IP Library › Granted Patent US 7,846,929

Granted Patent B2

US 7,846,929 · App. 11/789,427 · Granted Dec 7, 2010

Phosphoinositide 3-kinase inhibitor compounds and methods of use

Assignees: Genentech, Inc.; Piramed Limited

View Patent ↗

Loading inventors, assignments & file history…

Monitor This Case

Get email alerts when status or documents change.

Order Certified Copies

Most orders are placed with the USPTO same day — all within 24 business hours.

Order via The Patent Place →

Pre-filled with this patent's details

Quick Facts

Patent No.: US 7,846,929
App. No.: 11/789,427
Granted: Dec 7, 2010
Kind: B2

External Links

USPTO Patent Center↗ Full Patent PDF↗

Abstract

Compounds of Formulas Ia and Ib, and including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting lipid kinases including PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formula Ia and Ib for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

Claims (359)

1. A compound selected from Formula Ia and Formula Ib:

and stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof, wherein:

X is O or S;

R 1 is H;

R 2 is selected from H, F, Cl, Br, I, CN, CF 3 , —NO 2 , —C(═Y)R 10 , —C(═Y)OR 10 , —C(═Y)NR 10 R 11 , —(CR 14 R 15 ) m NR 10 R 11 , —(CR 14 R 15 ) n OR 10 , —(CR 14 R 15 ) t —NR 12 C(═O)(CR 14 R 15 )NR 10 R 11 , —NR 12 C(═Y)R 10 , —NR 12 C(═Y)OR 10 , —NR 12 C(═Y)NR 10 R 11 , —NR 12 SO 2 R 10 , —OC(═Y)R 10 , —OC(═Y)NR 10 R 11 , —OS(O) 2 (OR 10 ), —OP(═Y)(OR 10 )(OR 11 ), —OP(OR 10 )(OR 11 ), SR 10 , —S(O)R 10 , —S(O) 2 R 10 , —S(O) 2 NR 10 R 11 , —S(O)(OR 10 ), —S(O) 2 (OR 10 ), —SC(═Y)R 10 , —SC(═Y)OR 10 , —SC(═Y)NR 10 R 11 , C 1 -C 12 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, C 3 -C 12 carbocyclyl, C 2 -C 20 heterocyclyl, C 6 -C 20 aryl, and C 1 -C 20 heteroaryl;

R 3 is fused bicyclic C 4 -C 20 heterocyclyl or fused bicyclic C 1 -C 20 heteroaryl;

R 10 , R 11 and R 12 are independently H, C 1 -C 12 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, C 3 -C 12 carbocyclyl, C 2 -C 20 heterocyclyl, C 6 -C 20 aryl, or C 1 -C 20 heteroaryl,

or R 10 and R 11 together with the nitrogen to which they are attached optionally form a saturated, partially unsaturated or fully unsaturated C 3 -C 20 heterocyclic ring optionally containing one or more additional ring atoms selected from N, O or S, wherein said heterocyclic ring is optionally substituted with one or more groups independently selected from oxo, (CH 2 ) m OR 10 , NR 10 R 11 , CF 3 , F, Cl, Br, I, SO 2 R 10 , C(═O)R 10 , NR 12 C(═Y)R 11 , NR 12 S(O) 2 R 11 , C(═Y)NR 10 R 11 , C 1 -C 12 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, C 3 -C 12 carbocyclyl, C 2 -C 20 heterocyclyl, C 6 -C 20 aryl and C 1 -C 20 heteroaryl;

R 14 and R 15 are independently selected from H, C 1 -C 12 alkyl, or —(CH 2 ) n -aryl,

or R 14 and R 15 together with the atoms to which they are attached form a saturated or partially unsaturated C 3 -C 12 carbocyclic ring,

where said alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, fused bicyclic C 4 -C 20 heterocyclyl, and fused bicyclic C 1 -C 20 heteroaryl are optionally substituted with one or more groups independently selected from F, Cl, Br, I, CN, CF 3 , —NO 2 , oxo, R 10 , —C(═Y)R 10 , —C(═Y)OR 10 , —C(═Y)NR 10 R 11 , —(CR 14 R 15 ) n NR 10 R 11 , —(CR 14 R 15 ) n OR 10 , —NR 10 R 11 , —NR 12 C(═Y)R 10 , —NR 12 C(═Y)OR 11 , —NR 12 C(═Y)NR 10 R 11 , —NR 12 SO 2 R 10 , ═NR 12 , OR 10 , —OC(═Y)R 10 , —OC(═Y)OR 10 , —OC(═Y)NR 10 R 11 , —OS(O) 2 (OR 10 ), —OP(═Y)(OR 10 )(OR 11 ), —OP(OR 10 )(OR 11 ), SR 10 , —S(O)R 10 , —S(O) 2 R 10 , —S(O) 2 NR 10 R 11 , —S(O)(OR 10 ), —S(O) 2 (OR 10 ), —SC(═Y)R 10 , —SC(═Y)OR 10 , —SC(═Y)NR 10 R 11 , C 1 -C 12 optionally substituted alkyl, C 2 -C 8 optionally substituted alkenyl, C 2 -C 8 optionally substituted alkynyl, C 3 -C 12 optionally substituted carbocyclyl, C 2 -C 20 optionally substituted heterocyclyl, C 6 -C 20 optionally substituted aryl, C 1 -C 20 optionally substituted heteroaryl, —(CR 14 R 15 ) t —NR 12 C(═O)(CR 14 R 15 )NR 10 R 11 , and (CR 4 R 5 ) t —NR 10 R 11 ;

Y is O, S, or NR 12 ;

m is 0, 1, 2, 3, 4, 5 or 6;

n is 1, 2, 3, 4, 5 or 6; and

t is 2, 3, 4, 5 or 6.

2. A compound selected from Formula Ia and Formula Ib:

and stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof, wherein:

X is O or S;

R 1 is —(CR 14 R 15 ) n NR 12 S(O) 2 R 10 where n is 1 or 2; R 12 , R 14 , and R 15 are independently selected from H and C 1 -C 12 alkyl; and R 10 is C 1 -C 12 alkyl or C 6 -C 20 aryl; R 2 is selected from H, F, Cl, Br, I, CN, CF 3 , —NO 2 , —C(═Y)R 10 , —C(═Y)OR 10 , —C(═Y)NR 10 R 11 , —(CR 14 R 15 ) m NR 10 R 11 , —CR 14 R 15 ) n OR 10 , —(CR 14 R 15 ) t —NR 12 C(═O)CR 14 R 15 )NR 10 R 11 , —NR 12 C(═Y)R 10 , —NR 12 C(═Y)OR 10 , —NR 12 C(═Y)NR 10 R 11 , —NR 12 SO 2 R 10 , OR 10 , —OC(═Y)R 10 , —OC(═Y)OR 10 , —OC(═Y)NR 10 R 11 , —OS(O) 2 (OR 10 ), —OP(═Y)(OR 10 )(OR 11 ), —OP(OR 10 )(OR 11 ), SR 10 , —S(O)R 10 , —S(O) 2 R 10 , —S(O) 2 NR 10 R 11 , —S(O)(OR 10 ), —S(O) 2 (OR 10 ), —SC(═Y)R 10 , SC(═Y)OR 10 , —SC(═Y)NR 10 R 11 , C 1 -C 12 alkyl, C 2 -C 8 alkenyl, C 3 -C 12 carbocyclyl, C 2 -C 20 heterocyclyl, C 6 -C 20 aryl, and C 1 -C 20 heteroaryl;

R 3 is fused bicyclic C 4 -C 20 heterocyclyl or fused bicyclic C 1 -C 20 heteroaryl;

R 10 , R 11 and R 12 are independently H, C 1 -C 12 alkyl, C 2 -C 8 alkenyl, C 3 -C 12 carbocyclyl, C 2 -C 20 heterocyclyl, C 6 -C 20 aryl, or C 1 -C 20 heteroaryl,

R 14 and R 15 are independently selected from H, C 1 -C 12 alkyl, or —(CH 2 ) n -aryl,

or R 14 and R 15 together with the atoms to which they are attached form a saturated or partially unsaturated C 3 -C 12 carbocyclic ring,

where said alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, fused bicyclic C 4 -C 20 heterocyclyl, and fused bicyclic C 1 -C 20 heteroaryl are optionally substituted with one or more groups independently selected from F, Cl, Br, I, CN, CF 3 , —NO 2 , oxo, R 10 , —C(═Y)R 10 , —C(═Y)OR 10 , —C(═Y)NR 10 R 11 , —(CR 14 R 15 ) n OR 10 , —NR 10 R 11 , —NR 12 C(═Y)R 10 , —NR 12 C(═Y)OR 11 , —NR 12 C(═Y)NR 10 R 11 , —NR 12 SO 2 R 10 , ═NR 12 , OR 10 , —OC(═Y)R 10 , —OC(═Y)OR 10 , —OC(═Y)NR 10 R 11 , —OS(O) 2 (OR 10 ), —OP(═Y)(OR 10 )(OR 11 ), —OP(OR 10 )(OR 11 ), SR 10 , —S(O)R 10 , —S(O) 2 R 10 , —S(O) 2 NR 10 R 11 , —S(O)(OR 10 ), —S(O)(OR 10 ), —SC(═Y)R 10 , —SC(═Y)OR 10 , —SC(═Y)NR 10 R 11 , C 1 -C 12 optionally substituted alkyl, C 2 -C 8 optionally substituted alkenyl, C 2 ,-C 8 optionally substituted alkynyl, C 3 -C 12 optionally substituted carbocyclyl, C 2 -C 20 optionally substituted heterocyclyl, C 6 -C 20 optionally substituted aryl, C 1 -C 20 optionally substituted heteroaryl, —(CR 14 R 15 ) t —NR 12 C(═O)(CR 14 R 15 )NR 10 R 11 , and (CR 14 R 15 ) t —NR 10 R 11 ;

Y is O, S, or NR 12 ;

m is 0, 1, 2, 3, 4, 5 or 6;

n is 1, 2, 3, 4, 5 or 6; and

t is 2, 3, 4, 5 or 6.

