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1. (WO2001072751) PYRROLOPYRIMIDINES AS TYROSINE KINASE INHIBITORS
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CLAIMS
We Claim:

A compound represented by the following structural formula:


and pharmaceutically acceptable salts thereof, wherein:
Ring A is a six membered aromatic ring or a five or six membered heteroaromatic ring which is optionally substituted with one or more
substituents selected from the group consisting of a substituted or
unsubstituted aliphatic group, a halogen, a substituted or unsubstituted
aromatic group, substituted or unsubstituted heteroaromatic group,
substituted or unsubstituted cycloalkyl, substituted or unsubstituted
heterocycloalkyl, substituted or unsubstituted aralkyl, substituted or
unsubstituted heteroaralkyl, cyano, nitro, -NR4R5, -C(O)2H, -OH, a
substituted or unsubstituted alkoxycarbonyl, -C(O)2-haloalkyl, a substituted or unsubstituted alkylthio ether, a substituted or unsubstituted alkylsulfoxide, a substituted or unsubstituted alkylsulfone, a substituted or unsubstituted arylthio ether, a substituted or unsubstituted arylsulfoxide, a substituted or unsubstituted arylsulfone, a substituted or unsubstituted alkyl carbonyl, - C(O)-haloalkyl, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted aryloxy group, carboxamido, tefrazolyl,
trifluoromethylsulphonamido, trifluoromethylcarbonylamino, a substituted or unsubstituted alkynyl, a substituted or unsubstituted alkenyl, a substituted or unsubstituted alkyl amido, a substituted or unsubstituted aryl amido, - NR95C(O)R95, a substituted or unsubstituted styryl and a substituted or unsubstituted aralkyl amido, wherein Rg5 is an aliphatic group or an aromatic group;
L is -O-; -S-; -S(O)-; -S(O)2-; -N(R)-; -N(C(O)OR)-; -N(C(O)R)-; -N(SO2R); -CH2O-; -CH2S-; -CH2N(R)-; -C(NR)-;-CH2N(C(O)R))-; - CH2N(C(O)OR)-;-CH2N(SO2R)-; -CH(NHR)-; -CH(NHC(O)R)-; -CH(NHSO2R)-; -CH(NHC(O)OR)-;-CH(OC(O)R)-;-CH(OC(O)NHR)-; -CH=CH-; -C(-NOR)-; -C(O)-; -CH(OR)-;-C(O)N(R)-; -N(R)C(O)-; -N(R)S(O)-;-N(R)S(O)2-;-OC(O)N(R)-;-N(R)C(O)N(R)-; -NRC(O)O-;-S(O)N(R)-;-S(O)2N(R)-; N(C(O)R)S(O)-; N(C(O)R)S(O)2-; -N(R)S(O)N(R)- ; -N(R)S(O)2N(R)-; -C(O)N(R)C(O)-; -S(O)N(R)C(O)-; -S(O)2N(R)C(O)-; -OS(O)N(R)-; -OS(O)2N(R)-; -N(R)S(0)O-; -N(R)S(O)2O-; -N(R)S(O)C(O)-; -N(R)S(O),C(O)-; -SON(C(O)R)-; -SO2N(C(O)R)-; -N(R)SON(R)-; -N(R)SO2N(R)-; -C(O)O-; -N(R)P(OR')O-; -N(R)P(OR')-; -N(R)P(O)(OR')O-; -N(R)P(O)(OR')-; -N(C(O)R)P(OR')O-; - N(C(O)R)P(OR')-; -N(C(O)R)P(O)(OR')O-; -N(C(O)R)P(OR')-, -CH(R)S(O)-; -CH(R)S(O)2-; -CH(R)N(C(O)OR)-; -CH(R)N(C(O)R)-; -CH(R)N(SO2R); -CH(R)O-; -CH(R)S-; -CH(R)N(R)-; -CH(R)N(C(O)R))-; -CH(R)N(C(O)OR)-;-CH(R)N(SO2R)-; - CH(R)C(=NOR)-; -CH(R)C(O)-; -CH(R)CH(OR)-;-CH(R)C(O)N(R)-; - CH(R)N(R)C(O)-; -CH(R)N(R)S(O)-;- CH(R)N(R)S(O)2-;- CH(R)OC(O)N(R)-; -CH(R)N(R)C(O)N(R)-; -CH(R)N(R)C(O)O-;- CH(R)S(O)N(R)-;-CH(R)S(O)2N(R)-; -CH(R)N(C(O)R)S(O)-; - CH(R)N(C(O)R)S(O)2-; -CH(R)N(R)S(O)N(R)-; -CH(R)N(R)S(O)2N(R)-; -CH(R)C(O)N(R)C(O)-; -CH(R)S(O)N(R)C(O)-; -CH(R)S(O)2N(R)C(O)-; - CH(R)OS(O)N(R)-; -CH(R)OS(O)2N(R)-; - CH(R)N(R)S(O)O-; - CH(R)N(R)S(O)2O-; -CH(R)N(R)S(O)C(O)-; - CH(R)N(R)S(O)2C(O)-; - CH(R)SON(C(O)R)-; -CH(R)S(O)2N(C(O)R)-; -CH(R)N(R)SON(R)-; - CH(R)N(R)S(O)2N(R)-; -CH(R)C(O)O-; -CH(R)N(R)P(OR')O-; - CH(R)N(R)P(OR ; -CH(R)N(R)P(O)(OR')O-; -CH(R)N(R)P(O)(OR')-; - CH(R)N(C(O)R)P(OR')O-; -CH(R)N(C(O)R)P(OR')-; - CH(R)N(C(O)R)P(O)(OR')O- or - CH(R)N(C(O)R)P(OR')-, wherein each R and R' is, independently, -H, an acyl group, a substituted or unsubstituted aliphatic group, a substituted or unsubstituted aromatic group, a substituted or unsubstituted arylalkyl group, a substituted or unsubstituted heteroaromatic group, or a substituted or unsubstituted cycloalkyl group or a substituted or unsubstituted arylalkyl group; or
L is -RbN(R)S(O)2-, -RbN(R)P(O)-, or -RbN(R)P(O)0-, wherein Rb is an alkylene group which when taken together with the sulphonamide, phosphinamide, or phosphonamide group to which it is bound forms a/five or six membered ring fused to ring A; or

L is represented by one ofthe following structural formulas:




wherein R85 taken together with the phosphinamide, or
phosphonamide is a 5-, 6-, or 7-membered, aromatic, heteroaromatic or heterocycloalkyl ring system;
G is a direct bond; -(CH2)j-, wherein j is 1 to 6; a C2-C6- alkenylene group, a C3-C8-cycloalkylene group or a -Cg-oxaalkylene group;
Rj is a substituted aliphatic group, a substituted cycloalkyl, a substituted bicycloalkyl, a substituted cycloalkenyl, an optionally substituted aromatic group, an optionally substituted heteroaromatic group, an optionally substituted heteroaralkyl, an optionally substituted heterocycloalkyl, an optionally substituted heterobicycloalkyl, an optionally substituted alkylamido, and optionally substituted arylamido, an optionally substituted -S(O)2-alkyl or optionally substituted -S(O)2-cycloalkyl, a -C(O)-alkyl or an optionally substituted -C(O)-alkyl, provided that when Ri is an aliphatic group or cycloalkyl group, R: is not exclusively substituted with one or more substitutents selected from the group consisting of hydroxyl and lower alkyl ethers, provided that the heterocycloalkyl is not 2-phenyl-l,3-dioxan-5-yl and provided that an aliphatic group is not substituted exclusively with one or more aliphatic groups;
wherein one or more substituents are selected from the group consisting of a substituted or unsubstituted aliphatic group, a substituted or unsubstituted aromatic group, a substituted or unsubstituted heteroaromatic, a substituted or unsubstituted aralkyl, a substituted or unsubstituted heteroaralkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aromatic ether, a substituted or unsubstituted aliphatic ether, a substituted or unsubstituted alkoxycarbonyl, a substituted or unsubstituted alkylcarbonyl, a substituted or unsubstituted arylcarbonyl, a substituted or unsubstituted heteroarylcarbonyl, substituted or unsubstituted aryloxycarbonyl, -OH, a substituted or unsubstituted aminocarbonyl, an oxime, a substituted or unsubstituted azabicycloalkyl, heterocycloalkyl, oxo, aldehyde, a substituted or
unsubstituted alkyl sulfonamido group, a substituted or unsubstituted aryl sulfonamido group, a substituted or unsubstituted bicycloalkyl, a substituted or unsubstituted heterobicycloalkyl, cyano, -NH2, an alkylamino, ureido, thioureido; or
Rj is -B-E, wherein
B is a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aromatic, a substituted or unsubstituted heteroaromatic, an alkylene, an aminoalkyl, an alkylenecarbnonyl, or an aminoalkylcarbonyl; and
E is a substituted or unsubstituted azacycloalkyl, a substituted or unsubstituted azacycloalkylcarbonyl, a substituted or unsubstituted azacycloalkylsulfonyl, a substituted or unsubstituted azacycloalkylalkyl, a substituted or unsubstituted heteroaryl, a substituted or unsubstituted heteroarylcarbonyl, a substituted or unsubstituted heteroarylsulfonyl, a substituted or unsubstituted heteroaralkyl, a substituted or unsubstituted alkyl sulfonamido, a substituted or unsubstituted aryl sulfonamido, a substituted or unsubstituted bicycloalkyl, a substituted or unsubstituted ureido, a substituted or unsubstituted thioureido or a substituted or unsubstituted aryl;

R2 is -H, a substituted or unsubstituted aliphatic group, a substituted or unsubstituted cycloalkyl, a halogen, -OH, cyano, a substituted or unsubstituted aromatic group, a substituted or unsubstituted heteroaromatic group, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aralkyl, a substituted or unsubstituted heteroaralkyl, -(CH2)0.

