Benzopyran and benzoxepin PI3K inhibitor compounds and methods of use

1. A method of treating breast cancer, prostate cancer or pharynx cancer in a mammal comprised of administering to said mammal a pharmaceutical formulation comprised of:

(i) a pharmaceutically acceptable carrier, glidant, diluent, or excipient; and

(ii) a compound of Formula I:

or a stereoisomer, geometric isomer, tautomer, or pharmaceutically acceptable salt thereof, wherein:

Z 1 is CR 1 ;

Z 2 is CR 2 ;

Z 3 is CR 3 ;

Z 4 is CR 4 ;

where X 1 is S and X 2 is CR 7 ;

R 1 , R 2 , R 3 , R 4 , and R 7 are independently selected from H, F, Cl, Br, I, —CN, —CF 3 , —CH 2 OR 10 , —CH 2 R 10 , —(C 1 -C 12 alkylene)NR 10 R 11 , —(C 1 -C 12 alkylene)NR 12 C(═O)R 10 , —(C 1 -C 12 alkylene)C(═O)OR 10 , —(C 1 -C 12 alkylene)OR 10 , —CO 2 R 10 , —C(═O)N(R 10 )OR 11 , —NO 2 , —NR 10 R 11 , —OR 10 , —S(O) 2 R 10 , —C(═O)NR 10 R 11 , —C(═O)NR 10 (C 1 -C 12 alkylene)NR 10 R 11 , —C(═O)NR 10 (C 1 -C 12 alkylene)NR 10 C(═O)OR 11 , —C(═O)NR 10 (C 1 -C 12 alkylene)NR 10 C(═O)R 11 , —C(═O)NR 10 (C 1 -C 12 alkylene)R 10 , —C(═NR 10 )NR 10 R 11 , —NR 12 C(═O)R 10 , —NR 12 C(═O)OR 11 , —NR 12 C(═O)NR 10 R 11 , —NR 12 C(═O) (C 1 -C 12 alkylene)NR 10 R 11 , —NR 12 (C 1 -C 12 alkylene)NR 10 R 11 , —NR 12 (C 1 -C 12 alkylene)OR 10 , —NR 12 (C 1 -C 12 alkylene)C(═O)NR 10 R 11 , —C≡CR 10 , —CH═CHR 10 , C 2 -C 20 heterocyclyl, C 1 -C 20 heteroaryl, and phenyl, where heterocyclyl, heteroaryl, phenyl and alkylene are optionally substituted with one or more groups selected from F, Cl, Br, I, —CH 2 OH, —(CH 2 ) 2 OH, —CH 2 CO 2 H, —CN, —CH 2 NH 2 , —(CH 2 ) 2 N(CH 3 ) 2 , —CH 3 , —C(═O)CH 3 , —C(═O)NHCH 3 , —CO 2 H, —CH 2 CO 2 CH 3 , —NH 2 , —OCH 3 , —S(O) 2 CH 3 , 4-methylpiperazin-1-yl, and 4-morpholinyl;

A is selected from —C(═O)NR 5 R 6 , C 2 -C 20 heterocyclyl and C 1 -C 20 heteroaryl wherein C 2 -C 20 heterocyclyl and C 1 -C 20 heteroaryl are optionally substituted with one or more groups independently selected from F, Cl, Br, I, —CH 2 OH, —CH 2 CO 2 H, —CH(CH 3 )CH 2 OCH 3 , —CN, C 1 -C 12 alkyl, —(C 1 -C 12 alkylene)NR 10 R 11 , —(C 1 -C 12 alkylene)OR 10 , —CH 3 , —C(═O)CH 3 , —C(═O)NHCH 3 , —C(═O)N(CH 3 ) 2 , —CO 2 H, —CO 2 CH 3 , —CH 2 CO 2 CH 3 , —NH 2 , —NHC(═O)CH 3 , —OCH 3 , —S(O) 2 CH 3 , 1-methylpiperid-4-yl, 4-methylpiperazin-1-yl, 4-morpholinyl, isopropyl, isobutyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, triazolylmethyl, benzyl, and phenyl, where alkyl, alkylene, benzyl and phenyl are optionally substituted with one or more groups independently selected from F, Cl, Br, I, —CF 3 , —CH 2 OH, —CH 2 CO 2 H, —CN, —CH 2 NH 2 , —CH 3 , —C(═O)CH 3 , —C(═O)NHCH 3 , —CO 2 H, —CH 2 CO 2 CH 3 , —NH 2 , —OH, —OCH 3 , —S(O) 2 CH 3 , 1-methylpiperid-4-yl, (4-methylpiperazin-1-yl)carboxamide, —CH 2 (1H-1,2,4-triazol-5-yl), 4-methylpiperazin-1-yl, and 4-morpholinyl;