3. A compound selected from Formula Ia and Formula Ib:

and stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof, wherein:

X is O or S;

R 1 is —(CR 14 R 15 ) n OR 10 where n is 1 or 2, and R 10 , R 14 , and R 15 are independently selected from H and C 1 -C 12 alkyl;

R 2 is selected from H, F, Cl, Br, I, CN, CF 3 , —NO 2 , —C(═Y)R 10 , —C(═Y)OR 10 , —C(═Y)NR 10 R 11 , —(CR 14 R 15 ) m NR 10 R 11 , —(CR 14 R 15 ) n OR 10 , —CR 14 R 15 ) t —NR 12 C(═O)(CR 14 R 15 )NR 10 R 11 , —NR 12 C(═Y)R 10 , —NR 12 C(═Y)OR 10 , —NR 12 C(═Y)NR 10 R 11 , —NR 12 SO 2 R 10 , OR 10 , —OC(═Y)R 10 , —OC(═Y)OR 10 , —OC(═Y)NR 10 R 11 , —OS(O) 2 (OR 10 ), —OP(═Y)(OR 10 )(OR 11 ), —OP(OR 10 )OR 11 ), SR 10 , —S(O)R 10 , —S(O) 2 R 10 , —S(O) 2 NR 10 R 11 , —S(O)(OR 10 ), —S(O) 2 (OR 10 ), —SC(═Y)R 10 , —SC(═Y)OR 10 , —SC(═Y)NR 10 R 11 , C 1 -C 12 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, C 3 -C 12 carbocyclyl, C 2 -C 20 heterocyclyl, C 6 -C 20 aryl, and C 1 -C 20 heteroaryl;

R 3 is fused bicyclic C 4 -C 20 heterocyclyl or fused bicyclic C 1 -C 20 heteroaryl;

R 10 , R 11 and R 12 are independently H, C 1 -C 12 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, C 3 -C 12 carbocyclyl, C 2 -C 20 heterocyclyl, C 6 -C 20 aryl, or C 1 -C 20 heteroaryl,

or R 10 and R 11 together with the nitrogen to which they are attached optionally form a saturated, partially unsaturated or fully unsaturated C 3 -C 20 heterocyclic ring optionally containing one or more additional ring atoms selected from N, O or S, wherein said heterocyclic ring is optionally substituted with one or more groups independently selected from oxo, (C 2 ) m OR 10 , NR 10 R 11 , CF 3 , F, Cl, Br, I, SO 2 R 10 , C(═Y)R 10 , NR 12 C(═Y)R 11 , NR 12 S(O) 2R R 11 , C(═Y)NR 10 R 11 , C 1 -C 12 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, C 3 -C 12 carbocyclyl, C 2 -C 20 heterocyclyl, C 6 -C 20 aryl and C 1 -C 20 heteroaryl;

R 14 and R 15 are independently selected from H, C 1 -C 12 alkyl, or —(CH 2 ) n -aryl,

or R 14 and R 15 together with the atoms to which they are attached form a saturated or partially unsaturated C 3 -C 12 carbocyclic ring,

where said alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, fused bicyclic C 4 -C 20 heterocyclyl, and fused bicyclic C 1 -C 20 heteroaryl are optionally substituted with one or more groups independently selected from F, Cl, Br, I, CN, CF 3 , —NO 2 , oxo, R 10 , —C(═Y)R 10 , —C(═Y)OR 10 , —C(═Y)NR 10 R 11 , —(CR 14 R 15 ) n NR 10 R 11 , —(CR 14 R 15 ) n OR 10 , —NR 10 R 11 , —NR 12 C(═Y)R 10 , —NR 12 C(═Y)OR 11 , —NR 12 C(═Y)NR 10 R 11 , —NR 12 SO 2 R 10 , ═NR 12 , OR 10 , —OC(═Y)R 10 , —OC(═Y)OR 10 , —OC(═Y)NR 10 R 11 , —OS(O) 2 (OR 10 ), —OP(═Y)(OR 10 )(OR 11 ), —OP(OR 10 )(OR 11 ), SR 10 , —S(O)R 10 , —S(O) 2 R 10 , —S(O) 2 NR 10 R 11 , —S(O)(OR 10 ), —S(O) 2 (OR 10 ), —SC(═Y)R 10 , —SC(═Y)OR 10 , —SC(═Y)NR 10 R 11 , C 1 -C 12 optionally substituted alkyl, C 2 -C 8 optionally substituted alkenyl, C 2 -C 8 optionally substituted alkynyl, C 3 -C 12 optionally substituted carbocyclyl, C 2 -C 20 optionally substituted heterocyclyl, C 6 -C 0 optionally substituted aryl, C 1 -C 20 optionally substituted heteroaryl, —(CR 14 R 15 ) t —NR 12 C(═O)(CR 14 R 15 ) t NR 12 C(═O)(CR 14 R 15 )NR 10 R 11 , and (CR 14 R 15 ) t NR 10 R 11 ;

Y is O, S, or NR 12 ;

m is 0, 1, 2, 3, 4, 5 or 6;

n is 1, 2, 3, 4, 5 or 6; and

t is 2, 3, 4, 5 or 6.

4. A compound selected from Formula Ia and Formula Ib:

and stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof, wherein:

X is O or S;

R 1 is —(CR 14 R 15 ) n S(O) 2 R 10 where n is 1 or 2, and R 14 R 15 are H;

R 3 is fused bicyclic C 4 -C 20 heterocyclyl or fused bicyclic C 1 -C 20 heteroaryl;

R 10 , R 11 and R 12 are independently H, C 1 -C 12 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, C 3 -C 12 carbocyclyl, C 2 -C 20 heterocyclyl, C 6 -C 20 aryl, or C 1 -C 20 heteroaryl,

or R 10 and R 11 together with the nitrogen to which they are attached optionally form a saturated, partially unsaturated or fully unsaturated C 3 -C 20 heterocyclic ring optionally containing one or more additional ring atoms selected from N, O or S, wherein said heterocyclic ring is optionally substituted with one or more groups independently selected from oxo, (C 2 ) m OR 10 , NR 10 R 11 , CF 3 , F, Cl, Br, I, SO 2 R 10 , C(═O)R 10 , NR 12 C(═Y)R 11 , NR 12 S(O) 2 R 11 , C(═Y)NR 10 R 11 , C 1 -C 12 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, C 3 -C 12 carbocyclyl, C 2 -C 20 heterocyclyl, C 6 -C 20 aryl and C 1 -C 20 heteroaryl;

R 14 and R 15 are independently selected from H, C 1 -C 12 alkyl, or —(CH 2 ) n -aryl,

or R 14 and R 15 together with the atoms to which they are attached form a saturated or partially unsaturated C 3 -C 12 carbocyclic ring,

where said alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, fused bicyclic C 4 -C 20 heterocyclyl, and fused bicyclic C 1 -C 20 heteroaryl are optionally substituted with one or more groups independently selected from F, Cl, Br, I, CN, CF 3 , —NO 2 , oxo, R 10 , —C(═Y)R 10 , —C(═Y)OR 10 , —C(═Y)NR 10 R 11 , —(CR 14 R 15 ) n NR 10 R 11 , —(CR 14 R 15 ) n NR 10 R 11 , —(CR 14 R 15 ) n OR 10 , —NR 10 R 11 , —NR 12 C(═Y)R 10 , —NR 12 C(═Y)OR 11 , —NR 12 C(═Y)NR 10 R 11 , —NR 12 SO 2 R 10 , ═NR 12 , OR 10 , —OC(═Y)R 10 , —OC(═Y)OR 10 , —OC(═Y)NR 10 R 11 , —OS(O) 2 (OR 10 ), —OP(═Y)(OR 10 )(OR 11 ), —OP(OR 10 )(OR 11 ), SR 10 , —S(O)R 10 , —S(O) 2 R 10 , —S(O) 2 NR 10 R 11 , —S(O)(OR 10 ), —S(O) 2 (OR 10 ), —SC(═Y)R 10 , —SC(═Y)OR 10 , —SC(═Y)NR 10 R 11 , C 1 -C 12 optionally substituted alkyl, C 2 -C 8 optionally substituted alkenyl, C 2 ,-C 8 optionally substituted alkynyl, C 3 -C 12 optionally substituted carbocyclyl, C 2 -C 20 optionally substituted heterocyclyl, C 6 -C 20 optionally substituted aryl, C 1 -C 20 optionally substituted heteroaryl, —(CR 14 R 15 ) t —NR 12 C(═O)(CR 14 R 15 )NR 10 R 11 , and (CR 14 R 15 ) t —NR 10 R 11 ;

Y is O, S, or NR 12 ;

m is 0, 1, 2, 3, 4, 5 or 6;

n is 1, 2, 3, 4, 5 or 6; and

t is 2, 3, 4, 5 or 6.