3NR4R5, or-(CH2)0.3C(O)NR4R5;
R3 is a substituted or unsubstituted aliphatic group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted aromatic group, a substituted or unsubstituted heteroaromatic group, or a substituted or unsubstituted heterocycloalkyl;
provided that L is -SN(R)-, -S(O)N(R)-, -S(O)2N(R)-, -N(R)S-, -N(R)S(O)-, -N(R)S(O)2-, -N(R)SN(R')-, -N(R)S(O)N(R')-, or -N(R)S(O)2N(R')-when R3 is a substituted or unsubstituted aliphatic group, a substituted or unsubstituted alkenyl group;
provided that when L is -O-, -CH2NR-, -C(O)NR- or -NRC(O)- and

R3 is azacycloalkyl or azaheteroaryl, G is a direct bond; a C2-C6- alkenylene group, a C3-C3-cycloalkylene group or a Ci- -oxaalkylene; and
provided that when L is -O- and R3 is phenyl, G is a direct bond; a C2-C6-alkenylene group, a C3-C8-cycloalkylene group or a C,-C6-oxaalkylene;
R4, R5 and the nifrogen atom together form a 3, 4,.5, 6 or 7-membered, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heterobicycloalkyl or a substituted or unsubstituted
heteroaromatic; or
R4 and Rj are each, independently, -H, azabicycloalkyl,
heterocycloalkyl, a substituted or unsubstituted alkyl group or Y-Z;

Y is selected from the group consisting of -C(O)-, -(CH2)p-,-S(O)2-, -C(O)O-, -SO2NH-, -CONH-, -(CH2)pO-, -(CH2)pNH-, -(CH2)pS-, -(CH2)pS(O)-, and -(CH2)pS(O)2-;
p is an integer from 0 to 6; and
Z is -H, a substituted or unsubstituted alkyl, substituted or unsubstituted amino, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl or substituted or unsubstituted heterocycloalkyl group.

The compound of Claim 1 , wherein R3 is selected from the group consisting of a substituted or unsubstituted phenyl, a substituted or unsubstituted naphthyl, a substituted or unsubstituted pyridyl, a substituted or
unsubstituted thienyl, a substituted or unsubstituted benzoxriazole, a substituted or unsubstituted tetrahydropyranyl, a substituted or unsubstituted tefrahydrofuranyl, a substituted or unsubstituted dioxane, a substituted or unsubstituted dioxolane, a substituted or unsubstituted quinoline, a substituted or unsubstituted thiazole, substituted or unsubstituted isoxazole, substituted or unsubstituted cyclopentyl, a substituted or unsubstituted benzofuran, substituted or unsubstituted benzothiophene, substituted or unsubstituted benzisoxazole, substituted or unsubstituted benzisothiazole, substituted or unsubstituted benzothiazole, substituted or unsubstituted benzoxazole, substituted or unsubstituted benzoxazole, substituted or unsubstituted benzimidazole, substituted or unsubstituted benzoxadiazole, substituted or unsubstituted benzothiadiazole, substituted or unsubstituted isoquinoline, substituted or unsubstituted quinoxaline, substituted or unsubstituted indole and substituted or unsubstituted pyrazole.

The compound of Claim 2 wherein R3 is substituted with one or more substituent selected from the group consisting of F, Cl, Br, I, CH3, NO2, OCF3, OCH3, CN, CO2CH3, CF3, t-butyl, pyridyl, substituted or unsubstituted oxazolyl, substituted or unsubstituted benzyl, substituted or unsubstituted benzenesulfonyl, substituted or unsubstituted phenoxy, substituted or unsubstituted phenyl, substituted or unsubstituted amino, carboxyl, substituted or unsubstituted tefrazolyl, styryl, -S-(substituted or unsubstituted aryl), -S-(substixuted or unsubstituted heteroaryl), substituted or
unsubstituted heteroaryl, substituted or unsubstituted heterocycloalkyl, - NR^Rg, alkynyl, -C(O)NRfRg, Rc and CH2ORc.
Rf, Rg and the nifrogen atom together form a 3, 4, 5, 6 or 7-membered, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heterobicycloalkyl or a substituted or unsubstituted
heteroaromatic; or
Rf and Rg are each, independently, -H, a substituted or unsubstituted aliphatic group, or a substituted or unsubstituted aromatic group; and
R_ is hydrogen, or substituted or unsubstituted alkyl or substituted or unsubstituted aryl, -W-(CH2)t-NRdRe, -W-(CH2)t-O-alkyl, , -W-(CH2)t-S-alkyl, -W-(CH2)t-OH; or -W-(CH2)t-ORf;
t is an integer from 0 to 6;
W is a bond or -O-, -S-, -S(O , -S(O)2-, or -NRk-;
Rk is -H or alkyl; and
Rd, R,, and the nifrogen atom to which they are attached together form a 3, 4, 5, 6 or 7-membered substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heterobicyclic group; or
Rd and R<, are each, independently, -H, alkyl, alkanoyl or -K-D;
K is -S(O)2-, -C(O)-, -C(O)NH-, -C(O)2-, or a direct bond;
D is a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, a substituted or unsubstituted aralkyl, a substituted or
unsubstituted heteroaromatic group, a substituted or unsubstituted heteroaralkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted amino, a substituted or unsubstituted aminoalkyl, a substituted or unsubstituted
aminocycloalkyl, COORj, or substituted or unsubstituted alkyl; and
R^ is a substituted or unsubstituted aliphatic group or a substituted or unsubstituted aromatic group.

4. The compound of Claim 3, wherein R3 is a substituted or unsubstituted phenyl or phenyl fused to a five- or six-membered heterocyclic group.

5. The compound of Claim 4 wherein R3 is selected from the group consisting of




wherein R is hydrogen or alkyl.

6. The compound of Claim 5 wherein ring A is a 1 ,4-phenylene group substituted with methoxy or fluoro.
7. The compound of Claim 1, wherein ring A is selected from the group consisting of a substituted or unsubstituted phenyl, a substituted or unsubstituted naphthyl, a substituted or unsubstituted pyridyl, and a substituted or
unsubstituted indole.

8. The compound of Claim 7 wherein ring A is substituted with one or more substituent selected from the group consisting of -F, -Cl, -Br, -I, -OH, -CH3, -NO2, - OCF3, -OCH3, -CN, -CO2CH3, -CF3, -CH2OH, -CH2NMe2, -CH2NHMe, CH2NH2, t-butyl, pyridyl, methylenedioxy; substituted or unsubstituted oxazolyl, substituted or unsubstituted benzyl, substituted or unsubstituted benzenesulfonyl, substituted or unsubstituted phenoxy, substituted or unsubstituted phenyl, substituted or unsubstituted amino, carboxyl, substituted or unsubstituted tefrazolyl, styryl, -S-(substituted or unsubstituted aryl), -S-(substituted or unsubstituted heteroaryl), substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycloalkyl, -NRfRg, alkynyl, -C(O)NRfRg, R0 and CH^R,,
Rf, Rg and the nitrogen atom together form a 3, 4, 5, 6 or 7-membered, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heterobicycloalkyl or a substituted or unsubstituted heteroaromatic; or
Rf and Rg are each, independently, -H, a substituted or unsubstituted aliphatic group or a substituted or unsubstituted aromatic group; and
R_ is hydrogen, substituted or unsubstituted alkyl, substituted or
unsubstituted aryl, -W-(CH2)t-NRdRe, -W-(CH2)t-O-alkyl, , -W-(CH2)t-S-alkyl, - W-(CH2)t-OH; or -W-(CH2)t-ORf;
t is an integer from 0 to 6;
W is a bond or -O-, -S-, -S(O)-, -S(O)2-, or -NRk-;
Rk is -H or alkyl; and
, Re and the nitrogen atom to which they are attached together form a 3, 4,

5, 6 or 7-membered substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heterobicycloalkyl or a substituted or unsubstituted
heteroaromatic; or
Rd and R, are each, independently, -H, alkyl, alkanoyl or -K-D;
K is -S(O)2-, -C(O)-, -C(O)NH-, -C(O)2-, or a direct bond;
D is a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, a substituted or unsubstituted aralkyl, a substituted or unsubstituted
heteroaromatic group, a substituted or unsubstituted heteroaralkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted amino, a substituted or unsubstituted aminoalkyl, a substituted or unsubstituted aminocycloalkyl, COOR^, or a substituted or unsubstituted alkyl; and
R, is a substituted or unsubstituted aliphatic group or a substituted or
unsubstituted aromatic group.

9. The compound of Claim 8, wherein ring A is a substituted or unsubstituted phenyl.

10. The compound of Claim 9 wherein ring A is a substituted or unsubstituted 1,4-phenylene group.

11. The compound of Claim 1 wherein R, is of the formula


wherein m is an integer from 0 to 3.

2. The compound of Claim 1 wherein Rj is ofthe formula



wherein:
m is an integer from 0 to 3;
t is an integer from 1 to 6; and
R8, Rg and the nifrogen atom together form a 3, 4, 5, 6 or 7- membered, substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted heteroaromatic or substituted or unsubstituted
heterobicyclicalkyl group; or
R8 and Rg are each, independently, -H, azabicycloalkyl,
heterocycloalkyl or Y2-Z2;
Y2 is selected from the group consisting of -C(O)-, -(CH2)q-,-S(O)2-, - C(O)O-, -SO2NH-, -CONH-, (CH2)qO-, -(CH2)qNH-, -(CH2)qS-, -(CH2)qS(O)- and -(CH2)qS(O)2-;
q is an integer from 0 to 6; and
Z2 is -H, a substituted or unsubstituted alkyl, a substituted or unsubstituted amino, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl or a substituted or unsubstituted heterocycloalkyl group.

