered heteroalicyclic, -O(CRPR)),R’, -C(O)R?, -C(O)OR*, -CN, -NO,, -S(O)nR*, -SO:NR‘R’, -C(O)NR'R®, ’ NR'C(O)R®, -C(=NR®NR‘R®, Cys alkyl, Co alkenyl, and Caps alkynyl; and each hydrogen in R' is optionally substituted by one or more R® groups;
R?is hydrogen, halogen, Cq.12 alkyl, Cz.12 alkenyl, C,.42 alkynyl, Ca.12 cycloalkyl, Ce.12 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, -S(0)mR®, -SONR*R?, -S(0),0R’, -NO, -NR*R®,
ACR°R’),OR!, -CN, -CO)R’, -OC(O)R*, -O(CR°R).R' -NR‘C(OR’, -(CR°R’),C(O)OR’, -(CRPR’),NCR*R’, -C(=NR®NR’R®, -NR‘C(O)NR®R®, -NR*S(0),R® or -C(O)NR'R®, and each hydrogen in R? is optionally substituted by one or more R® groups;
R® is halogen, Cy.12 alkyl, C2.12 alkenyl, Cyz.12 alkynyl, C342 cycloalkyl, Ce 12 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, -S(O)mR’, -SONR'R’, -S(0).0R‘, -NO;, -NR'R’,
ACR°R™),OR?, -CN, -C(OR', -OC(O)R! -O(CRR)R' -NR'COR’, -(CR’R).C(O)OR’, (CR®R"),NCR’R®, -C(=NR®NR'R®, -NR‘C(O)NR°R®, -NR*S(0),R® or -C(O)NR’R®, each hydrogen in R® is optionally substituted by one or more R® groups, and R® groups on adjacent atoms may combine to form a Cg.q2 aryl, 5-12 membered heteroaryl, Cs.s2 cycloalkyl or 3-12 membered heterozalicyclic group; each RY, R®, R® and R’ is independently hydrogen, halogen, Cy.2 alkyl, Caz alkenyl, Coz alkynyl, Ca.12 cycloalkyl, Cs.2 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl; or any two of R, R®, R® and R’ bound to the same nitrogen atom may, together with the nitrogen to which they are bound, be combined to form a 3 to 12 membered heteroalicyclic or 5-12 membered heteroaryl group optionally containing 1 to 3 additional heteroatoms selected from N, O, and S; or any two of RY R° R® and R’ bound to the same carbon atom may be combined to form a Caqp cycloalkyl, Cayo aryl, 3-12 membsrad heteroalicyclic or 5-12 membered heteroaryl group; and each hydrogen in rR? R® R® and R’ is optionally substituted by one or more R® groups; each R® is independently halogen, Cy.12 alkyl, Cz.12 alkenyl, Caz alkynyl, Cs 42 cycloalkyl, Ce.12 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, -CN, -0-Cy.12 alkyl, -O-(CH2)xCa12 cycloalkyl, -O-(CH2)nCs-12 aryl, ~-O-(CHz),(3-12 membered heteroalicyclic) or ~O-(CHg)n(5-12 membered heteroaryl); and each hydrogen in R%is optionally substituted by one or more R" groups;
A! is -(CR°R'%),-A? except that: (i) when Y is N and R'is substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl, A’ is (CR°R'%),-A? and n is not zero; and (ii) when Y is N and R? is H and A’ is m-chlorobenzyl, R' is not unsubstituted . piperazine, each R® and R' is independently hydrogen, halogen, Cy.1 alkyl, Ca 12 cycloalkyl, Ce 12 aryl, 3-12 } membered heteroalicyclic, 5-12 membered heteroaryl, -S(0)mR’, -SO:NR'R®, -S(0),0R", -NO,, -NR*R’, -(CR°R),OR!, -CN, -C(OR' -OCO)R‘, -NR‘COR’, -(CR'R).C(O)OR‘, -(CR°R"),NCR'R’,
NR'C(O)NR®R®, -NR*S(O),R® or -C(O)NR*R®; R® and R'® may combine to form a Ca.2 cycloalkyl, 3-12 membered heteroalicyclic, Ce.12 aryl or 5-12 membered heteroaryl ring; and each hydrogen in R® and
R'® is optionally substituted by one or more R® groups;
A? is Cg.4o aryl, 5-12 membered heteroaryl, Cay, cycloalkyl or 3-12 membered heteroalicyclic, and A? is optionally substituted by one or more R® groups; ) each R'"' is independently halogen, Ci.1z alkyl, Cy.12 alkoxy, Ca12 cycloalkyl, Ce.42 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, -O-Ci.12 alkyl, ~O-(CHz)nCsz-12 cycloalkyl, ~O- (CH2).Ce1z aryl, -O-(CH2)y(3-12 membered heteroalicyclic), -O-(CHz)n(5-12 membered heteroaryl) or -CN, and each hydrogen in R" is optionally substituted by one or more groups selected from halogen, -OH, -CN, -C1.1; alkyl which may be partially or fully halogenated, -O-C1.12 alkyl which may be partially or fully halogenated, -CO, -SO and -SOg;
R'is hydrogen, halogen, C.1, alkyl, Cz.12 alkenyl, Cz.12 alkynyl, Cs.12 cycloalkyl, Ce 12 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, -S(O)nR?, -SO,NR'R, -S(0):0R", -NO2, -NR*R’, (CRPR), OR’, -CN, -C(O)R‘, -OCOR’, -OCR®R).R‘ -NR'COR’ -(CR°R"),C(O)OR?, (CRPRT).NCR’R®, -C(=NRONR'R®, -NRC(O)NR’R®, -NR*S(0),R® or -C(O)NR‘R®, and each hydrogen in R'2 is optionally substituted by one or more R® groups;
R' and R? or R! and R'2 may be combined together to form a Ce, aryl, 5-12 membered 16 heteroaryl, Ca.12 cycloalkyl or 3-12 membered heteroalicyclic group; mis 0, 1or2; nis0,1,2, 3o0r4; and pis lor or a pharmaceutically acceptable salt, solvate or hydrate thereof.
In a particular aspect of this embodiment, Yis N. Ina preferred aspect, R'is not piperazine. In another preferred aspect, R' is not heteroalicyclic.
In another particular aspect of this embodiment, Y is CR"™.
In particular aspects of this embodiment, and in combination with any other particular aspects of this embodiment, the compound has formula ia rR!
A K i R10 1a
N
SLA
NH, . wherein A? is Cg.¢2 ary! or 5-12 membered heteroaryl optionally substituted by one or more Rr? groups.
In particular aspects of this embodiment, and in combination with any other particular aspects of this embodiment, R' is selected from Cs.12 aryl and 5-12 membered heteroaryl, and each hydrogen in Rr! is optionally substituted by one or more R® groups.
In particular aspects of this embodiment, and in combination with any other particular aspects of this embodiment not inconsistent with the following definition of R', R'is selected from Cs, cycloalkyl, 3-12 membered heteroalicyclic, <O(CRPR)R", -C(O)R?, -C(O)OR?, -CN, -NO,, -S(O)nR’, -SO,NR*R",
C(O)NRR®, -NR*C(O)R®, -C(=NRYNR'R’, C14 alkyl, C5 alkenyl, and C4 alkynyl; and each hydrogen . in R! is optionally substituted by cne or more R? groups.
In particular aspects of this embodiment, and in combination with any other particular aspects of this embodiment, A? is substituted by at least one halogen atom. in particular aspects of this embodiment, and in combination with any other particular aspects of this embodiment, R? is hydrogen, R? and R'® are independently C1. alkyl, and A? is phenyl substituted by at least one halogen atom.
In particular aspects of this embodiment, and in combination with any other particular aspects of this embodiment not inconsistent with the following definition of R', R' is a furan, thiopene, pyrrole, pyrroline, pyrrolidine, dioxolane, oxazole, thiazole, imidazole, imidazoline, imidazolidine, pyrazole, pyrazoline, pyrazolidine, isoxazole, isothiazole, oxadiazole, triazole, thiadiazole, pyran, pyridine, piperidine, dioxane, morpholine, dithiane, thiomorpholine, pyridazine, pyrimidine, pyrazine, piperazine, triazine, trithiane or phenyl group, and each hydrogen in R' is optionally substituted by one or more Rr? groups.
In particular aspects of this embediment, and in combination with any other particular aspects of this embodiment not inconsistent with the following definition of R', R' is a furan, thiopene, pyrrole, pyrroline, pyrrolidine, dioxolane, oxazole, thiazole, imidazole, imidazoline, imidazolidine, pyrazole, pyrazoline, pyrazoliding, isoxazole, isothiazole, oxadizzole, triazole, thiadiazole, pyran, pyridine, piperidine, dioxane, morpholine, dithiane, thiomorpholine, pyridazine, pyrimidine, pyrazine, triazine, ftrithiane or phenyl group, and each hydrogen in R' is optionally substituted by one or more R® groups.
In a more perticular aspect, R'is not heteroalicyelic.
In particulzr aspecis of this embodiment, and in combination with any cihar particular aspecis of this embodiment not inconsistent with the following definition of R', R' is a fused ring hetsroaryl group, and each hydrogen in R' is optionally substituted by one or more R® groups.
In particular aspects of this embodiment, and in combination with any other particular aspects of this embodiment not inconsistent with the following definition of R', R' is 2 -SO.NR‘R® group.
In another embodiment, the invention provides a compound of formula 2
Rr!
R12 R2
Co | 2
Ne Ya 0
NH, wherein:
R' is selected from Ce.qz aryl, 5-12 membered heteroaryl, Catz cycloalkyl, 3-12 membered heteroalicyclic, -O(CR®R")R®, -C(O)R®, -C(O)OR’, -CN, -NO;, -S(O)uR", -SONR'R®, -C(ONR'R’,
NR*C(O)R®, -C(=NRONR*R®, Cis alkyl, Cz.5 alkenyl, and Cae alkynyl; and each hydrogen in R' is . optionally substituted by one or more R® groups;
R? is hydrogen, halogen, C1.12 alkyl, C242 alkenyl, Cp.12 alkynyl, Ca.12 cycloalkyl, Cg2 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, -S(O)mR", -SO,NR*R?, -S(0),0R*, -NO,, -NR*R’, -(CR°R),OR', -CN, -C(OR' -OC(O)R’ OCR R)R?, -NR'CO)R’, -(CR°R)IC(O)OR, -(CRPR").NCR'R’, -C(=NR®)NR'R’, -NR*C(O)NR°R’, -NR*S(0),R® or -C(O)NR'R®, and each hydrogen in R? is optionally substituted by one or more R® groups;
R® is halogen, Cy.12 alkyl, C2.12 alkenyl, Ca.12 alkynyl, Cs. cycloalkyl, Ce.12 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, -S(O)nR®, -SO,NR'R®, -S(0).0R%, -NO; -NR'R’, -(CR°R),OR’, -CN, -C(OR!, -OC(O)R’, -O(CR°R'MR’, NRCO)R®, ~(CRR"),C(O)OR?, (CRPR").NCR’R®, -C(=NRONR'R®, -NR*C(O)NR’R’, -NR*S(0),R°® or -C(O)NR*R®, each hydrogen in Rr? is optionally substituted by one or more R® groups, and R® groups on adjacent atoms may combine to form a Ce12 aryl, 5-12 membered heteroaryl, Ca.12 cycloalky! or 3-12 membered heteroalicyclic group; each R*. R%, R® and R’ is independently hydrogen, halogen, Ci.i2 alkyl, Caz alkenyl, Cz. i5 alkynyl, Caz cycloalkyl, Cs.2 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl; or any wo of R*. R°, R® and R” bound to the same nitrogen atom may, together with the nitrogen to which they are bound, be combined to form a 3 to 12 membered heteroalicyclic or 5-12 membered heteroaryl group optionally containing 1 to 3 additional heteroatoms selected from N, O, and S; or any two of RY, RY, R® and R’ bound to the same carbon atom may be combined to form a Caz cycloalkyl, Ce42 aryl, 3-12 membered heteroalicyclic or 5-12 membered heteroaryl group; and each hydrogen in R* R%, Rand R’ is optionally substitui2d by one or more R® groups; each RC is indspendanily halogen, Ci.iz alkyl, Co.e2 alkenyl, Co.12 alkynyl, Caz cycloalkyl, Coz aryl, 3-12 membered heterozlicyclic, 5-12 membered heteroaryl, -CN, -0-Cj.42 alkyl, -O-~(CH2)nC312 cycloalkyl, -O-(CH2)nCs-12 aryl, -O-(CHy)n(3-12 membered heteroalicyclic) or -O-(CHa)q(5-12 membered heteroaryl); and each hydrogen in R® is optionally substituted by one or more R'! groups;
A'is -(CR°R"),-A% each R® and R'is independently hydrogen, halogen, Cy.12 alkyl, Ca.12 cycloalkyl, Ce.q2 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, -S(O)uR’", -SO,NR'R?, -S(0),0R*, -NO;, -NR*R’, (CR°R"),OR’, -CN, -C(OR’, -OC(O)R?, -NR'C(O)R®, -(CR°R"),C(O)OR", -(CR°R").NCR’R®, -NR'C(ONRRS, -NR*S(O);R® or -C(O)NR'R®; R® and R'® may combine to form a Cs.12 cycloalkyl, 3-12 membered heteroalicyclic, Ce.12 aryl or 5-12 membered heteroaryl ring; and each hydrogen in R® and ’ R'? is optionally substituted by one or more R? groups;
A? is Cs. aryl, 5-12 membered heteroaryl, Cs.12 cycloalkyl or 3-12 membered heteroalicyclic, ) and A? is optionally substituted by one or more R® groups; each R'is independently halogen, Ci.» alkyl, C112 alkoxy, Ca.» cycloalkyl, Ce.12 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, -O-Cq.s2 alkyl, -O-(CHg)nCa.12 cycloalkyl, -O- (CH2)nCs-12 aryl, -O-(CH2)n(3-12 membered heteroalicyclic), -O-(CHz)n(5-12 membered heteroaryl) or -CN, and each hydrogen in R'is optionally substituted by one or more groups selected from halogen,
’ -OH, -CN, -C.42 alkyl which may be partially or fully halogenated, -O-C1.12 alkyl which may be partially or fully halogenated, -CO, -SO and -SO,; : R" is hydrogen, halogen, Cy.12 alkyl, C312 alkenyl, Ca.12 alkynyl, Ca.1, cycloalkyl, Ce. aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, -S(O)nR®, -SO2NR?R?, -S(0),0R", -NO, -NR*R’, +CR°R").OR% -CN, -C(O)R', -OC(O)R%, -O(CR°R')R® -NRC(O)R’, -(CR°R"),C(O)OR*,
ACRORT)NCR*R®, -C(=NRONR'R®, -NR'C(O)NR®R®, -NR*S(0),R® or -C(O)NR'R®, and each hydrogen in R' is optionally substituted by one or more R® groups;
R' and R? or R' and R™ may be combined together to form a Ce aryl, 5-12 membered heteroaryl, Cs.12 cycloalkyl or 3-12 membered heteroalicyclic group; mis 0, 1or2; nis0, 1,2, 30r4; and pis1or2; or a pharmaceutically acceptable salt, solvate or hydrate thereof.
In a particular aspect of this embodiment, the compound has formula 2a rR!
Rr" = R2 aN a | 2a
N oo A
NH, wherein A? is Cg.y2 aryl or 5-12 membered heteroaryl opiionzity substituizd by ons or mora Re groups. in particulzr aspects of this embodiment, and in combination with any other particular aspects of this embodim=nt, R' is selected from Cs.» aryl and 5-12 membered heteroaryl, and each hydrogen in R' is optionally substituted by one or more R? groups. in particular aspects of this embodiment, and in combination with any other particular aspects of this embodiment not inconsistent with the following definition of R!, R'is selected from C31, cycloalkyl, 3-12 membered heteroalicyclic, -O(CRPR"),R?, -C(O)R?, -C(O)OR?, -CN, -NO2, -S(O)nR*, -SONRR®, -CO)NRR’, -NR'C(O)R?, -C(=NRNR'R?, C5 alkyl, C25 alkenyl, and Cz. alkynyl; and each hydrogen in R' is optionally substituted by one or more R* groups. in particular aspects of this embodiment, and in combination with any other particular aspects of this embodiment, A? is substituted by at least one halogen atom. ’ In particular aspects of this embodiment, and in combination with any other particular aspects of this embodiment, R? is hydrogen, R® and R'® are independently Ci. alkyl, and A” is phenyl substituted ) by at least one halogen atom.
In particular aspects of this embodiment, and in combination with any other particular aspects of this embodiment not inconsistent with the following definition of R', R' is a furan, thiopene, pyrrole, pyroline, pyrrolidine, dioxolane, oxazole, thiazole, imidazole, imidazoline, imidazolidine, pyrazole, pyrazoline, pyrazolidine, isoxazole, isothiazole, oxadiazole, triazole, thiadiazole, pyran, pyridine,
piperidine, dioxane, morpholine, dithiane, thiomorpholine, pyridazine, pyrimidine, pyrazine, piperazine, triazine, trithiane or phenyl group, and each hydrogen in R'is optionally substituted by one or more R® ’ groups.
In particular aspects of this embodiment, and in combination with any other particular aspects of this embodiment not inconsistent with the following definition of R', R' is a fused ring heteroaryl group, and each hydrogen in R' is opticnally substituted by one or more R® groups.
In particular aspects of this embodiment, and in combination with any other particular aspects of this embodiment not inconsistent with the following definition of R’, R' is a -SO,NR*R® group.
In another embodiment, the invention provides a compound of formula 3
R'
R2
A
3
AN :
NH; wherein:
R' is selected from Cg.q2 aryl, 5-12 membered heteroaryl, Cs, cycloalkyl, 3-12 membered heteroalicyclic, <O(CR°R').R?, -C(O)R?, -C(O)OR?, -CN, -NO;, -S(O)rR®, -SO:NR'R®, -C(OINR*R’,
NRC(OIRS, -C(ENRONRR®, Cys alkyl, Cag zlkenyl, 2nd Cap alkynyl; and each hydrogen in R is optionally substituizd by one or more R® groups;
Ris hydrogen, halogen, Ci. alkyl, Cz.12 alkenyl, Co.12 alkynyl, Cy42 cycloalkyl, Ceq2 arvl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, -S(O)mR’, -SO:NR’R®, -8(0)20R", -NOz, -NR*R’, (CR°RORY, -CN, -C(OR -OCOR’ -O(CR°RNR‘ -NR'C(OR’ ~(CR°R"),C(O)OR*, «(CRPR7),INCR'R®, -C(=NRONR’R®, -NR*C(O)NR°R’, -NR'S(0),R°® or -C(O)NR'R®, and each hydrogen in R% is optionally substituted by one or more R® groups;
Ris halogen, Ci.12 alkyl, Co.2 alkenyl, Co.12 alkynyl, Caz cycloalkyl, Ce.» aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, -S(O)mR?, -SO:NR'R’, -S(0).0R’, -NO, -NRR®, (CR°R")OR!, -CN, -COR' -OCOR’ -OCRR)R' -NR'COR’ -(CR°R"),C(O)OR", (CRPR).NCR'R’, -C(=NRP)NR‘R®, -NR*C(O)NR°R’, -NR*S(O),R’ or -C(O)NR*R®, each hydrogen in R® ’ 25 is optionally substituted by one or more R® groups, and R® groups on adjacent atoms may combine to form a Ce.12 aryl, 5-12 membered heteroaryl, Ca.s2 cycloalkyl or 3-12 membered heteroalicyclic group; . each R*, R’, R® and R is independently hydrogen, halogen, Ci.12 alkyl, Cz.12 alkenyl, Cz.12 alkynyl, Caz cycloalkyl, Cs.12 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl; or any two of R*, R®, R® and R bound to the same nitrogen atom may, together with the nitrogen to which they are bound, be combined to form a 3 to 12 membered heteroalicyclic or 5-12 membered heteroaryt group optionally containing 1 to 3 additional heteroatoms selected from N, O, and S; or any two of RY RS, R® and R’ bound to the same carbon atom may be combined to form a Cs.2 cycloalkyl, Ce.1; aryl, 3-12 membered heteroalicyclic or 5-12 membered heteroaryl group; and each hydrogen in R*, R%, R® and R’ is optionally substituted by one or more R® groups; ‘ each R® is independently halogen, Ci.12 alkyl, Cz.12 alkenyl, Cz.42 alkynyl, Ca.12 cycloalkyl, Ce.12 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, -CN, -0-Cq.q2 alkyl, -O-(CH2)nCs.12 cycloalkyl, -O-(CH2)aCs.12 aryl, -O-(CHz)n(3-12 membered heteroalicyclic) or -O-(CHy)n(5-12 membered heteroaryl); and each hydrogen in R® is optionally substituted by one or more R" groups;
Allis —(CR°R'%),-A? except that: (i) when R' is substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl, A' is H(CRR"),-A? and n is not zero; and (ii) when R? is H and A' is m-chlorobenzyl, R' is not unsubstituted piperazine; each R® and R' is independently hydrogen, halogen, Ci.12 alkyl, Cs.12 cycloalkyl, Cs.12 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, -S(O)nR’, -SONR?R?, -S(0):0R", -NO,, ~NR*R’, (CR°RN,OR?, -CN, -C(O)R!, -OC(O)R', -NR'‘C(O)R®, -(CR'R")\C(O)OR, ~(CR°RN).NCR'R®, -NRC(O)NR®R®, -NR*S(0),R° or -C(O)NR’R®; R? and R'® may combine to form a Ca.2 cycloalkyl, 3-12 i5 membered heteroalicyclic, Cs.12 aryl or 5-12 membered heteroaryl ring; and each hydrogzsn in R® and
RC is optionally substituted by one or more R® groups;
A? is Cg.2 aryl, 5-12 membered heteroaryl, Ca.12 cycloalkyl or 3-12 membered heteroalicyclic, and AZ is optionally substituted by one or more R® groups; each R'' is independently halogen, Cy.42 alkyl, Ci.12 alkoxy, Ca.iz cycloalkyl, Ce2 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, -O-Cy.12 alkyl, -O-(CH).Cs42 cycloalkyl, -O- (CHo)nCe12 aryl, -O-(CH2)(3-12 membered heterozlicyelic), -O-(CHa)n(5-12 membersd heteroaryl) or -CN, and =ach hydrogan in R'is optionally substituied by one or more groups selected from halogen, -OH, -CN, -Cy.42 alkyl which may be partially or fully halegenatzd, -O-Cy.s2 alkyl which may be partially or fully halogenated, -CO, -SO and -SO;
R' and R? may be combined together to form a Ce.12 aryl, 5-12 membered heteroaryl, Cs.12 cycloalkyl or 3-12 membered heteroalicyclic group; mis 0, 1 org; nis0,1,2,3o0r4; and pis 1or2; ora pharmaceutically acceptable salt, solvate or hydrate thereof.
In a particular aspect of this embodiment, the compound has formula 3a . Rr! y A
R9 R10 3a
N
SLA
NH, wherein A? is Cg; aryl or 5-12 membered heteroaryl optionally substituted by one or more R® groups.
’ In particular aspects of this embodiment, and in combination with any other particular aspects of this embodiment, R' is selected from C4, aryl and 5-12 membered heteroaryl, and each hydrogen in R' * is optionally substituted by one or more Rr? groups. in particular aspects of this embodiment, and in combination with any other particular aspects of this embodiment not inconsistent with the following definition of R', R' is selected from Cs.12 cycloalkyl, 3-12 membered heteroalicyclic, -O(CR°R"),R?, -C(O)R?, -C(O)OR?, -CN, -NO,, -S(O)mR’, -SO.NR*R®, -C(O)NR’R®, -NR*C(O)R®, -C(=NR®)NR’R®, C3 alkyl, C,¢ alkenyl, and C, alkynyl; and each hydrogen inR'is optionally substituted by one or more Rr? groups.
In particular aspects of this embodiment, and in combination with any other particular aspects of this embodiment, A? is substituted by at least one halogen atom.
In particular aspects of this embodiment, and in combination with any other particular aspects of this embodiment, R? is hydrogen, R® and R'® are independently C4 alkyl, and A? is phenyl substituted by at least one halogen atom.
In particular aspects of this embodiment, and in combination with any other particular aspects of this embodiment not inconsistent with the following definition of RY, R'is a furan, thiopene, pyrrole, pyrroline, pyrrolidine, dioxolane, oxazole, thiazole, imidazole, imidazoline, imidazolidine, pyrazole, pyrazoline, pyrazolidine, isoxazole, isothiazole, oxadiazole, triazole, thiadizzole, pyran, pyridine, piperidine, dioxane, morpholine, dithiane, thiomorpholine, pyridazine, pyrimidine, pyrazine, piperazine, triazine, trithiane or phenyl group, and each hydrogen in R'is optionally substituted by one or more Rr? groups.
In particular aspects of thiz embodiment, and in combinztion with any other particular aspects of this embodiment not inconsistent with ths following definition of R', R' iz a furan, thiopene, pyrrole, pyrroline, pyrrolidine, dioxolane, oxazole, thiszole, imidazole, imidazoline, imidazolidine, pyrazole, pyrazoling, pyrazolidine, isoxazole, isothiazole, oxadiazole, triazole, thiadiazole, pyran, pyridine, piperidine, dioxane, morpholine, dithiane, thiomorpholine, pyridazine, pyrimidine, pyrazine, triazine, trithiane or phenyl group, and each hydrogen in R' is optionally substituted by one or more R® groups.
In still more particular aspects, R'is not heteroalicyclic.
In particular aspects of this embodiment, and in combination with any other particular aspects of this embodiment not inconsistent with the following definition of R', R' is a fused ring heteroaryl group, and each hydrogen in R'is optionally substituted by one or more R® groups.
In particular aspects of this embodiment, and in combination with any other particular aspects of ] this embodiment not inconsistent with the following definition of R', R' is a -SO,NR*R°® group.
In another embodiment, the invention provides a compound of formula 4
. "
R10 io 4
R® -
SL ~~
A? ©
NH, wherein:
R' is selected from Ce12 aryl, 5-12 membered heteroaryl, C34, cycloalkyl, 3-12 membered heteroalicyclic, -O(CR°R"),R*, -C(O)R?, -C(O)OR*, -CN, -NO,, -S(O)mR*, -SO.NR*R®, -C(O)NR‘R®, -NR'C(O)R®, -C(=NR®)NR’R®, Cis alkyl, Cs alkenyl, and Cy alkynyl; and each hydrogen in R' is optionally substituted by one or more R® groups;
Ris halogen, Ci.12 alkyl, C212 alkenyl, Coy, alkynyl, Ca.42 cycloalkyl, Ce.12 aryl, 3-12 membered heteroalicyclic, 5-12 memberad heteroaryl, -S(O)nR*, -SO;NRR®°, -S(0),OR*, -NO», -NR°RS, -(CR°RNOR?, -CN, -C(O)R’, -OC(O)R', -O(CR°R'R', -NR'CO)R}, '-(CR°R").C(O)OR® -(CR°R")NCR’R®, -C(=NR®NR'R®, -NR*C(O)NR°R®, -NR*S(0),R® or -C(O)NR’R®, each hydrogen in R® is optionzlly substituted by one or more R® groups, and R® groups on adjacent atoms mzy combine to form a Cg; aryl, 5-12 membered heteroaryl, Cs.4; cycloalkyl or 3-12 membered heteroalicyclic group; each R*, R®, R® and R’ is independently hydrogen, halogen, Cy.i» alkyl, Co. alkenyl, Cp. alkynyl, Caz cycloalkyl, Ceqz aryl, 3-12 mambsarad heterozlicyclic, 5-12 membered heteroziryl; or any 16 two of RY, R®, R® and R” bound to ths same nitrogen atom may, together wiih the nitrogen te which ihey are bound, be combined to form a 3 to 12 membered heteroalicyclic or 5-12 membered heteroaryl group optionally containing 1 to 3 additional heteroatoms selected from N, O, and S; or any two of R?, R®, R® and R’ bound to the same carbon atom may be combined to form a Cs; cycloalkyl, Cs.42 aryl, 3-12 membered heteroalicyclic or 5-12 membered heteroaryl group; and each hydrogen in R*, R®, R® and R’ is optionally substituted by one or more R® groups; each R® is independently halogen, Ci.12 alkyl, C..12 alkenyl, C,.12 alkynyl, Ca.» cycloalkyl, Cs 12 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, -CN, -O-Cy.42 alkyl, -O-(CH2),Cs.12 cycloalkyl, -O-(CH;)nCe-12 aryl, -O-(CHz)n(3-12 membered heteroalicyclic) or -O-(CH,)n(5-12 membered heteroaryl); and each hydrogen in R® is optionally substituted by one or more R'! groups; ~ 25 each R® and R" is independently hydrogen, halogen, Ci.2 alkyl, Cs.1, cycloalkyl, Ce.2 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, -S(0)mR?, -SO,NR*R®, -S(0),0R", -NO,, ~NR*R®, . <(CRRN,ORY, -CN, -COR, -OC(O)R* -NR*C(O)R’, -(CR°R"),C(O)OR*, -(CR°R"),NCR'R’ -NR*C(O)NR®R®, -NR*S(0),R’ or -C(O)NR’R®; R® and R'® may combine to form a Ca. cycloalkyl, 3-12 membered heteroalicyclic, Ce.12 aryl or 5-12 membered heteroaryl ring; and each hydrogen in R® and
R'"is optionally substituted by one or more R® groups;
A? is Cg.12 aryl, 5-12 membered heteroaryl, Cs, cycloalkyl or 3-12 membered heteroalicyclic, and A? is optionally substituted by one or more R® groups;
each R' is independently halogen, Ci.12 alkyl, Ci.1z alkoxy, Ca.gz cycloalkyl, Cs.z aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, -O-C.y2 alkyl, -O-(CH),C3.42 cycloalkyl, -O- ’ (CH2)nCe.12 aryl, -O-(CH,)a(3-12 membered heteroalicyclic), -O-(CHz)n(5-12 membered heteroaryl) or -CN, and each hydrogen in R'is optionally substituted by one or more groups selected from halogen, -OH, -CN, -C.1 alkyl which may be partially or fully halogenated, -O-C,.q2 alkyl which may be partially or fully halogenated, -CO, -SO and -SOy; mis0,1or2; . nis0,1,2,3or4; and pistor2; or a pharmaceutically acceptable salt, solvate or hydrate thereof.
In a particular aspect of this embodiment, A?is Ce.1z aryl or 5-12 membered heteroaryl optionally substituted by one or more R® groups.
In other particular aspects of this embodiment, preferred substituents and groups of substituents include those defined in particular aspects of the previous embodiments. :
In another @mbodiment, th2 invention provides 2 compound of formula §
R!
AN
R10 | 5 4 PY No p22 To he
NH, wherein:
R' is selected from Cg1p aryl, 5-12 membered heteroaryl, Ca» cycloalkyl, 3-12 membered heteroalicyclic, -O(CRR").R?, -C(O)R®, -C(O)OR’, -CN, -NO,, -S(O)mR*, -SO.NR'R®, -C(O)NR'R’, -NRC(O)R®, -C(=NR®NR’R®, Ci; alkyl, Cy alkenyl, and Cs alkynyl; and each hydrogen in R' is optionally substituted by one or more R® groups;
R3 is halogen, Ci.12 alkyl, Cz.12 alkenyl, Ca.12 alkynyl, Ca.42 cycloalkyl, Cg 42 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, -S(O)nR‘, -SO:NR'R®, -S(0),0R*, -NO, -NR'R’, (CR°R)OR!, -CN, -COR’ -OCOR! -OCRR)R! -NR'C(OR’, -(CR°R’),C(O)OR, : 25 -(CR°R").NCR'R’, -C(=NR)NR'R®, -NR*C(O)NR°R®, -NR*S(0),R°® or -C(O)NR*R®, each hydrogen in R® is optionally substituted by one or more Rr? groups, and Rr? groups on adjacent atoms may combine to . form a Ce 12 aryl, 5-12 membered heteroaryl, C,.1; cycloalkyl or 3-12 membered heteroalicyclic group; each R*, R% R® and R’ is independently hydrogen, halogen, Ci.i, alkyl, C,.1; alkenyl, Ca. alkynyl, Ca.12 cycloalkyl, Ce.12 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl; or any two of R*, R®, R®and R’ bound to the same nitrogen atom may, together with the nitrogen to which they are bound, be combined to form a 3 to 12 membered heteroalicyclic or 5-12 membered heteroaryl group optionally containing 1 to 3 additional heteroatoms selected from N, O, and S; or any two of R%, R®, R® and R’ bound to the same carbon atom may be combined to form a Ca, cycloalkyl, Ce.1» aryl, 3-12 membered heteroalicyclic or 5-12 membered heteroaryl group; and each hydrogen in R®, R%, R® and R’ ’ is optionally substituted by one or more R® groups; each R® is independently halogen, Ci.1; alkyl, C2.12 alkenyl, C,.12 alkynyl, Ca. cycloalkyl, Ce.12 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, CN, -O-Cy.42 alkyl, -O-(CHz)nCz12 cycloalkyl, -O-(CHp)xCs.12 aryl, -O-(CHa)a(3-12 membered heteroalicyclic) or -O-(CHz)n(5-12 membered heteroaryl); and each hydrogen in R® is optionally substituted by one or more R'" groups; each R® and R'is independently hydrogen, halogen, Ci.12 alkyl, Ca.12 cycloalkyl, Ce.12 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, -S(O)mR®, -SO:NR’R®, -8(0),0R", -NO;, -NR*R®, -(CR°R’),OR, -CN, -C(O)RY -OC(O)R* -NR'C(O)R®, -(CR°R").C(O)OR‘, -(CR°R).NCR'R’,
NR*C(O)NR®R®, -NR*S(0),R® or -C(0)NR*R® R? and R'® may combine to form a Cs.1» cycloalkyl, 3-12 membered heteroalicyclic, Ce.12 aryl or 5-12 membered heteroaryl ring; and each hydrogen in RY and
R'is optionally substituted by one or more R® groups;
A? is Cg.1z aryl, 5-12 membered heteroaryl, Cs, cycloalkyl or 3-12 membered heteroalicyclic, and A? ie optionally substituted by one or more R® groups; except that when R?, R® and R™ are all H and
A? is m-chlorophenyl, R' is not unsubsiituted piperazine; each R'' is independently halogen, Ci.i2 alkyl, Cy.12 alkoxy, Caz cycloalkyl, Ceo aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, -O-Cy.q» alkyl, -O~(CH2),Cz.12 cyclozlkyl, -O- (CH2)nCe.12 aryl, ~O-(CH;)n(3-12 membered heteroalicyclic), -O-(CH2)n(5-12 membered heteroaryl) or -CN, and each hydrogen in R'is optionally substituted by one or more groups selected from halogen, -OH, -CN, -C1.12 zlkyl which may be partially or fully halogenated, -O-Cy.12 alkyl which may be partially or fully helogenaied, -CO, -SC end -50, mis 0, 1o0r2; nis 0, 1,2, 3or4; and pis1or2; or a pharmaceutically acceptable salt, solvate or hydrate thereof.
In a particular aspect of this embodiment, AZ is Cg.12 aryl or 5-12 membered heteroaryl optionally substituted by one or more R® groups.
