Mitotic kinesin inhibitors

1. The compound of the Formula II:

wherein:

a is 0 or 1; b is 0 or 1; m is 0, 1 or 2; n is 0, 1, 2 or 3; and p is 0, 1, 2 or 3;

R 1 is selected from: H, CF 3 , NO 2 , (C═O) a O b (C 1 -C 10 )alkyl, (C═O) a O b (C 2 -C 10 )alkenyl, (C═O) a O b (C 2 -C 10 )alkynyl, (C═O) a O b (C 3 -C 8 )cycloalkyl, (C═O) a O b (C 0 -C 6 )alkylene-aryl, (C═O) a O b (C 0 -C 6 )alkylene-heterocyclyl, (C═O) a O b (C 0 -C 6 )alkylene-N(R b ) 2 , O b (C 1 -C 3 )perfluoroalkyl, (C 0 -C 6 )alkylene-S(O) m R a , C(O)R a , (C 0 -C 6 )alkylene-CO 2 R a , C(O)H, (C 0 -C 6 )alkylene-CO 2 H, and S(O) 2 N(R d ) 2 ; said alkyl, alkenyl, alkynyl, cycloalkyl, aryl, alkylene and heterocyclyl is optionally substituted with up to three substituents selected from R 5 ;

R 2 is selected from: H, CF 3 , NO 2 , (C═O) a O b (C 1 -C 10 )alkyl, (C═O) a O b (C 2 -C 10 )alkenyl, (C═O) a O b (C 2 -C 10 )alkynyl, (C═O) a O b (C 3 -C 8 )cycloalkyl, (C═O) a O b (C 0 -C 6 )alkylene-aryl, (C═O) a O b (C 0 -C 6 )alkylene-heterocyclyl, (C═O) a O b (C 0 -C 6 )alkylene-N(R c ) 2 , O b (C 1 -C 3 )perfluoroalkyl, (C 0 -C 6 )alkylene-S(O) m R a , C(O)R a , (C 0 -C 6 )alkylene-CO 2 R a , C(O)H, (C 0 -C 6 )alkylene-CO 2 H, and S(O) 2 N(R d ) 2 ; said alkyl, alkenyl, alkynyl, cycloalkyl, aryl, alkylene and heterocyclyl is optionally substituted with up to three substituents selected from R 5 ;

R 3 is independently selected from: halogen, (C 1 -C 6 )alkyl, (C 3 -C 8 )cycloalkyl, CF 3 , CF 2 H, CFH 2 , OCF 3 , OH, oxo, CN, (C 1 -C 6 )alkyl hydroxyl, N(R d ) 2 and O(C 1 -C 6 )alkyl;

R 4 is independently selected from: halogen, (C 1 -C 6 )alkyl, OH, oxo, CN, (C 1 -C 6 )alkyl hydroxyl, N(R d ) 2 and O(C 1 -C 6 )alkyl;

R 5 is independently selected from: halogen, (C 1 -C 6 )alkyl, (C═O)O(C 1 -C 6 )alkyl, (C═O)C 1 -C 6 alkyl, (C═O)cycloalkyl, (C═O)aryl, (C═O)heterocyclyl, (C 3 -C 8 )cycloalkyl, aryl, heterocyclyl, OH, oxo, CN, (C 1 -C 6 )alkyl hydroxyl, N(R d ) 2 , O(C 1 -C 6 )alkyl,

—OP(O)OH 2 and —O(C═O)(C 1 -C 6 )alkyl;

R a is selected from: (C 1 -C 6 )alkyl, (C 3 -C 8 )cycloalkyl, aryl and heterocyclyl; said alkyl, cycloalkyl, aryl and heterocyclyl is optionally substituted with one or more substituents selected from OH, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, halogen, CO 2 H, CN, (O)C═O(C 1 -C 6 )alkyl, oxo and N(R d ) 2 ;