R 5 is selected from H, C 1 -C 12 alkyl, optionally substituted with one or more groups independently selected from F, Cl, Br, I, —CN, —CO 2 H, —CONH 2 , —CONHCH 3 , —NH 2 , —NO 2 , —N(CH 3 ) 2 , —NHCOCH 3 , —NHS(O) 2 CH 3 , —OH, —OCH 3 , —OCH 2 CH 3 , —S(O) 2 NH 2 , and —S(O) 2 CH 3 ;

R 6 is selected from C 1 -C 12 alkyl, C 3 -C 12 carbocyclyl, C 2 -C 20 heterocyclyl, C 1 -C 20 heteroaryl, and C 6 -C 20 aryl, each optionally substituted with one or more groups independently selected from F, Cl, Br, I, —CH 2 OH, —CH 2 C 6 H 5 , —CN, —CF 3 , —CO 2 H, —C(═O)NR 10 R 11 , —NH 2 , —NO 2 , —N(CH 3 ) 2 , —NHCOCH 3 , —NHS(O) 2 CH 3 , —OH, —OCH 3 , —OCH 2 CH 3 , —S(O) 2 NH 2 , —S(O) 2 CH 3 , —C(═O)NR 10 (C 1 -C 12 alkylene)NR 10 R 11 , morpholin-4-yl, piperidin-1-yl, piperazinyl, piperazin-4-yl-2-one, piperazin-4-yl-3-one, pyrrolidin-1-yl, thiomorpholin-4-yl, S-dioxothiomorpholin-4-yl, —C≡CR 13 , —CH═CHR 13 , and —C(═O)NR 10 R 11 ;

or R 5 and R 6 together with the nitrogen atom to which they are attached form morpholin-4-yl, piperidin-1-yl, piperazinyl, piperazin-4-yl-2-one, piperazin-4-yl-3-one, pyrrolidin-1-yl, thiomorpholin-4-yl or S-dioxothiomorpholin-4-yl, each optionally substituted with one or more groups selected from F, Cl, Br, I, —CH 2 OH, —CH 2 C 6 H 5 , —CN, —CF 3 , —CO 2 H, —CONH 2 , —CONHCH 3 , —NO 2 , —N(CH 3 ) 2 , —NHCOCH 3 , —NHS(O) 2 CH 3 , —OH, —OCH 3 , —OCH 2 CH 3 , —S(O) 2 NH 2 , and —S(O) 2 CH 3 ;

R 10 , R 11 and R 12 are independently selected from H, C 1 -C 12 alkyl, C 1 -C 12 alkylene-C 2 -C 20 heterocyclyl, C 1 -C 12 alkylene-C 6 -C 20 aryl, 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, where 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 are optionally substituted with one or more groups independently selected from F, Cl, Br, I, —CH 2 OH, —CH 2 C 6 H 5 , —CN, —CF 3 , —CO 2 H, —CONH 2 , —CONHCH 3 , —NO 2 , —N(CH 3 ) 2 , —NHCOCH 3 , —NHS(O) 2 CH 3 , —OH, —OCH 3 , —OCH 2 CH 3 , 2-oxopyrrolidin-1-yl, —S(O) 2 NH 2 , and —S(O) 2 CH 3 ;

or R 10 and R 11 together with the nitrogen atom to which they are attached form a C 2 -C 20 heterocyclyl ring or C 1 -C 20 heteroaryl each optionally substituted with one or more groups independently selected from F, Cl, Br, I, —CH 3 , —CH 2 OH, —CH 2 C 6 H 5 , —CN, —CF 3 , —CO 2 H, —CONH 2 , —CONHCH 3 , —NO 2 , —N(CH 3 ) 2 , —NHCOCH 3 , —NHS(O) 2 CH 3 , —OH, oxo, —OCH 3 , —OCH 2 CH 3 , —S(O) 2 NH 2 , and —S(O) 2 CH 3 ; and

R 13 is selected from H, F, Cl, Br, I, —CH 3 , —CH 2 CH 3 , —CN, —CF 3 , —CH 2 N(CH 3 ) 2 , —CH 2 OH, —CO 2 H, —CONH 2 , —CON(CH 3 ) 2 , —NO 2 , and —S(O) 2 CH 3 .

2. The method of claim 1 wherein the pharmaceutical formulation is a pill, capsule, or tablet.

3. The method of claim 1 wherein the pharmaceutical formulation is a sterile injectable solution.

4. The method of claim 1 wherein the pharmaceutical formulation is administered by injection into the patient.

5. The method of claim 1 wherein the pharmaceutical formulation is a sustained-release preparation.

6. The method of claim 1 wherein the pharmaceutical formulation is administered to a patient by application as a topical ointment or cream.