In other particular aspects of this embodiment, preferred substituents and groups of substituents include those defined in particular aspects of the previous embodiments.
In another embodiment, the invention provides a compound selected from the group consisting . of: 4-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yl}-phenol; 3-(2,6-dichloro-benzyloxy)-5-[4-(2- morpholin-4-yl-ethoxy)-phenyl]-pyridin-2-ylamine; 3-(2,6-dichloro-benzyloxy)-5-[3-(2-morpholin-4-yl- . ethoxy)-phenyl}-pyridin-2-ylamine; 3-(2,6-dichloro-benzyloxy)-5-(1H-indol-4-yl)-pyridin-2-ylamine; 3-[2- chioro-6-(1H-indol-4-yl)-benzyloxyl-5-(1H-indol-4-yl)-pyridin-2-ylamine; 2-[6-amino-5-~(2,6-dichloro- benzyloxy)-pyridin-3-yl}-pyrrole-1-carboxylic acid tert-butyl ester; 3-(2,6-dichloro-benzyloxy)-5-(1H- pyrrol-2-yl)-pyridin-2-ylamine; 3-(2,6-dichloro-benzyloxy)-5-(4-fluoro-phenyl)-pyridin-2-ylamine; 3-(2,6- dichloro-benzyloxy)-5-phenyl-pyridin-2-ylamine; 3-(2,6-dichloro-benzyloxy)-5-(2-fluoro-phenyl)-pyridin-2- ylamine; 3-(2,6-dichloro-benzyloxy)-5-(3-fluoro-phenyl)-pyridin-2-ylamine; 5-(4-amino-phenyl)-3-(2,6-
i -15- dichloro-benzyloxy)-pyridin-2-ylamine; N-{4-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yl]-phenyl}- methanesulfonamide; N-{4-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yl]-phenyl}-acetamide; 3-[6- ’ amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yi}-phenol; 3-(2,6-dichloro-benzyloxy)-5-(4-methoxy-phenyl)- pyridin-2-ylamine; 5-(3-amino-phenyl)-3-(2,6-dichloro-benzyloxy)-pyridin-2-ylamine; 3-(2,6-dichloro- benzyloxy)-5-(3-trifluoromethoxy-phenyl)-pyridin-2-ylamine; 2-[6-amino-5-(2,6-dichloro-benzyloxy)- pyridin-3-yl]-phenol; 3-(2,6-dichloro-benzyloxy)-5-(2-phenoxy-phenyl)-pyridin-2-ylamine; 3-(2,6-dichloro- benzyloxy)-5-(3,4-difluoro-phenyl)-pyridin-2-ylamine; 3-(2,6-dichloro-benzyloxy)-5-(3-isopropyl-phenyl)- pyridin-2-ylamine; 3-(2,6-dichloro-benzyloxy)-5-(2-trifluoromethyl-phenyl)-pyridin-2-ylamine; ~~ 3-(2,6- dichioro-benzyloxy)-5-(2-methoxy-phenyl)-pyridin-2-ylamine; 3-(2,6-dichloro-benzyloxy)-5-(4- trifluoromethyl-phenyl)-pyridin-2-ylamine; N-{2-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yl}-phenyl}- methanesulfonamide; {4-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yl]-phenyl}-methanol; 5- benzol[1,3]dioxol-5-yl-3-(2,6-dichloro-benzyloxy)-pyridin-2-ylamine; 3-(2,6-dichloro-benzyloxy)-5-(2- trifluoromethoxy-phenyl)-pyridin-2-ylamine; 3-(2,6-dichloro-benzyloxy)-5-(4-methyl-thiophen-2-yl)- pyridin-2-ylamine; 5-(2-benzyloxy-phenyl)-3-(2,6-dichloro-benzyloxy)-pyridin-2-ylamine; 3-(2,6-dichloro- benzyloxy)-5-(3-methoxy-phenyl)-pyridin-2-ylamine; 3-(2,6-dichloro-benzyloxy)-5-(1H-indol-2-yl)-pyridin- 2-ylamine; 5-(4-benzyloxy-3-fluoro-phenyl)-3-(2,6-dichloro-benzyloxy)-pyridin-2-ylaming; 4-[6-amino-5- (2,6-dichloro-benzyloxy)-pyridin-3-ylj-benzoic acid; 4-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yl}-
N-(2-diethylamino-ethyl)-benzamide; 4-[B-a2mino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yi]-N-(3- diethylamino-propyl)-benzamide; {4-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yl}-phenyl}-(4-methyl- piperazin-1-yl)-methanone; {4-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yl]-phenyl}-[(2R)-2- pyrrolidin-1-yimsthyi-pyrrolidin-1-yi}-methanone; {4-[6-amino-5-(2,6-dichloro-benzylo:y)-pyridin-3-yi}- phanyl-[(2 S)-2-pyrrolidin-1-yimethyl-pyrrolidin-i-ylJ-rnsthanene; {4-[6-amine-5-(2,6-dichloro-banzyloiy)- pyridin-2-yl]-phenyl}-(4-pyrrolidin-1-yl-piparidin- 1-yl)-methanone; {4-[6-amino-5-(2,6-dichloro-benzyloxy)- pyridin-3-yl}-phenyl}-[4-(2-hydroxy-ethyl)-piperidin- 1-yl]-methanone; {4-[6-amino-5-(2,6-dichloro- benzyloxy)-pyridin-3-yi]-phenyl}-[(3S)-3-dimethylamino-pyrrolidin-1-yll-methanone; ~~ {4-[6-amino-5-(2,6- dichloro-benzyloxy)-pyridin-3-yl]-phenyl}-[(3R)-3-dimethylamino-pyrrolidin-1-yl}-methanone; {4-[6-amino- 5-(2,6-dichloro-benzyloxy)-pyridin-3-yll-phenyl}-[(3 S)-3-cyclopropylaminomethyl-piperidin-1-yl]- methanone; 4-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yl}-N-(2-hydroxy-3-pyrrolidin-1-yl-propyl)- benzamide; {4-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yi}-phenyl}-[(2S)-2-(3-fluoro-piperidin-1- ylmethyl)-pyrrolidin-1-yl]-methanone; {4-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yl}-phenyl}-(4- cyclopropyl-piperazin-1-yl)-methanone; {4-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yi]-phenyl}- - {(2R)-2-[(cyclopropylmethyl-amino)-methyl]-pyrrolidin-1-yl}-methanone; 4-[6-amino-5-(2,6-dichloro- benzyloxy)-pyridin-3-yl]-N-cyclopropylmethyl-N-(2R)-pyrrolidin-2-yimethyl-benzamide; 4-[6-amino-5-(2,6- . dichloro-benzyloxy)-pyridin-3-yl]-N-(2-hydroxy-3-pyrrolidin-1-yl-propyl)-N-methyl-benzamide; {4-[6- amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yi}-phenyl}-{(2S)-2-[(3R)-3-hydroxy-pyrrolidin-1-ylmethyl]- pyrrolidin-1-yl}-methanone; 3-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yl}-benzoic acid; {3-[6- amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yl]-phenyl}-{(2R)-2-pyrrolidin-1-yImethyl-pyrrolidin-1-yl}- methanone; {4-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yl]-phenoxy}-acetic acid; 2-{4-[6-amino-5- (2,6-dichloro-benzyloxy)-pyridin-3-yl]-phenoxy}-1-[(2R)-2-pyrrolidin-1-ylimethyl-pyrrolidin-1-yl}-ethanone;
2-{4-{6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yl}-phenoxy}- 1-[(2 S)-2-pyrrolidin-1-yimethyl-pyrrolidin- 1-yl}-ethanone; 3-(2,6-dichloro-benzyloxy)-5-(1H-indol-5-yl)-pyridin-2-ylamine; 3-(2,6-dichloro- benzyloxy)-5-[3-(1-methyl-1,2,3,6-tetrahydro-pyridin-4-yl)- 1H-indol-5-yi}-pyridin-2-ylamine; 3-(2,6- dichforo-benzyloxy)-5-{3-(1-methyl-piperidin-4-yl)-1 H-indol-5-yl}-pyridin-2-ylamine; 3-(2,6~dichloro- benzyloxy)-5-(3-morpholin-4-ylmethyl-1H-indol-5-yl)-pyridin-2-ylamine; 3-(2,6-dichloro-benzyloxy)-5-(3- piperidin-1-ylmethyl-1H-indol-5-yl)-pyridin-2-ylamine; 3-(2,6-dichloro-benzyloxy)-5-(3-pyrrotidin-1- ylmethyl-1H-indol-5-yl)-pyridin-2-ylamine; 3-(2,6-dichioro-benzyloxy)-5-(3-diethylaminomethyl-1H-indol-
S-yh)-pyridin-2-ylamine; (1-{5-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yl}- 1 H-indol-3-yimethyl}-(3R)- pyrrolidin-3-yl)-carbamic acid tert-butyl ester; 3-(2,6-dichloro-benzyloxy)-5-[3-(2,6-dimethyl-morpholin-4- ylmethyl)-1H-indol-5-yl}-pyridin-2-ylamine; N-(1-{5-[6-amino-5-(2,6-dichioro-benzyioxy)-pyridin-3-yl]-1H- indol-3-ylmethyl}-(3R)-pyrrolidin-3-yl)-acetamide; 1~(4-{5-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-
YI}-1H-indol-3-yImethyl}-piperazin-1-yl)-ethanone; 3-(2-chloro-3,6-diflucro-benzyloxy)-5-(1H-indol-5-yl)- pyridin-2-ylamine; 1-(4-{5-[6-amino-56-(2-chloro-3,6-diflucro-benzyloxy)-pyridin-3-yl]-1H-indol-3-ylmethyl}- piperazin-1-yl)-ethanone; 3-(2-chloro-3,6-difluoro-benzyloxy)-5-[3-(2,6-dimethyl-morpholin-4-yimethyl)- 1H-indol-5-yl}-pyridin-2-ylamine; ~~ N-(1-{5-[6-amino-5-(2-chioro-3,6-difluoro-benzyloxy)-pyridin-3-ylj-1H- indol-3-ylmethyl}-(3S)-pyrrolidin-3-yl)-acetamide; 3-(2-chloro-3,6-difluoro-benzyloxy)-5-(3-piperidin-1- ylmethyl-1H-indol-5-y!)-pyridin-2-ylamine; 3-(2-chloro-3,8-difluoro-benzyloxy)-5-(3-morpholin-4-yimethyl- 1H-indol-5-yl)-pyridin-2-ylamine; 3-(2-chloro-3,6-difluoro-benzyloxy)-5-(3-pyrrolidin-1i-yimethyl-1 H-indol- 5-yl)-pyridin-2-ylamine; 5-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yl]-1H-indole-2-carboxylic acid ethyl ester; 5-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yl]- 1 H-indole-2-carboxylic acid; {5-{6-amino- §-(2,8-dichloro-bznzylo:y)-pyridin-3-yiJ- 1 H-indol-2-y1}-(4-mathyl-piperazin-i-yl)-msthanong; {5-[6-amino- 5-(2,6-dichloro-banzyloxy)-pyridin-3-yil- 1 Atindol-2-vi}-[(3R)-3-dimethyiamino-pyrrolidin-i-y{j-msthanone; {5-{8-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yl}- 1H-indol-2-y}-[(2 R)-2-pyrrolidin-1-yimethyl- pyrrolidin-1-yll-methanone; ~~ 5-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-ylJ- 1H-indole-2-carboxylic acid (2-pyrrolidin-1-yl-ethyl}-amide; 5-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yi]-1H-indole-2- carboxylic acid (2-morpholin-4-yl-ethyl)-amide; (1-{5-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yl}- 1H-indole-2-carbonyl}--(3S)-pyrrolidin-3-yl)-carbamic acid tert-butyl ester; {5-[6-amino-5-(2,6-dichloro- benzyloxy)-pyridin-3-yl}-1H-indol-2-yl}-[(3 S)-3-amino-pyrrolidin-1-yl}-methanone; §-[6-amino-5-(2,6- dichloro-benzyloxy)-pyridin-3-yl}- 1H-indole-2-carboxylic acid (2-hydroxy-3-pyrrolidin-1-yl-propyl)-amide; 4-(6-amino-5-benzyloxy-pyridin-3-yl)-phenol; 3-benzyloxy-5-phenyi-pyridin-2-ylamine; 3-(3-methoxy- benzyloxy)-5-phenyl-pyridin-2-ylamine, 3-(2-chioro-4-fluoro-benzyloxy)-5-phenyl-pyridin-2-ylamine; 3-(2- : chloro-benzyloxy)-5-phenyl-pyridin-2-ylamine; 3-(2,5-dichloro-benzyloxy)-5-phenyl-pyridin-2-ylamine; 3- (2-chloro-5-trifluoromethyl-benzyloxy)-5-phenyl-pyridin-2-ylamine; 3-(2,4-dichloro-5-fluoro-benzyloxy)-5- . phenyl-pyridin-2-ylamine; 3-(2-chloro-3-trifluoromethyi-benzyloxy)-5-phenyl-pyridin-2-ylamine; ~~ 3-(2- chloro-3,6-difluoro-benzyloxy)-5-phenyi-pyridin-2-ylamine; 3-(3,4-dichloro-benzyloxy)-5-phenyl-pyridin-2- ylamine; 2-(2-amino-5-phenyl-pyridin-3-yloxymethyl)-benzonitrile; 3-(2-chloro-6-fluoro-3-methyl- benzyloxy)-5-phenyl-pyridin-2-ylamine; 5-Phenyl-3-(2,3,6-trifluoro-benzyloxy)-pyridin-2-ylamine; 3-(2,6- difluoro-benzyloxy)-6-phenyl-pyridin-2-ylamine; 3-(2,6-difluoro-3-methyl-benzyloxy)-5-phenyl-pyridin-2- ylamine; 3-(3-chloro-2,6-difluoro-benzyloxy)-5-phenyl-pyridin-2-ylamine; 3-(2-chloro-6-fluoro-benzyioxy)-
5-phenyl-pyridin-2-ylamine; ~~ 3-(3-Fluoro-4-methoxy-benzyloxy)-5-phenyl-pyridin-2-ylamine; ~~ N-[3-(2- amino-5-phenyl-pyridin-3-yloxymethyl)-phenyl}-methanesulfonamide; 5-[4-(2-morpholin-4-yl-ethoxy)- : phenyl}-3-(3-nitro-benzyloxy)-pyridin-2-ylamine; 5-[4-(2-morpholin-4-yl-ethoxy)-phenyl]-3-(naphthalen-1- ylmethoxy)-pyridin-2-ylamine; 3-(2-chloro-3,6-difluoro-benzyloxy)-5-{4-(2-morpholin-4-yl-ethoxy)-phenyi]- pyridin-2-ylamine; 2-{2-amino-5-[4-(2-morpholin-4-yl-ethoxy)-phenyl}-pyridin-3-yloxy}-N-(4-isopropyl- phenyl)-2-phenyl-acetamide; 3-(5-chloro-benzo[b]thiophen-3-ylmethoxy)-5-[4-(2-morpholin-4-yl-ethoxy)- phenyl]-pyridin-2-ylamine; {4-[6-amino-5-(4-fluoro-2-trifluoromethyl-benzyloxy)-pyridin-3-yl}-phenyl}- [(2R)-2-pyrrolidin-1-ylmethyl-pyrrolidin-1-yf}-methanone; {4-[6-amino-5-(2-fluoro-6-trifluoromethyl- benzyloxy)-pyridin-3-yl]-phenyi}-[(2R)-2-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl}-methanone; {4-[6-amino-5-
(6-fluoro-2-triflucromethyl-benzyloxy)-pyridin-3-yl}-phenyl}-[(2 R)-2-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl}- methanone; (4-{6-amino-5-[1-(2-trifluoromethyl-phenyl)-ethoxy]-pyridin-3-yl}-phenyl)-[(2R)-2-pyrrolidin-1- yimethyl-pyrrolidin-1-yl]-methanone; {4-[6-amino-5-(2-bromo-benzyloxy)-pyridin-3-yl}-phenyl}-{(2R)-2- pyrrolidin-1-yimethyl-pyrrolidin-1-yl}-methanone; {4-[6-amino-5-(3-fluoro-2-trifluoromethyl-benzyloxy)- pyridin-3-yl]-phenyi}-[(2R)-2-pyrrolidin-1-ylmethyl-pyrroiidin-1-yl}-methanone; {4-[6-amino-5-(2-chloro- 16 3,8-difluoro-benzyloxy)-pyridin-3-yl}-phenyl}-[(2 R)-2-pyrrofidin- i-ylmethyl-pyrrolidin-1-yl}-methanone; 4- [6-amino-5-(2,6-difluoro-benzyloxy)-pyridin-3-yi}-phenot; 3-(2,6-difluoro-benzyloxy)-5-(1H-indol-4-yl)- pyridin-2-ylamine; 3-(2,8-difluoro-benzyloxy)-5-{4-(2-morpholin-4-yl-ethoxy)-phenyl}-pyridin-2-ylamine; 4- [6-amino-5-(2,6-difluoro-benzyloxy)-pyridin-3-vil-benzoic acid; {4-[6-amino-5-(2,6-difluoro-benzyloxy)- pyridin-3-yl}-phenyi}~{(2 R)-2-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl}-methanone; {4-[6-amino-5-(2,6-difluoro- benzyloxy)-pyridin-3-yl}-phenyl}-[(2S)-2-pyrrolidin- 1-ylmethyl-pyrrolidin-1-yl]-methanone; {4-[6-amino-5- (2,6-difluoro-benzyloxy)-pyridin-3-yl}-phenoxy}-acetic acid ethyl ester; {4-[6-amino-5-(2,6-difluoro- benzyloxy)-pyridin-3-yl]-phenoxyl-acstic acid; 2-{4-[6-amino-5-(2,6-difluoro-benzyloiy)-pyridin-3-vi}- phenoxy}-1-[(2R)-2-pyrrolidin- 1-ylimethyl-pyrrolidin-i-yl]-ethanone; 2-{4-[8-amino-5-(2,6-diflucro- benzyloxy)-pyridin-3-yl]-phenoxy}-1-{(2S)-2-pyrrolidin-1-yimethyl-pyrrolidin-1-yl}-ethanone; 4-[6-amino-5- (2-chloro-6-fluoro-benzyloxy)-pyridin-3-yi}-phenol; 4-[6-amino-5-(2-chloro-4-fluoro-benzyloxy)-pyridin-3- yl}-phenol; 4-[6-amino-5-(2,4-dichloro-benzyloxy)-pyridin-3-yi]-phenol; 2-[2-amino-5-(4-hydroxy-phenyl)- pyridin-3-yloxymethyl]-benzonitrile; 4-[6-amino-5-(2-trifluoromethyl-benzyloxy)-pyridin-3-yi}-phenol; 4-[6- amino-5-(2-chloro-benzyloxy)-pyridin-3-yl}-phenol; 4-[6-amino-5-(4-tert-butyl-benzyloxy)-pyridin-3-yl]- phenol; N-{4-[6-amino-5-(2-cyano-benzyloxy)-pyridin-3-yl]-phenyl}-methanesuffonamide; 2-[2-amino-5- (4-methanesulfonylamino-phenyl)-pyridin-3-yloxymethyl]-benzamide; 2-[2-amino-5-(4- methanesulfonylamino-phenyl)-pyridin-3-yloxymethyl]-benzoic ~~ acid; N-(4-{6-amino-5-[2-(4-methyl- . piperazine-1-carbonyl)-benzyloxy]-pyridin-3-yl}-phenyl)-methanesulfonamide; 2-[2-amino-5-(4- methanesulfonylamino-phenyl)-pyridin-3-yloxymethyl]-N-(2-hydroxy-ethyl)-benzamide; 2-[2-amino-5-(4- methanesulfonylamino-phenyl)-pyridin-3-yloxymethyl]-N-isobutyl-benzamide; 4-[6-amino-5-(2-chloro-6- fluoro-benzyloxy)-pyridin-3-yl]-benzoic acid; {4-[6-amino-5-(2-chloro-6-fluoro-benzyloxy)-pyridin-3-yl)- phenyl}-{(2R)-2-pyrrolidin-1-yimethyl-pyrrolidin-1-yl}-methanone; {4-[6-amino-5-(2-chloro-6-fluoro- benzyloxy)-pyridin-3-yi]-phenyl}-[(2S)-2-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl]-methanone; {4-[6-amino-5- (2-chloro-6-fluoro-benzyloxy)-pyridin-3-yl]-phenyi}-[(3 S)-3-dimethylamino-pyrrolidin-1-yl}-methanone; {4- [6-amino-5-(2-chioro-6-fluoro-benzyioxy)-pyridin-3-yl}-phenyl}-[(3S)-3-amino-pyrrolidin-1-yl]-methanone;
{4-[6-amino-5-(2-chloro-6-fluoro-benzyloxy)-pyridin-3-yi}-phenyl}-(4-methyl-piperazin-1-yi}-methanone; 1-(4-{4-[6-amino-5-(2~-chloro-6-flucro-benzyloxy)-pyridin-3-yl}-benzoyl}-piperazin- 1-yl)-ethanone; ~~ 4-[6- amino-5-(2-chloro-6-fluoro-benzyloxy)-pyridin-3-ylj-N-(2-morpholin-4-yl-ethyl)-benzamide; 4-{6-amino-5- (2-chloro-6-fluoro-benzyloxy)-pyridin-3-yl]-N-(3-morpholin-4-yl-propyl)-benzamide; 4-[6-amino-5-(2- chloro-benzyloxy)-pyridin-3-yl}-benzoic acid; {4-{6-amino-5-(2-chloro-benzyloxy)-pyridin-3-y!]-phenyl}- [(2R)-2-pyrrolidin-1-yimethyl-pyrrolidin-1-yl}-methanone; {4-[6-amino-5-(2-chloro-benzyloxy)-pyridin-3-yl]- phenyl}-[(25)-2-pyrrolidin-1-ylmethyl-pyrrolidin-1-yll-methanone; {4-[6-amino-5-(2-chloro-benzyloxy)- pyridin-3-yl]-phenyi}-{(3 S)-3-dimethylamino-pyrrolidin-1-yf]-methanone; {4-[6-amino-5-(2-chloro- benzyloxy)-pyridin-3-yl}-phenyl}-[(3S)-3-amino-pyrrolidin-1-yl}-methanone; {4-[6-amino-5-(2-chloro- benzyloxy)-pyridin-3-yi}-phenyl}-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone; {4-[6-amino-5-(2-chloro- benzyloxy)-pyridin-3-yl]-phenyl}-(4-methyl-piperazin-1-yl)-methanone; 1-(4-{4-{6-amino-5-(2-chloro- benzyloxy)-pyridin-3-yl}-benzoyl}-piperazin-1-yl)-ethanone; 4-[6-amino-5-(2-chloro-benzyloxy)-pyridin-3- yl]-N-(2-morpholin-4-yl-ethyl)-benzamide; 4-[6-amino-5-(2-chioro-benzyloxy)-pyridin-3-yl}-N-(3- morpholin-4-yl-propyl)-benzamide; 4-[6-amino-5-(2-cyano-benzyloxy)-pyridin-3-yl]-benzoic acid; 2-{2- amino-5-[4-((2R)-2-pyrrolidin-1-ylmethyl-pyrrolidine-1-carbonyi)-phenyi}-pyridin-3-yloxymethyl}- benzonitrile; 2-{2-amino-5-[4-((2S)-2-pyrrolidin-1-ylmethyl-pyrrolidine-1-carbonyl)-phenyl}-pyridin-3- yloxymethyl}-benzonitrile; 2-{2-amino-5-{4-((3S)-3-dimethylamino-pyrrolidine- i-carbonyl)-phenyil-pyridin- 3-yloxymethyl}-benzonitrils; 2-{2-amino-5-[4-((3S)-3-amino-pyrrolidine-1-carbenyl)-phenyl}-pyridin-3- yloxymethyi}-benzonitrile, 2-{2-amino-5-{4-(4-pyrrolidin-1-yl-piperidine-1-carbonyl)-phenyl]-pyridin-3- yloxymethyi}-benzonitrile; 2-{2-amino-5-[4-(4-methyl-piperazine-1-carbonyl)-phenyl}-pyridin-3- vlo:xymathyl}-benzonitrile, 2-{5-[4-(4-acatyl-piperazine-1-carbonyl)-phenyl]-2-amino-pyridin-3- yloxymeihyl}-benzonitrile; 4-[6-amino-5-(2-cyano-benzyloxy)-pyridin-3-yi}-M-(i-methyl-piperidin-4-yh)- benzamide; 4-[6-amino-5-(2-cyano-benzyloxy)-pyridin-3-yl]-N-(2-morpholin-4-yl-ethyl)-benzamide; 4-[6- amino-5-(2-cyano-benzyloxy)-pyridin-3-yl]-N-(3-morpholin-4-yl-propyl)-benzamide; ~~ 4-[5-amino-5-(2,4- dichloro-benzyloxy)-pyridin-3-yil-benzoic acid; {4-[6-amino-5-(2,4-dichloro-benzyloxy)-pyridin-3-yl]- phenyl}-[(2R)-2-pyrrolidin-1-ylmethyi-pyrrolidin-1-yl]-methanone; {4-[6-amino-5-(2,4-dichloro-benzyloxy)- pyridin-3-yl}-phenyl}-[(2S)-2-pyrrolidin- 1-yimethyl-pyrrolidin-1-yl}-methanone; {4-[6-amino-5-(2,4- dichloro-benzyloxy)-pyridin-3-yi]-phenyl}-[(3S)-3-dimethylamino-pyrrolidin-1-yl}-methanone; {4-[6-amino- 5-(2,4-dichloro-benzyloxy)-pyridin-3-yl}-phenyl}-[(3S)-3-amino-pyrrolidin-1-ylj-methanone; {4-[6-amino-5- (24-dichloro-benzyloxy)-pyridin-3-yl}-phenyl}-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone; {4-[6-amino-5- (2 4-dichloro-benzyloxy)-pyridin-3-yl}-phenyl}-(4-methyl-piperazin-1 -yl)-methanone; 1-(4-{4-[6-amino-5- : (2 4-dichloro-benzyloxy)-pyridin-3-yl}-benzoyl}-piperazin- 1-yl)-ethanone; 4-[6-aminc-5-(2,4-dichloro- benzyloxy)-pyridin-3-yl]-N-(1-methyl-piperidin-4-yl)-benzamide; 4-[6-amino-5-(2,4-dichloro-benzyloxy)- . pyridin-3-yl]-N-(2-morpholin-4-yl-ethyl)-benzamide; 4-[6-amino-5-(2,4-dichloro-benzyloxy)-pyridin-3-yl]- N-(3-morpholin-4-yl-propyl)-benzamide; 4-{6-amino-5-(2-trifluoromethyl-benzyloxy)-pyridin-3-yi}-benzoic acid; {4-[6-amino-5-(2-trifluoromethyl-benzyloxy)-pyridin-3-yll-phenyl}-{(2 R)-2-pyrrolidin-1-ylmethyl- pyrrolidin-1-yi]-methanone; {4-[6-amino-5-(2-trifluoromethyl-benzyloxy)-pyridin-3-yl]-phenyl}-{(2S)-2- pyrrolidin-1-ylmethyl-pyrrolidin-1-yl}-methanone; {4-[6-amino-5-(2-triflucromethyl-benzyloxy)-pyridin-3- yil-phenyl}-[(3S)-3-dimethylamino-pyrrolidin-1-yl}-methanone; [(3S)-3-amino-pyrrolidin-1-yl}-{4-[6-amino-
) 5-(2-trifluoromethyl-benzyloxy)-pyridin-3-yl}-phenyl}-methanone; {4-[6-amino-5-(2-trifluoromethyl- benzyloxy)-pyridin-3-yl]-phenyl}-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone; {4-[6-amino-5-(2- : trifluoromethyl-benzyloxy)-pyridin-3-ylj-phenyi}-(4-methyl-piperazin-1-yl}-methanone; 1-(4-{4-[6-amino-5- . (2-trifluoromethyl-benzyloxy)-pyridin-3-yl}-benzoyi}-piperazin-1-yl)-ethanone; 4-[6-amino-5-(2- ftrifluoromethyl-benzyloxy)-pyridin-3-yi]-N-(1-methyl-piperidin-4-yl)-benzamide; 4-[6-amino-5-(2- trifiucromethyl-benzyloxy)-pyridin-3-yl}-N~(2-morpholin-4-yl-ethyl)-benzamide; 4-[6-amino-5-(2- trifluoromethyl-benzyloxy)-pyridin-3-yl]-N-(3-morpholin-4-yl-propyl)-benzamide; ~~ 4-[6-amino-5-(4-#tert!- butyl-benzyloxy)-pyridin-3-yl]-benzoic acid; {4-[6-amino-5-(4-teri-butyl-benzyloxy)-pyridin-3-yi]-phenyl}- [(2R)-2-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl]-methanone; {4-[6-amino-5-(4-tert-butyl-benzyloxy)-pyridin-3- yll-phenyi}-[(2S)-2-pyrrolidin-1-yimethyl-pyrrolidin-1-yl]-methanone; {4-[6-amino-5-(4-fert-butyl- benzyloxy)-pyridin-3-yl}-phenyl}-{(3R)-3-dimethylamino-pyrrolidin-1-yl}-methanone; {4-[6-amino-5-(4-teri- butyl-benzyloxy)-pyridin-3-yl}-phenyl}-(4-methyl-piperazin-1-yl)}-methanone; 1-(4-{4-[6-amino-5-(4-tert- butyl-benzyloxy)-pyridin-3-yi]-benzoyl}-piperazin-1-yl)-ethanone; . 4-[6-amino-5-(4-tert-butyl-benzyloxy)- pyridin-3-yl}-N-(1-methyl-piperidin-4-yl)-benzamide; 4-[6-amino-5-(4-tert-butyl-benzyloxy)-pyridin-3-yl}-N- 16 (2-morpholin-4-yl-ethyl)-benzamide; 4-[6-amino-5-(4-ferf-butyl-benzyloxy)-pyridin-3-yi}-N-(3-morpholin-4- yl-propyl)-benzamide; 4-[6-amino-5-(2-chloro-4-fluoro-benzyloxy)-pyridin-3-yl]-benzeic acid; {4-[6-amino-
5-(2-chloro-4-fluoro-benzyloxy)-pyridin-3-yi]-phenyl}-[(2R)-2-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl]- methanone; {4-[B-amino-5-(2-chloro-4-fluoro-benzyloxy)-pyridin-3-yll-pheny}-[(2S)-2-pyrrolidin-i - ylmethyl-pyrrolidin-1-yl]-methanone; {4-[6-amino-5-(2-chloro-4-fluoro-benzyloxy)-pyridin-3-yl]-phenyl}- [(3S)-3-dimethylamino-pyrrolidin-1-yl]-methanone; {4-[6~amino-5-(2-chloro-4-fluorc-benzyloxy)-pyridin-3- yll-phenyl}-(3S)-3-amino-pyrrolidin-1-yll-methanone, {4-]6-a2mino-5-(2-chloro-4-fluoro-benzyloy)- pyridin-3-y(]-phenyl}-(4-methyl-piperazin-i-yl}-methanone; -(4-{4-[6-amino-5-(2-chloro-4-fiuore- banzyloxy)-pyridin-3-yl]-benzoyl}-piperazin-i-yl)-ethanone; 4-[8-amino-5-(2-chloro-4-flucro-benzvio:y)- pyridin-3-yll-N-(2-morpholin-4-yl-ethyl)-benzamide; 4-[6-amino-5-(2-chloro-4-fluoro-benzyloxy)-pyridin-3- yl]-N-(3-morpholin-4-yl-propyl)-benzamide; 4-[6-amino-5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-yi]- benzoic acid; {4-[6-amino-5-(2-chloro-3,6-diflucro-benzyloxy)-pyridin-3-yl]-phenyl}-(4-methyl-piperazin-1- yl)-methanone; {4-[6-amino-5-(2-chioro-3,6-difluoro-benzyloxy)-pyridin-3-yl]-phenyi}-(4-pyrrolidin-1-yl- piperidin-1-yl)-methanone;, {4-[6-amino-5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-yl]-phenyl}-(4- amino-piperidin-1-yl)-methanone; {4-[6-amino-5-(2-chloro-3,6-difiuoro-benzyloxy)-pyridin-3-yl)-phenyi}- (3,5-dimethyl-piperazin-1-yl)-methanone; {4-[6-amino-5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-yl}- phenyl}-[(2S)-2-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl}-methanone; {4-[6-amino-5-(2-chloro-3,6-difluoro- . benzyloxy)-pyridin-3-yl}-pheny!}-[(3S)-3-dimethylamino-pyrrolidin-1-yl]-methanone; {4-[6-amino-5-(2- chloro-3,6-difluoro-benzyloxy)-pyridin-3-yi}-phenyl}-{(3R)-3-amino-pyrrolidin- 1-yl]-methanone; {4-[6- amino-5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-yl]-phenyl}-[(3S)-3-amino-pyrrolidin-1-yl]-methanone; 4-[6-amino-5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-yi}-N-(1-methyl-piperidin-4-yl)-benzamide; 4-[6- amino-5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-yi}-N-(2-pyrrolidin- 1-yl-ethyl)-benzamide; 4-[6-amino- 5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-y(]-N-(3-pyrrolidin-1-yl-propyl)-benzamide; 4-[6-amino-5-(2- chloro-3,6-difluoro-benzyloxy)-pyridin-3-yl}-N-(2-morpholin-4-yl-ethyl)-benzamide; 4-[6-amino-5-(2- chloro-3,6-difluoro-benzyloxy)-pyridin-3-yl}-N-(3-morpholin-4-yi-propyl)-benzamide; 3-[6-amino-5-(2-
chloro-3,6-difluoro-benzyloxy)-pyridin-3-yi]-benzoic acid; {3-[6-amino-5-(2-chioro-3,6-difluoro- benzyloxy)-pyridin-3-yl]-phenyl}-(4-methyl-piperazin-1-yi)-methanone; {3-[6-amino-5-(2-chloro-3,6- : difluoro-benzyloxy)-pyridin-3-yll-phenyl}-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone; {3-[6-amino-5-(2- chloro-3,6-difluoro-benzyloxy)-pyridin-3-yl}-phenyl}-(4-amino-piperidin-1-yl)-methanone; {3-[6-amino-5- (2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-yl}-phenyl}-(3,5-dimethyl-piperazin-1-yl}-methanone; ~~ {3-[6- amino-5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-yl}-phenyl}-[(2S)-2-pyrrolidin-1-ylmethyl-pyrrolidin-1- yll-methanone; {3-[6-amino-5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-yl}-phenyli}-{(3S)-3- dimethylamino-pyrrolidin-1-yl}-methanone; {3-[6-amino-5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-yl}- phenyl}-[(3R)-3-amino-pyrrolidin-1-yl}-methanone; {3-[6-amino-5-(2-chloro-3,6-difluoro-benzyloxy)- pyridin-3-yl}-phenyl}-[(3S)-amino-pyrrolidin-1-yl}-methanone; 3-[6-amino-5-(2-chloro-3,6-difluoro- benzyloxy)-pyridin-3-yl}-N-(1-methy!-piperidin-4-yl)-benzamide; 3-[6-amino-5-(2-chloro-3,6-difluoro- benzyloxy)-pyridin-3-yl}-N-(2-pyrrolidin-1-yl-ethyl)-benzamide,; 3-[6-amino-5-(2-chloro-3,6-difluoro- benzyloxy)-pyridin-3-yl]-N-(3-pyrrolidin-1-yl-propyl)-benzamide; 3-[6-amino-5-(2-chloro-3,6-difluoro- benzyloxy)-pyridin-3-yl]-N-(2-morpholin-4-yl-ethyl)-benzamide; 3-[6-amino-5-(2-chloro-3,6-difluoro- benzyloxy)-pyridin-3-y{]-N-(3-morpholiin-4-yl-propyl)-benzamide; ~~ N-[2-(4-acetyl-piperazin-1-yl)-ethyl}-3- [6-amino-5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-yl]-benzamide; 3-(2-chloro-3,6-difluoro- benzyloxy)-5-[4-(1,1-dioxo-1 AL-isothiazolidin-2-yl)-phenyi]-pyridin-2-yleming; 3-(2 6-dichloro-benzyloxy)- 5-[4-(1 ,1-dioxo-1A%-isothiazolidin-2-yl)-phenyl}-pyridin-2-ylaming; 5-{4-(1,1-dioxo-1 A%-isothiazolidin-2-yl)- phenyl]-3-(2-fluoro-6-trifluoromethyi-benzyloxy)-pyridin-2-ylamine; 2-diethylamino-ethanesulfonic acid {4-[6-amino-5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-yi]-phenyi}-amide; 2-cyclopropylamino- ethanssulfonic zcid {4-[6-aminc-5-(2-chloro-3,6-difluoro-benzylosy)-pyridin-3-yll-phenyll-amide; 2-