R b is independently selected from: H, oxo, OH, halogen, CO 2 H, CN, (O)C═O(C 1 -C 6 )alkyl, N(R d ) 2 , aryl, heterocyclyl, (C 3 -C 8 )cycloalkyl, (C═O) a O b (C 1 -C 6 )alkyl, (C═O)cycloalkyl, (C═O)aryl, (C═O)heterocyclyl, (C 1 -C 6 )alkyl-heterocyclyl and S(O) 2 R a ; said alkyl, cycloalkyl, aryl or heterocyclyl is optionally substituted with one or more substituents selected from R 5 ;

R c is independently selected from: H, oxo, OH, halogen, CO 2 H, CN, (O)C═O(C 1 -C 6 )alkyl, N(R d ) 2 , aryl, heterocyclyl, (C 3 -C 8 )cycloalkyl, (C═O) a O b (C 1 -C 6 )alkyl and S(O) 2 R a ; said alkyl, cycloalkyl, aryl or heterocyclyl is optionally substituted with one or more substituents selected from R 5 ;

R d is independently selected from: H and (C 1 -C 6 )alkyl;

with the proviso that R 1 cannot be (C═O)O—CH 2 CH 3 ;

or a pharmaceutically acceptable salt or stereoisomer thereof.

2. The compound according to claim 1 of the Formula II:

wherein:

R 1 is selected from: H, CF 3 , NO 2 , (C═O) a (C 1 -C 10 )alkyl, O(C 1 -C 10 )alkyl, (C═O) a O b (C 2 -C 10 )alkenyl, (C═O) a O b (C 2 -C 10 )alkynyl, (C═O) a O b (C 3 -C 8 )cycloalkyl, (C═O) a O b (C 0 -C 6 )alkylene-aryl, (C═O) a O b (C 0 -C 6 )alkylene-heterocyclyl, (C═O) a O b (C 0 -C 6 )alkylene-N(R b ) 2 , O b (C 1 -C 3 )perfluoroalkyl, (C 0 -C 6 )alkylene-S(O) m R a , C(O)R a , (C 1 -C 6 )alkylene-CO 2 R a , C(O)H, (C 1 -C 6 )alkylene-CO 2 H, and S(O) 2 N(R d ) 2 ; said alkyl, alkenyl, alkynyl, cycloalkyl, aryl, alkylene and heterocyclyl is optionally substituted with up to three substituents selected from R 5 ;

and all other substituents and variables are as defined in claim 1 ;

or a pharmaceutically acceptable salt or stereoisomer thereof.

3. The compound according to claim 2 of the Formula III:

wherein:

R 1 ′ is selected from: H, CF 3 , NH 2 , NO 2 , O b (C 1 -C 10 )alkyl, O b (C 2 -C 10 )alkenyl, O b (C 2 -C 10 )alkynyl, O b (C 3 -C 8 ) cycloalkyl, O b (C 0 -C 6 )alkylene-aryl, O b (C 0 -C 6 )alkylene-heterocyclyl, O b (C 0 -C 6 )alkylene-N (R b ) 2 , O b (C 1 -C 3 )perfluoroalkyl, (C 0 -C 6 )alkylene-S(O) m R a , C(O)R a , (C 0 -C 6 )alkylene-CO 2 R a , C(O)H, (C 0 -C 6 )alkylene-CO 2 H, and S(O) 2 N(R d ) 2 ; said alkyl, alkenyl, alkynyl, cycloalkyl, aryl, alkylene and heterocyclyl is optionally substituted with up to three substituents selected from R 5 ;

R 2 is selected from: H, CF 3 , NH 2 , NO 2 , (C═O) a O b (C 1 -C 10 )alkyl, (C═O) a O b (C 2 -C 10 )alkenyl, (C═O) a O b (C 2 -C 10 )alkynyl, (C═O) a O b (C 3 -C 8 )cycloalkyl, (C═O) a O b (C 0 -C 6 )alkylene-aryl, (C═O) a O b (C 0 -C 6 )alkylene-heterocyclyl, (C═O) a O b (C 0 -C 6 )alkylene-N(R c ) 2 , O b (C 1 -C 3 )perfluoroalkyl, (C 0 -C 6 )alkylene-S(O) m R a , C(O)R a , (C 0 -C 6 )alkylene-CO 2 R a , C(O)H, (C 0 -C 6 )alkylene-CO 2 H, and S(O) 2 N(R d ) 2 ; said alkyl, alkenyl, alkynyl, cycloalkyl, aryl, alkylene and heterocyclyl is optionally substituted with up to three substituents selected from R 5 ;

and all other substituents and variables are as defined in claim 1 ;

or a pharmaceutically acceptable salt or stereoisomer thereof.