5. The compound of claim 4 wherein R 10 is C 1 -C 12 alkyl or C 6 -C 20 aryl.

6. A compound selected from Formula Ia and Formula Ib:

and stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof, wherein:

X is O or S;

R 1 is —(CR 14 R 15 ) n S(O) 2 NR 10 R 11 where n is 1 or 2, and R 14 and R 15 are H;

R 3 is fused bicyclic C 4 -C 20 heterocyclyl or fused bicyclic C 1 -C 20 heteroaryl;

R 10 , R 11 and R 12 are independently H, C 1 -C 12 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, C 3 -C 12 carbocyclyl, C 2 -C 20 heterocyclyl, C 6 -C 20 aryl, or C 1 -C 20 heteroaryl,

R 14 and R 15 are independently selected from H, C 1 -C 12 alkyl, or —(CH 2 ) n -aryl,

or R 14 and R 15 together with the atoms to which they are attached form a saturated or partially unsaturated C 3 -C 12 carbocyclic ring,

R 16 and R 17 are independently H, C 1 -C 12 alkyl, C 2 -C 8 alkynyl, C 3 -C 12 carbocyclyl, or C 6 -C 20 aryl,

R 18 and R 19 together with the carbon to which they are attached form a C 3 -C 20 heterocyclic ring,

where said alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, fused bicyclic C 4 -C 20 heterocyclyl, and fused bicyclic C 1 -C 20 heteroaryl are optionally substituted with one or more groups independently selected from F, Cl, Br, I, CN, CF 3 , —NO 2 , oxo, R 10 , —C(═Y)R 10 , —C(═Y)OR 10 , —C(═Y)NR 10 R 11 , —(CR 14 R 15 ) n NR 10 R 11 , —(CR 14 R 15 ) n OR 10 , —NR 10 R 11 , —NR 12 C(═Y)R 10 , —NR 12 C(═Y)OR 11 , —NR 12 C(═Y)NR 10 R 11 , —NR 12 SO 2 R 10 , ═NR 12 , OR 10 , —OC(═Y)R 10 , —OC(═Y)OR 10 , —OC(═Y)NR 10 R 11 , —OS(O) 2 (OR 10 ), —OP(═Y)(OR 10 )(OR 11 ), —OP(OR 10 )(OR 11 ), SR 10 , —S(O)R 10 , —S(O) 2 R 10 , —S(O) 2 NR 10 R 11 , —S(O)(OR 10 ), —S(O) 2 (OR 10 ), —SC(═Y)R 10 , —SC(═Y)OR 10 , —SC(═Y)NR 10 R 11 , C 1 -C 12 optionally substituted alkyl, C 2 -C 8 optionally substituted alkenyl, C 2 ,-C 8 optionally substituted alkynyl, C 3 -C 12 optionally substituted carbocyclyl, C 2 -C 20 optionally substituted heterocyclyl, C 6 -C 20 optionally substituted aryl, C 1 -C 20 optionally substituted heteroaryl, —(CR 14 R 15 ) t —NR 12 C(═O)(CR 14 R 15 )NR 10 R 11 , and (CR 14 R 15 ) t —NR 10 R 11 ;

Y is O, S, or NR 12 ;

m is 0, 1, 2, 3, 4, 5 or 6;

n is 1, 2, 3, 4, 5 or 6; and

t is 2, 3, 4, 5 or 6.

7. A compound selected from Formula Ia and Formula Ib:

and stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof, wherein:

X is O or S;

R 1 is —C(═Y)NR 10 R 11 where Y is O and R 10 and R 11 together with the nitrogen to which they are attached form a C 2 -C 20 heterocyclic ring;

R 3 is fused bicyclic C 4 -C 20 heterocyclyl or fused bicyclic C 1 -C 20 heteroaryl;

R 10 , R 11 and R 12 are independently H, C 1 -C 12 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, C 3 -C 12 carbocyclyl, C 2 -C 20 heterocyclyl, C 6 -C 20 aryl, or C 1 -C 20 heteroaryl,

R 14 and R 15 are independently selected from H, C 1 -C 12 alkyl, or —(CH 2 ) n -aryl,

or R 14 and R 15 together with the atoms to which they are attached form a saturated or partially unsaturated C 3 -C 12 carbocyclic ring,

where said alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, fused bicyclic C 4 -C 20 heterocyclyl, and fused bicyclic C 1 -C 20 heteroaryl are optionally substituted with one or more groups independently selected from F, Cl, Br, I, CN, CF 3 , —NO 2 , oxo, R 10 , —C(═Y)R 10 , —C(═Y)OR 10 , —C(═Y)NR 10 R 11 , —(CR 14 R 15 ) n NR 10 R 11 , —(CR 14 R 15 ) n OR 10 , —NR 10 R 11 , —NR 12 C(═Y)R 10 , —NR 12 C(═Y)OR 11 , —NR 12 C(═Y)NR 10 R 11 , —NR 12 SO 2 R 10 , ═NR 12 , OR 10 , —OC(═Y)R 10 , —OC(═Y)OR 10 , —OC(═Y)NR 10 R 11 , —OS(O) 2 (OR 10 ), —OP(═Y)(OR 10 )(OR 11 ), —OP(OR 10 )(OR 11 ), SR 10 , —S(O)R 10 , —S(O) 2 R 10 , —S(O) 2 NR 10 R 11 , —S(O)(OR 10 ), —S(O) 2 (OR 10 ), —SC(═Y)R 10 , —SC(═Y)OR 10 , —SC(═Y)NR 10 R 11 , C 1 -C 12 optionally substituted alkyl, C 2 -C 8 optionally substituted alkenyl, C 2 ,-C 8 optionally substituted alkynyl, C 3 -C 12 optionally substituted carbocyclyl, C 2 -C 20 optionally substituted heterocyclyl, C 6 -C 20 optionally substituted aryl, C 1 -C 20 optionally substituted heteroaryl, —(CR 14 R 15 ) t —NR 12 C(═O)(CR 14 R 15 )NR 10 R 11 , and (CR 14 R 15 ) t —NR 10 R 11 ;

Y is O, S, or NR 12 ;

m is 0, 1, 2, 3, 4, 5 or 6;

n is 1, 2, 3, 4, 5 or 6; and

t is 2, 3, 4, 5 or 6.

8. The compound of claim 7 wherein R 10 and R 11 together with the nitrogen to which they are attached form a C 2 -C 20 heterocyclic ring selected from morpholinyl, piperidinyl, piperazinyl, and pyrrolidinyl.

9. A compound selected from Formula Ia and Formula Ib:

and stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof, wherein:

X is O or S;

R 1 is —C(═Y)NR 10 R 11 where Y is O and R 10 and R 11 are independently selected from H and C 1 -C 12 alkyl;

R 3 is fused bicyclic C 4 -C 20 heterocyclyl or fused bicyclic C 1 -C 20 heteroaryl;

R 10 , R 11 and R 12 are independently H, C 1 -C 12 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, C 3 -C 12 carbocyclyl, C 2 -C 20 heterocyclyl, C 6 -C 20 aryl, or C 1 -C 20 heteroaryl,

R 14 and R 15 are independently selected from H, C 1 -C 12 alkyl, or —(CH 2 ) n -aryl,

or R 14 and R 15 together with the atoms to which they are attached form a saturated or partially unsaturated C 3 -C 12 carbocyclic ring,

where said alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, fused bicyclic C 4 -C 20 heterocyclyl, and fused bicyclic C 1 -C 20 heteroaryl are optionally substituted with one or more groups independently selected from F, Cl, Br, I, CN, CF 3 , —NO 2 , oxo, R 10 , —C(═Y)R 10 , —C(═Y)OR 10 , —C(═Y)NR 10 R 11 , —(CR 14 R 15 ) n NR 10 R 11 , —(CR 14 R 15 ) n OR 10 , —NR 10 R 11 , —NR 12 C(═Y)R 10 , —NR 12 C(═Y)OR 11 , —NR 12 C(═Y)NR 10 R 11 , —NR 12 SO 2 R 10 , ═NR 12 , OR 10 , —OC(═Y)R 10 , —OC(═Y)OR 10 , —OC(═Y)NR 10 R 11 , —OS(O) 2 (OR 10 ), —OP(═Y)(OR 10 )(OR 11 ), —OP(OR 10 )(OR 11 ), SR 10 , —S(O)R 10 , —S(O) 2 R 10 , —S(O) 2 NR 10 R 11 , —S(O)(OR 10 ), —S(O) 2 (OR 10 ), —SC(═Y)R 10 , —SC(═Y)OR 10 , —SC(═Y)NR 10 R 11 , C 1 -C 12 optionally substituted alkyl, C 2 -C 8 optionally substituted alkenyl, C 2 ,-C 8 optionally substituted alkynyl, C 3 -C 12 optionally substituted carbocyclyl, C 2 -C 20 optionally substituted heterocyclyl, C 6 -C 20 optionally substituted aryl, C 1 -C 20 optionally substituted heteroaryl, —(CR 14 R 15 ) t —NR 12 C(═O)(CR 14 R 15 )NR 10 R 11 , and (CR 14 R 15 ) t —NR 10 R 11 ;

Y is O, S, or NR 12 ;

m is 0, 1, 2, 3, 4, 5 or 6;

n is 1, 2, 3, 4, 5 or 6; and

t is 2, 3, 4, 5 or 6.

10. A compound selected from Formula Ia and Formula Ib:

and stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof, wherein:

X is O or S;

R 1 is —C(═Y)NR 10 R 11 where Y is O and R 10 and R 11 are independently selected from H, C 3 -C 12 carbocyclyl, C 2 -C 20 heterocyclyl, C 6 -C 20 aryl, and C 1 -C 20 heteroaryl;

R 3 is fused bicyclic C 4 -C 20 heterocyclyl or fused bicyclic C 1 -C 20 heteroaryl;

R 10 , R 11 and R 12 are independently H, C 1 -C 12 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, C 3 -C 12 carbocyclyl, C 2 -C 20 heterocyclyl, C 6 -C 20 aryl, or C 1 -C 20 heteroaryl,

R 14 and R 15 are independently selected from H, C 1 -C 12 alkyl, or —(CH 2 ) n -aryl,

or R 14 and R 15 together with the atoms to which they are attached form a saturated or partially unsaturated C 3 -C 12 carbocyclic ring,

where said alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, fused bicyclic C 4 -C 20 heterocyclyl, and fused bicyclic C 1 -C 20 heteroaryl are optionally substituted with one or more groups independently selected from F, Cl, Br, I, CN, CF 3 , —NO 2 , oxo, R 10 , —C(═Y)R 10 , —C(═Y)OR 10 , —C(═Y)NR 10 R 11 , —(CR 14 R 15 ) n NR 10 R 11 , —(CR 14 R 15 ) n OR 10 , —NR 10 R 11 , —NR 12 C(═Y)R 10 , —NR 12 C(═Y)OR 11 , —NR 12 C(═Y)NR 10 R 11 , —NR 12 SO 2 R 10 , ═NR 12 , OR 10 , —OC(═Y)R 10 , —OC(═Y)OR 10 , —OC(═Y)NR 10 R 11 , —OS(O) 2 (OR 10 ), —OP(═Y)(OR 10 )(OR 11 ), —OP(OR 10 )(OR 11 ), SR 10 , —S(O)R 10 , —S(O) 2 R 10 , —S(O) 2 NR 10 R 11 , —S(O)(OR 10 ), —S(O) 2 (OR 10 ), —SC(═Y)R 10 , —SC(═Y)OR 10 , —SC(═Y)NR 10 R 11 , C 1 -C 12 optionally substituted alkyl, C 2 -C 8 optionally substituted alkenyl, C 2 ,-C 8 optionally substituted alkynyl, C 3 -C 12 optionally substituted carbocyclyl, C 2 -C 20 optionally substituted heterocyclyl, C 6 -C 20 optionally substituted aryl, C 1 -C 20 optionally substituted heteroaryl, —(CR 14 R 15 ) t —NR 12 C(═O)(CR 14 R 15 )NR 10 R 11 , and (CR 14 R 15 ) t —NR 10 R 11 ;

Y is O, S, or NR 12 ;

m is 0, 1, 2, 3, 4, 5 or 6;

n is 1, 2, 3, 4, 5 or 6; and

t is 2, 3, 4, 5 or 6.

11. A compound selected from Formula Ia and Formula Ib:

and stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof, wherein:

X is O or S;

R 1 is —NHR 12 where R 12 is C 3 -C 12 carbocyclyl, C 2 -C 20 heterocyclyl, C 6 -C 20 aryl, or C 1 -C 20 heteroaryl;

R 3 is fused bicyclic C 4 -C 20 heterocyclyl or fused bicyclic C 1 -C 20 heteroaryl;

R 10 , R 11 and R 12 are independently H, C 1 -C 12 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, C 3 -C 12 carbocyclyl, C 2 -C 20 heterocyclyl, C 6 -C 20 aryl, or C 1 -C 20 heteroaryl,

R 14 and R 15 are independently selected from H, C 1 -C 12 alkyl, or —(CH 2 ) n -aryl,

or R 14 and R 15 together with the atoms to which they are attached form a saturated or partially unsaturated C 3 -C 12 carbocyclic ring,

where said alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, fused bicyclic C 4 -C 20 heterocyclyl, and fused bicyclic C 1 -C 20 heteroaryl are optionally substituted with one or more groups independently selected from F, Cl, Br, I, CN, CF 3 , —NO 2 , oxo, R 10 , —C(═Y)R 10 , —C(═Y)OR 10 , —C(═Y)NR 10 R 11 , —(CR 14 R 15 ) n NR 10 R 11 , —(CR 14 R 15 ) n OR 10 , —NR 10 R 11 , —NR 12 C(═Y)R 10 , —NR 12 C(═Y)OR 11 , —NR 12 C(═Y)NR 10 R 11 , —NR 12 SO 2 R 10 , ═NR 12 , OR 10 , —OC(═Y)R 10 , —OC(═Y)OR 10 , —OC(═Y)NR 10 R 11 , —OS(O) 2 (OR 10 ), —OP(═Y)(OR 10 )(OR 11 ), —OP(OR 10 )(OR 11 ), SR 10 , —S(O)R 10 , —S(O) 2 R 10 , —S(O) 2 NR 10 R 11 , —S(O)(OR 10 ), —S(O) 2 (OR 10 ), —SC(═Y)R 10 , —SC(═Y)OR 10 , —SC(═Y)NR 10 R 11 , C 1 -C 12 optionally substituted alkyl, C 2 -C 8 optionally substituted alkenyl, C 2 ,-C 8 optionally substituted alkynyl, C 3 -C 12 optionally substituted carbocyclyl, C 2 -C 20 optionally substituted heterocyclyl, C 6 -C 20 optionally substituted aryl, C 1 -C 20 optionally substituted heteroaryl, —(CR 14 R 15 ) t —NR 12 C(═O)(CR 14 R 15 )NR 10 R 11 , and (CR 14 R 15 ) t —NR 10 R 11 ;

Y is O, S, or NR 12 ;

m is 0, 1, 2, 3, 4, 5 or 6;

n is 1, 2, 3, 4, 5 or 6; and

t is 2, 3, 4, 5 or 6.

12. The compound of claim 11 wherein R 12 is phenyl or 4-pyridyl.

13. A compound selected from Formula Ia and Formula Ib:

and stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof, wherein:

X is O or S;

R 1 is —NR 12 C(═Y)R 11 where Y is O, R 12 is H or C 1 -C 12 alkyl, and R 11 is C 1 -C 12 alkyl, C 3 -C 12 carbocyclyl, C 2 -C 20 heterocyclyl, C 6 -C 20 aryl, or C 1 -C 20 heteroaryl;

R 3 is fused bicyclic C 4 -C 20 heterocyclyl or fused bicyclic C 1 -C 20 heteroaryl;

R 10 , R 11 and R 12 are independently H, C 1 -C 12 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, C 3 -C 12 carbocyclyl, C 2 -C 20 heterocyclyl, C 6 -C 20 aryl, or C 1 -C 20 heteroaryl,

R 14 and R 15 are independently selected from H, C 1 -C 12 alkyl, or —(CH 2 ) n -aryl,

or R 14 and R 15 together with the atoms to which they are attached form a saturated or partially unsaturated C 3 -C 12 carbocyclic ring,

where said alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, fused bicyclic C 4 -C 20 heterocyclyl, and fused bicyclic C 1 -C 20 heteroaryl are optionally substituted with one or more groups independently selected from F, Cl, Br, I, CN, CF 3 , —NO 2 , oxo, R 10 , —C(═Y)R 10 , —C(═Y)OR 10 , —C(═Y)NR 10 R 11 , —(CR 14 R 15 ) n NR 10 R 11 , —(CR 14 R 15 ) n OR 10 , —NR 10 R 11 , —NR 12 C(═Y)R 10 , —NR 12 C(═Y)OR 11 , —NR 12 C(═Y)NR 10 R 11 , —NR 12 SO 2 R 10 , ═NR 12 , OR 10 , —OC(═Y)R 10 , —OC(═Y)OR 10 , —OC(═Y)NR 10 R 11 , —OS(O) 2 (OR 10 ), —OP(═Y)(OR 10 )(OR 11 ), —OP(OR 10 )(OR 11 ), SR 10 , —S(O)R 10 , —S(O) 2 R 10 , —S(O) 2 NR 10 R 11 , —S(O)(OR 10 ), —S(O) 2 (OR 10 ), —SC(═Y)R 10 , —SC(═Y)OR 10 , —SC(═Y)NR 10 R 11 , C 1 -C 12 optionally substituted alkyl, C 2 -C 8 optionally substituted alkenyl, C 2 ,-C 8 optionally substituted alkynyl, C 3 -C 12 optionally substituted carbocyclyl, C 2 -C 20 optionally substituted heterocyclyl, C 6 -C 20 optionally substituted aryl, C 1 -C 20 optionally substituted heteroaryl, —(CR 14 R 15 ) t —NR 12 C(═O)(CR 14 R 15 )NR 10 R 11 , and (CR 14 R 15 ) t —NR 10 R 11 ;

Y is O, S, or NR 12 ;

m is 0, 1, 2, 3, 4, 5 or 6;

n is 1, 2, 3, 4, 5 or 6; and

t is 2, 3, 4, 5 or 6.

14. The compound of claim 13 wherein R 11 is selected from methyl, ethyl, propyl, isopropyl, isobutyl, 2,2-dimethylpropyl, and tert-butyl.

15. The compound of claim 13 wherein R 11 is selected from cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

16. A compound selected from Formula Ia and Formula Ib:

and stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof, wherein:

X is O or S;

R 1 is —NR 12 S(O) 2 R 10 where R 12 is H or C 1 -C 12 alkyl, and R 10 is C 1 -C 12 alkyl, C 3 -C 12 carbocyclyl, C 2 -C 20 heterocyclyl, C 6 -C 20 aryl, or C 1 -C 20 heteroaryl;

R 3 is fused bicyclic C 4 -C 20 heterocyclyl or fused bicyclic C 1 -C 20 heteroaryl;

R 10 , R 11 and R 12 are independently H, C 1 -C 12 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, C 3 -C 12 carbocyclyl, C 2 -C 20 heterocyclyl, C 6 -C 20 aryl, or C 1 -C 20 heteroaryl,

R 14 and R 15 are independently selected from H, C 1 -C 12 alkyl, or —(CH 2 ) n -aryl,

or R 14 and R 15 together with the atoms to which they are attached form a saturated or partially unsaturated C 3 -C 12 carbocyclic ring,

where said alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, fused bicyclic C 4 -C 20 heterocyclyl, and fused bicyclic C 1 -C 20 heteroaryl are optionally substituted with one or more groups independently selected from F, Cl, Br, I, CN, CF 3 , —NO 2 , oxo, R 10 , —C(═Y)R 10 , —C(═Y)OR 10 , —C(═Y)NR 10 R 11 , —(CR 14 R 15 ) n NR 10 R 11 , —(CR 14 R 15 ) n OR 10 , —NR 10 R 11 , —NR 12 C(═Y)R 10 , —NR 12 C(═Y)OR 11 , —NR 12 C(═Y)NR 10 R 11 , —NR 12 SO 2 R 10 , ═NR 12 , OR 10 , —OC(═Y)R 10 , —OC(═Y)OR 10 , —OC(═Y)NR 10 R 11 , —OS(O) 2 (OR 10 ), —OP(═Y)(OR 10 )(OR 11 ), —OP(OR 10 )(OR 11 ), SR 10 , —S(O)R 10 , —S(O) 2 R 10 , —S(O) 2 NR 10 R 11 , —S(O)(OR 10 ), —S(O) 2 (OR 10 ), —SC(═Y)R 10 , —SC(═Y)OR 10 , —SC(═Y)NR 10 R 11 , C 1 -C 12 optionally substituted alkyl, C 2 -C 8 optionally substituted alkenyl, C 2 ,-C 8 optionally substituted alkynyl, C 3 -C 12 optionally substituted carbocyclyl, C 2 -C 20 optionally substituted heterocyclyl, C 6 -C 20 optionally substituted aryl, C 1 -C 20 optionally substituted heteroaryl, —(CR 14 R 15 ) t —NR 12 C(═O)(CR 14 R 15 )NR 10 R 11 , and (CR 14 R 15 ) t —NR 10 R 11 ;

Y is O, S, or NR 12 ;

m is 0, 1, 2, 3, 4, 5 or 6;

n is 1, 2, 3, 4, 5 or 6; and

t is 2, 3, 4, 5 or 6.

17. A compound selected from Formula Ia and Formula Ib:

and stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof, wherein:

X is O or S;

R 1 is S(O) 2 NR 10 R 11 where R 10 and R 11 together with the nitrogen to which they are attached form a C 2 -C 20 heterocyclic ring selected from morpholinyl, piperazinyl, and pyrrolidinyl;

R 3 is fused bicyclic C 4 -C 20 heterocyclyl or fused bicyclic C 1 -C 20 heteroaryl;

R 10 , R 11 and R 12 are independently H, C 1 -C 12 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, C 3 -C 12 carbocyclyl, C 2 -C 20 heterocyclyl, C 6 -C 20 aryl, or C 1 -C 20 heteroaryl,

R 14 and R 15 are independently selected from H, C 1 -C 12 alkyl, or —(CH 2 ) n -aryl,

or R 14 and R 15 together with the atoms to which they are attached form a saturated or partially unsaturated C 3 -C 12 carbocyclic ring,

where said alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, fused bicyclic C 4 -C 20 heterocyclyl, and fused bicyclic C 1 -C 20 heteroaryl are optionally substituted with one or more groups independently selected from F, Cl, Br, I, CN, CF 3 , —NO 2 , oxo, R 10 , —C(═Y)R 10 , —C(═Y)OR 10 , —C(═Y)NR 10 R 11 , —(CR 14 R 15 ) n NR 10 R 11 , —(CR 14 R 15 ) n OR 10 , —NR 10 R 11 , —NR 12 C(═Y)R 10 , —NR 12 C(═Y)OR 11 , —NR 12 C(═Y)NR 10 R 11 , —NR 12 SO 2 R 10 , ═NR 12 , OR 10 , —OC(═Y)R 10 , —OC(═Y)OR 10 , —OC(═Y)NR 10 R 11 , —OS(O) 2 (OR 10 ), —OP(═Y)(OR 10 )(OR 11 ), —OP(OR 10 )(OR 11 ), SR 10 , —S(O)R 10 , —S(O) 2 R 10 , —S(O) 2 NR 10 R 11 , —S(O)(OR 10 ), —S(O) 2 (OR 10 ), —SC(═Y)R 10 , —SC(═Y)OR 10 , —SC(═Y)NR 10 R 11 , C 1 -C 12 optionally substituted alkyl, C 2 -C 8 optionally substituted alkenyl, C 2 ,-C 8 optionally substituted alkynyl, C 3 -C 12 optionally substituted carbocyclyl, C 2 -C 20 optionally substituted heterocyclyl, C 6 -C 20 optionally substituted aryl, C 1 -C 20 optionally substituted heteroaryl, —(CR 14 R 15 ) t —NR 12 C(═O)(CR 14 R 15 )NR 10 R 11 , and (CR 14 R 15 ) t —NR 10 R 11 ;

Y is O, S, or NR 12 ;

m is 0, 1, 2, 3, 4, 5 or 6;

n is 1, 2, 3, 4, 5 or 6; and

t is 2, 3, 4, 5 or 6.

18. A compound selected from Formula Ia and Formula Ib:

and stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof, wherein:

X is O or S;

R 1 is S(O) 2 NR 10 R 11 where R 10 and R 11 are independently selected from H and C 1 -C 12 alkyl;

R 3 is fused bicyclic C 4 -C 20 heterocyclyl or fused bicyclic C 1 -C 20 heteroaryl;

R 10 , R 11 and R 12 are independently H, C 1 -C 12 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, C 3 -C 12 carbocyclyl, C 2 -C 20 heterocyclyl, C 6 -C 20 aryl, or C 1 -C 20 heteroaryl,

R 14 and R 15 are independently selected from H, C 1 -C 12 alkyl, or —(CH 2 ) n -aryl,

or R 14 and R 15 together with the atoms to which they are attached form a saturated or partially unsaturated C 3 -C 12 carbocyclic ring,

where said alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, fused bicyclic C 4 -C 20 heterocyclyl, and fused bicyclic C 1 -C 20 heteroaryl are optionally substituted with one or more groups independently selected from F, Cl, Br, I, CN, CF 3 , —NO 2 , oxo, R 10 , —C(═Y)R 10 , —C(═Y)OR 10 , —C(═Y)NR 10 R 11 , —(CR 14 R 15 ) n NR 10 R 11 , —(CR 14 R 15 ) n OR 10 , —NR 10 R 11 , —NR 12 C(═Y)R 10 , —NR 12 C(═Y)OR 11 , —NR 12 C(═Y)NR 10 R 11 , —NR 12 SO 2 R 10 , ═NR 12 , OR 10 , —OC(═Y)R 10 , —OC(═Y)OR 10 , —OC(═Y)NR 10 R 11 , —OS(O) 2 (OR 10 ), —OP(═Y)(OR 10 )(OR 11 ), —OP(OR 10 )(OR 11 ), SR 10 , —S(O)R 10 , —S(O) 2 R 10 , —S(O) 2 NR 10 R 11 , —S(O)(OR 10 ), —S(O) 2 (OR 10 ), —SC(═Y)R 10 , —SC(═Y)OR 10 , —SC(═Y)NR 10 R 11 , C 1 -C 12 optionally substituted alkyl, C 2 -C 8 optionally substituted alkenyl, C 2 ,-C 8 optionally substituted alkynyl, C 3 -C 12 optionally substituted carbocyclyl, C 2 -C 20 optionally substituted heterocyclyl, C 6 -C 20 optionally substituted aryl, C 1 -C 20 optionally substituted heteroaryl, —(CR 14 R 15 ) t —NR 12 C(═O)(CR 14 R 15 )NR 10 R 11 , and (CR 14 R 15 ) t —NR 10 R 11 ;

Y is O, S, or NR 12 ;

m is 0, 1, 2, 3, 4, 5 or 6;

n is 1, 2, 3, 4, 5 or 6; and

t is 2, 3, 4, 5 or 6.

19. The compound of claim 18 wherein R 10 and R 11 are independently selected from H, substituted ethyl, and substituted propyl.

20. A compound selected from Formula Ia and Formula Ib:

and stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof, wherein:

X is O or S;

R 1 is C 2 -C 12 alkyl;

R 3 is fused bicyclic C 4 -C 20 heterocyclyl or fused bicyclic C 1 -C 20 heteroaryl;

R 10 , R 11 and R 12 are independently H, C 1 -C 12 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, C 3 -C 12 carbocyclyl, C 2 -C 20 heterocyclyl, C 6 -C 20 aryl, or C 1 -C 20 heteroaryl,

R 14 and R 15 are independently selected from H, C 1 -C 12 alkyl, or —(CH 2 ) n -aryl,

or R 14 and R 15 together with the atoms to which they are attached form a saturated or partially unsaturated C 3 -C 12 carbocyclic ring,

where said alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, fused bicyclic C 4 -C 20 heterocyclyl, and fused bicyclic C 1 -C 20 heteroaryl are optionally substituted with one or more groups independently selected from F, Cl, Br, I, CN, CF 3 , —NO 2 , oxo, R 10 , —C(═Y)R 10 , —C(═Y)OR 10 , —C(═Y)NR 10 R 11 , —(CR 14 R 15 ) n NR 10 R 11 , —(CR 14 R 15 ) n OR 10 , —NR 10 R 11 , —NR 12 C(═Y)R 10 , —NR 12 C(═Y)OR 11 , —NR 12 C(═Y)NR 10 R 11 , —NR 12 SO 2 R 10 , ═NR 12 , OR 10 , —OC(═Y)R 10 , —OC(═Y)OR 10 , —OC(═Y)NR 10 R 11 , —OS(O) 2 (OR 10 ), —OP(═Y)(OR 10 )(OR 11 ), —OP(OR 10 )(OR 11 ), SR 10 , —S(O)R 10 , —S(O) 2 R 10 , —S(O) 2 NR 10 R 11 , —S(O)(OR 10 ), —S(O) 2 (OR 10 ), —SC(═Y)R 10 , —SC(═Y)OR 10 , —SC(═Y)NR 10 R 11 , C 1 -C 12 optionally substituted alkyl, C 2 -C 8 optionally substituted alkenyl, C 2 ,-C 8 optionally substituted alkynyl, C 3 -C 12 optionally substituted carbocyclyl, C 2 -C 20 optionally substituted heterocyclyl, C 6 -C 20 optionally substituted aryl, C 1 -C 20 optionally substituted heteroaryl, —(CR 14 R 15 ) t —NR 12 C(═O)(CR 14 R 15 )NR 10 R 11 , and (CR 14 R 15 ) t —NR 10 R 11 ;

Y is O, S, or NR 12 ;

m is 0, 1, 2, 3, 4, 5 or 6;

n is 1, 2, 3, 4, 5 or 6; and

t is 2, 3, 4, 5 or 6.

21. A compound selected from Formula Ia and Formula Ib:

and stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof, wherein:

X is O or S;

R 1 is C 2 -C 8 alkenyl;

R 3 is fused bicyclic C 4 -C 20 heterocyclyl or fused bicyclic C 1 -C 20 heteroaryl;

R 10 , R 11 and R 12 are independently H, C 1 -C 12 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, C 3 -C 12 carbocyclyl, C 2 -C 20 heterocyclyl, C 6 -C 20 aryl, or C 1 -C 20 heteroaryl,

R 14 and R 15 are independently selected from H, C 1 -C 12 alkyl, or —(CH 2 ) n -aryl,

or R 14 and R 15 together with the atoms to which they are attached form a saturated or partially unsaturated C 3 -C 12 carbocyclic ring,

where said alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, fused bicyclic C 4 -C 20 heterocyclyl, and fused bicyclic C 1 -C 20 heteroaryl are optionally substituted with one or more groups independently selected from F, Cl, Br, I, CN, CF 3 , —NO 2 , oxo, R 10 , —C(═Y)R 10 , —C(═Y)OR 10 , —C(═Y)NR 10 R 11 , —(CR 14 R 15 ) n NR 10 R 11 , —(CR 14 R 15 ) n OR 10 , —NR 10 R 11 , —NR 12 C(═Y)R 10 , —NR 12 C(═Y)OR 11 , —NR 12 C(═Y)NR 10 R 11 , —NR 12 SO 2 R 10 , ═NR 12 , OR 10 , —OC(═Y)R 10 , —OC(═Y)OR 10 , —OC(═Y)NR 10 R 11 , —OS(O) 2 (OR 10 ), —OP(═Y)(OR 10 )(OR 11 ), —OP(OR 10 )(OR 11 ), SR 10 , —S(O)R 10 , —S(O) 2 R 10 , —S(O) 2 NR 10 R 11 , —S(O)(OR 10 ), —S(O) 2 (OR 10 ), —SC(═Y)R 10 , —SC(═Y)OR 10 , —SC(═Y)NR 10 R 11 , C 1 -C 12 optionally substituted alkyl, C 2 -C 8 optionally substituted alkenyl, C 2 ,-C 8 optionally substituted alkynyl, C 3 -C 12 optionally substituted carbocyclyl, C 2 -C 20 optionally substituted heterocyclyl, C 6 -C 20 optionally substituted aryl, C 1 -C 20 optionally substituted heteroaryl, —(CR 14 R 15 ) t —NR 12 C(═O)(CR 14 R 15 )NR 10 R 11 , and (CR 14 R 15 ) t —NR 10 R 11 ;

Y is O, S, or NR 12 ;

m is 0, 1, 2, 3, 4, 5 or 6;

n is 1, 2, 3, 4, 5 or 6; and

t is 2, 3, 4, 5 or 6.

22. A compound selected from Formula Ia and Formula Ib:

and stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof, wherein:

X is O or S;

R 1 is C 2 -C 8 alkenyl;

R 3 is fused bicyclic C 4 -C 20 heterocyclyl or fused bicyclic C 1 -C 20 heteroaryl;

R 10 , R 11 and R 12 are independently H, C 1 -C 12 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, C 3 -C 12 carbocyclyl, C 2 -C 20 heterocyclyl, C 6 -C 20 aryl, or C 1 -C 20 heteroaryl,

R 14 and R 15 are independently selected from H, C 1 -C 12 alkyl, or —(CH 2 ) n -aryl,

or R 14 and R 15 together with the atoms to which they are attached form a saturated or partially unsaturated C 3 -C 12 carbocyclic ring,

where said alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, fused bicyclic C 4 -C 20 heterocyclyl, and fused bicyclic C 1 -C 20 heteroaryl are optionally substituted with one or more groups independently selected from F, Cl, Br, I, CN, CF 3 , —NO 2 , oxo, R 10 , —C(═Y)R 10 , —C(═Y)OR 10 , —C(═Y)NR 10 R 11 , —(CR 14 R 15 ) n NR 10 R 11 , —(CR 14 R 15 ) n OR 10 , —NR 10 R 11 , —NR 12 C(═Y)R 10 , —NR 12 C(═Y)OR 11 , —NR 12 C(═Y)NR 10 R 11 , —NR 12 SO 2 R 10 , ═NR 12 , OR 10 , —OC(═Y)R 10 , —OC(═Y)OR 10 , —OC(═Y)NR 10 R 11 , —OS(O) 2 (OR 10 ), —OP(═Y)(OR 10 )(OR 11 ), —OP(OR 10 )(OR 11 ), SR 10 , —S(O)R 10 , —S(O) 2 R 10 , —S(O) 2 NR 10 R 11 , —S(O)(OR 10 ), —S(O) 2 (OR 10 ), —SC(═Y)R 10 , —SC(═Y)OR 10 , —SC(═Y)NR 10 R 11 , C 1 -C 12 optionally substituted alkyl, C 2 -C 8 optionally substituted alkenyl, C 2 ,-C 8 optionally substituted alkynyl, C 3 -C 12 optionally substituted carbocyclyl, C 2 -C 20 optionally substituted heterocyclyl, C 6 -C 20 optionally substituted aryl, C 1 -C 20 optionally substituted heteroaryl, —(CR 14 R 15 ) t —NR 12 C(═O)(CR 14 R 15 )NR 10 R 11 , and (CR 14 R 15 ) t —NR 10 R 11 ;

Y is O, S, or NR 12 ;

m is 0, 1, 2, 3, 4, 5 or 6 ;

n is 1, 2, 3, 4, 5 or 6; and

t is 2, 3, 4, 5 or 6.

23. The compound of claim 22 wherein C 2 -C 8 alkynyl is substituted with C 2 -C 20 heterocyclyl.

24. The compound of claim 23 wherein C 2 -C 20 heterocyclyl is selected from morpholinyl, piperidinyl, piperazinyl, and pyrrolidinyl.

25. The compound of claim 22 wherein R 1 is selected from the groups:

26. A compound selected from Formula Ia and Formula Ib:

and stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof, wherein:

X is O or S;

R 1 is C 6 -C 20 aryl;

R 3 is fused bicyclic C 4 -C 20 heterocyclyl or fused bicyclic C 1 -C 20 heteroaryl;

R 10 , R 11 and R 12 are independently H, C 1 -C 12 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, C 3 -C 12 carbocyclyl, C 2 -C 20 heterocyclyl, C 6 -C 20 aryl, or C 1 -C 20 heteroaryl,

R 14 and R 15 are independently selected from H, C 1 -C 12 alkyl, or —(CH 2 ) n -aryl,

or R 14 and R 15 together with the atoms to which they are attached form a saturated or partially unsaturated C 3 -C 12 carbocyclic ring,

where said alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, fused bicyclic C 4 -C 20 heterocyclyl, and fused bicyclic C 1 -C 20 heteroaryl are optionally substituted with one or more groups independently selected from F, Cl, Br, I, CN, CF 3 , —NO 2 , oxo, R 10 , —C(═Y)R 10 , —C(═Y)OR 10 , —C(═Y)NR 10 R 11 , —(CR 14 R 15 ) n NR 10 R 11 , —(CR 14 R 15 ) n OR 10 , —NR 10 R 11 , —NR 12 C(═Y)R 10 , —NR 12 C(═Y)OR 11 , —NR 12 C(═Y)NR 10 R 11 , —NR 12 SO 2 R 10 , ═NR 12 , OR 10 , —OC(═Y)R 10 , —OC(═Y)OR 10 , —OC(═Y)NR 10 R 11 , —OS(O) 2 (OR 10 ), —OP(═Y)(OR 10 )(OR 11 ), —OP(OR 10 )(OR 11 ), SR 10 , —S(O)R 10 , —S(O) 2 R 10 , —S(O) 2 NR 10 R 11 , —S(O)(OR 10 ), —S(O) 2 (OR 10 ), —SC(═Y)R 10 , —SC(═Y)OR 10 , —SC(═Y)NR 10 R 11 , C 1 -C 12 optionally substituted alkyl, C 2 -C 8 optionally substituted alkenyl, C 2-C 8 optionally substituted alkynyl, C 3 -C 12 optionally substituted carbocyclyl, C 2 -C 20 optionally substituted heterocyclyl, C 6 -C 20 optionally substituted aryl, C 1 -C 20 optionally substituted heteroaryl, —(CR 14 R 15 ) t —NR 12 C(═O)(CR 14 R 15 )NR 10 R 11 , and (CR 14 R 15 ) t —NR 10 R 11 ;

Y is O, S, or NR 12 ;

m is 0, 1, 2, 3, 4, 5 or 6 ;

n is 1, 2, 3, 4, 5 or 6; and

t is 2, 3, 4, 5 or 6.

27. The compound of claim 26 wherein R 1 is optionally substituted phenyl.

28. The compound of claim 27 wherein phenyl is substituted with one or more groups selected from N-methylcarboxamide, isopropylsulfonylamino, methylsulfonyl, 2-hydroxy-2-methylpropanamide, 2-hydroxypropanamide, 2-methoxyacetamide, (propan-2-ol)sulfonyl, 2-amino-2-methylpropanamide, 2-aminoacetamide, 2-hydroxyacetamide, methylsulfonylamino, 2-9dimethylamino)acetamide, amino, acetylamino, carboxamide, (4-methylsulfonylpiperazino)-1-methyl, (4-methylpiperazino)-1-methyl, hydroxymethyl, and methoxy.

29. A compound selected from Formula Ia and Formula Ib:

and stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof, wherein:

X is O or S;

R 1 is C 3 -C 12 carbocyclyl;

R 3 is fused bicyclic C 4 -C 20 heterocyclyl or fused bicyclic C 1 -C 20 heteroaryl;

R 10 , R 11 and R 12 are independently H, C 1 -C 12 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, C 3 -C 12 carbocyclyl, C 2 -C 20 heterocyclyl, C 6 -C 20 aryl, or C 1 -C 20 heteroaryl,

R 14 and R 15 are independently selected from H, C 1 -C 12 alkyl, or —(CH 2 ) n -aryl,

or R 14 and R 15 together with the atoms to which they are attached form a saturated or partially unsaturated C 3 -C 12 carbocyclic ring,

where said alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, fused bicyclic C 4 -C 20 heterocyclyl, and fused bicyclic C 1 -C 20 heteroaryl are optionally substituted with one or more groups independently selected from F, Cl, Br, I, CN, CF 3 , —NO 2 , oxo, R 10 , —C(═Y)R 10 , —C(═Y)OR 10 , —C(═Y)NR 10 R 11 , —(CR 14 R 15 ) n NR 10 R 11 , —(CR 14 R 15 ) n OR 10 , —NR 10 R 11 , —NR 12 C(═Y)R 10 , —NR 12 C(═Y)OR 11 , —NR 12 C(═Y)NR 10 R 11 , —NR 12 SO 2 R 10 , ═NR 12 , OR 10 , —OC(═Y)R 10 , —OC(═Y)OR 10 , —OC(═Y)NR 10 R 11 , —OS(O) 2 (OR 10 ), —OP(═Y)(OR 10 )(OR 11 ), —OP(OR 10 )(OR 11 ), SR 10 , —S(O)R 10 , —S(O) 2 R 10 , —S(O) 2 NR 10 R 11 , —S(O)(OR 10 ), —S(O) 2 (OR 10 ), —SC(═Y)R 10 , —SC(═Y)OR 10 , —SC(═Y)NR 10 R 11 , C 1 -C 12 optionally substituted alkyl, C 2 -C 8 optionally substituted alkenyl, C 20-C 8 optionally substituted alkynyl, C 3 -C 12 optionally substituted carbocyclyl, C 2 -C 20 optionally substituted heterocyclyl, C 6 -C 20 optionally substituted aryl, C 1 -C 20 optionally substituted heteroaryl, —(CR 14 R 15 ) t —NR 12 C(═O)(CR 14 R 15 )NR 10 R 11 , and (CR 14 R 15 ) t —NR 10 R 11 ;

Y is O, S, or NR 12 ;

m is 0, 1, 2, 3, 4, 5 or 6 ;

n is 1, 2, 3, 4, 5 or 6; and

t is 2, 3, 4, 5 or 6.

30. A compound selected from Formula Ia and Formula Ib:

and stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof, wherein:

X is O or S;

R 1 is C 2 -C 20 heterocyclyl;

R 3 is fused bicyclic C 4 -C 20 heterocyclyl or fused bicyclic C 1 -C 20 heteroaryl;

R 10 , R 11 and R 12 are independently H, C 1 -C 12 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, C 3 -C 12 carbocyclyl, C 2 -C 20 heterocyclyl, C 6 -C 20 aryl, or C 1 -C 20 heteroaryl,

R 14 and R 15 are independently selected from H, C 1 -C 12 alkyl, or —(CH 2 ) n -aryl,

or R 14 and R 15 together with the atoms to which they are attached form a saturated or partially unsaturated C 3 -C 12 carbocyclic ring,

where said alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, fused bicyclic C 4 -C 20 heterocyclyl, and fused bicyclic C 1 -C 20 heteroaryl are optionally substituted with one or more groups independently selected from F, Cl, Br, I, CN, CF 3 , —NO 2 , oxo, R 10 , —C(═Y)R 10 , —C(═Y)OR 10 , —C(═Y)NR 10 R 11 , —(CR 14 R 15 ) n NR 10 R 11 , —(CR 14 R 15 ) n OR 10 , —NR 10 R 11 , —NR 12 C(═Y)R 10 , —NR 12 C(═Y)OR 11 , —NR 12 C(═Y)NR 10 R 11 , —NR 12 SO 2 R 10 , ═NR 12 , OR 10 , —OC(═Y)R 10 , —OC(═Y)OR 10 , —OC(═Y)NR 10 R 11 , —OS(O) 2 (OR 10 ), —OP(═Y)(OR 10 )(OR 11 ), —OP(OR 10 )(OR 11 ), SR 10 , —S(O)R 10 , —S(O) 2 R 10 , —S(O) 2 NR 10 R 11 , —S(O)(OR 10 ), —S(O) 2 (OR 10 ), —SC(═Y)R 10 , —SC(═Y)OR 10 , —SC(═Y)NR 10 R 11 , C 1 -C 12 optionally substituted alkyl, C 2 -C 8 optionally substituted alkenyl, C 2 ,-C 8 optionally substituted alkynyl, C 3 -C 12 optionally substituted carbocyclyl, C 2 -C 20 optionally substituted heterocyclyl, C 6 -C 20 optionally substituted aryl, C 1 -C 20 optionally substituted heteroaryl, —(CR 14 R 15 ) t —NR 12 C(═O)(CR 14 R 15 )NR 10 R 11 , and (CR 14 R 15 ) t —NR 10 R 11 ;

Y is O, S, or NR 12 ;

m is 0, 1, 2, 3, 4, 5 or 6 ;

n is 1, 2, 3, 4, 5 or 6; and

t is 2, 3, 4, 5 or 6.

31. A compound selected from Formula Ia and Formula Ib:

and stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof, wherein:

X is O or S;

R 1 is C 1 -C 20 heterocyclyl;

R 3 is fused bicyclic C 4 -C 20 heterocyclyl or fused bicyclic C 1 -C 20 heteroaryl;

R 10 , R 11 and R 12 are independently H, C 1 -C 12 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, C 3 -C 12 carbocyclyl, C 2 -C 20 heterocyclyl, C 6 -C 20 aryl, or C 1 -C 20 heteroaryl,

R 14 and R 15 are independently selected from H, C 1 -C 12 alkyl, or —(CH 2 ) n -aryl,

or R 14 and R 15 together with the atoms to which they are attached form a saturated or partially unsaturated C 3 -C 12 carbocyclic ring,

where said alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, fused bicyclic C 4 -C 20 heterocyclyl, and fused bicyclic C 1 -C 20 heteroaryl are optionally substituted with one or more groups independently selected from F, Cl, Br, I, CN, CF 3 , —NO 2 , oxo, R 10 , —C(═Y)R 10 , —C(═Y)OR 10 , —C(═Y)NR 10 R 11 , —(CR 14 R 15 ) n NR 10 R 11 , —(CR 14 R 15 ) n OR 10 , —NR 10 R 11 , —NR 12 C(═Y)R 10 , —NR 12 C(═Y)OR 11 , —NR 12 C(═Y)NR 10 R 11 , —NR 12 SO 2 R 10 , ═NR 12 , OR 10 , —OC(═Y)R 10 , —OC(═Y)OR 10 , —OC(═Y)NR 10 R 11 , —OS(O) 2 (OR 10 ), —OP(═Y)(OR 10 )(OR 11 ), —OP(OR 10 )(OR 11 ), SR 10 , —S(O)R 10 , —S(O) 2 R 10 , —S(O) 2 NR 10 R 11 , —S(O)(OR 10 ), —S(O) 2 (OR 10 ), —SC(═Y)R 10 , —SC(═Y)OR 10 , —SC(═Y)NR 10 R 11 , C 1 -C 12 optionally substituted alkyl, C 2 -C 8 optionally substituted alkenyl, C 2 ,-C 8 optionally substituted alkynyl, C 3 -C 12 optionally substituted carbocyclyl, C 2 -C 20 optionally substituted heterocyclyl, C 6 -C 20 optionally substituted aryl, C 1 -C 20 optionally substituted heteroaryl, —(CR 14 R 15 ) t —NR 12 C(═O)(CR 14 R 15 )NR 10 R 11 , and (CR 14 R 15 ) t —NR 10 R 11 ;

Y is O, S, or NR 12 ;

m is 0, 1, 2, 3, 4, 5 or 6 ;

n is 1, 2, 3, 4, 5 or 6; and

t is 2, 3, 4, 5 or 6.

32. The compound of claim 31 wherein R 1 is 2-pyridyl, 3-pyridyl, 4-pyridyl, or 5-pyrimidinyl.

33. A compound selected from Formula Ia and Formula Ib:

and stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof, wherein:

X is O or S;

R 1 is selected from H, F, Cl, Br, I, CN, —CR 14 R 15 —NR 16 R 17 , —CR 14 R 15 —NHR 10 , —(CR 14 R 15 ) t NR 10 R 11 , —C (R 14 R 15 ) n NR 12 C(═Y)R 10 , —(CR 14 R 15 ) n NR 12 S (O) 2 R 10 , —(CR 14 R 15 ) m OR 10 , —(CR 14 R 15 ) n S(O) 2 R 10 , —(CR 14 R 15 ) n S(O) 2 NR 10 R 11 , —C(OR 10 ,)R 11 R 14 , —C(R 14 )═CR 18 R 19 , —(═Y)R 10 , —C(═Y)OR 10 , —C(═Y)NR 10 R 11 , —C(═Y)NR 10 OR 10 , —C(═O)NR 12 S(O) 2 R 10 , —C(═O)NR 12 (CR 14 R 15 ) m NR 10 R 11 , —NO 2 , —NHR 12 , —NR 12 C(═Y)R 11 , —NR 12 C(═Y)OR 11 , —NR 12 C(═Y)NR 10 R 11 , —NR 12 S(O) 2 R 10 , —NR 12 SO 2 NR 10 R 11 , —S(O) 2 R 10 , —S(O) 2 NR 10 R 11 , —SC(═Y)R 10 , —SC(═Y)OR 10 , C 2 -C 12 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, C 3 -C 12 carbocycyclyl, C 2 -C 20 heterocyclyl, C 6 -C 20 aryl, or C 1 -C 20 heteroaryl;

R 3 is selected from:

where the wavy line indicates the site of attachment;

R 10 , R 11 and R 12 are independently H, C 1 -C 12 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, C 3 -C 12 carbocyclyl, C 2 -C 20 heterocyclyl, C 6 -C 20 aryl, or C 1 -C 20 heteroaryl,

R 14 and R 15 are independently selected from H, C 1 -C 12 alkyl, or —(CH 2 ) n -aryl,

or R 14 and R 15 together with the atoms to which they are attached form a saturated or partially unsaturated C 3 -C 12 carbocyclic ring,

R 16 and R 17 are independently H, C 1 -C 12 alkyl, C 2 -C 8 alkynyl, C 3 -C 12 carbocyclyl, or C 6 -C 20 aryl,

R 18 and R 19 together with the carbon to which they are attached form a C 3 -C 20 heterocyclic ring,

where said alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, fused bicyclic C 4 -C 20 heterocyclyl, and fused bicyclic C 1 -C 20 heteroaryl are optionally substituted with one or more groups independently selected from F, Cl, Br, I, CN, CF 3 , —NO 2 , oxo, R 10 , —C(═Y)R 10 , —C(═Y)OR 10 , —C(═Y)NR 10 R 11 , —(CR 14 R 15 ) n NR 10 R 11 , —(CR 14 R 15 ) n OR 10 , —NR 10 R 11 , —NR 12 C(═Y)R 10 , —NR 12 C(═Y)OR 11 , —NR 12 C(═Y)NR 10 R 11 , —NR 12 SO 2 R 10 , ═NR 12 , OR 10 , —OC(═Y)R 10 , —OC(═Y)OR 10 , —OC(═Y)NR 10 R 11 , —OS(O) 2 (OR 10 ), —OP(═Y)(OR 10 )(OR 11 ), —OP(OR 10 )(OR 11 ), SR 10 , —S(O)R 10 , —S(O) 2 R 10 , —S(O) 2 NR 10 R 11 , —S(O)(OR 10 ), —S(O) 2 (OR 10 ), —SC(═Y)R 10 , —SC(═Y)OR 10 , —SC(═Y)NR 10 R 11 , C 1 -C 12 optionally substituted alkyl, C 2 -C 8 optionally substituted alkenyl, C 2 ,-C 8 optionally substituted alkynyl, C 3 -C 12 optionally substituted carbocyclyl, C 2 -C 20 optionally substituted heterocyclyl, C 6 -C 20 optionally substituted aryl, C 1 -C 20 optionally substituted heteroaryl, —(CR 14 R 15 ) t —NR 12 C(═O)(CR 14 R 15 )NR 10 R 11 , and (CR 14 R 15 ) t —NR 10 R 11 ;

Y is O, S, or NR 12 ;

m is 0, 1, 2, 3, 4, 5 or 6 ;

n is 1, 2, 3, 4, 5 or 6; and

t is 2, 3, 4, 5 or 6.

34. A pharmaceutical composition comprised of a compound of claim 2 and a pharmaceutically acceptable carrier.

35. The composition according to claim 34 , further comprising a therapeutic agent selected from a chemotherapeutic agent, an anti-inflammatory agent, an immunomodulatory agent, a neurotropic factor, an agent for treating cardiovascular disease, an agent for treating liver disease, an anti-viral agent, an agent for treating blood disorders, an agent for treating diabetes, or an agent for treating immunodeficiency disorders.

36. A composition comprising a compound of claim 2 in an amount to detectably inhibit P13 kinase activity and a pharmaceutically acceptable carrier, adjuvant, or vehicle.

37. A kit comprising:

(a) a first pharmaceutical composition comprising a compound as defined in claim 2 ;

(b) a second pharmaceutical composition that comprises a compound having anti-hyperproliferative activity; and

(c) instructions for the simultaneous, sequential or separate administration of said first and second pharmaceutical compositions to a patient in need thereof;

wherein said first and second pharmaceutical compositions are contained in separate containers.

38. A pharmaceutical composition comprised of a compound of claim 1 and a pharmaceutically acceptable carrier.

39. A pharmaceutical composition comprised of a compound of claim 3 and a pharmaceutically acceptable carrier.

40. A pharmaceutical composition comprised of a compound of claim 4 and a pharmaceutically acceptable carrier.

41. A pharmaceutical composition comprised of a compound of claim 6 and a pharmaceutically acceptable carrier.

42. A pharmaceutical composition comprised of a compound of claim 7 and a pharmaceutically acceptable carrier.

43. A pharmaceutical composition comprised of a compound of claim 9 and a pharmaceutically acceptable carrier.

44. A pharmaceutical composition comprised of a compound of claim 10 and a pharmaceutically acceptable carrier.

45. A pharmaceutical composition comprised of a compound of claim 11 and a pharmaceutically acceptable carrier.

46. A pharmaceutical composition comprised of a compound of claim 13 and a pharmaceutically acceptable carrier.

47. A pharmaceutical composition comprised of a compound of claim 16 and a pharmaceutically acceptable carrier.

48. A pharmaceutical composition comprised of a compound of claim 17 and a pharmaceutically acceptable carrier.

49. A pharmaceutical composition comprised of a compound of claim 18 and a pharmaceutically acceptable carrier.

50. A pharmaceutical composition comprised of a compound of claim 20 and a pharmaceutically acceptable carrier.

51. A pharmaceutical composition comprised of a compound of claim 21 and a pharmaceutically acceptable carrier.

52. A pharmaceutical composition comprised of a compound of claim 22 and a pharmaceutically acceptable carrier.

53. A pharmaceutical composition comprised of a compound of claim 26 and a pharmaceutically acceptable carrier.

54. A pharmaceutical composition comprised of a compound of claim 29 and a pharmaceutically acceptable carrier.

55. A pharmaceutical composition comprised of a compound of claim 30 and a pharmaceutically acceptable carrier.

56. A pharmaceutical composition comprised of a compound of claim 31 and a pharmaceutically acceptable carrier.

57. A pharmaceutical composition comprised of a compound of claim 33 and a pharmaceutically acceptable carrier.

Assignments (3)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 12, 2011

From: PIRAMED LIMITED

To: F. HOFFMANN-LA ROCHE AG

Reel/Frame 026266/0543 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 9, 2008

From: FOLKES, ADRIAN; SHUTTLEWORTH, STEPHEN; OXENFORD, SALLY; HANCOX, TIM; BAYLISS, TRACY

To: PIRAMED LIMITED

Reel/Frame 020775/0546 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 23, 2007

From: CASTANEDO, GEORGETTE; GOLDSMITH, RICHARD; GUNZNER, JANET; HEFFRON, TIM; MALESKY, KIMBERLY; MATHIEU, SIMON; OLIVERO, ALAN; SUTHERLIN, DANIEL P.; TSUI, VICKIE; WANG, SHUMEI; WIESMANN, CHRISTIAN; ZHU, BING-YAN; DOTSON, JENNAFER

To: GENENTECH, INC.

Reel/Frame 019587/0321 →

Continuity (2)

Provisional Application 6079504700 · Apr 26, 2006

Related Publication 20080039459A1 · Feb 14, 2008