7. The method of claim 1 wherein A is a C 1 -C 20 heteroaryl selected from pyridyl, isoxazolyl, imidazolyl, pyrazolyl, pyrrolyl, thiazolyl, pyridazinyl, pyrimidinyl, pyrazinyl, oxazolyl, oxadiazolyl, 1,3,4-oxadiazol-2(3H)-one, furanyl, thienyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,4-triazol-5(4H)-one, 4,5-dihydro-1,2,4-triazin-6(1H)-one, tetrazolyl; pyrrolo[2,3-b]pyridinyl, indazolyl, 3,4-dihydroquinolinyl, and benzo[d]thiazole.

8. The method of claim 1 wherein A is selected from the structures:

where R 8 and R 9 are independently selected from H, F, Cl, Br, I, —CH 2 OH, —CH 2 CO 2 H, —CH(CH 3 )CH 2 OCH 3 , —CN, —CH 2 NH 2 , —CH 3 , —C(═O)CH 3 , —C(═O)NHCH 3 , —CO 2 H, —CH 2 CO 2 CH 3 , —NH 2 , —OCH 3 , —S(O) 2 CH 3 , 1-methylpiperid-4-yl, 4-methylpiperazin-1-yl, 4-morpholinyl, isopropyl, isobutyl, benzyl, and phenyl, where benzyl and phenyl are optionally substituted with one or more groups selected from F, Cl, Br, I, —CH 2 OH, —CH 2 CO 2 H, —CN, —CH 2 NH 2 , —CH 3 , —C(═O)CH 3 , —C(═O)NHCH 3 , —CO 2 H, —CH 2 CO 2 CH 3 , —NH 2 , —OCH 3 , —S(O) 2 CH 3 , 1-methylpiperid-4-yl, 4-methylpiperazin-1-yl, and 4-morpholinyl.

9. The method of claim 1 wherein A is selected from the structures:

where the wavy line indicates the site of attachment.

10. The method of claim 1 wherein the pharmaceutically acceptable excipient is selected from sodium carboxymethylcellulose, croscarmellose, povidone, methylcellulose, hydroxypropyl methylcellulose, sodium alginate, polyvinylpyrrolidone, gum tragacanth and gum acacia.

11. The method of claim 1 wherein the compound of formula I is selected from:

N2-(2-chlorophenyl)-N2,N8,N8-trimethyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide;

7-acetamido-N-(2-chlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N2-(2-chlorophenyl)-N8-(3-(diethylamino)propyl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide;

N-(2-chlorophenyl)-7-cyano-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(2-chlorophenyl)-N-(2-hydroxyethyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(2-chloro-4-fluorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(2,4-dichlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

2-(4-isopropyl-5-oxo-4,5-dihydro- 1H-1,2,4-triazol-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide;

1-(2-(4-(2-chlorophenyl)-4H-1,2,4-triazol-3-yl)-4, 5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-yl)-3-methylurea;

methyl 2-(4-(2-chlorophenyl)-4H-1,2,4-triazol-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-ylcarbamate;

7-bromo-N-(2-chlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(2-(4-(2-chlorophenyl)-4H-1,2,4-triazol-3-yl)-4, 5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-yl)acetamide;

N-(4-(3-amino-5-methyl-1H-pyrazole-1-carbonyl)-2-chlorophenyl)-N-(2-hydroxyethyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(4-(2-acetamidoethylcarbamoyl)-2-chlorophenyl)-N-(2-hydroxyethyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(2-chloro-4-((2-(dimethylamino)ethyl)(methyl)carbamoyl)phenyl)-N-(2-hydroxyethyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N2-(2-chlorophenyl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,9-dicarboxamide;

N-(2-chlorophenyl)-9-cyano-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(2-chlorophenyl)-N-methyl-8-(pyridin-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(2-chlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carbothioamide;

8-(3-aminophenyl)-N-(2-chlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(2-chlorophenyl)-8-(3-(dimethylamino)prop- 1-ynyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(2-chlorophenyl)-8-(3-hydroxyprop-1-ynyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-methyl-N-(2-(trifluoromethyl)phenyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(2-aminoethyl)-N-(2-chlorophenyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(2-chlorophenyl)-N-methyl-8-(1H-pyrazol-4-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(2-chlorophenyl)-8-ethynyl-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(2-chlorophenyl)-N-methyl-8-(pyridin-4-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(2-chlorophenyl)-N-methyl-8-phenyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

5-(4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-1H-pyrrolo[2,3-b]pyridine;

N2-(2-chlorophenyl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide;

methyl 2-((2-chlorophenyl)(methyl)carbamoyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxylate;

tert-butyl 2-(2-((2-chlorophenyl)(methyl)carbamoyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamido)ethyl(methyl)carbamate;

4-(4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-1H-indazole;

N-(2-chlorophenyl)-8-cyano-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

3-(2-((2-chlorophenyl)(methyl)carbamoyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-yl)benzoic acid;

N-(2-chlorophenyl)-N-methyl-8-(morpholine-4-carbonyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(2-chlorophenyl)-N-methyl-8-(3-(methylsulfonyl)phenyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