4. The compound according to claim 3 of the Formula IV:

wherein:

R 1 ′ is selected from: H, O b (C 1 -C 10 )alkyl, (C 3 -C 8 )cycloalkyl, heterocyclyl, N(R b ) 2 , (C 1 -C 6 )alkyl(O)(C 1 -C 6 )alkyl, said heterocyclyl optionally substituted with up to three substituents selected from R 5 ;

R 2 is selected from: H, (C 1 -C 6 )alkyl-N(R c ) 2 , (C 1 -C 6 )alkyl-heterocyclyl, (C 1 -C 6 )alkyl-OH, O b (C 1 -C 10 )alkyl, (C 3 -C 8 )cycloalkyl, heterocyclyl, N(R c ) 2 , (C 1 -C 6 )alkyl(O)(C 1 -C 6 )alkyl, said heterocyclyl optionally substituted with up to three substituents selected from R 5 ;

R 3 is selected from: H, halogen and (C 1 -C 6 )alkyl;

R 4 is OH;

R b is independently selected from: H, (C 1 -C 6 )alkyl, O(C 1 -C 6 )alkyl, (C 1 -C 6 )alkyl-heterocyclyl, (C 3 -C 8 )cycloalkyl, heterocyclyl, said alkyl, cycloalkyl and heterocyclyl optionally substituted with up to three substituents selected from R 5 ;

R c is independently selected from: H, (C 1 -C 6 )alkyl, O(C 1 -C 6 )alkyl, (C 1 -C 6 )alkyl-heterocyclyl, (C 3 -C 8 )cycloalkyl, heterocyclyl, said alkyl, cycloalkyl and heterocyclyl optionally substituted with up to three substituents selected from R 5 ;

R d is independently selected from: H and (C 1 -C 6 )alkyl;

and all other substituents and variables are as defined in claim 3 ;

or a pharmaceutically acceptable salt or stereoisomer thereof.

5. A compound which is selected from:

(3R,4R)-8-Fluoro-N-methoxy-N-methyl-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazine-2-carboxamide (1-7);

(3R,4R)-1-(8-Fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl)ethanone (1-8a);

(3R,4R)-1-(8-Chloro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl)ethanone (1-9);

(3R,4R)-1-(8-Fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl)propan-1-one (2-3);

(3R,4R)-1-(8-Fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl)-2,2,2-trimethylethan-1-one (2-4);

(3R,4R)-1-(8-Fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl)cyclopentylketone (2-5);

(3R,4R)-1-(8-Fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl)cyclopropylketone (2-6);

(3R,4R)-1-(8-Fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl)-2 (R and S)-methyl-butan-1-one (2-7);

(3R,4R)-1-(8-Fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl)-2-methyl-ethan-1-one (2-8);

(3R,4R) 8-Fluoro-N,N-dimethyl-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazine-2-carboxamide (3-2);

(3R,4R) 8-Fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazine-2-piperidinylcarboxamide (3-3);

(3R,4R) 8-Fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazine-2-(N-2-propyl)carboxamide (3-4);

(3R,4R) 8-Fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazine-2-(N-cyclopentyl)carboxamide (3-5);

(3R,4R) 8-Fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazine-2-[N-methyl-N-(1-methylpiperidin-4-yl)]carboxamide (3-6);

(3R,4R) 8-Fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazine-2-(N-methyl-N-tert-butyl) carboxamide (3-7);

(3R,4R) 8-Fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazine-2-(N-methyl-N-4-piperidinylmethyl)carboxamide (3-8);

(3R,4R) 8-Fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazine-2-(N-methyl-N-3-tetrahydrofuranyl)carboxamide (3-9);

(3R,4R) 8-Fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazine-2-(N-methyl-N-isobutyl) carboxamide (3-10);