3. The compound of Claim 1 wherein R: is ofthe formula


wherein:
m is an integer from 1 to 3;
s and t are each, independently, an integer from 0 to 6; and
R8, Rc, and the nifrogen atom together form a 3, 4, 5, 6 or 7-membered,
substituted or unsubstituted heterocycloalkyl group, substituted or
unsubstituted heteroaryl group, or a substituted heterobicyclicalkyl group; or

R8 and Rg are each, independently, -H, azabicycloalkyl, heterocycloalkyl;
alkyl; hydroxyalkyl; dihydroxyalkyl; or -Y2-Z2;
Y2 is selected from the group consisting of -C(O)-, -(CH2)q-,-S(O)2-, -C(O)O-, -SO2NH-, -CONH-, (CH2)qO-, -(CH2)qNH-, -(CH2)qS-, -(CH2)qS(O)- and- (CH2)qS(O)2-;
q is an integer from 0 to 6;
Z2 is -H, a substituted or unsubstituted alkyl, a substituted or unsubstituted amino, a substituted or unsubstituted aryl, a substituted or unsubstituted
heteroaryl or a substituted or unsubstituted heterocycloalkyl;
R77 is -H, -OR78, or -NR79RS0;
R78 is -H or a substituted or unsubstituted aliphatic group;
R79, R80 and the nifrogen atom together form a 3, 4, 5, 6 or 7-membered, substituted or unsubstituted heterocycloalkyl group, substituted or
unsubstituted heteroaryl group, or a substituted heterobicyclicalkyl group; or R79 and R80 are each, independently, -H, azabicycloalkyl, heterocycloalkyl or

-Y x 3 - _7_.3 , Y3is selected from the group consisting of -C(O)-, -(CH2)q-,-S(O)2-, -C(O)O-, -SO2NH-, -CONH-, (CH2)qO-, -(CH2)qNH-, -(CH2)qS-, -(CH2)qS(O)-, - (CH2)qN(CrC6-alkyl)-, -(CH2)q-C(O)O-(CH2)q- and-(CH2)qS(0)2-;
q is an integer from 0 to 6;
Z3 is -H, a substituted or unsubstituted alkyl, a substituted or unsubstituted amino, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl or a substituted or unsubstituted heterocycloalkyl.

14. The compound of Claim 13 wherein m is 2; s is 0; and R77 is -OH.

15. The compound of Claim 14 wherein Rj is selected from the group consisting of :



16. The compound of Claim 1 wherein Rj is ofthe formula



wherein:
v is an integer from 1 to 3
R10 is -H, azabicycloalkyl, heterocycloalkyl or Y2-Z2;
Y2 is selected from the group consisting of -C(O)-, -(CH2)q-,-S(O)2-, -C(O)O- , -SO2NH-, -CONH-, -(CH2)qO-, -(CH2)qNH-, -(CH2)qS-, -(CH2)qS(O)-, and - (CH2)qS(O)2-;
q is an integer from 0 to 6; and
Z2 is -H, a substituted or unsubstituted alkyl, a substituted or unsubstituted amino, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl or a substituted or unsubstituted heterocycloalkyl.

17. The compound of Claim 1 wherein R! is ofthe formula


wherein:
m is an integer from 0 to 3;
R10 is -H, azabicycloalkyl, heterocycloalkyl or Y2-Z2;

Y2 is selected from the group consisting of -C(O)-, -(CH2)p-,-S(O)2-, C(O)O-, - SO2NH-, -CONH-, -(CH2)qO-, -(CH2)qNH-, -(CH2)qS-, -(CH2)qS(O)-, and - (CH2)qS(O)2-;
q is an integer from 0 to 6; and
Z2 is -H, a substituted or unsubstituted alkyl, a substituted or unsubstituted amino, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl or a substituted or unsubstituted heterocycloalkyl; and
Rπ represents one or more substituents independently selected from the group consisting of hydrogen, hydroxy, oxo, a substituted or unsubstituted aliphatic group, a substituted or unsubstituted aromatic group, a substituted or unsubstituted heteroaromatic group, a substituted or unsubstituted
alkoxycarbonyl, a substituted or unsubstituted alkoxyalkyl, a substituted or unsubstituted aminocarbonyl, a substituted or unsubstituted alkylcarbonyl, a substituted or unsubstituted arylcarbonyl, a substituted or unsubstituted heteroarylcarbonyl, a substituted or unsubstituted aminoalkyl and a substituted or unsubstituted aralkyl groups, provided that the carbon atoms adjacent to the nifrogen atom are not substituted by a hydroxy group.

18. The compound of Claim 17 wherein Z2 is ofthe formula N(R35)R36, wherein R35 and R36 are each, independently, hydrogen, alkyl, alkoxycarbonyl, alkoxyalkyl, hydroxyalkyl, aminocarbonyl, cyano, alkylcarbonyl or aralkyl.

19. The compound of Claim 17 wherein Z2 is ofthe formula

wherein:
each X, is, independently, CH or N; and
R37 is hydrogen, cyano or a substituted or unsubstituted alkyl, a substituted or unsubstituted alkoxycarbonyl, a substituted or unsubstituted alkoxyalkyl, a substituted or unsubstituted hydroxyalkyl, a substituted or unsubstituted aminocarbonyl, a substituted or unsubstituted alkylcarbonyl or a substituted or unsubstituted aralkyl group.

20. The compound of Claim 17 wherein Z2 is ofthe formula



wherein
g is an integer from 0 to 3;
T is -O-, -C(O)-, -S-, -SO-, -SO.-, -CH2-, -CH(OR34)- or-N(R34)-;
R34 is hydrogen, substituted or unsubstituted alkyl, a substituted or unsubstituted aryl or a substituted or unsubstituted aralkyl; and
R37 is hydrogen, cyano or a substituted or unsubstituted alkyl, a substituted or unsubstituted alkoxycarbonyl, a substituted or unsubstituted alkoxyalkyl, a substituted or unsubstituted hydroxyalkyl, a substituted or unsubstituted aminocarbonyl, a substituted or unsubstituted alkylcarbonyl or a substituted or unsubstituted aralkyl group.

21. The compound of Claim 17 wherein Z2 is ofthe formula


wherein:
g is an integer from 0 to 3; and
R37 is hydrogen, cyano or a substituted or unsubstituted alkyl, a substituted or unsubstituted alkoxycarbonyl, a substituted or unsubstituted alkoxyalkyl, a substituted or unsubstituted hydroxyalkyl, a substituted or unsubstituted aminocarbonyl, a substituted or unsubstituted alkylcarbonyl or a substituted or unsubstituted aralkyl group.

22. The compound of Claim 17 wherein Z2 is ofthe formula



wherein:
T is -0-, -0(0)-, -S-, -SO-, -SO.-, -CH , -CH(OR34)- or-N(R34)-;
R34 is hydrogen, substituted or unsubstituted alkyl, a substituted or unsubstituted aryl or a substituted or unsubstituted aralkyl; and
g is an integer from 0 to 3; and
R37 is hydrogen, cyano or a substituted or unsubstituted alkyl, a substituted or unsubstituted alkoxycarbonyl, a substituted or unsubstituted alkoxyalkyl, a substituted or unsubstituted hydroxyalkyl, a substituted or unsubstituted aminocarbonyl, a substituted or unsubstituted alkylcarbonyl or a substituted or unsubstituted aralkyl.

23. The compound of Claim 17 wherein Z2 is of the formula


wherein:
R37 is hydrogen, cyano, a substituted or unsubstituted alkyl, a substituted or unsubstituted alkoxycarbonyl, a substituted or unsubstituted alkoxyalkyl, a substituted or unsubstituted hydroxyalkyl, a substituted or unsubstituted aminocarbonyl, a substituted or unsubstituted alkylcarbonyl , a substituted or unsubstituted thioalkoxy or a substituted or unsubstituted aralkyl; and
R38 is hydrogen, substituted or unsubstituted alkyl, a substituted or unsubstituted alkoxycarbonyl, a substituted or unsubstituted alkoxyalkyl, a substituted or unsubstituted aminocarbonyl, perhaloalkyl, a substituted or unsubstituted alkenyl, a substituted or unsubstituted alkylcarbonyl or a substituted or unsubstituted aralkyl.

4. The compound of Claim 1 wherein R! is ofthe formula


wherein:
Ri0 is H, azabicycloalkyl, heterocycloalkyl or Y2-Z2;
Y2 is selected from the group consisting of -C(O)-, -(CH2)q-,-S(O)2-, -C(O)O- SO2NH-, -CONH-, (CH2)qO-, -(CH2)qNH-, -(CH2)qS-, -(CH2)qS(O)-, and - (CH2)qS(O)2-;
q is an integer from 0 to 6; and
Z2 is -H, a substituted or unsubstituted alkyl, a substituted or unsubstituted amino, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl or a substituted or unsubstituted heterocycloalkyl.