8-acetamido-N-(2-chloro-4-(4-methylpiperazine-1-carbonyl)phenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N2-(2-chlorophenyl)-N2,N8-dimethyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide;

methyl 2-((2-chlorophenyl)(methyl)carbamoyl)-4, 5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-ylcarbamate;

8-bromo-N-(2-chlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

8-acetamido-N-(2-chlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

3-(4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)pyridine;

4-(4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)pyridine;

N2-(2-chlorophenyl)-N2-(2-hydroxyethyl)-N8-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2, 8-dicarboxamide;

N2-(4-chloropyridin-3-yl)-N2,N8-dimethyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide;

N-(2,4-difluorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(2-chlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(2-chlorophenyl)-8-(2-hydroxyacetamido)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(2-chlorophenyl)-8-(3-(dimethylamino)propanamido)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

5-(4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)pyrimidin-2-amine;

N-(2-chlorophenyl)-8-(3-ethylureido)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(2-chlorophenyl)-N-methyl-8-(3-methylureido)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(2-chlorophenyl)-N-methyl-8-ureido-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(2-chlorophenyl)-8-(2-(diethylamino)acetamido)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(2-chlorophenyl)-N-methyl-8-(2-morpholinoacetamido)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(2-chlorophenyl)-N-methyl-8-(2-(4-methylpiperazin-1-yl)acetamido)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

(3-chloro-4-(3-(4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4H-1,2,4-triazol-4-yl)phenyl)(4-methylpiperazin-1-yl)methanone;

N2-(2-chlorophenyl)-N2-methyl-N8-(pyridin-3-ylmethyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide;

N2-(2-chlorophenyl)-N8-(1-(hydroxymethyl)cyclopentyl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide;

N2-(2-chlorophenyl)-N8-((S)-1-hydroxy-3,3-dimethylbutan-2-yl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide;

N-(2-chlorophenyl)-8-(4-hydroxypiperidine-1-carbonyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N2-(2-chlorophenyl)-N8-(S)-2-hydroxypropyl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide;

N2-(2-chlorophenyl)-N8-((S)-1-hydroxypropan-2-yl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide;

N2-(2-chloro-4-(methylcarbamoyl)phenyl)-N2,N8-dimethyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2, 8-dicarboxamide;

N-(2-chloro-4-(methylcarbamoyl)phenyl)-8-cyano-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N2-(2-chloro-4-(4-methylpiperazine-1-carbonyl)phenyl)-N2,N8-dimethyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide;

N-(2-chloro-4-(4-methylpiperazine-1-carbonyl)phenyl)-8-cyano-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(3-chloropyridin-4-yl)-N-methyl-8-(1H-pyrazol-4-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(3-chloropyridin-4-yl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N8-(2-aminoethyl)-N2-(2-chlorophenyl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide;

N8-(2-acetamidoethyl)-N2-(2-chlorophenyl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide;

N2-(2-chlorophenyl)-N2-methyl-N8-(2-(methylamino)ethyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide;

N2-(2-chlorophenyl)-N8-methoxy-N2,N8-dimethyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide;

N2-(2-chlorophenyl)-N8-methoxy-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide;

N-(2-chlorophenyl)-8-(hydroxymethyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N8-(3-(1H-imidazol-1-yl)propyl)-N2-(2-chlorophenyl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide;

N8-(2-amino-2-methylpropyl)-N2-(2-chlorophenyl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide;

8-(3-(aminomethyl)phenyl)-N-(2-chlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(2-chlorophenyl)-8-(2-(dimethylamino)ethylamino)methyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

2-(3-(2-((2-chlorophenyl)(methyl)carbamoyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-yl)phenyl)acetic acid;

N-(2-chlorophenyl)-8-(3-cyanophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

methyl 2-(3-(2-((2-chlorophenyl)(methyl)carbamoyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-yl)phenyl)acetate;

N-(2-chlorophenyl)-8-(3-(hydroxymethyl)phenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(2-chlorophenyl)-N-methyl-8-(4-methylpiperazine-1-carbonyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N2-(2-chlorophenyl)-N2-methyl-N8-(2-(4-methylpiperazin-1-yl)ethyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide;

N2-(2-chlorophenyl)-N8-(2-(dimethylamino)ethyl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2, 8-dicarboxamide;

N2-(2-chlorophenyl)-N8-isopropyl-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide;

N2-(2-chlorophenyl)-N8-ethyl-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide;

N-(3-chloropyridin-2-yl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-methyl-N-(4-(trifluoromethyl)pyridin-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

3-chloro-4-(3-(4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4H-1,2,4-triazol-4-yl)-N-methylbenzamide;

N-(2-chlorophenyl)-8-(2-(dimethylamino)acetamido)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

8-(2-acetamidoacetamido)-N-(2-chlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

3-(8-(1H-pyrazol-4-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4,5-dihydro-1,2,4-triazin-6(1H)-one;