Pyrrolidin-1-yl-ethanseulfonic acid {4-[6-amino-5-(2-chiore-3,8-diflucro-benzyloxy)-pyridin-3-vil-phenyl}- amide; 2-(4-hydroxy-piperidin-1-yl)-ethanesulfonic acid {4-[6-amino-5-(2-chioro-3,6-difluoro-benzylaxy)- pyridin-3-yll-phenyf}-amide; 2-morpholin-4-yi-ethanesulfonic acid {4-[6-amino-5-(2-chloro-3,6-difiluoro- benzyloxy)-pyridin-3-yl]-phenyl}-amide; 2-Piperidin-1-yi-ethanesulfonic acid {4-[6-amino-5-(2-chloro-3,6- difluoro-benzyloxy)-pyridin-3-yl}-phenyl}-amide; 2-dimethylamine-ethanesulfonic acid {4-{6-amino-5-(2- chloro-3,6-difluoro-benzyloxy)-pyridin-3-yl]-phenyl}-amide; 2-(4-acetyl-piperazin-1-yl)-ethanesulfonic acid {4-[6-amino-5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-yi]-phenyl}-amide; 2-(cyclopropylmethyl- amino)-ethanesulfonic acid {4-[6-amino-5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-yl]-phenyl}-amide; 2-[(3R)-3-hydroxy-pyrrolidin-1-yl}-ethanesulfonic acid {4-[6-amino-5-(2-chloro-3,6-difluoro-benzyloxy)- pyridin-3-yl]-phenyl}-amide; 2-[(2S)-2-hydroxymethyl-pyrrolidin-1-yi]-ethanesulfonic acid {4-[6-amino-5- . (2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-y{]-phenyl}-amide; 2-[4-(2-hydroxy-acetyl)-piperazin-1-ylj- ethanesulfonic acid {4-[6-amino-5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-yl]-phenyl}-amide; 2-(4- ] acetyl-piperazin-1-yl)-ethanesulfonic acid {3-[6-amino-5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-yl}- phenyl}-amide; 2-Pyrrolidin-1-yl-ethanesulfonic acid {3-[6-amino-5-(2-chloro-3,6-difluoro-benzyloxy)- pyridin-3-yl}-phenyl}-amide; 2-morpholin-4-yl-ethanesulfonic acid {3-[6-amino-5-(2-chloro-3,6-difluoro- benzyloxy)-pyridin-3-yl]-phenyl}-amide; 2-diethylamino-ethanesulfonic acid {3-[6-amino-5-(2-chloro-3,6- difluoro-benzyloxy)-pyridin-3-yl]-phenyl}-amide; 2-dimethylamino-ethanesulfonic acid {3-[6-amino-5-(2- chloro-3,6-difluoro-benzyloxy)-pyridin-3-yl]-phenyl}-amide; 2-Piperidin-1-yl-ethanesulfonic acid {3-[6-
amino-5-(2-chioro-3,6-difluoro-benzyloxy)-pyridin-3-yl}-phenyl}-amide; 2-[(3R)-3-hydroxymethy!- pyrrolidin-1-yl}-ethanesulfonic acid {3-[6-amino-5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-yi}-phenyl}- ) amide; 2-(4-hydroxy-piperidin-1-yl)-ethanesulfonic acid {3-[6-amino-5-(2-chioro-3,6-difluoro-benzyloxy)- pyridin-3-yl]-phenyl}-amide; 2-[4-(2-hydroxy-acetyl)-piperazin-1-yl]-ethanesulfonic acid {3-[6-amino-5-(2- chloro-3,6-difluoro-benzyloxy)-pyridin-3-yl]-phenyl}-amide; 2-[(3R)-3-hydroxy-pyrrolidin-1-yl}- ethanesulfonic acid {3-[6-amino-5-(2-chloro-3,6-diflucro-benzyloxy)-pyridin-3-yi}-phenyi}-amide; 2- (cyclopropylmethyl-amino)-ethanesulfonic acid {3-[8-amino-5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin-3- yll-phenyl}-amide; 2-cyclopropylamino-ethanesulfonic acid ~~ {3-[6-amino-5-(2-chloro-3,6-difiuoro- benzyloxy)-pyridin-3-yl}-phenyl}-amide; 3-(2-chloro-3,6-difluoro-benzyloxy)-5-(2-dimethylaminomethyl- pheny!)-pyridin-2-ylamine; compound with trifluoro-acetic acid; 3-(2-chloro-3,6-difluoro-benzyloxy)-5-(3- pyrrolidin-1-yl-phenyl)-pyridin-2-ylamine; compound with triflucro-acetic acid; N-{4-[6-amino-5-(2-chloro- 3,6-difluoro-benzyloxy)-pyridin-3-yi}-phenyl}-methanesutfonamide; compound with trifluoro-acetic acid; 5-[6-amino-5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-yl]-thiophene-2-carboxylic acid; {5-[6-amino-5- (2-chloro-3,6-diflucro-benzyloxy)-pyridin-3-yl}-thiophen-2-yl}-(4-methyl-piperazin-1-yl)-methanone; {5-[6- 16 amino-5-(2-chioro-3,6-difluoro-benzyloxy)-pyridin-3-yl]-thiophen-2-y[}-[(2R)-2-pyrrolidin-1-yimethyl- pyrrolidin-1-yl}-methanone; 5-{6-amino-5-(2-chlaro-3,8-difluore-benzyloxy)-pyridin-3-yl}-thiophene-2- carboxylic acid (1-methyl-piperidin-4-yl)-amide; {5-[6-amino-5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin- 3-yli-thiophen-2-yl}-(3,5-dimethyl-pinerazin- 1-yl)-methanons; §-[6-amino-5-(2-chloro-3,6-difluoro- benzyloxy)-pyridin-3-yi}-thiophene-2-carboxylic acid (2-pyrrolidin-1-yl-ethyl)-amide; {5-[6-amino-5-(2- chioro-3,6-difluoro-benzyloxy)-pyridin-3-yl]-thiophen-2-yi}-(4-pyrrolidin- 1-yl-piperidin-1-yl)-methanone; 4- {6-amino-8-(3-fluoro-2-trifluoromethyl-benzylo:xy)-pyridin-3-vil-benzoic acid; {4-{6-zmino-5-(3-fluoro-2- triflucromathyl-banzyloxy)-pyridin-3-yll-phenyl}-(4-pyrrolidin-1-yl-pipzridin-i-yl)-meihznons; 4-[6-amino- 5-(3-fluoro-2-trifluoromethyl-benzylo:y)-pyridin-3-yI)-N-(1-methyl-piperidin-4-yl)-benzamide; {4-[6-aminc- 5-(3-fluoro-2-trifluoromethyl-benzyloxy)-pyridin-3-yl]-phenyl}-(3,5-dimethyl-piperazin-1-yl)-methanone; {4-[6-amino-5-(3-fluoro-2-trifluoromethyl-benzyloxy)-pyridin-3-yi]-phenyl}-(3-dimethylamino-pyrrolidin-1- yl)-methanone; {4-[6-amino-5-(3-fluoro-2-trifluoromethyl-benzyloxy)-pyridin-3-yi}-phenyl}-{(2 S)-2- pyrrolidin-1-ylmethyl-pyrrolidin-1-yl}-methanone; 4-[6-amino-5-(3-fluoro-2-trifluoromethyl-benzyloxy)- pyridin-3-yl}-#N!-(2-morpholin-4-yl-ethyl)-benzamide; {4-[6-amino-5-(3-fluoro-2-trifiluoromethyl- benzyloxy)-pyridin-3-yl}-phenyl}-(4-methyl-piperazin-1-yl)-methanone; N-[2-(4-acetyl-piperazin-1-yi)- ethyl)-4-[6-amino-5-(3-fluoro-2-trifluoromethyl-benzyloxy)-pyridin-3-yl]-benzamide; 2-Piperidin-1-yl- ethanesulfonic acid (4-{6-amino-5-[1-(2-chloro-3,6-difluoro-phenyl)-ethoxy]-pyridin-3-yl}-phenyl)-amide; } 2-(4-hydroxy-piperidin-1-yf)-ethanesulfonic acid (4-{6-amino-5-[1-(2-chloro-3,6-difluoro-phenyi)-ethoxyl- pyridin-3-yl}-phenyl)-amide; 2-dimethylamino-ethanesulfonic acid (4-{6-amino-5-[1-(2-chloro-3,6-diflucro- . phenyl)-ethoxy}-pyridin-3-yl}-phenyl)-amide; 2-cyclopropylamino-ethanesulfonic acid (4-{6-amino-5-[1- (2-chloro-3,6-diflucro-phenyl)-ethoxyl-pyridin-3-yi}-phenyl)-amide; 4-{6-amino-5-[1-(2,6-dichioro-3-fluoro- phenyl)-ethoxy]-pyridin-3-yl}-benzoic acid; (4-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]- pyridin-3-yl}-phenyl)-[(2R)-2-pyrrolidin-1-yimethyl-pyrrolidin- 1-yl)-methanone; 4-{6-amino-5-[1-(2,6- dichloro-3-fluoro-phenyi)-ethoxy]-pyridin-3-yl}-N-(1-methyi-piperidin-4-yl)-benzamide; (3-{6-amino-5-[1- (2,6-dichioro-3-fluoro-phenyl)-ethoxyl-pyridin-3-yl}-phenyl)-[(3R)-3-amino-pyrrolidin-1-yh}-methanone;
(4-{6-amino-5-[1-(2,6-dichioro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-phenyl)-(4-pyrrolidin-1-yl-piperidin-1- yl)-methanone; (4-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy}-pyridin-3-yl}-phenyl)-(4-methyl- piperazin-1-yl)-methanone; (4-{6-amino-5-[1-(2,6-dichioro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-phenyl)- (3,5-dimethyl-piperazin-1-yl)-methanone; 2-cyclopropylamino-ethanesulfonic acid (4-{8-amino-5-[1-(2,6- dichioro-3-fluoro-phenyl)-ethoxyl-pyridin-3-yi}-phenyl)-amide; 2-dimethylamino-ethanesulfonic acid (4-{6- amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-phenyl)-amide; 2-[(3R)-3-hydroxy- pyrrolidin-1-yl)}-ethanesulfonic acid (4-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}- phenyl)-amide; and pharmaceutically acceptable salts, hydrates and solvates thereof.
In another embodiment, the invention provides a compound selected from the group consisting of 4-[5-amino-6-(2,6-dichloro-benzyloxy)-pyrazin-2-yl}-phenol; 3-(2,6-dichloro-benzyloxy)-5-[4-(1,1- dioxo-12 -isothiazolidin-2-y!)-phenyl]-pyrazin-2-ylamine; 3-(2,6-dichloro-benzyloxy)-5-[3-(2-morpholin-4- yl-ethoxy)-phenyi}-pyrazin-2-ylamine; 3-(2,6-dichloro-benzyloxy)-5-[4-(2-morpholin-4-yl-ethoxy)-phenyl}- pyrazin-2-ylamine; 5-(4-amino-phenyi)-3-(2,6-dichloro-benzyloxy)-pyrazin-2-ylamine; 4-[5-amino-6-(2,6- dichloro-benzyloxy)-pyrazin-2-yl}-benzoic acid; {4-[5-amino-6-(2,6-dichloro-benzyloxy)-pyrazin-2-yl}- 16 phenyl}-[(2R)-2-pyrrolidin-1-yimethyl-pyrralidin-i-yi}-methanons; {4-[5-amino-6-(2,6-dichloro-benzyloxy)- pyrazin-2-yl]-phenyl}-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanons; 2-morpholin-4-yl-ethanesulfonic acid {4-[5-amino-6-(2-chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yil-phenyl}-amide; 2-piperidin-1-yl- ethanesulfonic zcid {4-[5-amino-8-(2-chloro-3 8-difluoro-benzyloxy)-pyrazin-2-yll-phenyl}-emide; 2-(4-
Hydroxy-piperidin-1-y!)-ethanesulfonic acid {4-[5-amino-6-(2-chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yl}- phenyl}-amide; 2-pyrrolidin-1-yl-ethanesulfonic acid {4-[5-amino-6-(2-chloro-3,6-difluoro-benzyloxy)- pyrazin-2-yil-phenyl}-amids; 2-[(3R)-3-Hydroxy-pyrrelidin-1-yl}-sthanssulfonic zcid {4-]8-amino-6-(2- chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yil-phenyl}-amids; 2-[(25)-2-Hydroxymethyl-pyrrolidin-i-yi]- sthanasulfonic acid {4-[5-amino-6-(2-chloro-3,6-difluoro-benzyloiy)-pyrazin-2-yl}-phenyl}-amids; 2- (cyclopropylmethyl-amino)-ethanesulfonic acid {4-[5-amino-6-(2-chloro-3,6-difluoro-benzyloxy)-pyrazin- 2-yll-phenyl}-amide; 2-dimethylamino-ethanesulfonic acid {4-[5-amino-6-(2-chloro-3,6-difluoro- benzyloxy)-pyrazin-2-yl}-phenyl}-amide; 2-diethylamino-ethanesulfonic acid {4-{5-amino-6-(2-chloro-3,6- difluoro-benzyloxy)-pyrazin-2-yl}-phenyl}-amide; 2-(4-acetyl-piperazin-1-yl)-ethanesulfonic acid {4-[5- amino-6-(2-chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yll-phenyl}-amide; 2-{4-(2-Hydroxy-acetyl)- piperazin-1-yl]-ethanesulfonic acid {4-[5-amino-6-(2-chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yl}-phenyi}- amide; 2-cyclopropylamino-ethanesulfonic acid {4-[5-amino-6-(2-chloro-3,6-difluoro-benzyloxy)-pyrazin- 2-yl]-phenyl}-amide; 2-[(3R)-3-Hydroxymethyl-pyrrolidin-1-yl]-ethanesulfonic acid {3-[5-amino-6-(2- ’ chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yl}-phenyl}-amide; 2-(4-Hydroxy-piperidin-1-yl)-ethanesulfonic acid {3-[5-amino-6-(2-chloro-3 6-difluoro-benzyloxy)-pyrazin-2-yi}-phenyl}-amide; 2-(4-acetyl-piperazin- : 1-yl)-ethanesutfonic acid {3-[5-amino-6-(2-chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yij-phenyl}-amide; 2- piperidin-1-yl-ethanesulfonic acid {3-[5-amino-6-(2-chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yl}-phenyl}- amide; 2-diethylamino-ethanesulfonic acid {3-[5-amino-6~(2-chioro-3,6-difluoro-benzyloxy)-pyrazin-2-yll- phenyl}-amide; 2-morpholin-4-yi-ethanesulfonic acid {3-[5-amino-6-(2-chloro-3,6-difluoro-benzyloxy)- pyrazin-2-yl}-phenyl}-amide; 2-pyrrolidin-1-yl-ethanesulfonic acid {3-[5-amino-6-(2-chioro-3,6-difluoro- benzyloxy)-pyrazin-2-yil-phenyi}-amide; 2-dimethylamino-ethanesulfonic acid {3-[5-amino-6-(2-chioro-
3,6-difluoro-benzyloxy)-pyrazin-2-yi]-phenyl}-amide; 2-{4-(2-Hydroxy-acetyl)-piperazin-1-yl]- } ethanesulfonic acid {3-[5-amino-6-(2-chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yl}-phenyl}-amide; 2- (cyclopropylmethyl-amino)-ethanesulfonic acid {3-[5-amino-6-(2-chioro-3,6-difluoro-benzyloxy)-pyrazin- 2-yl}-phenyi}-amide; 2-[(3R)-3-Hydroxy-pyrrolidin-1-yi]-ethanesulfonic acid {3-[{5-amino-6-(2-chloro-3,6- difluoro-benzyloxy)-pyrazin-2-yl}-phenyl}-amide; 2-cyclopropylamino-ethanesulfonic acid {3-[5-amino-6- (2-chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yl}-phenyl}-amide; 4-[5~-amino-6-(2-chloro-3,6-difluoro- benzyloxy)-pyrazin-2-yl}-benzoic acid; {4-[5-amino-6-(2-chloro-3,6-diflucro-benzyloxy)-pyrazin-2-yl}- phenyl}-[(2R)-2-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl}-methanone; 4-[5-amino-6-(2-chioro-3,6-difluoro- benzyloxy)-pyrazin-2-yl}-N-(2-pyrrolidin-1-yl-ethyl)-benzamide; {4-[5-amino-6-(2-chlore-3,6-difluore- benzyloxy)-pyrazin-2-ylJ-phenyl}-(3 S)-3-amino-pyrrolidin-1-y{]-methanone; N-[2-(4-acetyl-piperazin-1- yl)-ethyl}-4-[5-amino-6-(2-chioro-3,6-difluoro-benzyloxy)-pyrazin-2-yl]-benzamide; 4-[5-amino-6-(2- chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yi]-N-(3-pyrrolidin-1-yl-propyl)-benzamide; {4-[5-amino-6-(2-
chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yl}-phenyi}-{(3 S)-3-dimethylamino-pyrrolidin-1-yl}-methanone; {4-[5-amino-6-(2-chloro-3,6-diflucro-benzyloxy)-pyrazin-2-yl]-phenyl}-{(3R)-3-dimethylamino-pyrrolidin-1- 16 yi}-methanone; {4-[5-amino-6-(2-chioro-3,6-difluoro-bsnzyloxy)-pyrazin-2-yl-phenyl}-(3,5-dimethyl- piperazin-1-yl)-methanone; {4-[5-amino-6-(2-chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yl]-phenyl}-(4- pyrrolidin-1-yl-piperidin-1-yl)-methanone; 4-[5-amino-6-(2-chioro-3,6-difluoro-benzyloxy)-pyrazin-2-yli}-N- (3-morpholin-4-yl-propyl)-benzzamide; 4-[B-amino-6-(2-chloro-3,6-diflucro-benzyloxy)-pyrazin-2-yi}-N-(1- methy!-piperidin-4-yl)-benzamide; 4-[5-amino-6-(2-chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yi}-N-(2- morpholin-4-yl-ethyl)-benzamide; {4-[5-amino-6-(2-chloro-3,6-diflucro-benzyloxy)-pyrazin-2-yl]-phenyl}- (4-mzihyi-piperazin-i-yl)-methanone; 3-[5-z2mino-6-(2-chloro-3,6-difluora-benzyloxy)-pyrazin-2-¥ij- benzoic acid; {3-[5-2mino-6-(2-chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yll-phenyl-(4-msthyl-piperazin- i-yl)-methanone, {3-[5-amine-6-(2-chloro-3,8-difluare-benzyloxy)-pyrezin-2-yl}-phenyl}-[(3R)-2-armino- pyrrolidin-1-yl}-methanone; {3-[5-amino-6-(2-chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yl}-phenyl}-[(3 S)-3- amino-pyrrolidin-1-yl}methanone; {3-[5-amino-6-(2-chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yl}-phenyl}- (3,5-dimethyl-piperazin-1-yl)-methanone; 3-[5-amino-6-~(2-chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yl}-N- (3-morpholin-4-yi-propyl)-benzamide; {3-[5-amino-6-(2-chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yl}- phenyl}-(4-pyrrolidin- 1-y-piperidin-1-yl)-methanone; {3-[5-amino-6-(2-chloro-3,6-difluoro-benzyloxy)- pyrazin-2-yl}-phenyl}-[(35)-3-dimethylamino-pyrrolidin-1-yl}-methanone; 3-[5-amino-6-(2-chloro-3,6- difluoro-benzyloxy)-pyrazin-2-yl}-N-(2-pyrrolidin-1-yl-ethyl)-benzamide; 3-[5-amino-6-(2-chioro-3,6- difluoro-benzyloxy)-pyrazin-2-yl]-N-(1-methyl-piperidin-4-yl)-benzamide; {3-[5-amino-6-(2-chioro-3,6- ’ difluoro-benzyloxy)-pyrazin-2-ylj-phenyi}-[(2S)-pyrrolidin-1-yimethyl-pyrrolidin-1-yi}-methanone; 3-[5- amino-6-(2-chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yi}-N-(2-morpholin-4-yl-ethyl)-benzamide; N-[2-(4- . acetyl-piperazin-1-yl)-ethyl}-3-[5-amino-6-(2-chioro-3,6-difluoro-benzyloxy)-pyrazin-2-ylj-benzamide, 3- [5-amino-6-(2-chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yl}-N-(3-pyrrolidin-1-yl-propyl)-benzamide; 3-(2- chloro-3,6-difluoro-benzyloxy)-6-(1 H-indol-5-yl)-pyrazin-2-ylamine; 3-(2-chloro-3,6-difluoro-benzyloxy)-5- (3-pyrrolidin-1-ylmethyl-1H-indol-5-yl)-pyrazin-2-ylamine; 3-(2-chloro-3,6-difluoro-benzyloxy)-5-(3- diethylaminomethyl-1H-indol-5-yi)-pyrazin-2-ylamine; 1-(4-{5-[5-amino-6-(2-chloro-3,6-difluoro- benzyloxy)-pyrazin-2-yl}- 1H-indol-3-ylmethyi}-piperazin-1 -yl)-ethanone; 3-(2-chloro-3,6-difluoro-
benzyloxy)-5-[3-(2,6-dimethyl-morpholin-4-ylmethyl)-1H-indol-5-yi]-pyrazin-2-ylamine; N-(1-{5-[5-amino- 6-(2-chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yl}-1 H-indol-3-ylmethyf}-(3S)-pyrrolidin-3-yl)-acetamide; 3- } (2-chloro-3,6-difluoro-benzyloxy)-5-(3-piperidin-1-yimethyl-1H-indol-5-yl)-pyrazin-2-ylamine; 3-(2-chloro- 3,6-difluoro-benzyloxy)-5-(3-morpholin-4-ylmethyl-1H-indol-5-yl)-pyrazin-2-ylamine; 3-{1-(2-chloro-3,6- difluoro-phenyl)-2-methyl-propoxy]-5-[4-(2-morpholin-4-yl-ethoxy)-phenyl}-pyrazin-2-ylamine; 3-1-(2- chiore-3,6-difluoro-phenyl)-ethoxyl-5-[4-(2-morpholin-4-yl-ethoxy)-phenyi)-pyrazin-2-ylamine; compound with trifluoro-acetic acid; 3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5-[4-(2-morpholin-4-yi-ethoxy)- phenyl]-pyrazin-2-ylamine; compound with trifluoro-acetic acid; N-(4-{5-amino-6-[1-(2-chloro-3,6- difluoro-phenyl)-ethoxy}-pyrazin-2-yl}-phenyl)-methanesulfonamide; 2-pyrrolidin-1-yl-ethanesulfonic acid (4-{5-amino-6-[1-(2-chloro-3,6-difluoro-phenyl)-ethoxyl-pyrazin-2-yl}-phenyl)-amide; 2-(4-Hydroxy- piperidin-1-yl)-ethanesulfonic acid (4-{5-amino-6-[1-(2-chloro-3,6-difluoro-phenyl)-ethoxyl-pyrazin-2-yl}- phenyl)-amide; 2-piperidin-1-yl-ethanesulfonic acid (4-{5-amino-6-[1-(2-chloro-3,6-difluoro-phenyl)- ethoxy}-pyrazin-2-yl}-phenyl)-amide; 2-(cyclopropylmethyl-amino)-ethanesulfonic acid (4-{5-amino-6-[1- (2-chloro-3,6-difluoro-phenyl)-ethoxyl-pyrazin-2-yl}-phenyl)-amide; 2-[(3R)-3-Hydroxy-pyrrolidin-1-yl]- 16 ethanesulfonic acid (4-{5-amino-6-[1-(2-chloro-3,6-difluoro-phenyl)-sthoxy]-pyrazin-2-yl}-phenyl)-amide; 2-[(2S)-2-Hydroxymethyl-pyrrolidin-1-yi]-ethanesulionic acid (4-{5-amino-6-{1-(2-chloro-3,6-difluoro- phenyl)-ethoxyl-pyrazin-2-yl}-phenyl)-amide; 2-dimethyleminc-ethanesulfonic acid (4-{5-amino-8-{1-(2- chloro-3,6-difluoro-phenyl)-ethoxyl-pyrazin-2-yl}-phenyl)-amide; 2-morpholin-4-yl-ethanesulfenic acid (4- {5-amino-6-[1-(2-chloro-3,6-difluoro-phenyl)-ethoxy)-pyrazin-2-yl}-phenyl)-amide; 2-diethylamino- ethanesuifonic acid (4-{5-amino-6-[1-(2-chloro-3,6-difluoro-phenyl)-ethoxy]-pyrazin-2-yl}-phenyl)-amide; 2-cyclopropylamino-sthanesulfonic acid (4-{§-amino-6-[1-(2-chloro-3,6-difluore-phenyl)-ethoxyl-pyrazin- 2-yl}-phenyl)-amide; 3-{5-amino-6-[i-(2,8-dichloro-3-flucro-phenyi)-ethoxy]-pyrazin-2-yli-benzoic acid; (3-{5-amino-5-[1-(2,6-dichlore-3-fluoro-phenyl)-ethoxy]-pyrazin-2-yi}-phenyl)-{(35)-3-amino-pyrrolidin-1- yl)-m-zthanone; (3-{5-amino-6-[1-(2,6-dichloro-3-flucro-phenyl)-ethoxyl-pyrazin-2-yl}-phenyl)-{(3R)-3- amino-pyrrolidin-1-yl}-m-ethanone; (3-{5-amino-6-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy}-pyrazin-2-yl}- phenyl)-[(2R)-2-pyrrolidin-1-yimethyl-pyrrolidin-1-yl)-methanone; N-[2-(4-acetyl-piperazin-1-yl)-ethyl]-3- {5-amino-6-[1-(2,6-~dichloro-3-fluoro-phenyl)-ethoxy]-pyrazin-2-yl}-benzamide; (3-{5-amino-6-[1-(2,6- dichioro-3-fluoro-phenyl)-ethoxy]-pyrazin-2-yi}-phenyl)-[(2 S)-2-pyrrolidin-1-yimethyl-pyrrolidin-1-yl)- methanone; 3-{5-amino-6-{1-(2-chloro-3,6-difluoro-phenyl)-ethoxy]-pyrazin-2-yl}- benzoic acid; 3-{5- amino-6-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyrazin-2-yl}-N-(1-methyl-piperidin-4-yl)-benzamide; 3- {5-amino-6-{1-(2,6-dichloro-3-fluoro-phenyl)-ethoxyl-pyrazin-2-yl}-N-(3-pyrrolidin-1-yl-propyl)-benzamide; . (3-{5-amino-6-[1-(2,6-dichioro-3-fluoro-phenyl)-ethoxy}-pyrazin-2-yl}-phenyl)-(4-pyrrolidin-1-yl-piperidin- 1-yl)-methanone; 4-[5-amino-6-(3-fluoro-2-trifluoromethyl-benzyloxy)-pyrazin-2-ylj-benzoic acid; 4-{5- . amino-6-(3-fluoro-2-trifluoromethyl-benzyloxy)-pyrazin-2-yl}-N-(2-morpholin-4-yl-ethyl)-benzamide; 4-[5- amino-6-(3-fluoro-2-trifluoromethyl-benzyloxy)-pyrazin-2-yl]-N-(1-methyl-piperidin-4-yl)-benzamide; and pharmaceutically acceptable salts, hydrates and solvates thereof.
In another embodiment, the invention provides a compound selected from the group consisting of. (4-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-pheny!)-(4-methyl-piperazin-1-yl)- methanone; N-[2-(4-acetyl-piperazin-1-yl)-ethyl]-4-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy}-

Claims (55)

We Claim:
1. A compound of formula 1 R! 2 A i 1 A's ~~ NH, wherein: Yis Nor CR"; R' is selected from Ce.12 aryl, 5-12 membered heteroaryl, C34, cycloalkyl, 3-12 membered heteroalicyclic, -O(CR°R"),R", -C(O)R?, -C(O)OR*, -CN, -NOj, -S(O)nR*, -SO:NR'R®, -C(O)NR'R’, -NR'C(O)R®, -C(=NR®)NR’R®, Cy alkyl, C, alkenyl, and C,; alkynyl; and each hydrogen in R' is optionally substituted by one or more Rr? groups; Ris hydrogen, halogen, Cy.12 alkyl, Ca.12 alkenyl, Coq» alkynyl, Cs.1, cycloalkyl, Ce4y aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, -S(O)mR?, -SO,NR*R®, -S(0),0R?, -NO,, ~-NR'R®, «CR°R)OR?, -CN, -C(O)R!, -OCO)R’, -O(CR°R).R‘ -NR'C(O)R’, -(CR’R').C(O)OR", <CR°R)NCR'R®, -C(=NRNR'R?, -NR*C(O)NR®R®, -NR*S(0),R® or -C(O)NR’R®, and each hydrogen in R?is optionally substituted by ons or more R® groups; 16 Ris halogen, Cq.42 alkyl, Ca.42 alkenyl, C,.12 alkynyl, C34, cycloalkyl, Cg 2 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, -S(O),R*, -SONR'R®, -S(0),0R%, -NO, -NR°R’, -CR°R"):OR’, -CN, -C(O)R', -OCO)R’, -OCRR)R' -NR‘CO)R’, -(CRR").C(O)OR’, ~(CR°R")NCR'R’, -C(=NR®NR'R®, -NR*C(O)NR°R’, -NR*S(0),R° or -C(O)NR'R®, each hydrogen in R® is optionally substituted by one or more R® groups, and Rr? groups on adjacent atoms may combine to form a Ce.12 aryl, 5-12 membered heteroaryl, Cs 42 cycloalkyl or 3-12 membered heteroalicyclic group; each R%, R®, R® and R’ is independently hydrogen, halogen, Ci.i alkyi, Ca.12 alkenyl, Caz alkynyl, Cs.12 cycloalkyl, Ce.12 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl; or any two of R*, R®, R® and R’ bound to the same nitrogen atom may, together with the nitrogen to which they are bound, be combined to form a 3 to 12 membered heteroalicyclic or 5-12 membered heteroaryl group optionally containing 1 to 3 additional heteroatoms selected from N, O, and S; or any two of R*, R®, R® and R’ bound to the same carbon atom may be combined to form a Cz, cycloalkyl, Cg 4, aryl, 3-12 : membered heteroalicyclic or 5-12 membered heteroaryl group; and each hydrogen in R*, R®, R® and R’ is optionally substituted by one or more R® groups; each R® is independently halogen, Cy, alkyl, Cz.12 alkenyl, C,.12 alkynyl, Caz cycloalkyl, Ce.12 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, -CN, -O-C1.1z alkyl, -O-(CHz)xCs.12 cycloalkyl, -O-(CH2)nCe-12 aryl, -O-(CHz)a(3-12 membered heteroalicyclic) or -O-(CHy)n(5-12 membered heteroaryl); and each hydrogen in R® is optionally substituted by one or more R'! groups;
A'is —(CR°R"%),-A? except that: ‘ (i) when Y is N and R'is substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl, A' is ~(CR°R""),-A? and n is not zero; and (i) when Y is N and R? is H and A' is m-chiorobenzyl, R' is not unsubstituted piperazine; each R® and R" is independently hydrogen, halogen, Ci.12 alkyl, Ca.12 cycloalkyl, Ce 12 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, -S(O)nR*, -SO:NR*R®, -S(0),0R", -NO;, -NR*R’, (CR°R)OR*, CN, -C(O)R', -OC(O)R‘, -NR'C(O)R®, -(CR°R".C(O)OR’, -(CR°R").NCR'R’, -NR'C(O)NR®R®, -NR*S(0),R° or -C(O)NR*R®; R® and R'® may combine to form a Caz cycloalkyl, 3-12 membered heteroalicyclic, Cs.12 aryl or 5-12 membered heteroaryl ring; and each hydrogen in R® and R'is optionally substituted by one or more R® groups; A? is C42 aryl, 5-12 membered heteroaryl, Cs, cycloalkyl or 3-12 membered heteroalicyclic, and A is optionally substituted by one or more R® groups; each R'' is independently halogen, Cy.42 alkyl, Cy.12 alkoxy, Cs.p cycloalkyl, Ce2 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, -O-Cy.q2 alkyl, -O-(CH2),Cz12 cycloalkyl, -O- (CH) Ce.12 aryl, -O-(CHz)n(3-12 membered heteroalicyclic), -O-(CHp)s(5-12 membered heteroaryl) or -CN, and each hydrogen in R'! is optionally substituted by one or more groups selected from halogen, -OH, -CN, -C.12 alkyl which may be partially or fully halogenated, -O-Cy.12 alkyl which may be partially or fully halogenated, -CO, -SO and -SOq; R'2 is hydrogen, halogen, C1.12 alkyl, Cz.12 alkenyl, Cz. alkynyl, Ca, cycloalkyl, Coz aryl, 3-12 membered hetsroalicyclic, 5-12 membered heteroaryl, -S(O)mR*, -SO:NR*R®, -5(0);0R*, -NO,, -NRR’, (CRPR),OR®, -CN, -C(OR! -OCOR’, -O(CRR)R' -NR'C(OR®, -(CR°R"),C(O)OR’, -(CRPR"),NCRR’, -C(=NRENR’R®, -NR‘C(O)NR®R®, -NR*S(0),R’® or -C(O)NR'R®, and each hydrogen in R' is optionally substituted by one or more R® groups; R' and R? or R' and R™ may be combined together to form a Cg.q2 aryl, 5-12 membered heteroaryl, Ca.12 cycloalkyl or 3-12 membered heteroalicyclic group; mis 0, 1or2 nis 0, 1,2, 3 or4; and pis 1or2; ora pharmaceutically acceptable salt, solvate or hydrate thereof.
: 2. The compound of claim 1, wherein Y is N. . 3. The compound of claim 1, wherein Y is CR".