(3R,4R) 8-Fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazine-2-(N-methyl-N-3-thienylmethyl)carboxamide (3-11);

(3R,4R) 8-Fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazine-2-(N-methyl-N-2-tetrahydropyranylethyl)carboxamide (3-12);

(3R,4R) 8-Fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazine-2-[N-methyl-N-(1-methylpyrrolidinyl-3-yl)]carboxamide (3-13);

(3R,4R) 8-Fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazine-2-[N-methyl-N-(1-methylpyrazol-4-ylmethyl)]carboxamide (3-14);

(3R,4R) 8-Fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazine-2-[N-methyl-N-(tetrahydropyran-4-yl)]carboxamide (3-15);

(3R,4R) 8-Fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazine-2-[N-methyl-N-(2-methyl-1,3-thiazol-4-ylmethyl)]carboxamide (3-16);

(3R,4R) 8-Fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazine-2-[N-methyl-N-(1-methylpyrazol-5-ylethyl)]carboxamide (3-17);

(3R,4R) 8-Fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazine-2-[N-methyl-N-(tetrahydropyran-4-ylmethyl)]carboxamide (3-18);

(3R,4R) 1-{8-chloro-3-[3-(dimethylamino)propyl]-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl}ethanone (4-6);

(3R,4R) 1-[8-chloro-3-(3-morpholin-4-ylpropyl)-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl]ethanone (4-7);

(3R,4R) 1-{8-chloro-3-[3-(2-oxa-5-azabicyclo[2.2.1]hept-5-yl)propyl]-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl}ethanone (4-8);

(3R,4R) 1-(8-chloro-3-methyl-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl)ethanone (4-9);

(3R,4R) 8-chloro-3-(3-hydroxypropyl)-N-methyl-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazine-2-carboxamide (4-10);

(3R,4R) 8-fluoro-3-(3-hydroxypropyl)-N-methoxy-N-methyl-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazine-2-carboxamide (4-11);

(3R,4R) 1-[8-fluoro-3-(3-hydroxypropyl)-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl]ethanone (4-12);

(3R,4R) 1-{3-[3-(dimethylamino)propyl]-8-fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl}ethanone (4-13);

(3R,4R) 1-[8-fluoro-3-(3-morpholin-4-ylpropyl)-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl]ethanone (4-14);

(3R,4R) 1-{8-fluoro-3-[3-(2-oxa-5-azabicyclo[2.2.1]hept-5-yl)propyl]-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl}ethanone (4-15);

(3R,4R) 3-(3-hydroxypropyl)-N-methoxy-N,8-dimethyl-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazine-2-carboxamide (4-16);

(3R,4R) 1-[3-(3-hydroxypropyl)-8-methyl-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl]ethanone (4-17);

(3R,4R) 1-{3-[3-(dimethylamino)propyl]-8-methyl-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl}ethanone (4-18);

(3R,4R) 1-[8-methyl-3-(3-morpholin-4-ylpropyl)-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl]ethanone (4-19);

(3R,4R) 1-{8-methyl-3-[3-(2-oxa-5-azabicyclo[2.2.1]hept-5-yl)propyl]-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl}ethanone (4-20);

1-{3-[(3R,4R)-2-acetyl-8-fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-3-yl]propyl}-1,4-diazepan-5-one (4-21);

(3R,4R) 1-{8-fluoro-3-[3-(4-methylpiperazin-1-yl)propyl]-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl}ethanone (4-22);

(3R,4R) 1-[8-fluoro-3-phenyl-3-(3-piperazin-1-ylpropyl)-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl]ethanone (4-23);

tert-butyl 4-{3-[(3R,4R)-2-acetyl-8-fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-3-yl]propyl}piperazine-1-carboxylate (4-24);

1-{(3R,4R)-8-fluoro-3-[3-(4-glycoloylpiperazin-1-yl)propyl]-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl}ethanone (4-25);

1-((3R,4R)-8-fluoro-3-{3-[4-(methoxyacetyl)piperazin-1-yl]propyl}-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl)ethanone (4-26);

4-{3-[(3R,4R)-2-acetyl-8-fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-3-yl]propyl}piperazine-1-carboxamide (4-27);

4-{3-[(3R,4R)-2-acetyl-8-fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-3-yl]propyl}-N-methylpiperazine-1-carboxamide (4-28);

4-{3-[(3R,4R)-2-acetyl-8-fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-3-yl]propyl}-N,N-dimethylpiperazine-1-carboxamide (4-29);

1-((3R,4R)-3-{3-[4-(2,2-dimethylpropanoyl)piperazin-1-yl]propyl}-8-fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl)ethanone (4-30);

methyl (4-{3-[(3R,4R)-2-acetyl-8-fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-3-yl]propyl}piperazin-1-yl)(oxo)acetate (4-31);

methyl 3-(4-{3-[(3R,4R)-2-acetyl-8-fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-3-yl]propyl}piperazin-1-yl)-3-oxopropanoate (4-32);

1-((3R,4R)-8-fluoro-3-{3-[4-(2-furoyl)piperazin-1-yl]propyl}-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl)ethanone (4-33);

1-((3R,4R)-8-fluoro-3-{3-[4-(isoxazol-5-ylcarbonyl)piperazin-1-yl]propyl}-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl)ethanone (4-34);

1-[(3R,4R)-8-fluoro-3-(3-{4-[(5-methylisoxazol-3-yl)carbonyl]piperazin-1-yl}propyl)-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl]ethanone (4-35);

4-{3-[(3R,4R)-2-acetyl-8-fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-3-yl]propyl}piperazin-2-one (4-36);

4-{3-[(3R,4R)-2-acetyl-8-fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-3-yl]propyl}-1-methylpiperazin-2-one (4-37);

1-{3-[(3R,4R)-2-acetyl-8-fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-3-yl]propyl}-4-methyl-1,4-diazepan-5-one (4-38);

1-[(3R,4R)-3-(3-aminopropyl)-8-fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl]ethanone (4-39);

N-[2-({3-[(3R,4R)-2-acetyl-8-fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-3-yl]propyl}amino)ethyl]acetamide (4-40);

(3R,4R)—N,N,3,8-tetramethyl-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazine-2-carboxamide (4-41);

(3R,4R)-3-alkyl-N,N,8-trimethyl-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazine-2-carboxamide (4-42);

(3R,4R)-3-(3-hydroxypropyl)-N,N,8-trimethyl-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazine-2-carboxamide (4-43);

(3R,4R)—N,N,8-trimethyl-3-(3-oxopropyl)-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazine-2-carboxamide (4-44);

(3R,4R)-3-[3-(dimethylamino)propyl]-N,N,8-trimethyl-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazine-2-carboxamide (4-45);

1-{(3R,4R)-3-[3-(4-acetylpiperazin-1-yl)propyl]-8-fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl}ethanone (5-10);

1-{(3R,4R)-3-[3-(4-acetylpiperazin-1-yl)propyl]-8-chloro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl}ethanone;

(3R,4R)-8-Fluoro-3-[3-(3-fluoroazetidin-1-yl)propyl]-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl-ethanone;

(3S,4S)-8-Fluoro-3-[3-(3-fluoroazetidin-1-yl)propyl]-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl-ethanone;

(3R,4R)-8-Fluoro-3-[3-(3-methoxyazetidin-1-yl)propyl]-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl-ethanone;

(3S,4S)-8-Fluoro-3-[3-(3-methoxyazetidin-1-yl)propyl]-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl-ethanone;

(3R,4R)-8-Fluoro-3-[3-(3,3-difluoropyrrolidinyl-1-yl)propyl]-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl-ethanone;

(3S,4S)-8-Fluoro-3-[3-(3,3-difluoropyrrolidinyl-1-yl)propyl]-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl-ethanone;

(3R,4R)-3-[3-(4-cyclopropylpiperazin-1-yl)propyl]-8-fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl-ethanone;

(3S,4S)-3-[3-(4-cyclopropylpiperazin-1-yl)propyl]-8-fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl-ethanone;

1-{(3R,4R)-3-[3-(4-Acetylpiperazin-1-yl)butyl]-8-fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl}ethanone;

1-{(3S,4S)-3-[3-(4-Acetylpiperazin-1-yl)butyl]-8-fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl}ethanone;

1-{(3R,4R)-8-Fluoro-3-[4-(3-fluoroazetidin-1-yl)butyl]-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl}ethanone;

1-{(3S,4S)-8-Fluoro-3-[4-(3-fluoroazetidin-1-yl)butyl]-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl}ethanone;

1-{3-[(3R,4R)-2-acetyl-8-fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-3-yl]butyl}-1,4-diazepan-5-one;

1-{3-[(3S,4S)-2-acetyl-8-fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-3-yl]butyl}-1,4-diazepan-5-one;

Tert-butyl-4-{4-[(3R,4R)-2-acetyl-8-fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl)butyl]piperazine-1-carboxylate;

Tert-butyl-4-{4-[(3S,4S)-2-acetyl-8-fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl)butyl]piperazine-1-carboxylate;

1-[(3R,4R)-8-Fluoro-3-phenyl-3-(4-piperazin-1-ylbutyl)-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl]ethanone;

1-[(3S,4S)-8-Fluoro-3-phenyl-3-(4-piperazin-1-ylbutyl)-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl]ethanone;

1-[(3R,4R)-8-Fluoro-3-{4-[4-(2-furoyl)piperazin-1-yl]butyl}-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-C][1,4]benzoxazin-2-yl]ethanone;

1-[(3S,4S)-8-Fluoro-3-{4-[4-(2-furoyl)piperazin-1-yl]butyl}-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-C][1,4]benzoxazin-2-yl]ethanone;

1-[(3R,4R)-8-Fluoro-3-{4-[4-(3-methylisoxazol-3-yl)carbonyl]piperazin-1-yl}butyl]-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl]ethanone;

1-[(3S,4S)-8-Fluoro-3-{4-[4-(3-methylisoxazol-3-yl)carbonyl]piperazin-1-yl}butyl]-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl]ethanone;

1-[(3R,4R)-8-Fluoro-3-{4-[4-(1,1dioxidothiomorpholin-4-yl) butyl]-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl]ethanone;

1-[(3S,4S)-8-Fluoro-3-{4-[4-(1,1dioxidothiomorpholin-4-yl) butyl]-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl]ethanone;

1-{3-[(3R,4R)-2-acetyl-8-fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-3-yl]butyl}-4-methyl-1,4-diazepan-5-one;

1-{3-[(3S,4S)-2-acetyl-8-fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-3-yl]butyl}-4-methyl-1,4-diazepan-5-one;

1-(3R,4R)-3-(4-aminobutyl)-8-fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl}ethanone;

1-(3S,4S)-3-(4-aminobutyl)-8-fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl}ethanone;

1(R)-{(3R,4R)-3-[3-(4-acetylpiperazin-1-yl)propyl]-8-fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl}ethanol; and

1(S)-{(3R,4R)-3-[3-(4-acetylpiperazin-1-yl)propyl]-8-fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl}ethanol;

or a pharmaceutically acceptable salt or stereoisomer thereof.

6. The compound according to claim 5 which is

(3R,4R)-1-(8-Fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl)ethanone;

or a pharmaceutically acceptable salt or stereoisomer thereof.

7. The compound according to claim 5 which is

(3R,4R) 1-{8-chloro-3-[3-(dimethylamino)propyl]-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl}ethanone;

or a pharmaceutically acceptable salt or stereoisomer thereof.

8. The compound according to claim 5 which is

1-{(3R,4R)-3-[3-(4-acetylpiperazin-1-yl)propyl]-8-fluoro-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl}ethanone;

or a pharmaceutically acceptable salt or stereoisomer thereof.

9. A pharmaceutical composition that is comprised of a compound in accordance with claim 1 and a pharmaceutically acceptable carrier.

10. A pharmaceutical composition that is comprised of a compound in accordance with claim 6 and a pharmaceutically acceptable carrier.

11. A pharmaceutical composition that is comprised of a compound in accordance with claim 7 and a pharmaceutically acceptable carrier.

12. A pharmaceutical composition that is comprised of a compound in accordance with claim 8 and a pharmaceutically acceptable carrier.