2-(2-amino-5-(2-chlorophenyl)thiazol-4-yl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide;

2-(4-(2-chlorophenyl)-5-methyl-4H-1,2,4-triazol-3-yl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide;

(4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)(3,4-dihydroquinolin-1(2H)-yl)methanone N-(4-chloropyridin-3-yl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(2-chloro-4-(dimethylcarbamoyl)phenyl)-N-(2-hydroxyethyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(2-chloro-4-(4-methylpiperazine-1-carbonyl)phenyl)-N-(2-hydroxyethyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N2-(2-chloro-4-(piperazine-1-carbonyl)phenyl)-N2,N8-dimethyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide;

N2-(2-chloro-4-(dimethylcarbamoyl)phenyl)-N2,N8-dimethyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide;

3-(8-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4-isopropyl-4H-1,2,4-triazole;

3-(4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4-(1-methylpiperidin-4-yl)-1H-1,2,4-triazol-5(4H)-one;

N-(2-chloro-4-(2-hydroxypropylcarbamoyl)phenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(2-chloro-4-(1-hydroxypropan-2-ylcarbamoyl)phenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(4-(3-(1H-imidazol-1-yl)propylcarbamoyl)-2-chlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(4-(2-acetamidoethylcarbamoyl)-2-chlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(2-chloro-4-(isopropylcarbamoyl)phenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(2-chloro-4-(dipropylcarbamoyl)phenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

8-bromo-N-(2-chlorophenyl)-N-(2-hydroxyethyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

2-(4-(2-chlorophenyl)-4H-1,2,4-triazol-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxylic acid;

2-(4-(2-chlorophenyl)-4H-1,2,4-triazol-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-amine;

N-(2-(4-(2-chlorophenyl)-4H-1,2,4-triazol-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-yl)-2-morpholinoacetamide;

N-(2-(4-(2-chlorophenyl)-4H-1,2,4-triazol-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-yl)-2-(dimethylamino)acetamide;

N-(2-amino-2-methylpropyl)-2-(4-(2-chlorophenyl)-4H-1,2,4-triazol-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide;

2-(4-(2-chlorophenyl)-4H-1,2,4-triazol-3-yl)-N-ethyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide;

2-(4-(2-chlorophenyl)-4H-1,2,4-triazol-3-yl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide;

N-(2-chlorophenyl)-N-methyl-8-((4-methylpiperazin-1-yl)methyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(2-chlorophenyl)-8-((dimethylamino)methyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(2-chlorophenyl)-N-methyl-8-((methylamino)methyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

8-(aminomethyl)-N-(2-chlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

4-benzyl-3-(4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-1H-1,2,4-triazol-5(4H)-one;

N-(2,4-dichlorophenyl)-9-(4-(dimethylamino)piperidine-1-carbonyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(2-chloro-4-(2-(dimethylamino)ethylcarbamoyl)phenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(2-chloro-4-(dimethylcarbamoyl)phenyl)-N-methyl-4, 5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(2-chloro-4-(methylcarbamoyl)phenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(2-chloro-4-(morpholine-4-carbonyl)phenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(2-chloro-4-(4-methylpiperazine-1-carbonyl)phenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(2-chloro-4-(piperazine-1-carbonyl)phenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

3-(4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4-(1-hydroxypropan-2-yl)-1H-1,2,4-triazol-5(4H)-one;

3-(9-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4-(2,4-dichlorophenyl)-4H-1,2,4-triazole;

3-(4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4-(1-methoxypropan-2-yl)-1H-1,2,4-triazol-5(4H)-one;

N-(2-acetamidoethyl)-N-(2-chlorophenyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

2-(4-isopropyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carbonitrile;

3-(4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4-isobutyl-1H-1,2,4-triazol-5(4H)-one;

N-(2-chlorophenyl)-N-methyl-8-(morpholinomethyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

4-(8-(1H-pyrazol-4-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-5-(2-chlorophenyl)thiazol-2-amine;

3-(8-(1H-pyrazol-4-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4-isopropyl-1H-1,2,4-triazol-5(4H)-one;

3-(8-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4-isopropyl-1H-1,2,4-triazol-5(4H)-one;

5-(8-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-1,3,4-oxadiazol-2(3H)-one;

3-(9-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4-(2-chloro-4-fluorophenyl)-4H-1,2,4-triazole;

2-(2-amino-5-(2-chlorophenyl)thiazol-4-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide;

3-(8-(1H-pyrazol-4-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4-ethyl-1H-1,2,4-triazol-5(4H)-one;

2-(4-(2-chlorophenyl)-4H-1,2,4-triazol-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide;

4-(8-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-5-(2-chlorophenyl)thiazol-2-amine;

3-(8-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4-(2-chlorophenyl)-5-methyl-4H-1,2,4-triazole;

3-(8-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4-(2-chlorophenyl)-4H-1,2,4-triazole;