25. A compound of claim 24 wherein Rι0 is methyl; ring A is


L is -N(R)C(O)-, where R is H;
G is a direct bond, -CH2-O-, -O-CH2- cyclopropylene, -CH2-O-CH2- or -(CH2)3-; R3 is phenyl, 2,6-difluorophenyl, 2-methoxyphenyl, 2,6-dimethoxyphenyl, 3,4- dichlorophenyl, 3 -methoxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 4- methoxyphenyl, 4-trifluoromethylphenyl, 3-nifrophenyl, 2,5-difluorophenyl, 3- cyanophenyl, 2,3-difluorophenyl, 2-chloropyridin-5-yl, 4- trifluoromethoxyphenyl, 2,4,6-trifluorophenyl, 2-fluoro-6-chlorophenyl, 4- dimethylaminophenyl, 4-cyanophenyl, 3 -fluorophenyl, 2,5-dimethoxyphenyl, 3,4-methylenedioxyphenyl, 2,6-dimethylphenyl, 2-chloro-4-fluorophenyl, 4- nifrophenyl,


26. The compound of Claim 1 wherein R, is ofthe formula



wherein:
r is an integer from 1 to 6; and R8, Rg and the nifrogen atom together form a 3, 4, 5, 6 or 7-membered, substituted or unsubstituted heterocycloalkyl group, substituted or unsubstituted heteroaryl group, or a substituted heterobicyclicalkyl group; or
R8 and R_ are each, independently, -H, azabicycloalkyl, heterocycloalkyl or Y2- 2;
Y2 is selected from the group consisting of -C(O)-, -(CH2)q-,-S(O)2-, -C(O)O-, - SO2NH-, -CONH-, (CH2)qO-, -(CH2)qNH-, -(CH2)qS-, -(CH2)qS(O)-, and- (CH2)qS(O)2-;
q is an integer from 0 to 6; and
Z2 is -H, a substituted or unsubstituted alkyl, a substituted or unsubstituted amino, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl or a substituted or unsubstituted heterocycloalkyl group.

27. The compound of Claim 26 wherein R8, Rg and the nitrogen atom together form a heterocycloalkyl group; ofthe formula



wherein:
R13, R14, R15, R16, R17, R18, R19 and R20 are each, independently, lower alkyl or hydrogen; or
at least one pair of substituents R13 and R14; R15 and R16; R17 and R18; or R19 and

R20 together are an oxygen atom; or
at least one of R13 and R15 is cyano, CONHR21, COOR21, CH2OR21 or
CH2NR21(R22);

R21, R22 and the nifrogen atom together form a 3, 4, 5, 6 or 7-membered, substituted or unsubstituted heterocycloalkyl group, substituted or unsubstituted heteroaryl group, or a substituted heterobicyclicalkyl group; or
R21 and R22 are each, independently, -H, azabicycloalkyl, heterocycloalkyl or Y3-

Y3 is selected from the group consisting of -C(O)-, -(CH2)q-,-S(O)2-, -C(O)O-, - SO2NH-, -CONH-, (CH2)qO-, -(CH2)qNH-, -(CH2)qS-, -(CH2)qS(0)-; and - (CH2)qS(O)2-;
q is an integer from 0 to 6; and
Z3 is -H, a substituted or unsubstituted alkyl, a substituted or unsubstituted amino, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl or a substituted or unsubstituted heterocycloalkyl;
X is -O-, -S-, -SO-, -SO2-, -CH2-, -CH(OR23)- or NR23;
R23 is -H, substituted or unsubstituted alkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted aralkyl, -C(NH)NH2, -C(O)R24, or -C(O)OR24;
R24 is hydrogen, substituted or unsubstituted alkyl, a substituted or unsubstituted aryl or a substituted or unsubstituted aralkyl; and
u is 0 or 1.

28. The compound of Claim 26 wherein R8, Rg and the nifrogen atom together form a heterocycloalkyl ofthe formula



wherein:
R25 and R26 are each, independently, hydrogen or lower alkyl; or R25 and R26 together are an oxygen atom; and
R21, R22 and the nifrogen atom together form a 3, 4, 5 or 6-membered, substituted or unsubstituted heterocycloalkyl group; or
R21 and R22 are each, independently, -H, azabicycloalkyl, heterocycloalkyl or Y3-Z3;
Y3 is -H, selected from the group consisting of -C(O , -(CH2)s-,-S(O)2-, -C(O)O-, -SO2NH-, -CONH-, (CH2)sO-, -(CH2)SNH-, -(CH2)SS-, -(CH2)sS(O)-, and -(CH2)sS(O)2-;
s is an integer from 0 to 6; and
Z3 is a substituted or unsubstituted alkyl, a substituted or unsubstituted amino, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl or a substituted or unsubstituted heterocycloalkyl;
i is an integer from 1 to 6; and
t is an integer from 0 to 6.

29. The compound of Claim 26 wherein R8, Rg and the nitrogen atom together form a heterocycloalkyl group; ofthe formula


wherein:
i is an integer from 1 to 6; and
R27 is OH, CH2OH, C(O)NR24R28 or COOR24;
R24 and R28 are each, independently, hydrogen or a substituted or unsubstituted alkyl, a substituted or unsubstituted aryl or a substituted or unsubstituted aralkyl group.

30. The compound of Claim 26 wherein Rg, Rg and the nitrogen atom together form a heteroaromatic group ofthe formula


wherein:
R29 is a -Cl, substituted or unsubstituted alkyl, a substituted or unsubstituted aryl or a substituted or unsubstituted aralkyl group, carboxylic acid, cyano,
C(O)OR30, CH2OR30, CH2NR21R22 or C(O)NR21R22;
R30 is -H, a substituted or unsubstituted alkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted aralkyl, a substituted or unsubstituted
heterocycloalkyl or heterocycloaryl group; and
R21, R22 and the nifrogen atom together form a 3, 4, 5 or 6-membered, substituted or unsubstituted heterocycloalkyl group, a substituted or unsubstituted heteroaromatic or a substitutixuted or unsubstituted heterobicycloalkyl; or R21 and R22 are each, independently, H, azabicycloalkyl, heterocycloalkyl or Y3- z,3;
Y3 is selected from the group consisting of -C(O)-, -(CH2)t-,-S(O)2-, -C(O)O-, - SO2NH-, -CONH-, (CH2)tO-, -(CH2)^NH-, -(CH2)tS-, -(CH2)tS(O)-, and
-(CH2)tS(O)2-;
t is an integer from 0 to 6; and
Z3 is -H, a substituted or unsubstituted alkyl, a substituted or unsubstituted amino, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl or a substituted or unsubstituted heterocycloalkyl.

31. The compound of Claim 26 wherein at least one of R8 and Rg is of the formula Y3-D, wherein D is ofthe formula

wherein:
Y3 is selected from the group consisting of -C(O)-, -(CH2)t-,-S(O)2-, -C(O)O-, - SO2NH-, -CONH-, (CH2)tO-, -(CH,)^-, -(CH2)tS-, -(CH2)tS(O)-, and
-(CH2)tS(O)2-;
t is an integer from 0 to 6;
T is -O-, -C(O)-, -S-, -SO-, -SO2-, -CH2-, -CH(OR24)- or-N(R24)-;
R24 is hydrogen or a substituted or unsubstituted alkyl, aryl or aralkyl group; and
x is 0, 1 or 2.

32. The compound of Claim 26 wherein at least one of R8 and Rg is ofthe formula Y3-N(R31)R32, wherein:
Y3 is selected from the group consisting of -C(O)-, -(CH2)t-,-S(O)2-, -C(O)O-, - SO2NH-, -CONH-, (CH2)tO-, -(CH,)^-, -(CH2)tS-, -(CH2)tS(O)-, and
-(CH2)tS(O)2-;
t is an interger from 0 to 6;
R31 and R32 are each, independently, substituted or unsubstituted carboxyalkyl, a substituted or unsubstituted alkoxycarbonylalkyl, a substituted or unsubstituted hydroxyalkyl, a substituted or unsubstituted alkylsulfonyl, a substituted or unsubstituted alkylcarbonyl or a substituted or unsubstituted cyanoalkyl; or R31 and R32, together with the nifrogen atom, form a five- or six-membered heterocycloalkyl group, a substituted or unsubstituted heteroaromatic or a substituted or xmsubstituted heterobicycloalkyl.

3. The compound of Claim 1 wherein Rj is ofthe formula


wherein:
w is an integer from 0 to 4;
t is an integer from 0 to 6;
u is O or 1;
Ri2 is hydrogen, hydroxy or a substituted or unsubstituted alkoxy group;
R8, Rg and the nifrogen atom together form a 3, 4, 5 or 6-membered, substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted heteroaromatic, or a substituted or unsubstituted heterobicycloalkyl; or
R8 and Rg are each, independently, -H, azabicycloalkyl, heterocycloalkyl or Y2-

Y2 is selected from the group consisting of -C(O)-, -(CH2)q-,-S(O)2-, -C(O)O-, - SO2NH-, -CONH-, (CH2)qO-, -(CH2)qNH-, -(CH2)qS-, -(CH2)qS(O)-, and - (CH2)qS(O)2-;
q is an integer from 0 to 6; and Z2 is -H, a substituted or unsubstituted alkyl, a substituted or unsubstituted amino, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl or a substituted or unsubstituted heterocycloalkyl.

34. The compound of Claim 33 wherein R8, Rg and the nifrogen atom together form a heterocycloalkyl ofthe formula


wherein
R13, R14, R15, R16, R17, R18, R19 and R20 are each, independently, lower alkyl or hydrogen; or
at least one pair of substituents R13 and R14; R15 and R16; R17 and R,8; or R19 and
R20 together are an oxygen atom; or
at least one of R13 and R15is cyano, CONHR21, COOR21, CH2OR21 or
CH2NR21(R22);
R21, R22 and the nifrogen atom together form a 3, 4, 5, 6 or 7-membered, substituted or unsubstituted heterocycloalkyl group, substituted or unsubstituted heteroaryl group, or a substituted heterobicyclicalkyl group; or
R2] and R22 are each, independently, -H, azabicycloalkyl, heterocycloalkyl or Y3- J
Y3 is selected from the group consisting of -C(O)-, -(CH2)s-,-S(O)2-, -C(O)O- SO2NH-, -CONH-, (CH2)sO-, -(CH2)SNH-, -(CH2)SS-, -(CH2)sS(O)-and
-(CH2)sS(O)2-;
s is an integer from 0 to 6; and Z3 is — H, a substituted or unsubstituted alkyl, a substituted or unsubstituted amino, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl or a substituted or unsubstituted heterocycloalkyl;
X is -O-, -S-, -SO-, -SO2-, -CH2-, -CH(OR23)- or NR23;
R23 is hydrogen, substituted or unsubstituted alkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted aralkyl, -C(NH)NH2, -C(O)R24, or -C(O)OR24; R24 is hydrogen, substituted or unsubstituted alkyl, a substituted or unsubstituted aryl or a substituted or unsubstituted aralkyl; and
y is 0 or 1.