4. The compound of claim 1, wherein the compound has formula 1a
R} : i” vZ rR? rio 1a x oN p's NH; wherein AZ is Ce.12 aryl or 5-12 membered heteroaryl optionaily substituted by one or more R® groups.
5. The compound of claim 4, wherein R' is selected from Cg aryl and 5-12 membered heteroaryl, and each hydrogen in R' is optionally substituted by one or more R? groups.
6. The compound of claim 4, wherein R' is selected from Csqo cycloalkyl, 3-12 membered heteroalicyclic, O(CR®R),R?, -C(O)R?, -C(O)OR*, -CN, -NO,, -S(O),R*, -SO.NR'R®, -C(O)NR'R’, -NR‘C(O)R®, -C(=NR®)NR’R®, Cs alkyl, Cos alkenyl, and C,g alkynyl; and each hydrogen in R' is optionzlly substituted by one or more R® groups.
7. The compound of claim 4, wherein A? is substituted by at least one halogen atom.
8. The compound of claim 4, wherein R? is hydrogen, R® and R" are independently C4 alkyl, and Ais phenyl substituted by at least one halogen atom.
9. The compound of claim 1, wherein R' is 2 furan, thiopene, pyrrole, pyrroline, pyrrolidine, dioxolane, oxazole, thiazole, imidazole, imidazoline, imidzzolidine, pyrazole, pyrazoline, pyrazolidine, isoxazole, isothiazole, oxadiazole, triazole, thiadiazole, pyran, pyridine, piperidine, dioxane, morpholine, dithiane, thiomorpholine, pyridazine, pyrimidine, pyrazine, piperazine, triazine, trithiane or phenyl group, and each hydrogen in R'is optionally substituted by one or more R? groups.
10. The compound of claim 1, wherein R' is a fused ring heteroaryl group, and each hydrogen in R' is optionally substituted by one or more R® groups.
. 11. The compound of claim 1, wherein Rlisa -SO,NR‘R® group.
12. A compound of formula 2
R! R12 R2 = | 2 Al EN N 0 NH, wherein:
R! is selected from Ce1o aryl, 5-12 membered heteroaryl, Cs, cycloalkyl, 3-12 membered heteroalicyclic, -O(CR®R").R®, -C(O)R®, -C(O)OR’, -CN, -NO,, -S(O)mR’, -SONR'R’, -C(O)NR'R’, -NR‘C(O)R’, -C(ENRONR'R®, Cy4 alkyl, Cos alkenyl, and Cag alkynyl; and each hydrogen in R'is optionally substituted by one or more Rr? groups;
R? is hydrogen, halogen, Ci.12 alkyl, Cz.42 alkenyl, Ca.12 alkynyl, Cs.42 cycloalkyl, Ce.12 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, -S(O)mR?, -SO:NR*R®, -S(0);0R", -NOz, -NR*R’, (CR°R),OR®, -ON, -C(OR) -OC(OR! -O(CRR)R‘ -NR'C(OR’, -(CR°R,C(O)OR’,
-(CR°R").NCRR®, -C(=NR®NR’R®, -NR*C(O)NR’R®, -NR*S(0),R® or -C(O)NR’R’, and each hydrogen in R? is optionally substituted by one or more R® groups;
R? is halogen, Cy.12 alkyl, Cz.1> alkenyl, C2.12 alkynyl, Caz cycloalkyl, Ce. aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, -S(O)aR’, -SONR'R®, -S(0):0R‘, -NO; -NR'R’, ACR°R),OR, -CN, -C(O)R', -OC(O)R!, -OCR’R)R! -NR'CO)R’, -(CR°R").C(O)OR’,
-(CR°R.INCRIRS, -C(=NRENRR®, -NRC(O)NR®R?, -NR*S(0),R°® or -C(O)MNR'R’, each hydrogen in R® is optionally substituted by one or more R® groups, and Rr? groups on adjacent atoms may combine to form a Cs.12 aryl, 5-12 membered heteroaryl, C.12 cycloalkyl or 3-12 membered heteroalicyclic group;
each RY, R® R® and R’ is independently hydrogen, halogen, Ci.q2 alkyl, Ca.12 alkenyl, Cz.q2 alkynyl, Cz, cycloalkyl, Cs.12 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl; or any two of R% R®, R®and R’ bound to the same nitrogen atom may, together with the nitrogen to which they are bound, be combined to form a 3 to 12 membered heteroalicyclic or 5-12 membered heteroaryl group optionally containing 1 to 3 additional heteroatoms selected from N, O, and S; or any two of RY, R®, R® and R’ bound to the same carbon atom may be combined to form a Cs.42 cycloalkyl, Ce.12 aryl, 3-12 membered heteroalicyclic or 5-12 membered heteroaryl group; and each hydrogen in R*, R®, R® and R’
’ 25 is optionally substituted by one or more R® groups; each R® is independently halogen, Cy.12 alkyl, Ca.42 alkenyl, Ca.12 alkynyl, Cs. cycloalkyl, Ce.12 : aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, -CN, -O-Cy.42 alkyl, -O-(CH2)1Ca-12 cycloalkyl, -O-(CHz)nCe.12 aryl, -O-(CHz)n(3-12 membered heteroalicyclic) or -O-(CH,),(5-12 membered heteroaryl); and each hydrogen in R® is optionally substituted by one or more R"! groups;
Alis ~(CR°R"),-A%
each R® and R" is independently hydrogen, halogen, Ci.12 alkyl, Ca.12 cycloalkyl, Ce. aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, -S(O)nR*, -SO:NR’R®, -§(0),0R", -NO,, -NR*R’,
(CRPRT),OR!, -CN, -C(O)R!, -OC(O)R®, -NR'C(O)R®, -(CR°R)MC(O)OR®, -(CR'R")NCR'R®, NRC(O)NR®R®, -NR*S(0),R® or -C(OINR'R®; R® and R'’ may combine to form a Cyr, cycloalkyl, 3-12 membered heteroalicyclic, Ce.12 aryl or 5-12 membered heteroaryl ring; and each hydrogen in R® and R™ is optionally substituted by one or more R® groups; A? is Cer aryl, 5-12 membered heteroaryl, Cs.12 cycloalkyl or 3-12 membered heteroalicyclic, and A? is optionally substituted by one or more R® groups; each R'' is independently halogen, Cy2 alkyl, Ci.12 alkoxy, Caz cycloalkyl, Ce.12 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, -O-Cy.12 alkyl, -O-(CH2).Ca.12 cycloalkyl, -O- (CH2)xCe.12 aryl, -O-(CHz),(3-12 membered heteroalicyclic), -O-(CHg)a(5-12 membered heteroaryl) or -CN, and each hydrogen in R" is optionally substituted by one or more groups selected from halogen, -OH, -CN, -Cy.12 alkyl which may be partially or fully halogenated, -O-Cs.12 alkyl which may be partially or fully halogenated, -CO, -SO and -SOo; R"% is hydrogen, halogen, Ci.12 alkyl, Cz.12 alkenyl, Caz alkynyl, C312 cycloalkyl, Ce.12 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, -S(O)mR’, -SO:NR*R’, -5(0):0R", -NO2, ~NR*RS, 16 -(CR°R):OR', -CN, -C(OR, -OC(O)R’, -O(CRR')}R* -NR‘C(O)R’, -(CR°R"),C(O)OR", -(CR°R").NCRR?, -C(=NR®NR'R’, -NR*C(O)NRR®, -NR*S(0),R’ or -C(O)NR’R®, and each hydrogen in R' is optionally substituted by one or more R® groups; R! and RZ or R' and R"? may be combined together to form a Ce2 aryl, 5-12 membered heteroaryl, C312 cycloalkyl or 3-12 membered heteroalicyclic group; mis 0, 10r2; nis0, 1,2,30r4; and pis1or2; or a pharmaceutically acceptable salt, solvate or hydrate thereof.
13. The compound of claim 12, wherein the compound has formula 2a R' 12 2 : Re. R10 2a DLN AZ © . NH; wherein A? is Cg 12 aryl or 5-12 membered heteroaryl optionally substituted by one or more Rr? groups.
14. The compound of claim 13, wherein R! is selected from Cg.q2 aryl and 5-12 membered heteroaryl, and each hydrogen in R'is optionally substituted by one or more R?® groups.
15. The compound of claim 13, wherein R' is selected from Cj. cycloalkyl, 3-12 membered heteroalicydlic, -O(CR°RM):R’, -C(O)R?, -C(O)OR®, -CN, -NO, -S(O)mR*, -SONR‘R®, -C(O)NR‘R’,
-NR'C(O)R’, -C(=NR®)NR'R®, C5 alkyl, C,.g alkenyl, and Cas alkynyl; and each hydrogen in R' is : optionally substituted by one or more R® groups.
16. The compound of claim 13, wherein A?is substituted by at least one halogen atom.
17. The compound of claim 13, wherein R? is hydrogen, R® and R'° are independently Ci. alkyl, and A?is phenyl substituted by at least one halogen atom.
18. The compound of claim 12, wherein R' is a furan, thiopene, pyrrole, pyrroline, pyrrolidine, dioxolane, oxazole, thiazole, imidazole, imidazoline, imidazolidine, pyrazole, pyrazoline, pyrazolidine, isoxazole, isothiazole, oxadiazole, triazole, thiadiazole, pyran, pyridine, piperidine, dioxane, morpholine, dithiane, thiomorpholine, pyridazine, pyrimidine, pyrazine, piperazine, triazine, trithiane or phenyl group, and each hydrogen in R'is optionally substituted by one or more R® groups. 16
19. The compound of claim 12, wherein R'is a fused ring heteroaryl group, and each hydrogen in R! is optionally substituted by one or more R® groups.
20. The compound of claim 12, wherein R' is a ~SO,NR*R® group.
21. A compound of formula 3 Rr! R2 NF 3 N 1 A ~—o0 Xu NH, wherein: R! is selected from Cg.12 aryl, 5-12 membered heteroaryl, Css cycloalkyl, 3-12 membered heteroalicyclic, -O(CR°R),R’, ~C(O)R?, -C(O)OR?, -CN, -NO,, -S(0)nR*, -SO,NR'R®, -C(O)NR'R®, : 25 -NRC(O)R®, -C(=NR®)NR’R’, Cis alkyl, C25 alkenyl, and Cz alkynyl; and each hydrogen in R' is optionally substituted by one or more R3 groups; . R%is hydrogen, halogen, Ci.i» alkyl, C21; alkenyl, C,.12 alkynyl, Ca.12 cycloalkyl, Cs 4, aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, -S(0)mR", -SO:NR*R?, -S(0),0R*, -NO,, -NR*R®, (CR’R),ORY, -CN, -COO)RY, -OC(OR’, -OCRR)R‘ -NR'C(OR’, -(CR°R"),C(O)OR’, -(CR°R)WNCRR®, -C(=NRENR’R®, -NR*C(O)NR’R®, -NR*S(O),R® or -C(O)NR‘R’, and each hydrogen in R? Is optionally substituted by one or more R® groups;
R® is halogen, Cy.12 alkyl, Co.12 alkenyl, C,.4, alkynyl, Ca.s2 cycloalkyl, Ce.s2 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, -S(O)nR%, -SOMNR'R®, -S(0),0R‘, -NO, -NR'R’, (CR°R’),OR*, -CN, -C(O)R! -OC(O)R!, -O(CRR")R’ -NR'COO)R’, -(CR°R,C(O)OR®, «CR®R"),NCR*R®, -C(=NR®NR’RE, -NR*C(O)NR®R?, -NR*S(O),R® or -C(O)NR*R®, each hydrogen in R® is optionally substituted by one or more R® groups, and R® groups on adjacent atoms may combine to form a Ce 12 aryl, 5-12 membered heteroaryl, Ca.» cycloalkyl or 3-12 membered heteroalicyclic group;
each R*, R® R® and R’ is independently hydrogen, halogen, Ci.1; alkyl, C2 alkenyl, Cz12 alkynyl, Ca.i2 cycloalkyl, Ces.12 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl; or any two of R*, R®, R® and R” bound to the same nitrogen atom may, together with the nitrogen to which they are bound, be combined to form a 3 to 12 membered heteroalicyclic or 5-12 membered heteroaryl group optionally containing 1 to 3 additional heteroatoms selected from N, O, and S; or any two of RY R% R® and R’ bound to the same carbon atom may be combined to form a Ca.i» cycloalkyl, Cg; aryl, 3-12 membered heteroalicyclic or 5-12 membered heteroaryl group; and each hydrogen in R* R®, R® and R’ is optionally substituted by one or more R® groups;
each R® is independently halogen, Cy.q2 alkyl, C2.1» alkenyl, Ca.12 alkynyl, Ca.12 cycloalkyl, Ce12 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, -CN, -O-Cy.12 alkyl, -O-(CH;)aCs.12 cycloalkyl, -O-(CHa)nCe.12 aryl, -O-(CHa)n(3-12 membered heteroalicyclic) or -O-(CHg)q(5-12 membered heteroaryl); and each hydrogen in R® is optionally substituted by one or more rR" groups;
A'is /(CR°R™),-A? except that: (i) when R' is substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl, A' is =(CR°R'"),-A? and n is not zero; and (il) when R?is H and A' ie m-chlorobenzyl, R' is not unsubstituted piperazine; each R? and R" is independently hydrogen, halogen, Cy. alkyl, C12 cycloalkyl, Coz aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, -S(0)xR", -SONR'R®, -5(0).0R", -NO,, -NR'R’,
-(CR°R’)OR', -CN, -C(OR', -OC(O)R!, -NR'‘COR®, -(CR°RM.C(O)OR®, -(CR°R").NCR'R’, NR'C(O)NR®R®, -NR*S(0),R® or -C(O)NR*R®; R® and R'® may combine to form a Caz cycloalkyl, 3-12 membered heteroalicyclic, Ce. aryl or 5-12 membered heteroaryl ring; and each hydrogen in R® and R'is optionally substituted by one or more R® groups,
A? is Ce. aryl, 5-12 membered heteroaryl, Cs.12 cycloalkyl or 3-12 membered heteroalicyclic,
and AZ is optionally substituted by one or more R® groups;
each R'is independently halogen, Cy.12 alkyl, C112 alkoxy, Caz cycloalkyl, Ce.2 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, -O-Cy.12 alkyl, ~O-(CH2):Ca12 cycloalkyl, -O- (CH2)nCé-12 aryl, -O~(CHz)n(3-12 membered heteroalicyclic), -O-(CHz)n(5-12 membered heteroaryl) or : -CN, and each hydrogen in R" is optionally substituted by one or more groups selected from halogen, -OH, -CN, -Cy.12 alkyl which may be partially or fully halogenated, -O-Ci.12 alkyl which may be partially or fully halogenated, -CO, -SO and -SO; R! and R? may be combined together to form a Cg. aryl, 5-12 membered heteroaryl, Cs-12 cycloalkyl or 3-12 membered heteroalicyclic group; mis0, 1or2;
nis 0, 1, 2,3 or 4; and . pis1or2; or a pharmaceutically acceptable salt, solvate or hydrate thereof.
22 The compound of claim 21, wherein the compound has formula 3a rR’ RZ NZ rR". R10 | 3a x AN D'S NH, wherein A? is Cs.12 aryl or 5-12 membered heteroaryl optionally substituted by one or more R® groups.
23. The compound of claim 22, wherein R! is selected from Ce12 aryl and 5-12 membered heteroaryl, and each hydrogen in R'is optionally substituted by one or more Rr? groups.
24. The compound of claim 22, wherein R' is selected from Caq, cycloalkyl, 3-12 membered heteroalicyclic, -O(CRPR")R*, -C(O)R?, -C(O)OR?, -CN, -NO;, -S(O)mR®, -SONR’R®, -C(O)NR*R®, -NRC(O)R®, -C(=NR®)NR*R®, C3 alkyl, C25 alkenyl, and Cs alkynyl; and each hydrogen in R' is 16 optionally substituted by one or more R? groups.
25. The compound of claim 22, wherein A? is substituted by at least one halogen atom.
26. The compound of claim 22, wherein R? is hydrogen, R? and R" are independently C4 alkyl, and A’is phenyl substituted by at least one halogen atom.
27. The compound of claim 21, wherein R' is a furan, thiopene, pyrrole, pyrroline, pyrrolidine, dioxolane, oxazole, thiazole, imidazole, imidazoline, imidazolidine, pyrazole, pyrazoline, pyrazolidine, isoxazole, isothiazole, oxadiazole, triazole, thiadiazole, pyran, pyridine, piperidine, dioxane, morpholine, dithiane, thiomorpholine, pyridazine, pyrimidine, pyrazine, piperazine, triazine, trithiane or phenyl group, } and each hydrogen in R' is optionally substituted by one or more R® groups.
28. The compound of claim 21, wherein R! is a fused ring heteroaryl group, and each hydrogen in R' is optionally substituted by one or more R® groups.
29. The compound of claim 21, wherein R' is a ~SO,NR*R® group.
30. A compound of formula 4
Rr R10 7 | 4
R® pa So \
A? © NH,
wherein:
R' is selected from Cg42 aryl, 5-12 membered heteroaryl, Cao cycloalkyl, 3-12 membered heteroalicyclic, -O(CR®R)aR?, -C(O)R?, -C(O)OR?, -CN, -NO;, -S(O)nR’, -SONR'R®, -C(O)NR'R®, -NR'CO)R®, -C(=NRONR’R®, Cys alkyl, Cos alkenyl, and Co. alkynyl; and each hydrogen in R'is optionally substituted by one or more R® groups;
Ris halogen, Cy.12 alkyl, Ca.12 alkenyl, Ca.12 alkynyl, Caz cycloalkyl, Ce.12 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, -S(O)mR’, -SO:NR'R®, -S(0)0R’, -NO, -NR'R’, (CRPR)OR?, -CN, -CO)R', -OC(O)R’, -OCRR’)R' -NR'C(OR’, -(CR°R).C(O)OR’,
~(CR°R").NCR'R®, -C(=NRENR'R®, -NR‘C(O)NR’R®, -NR*S(O),R® or -C(O)NR*R®, each hydrogen in R® is optionally substituted by one or more R® groups, and Rr? groups on adjacent atoms may combine to form a Cg 12 aryl, 5-12 membered heteroaryl, Cs.12 cycloalkyl or 3-12 membered heteroalicyclic group;
each RY, R®, R® and R’ is independently hydrogen, halogen, Ci.;2 alkyl, Ca.12 alkenyl, Ca. alkynyl, Caz cycloalkyl, Cs.12 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl; or any iwo of R%, R®, R® and R’ bound to the same nitrogen atom may, together with the nitrogen io which they are bound, be combined to form a 3 to 12 membered heterozlicyclic or 5-12 membered heteroaryl group optionally containing 1 to 3 additional heteroatoms selected from N, O, and S; or any two of RY R®, R® and R’ bound to the same carbon atom may be combined to form a Cs4; cycloalkyl, Cg.42 aryl, 3-12 membered heteroalicyclic or 5-12 membered heteroaryl group; and each hydrogen in R*, R® R®and R’
is optionally substituted by one or more R® groups;
each R® is independently halogen, Ci.12 alkyl, Cz, alkenyl, Ca.42 alkynyl, Ca.12 cycloalkyl, Cg12 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, -CN, -0-Cy.42 alkyl, -O-(CH2)nCa.12 cycloalkyl, -0-(CHg)nCe.12 aryl, -O-(CHz)a(3-12 membered heteroalicyclic) or -O-(CHg)n(5-12 membered heteroaryl); and each hydrogen in R® is optionally substituted by one or more R'' groups;
’ 25 each R® and R" is independently hydrogen, halogen, Cy.12 alkyl, Ca.42 cycloalkyl, Ce, aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, -S(O)nR*, -SO,NR*R?, -8(0),0R*, -NOz, -NR*R’, . (CRPR).OR!, -CN, -C(OR’, -OC(O)R’, -NR‘C(O)R’, -(CR°R),C(O)OR’, -(CR°R"),NCRR®, NRC(O)NR®RE, -NR*S(0),R® or -C(O)NR*R®; R® and R'® may combine to form a Ca. cycloalkyl, 3-12 membered heteroalicyclic, Ce.1; aryi or 5-12 membered heteroaryl ring; and each hydrogen in R® and
R'is optionally substituted by one or more R® groups;
A? is Cg1z aryl, 5-12 membered heteroaryl, Ca.12 cycloalkyl or 3-12 membered heteroalicyclic, and A? is optionally substituted by one or more R?® groups;
each R" is independently halogen, C,, alkyl, Ci.12 alkoxy, Ca.1z cycloalkyl, Ce.12 aryl, 3-12 : membered heteroalicyclic, 5-12 membered heteroaryl, -O-C1.12 alkyl, -O-(CH;),Cs.12 cycloalkyl, -O- (CH2)nCeg.12 aryl, -O-(CHg)n(3-12 membered heteroalicyclic), -O-(CH2)n(5-12 membered heteroaryl) or -CN, and each hydrogen in R" is optionally substituted by one or more groups selected from halogen, -OH, -CN, -C4.12 alkyl which may be partially or fully halogenated, -O-Cy.;, alkyl which may be partially or fully halogenated, -CO, -SO and -SOq; mis 0, 1or2; nis 0,1, 2, 3 or4; and pisior2; or a pharmaceutically acceptable salt, solvate or hydrate thereof.
31. The compound of claim 30, wherein A? is C12 aryl or 5-12 membered heteroaryl optionally substituted by one or more R® groups. 16
32. A compound of formula & R! A R10 | 5 “SL AN AZ © NH; wherein: R' is selected from Cgi2 aryl, 5-12 membered heteroaryl, Caz cycloalkyl, 3-12 membered heteroalicyclic, -O(CR®R").R?, -C(O)R?, -C(O)OR?, -CN, -NO;, -S(O)nR*, -SONR’R®, -C(O)NR’R®, -NR'C(O)R®, -C(=NR®)NR’R’, Cys alkyl, Ca alkenyl, and Cag alkynyl; and each hydrogen in R' is optionally substituted by one or more R® groups; R3is halogen, Cj.q2 alkyl, Ca.42 alkenyl, C,.42 alkynyl, C342 cycloalkyl, Cg42 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, -S(O)nR’ -SONR'R®, -S(0),0R?, -NO, -NR'R® -(CR°R"),OR?, -CN, -CO)R’, -OC(OR' -O(CRR)R', -NR'CO)R’, -(CR°R"),C(O)OR‘, -(CR°R"),NCR*R®, -C(=NR®)NR*R?, -NR*C(O)NR®R®, -NR*S(0),R® or -C(O)NR’R®, each hydrogen in R® is optionally substituted by one or more R® groups, and R® groups on adjacent atoms may combine to : form a Ce.12 aryl, 5-12 membered heteroaryl, C,.¢, cycloalkyl or 3-12 membered heteroalicyclic group; each R*, R% R® and R is independently hydrogen, halogen, Ci.i2 alkyl, C,, alkenyl, Cp.2 alkynyl, Caz cycloalkyl, Ce.s2 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl; or any two of R%, R® R® and R’ bound to the same nitrogen atom may, together with the nitrogen to which they are bound, be combined to form a 3 to 12 membered heteroalicyclic or 5-12 membered heteroaryl group optionally containing 1 to 3 additional heteroatoms selected from N, O, and S; or any two of R*, R®, R® and R7 bound to the same carbon atom may be combined to form a Cj, cycloalkyl, Ce.2 aryl, 3-12 membered heteroalicyclic or 5-12 membered heteroaryl group; and each hydrogen in R* R% R®and R’ is optionally substituted by one or more R® groups, each R® is independently halogen, Cy.12 alkyl, Ca.42 alkenyl, Cy.q2 alkynyl, Ca.q2 cycloalkyl, Ce.12 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, -CN, -O-Cy.42 alkyl, -O-(CH2)nC3-12 cycloalkyl, -O-(CH2)nCe.12 aryl, -O~(CH,)a(3-12 membered heteroalicyclic) or -O-(CH;)n(5-12 membered heteroaryl); and each hydrogen in R%is optionally substituted by one or more rR" groups; each R® and R™ is independently hydrogen, halogen, Ci.1z alkyl, Cz.12 cycloalkyl, Ce.q2 ary, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, -S(O)rR*, -SONR*R®, -S(0)20R*, -NO, -NR'R®, -CRR),0R’, -CN, -COR', -OCOR' -NR'COR®, -(CR'R).C(O)OR’, -(CR°R’),NCR'R’, -NR*C(O)NR®R®, -NR*S(0),R® or -C(O)NR'R’; R® and R'° may combine to form a Cs, cycloalkyl, 3-12 membered heteroalicyclic, Ce.12 aryl or 5-12 membered heteroaryl ring; and each hydrogen in R® and Ris optionally substituted by one or more R® groups; A? is Ce.12 aryl, 5-12 membered heteroaryl, Cs.42 cycloalkyl or 3-12 membered heteroalicyclic, and A? is optionally substituted by one or more R® groups; except that when R?, R® and R™ are all H and AZ is m-chiorophenyl, R' is not unsubstituted piperazine; each R'is independently halogen, Ci.12 alkyl, Cy.12 alkoxy, Ca.12 cycloalkyl, Ce.qz aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, -O-Cy.12 alkyl, -O-(CH2)sCa.12 cycloalkyl, -0- (CH2)nCe12 aryl, -O-(CHjy)n(3-12 membered heteroalicyclic), -O-(CH;)n(5-12 membered heteroaryl) or -CN, and each hydrogen in R' is optionally substituted by one or more groups selected from halogen, -OH, -CN, -C1.12 alkyl which may be partially or fully halogenated, -O-C.12 alkyl which may be partially or fully halogenated, -CO, -SO and -S0;; mis 0, 1or2; nis 0, 1, 2, 3 or4; and pis1or2; or a pharmaceutically acceptable salt, solvate or hydrate thereof.
33. The compound of claim 32, wherein A? is Ceo aryl or 5-12 membered heteroaryl optionally substituted by one or more Rr? groups.
34. A compound of formula 6
R= RZ R% AN 6) MC Ar N Aryl 0 NH,
wherein,
ZisCHorN;
Aryl is an optionally fused aryl or an optionally fused heteroaryl group which is optionally substituted by one or more substituents selected from the group consisting of a halogen, -OR¥, -COR%, -COOR%, -CONR¥R®, -CN, -NO,, -S(O)mR?*, -SO,NR¥R?, perfluoroalkyl, lower alkyl, cycloalkyl, heterocycle, alkenyl, alkynyl, aryl, -NR¥R%, -NR*C(0)R?® and -NR**S(0),R*;
R? and R% are independently selected from the group consisting of hydrogen, halogen, -
COR®, -COOR?, -CONR¥R®, -CN, perfluoroalkyl, lower alkyl, cycloalkyl, heterocycle, alkenyl, alkynyl, and aryl;
R® is selected from the group consisting of:
an optionally fused aryl, heteroaryl, alicyclic or heterocyclic group, optionally substituted by one or more substituents selected from the group consisting of a halogen,
-(CHp)-OR™, -COR¥, -COORY, -CONR¥R®, CN, -NO;, -S(0)nR*, -80,NR*'R¥, perflucroalkyl, -O- perfiuoroalkyl, lower alkyl, cycloalkyl, heterocycle, heteroaryl, alkenyl, alkynyl, aryl, -(CHz):-NR*'R%, - NR¥C(O)R®® and -NR?**S(0),R?, wherein said heterocycle, heteroaryl and aryl substituents may be optionally substituted by a group selected from the group consisting of lower alkyl, halogen, - C(O)NR¥R®, NR¥R?, NR¥C(O)R® and NR*S(O),R*;
-OR%* -COR¥, -COOR¥, -CN, -NO,, -S(0)mR*, -SO,NR¥R?, perfiuoroalkyl, cycloalkyl, heterocycle, alkenyl, and alkynyl;
R? and R® are independently selected from the group consisting of hydrogen, lower alkyl, cycloalkyl, alkenyl, alkynyl, aryl, aminoalkyl, alkylaminoalkyl, alkylaminocycloalkyl, dialkylaminoalkyl and ~(CHg)s-heterocycle, wherein said —(CHy),-heterocycle may be further substituted by one or more of lower alkyl, ~(CHy),-hydroxy, heterocycle and -C(O)R%, or R* and R® can combine to form a 5- to 6-membered heterocyclic ring having one or more - heteroatoms selected from the group consisting of N, O, S, S(O) and SO,, said 5- to 6-membered heterocyclic ring may be optionally substituted by lower alkyl, —(CH,),-heterocycle, cycloalkyl, halo, - (CH2)-NRZR?, amino, -C(O)R®, -NR?-C(O)OR? and -NR*-C(O)R?;
wherein R? and R? are independently selected from the group consisting of hydrogen, lower alkyl, —|(CHg)-cycloalky!l and -C(0)-(CHg),-OH,
except that when Z is N and R?! and R? are H and Aryl is m-chlorophenyl, R* is not piperazine; ' mis0, 1or2; nis0,1,2o0r3; pis 1or2; ora pharmaceutically acceptable sait thereof,