2-(4-(2-chlorophenyl)-1H-pyrazol-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide;

2-(4-(2-chlorophenyl)-1H-pyrazol-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carbonitrile;

3-(8-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4-(2-chlorophenyl)-1H-pyrazole;

3-(8-(1H-pyrazol-4-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4-(2-chlorophenyl)-1H-1,2,4-triazol-5(4H)-one;

2-(4-(2-chlorophenyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carbonitrile;

3-(8-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4-(2-chlorophenyl)-1H-1,2,4-triazol-5(4H)-one;

5-(2-chlorophenyl)-4-(4, 5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)thiazol-2-amine;

2-(4-(2-chloro-4-fluorophenyl)-4H-1,2,4-triazol-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-9-carboxamide;

5-(2-chlorophenyl)-4-(4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)pyrimidin-2-amine;

4-(2-chlorophenyl)-3-(4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-1H-pyrazole;

4-(2-chlorophenyl)-3-(4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-1H-1,2,4-triazol-5(4H)-one;

2-(1-(2-chlorophenyl)-1H-tetrazol-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide;

5-(8-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-1-(2-chlorophenyl)-1H-tetrazole;

5-(8-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4-(2-chlorophenyl)-4H-1,2,4-triazol-3-amine;

N2-(2,4-dichlorophenyl)-N2,N9,N9-trimethyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,9-dicarboxamide;

3-(9-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4-(2-chloro-4-(trifluoromethyl)phenyl)-4H-1,2,4-triazole;

N-(2-chloro-4-fluorophenyl)-9-cyano-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

9-cyano-N-(2,4-difluorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

3-(9-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4-(2,4-difluorophenyl)-4H-1,2,4-triazole;

2-(4-(2-chlorophenyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide;

N-(2-aminoethyl)-2-(4-(2-chlorophenyl)-4H-1,2,4-triazol-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide;

N-(2-chloro-4-(methylcarbamoyl)phenyl)-9-cyano-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N2-(2-chlorophenyl)-N9-ethyl-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,9-dicarboxamide;

N-(2,4-dichlorophenyl)-N-methyl-9-(piperazine-1-carbonyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(2-acetamidoethyl)-2-(4-(2-chlorophenyl)-4H-1,2,4-triazol-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide;

2-(4-(2-chlorophenyl)-4H-1,2,4-triazol-3-yl)-N-(2-morpholinoethyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide;

2-(4-(2-chlorophenyl)-4H-1,2,4-triazol-3-yl)-N-(2-(dimethylamino)ethyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide;

2-(4-(2-chlorophenyl)-4H-1,2,4-triazol-3-yl)-N-(1,3-dihydroxypropan-2-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide;

N2-(2-chloro-4-(methylcarbamoyl)phenyl)-N2-methyl-4, 5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,9-dicarboxamide;

5-(8-(1H-pyrazol-4-yl)-4, 5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4-(2-chlorophenyl)-4H-1,2,4-triazol-3-amine;

N-(2-chlorophenyl)-N-methyl-8-1H-pyrazol-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

2-(4-(2-chlorophenyl)-4H-1,2,4-triazol-3-yl)-N-((R)-2-hydroxypropyl)-4, 5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide;

2-(4-(2-chlorophenyl)-4H-1,2,4-triazol-3-yl)-N-(2-hydroxyethyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide;

4-(2-chlorophenyl)-3-(4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4H-1,2,4-triazole;

N-(2-chloro-4-(piperazine-1-carbonyl)phenyl)-N-(2-hydroxyethyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(2-chlorophenyl)-N-methyl-8-(3-methyl-1H-pyrazol-4-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(4-carbamoyl-2-chlorophenyl)-N-(2-hydroxyethyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N2-(2,4-dichlorophenyl)-N2,N8-dimethyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide;

2-(1-(2-chlorophenyl)-1H-1,2,4-triazol-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carbonitrile;

2-(1-(2,4-difluorophenyl)-1H-1,2,4-triazol-5-yl)-4, 5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide;

2-(4-(2-chloro-4-(methylcarbamoyl)phenyl)-4H-1,2,4-triazol-3-yl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide;

2-(4-(2-chlorophenyl)-5-oxo-4,5-dihydro-11-1-1,2,4-triazol-3-yl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide;

N-(2-acetamidoethyl)-2-(4-(2-chlorophenyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide;

N-(2-amino-2-methylpropyl)-2-(4-(2-chlorophenyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide;

N8-(2-acetamidoethyl)-N2-(2-chloro-4-(dimethylcarbamoyl)phenyl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide;

N2-(2-chloro-4-(dimethylcarbamoyl)phenyl)-N8-(2-(dimethylamino)ethyl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2, 8-dicarboxamide;

9-cyano-N-(2,4-dichlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N2-(2-chloro-4-(dimethylcarbamoyl)phenyl)-N8-(2-hydroxyethyl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide;