35. The compound of Claim 33 wherein R8, Rg and the nifrogen atom together form a heterocycloalkyl ofthe formula

wherein

κ21
R25 and R26 are each, independently, hydrogen or lower alkyl; or
R25 and R26 together are an oxygen atom;
R21, R22 and the nitrogen atom together form a 3, 4, 5 or 6-membered, substituted or unsubstituted heterocycloalkyl group, a substituted or unsubstituted heteroaromatic or a substixutituted or xmsubstituted heterobicycloalkyl; or

R21 and R22 are each, independently, -H, azabicycloalkyl, heterocycloalkyl or Y3- z3;

Y3 is selected from the group consisting of -C(O)-, -(CH2)s-,-S(O)2-, -C(O)O-, ■ SO2NH-, -CONH-, (CH2)sO-, -(CH2)SNH-, -(CH2)SS-, -(CH2)sS(O)-, and
-(CH2)sS(O)2-;
s is an integer from 0 to 6; and
Z3 is -H, a substituted or unsubstituted alkyl, a substituted or unsubstituted amino, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl or a substituted or unsubstituted heterocycloalkyl group; or r is an integer from 1 to 6; and
z is an integer from 0 to 6.

36. The compound of Claim 33 wherein R8, Rg and the nifrogen atom together form a heterocycloalkyl group ofthe formula



wherein
i is an integer from 1 to 6; and
R27 is CH2OH C(O)NR24R28 or COOR24;
R24 and R28 are each, independently, hydrogen or a substituted or unsubstituted alkyl, a substituted or unsubstituted aryl or a substituted or unsubstituted aralkyl group.

37. The compound of Claim 33 wherein R8, Rg and the nifrogen atom together form a heteroaromatic group ofthe formula


wherein:
R29 is a substituted or unsubstituted alkyl, a substituted or unsubstituted aryl or a substituted or unsubstituted aralkyl group, carboxyl, cyano, C(O)OR30, CH2OR30, CH2NR21R22 or C(O)NR21R22;
R30 is a -H, substituted or unsubstituted alkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted aralkyl, a substituted or unsubstituted
heterocycloalkyl or a substituted or unsubstituted heterocycloaryl group;
R21, R22 and the nitrogen atom together form a 3, 4, 5 or 6-membered, substituted or unsubstituted heterocycloalkyl group, a substituted or unsubstituted heteroaromatic or a substixutituted or unsubstituted heterobicycloalkyl; or R21 and R22 are each, independently, -H, azabicycloalkyl, heterocycloalkyl or Y3-Z3;
Y3 is selected from the group consisting of -C(O)-, -(CH2)s-,-S(O)2-, -C(O)O-, - SO2NH-, -CONH-, (CH2)sO-, -(CH2)SNH-, -(CH2)SS-, -(CH2)sS(O)-, and
-(CH2)sS(O)2-;
s is an integer from 0 to 6; and
Z3 is -H, a substituted or unsubstituted alkyl group, a substituted or unsubstituted amino, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group or a substituted or unsubstituted heterocycloalkyl group.

38. The compound of Claim 33 wherein at least one of R8 and Rg is ofthe formula Y3-D, wherein D is ofthe formula



wherein:
Y3 is selected from the group consisting of -C(O)-, -(CH2)s-,-S(O)2-, -C(O)O-, - S02NH-, -CONH-, (CH2)sO-, -(CH2)SNH-, -(CH2)SS-, -(CH2)sS(O)-, and
-(CH2)sS(O)2-;
s is an integer from 0 to 6;
T is -O-, -C(O)-, -S-, -SO-, -SO2-, -CH2-, -CH(OR33)- or -NR33-;
R33 is hydrogen, a substituted or unsubstituted alkyl, a substituted or
unsubstituted aryl, a substituted or unsubstituted aralkyl, -C(NH)NH2, -C(O)R34, or -C(O)OR34;
R34 is hydrogen, substituted or unsubstituted alkyl, aryl or aralkyl,; and x is 0, 1 or 2.

39. The compound of Claim 33 wherein at least one of R8 and Rg is of the formula Y3-N(R31)R32, wherein:
Y3 is selected from the group consisting of -C(O)-, -(CH2)s-,-S(O)2-, -C(O)O-, - .S02NH-, -CONH-, (CH2)sO-, -(CH2)SNH-, -(CH2)SS-, -(CH2)sS(O)-, and
-(CH2)sS(O)2-;
s is an integer from 0 to 6;
R31 and R32 are each, independently, substituted or unsubstituted carboxyalkyl, a substituted or unsubstituted alkoxycarbonylalkyl, a substituted or unsubstituted hydroxyalkyl, a substituted or unsubstituted alkylsulfonyl, a substituted or unsubstituted alkylcarbonyl or a substituted or unsubstituted cyanoalkyl; or R31 and R32, together with the nitrogen atom, form a five- or six-membered heterocycloalkyl group, a substituted or unsubstituted heteroaromatic or a substitutituted or unsubstituted heterobicycloalkyl.

40. The compound of Claim 1 wherein Rl is ofthe formula


wherein:
w is an integer from 0 to 4;
t is an integer from 0 to 6;
R10 is hydrogen or a substituted or unsubstituted alkyl group;
RJ2 is -H, azabicycloalkyl, heteocycloalkyl or Y2-Z2;
Y2is selected from the group consisting of -C(O)-, -(CH2)q-,-S(O)2-, -C(O)O- SO2NH-, -CONH-, (CH2)qO-, -(CH2)qNH-, -(CH2)qS-, -(CH2)qS(O)-, and

-(CH2)qS(O)2-;
q is an integer from 0 to 6; and
Z2 is -H, a substituted or unsubstituted alkyl, a substituted or unsubstituted amino, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl or a substituted or unsubstituted heterocycloalkyl.

41. The compound of Claim 1 wherein Rj is ofthe formula


wherein:
u is 0 or 1 ;
R39, R40, R41, R42, R43, R^, R45 and R46 are each, independently, methyl or hydrogen; or
at least one pair of substituents R39 and R40; R41 and R42; R43 and
R44; or R45 and R46 together are an oxygen atom; and
R47 is H, azabicycloalkyl, heterocycloalkyl or Y2-Z2;
Y2 is selected from the group consisting of -C(O)-, -(CH2)q-,-S(O)2-, -C(O)O-SO2NH-, -CONH-, (CH2)qO-, -(CH2)qNH-, -(CH2)qS-, -(CH2)qS(O)-, and -(CH2)qS(O)2-;
q is an integer from 0 to 6; and
Z2 is -H, a substituted or unsubstituted alkyl, a substituted or unsubstituted amino, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl or a substituted or unsubstituted heterocycloalkyl group; or R47 is ofthe formula


wherein:
y is 0 or 1;
R48, R49, R50, R51, R52, R53, R54 and R55 are each, independently, methyl or hydrogen; or
at least one pair of substituents R48 and R49; R50 and R51; R52 and R53; or R54 and R55 together are an oxygen atom; and
R56 is -H, azabicycloalkyl, heterocycloalkyl or Y3-Z3,
Y3 is selected from the group consisting of -C(O)-, -(CH2)t-,-S(O)2-, -C(O)O-, -SO2NH-, -CONH-, (CH2)tO-, -(CH2)tNH-, -(CH2)tS-, -(CH2)tS(O)-; and -(CH2)tS(O)2-;
t is an integer from 0 to 6; and
Z3 is -H, a substituted or unsubstituted alkyl, a substituted or unsubstituted amino, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl or a substituted or unsubstituted heterocycloalkyl.

42. The compound of Claim 1 wherein R! is ofthe formula


wherein:
e, f, h, u and y are independently 0 or 1;

R57, R58, R59, Rgo, R61, R62, R^, R^, R_5 and R_6 are each, independently, methyl or hydrogen; or
at least one pair of substituents R^ and R^; R_g and Rg0; R_t and Rg2; or ^ and
R^ together are an oxygen atom; and
R^ is H, azabicycloalkyl, heterocycloalkyl or Y2-Z2;
Y2 is selected from the group consisting of -C(O)-, -(CH2)q-,-S(O)2-, -C(O)O-, - SO2NH-, -CONH-, (CH2)qO-, -(CH2)qNH-, -(CH2)qS-, -(CH2)qS(O)-, and
-(CH2)qS(O)2-;
p is an integer from 0 to 6; and
Z2 is -H, a substituted or unsubstituted alkyl, a substituted or unsubstituted amino, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl or a substituted or unsubstituted heterocycloalkyl; or
R67 is ofthe formula


wherein:
d is 0 or 1;
R__, R_9, R70, R71, R72, R73, R74 and R75 are each, independently, lower alkyl or hydrogen; or
at least one pair of substituents R<;8 and R69; R70 and R71; R72 and R73;
and R74 and R75 together are an oxygen atom; and
R76 is -H, azabicycloalkyl, heterocycloalkyl or Y3-Z3;
Y3 is selected from the group consisting of -C(O)-, -(CH2)t-,-S(O)2-, -C(O)O-,

-SO2NH-, -CONH-, (CH2)tO-, -(CH^jNH-, -(CH2)tS-, -(CH2)tS(O)-, and
-(CH2)tS(O)2-;

p is an integer from 0 to 6;
Z3 is -H, a substituted or unsubstituted alkyl, a substituted or unsubstituted amino, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl or a substituted or unsubstituted heterocycloalkyl group.

43. The compound of Claiml , wherein R2 is -H.
44. The compound of Claim 1 , wherein L is -O-, -NHSO2R-, -NC(O)O-, or NHC(O)-.

45. The compound of Claim 1 wherein R! is ofthe formula


wherein m is 0, 1 or 2;
R8ι and R82 are each, independently, selected from the group consisting of hydrogen, hydroxyl, cyanomethyl, carboxymethyl, aminocarbonylmethyl, aminocarbonyl, aminomethyl, hydroxymethyl and amino, provided that no more than one of R8i and RS2 is hydrogen; or
R8ι and R82 together are oxo; -O-(CH2)rO, wherein i is 2 or 3;
-NH-C(O)-NH-C(O)-; or -NH-C(O)-NH-CH2- provided that m is not 1 when RS2 is hydroxy.

46. The compound of Claim 45 wherein Rl is selected from the group consisting of




47. The compound of Claim 1 wherein G is selected from the group consisting of a direct bond; -(CH2)j-, wherein j is 1 or 2; trans -CH=CH-; -cycloC3H4-; and CH20-

48. The compound of Claim 13 wherein m is 2.

49. The compound of Claim 48 wherein S is 0 and R77 is hydrogen.

50. The compound of Claim 49 wherein the -(CH2)t-NR8Rg group is



51. The compound of Claim 49 wherein L is -O-, j is 0 or 1 and R3 is phenyl.

52. The compound of Claim 48 wherein
L is -CH2NHC(O)-; -CH2NHC(O)NH-; -CH2NHC(O)O-; - CH2C(O)NH-; -CH2NHS(O)2-; -NHC(O)-; -NHC(O)NH-; - NHC(O)O-; -C(O)NH-; or -NS(O)2-;
A is 1,4-phenylene or 1,4-phenylene substituted with one or more methoxy groups or fluorine atoms;
R3 is phenyl or phenyl substituted with one or more substituents
selected from the group consisting of chloro, cyano, bromo, fluoro, trifluoromethoxy, methoxy, methylenedioxy, methyl, amino,
dimethylamino and nitro;
R2 is hydrogen; and
G is a direct bond or -(CH2)j-, wherein j is 0 to 4.
53. The compound of Claim 24 wherein R10 is methyl, isopropyl or methoxyethyl.

54. A compound of claim 24, 26, 27, 28, 29, 30, 31, 45 or 47 wherein ring A is



L is -O-;
G is a direct bond; and
R3 is phenyl.

55. A compound selected from the group consisting of:
Ct5-5-(4-phenoxyphenyl)-7-(4-pynolidinocyclohex-l-yl)-7H-pynolo[2,3-d]pyrimidin-4-ylamine,
Trans-5 -(4-phenoxyphenyl)-7-(4-pynolidinocyclohex- 1 -yl)-7H-pynolo [2,3 -d]pyrimidin-4-ylamine ,
Ct-?-5-(4-phenoxyphenyl)-7-(4-piperidinocyclohex- 1 -yl)-7H-pyπolo[2,3-d]pyrimidin-4-ylamine hydrochloride,
rrα7.5-5-(4-phenoxyphenyl)-7-(4-piperidinocyclohex-l-yl)-7H-pynolo[2,3-d]pyrimidin-4-ylamine,
Erα/.i'-7-(4-dimethylaminocyclohexyl)-5-(4-phenoxyphenyl)-7H-pynolo [2,3-d]pyrimidin-4-ylamine,
Ct-f-7-(4-dimethylaminocyclohexyl)-5-(4-phenoxyphenyl)-7H-pynolo[2,3-d]pyrimidin-4-ylamine,
5-(4-phenoxyphenyl)-7-(4-piperidyl)-7H-pynolo[2,3- ]pyrimidin-4-ylamine dihydrochlorid,
5-(4-phenoxyphenyl)-7-(3-pynolidinyl) -7H-pynolo[2,3-_ ]pyrimidin-4-ylamine dihydrochloride,
Cw-7-[4-(4-isopropylpiperazino)cyclohexyl]-5-(4-phenoxyphenyl)-7H-pynolo[2,3-_i]pyrimidin-4-amine,
rrαπ_.-7-[4-(4-isopropylpiperazino)cyclohexyl]-5-(4-phenoxyphenyl)-7H-pynolo[2,3-^]pyrimidin-4-amine,
Cw-7-{4-[4-(2-methoxyethyl)piperazino]cyclohexyl}-5-(4-phenoxyphenyl)-7H-pyπolo[2,3-_f]pyrimidin-4-amine,
rrαn ,-7-{4-[4-(2-methoxyethyl)piperazino]cyclohexyl}-5-(4-phenoxyphenyl)-7H-pynolo[2,3-<i]pyrimidin-4-amine, Cw-7-[-4-(4-ethylpiperazino)cyclohexyl]-5-(4-phenoxyphenyl)-7H-pynolo[2,3- ]pyrimidin-4-amine,
tran5-7-[4-(4-ethylpiperazino)cyclohexyl]-5-(4-phenoxyphenyl)-7H-ρynolo[2,3- _f]pyrimidin-4-amine,
Cw-7-[4-(4-isopropylpiperazino)cyclohexyl]-5-(4-phenoxyphenyl)-7H-pynolo[2,3- J]pyrimidin-4-amine tris maleate,
rrα«^-7-[4-(4-isopropylpiperazino)cyclohexyl]-5-(4-phenoxyphenyl)-7H-pynolo[2,3-</]pyrimidin-4-amine tris maleate,
Cw-7-{4-[4-(2-methoxyethyl)piperazino]cyclohexyl}-5-(4-phenoxyphenyl)-7H-pynolo[2,3- ]pyrimidin-4-amine tris maleate,
Erα..5-7-{4-[4-(2-methoxyethyl)piperazino]cyclohexyl}-5-(4-phenoxyphenyl)-7H-pynolo[2,3-_f]pyrimidin-4-amine tris maleate,
Ct-.-7-(4-{[3-(lH-l-imidazolyl)propyl]amino}cyclohexyl)-5-(4-phenoxyphenyl)-7H-pynolo[2,3-_φyrimidin-4-amine trimaleate salt,
Trans-l-(4- {[3-(lH- 1 -imidazolyl)propyl]amino} cyclohexyl)-5-(4-phenoxyphenyl)- 7H-pynolo[2,3-_/]pyrimidin-4-amine dimaleate salt,
Cw-7-[4-(dimethylamino)cyclohexyl]-5-(4-phenoxyphenyl)-7H-pynolo[2,3- _7jpyrimidin-4-amine dimaleate salt,
rα«5-5-(4-phenoxyphenyl)-7-(4-piperidinocyclohexyl)-7H-pynolo[2,3-<f]pyrimidin-4-amine dimaleate salt,
rr_z/._?-5-(4-phenoxyphenyl)-7-(4-tefrahydro-lH-l-pynolylcyclohexyl)-7H-pynolo[2,3- ]pyrimidin-4-amine dimaleate salt,
Cw-5-(4-phenoxyphenyl)-7-(4-piperazinocyclohexyl)-7H-pynolo[2,3-- |pyrimidin-4-amine trimaleate salt,
rr-.7.-?-5-(4-phenoxyphenyl)-7-(4-piperazinocyclohexyl)-7H-pynolo[2,3-_ ipyrimidin-4-amine trimaleate salt,
7-[3-(4-methylpiperazino)cyclopentyl]-5-(4-phenoxyphenyl)-7H-pynolo[2,3-_ ]pyri.midin-4-amine tri-maleate,
Trans-1- [3 -(4-methylpiperazino)cyclohexyl]-5 -(4-phenoxyphenyl)-7H-pynolo [2,3 -_ ]pyrimidin-4-amine,
rrαn_.-7-[3-(4-methylρiperazino)cyclohexyl]-5-(4-phenoxyphenyl)-7H-pynolo[2,3-_i]pyrimidin-4-amine tri-maleate,
trα«_f-7-[3-(4-methylpiperazino)cyclohexyl]-5-(4-phenoxyphenyl)-7H-pynolo[2,3-_i]pyrimidin-4-amine tri-hydrochloride,
cis-1 - [3 -(4-methylpiperazino)cyclohexyl] -5 -(4-phenoxyphenyl)-7H-pynolo [2,3 -_ ]pyrimidin-4-amine tri-maleate salt,
cw-7 -[3-(4-methylpiperazino)cyclohexyl]-5-(4-phenoxyphenyl)-7H-pynolo[2,3-
tri-hydrochloride, rran5-5-(2-methyl-4-phenoxyphenyl)-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-_i]pyrimidin-4-amine trimaleate,
Cis- benzyl N-(4- {4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7Η-pynolo[2,3-d]pyrimidin-5-yl} 2-methoxyphenyl)carbamate tri-maleate,
Trans- benzyl N-(4- {4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl}-2-methoxyphenyl)carbamate tri-maleate,
_ r_zπ..-Nl-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl}-2-methoxyphenyl)benzamide,
rrα7.5-Nl-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl}-2-methoxyphenyl)benzamide tri-maleate,
Cώ-Nl-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl}-2-methoxyphenyl)-3-phenylpropanamide,
Trans- Nl -(4- {4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl}-2-methoxyphenyl)-3-phenylρropanamide,
cis- Nl -(4-4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3- ]ρyrimidin-5-yl-2-methoxyphenyl)-3-phenylpropanamide trimaleate salt, trαn_f-Nl-(4-4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-J]pyrimidin-5-yl-2-methoxyphenyl)-3-phenylpropanamide tri-maleate,
c/_.-2-(4-4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-_f]pyrimidin-5-ylphenoxy)-6-[(3-methoxypropyl)amino]benzonitrile tri-maleate, tr_.7.5'-2-(4-4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3- ]pyrimidin-5-ylphenoxy)-6-[(3-methoxypropyl)amino]benzonitrile tri-maleate, t_?-2-amino-6-(4-4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-J]pyrimidin-5-ylphenoxy)benzonitrile tri-maleate,
t «5-2-amino-6-(4-4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-_f]pyrimidin-5-ylphenoxy)benzonitrile tri-maleate,
ct5-2-(4-4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-_ ]pyrimidin-5-ylphenoxy)-6-[(4-methylphenyl)sulfanyl]benzonitrile tri-maleate, tra7._f-2-(4-4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3- ]pyrimidin-5-ylphenoxy)-6-[(4-metnylphenyl)sulfanyl]benzonitrile tri-maleate, ct_.-2-(4-4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-_i]pyrimidin-5-ylphenoxy)-6-(2-pyridylsulfanyl)benzonitrile tri-maleate, trα«_.-2-(4-4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-_ ]pyrimidin-5-ylphenoxy)-6-(2-pyridylsulfanyl)benzonitrile tri-maleate, c/5'-5-(2-methyl-4-phenoxyphenyl)-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-cT]pyrimidin-4-amine tri-maleate,
trα«-.-5-(2-methyl-4-phenoxyphenyl)-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-c?]pyrimidin-4-amine tri-maleate, cis-Nl-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-4-fluoro-l-benzenesulfonamide tri-maleate, trans-Nl-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-4-fluoro-l-benzenesulfonamide tri-maleate, Nl -4-[4-amino-7-(l -benzyl-4-piperidyl)-7H-ρynolo[2,3-d]pyrimidin-5-yl]-2-fluorophenyl-4-fluoro- 1 -benzenesulfonamide,
Nl-4-[4-amino-7-(l-benzyl-4-piperidyl)-7H-pynolo[2,3-d]pyrimidin-5-yl]-2-fluorophenyl-2,3-dichloro-l-benzenesulfonamide,
Nl-4-[4-amino-7-(4-piperidyl)-7H-pynolo[2,3-d]pyrimidin-5-yl]-2-fluorophenyl-4-fluoro- 1 -benzenesulfonamide,
Nl-4-[4-amino-7-(l-formyl-4-piperidyl)-7H-pynolo[2,3-d]pyrimidin-5-yl]-2-fluorophenyl-4-fluoro- 1 -benzenesulfonamide,
Nl-[4-(4-amino-7-l-[(l-methyl-lH-4-imidazolyl)sulfonyl]-4-piperidyl-7H-pynolo[2,3-d]pyrimidin-5-yl)-2-fluorophenyl]-4-fluoro-l-benzenesulfonamide dimaleate,
Nl-[4-(4-amino-7-l-[(l,2-dimethyl-lH-4-imidazolyl)sulfonyl]-4-piperidyl-7H-pynolo[2,3-d]pyrimidin-5-yl)-2-fluorophenyl]-4-fluoro-l-benzenesulfonamide,

Nl-[4-(4-amino-7-l-[(l,3-dimethyl-lH-5-pyrazolyl)carbonyl]-4-piperidyl-7H-pynolo[2,3-d]pyrimidin-5-yl)-2-fluorophenyl3-4-fluoro-l-benzenesulfonamide, Nl-(4-{4-amino-7-[l-(2-pyridylcarbonyl)-4-piperidyl]-7H-pynolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-4-fluoro-l-benzenesulfonamide,
Nl-4-(4-amino-7-{4-[l-(l-methylpiperid-4-yl)piperidyl]-7H-pynolo[2,3-d]pyrimidin-5-yl} )-2-fluorophenyl-4-fluoro- 1 -benzenesulfonamide tri-maleate,

Trans-N-l-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl} -2-fluorophenyl)-2-(trifluoromethoxy)- 1 -benzenesulfonamide trimaleate,

Trans-N- 1 -(4- {4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-5-chloro-2-thiophenesulfonamide
benzenesulfonamide trimaleate,

Trans-N-l-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2-chloro-4-fluoro-l-benzenesulfonamide benzenesulfonamide trimaleate,

Trans-N- 1 -(4- {4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2,3-dichloro-l-benzenesulfonamide trimaleate, cis-N-l-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5 -yl} -2-fluorophenyl)-2-chloro-4-fluoro- 1 -benzenesulfonamide trimaleate,

cis-N-l-(4-4-anfino-7-[4-(4-methylpiper_ιzino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl-2-fluorophenyl)-2,5-difluoro-l-benzenesulfonamide trimaleate,

Trans-N-l-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2,6-difluoro-l-benzenesulfonamide trimaleate,

Trans- N-4-(4-{4-amino-7-[4-(4-methylpiρerazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2,l,3-benzothiadiazole-4-sulfonamide trimaleate,

Trans-N-l-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2,3,4-trifluoro-l-benzenesulfonamide trimaleate,

cis-N-l-(4-{4-amino-7-[4-(4-methylpiperazmo)cyclohexyl]-7H-pynolo[2,3-d]ρyrimidin-5-yl} -2-fluorophenyl)-2-nitro- 1 -benzenesulfonamide trimaleate,

cis-N-l-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2-fluoro-l-benzenesulfonamide trimaleate,

cis-N-l-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl} -2-fluorophenyl)-2,4,6-trichloro- 1 -benzenesulfonamide trimaleate,

cis-N-l-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2,6-dichloro-l-benzenesulfonamide trimaleate,

cis-N-l-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl} -2-fluorophenyl)-2-chloro- 1 -benzenesulfonamide trimaleate,

cis-N-l-(4-{4-ammo-7-[4-(4-methylρiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)- 3-fluoro-l-benzenesulfonamide dimaleate,

cis-N- 1 -(4- {4-anfino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin- 5-yl} -2-fluorophenyl)-5-chloro-2-thiophenesulfonamide dimaleate,

cis-N-l-(4-{4-ammo-7-[4-(4-memylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl} -2-fluorophenyl)-4-bromo-2,6-difluoro- 1 -benzenesulfonamide trimaleate,

cis-N-l-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-3-chloro-4-fluoro-l-benzenesulfonamide trimaleate,
cis-N-l-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl-2-iodo-l-benzenesulfonamide trimaleate,

cis-N-l-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d3pyrimidin-5-yl}-2-fluorophenyl)-2-(trifluoromethoxy)-l-benzenesulfonamide trimaleate,

cis-N-l-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2,3-dichloro-l-benzenesulfonamide trimaleate,

cis-N-l-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-ρynolo[2,3-d]pyrimidin-5-yl} -2-fluorophenyl)-2-chloro-6-methyl- 1 -benzenesulfonamide trimaleate,

cis-N-l-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl} -2-fluorophenyl)-2-chloro-4-cyano- 1 -benzenesulfonamide trimaleate,

cis-N-l-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2,3,4-trifluoro-l-benzenesulfonamide trimaleate,

cis-N- 1 -(4- {4-amino-7- [4-(4-methylpiperazino)cyclohexyl] -7H-pynolo [2,3 -d]pyrimidin-5-yl} -2-fluorophenyl)-3 ,4-difluoro- 1 -benzenesulfonamide trimaleate,

cis-N-l-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-4-bromo-2-fluoro-l-benzenesulfonamide trimaleate,

cis-N-l-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-ρynolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-5-bromo-2-thiophenesulfonamide trimaleate, cis-N-l-(4-{4-ammo-7-[4-(4-methylpiperazmo)cyclohexyl]-7H-pynolo[2,3-d]pyrimJ.din-5-yl}-2-fluorophenyl)-2,4-dichloro-l-benzenesulfonamide trimaleate,

cis-N-l-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5 -yl} -2-fluorophenyl)-2,3 ,4-trichloro- 1 -benzenesulfonamide trimaleate,

cis-N- 1 -(4- {4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5 -yl} -2-fluorophenyl)-3 -bromo-5 -chloro-2-thiophenesulfonamide trimaleate,

cis- N-4-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2,l,3-benzothiadiazole-4-sulfonamide trimaleate,

cis- N-4-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl} -2-fluorophenyl)-2, 1 ,3-benzoxadiazole-4-sulfonamide trimaleate,

cis-N-l-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2,5-m-chloro-l-thiophenesulfonamide trimaleate,
cis- N-4-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl} -2-fluorophenyl)-(7-chloro-2, 1 ,3-benzoxadiazole)-4-sulfonamide trimaleate,

cis- N-4-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-(7-methyl-2,l,3-benzothiadiazole)-4-sulfonamide trimaleate,
cis- N-4-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl} -2-fluorophenyl)-(5-methyl-2, 1 ,3-benzothiadiazole)-4-sulfonamide trimaleate,
cis- N-4-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl} -2-fluorophenyl)-(5-chloro-2, 1 ,3-benzothiadiazole)-4-sulfonamide trimaleate,
cis-N-l-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-3-chloro-2-methyl-l-benzenesulfonamide trimaleate,

cis-N-l-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl} -2-fluorophenyl)-2-bromo- 1 -benzenesulfonamide trimaleate,

cis-N-l-(4-{4-anfrno-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin- 5-yl}-2-fluorophenyl)-2,5-dibromo-3,6-difluoro-l-benzenesulfonamide trimaleate,

cis-N-l-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2,3-dichloro-l-benzenesulfonamide trimaleate,

cis-N- 1 -(4- {4-amino-7-[4-(4-methylpiperazino)cyclohexyl] -7H-pynolo [2,3 -d]pyrimidin-5-yl}-2-fluorophenyl)- (2-nifrophenyl)methanesulfonamide trimaleate,

Trans-N-l-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyri.midin-5-yl}-2-fluorophenyl)-2-nitro-l-benzenesulfonamide trimaleate,

Trans-N- 1 -(4- {4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2-fluoro-l-benzenesulfonamide trimaleate,

Trans-N-l-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2,4,6-trichloro-l-benzenesulfonamide trimaleate,

Trans-N-l-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2,6-dichloro-l-benzenesulfonamide trimaleate,

Trans-N-l-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2-chloro-l-benzenesulfonamide trimaleate,

Trans-N- 1 -(4- {4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)- 3-fluoro-l-benzenesulfonamide dimaleate,

Trans-N-l-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-4-bromo-2,5-difluoro-l-ber_zenesulfonamide trimaleate,

Trans-N-l-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-3-chloro-4-fluoro-l-benzenesulfbnamide trimaleate,

Trans-N-l-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl-2-iodo-l-benzenesuIfonamide trimaleate, Trans-N-l-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2,3-dichloro-l-benzenesulfonamide trimaleate,

Trans-N-l-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5 -yl} -2-fluorophenyl)-2-chloro-6-methyl- 1 -benzenesulfonamide trimaleate,

Trans-N-l-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2-chloro-4-cyano-l-benzenesulfonamide trimaleate,

Trans-N-l-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-3,4-difluoro-l-benzenesulfonamide trimaleate,

Trans-N- 1 -(4- {4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl} -2-fluorophenyl)-4-bromo-2-fluoro- 1 -benzenesulfonamide trimaleate,

Trans-N-l-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-5-bromo-2-thiophenesulfonamide trimaleate,

Trans-N-l-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl} -2-fluorophenyl)-2,4-dichloro- 1 -benzenesulfonamide trimaleate,

Trans-N- 1 -(4- {4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2,3,4-trichloro-l-benzenesulfonamide trimaleate,

Trans-N-l-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-3-bromo-5-chloro-2-thiophenesulfonamide trimaleate,

Trans- N-4-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2,l,3-benzoxadiazole-4-sulfonamide trimaleate,

Trans-N-l-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2,5-dichloro-l-thiophenesulfonarnide trimaleate, Trans- N-4-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl} -2-fluorophenyl)-(7-chloro-2, 1 ,3-benzoxadiazole)-4-sulfonamide trimaleate,

Trans- N-4-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl} -2-fluorophenyl)-(7 -methyl-2, 1 ,3-benzothiadiazole)-4-sulfonamide trimaleate,

Trans- N-4-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl} -2-fluorophenyl)-(5-methyl-2, 1 ,3-benzothiadiazole)-4-sulfonamide trimaleate,
Trans- N-4-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-(5-chloro-2,l,3-benzothiadiazole)-4-sulfonamide trimaleate,
Trans-N-l-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-3-chloro-2-methyl-l-benzenesulfonamide trimaleate,

Trans-N-l-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl} -2-fluorophenyl)-2-bromo-l -benzenesulfonamide trimaleate,

Trans-N- 1 -(4- {4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2,5-dibromo-3,6-difluoro-l-benzenesulfonamide trimaleate, or

Trans-N- 1 -(4- {4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pynolo[2,3-d]pyrimidin-5-yl} -2-fluorophenyl)- (2-nitrophenyl)methanesulfonamide trimaleate.

56 .A method of inhibiting protein kinase activity comprising administering a compound of Claim 1 or a physiologically acceptable salt, prodrug or biologically active metabolites thereof.

57. The method of Claim 56 wherein said protein kinase is selected from the group consisting of KDR, FGFR-l, PDGFRβ, PDGFRα, IGF-IR, c-Met, Flt- 1, TIE-2, Lck, Src, fyn, Lyn, Blk, and yes.

58. The method of Claim 56 wherein the activity of said protein kinase affects hyperproliferative disorders.

59. The method of Claim 56 wherein the activity of said protein kinase affects angiogenesis, vascular permeability, immune response or inflammation.

60. A method of treating a patient having a condition which is mediated by protein kinase activity, said method comprising the step of administering to the patient a therapeutically effective amount of a compound of Formula I as defined in Claim 1 or a physiologically acceptable salt, prodrug or biologically active metabolite thereof.

61. The method of Claim 60 wherein said protein kinase is selected from the group consisting of KDR, Flt-1, PDGFRβ, PDGFRα, IGF-IR, c-Met, TIE-2, Lck, Src, fyn, Lyn, Blk, and yes.

62. The method of Claim 60 wherein the condition mediated by protein kinase activity is a hyperproliferative disorder.

63. The method of Claim 60 wherein the activity of said protein kinase affects angiogenesis, vascular permeability, an immulogic response or an
inflammatory response.

64. The method of Claim 60 wherein the protein kinase is a protein
serine/threonine kinase or a protein tyrosine kinase.

65. The method of Claim 60 wherein the condition mediated by protein kinase activity is one or more ulcers.

66. The method of Claim 65 wherein the ulcer or ulcers are caused by a bacterial or fungal infection; or the ulcer or ulcers are Mooren ulcers; or the ulcer or ulcers are a symptom of ulcerative colitis.

67. The method of Claim 60 wherein the condition mediated by protein kinase activity is Lyme disease, sepsis or infection by Herpes simplex, Herpes Zoster, human immunodeficiency virus, parapoxvirus, protozoa or toxoplasmosis.

68. The method of Claim 60 wherein the condition mediated by protein kinase activity is von Hippel Lindau disease, pemphigoid, psoriasis, Paget's disease or polycystic kidney disease.

69. The method of Claim 60 wherein the condition mediated by protein kinase activity is fibrosis, sarcoidosis, cinhosis, thyroiditis, hyperviscosity syndrome, Osier- Weber-Rendu disease, chronic occlusive pulmonary disease, asthma, exudtaes, ascites, pleural effusions, pulmonary edema, cerebral edema or edema following burns, trauma, radiation, stroke, hypoxia or ischemia.

70. The method of Claim 60 wherein the condition mediated by protein kinase activity is ovarian hyperstimulation syndrome, preeclampsia, menomefronhagia, or endometriosis.

71. The method of Claim 60 wherein the condition mediated by protein kinase activity is chronic inflammation, systemic lupus, glomerulonephritis, synovitis, inflammatory bowel disease, Crohn' s disease, glomerulonephritis, rheumatoid arthritis and osteoarthritis, multiple sclerosis or graft rejection.

72. The method of Claim 60 wherein the condition mediated by protein kinase activity is sickle cell anaemia.

73. The method of Claim 60 wherein the condition mediated by protein kinase activity is an ocular condition.

74. The method of Claim 73 wherein the ocular condition is ocular or macular edema, ocular neovascular disease, scleritis, radial keratotomy, uveitis, vitritis, myopia, optic pits, chronic retinal detachment, post-laser treatment complications, conjunctivitis, Stargardt's disease, Eales disease, retinopathy or macular
degeneration.

75. The method of Claim 60 wherein the condition mediated by protein kinase activity is a cardiovascular condition.

76. The method of Claim 75 wherein the condition mediated by protein kinase acitivixy is atherosclerosis, restenosis, ischemia/reperfusion injury, vascular occlusion, venous malformation or carotid obstructive disease.

77. The method of Claim 60 wherein the condition mediated by protein kinase activity is cancer.

78. The method of Claim 77 wherein the cancer is a solid tumor, a sarcoma, fibrosarcoma, osteoma, melanoma, retinoblastoma, a rhabdomyosarcoma, glioblastoma, neuroblastoma, teratocarcinoma, an hematopoietic malignancy and malignant ascites.

79. The method of Claim 78 wherein the cancer is Kaposi's sarcoma, Hodgkin's disease, lymphoma, myeloma or leukemia.

80. The method of Claim 60 wherein the condition mediated by protein kinase actitivity is Crow-Fukase (POEMS) syndrome or a diabetic condition.

81. The method of Claim 80 wherein the diabetic condition is insulin-dependent diabetes mellitus glaucoma, diabetic retinopathy or microangiopathy.

82. The method of Claim 60 wherein the compound of Formula I or a physiologically acceptable salt, prodrug or biologically active metabolite thereof is admimstered in an amount effective to promote angiogenesis or vasculogenesis.

83. The method of Claim 82 wherein the protein kinase is Tie-2.

84. The method of Claim 82 wherein the compound of Formula I, or physiologically acceptable salt, prodrug or biologically active metabolite thereof, is administered in combination with a pro-angiogenic growth factor.

85. The method of Claim 84 wherein the pro-angiogenic growth factor is selected from the group consisiting of VEGF, NEGF-B, NEGF-C, NEGF-D, NEGF-E, HGF, FGF-1, FGF-2, derivatives thereof and antiiodotypic antibodies.

86. The method of Claim 82 wherein the protein kinase-mediated condition is anemia, ischemia, infarct, transplant rejection, a wound, gangrene or necrosis.

87. The method of Claim 60 wherein the protein kinase activity is involved in T cell activation, B cell activation, mast cell degranulation, monocyte activation, the potentiation of an inflammatory response or a combination thereof.

88. A method of decreasing fertility in a patient, said method comprising the step of administering to the patient an effective amount of a compound of Formula I as defined in Claim 1 or a physiologically acceptable salt, prodrug or biologically active metabolite thereof.