35. The compound of claim 34, wherein R?® is aryl or heteroaryl.
36. A compound selected from the group consisting of: 4-[6-amino-5-(2,6-dichioro-benzyloxy)- pyridin-3-yl}-phenol; 3-(2,6-dichloro-benzyloxy)-5-[4-(2-morpholin-4-yl-ethoxy)-phenyl]-pyridin-2-ylamine; 3-(2,6-dichloro-benzyioxy)-5-[3-(2-morpholin-4-yl-ethoxy)-phenyl}-pyridin-2-ylamine; 3-(2,6-dichloro- benzyloxy)-5-(1H-indol-4-yl)-pyridin-2-ylamine; 3-[2-chloro-6-(1H-indol-4-yl)-benzyloxy]-5-(1 H-indol-4-yl)- pyridin-2-ylamine; 2-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yl}-pyrrole-1-carboxylic acid tert-butyl ester; 3-(2,6-dichloro-benzyloxy)-5-(1H-pyrrol-2-yl)-pyridin-2-ylamine; 3-(2,6-dichloro-benzyloxy)-5-(4- fluoro-phenyl)-pyridin-2-ylamine; 3-(2,6-dichloro-benzyloxy)-5-phenyl-pyridin-2-ylamine; 3-(2,6-dichloro- benzyloxy)-5-(2-fluoro-phenyl)-pyridin-2-ylamine; 3-(2,6-dichloro-benzyloxy)-5-(3-fluocro-phenyl)-pyridin- 2-ylamine; 5-(4-amino-phenyl)-3-(2,6-dichloro-benzyloxy)-pyridin-2-ylamine; N-{4-[6-amino-5-(2,6- dichloro-benzyloxy)-pyridin-3-yi}-phenyl}-methanesuifonamide; N-{4-[6-amino-5-(2,6-dichloro- benzyloxy)-pyridin-3-yl}-phenyl}-acetamide; 3-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yi}-phenol; 3-(2,6-dichloro-benzyloxy)-5-(4-methoxy-phenyl)-pyridin-2-ylamine; 5-(3-amino-phenyl)-3-(2,6-dichloro- benzyloxy)-pyridin-2-ylamine; 3-(2,6-dichloro-benzyloxy)-5-(3-trifluoromethoxy-phenyl)-pyridin-2- ylamine; 2-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yl]-phenol; 3-(2,6-dichloro-benzylo:y)-5-(2- phenoxy-phenyl)-pyridin-2-ylamine; 3-(2,6-dichloro-benzyloxy)-5-(3,4-difluoro-phenyl)-pyridin-2-ylamine; 3-(2,6-dichloro-benzyloxy)-5-(3-isopropyl-phenyl)-pyridin-2-ylamine; 3-(2,6-dichioro-benzyloxy)-5-(2- triflucromethyl-phenyl)-pyridin-2-ylamine; 3-(2,6-dichloro-benzyloxy)-5-(2-methoxy-phenyl)-pyridin-2- ylamine; 3-(2,6-dichloro-benzyloxy)-5-(4-trifluoromethyl-phenyl)-pyridin-2-ylamine; N-{2-[6-amino-5-(2,6- dichloro-benzyloxy)-pyridin-3-yi}-phenyl}-methanesulfonamide; {4-[6-amino-5-(2,6-dichloro-benzyloxy)- pyridin-3-yl]-phenyl}-methanol; 5-benzo[1,3]dioxol-5-yl-3-(2,6-dichloro-benzyloxy)-pyridin-2-ylamine; 3- (2,6-dichloro-benzyloxy)-5-(2-trifluoromethoxy-phenyl)-pyridin-2-ylamine; 3-(2,6-dichioro-benzyloxy)-5- (4-methyl-thiophen-2-yl)-pyridin-2-ylamine; 5-(2-benzyloxy-phenyl)-3-(2,6-dichloro-benzyloxy)-pyridin-2- ylamine, 3-(2,6-dichloro-benzyloxy)-5-(3-methoxy-phenyl)-pyridin-2-ylamine; 3-(2,6-dichloro-benzyloxy)- ’ 5-(1H-indol-2-yl)-pyridin-2-ylamine, 5-(4-benzyloxy-3-fluoro-phenyl)-3-(2,6-dichloro-benzyloxy)-pyridin-2- ylamine; 4-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yl}-benzoic acid; 4-[6-amino-5-(2,6-dichloro- . benzyloxy)-pyridin-3-yl]-N-(2-diethylamino-ethyl)-benzamide; 4-[6-amino-5-(2,6-dichloro-benzyloxy)- pyridin-3-yl}-N-(3-diethylamino-propyl)-benzamide; {4-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yl}- phenyl}-(4-methyl-piperazin-1-yl)-methanone; {4-]6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yl}- phenyl}-{(2R)-2-pyrrolidin-1-yimethyl-pyrrolidin-1-yl]-methanone; {4-[6-amino-5-(2,6-dichloro-benzyloxy)- pyridin-3-yl]-phenyi}-[(2S)-2-pyrrolidin-1-yimethyl-pyrrolidin-1-yl-methanone; {4-[6-amino-5-(2,6- dichloro-benzyloxy)-pyridin-3-yl]-phenyl}-(4-pyrrolidin-1-yl-piperidin-1-yl}-methanone; {4-{6-amino-5-(2,6-
dichloro-benzyloxy)-pyridin-3-yi]-phenyl}-[4-(2-hydroxy-ethyl)-piperidin-1-yl]-methanone; {4-[6-amino-5- . (2,6-dichloro-benzyloxy)-pyridin-3-yl}-phenyl}-[(3S)-3-dimethylamino-pyrrolidin-1-yl}-methanone; {4-[6- amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yl}-phenyl}-[(3R)-3-dimethylamino-pyrrolidin-1-yl]- methanone; {4-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yl}-phenyl}-[(3S)-3- cyclopropylaminomethyl-piperidin-1-yl}-methanone; 4-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yl}- N-(2-hydroxy-3-pyrrolidin-1-yl-propyl)-benzamide; {4-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yl}- phenyl}-[(2S)-2-(3-fluoro-piperidin-1-ylmethyl)-pyrrolidin-1-yl]-methanone; {4-[6-amino-5-(2,6-dichloro- benzyloxy)-pyridin-3-yl}-phenyl}-(4-cyclopropyl-piperazin-1-yl)-methanone; {4-J6-amino-5-(2,6-dichloro- benzyloxy)-pyridin-3-yi}-phenyl}-{(2R)-2-{(cyclopropylmethyl-amino)-methyll-pyrrolidin-1-yl}-methanone; 4-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yl]-N-cyclopropylmethyl-N-(2R)-pyrrolidin-2-ylmethyl- benzamide; 4-[6-amino-5-(2,6-dichioro-benzyloxy)-pyridin-3-yl}-N-(2-hydroxy-3-pyrrolidin-1-yl-propyl)-N- methyl-benzamide; {4-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yl]-phenyl}{(2S)-2-[(3R)-3-hydroxy- pyrrolidin-1-yimethyl}-pyrrolidin-1-yi}-methanone; 3-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yl}- benzoic acid; {3-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yiJ-phenyl}-{(2R)-2-pyrrolidin-1-ylmethyl- 16 pyrmrolidin-1-yl]-methanone; {4-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yl}-phenoxy}-acetic acid; 2- {4-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yl]-phenoxy}-1-[(2R)-2-pyrrolidin- 1-ylmethyl-pyrrolidin- 1-yl}-ethanone; 2-{4-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yi}-phenoxy}-1-[(2S)-2-pyrrolidin-1- ylmethyl-pyrrolidin-1-ylj-ethanone; 3-(2,6-dichioro-benzyloxy)-5-(1H-indol-5-yl)-pyridin-2-ylamine; 3-(2,8- dichloro-benzyloxy)-5-[3-(1-methyl-1,2,3,6-tetrahydro-pyridin-4-yl}- 1H-indol-5-yl}-pyridin-2-ylamine; ~~ 3- (2,6-dichloro-benzyloxy)-5-[3-(1-methyl-piperidin-4-yl)-1H-indol-5-y[}-pyridin-2-ylamine; 3-(2,6-dichloro- benzyloxy)-5-(3-morpholin-4-ylmethyl-1H-indol-5-yl)-pyridin-2-ylamine; 3-(2,6-dichloro-benzyloxy)-5-(3- piperidin-1-ylmethyl-1 H-indol-5-yl)-pyridin-2-ylaming; 3-(2,6-dichloro-benzylosy)-5-(3-pyrrolidin-i- ylmethyl-1H-indol-5-yl)-pyridin-2-ylamine; 3-(2,6-dichloro-benzyloxy)-5-(3-diethylaminomethy!- H-indol- 5-yl)-pyridin-2-ylamine; (1-{56-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-ylj-1H-indol-3-yimethyl}-(3R)- pyrrolidin-3-yl)-carbamic acid tert-butyl ester; 3-(2,6-dichloro-benzyloxy)-5-[3-(2,6-dimethyl-morpholin-4- yimethyl)-1H-indol-5-yi]-pyridin-2-ylamine; N-(1-{5-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-ylj-1H- indol-3-yimethyl}-(3R)-pyrrolidin-3-yl)-acetamide, 1-(4-{5-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3- yl}-1H-indol-3-yimethyl}-piperazin-1-yl)-ethanone; 3-(2-chloro-3,6-difluoro-benzyloxy)-5-(1H-indol-5-yl)- pyridin-2-ylamine; 1-(4-{5-[6-amino-5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-yl}-1H-indol-3-ylmethyl}- piperazin-1-yl)-ethanone; 3-(2-chloro-3,6-difluoro-benzyloxy)-5-[3-(2,6-dimethyl-morpholin-4-yimethyl)- 1H-indol-5-yl}-pyridin-2-ylamine; ~~ N-(1-{5-[6-amino-5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-yl}-1H- - indol-3-ylmethyl}-(3S)-pyrrolidin-3-yl)-acetamide; 3-(2-chloro-3,6-difiuoro-benzyloxy)-5-(3-piperidin-1- ylmethy}-1H-indol-5-yl)-pyridin-2-ylamine; 3-(2-chloro-3,6-difluoro-benzyloxy)-5-(3-morpholin-4-yimethyl- ] 1H-indol-5-yl)-pyridin-2-ylamine; 3-(2-chloro-3,6-difluoro-benzyloxy)-5-(3-pyrrolidin-1-ylmethyl-1H-indol- 5-yl)-pyridin-2-ylamine; 5-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yi}-1H-indole-2-carboxylic acid "ethyl ester; 5-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yi]-1H-indole-2-carboxylic acid; {5-[6-amino- 5-(2,6-dichloro-benzyloxy)-pyridin-3-yl}-1 H-indol-2-yl}-(4-methyl-piperazin-1-yl)}-methanone; {5-[6-amino- 5-(2,6-dichloro-benzyloxy)-pyridin-3-yl}-1 H-indol-2-yl}-[(3 R)-3-dimethylamino-pyrrolidin-1-yl}-methanone; {5-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yl]- 1 H-indol-2-yl}-[(2R)-2-pyrrolidin-1-yimethyi-
: pyrrolidin-1-yl}-methanone; 5-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yl}-1 H-indole-2-carboxylic . acid (2-pyrrolidin-1-yl-ethyl)-amide; 5-{6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-ylJ- 1 H-indole-2- carboxylic acid (2-morpholin-4-yl-ethyl)-amide: (1-{5-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yl]- 1H-indole-2-carbonyl}—(3S)-pyrrolidin-3-yl)-carbamic acid tert-butyl ester; {5-[6-amino-5-(2,6-dichloro- benzyloxy)-pyridin-3-yl}-1H-indol-2-yl}-[(3S)-3-amino-pyrrolidin-1-y(}-methanone; 5-[6-amino-5-(2,6- dichloro-benzyloxy)-pyridin-3-yll- 1 H-indole-2-carboxylic acid (2-hydroxy-3-pyrrolidin-1-yl-propyl)-amide; 4-(6-amino-5-benzyloxy-pyridin-3-yl)-phenol; 3-benzyloxy-5-phenyl-pyridin-2-ylamine; 3-(3-methoxy- benzyloxy)-5-phenyl-pyridin-2-ylamine; 3-(2-chloro-4-fluoro-benzyloxy)-5-phenyl-pyridin-2-ylamine; 3-(2- chloro-benzyloxy)-5-phenyl-pyridin-2-ylamine; 3-(2,5-dichloro-benzyloxy)-5-phenyl-pyridin-2-ylamine; 3- (2-chloro-5-trifluoromethyl-benzyloxy)-5-phenyl-pyridin-2-ylamine; 3-(2,4-dichloro-5-fluoro-benzyloxy)-5- phenyl-pyridin-2-ylamine; 3-(2-chioro-3-frifiucromethyl-benzyloxy)-5-phenyl-pyridin-2-ylamine; 3-(2- chloro-3,6-difluoro-benzyloxy)-5-phenyl-pyridin-2-ylamine; 3-(3,4-dichloro-benzyloxy)-5-phenyl-pyridin-2- ylamine; 2-(2-amino-5-phenyl-pyridin-3-yloxymethyl)-benzonitrile; 3-(2-chloro-6-fluoro-3-methyl- benzyloxy)-5-phenyl-pyridin-2-ylamine; 5-Phenyi-3-(2,3,6-trifluoro-benzyloxy)-pyridin-2-ylamine:; 3~(2,6- difluoro-benzyloxy)-5-phenyl-pyridin-2-ylamine; 3-(2,6-difluoro-3-methyl-benzyloxy)-5-phenyi-pyridin-2- ylamine; 3-(3-chloro-2,6-difluoro-benzyloxy)-5-phenyl-pyridin-2-ylamine; 3~(2-chloro-6-fluoro-benzyloxy)- 5-phenyl-pyridin-2-ylamine; 3-(3-Fluoro-4-metho:y-benzyloxy)-5-phenyl-pyridin-2-ylamine; N-[3-(2- amino-5-phenyi-pyridin-3-yloxymethyl)-phenyi]-methanesulfonamide; §-{4-(2-morpholin-4-yi-ethoxy)- phenyl]-3-(3-nitro-benzyloxy)-pyridin-2-ylamine; 5-[4-(2-morpholin-4-yl-ethoxy)-phenyl}-3-(naphthalen-1- yimethoxy)-pyridin-2-ylamine; 3-(2-chloro-3,6-difluoro-benzyloxy)-6-[4-(2-morpholin-4-yl-ethoxy)-phenyl}- pyridin-2-ylamine; 2-{2-amino-5-[4-(2-morpholin-4-yl-ethoxy)-phenyl]-pyridin-3-yloxy}-N-(4-isopropyl- phenyl)-2-phenyl-acetamide; 3-(S-chloro-benzo[bjthiophen-3-ylmethoxy)-5-[4-(2-morpholin-4-yl-ethoxy)- phenyl}-pyridin-2-ylamine; {4-[6-amino-5-(4-fluoro-2-trifiuoromethyl-benzyloxy)-pyridin-3-yl}-phenyl}- [(2R)-2-pyrrolidin- 1-ylmethyl-pyrrolidin-1-yil-methanone; {4-[6-amino-5-(2-fluoro-8-trifluoromethyl- benzyloxy)-pyridin-3-yl]-phenyl}-[(2R)-2-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl}-methanone; {4-[6-amino-5-
(S-fiuoro-2-triflucromethyi-benzyloxy)-pyridin-3-yl]-phenyl}-[(2R)-2-pyrrolidin-1-yimethyi-pyrrolidin-1-yi}- methanone; (4-{6-amino-5-[1-(2-trifluoromethyl-phenyl)-ethoxy]-pyridin-3-yl}-phenyl)-[(2R)-2-pyrrolidin-1- yimethyl-pyrrolidin-1-yl]-methanone; {4-[6-amino-5-(2-bromo-benzyloxy)-pyridin-3-yl]-phenyi}-[(2R)-2- pyrrolidin-1-yimethyl-pyrrolidin-1-yi}-methanone; {4-[6-amino-5-(3-fluoro-2-trifluoromethyl-benzyloxy)- pyridin-3-yl}-phenyl}-[(2R)-2-pyrrolidin-1-yimethyi-pyrrolidin-1-yl]-methanone; {4-[6-amino-5-(2-chioro- 3,6-difluoro-benzyloxy)-pyridin-3-yl}-phenyl}-{(2R)-2-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl}-methanone; 4- ) [6-amino-5-(2,6-difluoro-benzyloxy)-pyridin-3-yi}-phenol; 3-(2,6-difluoro-benzyloxy)-5-(1H-indol-4-yl)- pyridin-2-ylamine; 3-(2,6-difluoro-benzyloxy)-5-[4-(2-marpholin-4-yl-ethoxy)-phenyl}-pyridin-2-ylamine: 4- [6-amino-5-(2,6-difluoro-benzyloxy)-pyridin-3-yl]-benzoic acid; {4-[6-amino-5-(2,6-difluoro-benzyloxy)- ’ 35 pyridin-3-yl]-phenyl}-{(2R)-2-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl}-methanone; {4-[6-amino-5-(2,6-difluoro- benzyloxy)-pyridin-3-yl]-phenyl}-[(2S)-2-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl}-methanone; {4-[6-amino-5- (2,6-diflucro-benzyloxy)-pyridin-3-yl}-phenoxy}-acetic acid ethyl ester; {4-[6-amino-5-(2,6-difluoro- benzyloxy)-pyridin-3-yl]-phenoxy}-acetic acid: 2-{4-[6-amino-5-(2,6-difluoro-benzyloxy)-pyridin-3-yi]- phenoxy}-1-[(2R)-2-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl]-ethanone; 2-{4-[6-amino-5-(2,6-difluoro-
benzyloxy)-pyridin-3-yi]-phenoxy}-1-{(2 S)-2-pyrrolidin-1-yimethyl-pyrrolidin-1-yl}-ethanone; 4-[6-amino-5- : (2-chloro-6-fluoro-benzyloxy)-pyridin-3-yl}-phenol; 4-[6-amino-5-(2-chloro-4-fluoro-benzyloxy)-pyridin-3- yll-phenol; 4-[6-amino-5-(2,4-dichloro-benzyloxy)-pyridin-3-yil-phenol; 2-[2-amino-5-(4-hydroxy-phenyl)- pyridin-3-yloxymethyl}-benzonitrile; 4-[6-amino-5-(2-trifluoromethyl-benzyloxy)-pyridin-3-yi}-phenol; 4-[6- amino-5-(2-chloro-benzyloxy)-pyridin-3-yl}-phenol; 4-[6-amino-5-(4-teri-butyl-benzyloxy)-pyridin-3-yl}- phenol; N-{4-[6-amino-5-(2-cyano-benzyloxy)-pyridin-3-yl}-phenyl}-methanesulfonamide; 2-[2-amino-5- (4-methanesulifonylamino-phenyl)-pyridin-3-yloxymethy(]-benzamide; 2-[2-amino-5-(4- methanesulfonylamino-phenyl)-pyridin-3-yloxymethyl}-benzoic acid; N-(4-{6-amino-5-[2-(4-methyl- piperazine-1-carbonyl)-benzyloxyl-pyridin-3-yl}-phenyl)-methanesulfonamide; 2-[2-amino-5-(4- methanesulfonylamino-phenyl)-pyridin-3-yloxymethyi]-N-(2-hydroxy-ethyl)-benzamide; 2-[2-amino-5-(4- methanesulfonylamino-phenyl)-pyridin-3-yloxymethyl]-N-isobutyl-benzamide; 4-[6-amino-5-(2-chloro-6- fluoro-benzyloxy)-pyridin-3-yl}-benzoic acid; {4-[6-amino-5-(2-chloro-6-fluoro-benzyloxy)-pyridin-3-yl}- phenyl}-{(2R)-2-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl}-methanone, {4-[6-amino-5-(2-chloro-6-fluoro- benzyloxy)-pyridin-3-yl-phenyl}-[(2S)-2-pyrrolidin- 1-ylmethyl-pyrrolidin-1-yl}-methanone; {4-[6-amino-5- (2-chloro-6-fluoro-benzyloxy)-pyridin-3-yll-phenyi}-[(3 S)-3-dimethylamino-pyrrolidin-1-yl}-methanone; {4- [6-amino-5-(2-chloro-6-fluaro-benzyloxy)-pyridin-3-yl}-phenyl}-{(3S)-3-amino-pyrrolidin-1-yl]-methanone; {4-[6-amino-5-(2-chloro-6-fluoro-benzyloxy)-pyridin-3-yl}-phenyl}-(4-methyl-piperazin-1-yl)-methanone; 1-(4-{4-[6-amino-5-(2-chioro-6-fluoro-benzyloxy)-pyridin-3-yl}-benzoyl}-piperazin-1-yl)-ethanone; ~~ 4-[6- amino-5-(2-chloro-6-fluoro-benzyloxy)-pyridin-3-yl}-N-(2-morpholin-4-yl-ethyl)-benzamide; 4-[6-amino-5- (2-chioro-6-fluoro-benzyloxy)-pyridin-3-yli]-N-(3-morpholin-4-yl-propyl)-benzamide; 4-[6-amino-5-(2- chloro-benzyloxy)-pyridin-3-yl]-benzoic acid; {4-[6-amino-5-(2-chloro-benzyloxy)-pyridin-3-yl}-phenyl}- [(2R)-2-pyrrolidin-1-yimethyl-pyrrolidin- 1-yl}-methanons; {4-[6-amino-5-(2-chloro-benzylo:y)-pyridin-3-yl}- phenyl}-{(2 S)-2-pyrrolidin-1-ylmethyl-pyrrolidin-1-yi}-methanone; {4-[6-2mino-5-(2-chloro-benzyloxy)- pyridin-3-yl]-phenyl}-[(3 S)-3-dimethylamino-pyrrolidin-1-yi}-methanone; {4-[6-amino-5-(2-chloro- benzyloxy)-pyridin-3-yi]-phenyl}-[(3S)-3-amino-pyrrolidin-1-yl]-methanone; {4-[6-amino-5-(2-chloro- benzyloxy)-pyridin-3-yi}-phenyl}-(4-pyrrolidin-1-yl-piperidin-1-yl}-methanone; {4-[6-amino-5-(2-chloro- benzyloxy)-pyridin-3-yi}-phenyl}-(4-methyl-piperazin-1-yl)-methanone; 1-(4-{4-[6-amino-5-(2-chloro- benzyloxy)-pyridin-3-yl}-benzoyl}-piperazin-1-yl)-ethanone; 4-[6-amino-5-(2-chloro-benzyloxy)-pyridin-3- yl]-N-(2-morpholin-4-yl-ethyl)}-benzamide; 4-[6-amino-5-(2-chloro-benzyloxy)-pyridin-3-yl]-N-(3- morpholin-4-yl-propyl)-benzamide; 4-[6-amino-5-(2-cyano-benzyloxy)-pyridin-3-yi]-benzoic acid; 2-{2- amino-5-[4-((2R)-2-pyrrolidin-1-ylmethyl-pyrrolidine-1-carbonyl)-phenyl}-pyridin-3-yloxymethyl}- ‘ benzonitrile; 2-{2-amino-5-[4-((2 S)-2-pyrrolidin-1-ylmethyl-pyrrolidine-1-carbonyl)-phenyl}-pyridin-3- yloxymethyl}-benzonitrile; 2-{2-amino-5-[4-((3S)-3-dimethylamino-pyrrolidine-1-carbonyl)-phenyl}-pyridin- . 3-yloxymethyl}-benzonitrile; 2-{2-amino-5-[4-((3S)-3-amino-pyrrolidine-1-carbonyi)-phenyl}-pyridin-3- yloxymethyl}-benzonitrile; 2-{2-amino-5-[4-(4-pyrrolidin-1-yl-piperidine-1-carbonyl)-phenyl}-pyridin-3- yloxymethyl}-benzonitrile; 2-{2-amino-5-[4~(4-methyi-piperazine-1-carbonyl)-phenyl}-pyridin-3- yloxymethyl}-benzonitrile; 2-{5-[4-(4-acetyl-piperazine-1i-carbonyl)-phenyl]-2-amino-pyridin-3- yloxymethyl}-benzonitrile; 4-[6-amino-5-(2-cyano-benzyloxy)-pyridin-3-yI}-N-(1-methyl-piperidin-4-yl)- benzamide; 4-[6-amino-5-(2-cyano-benzyloxy)-pyridin-3-yl}-N-(2-morpholin-4-yl-ethyl)-benzamide; 4-[6-
: amino-5-(2-cyano-benzyloxy)-pyridin-3-yl}-N-(3-morpholin-4-yl-propyl)-benzamide; ~~ 4-[6-amino-5-(2,4- . dichloro-benzyloxy)-pyridin-3-yl-benzoic acid; {4-[6-amino-6-(2,4-dichioro-benzyloxy)-pyridin-3-yl}- phenyl}-[(2R)-2-pyrrolidin-1-yimethyl-pyrrolidin-1-yll-methanone; {4-[6-amino-5-(2,4-dichloro-benzyloxy)- pyridin-3-yl}-phenyl}-[(2 S)-2-pyrrolidin-1-ylmethyl-pyrrolidin-1-y(} methanone; {4-{6-amino-5-(2,4- dichloro-benzyloxy)-pyridin-3-yl}-phenyl}-[(3S)-3-dimethylamino-pyrrolidin-1-yl}-methanone; {4-[6-amino- ’ 5-(2,4-dichloro-benzyloxy)-pyridin-3-yl]-phenyl}-[(3S)-3-amino-pyrrolidin-1 -yl}-methanone; {4-[6-amino-5- (2,4-dichloro-benzyloxy)-pyridin-3-yl}-phenyl}-(4-pyrrolidin-1-yl-piperidin-1 -yl)-methanone; {4-[6-amino-5- (2,4-dichloro-benzyloxy)-pyridin-3-yi}-phenyl}-(4-methyl-piperazin-1-yl)-methanone; 1-(4-{4-[6-amino-5- (2,4-dichloro-benzyloxy)-pyridin-3-yl]-benzoyl}-piperazin-1-yl)-ethanone; 4-[6-amino-5-(2,4-dichloro- benzyloxy)-pyridin-3-yl]-N-(1-methyl-piperidin-4-yl)-benzamide; 4-[6-amino-5-(2,4-dichloro-benzyloxy)- pyridin-3-yi}-N-(2-morpholin-4-yl-ethyl)-benzamide; 4-[6-amino-5-(2,4-dichloro-benzyloxy)-pyridin-3-yll- N-(3-morpholin-4-yl-propyl)-benzamide, 4-[6-amino-5-(2-trifluoromethyl-benzyloxy)-pyridin-3-ylj-benzoic acid; {4-[6-amino-5-(2-trifluoromethyl-benzyloxy)-pyridin-3-yl}-phenyl}-(2R)-2-pyrrolidin-1-ylmethyl- pyrrolidin-1-yl}-methanone; {4-[6-amino-5-(2-trifluoromethyi-benzyloxy)-pyridin-3-yi}-phenyi}-[(2S)-2- pyrrolidin-1-yimethyl-pyrrolidin-1-yl}-methanone; {4-[6-amino-5-(2-trifluoromethyl-benzyloxy)-pyridin-3- yll-phenyl}-[(3S)-3-dimethylamino-pyrrolidin-1i-yll-methanone; [(3S)-3-amino-pyrrolidin-1-yi}-{4-[6-amino- 5-(2-trifluoromethyl-benzyloxy)-pyridin-3-yl}-phenyl}-methanone; {4-[6-amino-5-(2-trifluoromeihyi- benzyloxy)-pyridin-3-yl}-phenyl}-(4-pyrrolidin-1-yi-piperidin-1-yl)-methanone; {4-[6-amino-5-(2- trifluoromethyl-benzyloxy)-pyridin-3-yi]-phenyl}-(4-methyl-piperazin-1-yl)-methanone; 1-(4-{4-[6-amino-5- (2-trifluoromethyl-benzyloxy)-pyridin-3-yl}-benzoyl}-piperazin-1-yl)-ethanone; 4-[6-amino-5-(2- trifluoromethyl-benzyloxy)-pyridin-3-yi}-N-(1-methyl-piperidin-4-yl)-benzamide; 4-[6-amino-5-(2- trifluoromethyl-benzylosy)-pyridin-3-yi]-V-(2-morpholin-4-yl-sthyl)-benzamide; 4-[6-amino-5-(2- trifluoromethyl-benzyloxy)-pyridin-3-yi}-N-(3-morpholin-4-yl-propyl)-benzamide; 4-[6-amino-5-(4-#Hert!- butyl-benzyloxy)-pyridin-3-y(]-benzoic acid; {4-[6-amino-5-(4-tert-butyl-benzyloxy)-pyridin-3-yl]-phenyl}- [(2R)-2-pyrrolidin-1-yimethyl-pyrrolidin-1-yl}-methanone; {4-[6-amino-5-(4-tert-butyl-benzyloxy)-pyridin-3- yll-phenyl}-[(2S)-2-pyrrolidin-1-yimethyi-pyrrolidin-1-yil-methanone; {4-[6-amino-5-(4-tert-buty!- benzyloxy)-pyridin-3-yl}-phenyl}-{(3R)-3-dimethylamino-pyrrolidin-1-yll-methanone; {4-[6-amino-5-(4-tert- butyl-benzyloxy)-pyridin-3-yi}-phenyl}-(4-methyl-piperazin-1-yl)-methanone; 1-(4-{4-[6-amino-5-(4-tert- butyl-benzyloxy)-pyridin-3-yl}-benzoyl}-piperazin-1-yl)-ethanone; 4-[6-amino-5-(4-feri-butyl-benzyloxy)- pyridin-3-yl}-N-(1-methyl-piperidin-4-yi)-benzamide; 4-[6-amino-5-(4-tert-butyl-benzyloxy)-pyridin-3-yl}-N- (2-morpholin-4-yl-ethyl)-benzamide; 4-[6-amino-5-(4-tert-butyl-benzyloxy)-pyridin-3-yl]-N-(3-morpholin-4- - yl-propyl)-benzamide; 4-[6-amino-5-(2-chloro-4-fluoro-benzyloxy)-pyridin-3-yl}-benzoic acid; {4-[6-amino- 5-(2-chloro-4-fluoro-benzyloxy)-pyridin-3-yl]-phenyl}-[(2R)-2-pyrrolidin-1-yimethyl-pyrrolidin-1-yi]- . methanone; {4-[6-amino-5-(2-chioro-4-fluoro-benzyloxy)-pyridin-3-yl}-phenyi}-[(2S)-2-pyrrolidin-1- ylmethyl-pyrrolidin-1-yl}-methanone; {4-[6-amino-5-(2-chioro-4-fluoro-benzyloxy)-pyridin-3-yi]-phenyl}- [(3S)-3-dimethylamino-pyrrolidin-1-yl}-methanone; {4-[6-amino-5-(2-chloro-4-fluora-benzyloxy)-pyridin-3- : yl}-phenyi}-{(35)-3-amino-pyrrolidin-1-yl}-methanone; {4-[6-amino-5-(2-chloro-4-fluoro-benzyloxy)- pyridin-3-yl}-phenyl}-(4-methyl-piperazin-1-yl)-methanone; 1-(4-{4-[6-amino-5-(2-chloro-4-fluoro- benzyloxy)-pyridin-3-yll-benzoyl}-piperazin-1-yl)-ethanone; 4-{6-amino-5-(2-chloro-4-fluoro-benzyloxy)-
pyridin-3-yl]-N-(2-morpholin-4-yi-ethyl)-benzamide; 4-[6-amino-5-(2-chloro-4-fluoro-benzyloxy)-pyridin-3- ’ yl]-N-(3-morpholin-4-yl-propyl)-benzamide; 4-[6-amino-5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-yi}- benzoic acid; {4-[6-amino-5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-yl}-phenyl}-(4-methyl-piperazin-1- yl)-methanone; {4-[6-amino-5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-yl]-phenyl}-(4-pyrrolidin-1-yl- piperidin-1-yl)-methanone; {4-[6-amino-5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-yi]-phenyl}-(4- amino-piperidin-1-yl)-methanone; {4-[6-amino-5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-yl]-pheny}- (3,5-dimethyl-piperazin-1-yl)-methanone; {4-[6-amino-5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-yi}- phenyl}-[(2S)-2-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl]-methanone; {4-[6-amino-5-(2-chloro-3,6-difluoro- benzyloxy)-pyridin-3-yl]-phenyi}-{(3S)-3-dimethylamino-pyrrolidin-1-yl}-methanone; {4-[6-amino-5-(2- chloro-3,6-diflucro-benzyloxy)-pyridin-3-yi]-phenyl}-[(3R)-3-amino-pyrrolidin-1-yl}-methanone; {4-[6- amino-5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-yl}-phenyi}-{(3S)-3-amino-pyrrolidin-1-yl]-methanone; 4-[6-amino-5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-yl]-N-(1-methyl-piperidin-4-yl)-benzamide; 4-[6- amino-5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-yiJ-N-(2-pyrrolidin-1-yl-ethyl)-benzamide; 4-[6-amino- 5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-yi]-N-(3-pyrrolidin-1-yl-propyl)-benzamide, 4-[6-amino-5-(2- chloro-3,6-difluoro-benzyloxy)-pyridin-3-yi]-N-(2-morpholin-4-yl-ethyl)-benzamide; 4-[6-amino-5-(2- chloro-3,6-difluoro-benzyloxy)-pyridin-3-yi]-N-(3-morpholin-4-yl-propyl)-benzamide; 3-[6-amino-5-(2- chloro-3,6-difluoro-benzyloxy)-pyridin-3-yl]-benzoic acid; {3-[6-amino-5-(2-chloro-3,6-difiuoro- benzyloxy)-pyridin-3-yi}-phenyl}-(4-methyl-piperazin-1-yl)-methanone; {3-[6-amino-5-(2-chloro-3,6- difluoro-benzyloxy)-pyridin-3-yl}-phenyl}-(4-pyrrolidin-1-yi-piperidin-1-yl)-methanone; {3-[6~amino-5-(2- chioro-3,6-difluoro-benzyloxy)-pyridin-3-yll-phenyl}-(4-amino-piperidin-1-yl)-methanone; {3-[6-amino-5- (2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-yl}-phenyl}-(3,5-dimethyl-piperazin-1-yl)-methanone; {3-[6- amino-5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-yl}-phenyl}-[(2€)-2-pyrrolidin- 1-ylimathyl-pyrrolidin-1- yl}-methanone; {3-[6-amino-5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-yll-pheny}-[(3S)-3- dimethylamino-pyrrolidin-1-yi]-methanone; {3-[6-amino-5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-yl]- phenyl}-[(3R)-3-amino-pyrrolidin-1-yl}-methanone, {3-[6-amino-5-(2-chloro-3,6-difluoro-benzyloxy)- pyridin-3-yll-phenyl}-[(3S)-amino-pyrrolidin-1-yl}-methanone; 3-[6-amino-5-(2-chloro-3,6-difluoro- benzyloxy)-pyridin-3-yl}-N-(1-methyl-piperidin-4-yl)-benzamide; 3-[6-amino-5-(2-chloro-3,6-difluoro- benzyloxy)-pyridin-3-yl]-N-(2-pyrrolidin-1-yl-ethyl)-benzamide; 3-[6~amino-5-(2-chloro-3,6-difluoro- benzyloxy)-pyridin-3-yl]-N-(3-pyrrolidin-1-yl-propyl)-benzamide; 3-[6-amino-5-(2-chloro-3,6-difluoro- benzyloxy)-pyridin-3-yl}-N-(2-morpholin-4-yl-ethyl)-benzamide, 3-[6-amino-5-(2-chioro-3,6-difluoro- benzyloxy)-pyridin-3-yl]-N-(3-morpholin-4-yl-propyl)-benzamide; N-[2-(4-acetyl-piperazin-1-yl)-ethyl}-3- B [6-amino-5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-yl}-benzamide; 3-(2~chioro-3,6-difluoro- benzyloxy)-5-[4-(1,1-dioxo-1 AS-isothiazolidin-2-yl)-phenyl}-pyridin-2-ylamine; 3-(2,6-dichloro-benzyloxy)- . 5-[4-(1 ,1-dioxo-113-isothiazolidin-2-yl)-phenyl]-pyridin-2-ylamine; 5-[4-(1,1-dioxo-1 A%-isothiazolidin-2-yl)- phenyl}-3-(2-fluoro-6-trifluoromethyl-benzyloxy)-pyridin-2-ylamine; 2-diethylamino-ethanesulfonic acid {4-[6-amino-5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-yll-phenyl}-amide; 2-cyclopropylamino- " ethanesulfonic acid {4-[6-amino-5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-yi}-phenyl}-amide; 2- Pyrrolidin-1-yi-ethanesulfonic acid {4-[6-amino-5-(2-chioro-3,6-difluoro-benzyloxy)-pyridin-3-yl}-phenyl}- amide; 2-(4-hydroxy-piperidin-1-yl)-ethanesulfonic acid {4-[6-amino-5-(2-chloro-3,6-difluoro-benzyloxy)-
pyridin-3-yl]-phenyl}-amide; 2-morpholin-4-yl-ethanesulfonic acid {4-[6-amino-5-(2-chloro-3,6-difluoro- ) benzyloxy)-pyridin-3-yl}-phenyl}-amide; 2-Piperidin-1-yl-ethanesulfonic acid {4-[6-amino-5-(2-chloro-3,6- difluoro-benzyloxy)-pyridin-3-yil-phenyl}-amide; 2-dimethylamino-ethanesulfonic acid {4-[6-amino-5-(2- chloro-3,6-difluoro-benzyloxy)-pyridin-3-yl}-phenyi}-amide; 2-(4-acetyl-piperazin-1-yl)-ethanesulfonic acid {4-[6-aminc-5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-yl}-phenyi}-amide; 2-(cyclopropyimethyl- amino)-ethanesulfonic acid {4-[6-amino-5-(2-chloro-3,6-diflucro-benzyloxy)-pyridin-3-yl]-phenyl}-amide; 2-[(3R)-3-hydroxy-pyrrolidin-1-yl}-ethanesulfonic acid {4-[6-amino-5-(2-chloro-3,6-difiuoro-benzyloxy)- pyridin-3-yl)-phenyi}-amide; 2-[(2S)-2-hydroxymethyl-pyrrolidin-1-yl}-ethanesulfonic acid {4-[6-amino-5- (2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-yi]-phenyl}-amide; 2-[4-(2-hydroxy-acetyl)-piperazin-1-yi]- ethanesulfonic acid {4-[6-amino-5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-yl]-phenyl}-amide; 2-(4- acetyl-piperazin-1-yl)-ethanesulfonic acid {3-]6-amino-5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-yl}- phenyl}-amide; 2-Pyrrolidin-1-yl-ethanesulfonic acid {3-[6-amino-5-(2-chloro-3,6-difluoro-benzyloxy)- pyridin-3-yl}-phenyl}-amide; 2-morpholin-4-yl-ethanesulfonic acid {3-[6-amino-5-(2-chloro-3,6-difiuoro- benzyloxy)-pyridin-3-yl}-phenyl}-amide; 2-diethylamino-ethanesulfonic acid {3-[6-amino-5-(2-chloro-3,6- 16 difluoro-benzyloxy)-pyridin-3-yil-phenyl}-amide; 2-dimethylamino-ethanesulfonic acid {3-[6-amino-5-(2- chioro-3,8-difluoro-benzyloxy)-pyridin-3-yll-phenyl}-amide; 2-Piperidin-1-yl-ethanesulfonic acid {3-[6- amino-5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-yi]-phenyl}-amide; 2-[(3R)-3-hydroxymethyl- pyrrolidin-1-yl}-ethanesulfonic acid {3-[6-amino-5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-yi}-phenyl}- amide; 2-(4-hydroxy-piperidin-1-yl)-ethanesulfonic acid {3-[6-amino-5-(2-chloro-3,6-difluoro-benzyioxy)- pyridin-3-yll-phenyl}-amide; 2-[4-(2-hydroxy-acetyl)-piperazin-1 -yl}-ethanesulfonic acid {3-[6-amino-5-(2- chloro-3,6-difluoro-benzyloxy)-pyridin-3-yl}-phenyl}-amide; 2-[(3R)-3-hydroxy-pyrrolidin-1-yl}- sthanesulfonic acid {3-[6-amino-5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-yl}-phenyl}-amide; 2- (cyclopropylmethyl-amino)-ethanesulfonic acid {3-[6-amino-5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin-3- yll-phenyl}-amide; ~~ 2-cyclopropylamino-ethanesulfonic acid {3-[6-amino-5-(2-chloro-3,6-difluoro- benzyloxy)-pyridin-3-yl]-phenyl}-amide; 3-(2-chloro-3,6-difluoro-benzyloxy)-5-(2-dimethylaminomethyl- phenyl)-pyridin-2-ylamine; compound with trifluoro-acetic acid; 3-(2-chloro-3,6-difluoro-benzyloxy)-5-(3- pyrrolidin-1-yl-phenyl)-pyridin-2-ylamine; compound with trifluoro-acetic acid; N-{4-[6-amino-5-(2-chloro- 3,6-difluoro-benzyloxy)-pyridin-3-ylJ-phenyl}-methanesuifonamide; compound with trifluoro-acetic acid; 5-[6-amino-5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-yl}-thiophene-2-carboxylic acid; {5-[6-amino-5- (2-chloro-3,6-difiuoro-benzyloxy)-pyridin-3-yi]-thiophen-2-yi}~(4-methyl-piperazin-1-yl)-methanone; {56- amino-5-(2-chioro-3,6-difluoro-benzyloxy)-pyridin-3-ylJ-thiophen-2-yi}-[(2R)-2-pyrrolidin-1-yimethyl- pyrrolidin-1-yll-methanone; 5-[6-amino-5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin-3-yi}-thiophene-2- carboxylic acid (1-methyl-piperidin-4-yl)-amide; {5-[6-amino-5-(2-chloro-3,6-difluoro-benzyloxy)-pyridin- . 3-yl}-thiophen-2-yl}-(3,5-dimethyl-piperazin-1-yl)-methanone; . 5-[6-amino-5-(2-chloro-3,6-difluoro- benzyloxy)-pyridin-3-yl)-thiophene-2-carboxylic acid (2-pyrrolidin-1-yl-ethyl)-amide; {5-[6-amino-5-(2- chloro-3,6-difluoro-benzyloxy)-pyridin-3-yl]-thiophen-2-yi}-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone; 4- [6-amino-5-(3-fluoro-2-trifluoromethyl-benzyloxy)-pyridin-3-yl}-benzoic acid; {4-~[6-amino-5-(3-fluoro-2- trifiuoromethyl-benzyloxy)-pyridin-3-yl}-phenyl}-(4-pyrrolidin~1-yl-piperidin-1-yl)-methanone; 4-[6-amino- 5-(3-fluoro-2-trifluoromethyl-benzyloxy)-pyridin-3-yl-N-(1-methyl-piperidin-4-yl)-benzamide; {4-]6-amino-
5-(3-fluoro-2-trifluoromethyl-benzyloxy)-pyridin-3-yl}-phenyl}-(3,5-dimethyl-piperazin-1-yl)-methanone;
. {4-[6-amino-5-(3-fluoro-2-triflucromethyl-benzyloxy)-pyridin-3-yi]-phenyl}-(3-dimethylamino-pyrrolidin-1- yl)-methanone; {4-[6-amino-5-(3-fluoro-2-triflucromethyl-benzyloxy)-pyridin-3-yl]-phenyl}-[(2S)-2- pyrrolidin-1-ylmethyl-pyrrolidin-1-yl}-methanone; 4~[6-amino-5-(3-fluoro-2-trifiucromethyl-benzyloxy)- pyridin-3-yl]-#N!-(2-morpholin-4-yl-ethyl)-benzamide; {4-[6-amino-5-(3-fluoro-2-trifiuoromethy!- benzyloxy)-pyridin-3-yl}-phenyl}-(4-methyl-piperazin-1-yl)-methanone; N-[2-(4-acetyl-piperazin-1-yl)- ethy(}-4-[6-amino-5-(3-fluoro-2-trifluoromethyl-benzyloxy)-pyridin-3-yll-benzamide; 2-Piperidin-1-yl- ethanesulfonic acid (4-{6-amino-5-[1-(2-chloro-3,6-difluoro-phenyl)-ethoxy}-pyridin-3-yl}-phenyl)-amide; 2-(4-hydroxy-piperidin-1-yl)-ethanesulfonic acid (4-{6-amino-5-[1-(2-chloro-3,6-difluoro-phenyl)-ethoxy]- pyridin-3-yl}-phenyl)-amide; 2-dimethylamino-ethanesulfonic acid (4-{6-amino-5-[1-(2-chloro-3,6-difluoro- phenyl)-ethoxy]-pyridin-3-yi}-phenyl)-amide; 2-cyclopropylamino-ethanesulfonic acid (4-{6-amino-5-{1- (2-chloro-3,6-difluoro-phenyl)-ethoxy]-pyridin-3-yl}-phenyl)-amide; 4-{6-amino-5-{1-(2,6-dichloro-3-fluoro- phenyl)-ethoxy]-pyridin-3-yl}-benzoic acid; (4-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]- pyridin-3-yl}-phenyl)-[(2R)-2-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl)-methanone; 4-{6-amino-5-[1-(2,6- 16 dichloro-3-fluoro-phenyi)-ethoxyl-pyridin-3-yl}-N-(1-methyl-piperidin-4-yl)-benzamide; (3-{6-amino-5-[1- (2,6-dichioro-3-fluoro-phenyl)-ethoxyl-pyridin-3-yl}-phenyl)-[(3R)-3-amino-pyrrolidin-1-y)]-methanone; (4-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxyl-pyridin-3-yl}-phenyl)-(4-pyrrolidin-1-yl-piperidin- 1- yl)-methanone; (4-{6-amino-5-[1-(2,6-dichioro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-phenyl)-(4-methyl- piperazin-1-yl}-methanone; (4-{6-amino-5-[1~(2,6-dichloro-3-flucro-phenyl)-ethoxy]-pyridin-3-yi}-phenyl)- (3,5-dimethyl-piperazin-1-yl}-methanone; 2-cyclopropylamino-ethanesulfonic acid (4-{6-amino-5-[1-(2,6- dichloro-3-flucro-phenyi)-ethoxy}-pyridin-3-yi}-phenyl)-amide; 2-dimethylamino-ethanesulfonic acid (4-{6- amino-5-[1-(2,6-dichloro-3-fiuoro-phenyl)-sthoxyl-pyridin-3-yl}-phenyl)-amide; 2-[(3R)-3-hydro:y- pyrrolidin-1i-yl)]-ethanesuifonic acid (4-{6-amino-5-]1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yf}- phenyl)-amide; and pharmaceutically acceptable salts, hydrates and solvates thereof.
37. A compound selected from the group consisting of. 4-[5-amino-6-(2,6-dichloro-benzyloxy)- pyrazin-2-yl}-phenol; 3-(2,6-dichloro-benzyloxy)-5-[4-(1,1-dioxo-1 A%-isothiazolidin-2-yl)-phenyl}-pyrazin- 2-ylamine; 3-(2,6-dichloro-benzyloxy)-5-[3-(2-morpholin-4-yl-ethoxy)-phenyl]-pyrazin-2-ylamine; 3-(2,6- dichloro-benzyloxy)-5-{4-(2-morpholin-4-yl-ethoxy)-phenyl}-pyrazin-2-ylamine; 5-(4-amino-phenyl)-3- (2 6-dichloro-benzyloxy)-pyrazin-2-ylamine; 4-[5-amino-6-(2,6-dichloro-benzyloxy)-pyrazin-2-yl}-benzoic acid; {4-[5-amino-6-(2,6-dichloro-benzyloxy)-pyrazin-2-yl}-phenyi}-[(2R)-2-pyrrolidin-1-ylmethyl-
. pyrrolidin-1-yll-methanone; {4-[5-amino-6-(2,6-dichloro-benzyloxy)-pyrazin-2-yl]-phenyl}-(4-pyrrolidin-1- yl-piperidin-1-yl)-methanone; 2-morpholin-4-yl-ethanesulfonic acid {4-[5-amino-6-(2-chloro-3,6-difluoro- ] benzyloxy)-pyrazin-2-yi}-phenyl}-amide; 2-piperidin-1-yl-ethanesulfonic acid {4-[5-amino-6-(2-chloro-3,6- difluoro-benzyloxy)-pyrazin-2-yl}-phenyl}-amide; 2-(4-Hydroxy-piperidin-1-yl)-ethanesulfonic acid {4-[5- amino-6-(2-chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yl}-phenyl}-amide; 2-pyrrolidin-1-yl-ethanesulfonic acid {4-[5-amino-6-(2-chioro-3,6-difluoro-benzyloxy)-pyrazin-2-ylj-phenyl}-amide; 2-[(3R)-3-Hydroxy- pyrrolidin-1-yi}-ethanesulfonic acid {4-[5-amino-6-(2-chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yli}-phenyi}- amide; 2-[(2S)-2-Hydroxymethyl-pyrrolidin-1-yi}-ethanesulfonic acid {4-[5-amino-6-(2-chloro-3,6-difluoro-
benzyloxy)-pyrazin-2-yi]-phenyl}-amide; 2-(cyclopropylmethyl-amino)-ethanesulfonic acid {4-[5-amino-6- i (2-chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yl}-phenyl}-amide; 2-dimethylamino-ethanesulfonic acid {4- [5-amino-6-(2-chloro-3,6-diflucro-benzyloxy)-pyrazin-2-yl]-phenyl}-amide; 2-diethylamino-ethanesulfonic acid {4-[5-amino-6-(2-chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yl}-phenyl}-amide; 2-(4-acetyl-piperazin- 1-yl)-ethanesulfonic acid {4-[5-amino-6-(2-chioro-3,6-difluoro-benzyloxy)-pyrazin-2-yl}-phenyl}-amide; 2- [4-(2-Hydroxy-acetyl)-piperazin-1-yi]-ethanesulfonic acid {4-[5-amino-6-(2-chloro-3,6-difluoro- benzyloxy)-pyrazin-2-yll-phenyl}-amide; 2-cyclopropylamino-ethanesulfonic acid {4-[5-amino-6-(2- chioro-3,6-difluoro-benzyloxy)-pyrazin-2-yl]-phenyl}-amide; 2-[(3R)-3-Hydroxymethyl-pyrrolidin-1-yl}- ethanesulfonic acid {3-[5-amino-6-(2-chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yl}-phenyl}-amide; 2-(4- Hydroxy-piperidin-1-yl)-ethanesulfonic acid {3-[5-amino-6-(2-chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yi}- phenyl}-amide; 2-(4-acetyl-piperazin-1-yl)-ethanesulfonic acid {3-[5-amino-6-(2-chloro-3,6-difluoro- benzyloxy)-pyrazin-2-yl]-phenyl}-amide; 2-piperidin-1-yl-ethanesulfonic acid {3-[5-amino-6-(2-chloro-3,6- difluoro-benzyloxy)-pyrazin-2-yl}-phenyl}-amide; 2-diethylamino-ethanesulfonic acid {3-[5-amino-6-(2- chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yl]-phenyi}-amide; 2-morpholin-4-yl-ethanesuifonic acid {3-[5- amino-6-(2-chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yl}-phenyl}-amide; 2-pyrrolidin-1-yl-ethanesulfonic acid {3-[6-amino-8-(2-chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yl}-phenyl}-amide; 2-dimethylamino- ethanesulfonic acid {3-[5-amino-6-(2-chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yi]-phenyl}-amide; 2-[4-(2- Hydroxy-acetyl)-piperazin-1-yi]-ethanesulfonic acid {3-[5-amino-6-(2-chloro-3,6-difluoro-benzyloxy)- pyrazin-2-yl]-phenyl}-amide; 2-(cyclopropylmethyl-amino)-ethanesulfonic acid {3-[5-amino-6-(2-chioro- 3,6-difluoro-benzyloxy)-pyrazin-2-yll-phenyl}-amide; 2-[(3R)-3-Hydroxy-pyrrolidin-1-yl}-ethanesulfanic acid {3-[5-amino-6-(2-chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yil-phenyl}-amide; 2-cyclopropylamino- ethanesulfonic acid {3-[5-amino-6-(2-chioro-3,6-difluoro-benzylo:y)-pyrazin-2-yl}-phenyl}-amide; 4-[5- amino-6-(2-chioro-3,6-difluoro-benzyloxy)-pyrazin-2-yl]-benzoic ~~ acid; {4-[5-amino-8-(2-chloro-3,6- difluoro-benzyloxy)-pyrazin-2-yl]-phenyl}-[(2R)-2-pyrrolidin-1-yImethyl-pyrrolidin-1-yl}- methanone; 4-[5- amino-6-(2-chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yi}-N-(2-pyrrolidin-1-yl-ethyl)-benzamide; {4-[5- amino-6-(2-chloro-3,6-diflucro-benzyloxy)-pyrazin-2-yl}-phenyl}-{(3 S)-3-amino-pyrrolidin-1-yl}- methanone; N-[2-(4-acetyl-piperazin-1-yl)-ethyl]-4-[5-amino-6-(2-chloro-3,6-difluoro-benzyloxy)-pyrazin- 2-yll-benzamide; 4-[5-amino-6-(2-chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yl}-N-(3-pyrrolidin-1-y}- propyl)-benzamide; {4-[5-amino-6-(2-chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yI}-phenyl}~[(3S)-3- dimethylamino-pyrrolidin-1-yll-methanone; {4-[5-amino-6-(2-chloro-3,6-diflucro-benzyloxy)-pyrazin-2-yi}- phenyl}H(3R)-3-dimethylamino-pyrrolidin-1-yl}-methanone; {4-[5-amino-6-(2-chloro-3,6-difluoro- . benzyloxy)-pyrazin-2-yi}-phenyl}-(3,5-dimethyl-piperazin-1-yl)-methanone; {4-[5-amino-6-(2-chloro-3,6- difluoro-benzyloxy)-pyrazin-2-yl}-phenyl}-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone; 4-[5-amino-6-(2- chioro-3,6-difluoro-benzyloxy)-pyrazin-2-ylj-N-(3-morpholin-4-yl-propyl)-benzamide; 4-[5-amino-6-(2- ) 35 chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yl]-N-(1-methyl-piperidin-4-yl)-benzamide; 4-[5-amino-6-(2- chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yl}-N-(2-morpholin-4-yl-ethyl)-benzamide; {4-[5-amino-6-(2- chioro-3,6-difluoro-benzyloxy)-pyrazin-2-yl}-phenyl}-(4-methyl-piperazin-1-yl)-methanone; 3-[5-amino-6- (2-chloro-3,6-difluoro-benzyloxy)-pyrazin-2-ylj-benzoic acid; . {3-[5-amino-6-(2-chloro-3,6-difluoro- benzyloxy)-pyrazin-2-yl}-phenyi}-(4-methyl-piperazin-1-yl)-methanone; {3-[5-amino-6-(2-chioro-3,6-
oo -296 - difluoro-benzyloxy)-pyrazin-2-yl]-phenyl}-[(3R)-3-amino-pyrrolidin-1-yl]-methanone; {3-[5-amino-6-(2- ’ chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yl}-phenyl}-[(3S)-3-amino-pyrrolidin-1-yl}-methanone; {3-[5- amino-6-(2-chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yl}-phenyi}-(3,5-dimethyl-piperazin-1-yl)-methanone; 3-[5-amino-6-(2-chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yl}-N-(3-morpholin-4-yl-propyl)-benzamide; {3- [5-amino-6-(2-chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yi}-phenyl}-(4-pyrrolidin-1-yl-piperidin-1-yl)- methanone; {3-[5-amino-6-(2-chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yl}-phenyl}-[(3S)-3- dimethylamino-pyrrolidin-1-yl}-methanone; 3-[5-amino-6-(2-chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yl}- N-(2-pyrrolidin-1-yi-ethyl)-benzamide; 3-{5-amino-6-(2-chloro-3,6-difiuoro-benzyloxy)-pyrazin-2-yi}-N-(1- methyl-piperidin-4-yl)-benzamide; {3-[5-amino-6-(2-chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yl}-phenyl}- [(2S)-pyrrolidin-1-yimethyi-pyrrolidin-1-yl}-methanone; ~~ 3-[5-amino-6-(2-chloro-3,6-difluoro-benzyloxy)- pyrazin-2-yl}-N-(2-morpholin-4-yl-ethyl)-benzamide; N-[2-(4-acetyl-piperazin-1-yl)-ethyl}-3-[5-amino-6-(2- chioro-3,6-difluoro-benzyloxy)-pyrazin-2-yil-benzamide; 3-[5-amino-6-(2-chloro-3,6-difluoro-benzyloxy)- pyrazin-2-yl}-N-(3-pyrrolidin-1-yl-propyl)-benzamide; 3-(2-chloro-3,6-difluoro-benzyloxy)-5-(1H-indol-5- yl)-pyrazin-2-ylamine; 3-(2-chloro-3,6-difluoro-benzyloxy)-5-(3-pyrrolidin-1-ylmethyl- 1 H-indol-5-yl)- pyrazin-2-ylamine; 3-(2-chloro-3,6-difluoro-benzyloxy)-5-(3-diethylaminomethyl-1H-indol-5-yl)-pyrazin-2- ylamine; 1-(4-{5-[5-amino-6-(2-chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yi}- 1H-indol-3-yimethyl}- piperazin-1-yl)-ethanone; 3-(2-chloro-3,6-difluoro-benzyloxy)-6-[3-(2,6-dimethyl-morpholin-4-yimethyl)- 1H-indol-5-yl)-pyrazin-2-ylamine; N-(1-{5-[5-amino-6-(2-chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yl]-1H- indol-3-yimethyl}-(3S)-pyrrolidin-3-yl)-acetamide; 3-(2-chioro-3,6-difluoro-benzyloxy)-5-(3-piperidin-1- ylmethyk1H-indol-5-yl)-pyrazin-2-ylamine; 3-(2-chloro-3,6-difluoro-benzyloxy)-5-(3-morpholin-4-yimethyl- 1 H-indol-5-yl)-pyrazin-2-ylamine; 3-[1-(2-chloro-3,6-difluoro-phenyl)-2-methyl-propoxy]-5-14-(2- morpholin-4-yl-ethoxy)-phenyl]-pyrazin-2-ylamine; 3-[1-(2-chloro-3,6-difluoro-phenyl)-ethosyl-5-[4-(2- morpholin-4-yl-ethoxy)-phenyl]-pyrazin-2-ylamine; compound with frifluoro-acetic acid; 3-[1-(2,6- dichloro-3-fluoro-phenyl)-ethoxy]-5-[4-(2-morpholin-4-yl-ethoxy)-phenyi]-pyrazin-2-ylamine; compound with trifluoro-acetic acid; N-(4-{5-amino-6-[1-(2-chloro-3,6-difluoro-phenyl)-ethoxy]-pyrazin-2-yl}-phenyl)- methanesuifonamide; 2-pyrrolidin-1-yl-ethanesulfonic acid (4-{5-amino-6-[1-(2-chloro-3,6-difluoro- phenyl)-ethoxy}-pyrazin-2-yi}-phenyl)-amide; 2-(4-Hydroxy-piperidin-1-yl)-ethanesulfonic acid (4-{5- amino-6-[1-(2-chloro-3,6-difluoro-phenyl)-ethoxy}-pyrazin-2-yl}-phenyl)-amide; 2-piperidin-1-yl- ethanesulfonic acid (4-{5-amino-6-[1-(2-chloro-3,6-difluoro-phenyl)-ethoxyl-pyrazin-2-yl}-phenyl)-amide; 2-(cyclopropylmethyl-amino)-ethanesutfonic acid (4-{5-amino-6-[1-(2-chloro-3 6-difiluoro-phenyl)-ethoxy]- pyrazin-2-yl}-phenyl)-amide; 2-[(3R)-3-Hydroxy-pyrolidin-1-yl]-ethanesulfonic acid (4-{5-amino-6-[1-(2- ’ chloro-3,6-diflucro-phenyl)-ethoxyl-pyrazin-2-yl}-phenyl)-amide; 2-[(2S)-2-Hydroxymethyl-pyrrolidin-1-yl}- ethanesulfonic acid (4-{5-amino-6-[1-(2-chloro-3,6-difluoro-phenyl)-ethoxy]-pyrazin-2-yl}-phenyl)-amide; . 2-dimethylamino-ethanesulfonic acid (4-{5-amino-6-{1-(2-chloro-3,6-difluoro-phenyi)-ethoxyl-pyrazin-2- yl}-phenyl)-amide; 2-morpholin-4-yl-ethanesulfonic acid (4-{6-amino-6-[1-(2-chloro-3,6-difluoro-phenyl)- ethoxy]-pyrazin-2-yl}-phenyl)-amide; 2-diethylamino-ethanesulfonic acid (4-{5-amino-6-[1-(2-chloro-3,6- difluoro-phenyl)-ethoxyl-pyrazin-2-yl}-phenyl)-amide; 2-cyclopropylamino-ethanesulfonic acid (4-{5- amino-6-[1-(2-chioro-3,6-diflucro-phenyl)-ethoxyl-pyrazin-2-yl}-phenyl)-amide; 3-{5-amino-6-[1-(2,6- dichloro-3-fluoro-phenyl)-ethoxyl-pyrazin-2-yl}-benzoic acid; (3-{5-amino-6-{1-(2,6-dichloro-3-fluoro-
phenyl)-ethoxy}-pyrazin-2-yl}-pheny!)-[(3S)-3-amino-pyrrolidin-1-yl)-m-ethanone; (3-{5-amino-6-[1-(2,6- . dichloro-3-fluoro-phenyl)-ethoxyl-pyrazin-2-yl}-phenyl)-[(3R)-3-amino-pyrrolidin-1-yl)-m-ethanone; (3-{5- amino-6-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyrazin-2-yl}-phenyl)-[(2R)-2-pyrrolidin-1-ylmethyl- pyrrolidin-1-yl)-methanone; ~~ N-[2-(4-acetyl-piperazin-1-yl)-ethyl]-3-{5-amino-6-[1-(2,6-dichloro-3-fluoro- phenyl)-ethoxyl-pyrazin-2-yl}-benzamide; (3-{5-amino-6-[1-(2,6-dichloro-3-fluoro-phenyi)-ethoxy}- pyrazin-2-yl}-phenyl)-[(2S)-2-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl)-methanone; 3-{5-amino-6-[1-(2-chloro- 3,6-difluoro-phenyl)-ethoxyl-pyrazin-2-yl}-benzoic acid; 3-{5-amino-6-[1-(2,6-dichloro-3-fluoro-phenyl)- ethoxy]-pyrazin-2-yl}-N-(1-methyl-piperidin-4-yl)-benzamide; 3-{5-amino-6-[1-(2,6-dichloro-3-fluoro- phenyl)-ethoxy]-pyrazin-2-yl}-N-(3-pyrrolidin-1-yl-propyl)-benzamide; ~~ (3-{5-amino-6-[1-(2,6-dichloro-3- fluoro-phenyl)-ethoxy]-pyrazin-2-yl}-phenyl)-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone; 4-{5-amino-6- (3-fluoro-2-trifiuoromethyl-benzyloxy)-pyrazin-2-yl}-benzoic acid; 4-[5-amino-6-(3-fluoro-2-trifluoromethyl- benzyloxy)-pyrazin-2-yl}-N-(2-morpholin-4-yl-ethyl)-benzamide; 4-[5-amino-6-(3-fluoro-2-trifluoromethyi- benzyloxy)-pyrazin-2-yl}-N-(1-methyl-piperidin-4-yl)-benzamide; and pharmaceutically acceptable salts, hydrates and solvates thereof.
38. A compound selected from the group consisting of: (4-{6-amino-5-[1-(2,6-dichloro-3-fluoro- phenyl)-ethoxyl-pyridin-3-yi}-phenyl)-(4-methyl-piperazin-1-yl)-methanone; N-[2-(4-acetyl-piperazin-1-yl)- ethyl}-4-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy}-pyridin-3-yl}-benzamide; 4-{6-amino-5-[1- (2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yi}-N-(3-pyrrolidin-1-yl-propyl)-benzamide; 4-{6-amino-5- [1-(2,6-dichlioro-3-fluoro-phenyl)-ethoxy}-pyridin-3-yi}-N-(2-morpholin-4-yl-ethyl}-benzamide; (4-{6- amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy}-pyridin-3-yi}-phenyl)-((S)-3-amino-pyrrolidin-1-yl)- methanone; (4-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-sthoiy}-pyridin-3-yl}-phenyl)-((R)-3-amino- pyrrolidin-1-yl)-methanone; (4-{8-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxyl-pyridin-3-yi}-phenyl)- (4-amino-piperidin-1-yl)-methanone; (4-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yi}- phenyl)-((S)-3-hydroxy-pyrrolidin-1-yl)-methanone; (4-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)- ethoxy]-pyridin-3-yl}-phenyl)-((R)-3-hydroxy-pyrrolidin-1-yl)-methanone; (4-{6-amino-5-[1-(2,6-dichloro-~3- fluoro-phenyl)-ethoxy]-pyridin-3-yl}-phenyl)-((R)-2-hydroxymethyl-pyrrolidin- 1-yl)-methanone; 4-{6- amino-5-[1-(2,6-dichloro-3-flucro-phenyl)-ethoxy}-pyridin-3-yl}-N-(2-diethylaminc-ethyl)-benzamide; 4-{6- amino-5-[1-(2,6-dichlioro-3-fluoro-phenyl)-ethoxy]-pyridin-3-y}-N-(2-pyrrolidin-1-yl-ethyl)-benzamide; 3- {6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy}-pyridin-3-yi}-benzoic acid; (3-{6-amino-5-[1-(2,6- dichloro-3-fluoro-phenyl)-ethoxy}-pyridin-3-yl}-phenyl)-(4-methyl-piperazin-1-yl)}-methanone; 3-{6-amino- “ 5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxyl-pyridin-3-yl}-N-(1-methyl-piperidin-4-yl)-benzamide; (3-{6- amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-phenyl)-((S)-2-pyrrolidin-1-yimethyl- pyrrolidin-1-yl)-methanone; N-[2-(4-acetyl-piperazin-1-yi)-ethyi]-3-{6-amino-5-[1-(2,6-dichloro-3-fluoro- phenyl)-ethoxyl-pyridin-3-yl}-benzamide; (3-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyi)-ethoxy]-pyridin- 3-yi}-phenyl)-((S)-3-amino-pyrrolidin-1-yl)}-methanone; ~~ 3-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)- ethoxy}-pyridin-3-yi}-N-(3-morpholin-4-yi-propyl)-benzamide; (3~{6~amino-5-[1-(2,6-dichioro-3-fluoro- phenyl)-ethoxy}-pyridin-3-yi}-phenyl)-((R)-2-pyrrolidin-1-yimethyl-pyrrolidin-1-yl)-methanone; 3-{6-amino- 5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-N-(2-pyrrolidin-1-yl-ethyl)-benzamide; 3-{6-
amino-5-[1-(2,6-dichloro-3-fluoro-phenyi)-ethoxy}-pyridin-3-yi}-N-(3-pyrrolidin-1-yl-propyl)-benzamide; 3- . {6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-N-(2-morpholin-4-yl-ethyl)-benzamide; (3-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-phenyl)-(4-pyrrolidin-1-yl-piperidin-1- yl)-methanone; 2-diethylamino-ethanesulfonic acid (4-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)- ethoxy]-pyridin-3-yl}-phenyl)-amide; 2-(4-Hydroxy-piperidin-1-yl)-ethanesulfonic acid (4-{6-amino-5-[1- (2,6-dichloro-3-fluoro-phenyi)-ethoxy}-pyridin-3-yl}-phenyl)-amide; 2-piperidin-1-yl-ethanesulfonic acid (4-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxyl-pyridin-3-yl}-phenyl)-amide; 2- (cyclopropylmethyl-amino)-ethanesulfonic acid (4-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxyl- pyridin-3-yl}-phenyl)-amide; 2-((R)-3-Hydroxy-pyrrolidin-1-yl)-ethanesulfonic acid (4-{6-amino-5-[1-(2- chloro-3,6-difluoro-phenyl)-ethoxyl-pyridin-3-yl}-phenyl)-amide; 2-cyclopropylamino-ethanesulfonic acid (4-{6-amino-5-[1-(2-chloro-3,6-difluoro-phenyl)-ethoxy]-pyridin-3-yl}-phenyl)-amide; 2-diethylamino- ethanesulfonic acid (4-{6-amino-5-[1-(2-chloro-3,6-difluoro-phenyf)-ethoxy]-pyridin-3-yl}-phenyl)-amide; 4-{6-amino-5-[1-(2-chloro-3,6-difluoro-phenyl)-ethoxy]-pyridin-3-yl}-benzoic acid; 4-{6-amino-5-[1-(2- . chloro-3,6-difluoro-phenyl)-ethoxyl-pyridin-3-yl}-N-(2-morpholin-4-yl-ethyl)-benzamide; 4-{6-amino-5-[1- (2-chloro-3,6-difluoro-phenyl)-ethoxy]-pyridin-3-yi}-N-(1-methyl-piperidin-4-yl)-benzamide; (4-{6-amino-5- [1-(2-chloro-3,6-diflucro-phenyl)-ethoxy]-pyridin-3-yi}-phenyl)-((R)-2-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl)- methanone; (4-{6-amino-5-[1-(2-chloro-3,6-difluoro-phenyl)-ethoxy]-pyridin-3-yl}-phenyl)-((R)-3-amino- pyrrolidin-1-yl)-methanone; (4-{6-amino-5-[1-(2-chioro-3,6-difluoro-phenyl)-ethoxy}-pyridin-3-yl}-phenyl)- ((3R,58)-3,5-dimethyl-piperazin-1-yl)-methanone; 4-{6-amine-5-[1-(2-chloro-3,6-difluoro-phenyl)-ethoxy}- pyridin-3-yl}-N-(3-pyrrolidin-1-yi-propyl)-benzamide; (4-{6-amino-5+1-(2-chloro-3,6-difluoro-phenyl)- ethoxy]-pyridin-3-yl}-phenyl)-((S)-2-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl}-methanone; (4-{6-amino-5-[1-(2- chloro-3,8-difluoro-phenyl)-sthoxy]-pyridin-3-yl}-phenyl)-(4-methyl-piperazin-1-yl)-methanone; (4-{6- amino-5-{1-(2-chloro-3,6-difluore-phenyl)-ethoxyl-pyridin-3-yi}-phenyl)-(4-pyrrolidin-1-yl-piperidin-1-yl)- methanone; 4-{6-amino-5-[1~(2-chloro-3,6-difluoro-phenyl)-ethoxy]-pyridin-3-yl}-N-(2-pyrrolidin-1-yt- ethyl)-benzamide; (4-{6-amino-5-[1-(2-chloro-3,8-difluoro-phenyl)-ethoxy}-pyridin-3-yl}-phenyl)-((S)-3- amino-pyrrolidin-1-yl}-methanone; 3-{6-amino-5-{1-(2-chloro-3,6-difluoro-phenyl)-ethoxyj-pyridin-3-yl}- benzoic acid; (3-{6-amino-5-{1-(2-chioro-3,6-difluoro-phenyl}-ethoxy}-pyridin-3-yl}-phenyl)-((3R,58)-3,5- dimethyl-piperazin-1-yl)-methanone; (3-{6-amino-5-[1-(2-chloro-3,6-difluoro-phenyf)-ethoxy]-pyridin-3- yi}-phenyl)-((R)-3-amino-pyrrolidin-1-yl)-methanone; 3-{6-amino-5-[1-(2-chloro-3,6-difluora-phenyi)- ethoxy]-pyridin-3-yl}-N-(1-methyl-piperidin-4-yl)-benzamide; (3-{6-amino-~5-[1-(2-chioro-3,6-difiuoro- phenyl)-ethoxy]-pyridin-3-yi}-phenyl)-(4-methyl-piperazin-1-yl)-methanone; ~~ 3-{6-amino-5-[1-(2-chloro- . 3,6-difluoro-phenyl)-ethoxyl-pyridin-3-yl}-N-(3-pyrrolidin-1-yl-propyl)-benzamide; 3-{6-amino-5-[1-(2- chloro-3,6-difluoro-phenyl}-ethoxyl-pyridin-3-yl}-N-(2-pyrrolidin-1-yl-ethyl)-benzamide; (3-{6-amino-5-[1- (2-chloro-3,6-difluoro-phenyl)-ethoxy]-pyridin-3-yl}-phenyl)-((S)-3-amino-pyrrolidin-1-yl)-methanone; 3- {6-amino-5-[1-(2-chloro-3,6-difluora-phenyl)-ethoxy]-pyridin-3-yi}-N-(2-morphaolin-4-yl-ethyl)-benzamide; (3-{6-amino-5-[1-(2-chloro-3,6-difluoro-phenyl)-ethoxy]-pyridin-3-yl}-phenyl)-((R)-2-pyrrolidin-1-ylmethyk- pyrrolidin-1-yl)-methanone; (3-{6-amino-5-{1-(2-chloro-3,6-difluoro-phenyl)-ethoxy]-pyridin-3-yi}-phenyl)- ((S)-2-pyrrotidin-1-yimethyl-pyrrolidin-1-yl)-methanone; 3-[1-(2-chloro-3,6-difluoro-phenyl)-ethoxy]-5-[4- (2-morpholin-4-yl-ethoxy)-phenyl}-pyridin-2-ylamine; 3-[1-(2-chloro-3,6-difluoro-phenyl)-ethoxy}-5-[3-(2-
: morpholin-4-yl-ethoxy)-phenyl]-pyridin-2-ylamine; 3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5-[4-(2- pyrrolidin-1-yl-ethoxy)-phenyl]-pyridin-2-ylamine; 3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5-{4-[2-(1- methyl-pyrrolidin-2-yl)-ethoxy]-phenyi}-pyridin-2-ylamine; 3-[1-(2,6-dichloro-3-fluoro-phenyi)-ethoxyl-5- {4-(2-morpholin-4-yl-ethoxy)-phenyl]-pyridin-2-ylamine; 3-[1~(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5-[3- (2-morpholin-4-yl-ethoxy)-phenyl)-pyridin-2-ylamine; ~~ 1-(4-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)- ethoxy}-pyridin-3-yl}-phenoxy)-3-morpholin-4-yl-propan-2-ol; 3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]- 5-[4-(2-diethylamino-ethoxy)-phenyll-pyridin-2-ylamine; 3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5-{4- (1-methyl-piperidin-3-yimethoxy)-phenyl}-pyridin-2-ylamine; 3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5- [4-(2-diisopropylamino-ethoxy)-phenyl]-pyridin-2-ylamine; 3-[1-(2,6-dichioro-3-fluoro-phenyl)-ethoxy}-5- [4-(1-methyl-piperidin-4-yloxy)-phenyl}-pyridin-2-ylamine; N-(4-{6-amino-5-[1-(2-chloro-3,6-difluoro- phenyl)-ethoxy]-pyridin-3-yl}-phenyl)-methanesulfonamide; 3-[1-(2-chloro-3,8-difluoro-phenyl)-ethoxy}-5- [4-(1,1-dioxo-1lambda*6*-isothiazolidin-2-yl)-phenyl]-pyridin-2-ylamine; N-(4-{6-amino-5-[1-(2,6-dichloro- 3-fluoro-phenyl)-ethoxy}-pyridin-3-yl-phenyl)-methanesulfonamide; 3-[1-(2,6-dichloro-3-fluoro-phenyl)- ethoxy]-5-phenyl-pyridin-2-ylamine; N-(4-{6-amino-5-[(R)-1-(2-chloro-3,6-difluoro-pheny!)-ethoxy]- pyridin-3-yl}-phenyi)}-methanesulfonamide; 3-[1-(2,6-dichioro-3-fluoro-phenyl)-ethoxy]-5-thiophen-3-yl- pyridin-2-ylamine; 5-benzolblthiophen-2-yl-3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-2-ylamine, 4-methyl-piperazine-1-carboxylic acid (4-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxyl-pyridin-3- yl}-phenyl)-amide; 1-(4-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy}-pyridin-3-yl}-phenyl)-3-(2- pyrrolidin-1-yl-ethyl)-urea; 1-(4-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl}-ethoxy]-pyridin-3-yl}-phenyl)- 3-(2-hydroxy-ethyl)-urea; 1-(4-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxyl-pyridin-3-yl}-phenyl)- 3-(2-morpholin-4-yl-ethyl)-urea; (R)-3-amino-pyrrolidine-1-carboxylic acid (4-{6-amino-5-[1-(2,6-dichloro- 3-fluoro-phenyl)-zthoxyl-pyridin-3-yi}-phenyl)-amide; (S)-3-amine-pyrrolidine-1-carboiylic acid (4-{6- amino-5-{1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-phenyl)-amide; 1-(4-{6-amino-5-{1-(2,6- dichloro-3-fluoro-phenyl)-ethoxy}-pyridin-3-yi}-phenyl)-3-(1-methyl-piperidin-4-yl)-urea; 1-(4-{6-amino-5- [1-(2-chloro-3,6-difluoro-phenyl)-ethoxy]-pyridin-3-yl}-phenyl)-3-(1-methyl-piperidin-4-yl)-urea; (R)-3- amino-pyrrolidine-1-carboxylic acid (4-{6-amino-5-[1-(2-chloro-3,6-difluoro-phenyl)-ethoxy]-pyridin-3-yl}- phenyl)-amide; (S)-3-amino-pyrrolidine-1-carboxylic acid (4-{6-amino-5-[1-(2-chloro-3,6-difiuoro-phenyl)- ethoxyl-pyridin-3-yl}-phenyl)-amide; 1-(4-{6-amino-5-[1-(2-chloro-3,6-difluoro-phenyl)-ethoxyl-pyridin-3- yi}-phenyl)-3-(2-hydroxy-ethyl)-urea; 4-methyl-piperazine-1-carboxylic acid (4-{6-amino-5-[1-(2-chloro- 3,6-difluoro-phenyl)-ethoxy]-pyridin-3-yi}-phenyl)-amide; 1-(4-{6-amino-5-[1-(2-chloro-3,6-difluoro- phenyl)-ethoxy]-pyridin-3-y!}-phenyl)-3~(2-pyrrolidin- 1-yl-ethyl)-urea; 1-(4-{6-amino-5-[1-(2-chloro-3,6- . difluoro-phenyi)-ethoxy]-pyridin-3-yi}-phenyl)-3-(2-morpholin-4-yl-ethyl)-urea; (R)-2-pyrrolidin-1-ylmethyi- pyrrolidine-1-carboxylic acid (4-{6-amino-5-[1-(2-chloro-3,6-difluoro-phenyl)-ethoxy]-pyridin-3-yl}- Rk phenyl)-amide; 3-{6-amino-5-[1-(2,6-dichloro-phenyl)-ethoxy]-pyridin-3-y(}-benzoic acid; (3-{6-amino-5- [1-(2,6-dichloro-phenyl)-ethoxyl-pyridin-3-yl}-phenyl)-((3R,5S)-3,5-dimethyl-piperazin-1-yl)-methanone; (3-{6-amino-5-[1-(2,6-dichloro-phenyl)-ethoxy]-pyridin-3-yi}-phenyl)-(4-pyrrolidin-1-yl-piperidin-1-yl)- methanone; 3-{6-amino-5-[1-(2,6-dichloro-phenyl)-ethoxy}-pyridin-3-yl}-N-(2-pyrrolidin-1-yl-ethyl)- benzamide; 3-{6-amino-5-[1~(2,6-dichloro-phenyl)-ethoxy]-pyridin-3-yi}-N-(2-morpholin-4-yl-ethyl)- benzamide; (3-{8-amino-5-[1-(2,6-dichloro-phenyl)-ethoxy}-pyridin-3-y{}-phenyl)-((S)-2-pyrrolidin-1-
yimethyl-pyrrolidin-1-yl)}-methanone; 3-{6-amino-5-[1-(2,6-dichloro-phenyl)-ethoxy}-pyridin-3-yl}-N-(3-
. pyrrolidin-1-yl-propyl)-benzamide; N-[2-(4-acetyl-piperazin-1-yl)-ethyi]}-3-{6-amino-5-[1-(2,6-dichloro- phenyl)-ethoxy]-pyridin-3-yl}-benzamide; 3-{6-amino-5-[1-(2,6-dichloro-phenyl)-ethoxy]-pyridin-3-yi}-N- (1-methyl-piperidin-4-yl)-benzamide; (3-{6-amino-5-[1-(2,6-dichloro-phenyi)-ethoxyl-pyridin-3-y(}-phenyl)- § (4-methyl-piperazin-1-yl)-methanone; (3-{6-amino-5-[1-(2,6-dichloro-phenyl)-ethoxy}-pyridin-3-yl}- phenyl)-((R)-2-pyrrolidin- 1-ylmethyl-pyrrolidin-1-yl)}-methanone; (3-{6-amino-5-[1-(2,6-dichloro-phenyl)- ethoxy]-pyridin-3-yl}-pheny!)-((S)-3-amino-pyrrolidin-1-yl)-methanone; (3-{6-amino-5-[1-(2,6-dichloro- phenyi)~ethoxy]-pyridin-3-yl}-phenyl)-((R)-3-amino-pyrrolidin-1-yl)-methanone; 4-{6-amino-5-[1-(2,6- dichloro-phenyl)-ethoxy}-pyridin-3-yl}-benzoic acid; 4-{6-amino-5-[1-(2,6-dichloro-phenyl)-ethoxy]- pyridin-3-yi}-N-(2-pyrrolidin-1-yl-ethyl)-benzamide; 4-{6-amino-5-[1-(2,6-dichloro-phenyl)-ethoxy]-pyridin- 3-yl}-N-(2-morpholin-4-yl-ethyl)}-benzamide; (4-{6-amino-5-[1-(2,6-dichloro-phenyl)-ethoxyl-pyridin-3-yl}- phenyl)-((S)-2-pyrrolidin-1-ylmethyl-pyrrolidin-1-yi)-methanone; 4-{6-amino-5-[1-(2,6-dichloro-phenyl)- ethoxy}-pyridin-3-yl}-N-(1-methyl-piperidin-4-yl)-benzamide; (4-{6-amino-5-{1-(2,6-dichloro-phenyl)- ethoxy]-pyridin-3-yf}-phenyl)-((3R,58)-3,5-dimethyl-piperazin-1-yl)}-methanone; N-[2-(4-acetyl-piperazin- 1-yl)-ethyl]-4-{6-amino-5-[1-(2,6-dichloro-phenyl)-ethoxy}-pyridin-3-yl}-benzamide; 4-{6-amino-5-[1-(2,6- dichloro-phenyl)-ethoxy]-pyridin-3-yi}-N-(3-pyrrolidin-1-yl-propyl)-benzamide; (4-{6-amino-5-[1-(2,6- dichloro-phenyl)-ethoxy]-pyridin-3-yl}-phenyl)-((S)-3-aminopyrrolidin-i-yl)-methanone; (4-{6-amino-5-[1- (2,6-dichloro-phenyl)-ethoxy]-pyridin-3-yl}-phenyl)-((R)-3-amino-pyrrolidin-1-yl)-methanone; (4-{6-amino- 5-[1-(2,8-dichloro-phenyl)-ethoxy]-pyridin-3-yl}-phenyl)-((R)-2-pyrrolidin-1-ylmethyl-pyrrolidin-i-yl)- methanone; (4-{6-amino-5-[1-(2,6-dichloro-phenyl)-ethoxy]-pyridin-3-yi}-phenyl)-(4-pyrrolidin-1-yl- piperidin-1-yl)-methanone; (4-{6-amino-5-[1-(2,6-dichloro-phenyl)-ethoxyl-pyridin-3-yi}-phenyl)-(4- methyl-piperazin-1-yl)-methanone; (S)-2-pyrrolidin-1-ylmsathyl-pyrrolidine-i-carboiylic acid (3-{6-amino- 5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-prop-2-ynyl)-amide; 4-methyl-piperazine-1- carboxylic acid (3-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy}-pyridin-3-yl}-prop-2-ynyl)-amide;, 4-pyrrolidin-1-yl-piperidine-1-carboxylic acid (3-{6-amino-5-[1-(2,6-dichioro-3-fluoro-phenyl)-ethoxy]- pyridin-3-yl}-prop-2-ynyl)-amide; (3R,5S)-3,5-dimethyl-piperazine-1-carboxylic acid (3-{6-amino-5-(1- (2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yi}-prop-2-ynyl)-amide; 1-(3-{6-amino-5-{1-(2,6-dichloro- 3-fluoro-phenyl)-ethoxy}-pyridin-3-yl}-prop-2-ynyl)-3-(1-methyl-piperidin-4-yl)-urea; 1-(3-{6-amino-5-{1- (2,6-dichloro-3-fluoro-phenyl)-ethoxy-pyridin-3-yl}-prop-2-ynyl)-3-(3-pyrrolidin-1-yl-propyl)-urea; 1-(3-{6- amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy}-pyridin-3-yl}-prop-2-ynyl)-3-(2-pyrrolidin-1-yl-ethyl)- urea; 1-(3-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxyl-pyridin-3-yl}-prop-2-ynyl)-3-(2-morpholin-
. 4-yl-ethyl)-urea; 1-(3-{6-amino-5-{1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy}-pyridin-3-yl}-prop-2-ynyl)-3-(3- morpholin-4-yi-propyl)-urea; (R)-2-pyrrolidin-1-ylmethyl-pyrrolidine-1-carboxylic acid (3-{6-amino-5-[1- (2,6-dichloro-3-flucro-phenyl)-ethoxy]-pyridin-3-yi}-prop-2-ynyl)-amide; 3-[1-(2,6-dichloro-3-fiuoro- phenyl)-ethoxyl-5-(3-dimethylamino-prop-1-ynyl)-pyridin-2-ylamine; (3-{6-amino-5-[1-(2,6-dichloro-3- fluoro-phenyl)-ethoxy]-pyridin-3-yl}-prop-2-ynyl)-urea; N-(3-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)- ethoxy]-pyridin-3-yl}-prop-2-ynyl)-2-piperidin-1-yl-acetamide; N-(3-{6-amino-5-[1-(2,6-dichloro-3-fluoro- phenyl)-ethoxy]-pyridin-3-yi}-prop-2-ynyl)-2-morpholin-4-yl-acetamide; N-(3-{6-amino-5-[1-(2,6-dichloro- 3-fluoro-phenyl)-ethoxyl-pyridin-3-yi}-prop-2-ynyl)-2-pyrrolidin-1-yl-acetamide; N-(3-{6-amino-5-[1-(2,6-
dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-prop-2-ynyl)-2-((R)-3-hydroxy-pyrrolidin-1-yl)-acetamide;
. N-(3-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy}-pyridin-3-yl}-prop-2-ynyl)-2-(4-hydroxy- piperidin-1-yl)-acetamide; N-(3-{6-amino-5-[1-(2,6-dichloro-3-fiuoro-phenyl)-ethoxy}-pyridin-3-yl}-prop-2- ynyl)-2-dimethylaminoc-acetamide; N-(3-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3- yl}-prop-2-ynyl)-2-diethylamino-acetamide; 2-(4-acetyl-piperazin-1-yl)-N-(3-{6-amino-5-[{1-(2,6-dichloro- 3-fluoro-phenyl)-ethoxy]pyridin-3-yl}-prop-2-ynyl)-acetamide; 4-methyl-piperazine-1-carboxylic acid (3- {6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yi}-1,1-dimethyl-prop-2-ynyl)-amide; (3R,58)-3,5-dimethyl-piperazine-1-carboxylic acid (3-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)- ethoxy]-pyridin-3-yl}-1,1-dimethyl-prop-2-ynyl)-amide; (R)-2-pyrrolidin-1-yimethyl-pyrrolidine-1-carboxylic acid (3-{6-amino-5-{1-(2,6-dichloro-3-fluoro-phenyl)-ethoxyl-pyridin-3-yl}-1,1-dimethyl-prop-2-ynyl)- amide; (S)-2-pyrrolidin-1-yimethyi-pyrrolidine-1-carboxylic acid (3-{6-amino-5-[1-(2,6-dichioro-3-fluoro- phenyl)-ethoxy}-pyridin-3-yl}-1, 1-dimethyl-prop-2-ynyl)-amide; 1-(3-{6-amino-5-{1-(2,6-dichioro-3-fluoro- phenyl)-ethoxyl-pyridin-3-yl}-1,1-dimethyl-prop-2-ynyl)-3-(2-morpholin-4-yl-ethyl)-urea; 1-(3-{6-amino-5- [1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy}-pyridin-3-yl}-1,1-dimethyl-prop-2-ynyl)-3-(2-pyrrolidin-1-yl- ethyl)-urea; 4-pyrrolidin-1-y!-piperidine-1-carboxylic acid (3-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)- ethoxy]-pyridin-3-yl}-1,1-dimethyl-prop-2-ynyl)-amide; 3-{6-amino-5-{1-(2,6-dichloro-3-fluoro-phenyl)- ethoxy]-pyridin-3-yl}-propynoic acid cyclohexylamide; 3-{6-amino-5-[1-(2,6-dichloro-3-flucro-phenyl)- ethoxy}-pyridin-3-yl}-propynoic acid isopropylamide; 4-(3-amino-3-methyl-but-1-ynyl)-2-[1-(2,6-dichloro- 3-fluoro-phenyl)-ethoxy]-phenylamine; (4-{6-amino-5-[1-(3-fluoro-2-trifluoromethyl-phenyl)-ethoxy}- pyridin-3-yl}-phenyl)-(4-methyl-piperazin-1-yl)-methanone; (4-{6-amino-5-[1-(3-fiuoro-2-trifluoromethyl- phenyl)-ethoxy]-pyridin-3-yi}-phenyl)-(4-pyrrolidin-1-yl-piperidin-1yl)-methanone; (4-{6-amino-5-[1-(3- fluoro-2-trifluocromsthyl-phenyl)-sthostyl-pyridin-3-yl}-phenyl)-((3R,53)-3,5-dimathyl-piperazin-1-yl)- methanone; (4-{6-amino-5-[1-(3-fluoro-2-trifiuoromethyl-phenyl)-ethosy]-pyridin-3-yl}-phenyl)-((S)-2- pyrrolidin-1-yimethyl-pyrrolidin-1-yl)-methanone; (4-{6-amino-5-[1-(3-fluoro-2-trifiuoromethyl-phenyl)- ethoxy]-pyridin-3-yl}-phenyl)-((R)-2-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl)-methanone; 4-{6-amino-5-[1-(3- fluoro-2-trifluoromethyi-phenyl)-ethoxyl-pyridin-3-yl}-N-(1-methyl-piperidin-4-yl)-benzamide; 4-{6-amino- 5-[1-(3-fluoro-2-trifiuoromethyl-phenyl)-ethoxyl-pyridin-3-yl}-N-(2-pyrrolidin-1-yl-ethyl)-benzamide; 4-{6- amino-5-[1-(3-fluoro-2-triflucromethyl-phenyi)-ethoxyl-pyridin-3-yl}-N-(2-morpholin-4-yl-ethyl)- benzamide; 4-{6-amino-5-[1-(3-fluoro-2-trifluoromethyl-phenyl)-ethoxyl-pyridin-3-yl}-N-(3-pyrrolidin-1-yl- propyl)-benzamide; 4-{6-amino-5-[1-(3-fluoro-2-trifluoromethyl-phenyl)-ethoxy}-pyridin-3-yl}-N-(3- morpholin-4-yl-propyl)-benzamide; 6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-nicotinonitrile; 6- , amino-5-[1-(2,6-dichloro-3-cyano-phenyi)-ethoxyl-nicotinonitrile; 5-aminomethyl-3-[1-(2,6-dichloro-3- fluoro-phenyl)-ethoxy]-pyridin-2-ylamine; (R)-2-pyrrolidin-1-ylmethyl-pyrrolidine-1-carboxylic acid {6- amino-5-{1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-ylmethyl}-amide; N-{6-amino-5-{1-(2,6- dichloro-3-fluoro-phenyl)-ethoxyl-pyridin-3-yimethyl}-methanesuifonamide; N-{6-amino-5-1-(2,6- dichloro-3-fluoro-phenyl)-ethoxyl-pyridin-3-ylmethyl}-acetamide; N-{6-amino-5-[1-(2,6-dichloro-3-fluoro- phenyl)-ethoxy]-pyridin-3-yimethyl}-4-methyl-benzenesulfonamide; ~~ 3-{1-(2,6-dichloro-3-fiuoro-phenyl)- ethoxy}-5-vinyl-pyridin-2-ylamine; ~~ (S)-1-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxyl-pyridin-3- yl}-ethane-1,2-diol; (R)-1-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxyl-pyridin-3-yl}-ethane-1,2-
diol; 3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5-(1H-pyrazol-4-yl)-pyridin-2-ylamine; 3-[1-(2,6-dichloro- . 3-fluoro-phenyl)-ethoxyl-5-[1-(2-pyrrolidin-1-yl-ethyl)- 1H-pyrazol-4-yl]-pyridin-2-ylamine; 3-[1-(2,6- dichloro-3-fluoro-phenyl)-ethoxy]-5-[ 1-(2-diisopropylamino-ethyl)-1H-pyrazol-4-yl}-pyridin-2-ylamine; 3- [1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy}-5-[1 -(2-morpholin-4-yl-ethyl)-1H-pyrazol-4-yl]-pyridin-2-ylamine; 5-bromo-3-(3-fluoro-2-methoxy-benzyloxy)-pyridin-2-ylamine; 5-bromo-3-{1-(3-fluoro-2-methoxy-phenyl)- ethoxy}-pyridin-2-ylamine; {4-[6-amino-5-(3-fluoro-2-methoxy-benzyloxy)-pyridin-3-yi]-phenyl}-((3R,5S)- 3,5-dimethyl-piperazin-1-yl)-methanone; (4-{6-amino-5-[1-(3-fluoro-2-methoxy-phenyl)-ethoxy}-pyridin-3- yi}-phenyl)-((3R,5S)-3,5-dimethyl-piperazin-1-y!)-methanone; 5-bromo-3-(3-fluoro-2-isopropoxy- benzyloxy)-pyridin-2-ylamine; {4-[6-amino-5-(3-fluoro-2-isopropoxy-benzyloxy)-pyridin-3-yl}-phenyl}- ((3R,5S)-3,5-dimethyl-piperazin-1-yl)-methanone; 5-(4-amino-phenyl)-3-[1-(2,6-dichloro-3-fluoro- - phenyl)-ethoxy]-pyridin-2-ylamine; (4-{6-amino-5-[1-(2,6-dichioro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yi}- phenoxy)-acetic acid methyl ester; (4-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}- phenoxy)-acetic acid; 2-(4-{6-amino-5-[1-(2,6-~dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yi}-phenoxy)-1- ((3R,5S)-3,5-dimethyl-piperazin-1-yl)-ethanone; 2-(4-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)- 16 ethoxy)-pyridin-3-yl}-phenoxy)-1-((R)-3-hydroxy-pyrrolidin-1-yl)-ethanone; 4-[2-(4-{6-amino-5-]1-(2,6- dichloro-3-fluoro-phenyl)-ethoxyl-pyridin-3-yl}-phenoxy)-acetyl}-piperazine-1-carboxylic acid tert-butyl ester; 2-(4-{6-amino-5-[1-(2,6-dichloro-3-flucro-phenyl)-ethoxyl-pyridin-3-yl}-phenoxy)-1-((R)-2- pyrrolidin-1-ylmethyl-pyrrolidin-1-yl)-ethanone; §-bromo-3-(3-fluoro-6,7,8,9-tetrahydro-5H- benzocyclohepten-5-yloxy)-pyridin-2-ylamine; {4-[6-amino-5-(3-fluoro-6,7,8,9-tetrahydro-5H- benzocyclohepten-5-yioxy)-pyridin-3-yi}-phenyl}-((3R,58)-3,5-dimethyi-piperazin- 1-yl)-methanone; 3-(3- fluoro-6,7,8,9-tetrahydro-56H-benzocyclohepten-5-yloxy)-5-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-pyridin-2- ylamine; N-{4-[6-amino-5-(3-fluoro-6,7,8,8-tefrahydro-5H-benzocyclohepien-5-yloxy)-pyridin-3-yl}- phenyl}-methanesulfonamide, 3-(3-fluoro-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ylosy)-5-(1H- pyrazol-4-yl)-pyridin-2-ylamine; 5-bromo-3-[1-(2-chloro-3-fluoro-phenyl)-ethoxy}-pyridin-2-ylamine; 3-[1- (2-chloro-3-fluoro-phenyl)-ethoxyl-5-{4-(2-pyrrolidin- 1-yl-ethoxy)-phenyl}-pyridin-2-ylamine; 5'-benzyloxy- [2,3bipyridinyl-6'-ylamine; 5-benzyloxy-[3,3'lbipyridinyl-6-ylamine; 3-benzyloxy-5-pyrimidin-5-yl-pyridin- 2-ylamine; 5-benzyloxy-(3,3'bipyridinyi-6,6'-diamine; 5'-(2-chioro-benzyioxy)-[2,3'Tbipyridinyl-6'-ylamine; 5-(2-chloro-benzyloxy)-[3,3']bipyridinyl-6-ylamine; 3-(2-chloro-benzyloxy)-5-pyrimidin-5-yl-pyridin-2- ylamine; 5-(2-chloro-benzyloxy)-[3,3'bipyridinyl-6,6'-diamine; 5'-(4-chloro-benzyloxy)-[2,3']bipyridinyl-6'- vylamine; 5-(4-chloro-benzyloxy)-[3,3'bipyridinyl-6-ylamine; 3-(4-chloro-benzyloxy)-5-pyrimidin-5-yl- pyridin-2-ylamine; 5-(4~chloro-benzyloxy)-[3,3'|bipyridinyl-6,6'-diamine; 5'-(2-chloro-3,6-difluoro- . benzyloxy)-[2,3"bipyridinyl-6'-ylamine; 5-(2-chloro-3,6-difluoro-benzyloxy)-[3,3bipyridinyl-6-ylamine; 5- (2-chloro-3,6-difluoro-benzyloxy)-{3,4bipyridinyl-6-ylamine; 3-(2-chloro3,6-difluoro-benzyloxy)-5- ] pyrimidin-5-yl-pyridin-2-ylamine; 5-(2-chloro-3,6-difluoro-benzyloxy)-[3,3'Tbipyridinyi-6,6'-diamine; 5'-(2,6- dichloro-benzyloxy)-2,3bipyridinyl-6'-ylamine; 5-(2,6-dichloro-benzyloxy)-[3,3'Ibipyridinyl-6-ylamine; 5- (2,6-dichloro-benzyloxy)-[3,4"bipyridinyl-6-ylamine; 3-(2,6-dichloro-benzyloxy)-5-pyrimidin-5-yl-pyridin-2- ylamine; 5-(2,6-dichloro-benzyloxy)-[3,3']bipyridinyl-6,6'-diamine; 5-[1-(2,6-dichloro-3-fluoro-phenyl)- ethoxyl-[3,3']bipyridinyl-6,6'-diamine; {6'-amino-5'-{1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]- [2,3bipyridinyl-4-yl}-(4-methyl-piperazin-1-yl)-methanone; {6'-amino-5'-[1-(2,6-dichloro-3-fluoro-phenyl)-
ethoxy]-[2,3'bipyridinyl-6-y!}-(4-methyl-piperazin-1-yl)-methanone; {6-amino-5'-[1 -(2,6-dichloro-3-fluoro- ’ phenyl)-ethoxy]-{3,3']bipyridinyl-5-yi}-(4-methyl-piperazin-1-yl)-methanone; {6'-amino-5'-{1-(2,6-dichloro- 3-fluoro-phenyl)-ethoxy)-[3,3'Ibipyridinyl-6-yi}-(4-methyl-piperazin-1-yi)-methanone; {6-amino-5-[1-(2,6- dichloro-3-fluoro-phenyl)-ethoxy]-[3,4'Ibipyridinyl-2'-yl}-(4-methyl-piperazin-1-yl)}-methanone; 5-[1-(2- chloro-3,6-difluoro-phenyl)-ethoxyl-(3,3bipyridinyl-6,6'-diamine; {6'-amino-5'-[1-(2-chloro-3,6-difluoro- phenyl)-ethoxy}-[2,3'bipyridinyl-5-yl}-(4-methyl-piperazin-1-yl)-methanone; {6'-amino-5'-{1-(2-chloro-3,6- difluoro-phenyl)-ethoxyl-[2,3'Ibipyridinyl-4-yl}-(4-methyi-piperazin-1-yl)-methanone; {6"-amino-5'-[1-(2- chioro-3,6-difluoro-phenyl)-ethoxy]-[2, 3'bipyridinyi-6-yl}-(4-methyl-piperazin-1-yl)-methanone; {6'-amino-
5'.[1-(2-chioro-3,6~diflucro-phenyl)-ethoxy}-{3, 3']bipyridinyl-5-yi}-(4-methyl-piperazin-1-yi)-methanone; {6'-amino-5'-[1 -(2-chloro-3,6-difluoro-phenyl)-ethoxy]-[3,3')bipyrid inyl-6-yl}-(4-methyl-piperazin-1-yl)- methanone; {6-amino-5-[1-(2-chloro-3,6-difluoro-phenyl)-ethoxy}-[3,4 Toipyridinyl-2'-yl}-(4-methyl- piperazin-1-yl)-methanone; 5'-{1-(2,6-dichloro-3-fluoro-phenyl)-ethoxyl-{2,3'Ibipyridinyl-6'-ylamine; 5-[1- (2-chloro-3,6-diflucro-phenyi)-ethoxy]-[2,3'|bipyridinyl-6'-ylamine; 5-{1-(2-chloro-3,6-difluoro-phenyl)- ethoxy)-[3,3"|bipyridinyl-6-ylamine; 3-[1-(2-chloro-3,6-difluoro-phenyl)-ethoxy]-5-pyrimidin-5-yl-pyridin-2- ylamine; {6'-amino-5'-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy}-[2,3 Tbipyridinyl-5-yl}-(4-methyl-piperazin- 1-yl)}-methanone; 5-[1-(2-chloro-3,6-difluoro-phenyl)-ethoxy}-[3,4']bipyridinyl-6-ylamine; 5-benzyloxy-3- [1-(2-chloro-3,6-difluoro-phenyl)-ethoxy]-pyridin-2-ylamine; 3-[1-(2-chloro-3,6-difluoro-phenyl)-ethoxy}-5- (2-ethyl-butoxy)-pyridin-2-ylamine; 3-[1-(2-chloro-3,6-difluoro-phenyl)-ethoxy]-5-(3-methyi-butoxy)- pyridin-2-ylamine; 3-[1-(2-chloro-3,6-difluoro-phenyl)-ethoxy}-5-butoxy-pyridin-2-ylamine; 3-[1-(2-chloro- 3,6-difluoro-phenyl)-ethoxy]-5-propoxy-pyridin-2-ylamine; 3-[1-(2-chloro-3,6-difluoro-phenyl)-ethoxy}-5- cyclohexylmethoxy-pyridin-2-ylamine; 6-amino-5-]1-(2-chloro-3,8-difluoro-phenyl)-ethoxyl-pyridin-3-ol; 3- [1-(2-chloro-3,6-difluoro-phenyl)-ethosy}-6-(2-cyclohexyl-ethoicy)-pyridin-2-ylamine; 3-[i-(2-chiore-3,6- difiuoro-phenyl)-athoxy}-5-isobutoxy-pyridin-2-ylamine; 3-[1-(2-chloro-3,6-difluoro-phenyl)-ethoxy]-5- phenethyloxy-pyridin-2-ylamine; 3-[1-(2-chloro-3,6-difluoro-phenyl)-ethoxy]-5-(pyridin-2-yimethoxy)- pyridin-2-ylamine; 3-[1-(2-chloro-3,6-difluoro-phenyl)-ethoxy}-5-(pyridin-4-ylmethoxy)-pyridin-2-ylamine; (4-{6-amino-5-[1-(2,6-dichioro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-phenyl)-((3R,58)-3,5-dimethyl- piperazin-1-yl)-methanone; (4-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyi)-ethoxy]-pyridin-3-yi}-phenyl)- ((3R,58)-3,5-dimethyl-piperazin-1-yl}-methanone; 5-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy}- pyridin-3-yl}-2-fluoro-benzonitrile; 4-(4~{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yi}- phenyl)-piperidin-4-ol; (4-{6-amino-5-[1-(2,6-dichioro-3-flucro-phenyl)-ethoxy]-pyridin-3-yl}-phenyl)- piperidin-1-yl-methanone; (4-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-phenyl)- ’ pyrrolidin-1-yl-methanone; 4-{6-amino-5-{1-(2,6-dichloro-3-fiuoro-phenyl)-ethoxyl-pyridin-3-yi}-3-methyl- benzoic acid methyl ester 3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy}-5-[4-(dimethyl-piperazin-1- - ylmethyl)-phenyl]-pyridin-2-ylamine; (4-{6-amino-5-{1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yi}- 3,5-dimethoxy-phenyl)-(dimethyl-piperazin-1-yl)-methanone; (4-{6-amino-5-[1-(2,6-dichloro-3-fiuoro- phenyl)-ethoxy}-pyridin-3-yl}-2-fiuoro-phenyl)-(dimethyl-piperazin-1-yl)-methanone; (4-{6-amino-5-[1- : (2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-3-fluoro-phenyl)-(dimethyl-piperazin-1-yl)-methanone; (4-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-3-methyl-phenyl)-(dimethyl- piperazin-1-yl)-methanone; (4-{6-amino-5-[1 -(2,6-dichloro-3-fluoro-phenyl)-ethoxyl-pyridin-3-yi}-phenyl)-
(4-methyl-[1,4)diazepan-1-yl)-methanone; (4-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxyl- ~ pyridin-3-yl}-phenyl)-[1,4]diazepan-1-yl-methanone; (4-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)- ethoxy]-pyridin-3-yl}-phenyl)-piperazin-1-yl-methanone; 3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5- vinyl-pyridin-2-ylamine; (4-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy}-pyridin-3-yi}-phenyl)- ((3R,4S)-3,4-dihydroxy-pyrrolidin-1-yl)-methanone; 5-{(1-benzyl-pyrrolidin-3-ylamino)-methyl}-3-[1-(2,6- dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-2-ylamine; 4-{6-amino-5-[1-(2,6-dichloro-3-fiuoro-phenyl)- ethoxy]-pyridin-3-yl}-N-azetidin-3-yl-benzamide; 4-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]- pyridin-3-yl}-N,N-dimethyl-benzenesulfonamide; 3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy}-5-(6- methoxy-1H-benzoimidazol-2-yl)-pyridin-2-ylamine; 3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy}-5-(6- methoxy-1-methyl-1H-benzoimidazol-2-yl)-pyridin-2-ylamine; 3-[1 ~(2,6-dichloro-3-fluoro-phenyl)-ethoxy]- 5-{4-(4-methyl-[1,4]diazepane-1-sulfonyl)-phenyl}-pyridin-2-ylamine; 6-{6-amino-5-[1-(2,6-dichloro-3- fluoro-phenyl)-ethoxy]-pyridin-3-yl}-1-methyl-1H-indazole-3-carboxylic acid amide; 3-[1-(2,6-dichloro-3- fluoro-phenyl)-ethoxy}-5-(1-methyl- 1H-pyrazol-4-yl)-pyridin-2-ylamine; 5-(3-chloro-phenyl)-3-[1-(2,6- dichloro-3-fluoro-phenyl)-ethoxyl-pyridin-2-ylamine; 3-{1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy}-5-(4- fluoro-3-methyl-phenyl)-pyridin-2-ylamine; 3-[1-(2,6-dichloro-3-fiuoro-phenyl)-ethoxy]-5-(3- trifluoromethyl-phenyl)-pyridin-2-ylamine; 3-[1-(2,6-dichloro-3-flucro-phenyl)-ethoxy]-5-(3-flucro-phenyl)- pyridin-2-ylamine; 3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5-(3-trifluoromethoxy-phenyl)-pyridin-2- ylamine; 5-benzo[1,3]dioxol-5-yl-3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy}-pyridin-2-ylamine; ~~ 3-{6- amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-phenol; (3-{6-amino-5-[1-(2,6-dichloro-3- fluoro-phenyl)-ethoxy]-pyridin-3-yl}-phenyl)-methanol; 3-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyi)- ethoxy]-pyridin-3-yl}-benzonitrile; 3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5-(3-methoxy-phenyl)- pyridin-2-ylamine; 3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoity]-5-(3,5-dichioro-phenyl)-pyridin-2-ylamine; 3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxyl-5-(2,5-dimethyl-phenyl)-pyridin-2-ylamine; 5-(5-chloro-2- methoxy-phenyl)-3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-2-yiamine; 5-(3-chloro-4-fluoro- phenyl)-3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxyl-pyridin-2-ylamine; 3-[1-(2,6-dichloro-3-fluoro-phenyl)- ethoxy]-5-(5-fluoro-2-methoxy-phenyl)-pyridin-2-ylamine; ~~ 3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5- (3-isopropyl-phenyl)-pyridin-2-ylamine; 3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy}-5-(3,4-dichloro- phenyl)-pyridin-2-ylamine; 4-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yi}- benzonitrile; 3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy}-5-(3,4-difluoro-phenyl)-pyridin-2-ylamine; (4-{6-
amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy}-pyridin-3-yl}-phenyl)-((2R,6S)-2,6-dimethyl-morpholin- 4-yl)-methanone; 3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5-(2-ethoxy-phenyl)-pyridin-2-ylamine; 3-[1- : (2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5-(2,5-dimethoxy-phenyl)-pyridin-2-ylamine; 3-{1-(2,6-dichloro-3- fluoro-phenyl)-ethoxy]-5-(2,4-dimethoxy-phenyl)-pyridin-2-ylamine; 3-[1-(2,6-dichloro-3-fluoro-phenyl)- i ethoxy}-5-(2,6-dimethoxy-phenyl)-pyridin-2-ylamine; 3-[1~(2,6-dichloro-3-fluoro-phenyl)-ethoxy}-5-(2- ftrifluoromethyl-phenyl)-pyridin-2-ylamine; 5-(2-chloro-phenyl)-3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxyl- pyridin-2-ylamine; 3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5-(2-trifluoromethoxy-phenyl)-pyridin-2- ylamine; 1-(2-{6-amino-5-{1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-phenyl)-ethanone; 3-[1- (2,6-dichloro-3-fluoro-phenyl)-ethoxy}-5-(2-fluoro-phenyl)-pyridin-2-ylamine; (2-{6-amino-5-[1-(2,6- dichloro-3-fluoro-phenyl)-ethoxyl-pyridin-3-yl}-phenyl)-methanol; 3-[1-(2,6-dichloro-3-fluoro-phenyl)-
ethoxyl]-5-o-tolyl-pyridin-2-ylamine; 3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5-(2-methoxy-phenyl)- - pyridin-2-ylamine; 3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxyl-5-(2,6-dimethyl-phenyl)-pyridin-2-ylamine; (4-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxyl-pyridin-3-yl}-phenyl)-morpholin-4-yl-methanone; (4-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxyl-pyridin-3-yl}-2-chloro-phenyl)-((3R,5S)-dimethyl- piperazin-1-yl)-methanone; 4-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy}-pyridin-3-yl}-2-methy}- phenyl)-((3R,5S)-dimethyl-piperazin-1-yl)-methanone; 3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5-[4- ((2R,8S)-2,6-dimethyl-morpholin-4-yimethyl)-phenyl]-pyridin-2-ylamine; 3-[1-(2,6-dichloro-3-fluoro- phenyl)-ethoxy}-5-(4-morphalin-4-yimethyi-phenyl)-pyridin-2-ylamine; 3-[1-(2,6-dichloro-3-fluoro-phenyl)- ethoxy]-5-(3,5-dimethyi-phenyi)-pyridin-2-ylamine; 3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5-m-tolyl- pyridin-2-ylamine; 3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy}-5-(3,4-dimethoxy-phenyl)-pyridin-2- ylamine; 5-biphenyl-3-y}-3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-2-ylamine; 5-(3,5-bis- trifluoromethyl-phenyl)-3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy}-pyridin-2-ylamine; 3-[1-(2,6-dichloro-3- fluoro-phenyl)-ethoxy}-6-(3,4-dichloro-phenyl)-pyridin-2-ylamine; 1-(3-{6-amino-5-[1-(2,6-dichloro-3- fluoro-phenyl)-ethoxy]-pyridin-3-yl}-phenyl)-ethanone; 3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy}-5-(3,5- 16 difluoro-phenyl)-pyridin-2-ylamine; ~~ 3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxyl]-5-(2,5-dichloro-phenyl)- ) pyridin-2-ylamine; (4-{6-amino-5-[1-(2,6-dichloro-4-trifluoromethyl-phenyl)-ethoxy}-pyridin-3-yl}-phenyl)- ((3R,58)-3,5-dimethyl-piperazin-1-yl)-methanone; 3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5-(3- ethoxy-phenyl)-pyridin-2-ylamine; (4-{6-amino-5-[1-(2-trifluoromethyl-phenyl)-ethoxy]-pyridin-3-yi}- phenyl)-(3,5-dimethyi-piperazin-1-yl)methanone; (4-{6-amino-5-[1-(3-trifluoromethyl-phenyl)-ethoxy}- pyridin-3-yl}-phenyl)-(3,5-dimethyl-piperazin-1-yl)-methanone; 7-[4-(3,5-dimethyl-piperazine-1-carbonyl)- phenyl]-2-phenyl-4H-pyrido[3,2-b][1,4]oxazin-3-one; {4-[6-amino-5-(3-fluoro-2-triflucromethyl- benzyloxy)-pyridin-3-yll-phenyl}-(3,6-dimethyl-piperazin-1-yl)-methanone; {4-[6-amino-5-(2,6-difluoro- benzyloxy)-pyridin-3-yll-phenyi}-(3,5-dimethyl-piperazin-1-yl)-methanons; [4-(6-amino-5-benzyloxy- pyridin-3-yl}-phenyli]-(3,5-dimethyl-piperazin-1-yl}-methanone; (4-{6-amino-5-[1-(2-chloro-3,6-difluoro- phenyl)-ethoxy]-pyridin-3-yi}-phenyl)-(4-ethyl-piperazin-1-yl)-methanone; [4-(6-amino-5-benzyloxy- pyridin-3-yl}-phenyl])-(4-ethyl-piperazin-1-yl)-methanone; {4-[6-amino-5-(2-methyl-benzyloxy)-pyridin-3- yl-phenyl}-(3,5-dimethyl-piperazin-1-yl)-methanone; 3-{2-amino-5-[4-(4-pyrrolidin-1-yl-piperidine-1- carbonyl)-phenyl}-pyridin-3-yloxymethyl}-benzoic acid methyl ester; 3-{2-amino-5-[4-(3,5-dimethyl- piperazine-1-carbonyl)-phenyl]-pyridin-3-yloxymethyl}-benzoic acid methyl ester; {4-[6-amino-5-(2- methyl-benzyloxy)-pyridin-3-yi}-phenyl}-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone; [4-(6-amino-5- cyclohexylmethoxy-pyridin-3-yl)-phenyl]-(4-pyrrolidin-1-yl-piperidin-1-yl}-methanone; 4-(1-{2-amino-5-[4- . (4-pymrolidin-1-yl-piperidine-1-carbonyli)-phenyl]-pyridin-3-yloxy}-ethyl)-[2-(3-hydroxy-phenyi)-ethyl}- benzamide; 4-(1-{2-amino-5-{4-(4-pyrrolidin-1-yl-piperidine-1-carbonyl)-phenyl}-pyridin-3-yioxy}-ethyl)-[2- ] (2,6-dichloro-phenyl)-ethyl}-benzamide; 4-(1-{2-amino-5-[4-(4-pyrrolidin-1-yl-piperidine-1-carbonyl)- phenyl}-pyridin-3-yloxy}-ethyl)-(1-benzyl-piperidin-4-yl)-benzamide; 4-(1-{2-amino-5-[4-(4-pyrrolidin-1-yl- piperidine-1-carbonyl)-phenyl]-pyridin-3-yloxy}-ethyl)-[3-(2-oxo-pyrrolidin-1-yl)-propyl]-benzamide; (4-{6- amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy}-pyridin-3-yl}-phenyl)-(4-ethyl-piperazin-1-yl)- methanone; {4-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yl}-phenyl}-(3,5-dimethyl-piperazin-1-y)- methanone; (6-amino-3-aza-bicyclo[3.1.0)hex-3-yl)-(4-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-
i -306 - ethoxy]-pyridin-3-yl}-phenyl)-methanone; 5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy}-6'-(2-morpholin-4-yl- i ethoxy)-[3,3']bipyridinyl-6-ylamine; 6'-amino-5'-[1-(2,6-dichloro-3-fluoro-phenyt)-ethoxy}-1-(2-pyrrofidin-1- yi-ethyl)-1H-[3,3'bipyridinyl-6-one; 5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-6'-(2-pyrrolidin-1-y- ethoxy)-[3,3']bipyridinyl-6-ylamine; 6'-amino-5'-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-1-[2-(1 -methyl- pyrrolidin-2-yl)-ethyl]-1H-[3,3'Ibipyridinyl-6-one; (4-{6-amino-5-[1-(2,4,6-trimethyl-phenyl)-ethoxy]-pyridin- 3-yl}-phenyi)-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone; (4-{6-amino-5-[1-(2-chloro-6-fluoro-phenyl)- ethoxy]-pyridin-3-yl}-phenyl)-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone; 3-[1-(2,6-dichloro-3-fluoro- phenyl)-ethoxy]-5-(4-fluoro-phenyl)-pyridin-2-ylamine; 6'-amino-5'-[1-(2,6-dichloro-3-fluoro-phenyl)- ethoxy}-1H-[3,3"]bipyridinyl-6-one; 5'-bromo-5-[1-(2,6-dichioro-3-fluoro-phenyl)-ethoxy}-{3,3bipyridinyl-6- ylamine; 3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxyl-5-(4-dimethylamino-phenyl)-pyridin-2-ylamine; 5-[1- (2,6~dichloro-3-fluoro-phenyl)-ethoxy}-2'-methoxy-[3,3'Ibipyridinyl-6-ylamine; 3-[1-~(2,6-dichloro-3-fluoro- phenyl)-ethoxy)-5-(1H-indol-5-yi)-pyridin-2-ylamine; (4-{6-amino-5-[1-(2,6-dichloro-phenyl)-propoxyl- pyridin-3-yl}-phenyl)-(3,5-dimethyl-piperazin-1-yl)-methanone; [4-(6-amino-5-benzyloxy-pyridin-3-yl)- phenyl]-(4-pyrrolidin-1-y!-piperidin-1-yl)-methanone; 3-(2,6-dichloro-3-fluoro-benzyloxy)-5-thiazol-2-yl- pyridin-2-ylamine; (4-{6-amino-5-[1-(2-fluoro-6-trifiuoromethyl-phenyl)-ethoxy}-pyridin-3-yi}-phenyl)-(4- pyrrolidin-1-yl-piperidin-1-yl)-methanone; 3-(2,6-dichloro-3-fluoro-benzyloxy)-5-(1-methyl-1 H-imidazol-2- yl)-pyridin-2-ylamine; {4-[6-amino-5-(2,4,6-trimethyl-benzyloxy)-pyridin-3-yl]-phenyl}-(4-pyrrolidin-1-yl- piperidin-1-yl)-methanone; {4-{6-amino-5-(2,3,5,6-tetramethyl-benzyloxy)-pyridin-3-yl]-phenyl}-(4- pyrrolidin-1-yl-piperidin-1-yl)-methanone; {4-[6-amino-5-(2,4,B-trifluoro-benzyloxy)-pyridin-3-yi]-pheny!}- (4-pyrrolidin-1-yl-piperidin-1-yl)-methanone; (4-{6-amino-5-[1-(2-fluoro-6-trifluoromethyi-phenyl)-ethoxy}- pyridin-3-yl}-phenyl)-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone; 6-amino-5-[1-(2,6-dichloro-3-fluoro- phenyl)-ethoxy]-N-methyl-nicotinamiding; 6-amino-5-{1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-N-(2- morpholin-4-yl-ethyl)-nicotinamidine; (4-{6-amino-5-[1-(2,4,5-trifluoro-phenyl)-propoxy}-pyridin-3-yl}- phenyl)-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone; (4-{6-amino-5-[1-(6-chloro-2-fluoro-3-methyl- phenyl)-ethoxy]-pyridin-3-yi}-phenyl)-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone; 3-(1-{2-amino-5-[4-(4- pyrrolidin-1-yl-piperidine-1-carbonyl)-phenyl]-pyridin-3-yloxy}-ethyl)-benzoic acid; and pharmaceutically acceptable salts, hydrates and solvates thereof.
39. A compound selected from the group consisting of: 3-{5-amino-6-[1-(2,6-dichloro-3-fluoro- phenyl)-ethoxy]-pyrazin-2-yl}-N-(3-pyrrolidin-1-yi-propyl)-benzamide; 3-{5-amino-6-{1-(2-chloro-3,6- difluoro-phenyl)-ethoxy}-pyrazin-2-yl}-N-(3-pyrrolidin-1-yi-propyl)-benzamide; 3-{5-amino-6-{1-(2-chloro- ’ 3,6-difluoro-phenyl)-ethoxy)-pyrazin-2-yl}-N-(1-methyl-piperidin-4-yl)-benzamide; 3-{6-amino-6-[1-~(2- chloro-3,6-difluoro-phenyl)-ethoxy}-pyrazin-2-yi}-N-(2-pyrrolidin-1-yl-ethyl)-benzamide; 3-{5-amino-6-[1-
. (2-chloro-3,6-difluoro-phenyl)-ethoxy]-pyrazin-2-yl}-N-(2-morpholin-4-yl-ethyl)-benzamide; N-[2-(4- acetyl-piperazin-1-yl)-ethyl]-3-{6-amino-6-[1-(2-chloro-3,6-diflucro-phenyl)-ethoxy]-pyrazin-2-yi}- benzamide; (3-{5-amino-6-[1-(2-chloro-3,6-difluoro-phenyl)-ethoxy]-pyrazin-2-yi}-phenyl)-(4-methyl- piperazin-1-yl)-methanone; (3-{5-amino-6-[1 -(2-chloro-3,6-difluoro-phenyl)-ethoxy]-pyrazin-2-yi}-phenyl)- (4-pyrrolidin-1-yl-piperidin-1-yl)-methanone; (3-{5-amino-6-[1-(2-chloro-3,6-difluoro-phenyf)-ethoxy]- pyrazin-2-yl}-phenyl)-((3R,5S)-3,5-dimethyl-piperazin-1-yl}-methanone; (3-{5-amino-6-[1-(2-chloro-3,6-
difiuoro-phenyl)-ethoxy]-pyrazin-2-yi}-phenyi)-((S)-2-pyrrolidin- 1-yimethyl-pyrrolidin-1-yl)-methanone; (3- - {5-amino-6-[1-(2-chloro-3,6-difluoro-phenyl)-ethoxy}-pyrazin-2-yl}-phenyl)-((R)-3-amino-pyrrolidin-1-yl)- methanone; (3-{5-amino-6-[1-(2-chloro-3,6-difluoro-phenyl)-ethoxy}-pyrazin-2-yi}-phenyl)-((S)-3-amino- pyrrolidin-1-yl)-methanone; 4-{5-amino-6-{1-(2-chloro-3,6-difluoro-phenyt)-ethoxy}-pyrazin-2-yi}-benzoic acid; 4-{5-amino-6-[1-(2-chloro-3,6-difluoro-phenyl)-ethoxy}-pyrazin-2-yI}-N-(3-pyrrolidin-1-yi-propyl)- benzamide; (4-{5-amino-6-[1-(2-chloro-3,6-difluoro-phenyl)-ethoxy]-pyrazin-2-yl}-phenyi)-(4-methyl- piperazin-1-yl)-methanone; (4-{5-amino-8-[1-(2-chloro-3,6-difluoro-phenyl)-ethoxy]-pyrazin-2-yl}-phenyl)- (4-pyrrolidin-1-yl-piperidin-1-yl)-methanone; 4-{5-amino-6-[1-(2-chloro-3,6-difluoro-phenyl)-ethoxy}- pyrazin-2-yl}-phenyl)-((3R,5S)-3,5-dimethyl-piperazin-1-yl)-methanone; (4-{5-amino-6-[1-(2-chloro-3,6- difluoro-phenyl)-ethoxy]-pyrazin-2-yl}-phenyl)-((S)-2-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl)-methanone; (4- {5-amino-6-[1-(2-chloro-3,6-difluoro-phenyl)-ethoxyl-pyrazin-2-yl}-phenyl)-((R)-2-pyrrolidin-1-ylmethyl- pyrrolidin-1-yl)-methanone; (4-{5~amino-6-[1-(2-chloro-3,6-difluoro-pheny!)-ethoxy}-pyrazin-2-yl}-phenyl)- ((R)-3-amino-pyrrolidin-1-yl)-methanone; 4-{5-amino-6-[1-(2-chloro-3,6-difluoro-phenyl)-ethoxy}-pyrazin- 2-yi}-N-(1-methyl-piperidin-4-yl)-benzamide; 4-{5-amino-6-[1-(2-chloro-3,6-difluoro-phenyl)-ethoxy}- pyrazin-2-yl}-N-(2-pyrrolidin-1-yl-ethyl)-benzamide; 4-{5-amino-6-[1-(2-chloro-3,6-difluoro-phenyl)- ethoxy}-pyrazin-2-yl}-N-(2-morpholin-4-yl-ethyl)-benzamide; N-[2-(4-acetyl-piperazin-1-yl)-ethyl]-4-{5- amino-6-{1-(2-chloro-3,6-difluoro-phenyl)-ethoxyl-pyrazin-2-yl}-benzamide; 2-{4-(2-Hydroxy-acetyl)- piperazin-1-yl]-ethanesulfonic acid (4-{5-amino-6-[1 -(2-chioro-3,6-difluoro-phenyl)-ethoxyl-pyrazin-2-yl}- phenyl)-amide; 3-[5-amino-6-(3-fluoro-2-trifluoromethyl-benzyloxy)-pyrazin-2-yl]-benzoic acid; {3-[5- amino-6-(3-fluoro-2-trifiuoromethyl-benzyloxy)-pyrazin-2-yl]-phenyl}-(4-pyrrolidin-1-yl-piperidin-1-yl)- methanone; 3-[5-amino-6-(3-fluoro-2-triflucromethyl-benzyloxy)-pyrazin-2-yi}-N-{2-[ethyi-(2-methoxy- sthyl)-amino]-sthyl}-benzamide; {3-[5-amino-6-(3-iluoro-2-trifluoromethyl-benzyloxy)-pyrazin-2-yl}- phenyl}-(4-meihyl-piperazin-1-yl)-methanone; 3-[5-amino-6-(3-fluoro-2-trifluoromethyl-benzyloxy)- pyrazin-2-yl]-N-(3-pyrrolidin-1-yl-propyl)-benzamide; N-[2-(4-acetyl-piperazin-1-yl)-ethyl]-3-[5-amino-6- (3-fluoro-2-trifluoromethyl-benzyloxy)-pyrazin-2-yl}-benzamide; {4-[5-amino-6-(3-fluoro-2-triftuoromethyl- benzyloxy)-pyrazin-2-yl}-phenyl}~(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone; {4-[5-amino-8-(3-fluoro-2- triflucromethyl-benzyloxy)-pyrazin-2-yl}-phenyi}-(4-methyl-piperazin-1-yl)-methanone; {4-[5-amino-6-(3- fluoro-2-trifluoromethyl-benzyloxy)-pyrazin-2-yl]-phenyl}-((S)-2-pyrrolidin-1-ylmethyl-pymrolidin-1-yl)- methanone; (3-{6-amino-6-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyrazin-2-yl}-phenyl)-(4-methyl- piperazin-1-yl)-methanone; (3-{5-amino-6-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxyl-pyrazin-2-yi}-phenyl)- ((3R,5S)-3,5-dimethyl-piperazin-1-yl)-methanone; 3-{5-amino-6-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxyl- ‘ pyrazin-2-yl}-N-(1-methyl-piperidin-4-yl)-benzamide; 3-{5-amino-6-{1-(2,6-dichioro-3-fluoro-phenyl)- ethoxyl-pyrazin-2-yl}-N-(2-pyrrolidin-1-yl-ethyl)-benzamide; 3-{5-amino-6-[1-(2,6-dichloro-3-fluoro- “ phenyl)-ethoxy}-pyrazin-2-y[}-N-(2-morpholin-4-yl-ethyi)-benzamide; 3-{5-amino-6-[1-(2,6-dichloro-3- fluoro-phenyl)-ethoxy}-pyrazin-2-yl}-N-(3-morpholin-4-yl-propyl)-benzamide; (3-{5-amino-6-[1-(2,6- dichloro-3-fluoro-phenyl)-ethoxy]-pyrazin-2-yl}-phenyl)-(4-cyclopropylamino-piperidin-1-yl)-methanone; 3-{5-amino-6-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyrazin-2-yl}-N-((S)-2-hydroxy-3-morpholin-4-yi- propyl)-benzamide; 3-{5-amino-6-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyrazin-2-yl}-N-((R)-2- hydroxy-3-pyrrolidin-1-yl-propyl)-benzamide; (3-{6-amino-5-{1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-
pyridin-3-yi}-phenyl)-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone; 2-diethylamino-ethanesulfonic acid (4- ; {5-amino-6-[1-(2,6~dichloro-3-fluoro-phenyl)-ethoxy]-pyrazin-2-yl}-phenyl)-amide; 2-(4-Hydroxy-piperidin- 1-yl)-ethanesulfonic acid (4-{5-amino-6-[1-(2,6-dichloro-3-fluoro-phenyi)-ethoxy]-pyrazin-2-yi}-phenyl)- amide; 2-dimethylamino-ethanesulfonic acid (4-{5-amino-6-[1-(2,6-dichloro-3-flucro-phenyl)-ethoxy}- pyrazin-2-yl}-phenyl)-amide; 2-((R)-3-Hydroxy-pyrrolidin-1-yl)-ethanesulfonic acid (4-{5-amino-6-[1-(2,6- dichloro-3-fluoro-phenyl)-ethoxy]-pyrazin-2-yl}-phenyl)-amide; 2-pyrrolidin-1-ylethanesulfonic acid (4-{5- amino-6-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxyj-pyrazin-2-yl}-phenyl)-amide; 4-{5-amino-6-[1-(2,6- dichloro-3-fluoro-phenyl)-ethoxy)-pyrazin-2-yl}-benzoic ~~ acid; 4-{5-amino-6-{1-(2,6-dichloro-3-fluoro- phenyi)-ethoxyl-pyrazin-2-yl}-N-((R)-2-hydroxy-3-pyrrolidin-1-yl-propyl)-benzamide; (4-{5-amino-6-{1- (2,6-dichloro-3-fluoro-phenyl)-ethoxyl-pyrazin-2-yl}-phenyl)-(4-cyclopropylamino-piperidin-1-yl)- methanone; 4-{5-amino-6-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyrazin-2-yl}-N-((S)-2-hydroxy-3- pyrrolidin-1-y-propyl)-benzamide; 4-{5-amino-6-[1-(2,6-dichloro-3-filuoro-phenyl)-ethoxy}-pyrazin-2-yl}-N- ((R)-2-hydroxy-3-morpholin-4-yl-propyl)-benzamide; 4-{5-amino-6-[1-(2,6-dichloro-3-fluoro-phenyl)- ethoxy]-pyrazin-2-yl}-N-(1-methyl-piperidin-4-yl)-benzamide; (4-{5-amino-6-[1-(2,6-dichioro-3-fluoro- phenyl)-ethoxyl-pyrazin-2-yl}-phenyl)-((S)-2-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl)-methanone; (4-{5- amino-6-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyrazin-2-y(}-phenyl)-(4-pyrrolidin-1-yl-piperidin-1i-y)- methanone; 4-{5-amino-6-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyrazin-2-yi}-N-(2-morpholin-4-yi- ethyl)-benzamide; (4-{5-2mino-6-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyrazin-2-yl}-phenyl)-(4- methyl-piperazin-1-yl}-methanone; (4-{5-amino-6-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxyl-pyrazin-2-yi}- phenyl)-((3R,5S)-3,5-dimethyl-piperazin-1-yl}-methanone; 4-{5-amino-6-[1-(2,6-dichloro-phenyl)-ethoxy]- pyrazin-2-yi}-benzoic &cid; (4-{5-amino-6-[1-(2,6-dichloro-phenyl)-sthoxy]-pyrazin-2-yi}-phenyl)-(4- pyrrolidin-1-yl-piperidin-1i-yl)-methanone; 4-{5-amino-8-[ 1-(2,6-dichloro-phenyl)-ethoiy]-pyrazin-2-yI}-N- (2-morpholin-4-yl-ethyl)-benzamide; (4~{5-2mino-6-[1-(2,6-dichioro-phenyl)-ethoxy}-pyrazin-2-yl}- phenyl)-((3R,59)-3,5-dimethyl-piperazin-1-yl)-methanone; 4-{5-amino-6-[1-(2,6-dichloro-phenyl)-ethoxy)- pyrazin-2-yl}-N-(1-methyl-piperidin-4-yl)-benzamide; (4-{5-amino-6-[1-(2,6-dichloro-phenyl)-ethoxy]- pyrazin-2-yl}-phenyl)-((R)-2-pyrrolidin-1-yimethyl-pyrrolidin-1-yl)-methanone; (4-{5-amino-6-[1-(2,6- dichloro-phenyl)-ethoxy]-pyrazin-2-yl}-phenyl)-((S)-2-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl)-methanone; (4- {5-amino-6-{1-(2,6-dichloro-phenyl)-ethoxy]-pyrazin-2-yl}-phenyl)-(4-methyl-piperazin-1-yi)-methanone; (4-{5-amino-6-[1 -(2,6-dichloro-phenyl)-ethoxy}-pyrazin-2-yl}-phenyl)-((R)-3-aminopyrrolidin-1-yl)- methanone; (4-{5-amino-6-[1-(2,6-dichioro-phenyl)-ethoxyl-pyrazin-2-yl}-phenyl)-((S)-3-aminopyrrolidin- 1-yl)-methanone hydrogen chloride; 4-{5-amino-6-[1-(2,6-dichioro-phenyl)-ethoxy]-pyrazin-2-y(}-N-(2- k pyrrolidin-1-yl-ethyl)-benzamide; 4-{5-amino-6-[1-(2,6-dichloro-phenyi)-ethoxy]-pyrazin-2-yi}-N-(3- pyrrolidin-1-yl-propyl)-benzamide; ~~ 3-{5-amino-6-{1-(2,6-dichloro-phenyl)-ethoxyl-pyrazin-2-yi}-benzoic . acid; 3-{5-amino-6-{1-~(2,6-dichloro-phenyl)-ethoxy]-pyrazin-2-yl}-N-(1-methyl-piperidin-4-yl)}-benzamide; 3-{5-amino-6-[1-(2,6-dichloro-phenyl)-ethoxyl-pyrazin-2-yl}-N-(2-pyrrolidin-1-yl-ethyl)-benzamide; (3-{5- amino-6-[1-(2,6-dichloro-phenyl)-ethoxy]-pyrazin-2-yl}-phenyl)-((3R,5S)-3,5-dimethyl-piperazin-1-yl)- methanone; 3-{5-amino-6-[1-(2,6-dichloro-phenyl)-ethoxy]-pyrazin-2-yl}-N-(2-morpholin-4-yl-ethyl)- benzamide; (3-{5-amino-6-[1-(2,6-dichloro-phenyl)-ethoxy]-pyrazin-2-yi}-phenyl)-((S)-2-pyrrolidin-1- ylmethyl-pyrrolidin-1-yl)-methanone; (3-{5-amino-6-{1-(2,6-dichloro-phenyl)-ethoxy]-pyrazin-2-yl}-
phenyl)-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone; N-[2-(4-acetyl-piperazin-1-yl)-ethyl]-4-{5-amino-6-[1- i (2,6-dichloro-phenyl)-ethoxy]-pyrazin-2-yi}-benzamide; N-[2-(4-acetyl-piperazin-1-yl)-ethyl}-3-{5-amino- 6-[1-(2,6-dichloro-pheny!)-ethoxyl-pyrazin-2-yl}-benzamide; (3-{5-amino-6-[1-(2,6-dichloro-phenyl)- ethoxy]-pyrazin-2-yl}-phenyl)-((R)-2-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl)-methanone; ~~ 3-{5-amino-6-[1- (2,6-dichloro-phenyl)-ethoxy}-pyrazin-2-yl}-N-(3-pyrrolidin-1-yl-propyl)-benzamide; (3-{5-amino-6-[1-(2,6- dichloro-phenyl)-ethoxy]-pyrazin-2-yl}-phenyl)-((S)-3-amino-pyrrolidin-1-yl)-methanone; (3-{5-amino-6- [1-(2,6-dichloro-phenyi)-ethoxyl-pyrazin-2-yl}-phenyl)-((R)-3-amino-pyrrolidin-1-yl)-methanone hydrochloride salt; (3-{5-amino-6-[1-(2,6-dichloro-phenyl)-ethoxyl-pyrazin-2-yl}-phenyl)-(4-methyl- piperazin-1-yl)-methanone; 1-(4-{5-amino-6-[1-(2-chloro-3,6-difluoro-phenyl)-ethoxy]-pyrazin-2-yl}- phenyl)-3-(2-morpholin-4-yl-ethyl)-urea; (R)-2-pyrrolidin-1-ylmethyl-pyrrolidine-1-carboxylic acid (4-{5- amino-6-[1-(2-chloro-3,6-difluoro-phenyl)-ethoxy]-pyrazin-2-yl}-phenyl)-amide; 1-(4-{5-amino-6-{1-(2- chloro-3,6-difluoro-phenyl)-ethoxy}-pyrazin-2-yl}-phenyl)-3-(2-pyrrolidin-1-yl-ethyl)-urea; 4-methyl- piperazine-1-carboxylic acid (4-{5-amino-6-{1-(2-chloro-3,6-difluoro-phenyl)-ethoxy]-pyrazin-2-yl}- phenyl)-amide; 1-(4-{5-amino-6-[1-(2-chloro-3,6-difluoro-phenyl)-ethoxy]-pyrazin-2-yl}-phenyl)-3-(2- 16 hydroxy-ethyl)-urea; (S)-3-amino-pyrrolidine-1-carboxylic acid (4-{5-amino-6-[1-(2-chloro-3 6-difluoro- phenyl)-ethoxy]-pyrazin-2-yl}-phenyl)-amide; 1-(4-{5-amino-8-[1-(2-chloro-3,6-difluoro-phenyl)-ethoxy}- pyrazin-2-yi}-phenyi)-3-(1-methyl-piperidin-4-yl)-urea; 4-methyl-piperazine-1-carboxylic acid (4-{5-amino- 6-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy}-pyrazin-2-yl}-phenyl)-amide; 1-(4-{5-amino-6-[1-(2,6-dichloro- 3-fluoro-phenyl)-ethoxyl-pyrazin-2-yl}-phenyl)-3-(2-hydroxy-ethyl)-urea; (S)-3-amino-pyrrolidine-1- carboxylic acid (4-{5-amino-6-[1-(2,6-dichioro-3-fluoro-phenyl)-ethoxy}-pyrazin-2-yl}-phenyl)-amide; 1-(4- {5-amino-6-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxyl-pyrazin-2-yl}-phenyl)-3-(1-methyl-piperidin-4-yl)- urea, 5-[5-amino-6-(2-chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yl]-thiophene-2-carboxylic acid; {5-[5- amino-6-(2-chloro-3,6-difluoro-benzyloiy)-pyrazin-2-yl]-thiophen-2-yl}-(4-methyl-piperazin-1i-yl)- methanone; {5-[5-amino-6-(2-chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yl}-thiophen-2-yl}-(4-pyrrolidin-1- yl-piperidin-1-yl)-methanone; {5-[5-amino-6-(2-chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yl}-thiophen-2- yi}-((3R,5S)-3,5-dimethyl-piperazin-1-yl}-methanone; {5-[5-amino-6-(2-chloro-3,6-diflucro-benzyloxy)- pyrazin-2-yl}-thiophen-2-yl}-((R)-2-pyrrolidin-1-ylmethyl-pyrrolidin-1-yi)-methanone; 5-[6-amino-6-(2- chloro-3,6-difluoro-benzyloxy)-pyrazin-2-yi]-thiophene-2-carboxylic acid (2-morpholin-4-yl-ethyi)-amide; 3-[1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-{5-{(4-methylpiperazin-1-yl)carbonyl]pyridin-2-yl}pyrazin-2- amine trifluoroacetate; 3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5-pyridin-4-yl-pyrazin-2-ylamine; 3-[1- (2,6-dichloro-3-fluoro-phenyl)-ethoxy}-5-(1 H-pyrrol-2-yl)-pyrazin-2-ylamine; (6-{5-amino-6-{1-(2,6- ‘ dichloro-3-fluoro-phenyl)-ethoxy)-pyrazin-2-yi}-pyridin-3-yl)-(4-methyl-piperazin-1-yl)-methanone; (2-{5- amino-6-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyrazin-2-yi}-pyridin-4-yl)-(4-methyl-piperazin-1-yl)- “ methanone; (6~{5-amino-6-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy}-pyrazin-2-yl}-pyridin-2-yl)-(4-methyl- piperazin-1-yl)}-methanone; (5-{5-amino-6-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyrazin-2-yi}-pyridin- 3-yl)-(4-methyl-piperazin-1-yl)-methanone; (4-{5-amino-6-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy}- pyrazin-2-yl}-pyridin-2-yl)-(4-methyl-piperazin-1-yl)-methanone; 6-{5-amino-6-[1-(2,6-dichloro-3-fluoro- phenyl)-ethoxy}-pyrazin-2-yl}-N-(2-morpholin-4-yl-ethyl)-nicotinamide; 5-{5-amino-6-[1-(2,6-dichloro-3- fluoro-phenyl)-ethoxyl-pyrazin-2-yl}-N-(2-morpholin-4-yl-ethyl)-nicotinamide; 6-{5-amino-6-[1-(2,6-
dichloro-3-tluoro-phenyl)-ethoxy]-pyrazin-2-yi}-N-(3-morpholin-4-yl-propyl)-nicotinamide; 5-{5-amino-6- (1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyrazin-2-yl}-N-(3-morpholin-4-yi-propyl)-nicotinamide; ~~ (6-{5- amino-6-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy}-pyrazin-2-yl}-pyridin-3-yl)-(4-isopropyl-piperazin- 1-yl)- methanone; and pharmaceutically acceptable salts, hydrates and solvates thereof.
40. A compound selected from the group consisting the compounds shown in Table 5 and pharmaceutically acceptable salts, hydrates and solvates thereof.
41. A compound selected from the group consisting the compounds shown in Table 6 and pharmaceutically acceptable salts, hydrates and solvates thereof.
42. A compound selected from the group consisting the compounds shown in Table 7 and pharmaceutically acceptable salts, hydrates and solvates thereof.
43, A compound selected from the group consisting the compounds shown in Table 8 and pharmaceutically acceptable salts, hydrates and solvates thereof.
44, Use of a compound, salt, hydrate or solvate of any of claims 1-43, in the manufacture of a medicament for treating abnormal cell growth in a mammal.
45. The use of claim 44, wherein the abnormal cell growth is cancer.
46. The use of claim 45, wherein the cancer is selected from lung cancer, bone cancer, pancreatic cancer, skin cancer, cancer of the head or neck, cutaneous or intraocular melanoma, uterine cancer, ovarian cancer, rectal cancer, cancer of the anal region, stomach cancer, colon cancer, breast cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, Hodgkin's Disease, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, cancer of the adrenal gland, sarcoma of soft tissue, cancer of the urethra, cancer of the penis, prostate cancer, chronic or acute leukemia, lymphocytic lymphomas, cancer of the bladder, cancer of the kidney or ureter, renal cell carcinoma, carcinoma of the renal pelvis, neoplasms of the central nervous system (CNS), primary CNS lymphoma, spinal axis tumors, brain stem glioma, pituitary adenoma, and combinations thereof.
47. The use of 45, wherein the cancer is selected from gastrointestinai stromal tumors, renal cell carcinoma, breast cancer, colorectal cancer, non-small cell lung cancer, neuroendocrine tumors, thyroid cancer, small cell lung cancer, mastocytosis, glioma, sarcoma, acute myeloid leukemia, prostate cancer, lymphoma, and combinations thereof. AMENDED SHEET ’ 1 4
48. The use of claim 44, wherein an anti-tumor agent selected from the group consisting of mitotic inhibitors, alkylating agents, anti-metabolites, intercalating antibiotics, growth factor inhibitors, cell cycle inhibitors, enzymes, topoisomerase inhibitors, biological response modifiers, antibodies, cytotoxics, anti-hormones, anti-androgens and mixtures thereof, is co-administered with the medicament.
49. A compound, salt, hydrate or solvate of any of claims 1-43, for use in treating abnormal cell growth,
50. The compound of claim 49, wherein the abnormal cell growth is cancer.
51. The compound of claim 50, wherein the cancer is selected from lung cancer, bone cancer, pancreatic cancer, skin cancer, cancer of the head or neck, cutaneous or intraocular melanoma, uterine cancer, ovarian cancer, rectal cancer, cancer of the anal region, stomach cancer, colon cancer, breast cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, Hodgkin's Disease, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, cancer of the adrenal gland, sarcoma of soft tissue, cancer of the urethra, cancer of the penis, prostate cancer, chronic or acute leukemia, lymphocytic lymphomas, cancer of the bladder, cancer of the kidney or ureter, renal cell carcinoma, carcinoma of the renal pelvis, neoplasms of the central nervous system (CNS), primary CNS lymphoma, spinal axis tumors, brain stem glioma, pituitary adenoma, and combinations thereof.
52. The compound of claim 50, wherein the cancer is selected from gastrointestinal stromal tumors, renal cell carcinoma, breast cancer, colorectal cancer, non-small cell lung cancer, neuroendocrine tumors, thyroid cancer, small cell lung cancer, mastocytosis, glioma, sarcoma, acute myeloid leukemia, prostate cancer, lymphoma, and combinations thereof.
53. The compound of claim 49, for use in co-administration with an anti-tumor agent selected from the group consisting of mitotic inhibitors, alkylating agents, anti-metabolites, intercalating antibiotics, growth factor inhibitors, cell cycle inhibitors, enzymes, topoisomerase inhibitors, biological response modifiers, antibodies, cytotoxics, anti-hormones, anti-androgens and mixtures thereof.
54. A compound according to any one of claims 1, 12, 21, 30, 32 or 34, substantially as herein described and exemplified.
55. Use of claim 44, substantially as herein described and exemplified. AMENDED SHEET
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