N2-(2-chloro-4-(dimethylcarbamoyl)phenyl)-N8-isopropyl-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide;

N8-(2-amino-2-methylpropyl)-N2-(2-chloro-4-(dimethylcarbamoyl)phenyl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide;

2-(1-(2-chloro-4-(dimethylcarbamoyl)phenyl)-1H-1,2,4-triazol-5-yl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide;

4-(5-(8-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-1H-1,2,4-triazol-1-yl)-3-chloro-N,N-dimethylbenzamide;

N-(2-chloro-4-(dimethylcarbamoyl)phenyl)-9-cyano-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide;

N2-(2-chloro-4-(dimethylcarbamoyl)phenyl)-N8-isobutyl-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide;

N2-(2-chloro-4-(dimethylcarbamoyl)phenyl)-N8-ethyl-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide;

N2-(2-chloro-4-(dimethylcarbamoyl)phenyl)-N8-isobutyl-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide;

N2-(2-chloro-4-(dimethylcarbamoyl)phenyl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide;

N8-(2-aminoethyl)-N2-(2-chloro-4-(dimethylcarbamoyl)phenyl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2, 8-dicarboxamide;

N-(2-chloro-4-(2-hydroxypropylcarbamoyl)phenyl)-9-cyano-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

3-(9-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4-(2-chlorophenyl)-4H-1,2,4-triazole;

2-(4-(2-chloro-4-fluorophenyl)-4H-1,2,4-triazol-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-9-carbonitrile;

9-bromo-N-(2,4-dichlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(2-chloro-4-cyanophenyl)-9-cyano-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(2-chloro-4-(trifluoromethyl)phenyl)-9-cyano-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(2,4-dichlorophenyl)-N-methyl-9-(4-methylpiperazine-1-carbonyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N-(2,4-dichlorophenyl)-9-((3S,5R)-3,5-dimethylpiperazine-1-carbonyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide;

N2-(2,4-dichlorophenyl)-N9-(2-hydroxyethyl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,9-dicarboxamide;

2-(4-(2-chlorophenyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide; and

2-(4-(2-chlorophenyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)-N-methyl-4, 5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide.

12. The method of claim 1 wherein the compound of formula I is selected from:

N2-(2-chloro-4-fluorophenyl)-N2,N8-dimethyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide;

2-(1-(2-chloro-4-(dimethylcarbamoyl)phenyl)-1H-1,2,4-triazol-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide;

2-(1-(2,4-difluorophenyl)-1H-1,2,4-triazol-5-yl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide;

N2-(2-chloro-4-(methylcarbamoyl)phenyl)-N2-(2-hydroxyethyl)-N8-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide;

(2(4-(2,4-difluorophenyl)-4H-1,2,4-triazol-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-9-yl)(4-methylpiperazin-1-yl)methanone;

2-(4-(2,4-difluorophenyl)-4H-1,2,4-triazol-3-yl)-N-(2-hydroxyethyl)-4, 5-dihydrobenzo[b]thieno[2,3-d]oxepine-9-carboxamide;

2-(4-(2,4-difluorophenyl)-4H-1,2,4-triazol-3-yl)-N42-hydroxyethyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-9-carboxamide;

2-(1-(2,4-difluorophenyl)-1H-1,2,4-triazol-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carbonitrile;

2-(1-(2-hydroxyethyl)-1H-1,2,4-triazol-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide;

5-(9-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-1-(2,4-difluorophenyl)-1H-1,2,4-triazole;

5-(9-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-1-isopropyl-1H-1,2,4-triazole;

N2-(2-chloro-4-fluorophenyl)-N2-methyl-4, -dihydrobenzo[b]thieno[2,3-d]oxepine-2, 8-dicarboxamide;

N2-(2-chloro-5-(dimethylcarbamoyl)phenyl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide;

N2-(2-chloro-5-(dimethylcarbamoyl)phenyl)-N2,N8-dimethyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide;

2-(4-isopropyl-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide;

5-(8-(1H-pyrazol-4-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-1-isopropyl-1H-1,2,4-triazole;

1-(2,4-difluorophenyl)-5-(4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-1H-1,2,4-triazole;

2-(1-(2,4-difluorophenyl)-1H-1,2,4-triazol-5-yl)-N-(2-hydroxyethyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-9-carboxamide;

5-(9-(1H-pyrazol-4-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-1-(2,4-difluorophenyl)-1H-1,2,4-triazole;

2-(1-(2,4-difluorophenyl)-1H-1,2,4-triazol-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-9-carboxamide;

(2-(1-(2,4-difluorophenyl)-1H-1,2,4-triazol-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-9-yl)(piperazin-1-yl)methanone;

N2-(4-carbamoyl-2-chlorophenyl)-N2,N8-dimethyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide;

2-(1-(2-chloro-5-(dimethylcarbamoyl)phenyl)-1H-1,2,4-triazol-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide;

3-(2-(1-(2,4-difluorophenyl)-1H-1,2,4-triazol-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-9-yl)pyridine;

2-(1-(1,1,1-trifluoropropan-2-yl)-1H-1,2,4-triazol-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide;

N2-(2-chloro-4-(4-methylpiperazine-1-carbonyl)phenyl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide;

2-(1-(2,4-difluorophenyl)-1H-1,2,4-triazol-5-yl)-N-(2-hydroxyethyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide;

N-(2-acetamidoethyl)-2-(1-(2,4-difluorophenyl)-1H-1,2,4-triazol-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide;

2-(1-(2,4-difluorophenyl)-1H-1,2,4-triazol-5-yl)-N-(2-(pyrrolidin-1-yl)ethyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide;

(2-(1-(2,4-difluorophenyl)-1H-1,2,4-triazol-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-9-yl)((R)-3-(dimethylamino)pyrrolidin-1-yl)methanone;

2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-9-carboxamide;

(2-(1-(2,4-difluorophenyl)-1H-1,2,4-triazol-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-9-yl)((S)-3-(dimethylamino)pyrrolidin-1-yl)methanone;

2-(1-(2,2,2-trifluoroethyl)-1H-1,2,4-triazol-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide;

N2-(2-chloro-4-(piperazine-1-carbonyl)phenyl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide;

N2-(4-(4-acetylpiperazine-1-carbonyl)-2-chlorophenyl)-N2,N8-dimethyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide;

2-(1-isobutyl-1H-1,2,4-triazol-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide;

2-(1-(1,1,1-trifluoropropan-2-yl)-1H-1,2,4-triazol-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide;

2-(1-(1,1,1-trifluoropropan-2-yl)-1H-1,2,4-triazol-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide;

2-(1-(2-hydroxy-2-methylpropyl)-1H-1,2,4-triazol-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide;

N2-(4-carbamoyl-2-chlorophenyl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide;

N2-(2-chloro-4-(2-hydroxypropylcarbamoyl)phenyl)-N2,N8-dimethyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide;

N2-(2-chloro-4-(2-hydroxypropylcarbamoyl)phenyl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide;

2-(1-cyclobutyl-1H-1,2,4-triazol-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-9-carboxamide;

2-(1-cyclobutyl-1H-1,2,4-triazol-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide;

(3-chloro-4-(5-(4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-1H-1,2,4-triazol-1-yl)phenyl)(4-methylpiperazin-1-yl)methanone;

2-(1-(2-(dimethylamino)ethyl)-1H-1,2,4-triazol-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide;

(2-(1-(2-hydroxy-2-methylpropyl)-1H-1,2,4-triazol-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-9-yl)(4-methylpiperazin-1-yl)methanone;

N2-(2-chloro-4-(2-(dimethylamino)ethylcarbamoyl)phenyl)-N2,N8-dimethyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide;

N2-(2-chloro-4-(2-(dimethylamino)ethylcarbamoyl)phenyl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide;

5-(8-(4H-1,2,4-triazol-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-1-isopropyl-1H-1,2,4-triazole;

2-(2-aminopyridin-4-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carbonitrile;

(2-(1-(2,4-difluorophenyl)-1H-1,2,4-triazol-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-9-yl)(4-methylpiperazin-1-yl)methanone;

(2-(1-(2-chlorophenyl)-1H-1,2,4-triazol-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-9-yl)(4-methylpiperazin-1-yl)methanone;

2-(1-(3-methylbutan-2-yl)-1H-1,2,4-triazol-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide;

2-(5-(2-(4-(2-chlorophenyl)-4H-1,2,4-triazol-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-yl)-1H-1,2,4-triazol-1-yl)-N,N-dimethylethanamine;

2-(5-(2-(4-(2-chlorophenyl)-4H-1,2,4-triazol-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-yl)-1H-1,2,4-triazol-1-yl)ethanol;

2-(1-(2-(trifluoromethyl)-1H-benzo [d] imidazol-5-yl)-1H-1,2,4-triazol-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide;

2-(1-(4-((1H-1,2,4-triazol-1-yl)methyl)phenyl)-1H-1,2,4-triazol-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide;

(4-methylpiperazin-1-yl)(2-(1-(2,2,2-trifluoroethyl)-1H-1,2,4-triazol-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-9-yl)methanone;

2-(1-(1,1,1-trifluoro-3-methylbutan-2-yl)-1H-1,2,4-triazol-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide;

5-(8-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-1-isopropyl-1H-1,2,4-triazole;

2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carbonitrile;

3-(9-bromo-4,5-dihydro-6-oxa-1-thia-benzo [e] azulen-2-yl)-4-(2,4-dichloro-phenyl)-4H-[1,2,4]triazole; and

N-(2-aminoethyl)-2-(4-(2-chlorophenyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxamide.