2-oxo-1,2-dihydrobenzo[cd]indole compound and use thereof

Abstract

The present invention relates to the technical field of medicinal chemistry, and in particular discloses a 2-oxo-1,2-dihydrobenzo[cd]indole compound and use thereof. The compound and pharmaceutically acceptable salt, isomer, racemate, prodrug, co-crystallized complex, hydrate, and solvate thereof can effectively inhibit the BET bromodomain receptor, and can be used for preparing a medicine for treating cancers, cell proliferative disorders, inflammatory diseases, and autoimmune disorders, sepsis, and viral infections.

Claims

1-10. (canceled)

11. A 2-oxo-1,2-dihydrobenzo[cd]indole compound having a structure represented by formula I, II, III or IV: ##STR00142## wherein, R.sub.1 is selected from H or C.sub.1-C.sub.4 linear or branched alkyl, R.sub.2 is selected from C.sub.1-C.sub.7 alkyl, C.sub.1-C.sub.4 alkylene-R.sub.6, C.sub.1-C.sub.4 alkylene-R.sub.7-cyclic ring, —R.sub.7-cyclic ring or -cyclic ring, R.sub.3 is selected from C.sub.1-C.sub.7 alkyl, C.sub.1-C.sub.4 alkylene-R.sub.6′, C.sub.1-C.sub.4 alkylene-R.sub.7-cyclic ring, —R.sub.7-cyclic ring or -cyclic ring, R.sub.4 is selected from C.sub.1-C.sub.7 alkyl, C.sub.1-C.sub.4 alkylene-R.sub.6″, C.sub.1-C.sub.4 alkylene-R.sub.7-cyclic ring, —R.sub.7-cyclic ring or -cyclic ring, R.sub.5 is selected from C.sub.1-C.sub.7 alkyl, C.sub.1-C.sub.4 alkylene-R.sub.6″, C.sub.1-C.sub.4 alkylene-R.sub.7-cyclic ring, —R.sub.7-cyclic ring or -cyclic ring, wherein R.sub.6 is selected from —OR.sub.8, —COR.sub.8, —CONHR.sub.8, —COOR.sub.8, —S(O).sub.mR.sub.8, —NHCOOR.sub.8, —NHCOR.sub.8 or —NH.sub.2, wherein m is 0 or 2, R.sub.6′ is selected from —OR.sub.8, —COR.sub.8, —CONHR.sub.8, —COOR.sub.8 or —S(O).sub.mR.sub.8, wherein m is 0 or 2, R.sub.6″ is selected from —OR.sub.8, —COR.sub.8, —CONHR.sub.8, —COOR.sub.8, —S(O).sub.mR.sub.8, —NHCOOR.sub.8 or —NHCOR.sub.8, wherein m is 0 or 2, R.sub.8 is selected from hydrogen or C.sub.1-C.sub.3 alkyl, and R.sub.7 is selected from —COR.sub.9, —COOR.sub.9 or —OR.sub.9, wherein R.sub.9 is selected from C.sub.1-C.sub.3 alkylene, wherein cyclic ring is selected from C.sub.3-C.sub.10 cycloalkyl, phenyl, or heterocyclic group, or a pharmaceutically acceptable salt, isomer, racemate, prodrug, cocyrstalline complex, hydrate or solvate thereof.

12. The compound according to claim 11, wherein R.sub.1 is selected from H, methyl, ethyl, propyl, isopropyl or tert-butyl.

13. The compound according to claim 11, wherein the cyclic ring is selected from cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, phenyl, naphthyl, azetidine, oxetane, azacyclopentane, oxacyclopentane, azacyclohexane, oxacyclohexane, azacyclohexyl, imidazol-2-one ring, imidazolyl, furyl, thienyl, oxazolyl, isoxazolyl, pyrimidinyl, pyrrolyl, piperazinyl, tetrahydropyrrolyl, piperidinyl, morpholinyl, 1,3-dioxolanyl or benzo[d]thiazolyl, wherein the cyclic ring is substituted by 0, 1, 2 or 3 group(s) each independently selected from halogen, methyl, ethyl, propyl, isopropyl, tert-butyl, trifluoromethyl, cyano, nitro, amino, amide, —COOR.sub.10, —COR.sub.10, —OR.sub.10, —NHCOR.sub.10, —NHCOOR.sub.10, —C.sub.6H.sub.5R.sub.11, morpholinyl, piperidinyl, tetrahydrofuranyl or pyridyl, wherein R.sub.10 is selected from hydrogen, C.sub.1-C.sub.4 alkyl or phenyl, and R.sub.11 is selected from C.sub.1-C.sub.4 alkyl, halogen, acetyl, methoxy or ethoxy.

14. The compound according to claim 11, wherein the compound is selected from a group consisting of: N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)butane-1-sulfonamide; 2-chloro-N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-4-fluorobenzenesulfonamide; N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)thiophene-2-sulfonamide; 5-chloro-N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-2-methoxybenzenesulfonamide; N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)cyclohexanesulfonamide; 2-(N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)sulfamoyl)benzoate; 2-(N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)sulfamoyl)benzoic acid; N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)benzenesulfonamide; N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-4-fluorobenzenesulfonamide; N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-3-fluorobenzenesulfonamide; N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)ethanesulfonamide; N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-4-methoxybenzenesulfonamide; 4-cyano-N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)benzenesulfonamide; N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-4-nitrobenzenesulfonamide; 4-(tert-butyl)-N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)benzenesulfonamide; N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-4-(trifluoromethoxy)benzenesulfonamide; 3-chloro-N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-2-fluorobenzenesulfonamide; N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-4-methylbenzenesulfonamide; N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-2,4-difluorobenzenesulfonamide; N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)propane-1-sulfonamide; N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)cyclopentanesulfonamide; N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-4-(trifluoromethyl)benzenesulfonamide; N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-3-(methylsulfonyl)benzenesulfonamide; N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)naphthalene-2-sulfonamide; 4-(N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)sulfamoyl)benzoate; 4-(N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)sulfamoyl)benzoic acid; 3-(N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)sulfamoyl)benzoate; 3-(N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)sulfamoyl)benzoic acid; N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-2,3-dihydrobenzo[b][1,4]dioxine-6-sulfonamide; 2-bromo-N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)benzenesulfonamide; 5-bromo-N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-2-methoxybenzenesulfonamide; 2,6-dichloro-N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)benzenesulfonamide; N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-2,3-dimethoxybenzenesulfonamide; 3,5-dichloro-N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)benzenesulfonamide; 2,3-dichloro-N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)benzenesulfonamide; 4-((N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)sulfamoyl)methyl)benzoate; 4-((N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)sulfamoyl)methyl)benzoic acid; N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-1-(3-fluorophenyl)methanesulfonamide; 3-((N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)sulfamoyl)methyl)benzoate; N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-1-(4-(trifluoromethyl)phenyl) methanesulfonamide; N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-1-(p-tolyl)methanesulfonamide; N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-1-(2-fluorophenyl)methanesulfonamide; 1-(4-chlorophenyl)-N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)methanesulfonamide; 1-(4-cyanophenyl)-N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)methanesulfonamide; N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-1-(4-fluorophenyl)methanesulfonamide; N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-4-fluorobenzamide; 2-(4-chlorophenyl)-N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)acetamide; 2-(3,4-dimethoxyphenyl)-N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)acetamide; 2-(2,4-dichlorophenyl)-N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)acetamide; N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-3-phenylpropanamide; N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-4,4,4-trifluorobutanamide; N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)propionamide; 4-chloro-N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)benzamide; N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-2-(p-tolyl)acetamide; (E)-N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-3-(furan-2-yl)acrylamide; 1-ethyl-6-((3-phenylpropyl)amino)benzo[cd]indol-2(1H)-one; 1-ethyl-6-((3-morpholinopropyl)amino)benzo[cd]indol-2(1H)-one; 1-ethyl-6-((4-methoxybenzyl)amino)benzo[cd]indol-2(1H)-one; 1-ethyl-6-((4-methylbenzyl)amino)benzo[cd]indol-2(1H)-one; 1-ethyl-6-((4-(trifluoromethyl)benzyl)amino)benzo[cd]indol-2(1H)-one; 6-((4-chlorobenzyl)amino)-1-ethylbenzo[cd]indol-2(1H)-one; 1-ethyl-6-((4-fluorobenzyl)amino)benzo[cd]indol-2(1H)-one; N-((1-acetylpiperidin-4-yl)methyl)-1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide; 1-((1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole)-6-sulfonamido)cyclohexane-1-carboxamide; 1-ethyl-N-((3-isopropyl-4,5-dihydroisoxazol-5-yl)methyl)-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide; N-((3,5-dimethyl-4,5-dihydroisoxazol-5-yl)methyl)-1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide; N-(4-acetylphenyl)-1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide; N-(2-chlorobenzyl)-1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide; 1-ethyl-N-(2-fluorobenzyl)-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide; N-(1-acetylpiperidin-4-yl)-1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide; Tert-butyl4-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamido)piperidine-1-carboxylate; N-cyclopentyl-1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide; Ethyl1-((1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamido)methyl)cyclopentanecarboxylate; 1-((1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamido)methyl)cyclopentanecarboxylic acid; N-(4-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamido)phenyl)acetamide; 2-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamido)benzoic acid; 1-ethyl-N-(4-fluorophenyl)-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide; N-butyl-1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide; N-(2-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamido)ethyl)acetamide; 1-ethyl-N-(2-(methylsulfonyl)ethyl)-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide; 1-ethyl-2-oxo-N-(2-(2-oxoimidazolidin-1-yl)ethyl)-1,2-dihydrobenzo[cd]indole-6-sulfonamide; Tert-butyl(4-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamido)butyl)carbamate; N-(5-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamido)pyridin-2-yl)acetamide; Tert-butyl3-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamido)pyrrolidine-1-carboxylate; Tert-butyl3-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamido)azetidine-1-carboxylate; N-(2-cyclohexylethyl)-1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide; 1-ethyl-2-oxo-N-(pyrrolidin-3-yl)-1,2-dihydrobenzo[cd]indole-6-sulfonamide; N-(azetidin-3-yl)-1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide; 1-ethyl-N-hexyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide; 1-ethyl-2-oxo-N-(2-(pyrrolidin-1-yl)ethyl)-1,2-dihydrobenzo[cd]indole-6-sulfonamide; 1-ethyl-2-oxo-N-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-1,2-dihydrobenzo[cd]indole-6-sulfonamide; 1-ethyl-2-oxo-N-(tetrahydrofuran-3-yl)-1,2-dihydrobenzo[cd]indole-6-sulfonamide; N-(2-(4-chlorophenoxy)ethyl)-1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide; N,1-diethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide; 1-ethyl-2-oxo-n-pentyl-1,2-dihydrobenzo[cd]indole-6-sulfonamide; 1-ethyl-N-methyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide; N-cyclohexyl-1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide; Tert-butyl3-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamido)piperidine-1-carboxylate; 1-ethyl-N-isobutyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide; 1-ethyl-2-oxo-N-propyl-1,2-dihydrobenzo[cd]indole-6-sulfonamide; 1-ethyl-N-(3-(4-methylpiperazin-1-yl)propyl)-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide; 1-ethyl-2-oxo-N-(2-(piperidin-1-yl)ethyl)-1,2-dihydrobenzo[cd]indole-6-sulfonamide; N-(4,4-diethoxybutyl)-1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide; Ethyl 3-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamido)propanoate; 1-ethyl-N-((1-ethylpyrrolidin-2-yl)methyl)-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide; 1-ethyl-N-(1-methylpiperidin-4-yl)-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide; N-cycloheptyl-1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide; 1-ethyl-2-oxo-N-(tetrahydro-2H-pyran-4-yl)-1,2-dihydrobenzo[cd]indole-6-sulfonamide; Tert-butyl4-(2-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamido)ethyl)piperazine-1-carboxylate; N-cyclohexyl-1-methyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide; N-butyl-1-methyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide; N-cyclohexyl-2-oxo-1-propyl-1,2-dihydrobenzo[cd]indole-6-sulfonamide; 2-oxo-N,1-dipropyl-1,2-dihydrobenzo[cd]indole-6-sulfonamide; N-butyl-2-oxo-1-propyl-1,2-dihydrobenzo[cd]indole-6-sulfonamide; N-butyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide; N-butyl-1-isobutyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide; N-cyclohexyl-1-isobutyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide; N-cyclohexyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide; N-(3-acetylphenyl)-1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide; N-(4-chlorophenyl)-1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide; 1-ethyl-2-oxo-N-phenyl-1,2-dihydrobenzo[cd]indole-6-sulfonamide; N-(2-chlorophenyl)-1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide; and N-(3-chlorophenyl)-1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide.

15. A pharmaceutical composition comprising a therapeutically effective amount of the compound according to claim 11 and a pharmaceutically acceptable carrier.

16. A method of inhibiting a BET bromodomain receptor in a subject in need thereof, comprising: administering to the subject a therapeutically effective amount of the compound according to claim 11.

17. A method for treating a disease or a condition selected from the group consisting of cancers, cell proliferative disorders, inflammatory diseases, and autoimmune disorders, sepsis, and viral infections, in a subject in need thereof, comprising: administering to the subject a therapeutically effective amount of the compound according to claim 11.

18. The method according to claim 17, wherein the cancers comprise: adrenal tumor, acoustic neuroma, acral lentiginous melanoma, acrospiroma, acute eosinophilic leukemia, acute erythroid leukemia, acute lymphoblastic leukemia, acute megakaryoblastic leukemia, acute monocytic leukemia, actue promyelocytic leukemia, adenocarcinoma, adenoid cystic carcinoma, adipose tissue tumor, adrenocortical carcinoma, adult T-cell leukemia/lymphoma, AIDS-related lymphoma, alveolar rhabdomyosarcoma, alveolar soft part sarcoma, ameloblastic fibroma, anaplastic large cell lymphoma, anaplastic thyroid cancer, angiomyolipoma, angiosarcoma, astrocytoma, atypical teratoid rhabdoid tumor, B-cell chronic lymphocytic leukemia, B-cell prolymphocytic leukemia, B-cell lymphoma, basal cell carcinoma, biliary tract cancer, bladder cancer, blastoma, bone tumor, brown tumor, Burkitt's lymphoma, breast cancer, brain cancer, carcinoma in situ, chondroma, cementoma, myeloid sarcoma, chondroma, chordoma, choriocarcinoma, choroid plexus papilloma, clear-cell sarcoma of the kidney, craniopharyngioma, cutaneous T-cell lymphoma, cervical cancer, colon cancer, small round cell tumor, diffuse large B-cell lymphoma, neuroepithelial tumor, dysgerminoma, embryonal carcinoma, endocrine gland neoplasm, endodermal sinus tumor, esophageal cancer, fibroma, fibrosarcoma, follicular lymphoma, follicular ganglioneuroma, thyroid cancer, gastrointestinal cancer, germ cell tumor, gestational choriocarcinoma, giant cell fibroblastoma, giant cell tumor of the bone, neurogliocytoma, glioblastoma multiforme, glioma, granulosa cell tumor, andreoblastoma, gallbladder cancer, gastric cancer, hemangioblastoma, head and neck cancer, hemangiopericytoma, hepatoblastoma, cell lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, invasive lobular carcinoma, intestinal cancer, kidney cancer, laryngeal cancer, lethal midline carcinoma, leukemia, leydig cell tumor, liposarcoma, lung cancer, lymphangioma, lymphoepithelioma, lymphoma, acute lymphangiosarcoma, lymphoblastic leukemia, chronic lymphocytic leukemia, liver cancer, small cell lung cancer, non-small cell lung cancer, MALT lymphoma, malignant fibrous histiocytoma, malignant peripheral nerve sheath tumor, marginal zone B-cell lymphoma, mast cell leukemia, mediastinal germ cell tumor, medullary carcinoma of the breast, medullary thyroid cancer, medulloblastoma, melanoma, meningioma, merkel cell cancer, mesothelioma, metastatic cell carcinoma, mixed Mullerian tumor, mucinous tumor, multiple myeloma, muscle tissue neoplasm, mycosis fungoides, myxoid liposarcoma, myxoma, myxosarcoma, nasopharyngeal carcinoma, neuroblastoma, neurofibroma, neuroma, ocular cancer, oncocytoma, optic nerve sheath meningioma, tumor, oral cancer, osteosarcoma, ovarian cancer, papillary thyroid cancer, tumor paraganglioma, pinealoblastoma, pituicytoma, precursor T-lymphoblastic lymphoma, primary central nervous system lymphoma, peritoneal cancer, prostate cancer, pancreatic cancer, pharyngeal cancer, renal cell carcinoma, renal medullary carcinoma, retinoblastoma, rhabdomyoma, rhabdomyosarcoma, rectal cancer, sarcoma, seminoma, Sertoli cell tumor, skin cancer, small round cell tumor, small cell carcinoma, soft tissue sarcoma, somatostatinoma, spinal tumor, splenic marginal zone lymphoma, squamous cell carcinoma, synovial sarcoma, small intestine cancer, squamous carcinoma, stomach cancer, T-cell lymphoma, testicular cancer, thyroid cancer, transitional cell carcinoma, throat cancer, urachal cancer, urogenital cancer, uterine cancer, verrucous carcinoma, visual pathway glioma, vulvar cancer, and vaginal cancer.

19. The method according to claim 17, wherein the cell proliferative disorders comprise: benign soft tissue tumor, brain and spinal tumor, eyelid and orbital tumor, granuloma, lipoma, meningioma, multiple endocrine neoplasia, nasal polyp, pituitary tumor, prolactinoma, seborrheic keratose, stomach polyp, thyroid nodule, liver hemangioma, vocal cord nodule, polyp, cyst, pilonidal disease, dermatofibroma, pilar cyst, and pyogenic granuloma.

20. The method according to claim 17, wherein the inflammatory diseases comprise: inflammatory pelvic disease, urethritis, skin sunburn, nasosinusitis, pneumonitis, encephalitis, meningitis, myocarditis, nephritis, osteomyelitis, myositis, hepatitis, gastritis, enteritis, dermatitis, gingivitis, pancreatitis, psoriasis, allergy, Crohn's disease, bowel syndrome, ulcerative colitis, rejection of transplanted tissues, rejection of transplanted organs, asthma, allergic rhinitis, chronic obstructive pulmonary disease, autoimmune disease, autoimmune alopecia, anemia, glomerulonephritis, dermatomyositis, multiple sclerosis, scleroderma, vasculitis, autoimmune hemolytic and thrombocytopenic states, Goodpasture's syndrome, athersclerosis, Addison's disease, Parkinson's disease, Alzheimer's disease, diabetes, septic shock, systemic lupus erythematosus, rheumatoid arthritis, psoriatic arthritis, osteoarthritis, chronic idiopathic thrombocytopenic purpura, myasthenia gravis, Hashimoto's thyroiditis, atopic dermatitis, degenerative joint disease, Guillain-Barre syndrome, mycosis fungoides, and acute inflammatory responses.

21. The method according to claim 17, wherein the viral infections comprise: human papillomavirus, Herpesvirus, Epstein-Barr virus, human immunodeficiency virus, hepatis B virus, and hepatitis C virus infections.

Description

DETAILED DESCRIPTION

[0156] In the compounds of the present invention, when any variable (e.g., R.sub.1, R.sub.2, etc.) appears more than once in any component, the definition of each occurrence is independent of the other occurrence of each occurrence. Likewise, a combination of substituents and variables is allowed, as long as the combination stabilizes the compound. The lines from the substituents into the ring system indicate that the indicated bond can be attached to any of the substitutable ring atoms. If the ring system is a polycyclic, it means that the bond is only attached to any suitable carbon atom adjacent to the ring. It is to be understood that one of ordinary skill in the art can select the substituents and substitutions of the compounds of the present invention to provide compounds that are chemically stable and readily synthesizable from readily available starting materials by techniques of the art and the methods set forth below. If the substituents themselves are substituted by more than one group, it is to be understood that these groups may be on the same carbon atom or on different carbon atoms as long as the structure is stable. The term “alkyl”, “alkylene” as used herein mean to include branched and straight chain saturated aliphatic hydrocarbon groups having a specific number of carbon atoms. For Example, the definition of “C1-C4” in the “C1-C4” alkyl group includes a group having 1, 2, 3, 4 carbon atoms in a straight chain or branched chain. For Example, the “C1-C4” alkyl group specifically includes methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl and isobutyl. Unless additional defined, alkyl, cycloalkyl and heterocyclyl substituents may be unsubstituted or substituted. For Example, the C1-C4 alkyl group may be substituted by one, two or three substituents selected from halogen, methyl, ethyl, propyl, isopropyl, tert-butyl, trifluoromethyl, cyano, amino, phenyl diazenyl, —CONH.sub.2, —COOR, —COR.sub.7, —OR.sub.7, —NHCOR.sub.7, —NHCOOR.sub.7, —C.sub.6H.sub.5R.sub.8, morpholinyl, piperidinyl, tetrahydrofuranyl, pyridyl, wherein R.sub.7 is selected from C1-C4 alkyl, phenyl; R.sub.8 is optionally substituted with a substituent selected from C1 to C4 alkyl, halogen, acetyl, methoxy, ethoxy.

[0157] The present invention includes compounds of formulas I, II, III, IV, and their pharmaceutically acceptable salts and stereoisomers thereof. Pharmaceutically acceptable salts include not only exemplary salts of specific compounds described herein, and also included pharmaceutically acceptable salts from compounds of formula I, II, III, IV or the free form of the compound-specific salt can be isolated using techniques known in the art. For Example, when treated with a suitable dilute aqueous solution of dilute aqueous solution, such as NaOH, K.sub.2CO.sub.3, dilute aqueous ammonia, and NaHCO.sub.3, the free form of formula I, II, III, IV was regenerated. The free form may be different from salt forms in some physical properties, such as the dissociation in polar solvents, but for the purposes of this invention, the acid salts and base salts are comparable to their respective free forms in other pharmaceuticals.

[0158] The pharmaceutically acceptable salts of the present invention can be synthesized from compounds containing the basic or acidic moiety by conventional chemical methods. Typically, the salt of the basic compound is prepared by ion exchange chromatography, or free base with reaction of stoichiometric or excess amount of inorganic/organic acid in a suitable solvent or combination of a plurality of solvents. Similarly, salts of acidic compounds are formed by reaction with an appropriate inorganic/organic base.

[0159] Thus, the pharmaceutically acceptable salts of the compounds of the present invention include conventional non-toxic salts by the reaction of a compound of the present invention with an inorganic or organic acid. For Example, conventional non-toxic salts include those derived from inorganic acids, e g. from hydrochloric acid, hydrobromic acid, sulfuric acid, sulfamic acid, phosphoric acid, nitric acid; from organic acids, e g. from acetic acid, propionic acid, glycolic acid, lactic acid, malic acid, tartaric acid, citric acid, ascorbic acid, picric acid, maleic acid, hydroxymaleic acid, phenylacetic acid, glutamic acid, benzoic acid, water 2-acetoxy-benzoic acid, fumaric acid, toluenesulfonic acid, methanesulfonic acid, ethane disulfonic acid, oxalic acid, isethionate, trifluoroacetic acid.

[0160] For Example, conventional non-toxic salts include those derived from inorganic bases, e g. from aluminum salts, ammonium salts, calcium salts, copper salts, iron salts, ferrous salts, lithium salts, magnesium salts, manganese salts, manganese salts, potassium salts, sodium salts and zinc salts. Particularly preferred are ammonium salts, calcium salts, magnesium salts, potassium salts and sodium salts; from organic bases, e g., from primary amine, secondary amine, tertiary amine and naturally substituted amines, cyclic amines and basic ion exchange resins, such as arginine, betaine, caffeine, choline, N, N′-dibenzylethylenediamine, diethylamine, 2-diethylamino ethanol, 2-dimethylaminoethanol, aminoethanol, ethanolamine, ethylenediamine, N-ethylmorpholine, N-ethylpiperidine, glucosamine, glucosamine, histidine, hydroxypropylamine, isopropylamine, lysine, methylglucosamine, morpholine, piperazine, piperidine, guanza, polyamine resin, procaine, purine, theobromine, triethylamine, trimethylamine, tripropylamine, tromethamine.

[0161] In addition to the standard methods known in the literature or exemplified in the experimental procedure, the compounds of the present invention can be prepared using the reactions shown in the following schemes. Accordingly, the following illustrative protocols are for illustrative purposes and are not intended to be limited to the listed compounds or any particular substituents. The number of substituents shown in the scheme is not necessarily to be used in the claims. For the sake of clarity, monosubstituted group is attached to a compound showed in invention which is allowed to have a plurality of substituents under the definitions of the formulas I, II, III, IV.

Synthetic Procedures

[0162] Synthesis of compounds of formula I. The compounds may be prepared by reacting the 1,8-naphthalenedicarboxylic anhydride as a starting material in 6 steps:

##STR00002##

##STR00003##

[0163] Or by reacting the 1,8-naphthalenedicarboxylic anhydride as a starting material in 5 steps:

##STR00004##

[0164] Synthesis of compounds of formula II. The compounds may be prepared by reacting the 1,8-naphthalenedicarboxylic anhydride as a starting material in 6 steps:

##STR00005##

##STR00006##

[0165] Or by reacting the 1,8-naphthalenedicarboxylic anhydride as a starting material in 5 steps:

##STR00007##

[0166] Synthesis of compounds of formula III. The compounds may be prepared by reacting the 1,8-naphthalenedicarboxylic anhydride as a starting material in 6 steps:

##STR00008##

##STR00009##

[0167] Or by reacting the 1,8-naphthalenedicarboxylic anhydride as a starting material in 5 steps:

##STR00010##

[0168] Synthesis of compounds of formula IV. The compounds may be prepared by reacting the 1,8-naphthalenedicarboxylic anhydride as a starting material in 5 steps:

##STR00011##

##STR00012##

[0169] The present invention will be described in greater detail by way of special Examples. The following Examples are offered for illustrative purposes, and are not intended to limit the invention in any manner.

EXAMPLES

[0170] The synthesis of formula I:

Example 1: Synthesis of N-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)butane-1-sulfonamide

[0171] ##STR00013##

Step 1. Synthesis of 1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl 4-methylbenzenesulfonate

[0172] ##STR00014##

[0173] 1,8-naphthalenedicarboxylic anhydride (11.9 g, 0.06 mol) and hydroxylamine hydrochloride (4.18 g, 0.06 mol) were combined as a solution in pyridine (70 mL). The reaction was conducted under reflux for 1 h followed by cooling to 80° C. To the reaction system mixture was added powdered p-toluenesulfonyl chloride (22.88 g, 0.12 mol). After the addition, the reaction was performed under reflux for 1 h. After cooling to room temperature, the reaction mixture was poured into ice water (200 mL) and stirred to precipitate crystals. The precipitate was filtered and rinsed with additional cool water (100 mL) and saturated NaHCO.sub.3 (100 mL) to give 1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl 4-methyl benzenesulfonate (17 g, 78%) as a yellow solid.

Step 2. Synthesis of benzo[cd]indol-2(1H)-one

[0174] ##STR00015##

[0175] To a solution of 1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl 4-methyl benzenesulfonate (17 g, 0.048 mol) in ethanol (50 mL) and water (40 mL) was added an aqueous solution of sodium hydroxide (2.7 mol/L, 60 mL) at room temperature. The mixture was heated to reflux temperature for 3 h while distilling the ethanol. After the reaction was completed, the reaction mixture was cooled to 75° C., concentrated hydrochloric acid was added dropwise, and a yellow precipitate was formed. Then, the mixture was further cooled. The precipitate was collected by filtration and washed with water (100 mL×2). The resulting crude product was purified by silica gel chromatography with dichloromethane to give Benzo[cd]indol-2(1H)-one (6.65 g, 82%) as a yellow solid. MS (ESI), m/z: M+170.0.

Step 3. Synthesis of 1-ethylbenzo[cd]indol-2(1H)-one

[0176] ##STR00016##

[0177] The product benzo[cd]indol-2(1H)-one (6.65 g, 0.04 mol) and NaH (2.81 g, 0.18 mol) were dissolved in DMF (100 mL). Ethyl iodide (7.33 g, 0.047 mol) was added dropwise at 0° C. The reaction mixture was stirred at rt 3 h. The reaction mixture was extracted with ethyl acetate (150 mL×2). The organic layer was washed with brine and dried over Na.sub.2SO.sub.4. The solid was filtered off, and the filtrate was concentrated under reduced pressure. The resulting crude product was purified by silica gel chromatography with petroleum ether/ethyl acetate (10/1, v/v) to yield 1-ethylbenzo[cd]indol-2(1H)-one (6.46 g, 84%) as a yellow oil. MS (ESI), m/z: M.sup.+ 198.0.

Step 4. Synthesis of 1-ethyl-6-nitrobenzo[cd]indol-2(1H)-one

[0178] ##STR00017##

[0179] To a solution of 1-ethylbenzo[cd]indol-2(1H)-one (500 mg, 2.53 mmol) in AcOH (5 mL) was added HNO.sub.3 (154 mg, 2.53 mmol) at 0° C. then the reaction mixture was stirred at 50° C. for 1 h. After the reaction was completed, the reaction mixture was cooled to rt. The reaction mixture was extracted with ethyl acetate (150 mL×2). The organic layer was washed with brine and dried over Na.sub.2SO.sub.4. The solid was filtered off, and the filtrate was concentrated under reduced pressure. The resulting crude product was purified by silica gel chromatography with petroleum ether/ethyl acetate (6/1, v/v) to yield 1-ethyl-6-nitrobenzo[cd]indol-2(1H)-one (400 mg, 65%) as a yellow solid.

Step 5. Synthesis of 6-amino-1-ethylbenzo[cd]indol-2(1H)-one

[0180] ##STR00018##

[0181] A reaction mixture of Fe power (462 mg, 8.26 mmol) and NH.sub.4Cl (131 mg, 2.47 m mol) in AcOH (2 mL) and water (20 mL) was heated at 50° C. for 5 min. 1-ethyl-6-nitro benzo[cd]indol-2(1H)-one (400 mg, 1.65 mmol) was dissolved in DMF (10 mL) and added to the reaction mixture. After the reaction was completed, the reaction mixture was cooled to rt. The reaction mixture was extracted with ethyl acetate (150 mL×2). The organic layer was washed with brine and dried over Na.sub.2SO.sub.4. The solid was filtered off, and the filtrate was concentrated under reduced pressure. The resulting crude product was purl fled by silica gel chromatography with petroleum ether/ethyl acetate (3/1, v/v) to yield 6-amino-1-ethylbenzo[cd]indol-2(1H)-one (316 mg, 90%) as a yellow solid.

Step 6. Synthesis of N-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)butane-1-sulfonamide

[0182] A reaction mixture of compound 6-amino-1-ethylbenzo[cd]indol-2(1H)-one (80 mg, 0.38 mmol) and butane-1-sulfonyl chloride (89 mg, 0.57 mmol) in pyridine (5 mL) was stir red at 80° C. for 1 h. Dilute HCl was added, the aqueous layer was extracted with ethyl acetate (50 mL×3), and the organic layer was washed with water and brine, dried with Na.sub.2SO.sub.4 and evaporated. The residue was purified by silica gel chromatography with petroleum and ether/ethyl acetate (4/1, v/v) to afford N-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)butane-1-sulfonamide (66 mg, 52%). .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.21 (d, J=8.4 Hz, 1H), 8.10 (d, J=7.2 Hz, 1H), 7.90-7.69 (m, 1H), 7.53 (d, J=7.6 Hz, 1H), 6.88 (d, J=7.6 Hz, 1H), 6.77 (s, 1H), 3.97 (q, J=7.2 Hz, 2H), 3.27-2.89 (m, 2H), 1.94-1.75 (m, 2H), 1.51-1.30 (m, 5H), 0.90 (t, J=7.2 Hz, 3H).

Example 2: Synthesis of 2-chloro-N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-4-fluorobenzenesulfonamide

[0183] ##STR00019##

[0184] The synthesis can refer to Example 1. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.22 (d, J=8.4 Hz, 1H), 8.06 (d, J=7.2 Hz, 1H), 7.86 (dd, J=8.8, 5.6 Hz, 1H), 7.82-7.65 (m, 1H), 7.33 (dd, J=8.0, 2.4 Hz, 1H), 7.26 (s, 1H), 7.13 (d, J=7.6 Hz, 1H), 7.00-6.83 (m, 1H), 6.71 (d, J=7.6 Hz, 1H), 3.91 (q, J=7.2 Hz, 2H), 1.32 (t, J=7.2 Hz, 3H).

Example 3: Synthesis of N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)thiophene-2-sulfonamide

[0185] ##STR00020##

[0186] The synthesis can refer to Example 1. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.03 (d, J=7.2 Hz, 1H), 7.92 (d, J=8.4 Hz, 1H), 7.74-7.58 (m, 1H), 7.52 (d, J=5.2 Hz, 1H), 7.41 (d, J=3.6 Hz, 1H), 7.31 (d, J=7.6 Hz, 1H), 7.01-6.93 (m, 1H), 6.91 (s, 1H), 6.82 (d, J=7.6 Hz, 1H), 3.95 (q, J=7.2 Hz, 2H), 1.36 (t, J=7.2 Hz, 3H).

Example 4: Synthesis of 5-chloro-N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-2-methoxybenzenesulfonamide

[0187] ##STR00021##

[0188] The synthesis can refer to Example 1. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.18 (d, J=8.4 Hz, 1H), 8.05 (d, J=7.2 Hz, 1H), 7.71 (dd, J=15.2, 5.2 Hz, 2H), 7.45 (dd, J=8.8, 2.4 Hz, 1H), 7.25 (s, 1H), 7.13 (d, J=7.6 Hz, 1H), 7.00 (d, J=8.8 Hz, 1H), 6.72 (d, J=7.6 Hz, 1H), 4.08 (s, 3H), 3.91 (q, J=7.2 Hz, 2H), 1.32 (t, J=7.2 Hz, 3H).

Example 5: Synthesis of N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)cyclohexanesulfonamide

[0189] ##STR00022##

[0190] The synthesis can refer to Example 1. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.23 (d, J=8.4 Hz, 1H), 8.09 (d, J=7.2 Hz, 1H), 7.78 (t, J=7.6 Hz, 1H), 7.55 (d, J=7.6 Hz, 1H), 7.00-6.72 (m, 2H), 3.96 (q, J=7.2 Hz, 2H), 3.21-2.96 (m, 1H), 2.23 (d, J=112.0 Hz, 2H), 1.87 (d, J=7.6 Hz, 2H), 1.65-1.61 (m, 4H), 1.37 (t, J=7.2 Hz, 3H), 1.19 (d, J=9.2 Hz, 2H).

Example 6: Synthesis of Methyl 2-(N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)sulfamoyl)benzoate

[0191] ##STR00023##

[0192] The synthesis can refer to Example 1. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.27 (s, 1H), 8.14 (d, J=8.4 Hz, 1H), 8.01 (d, J=7.2 Hz, 1H), 7.86 (d, J=7.2 Hz, 1H), 7.72-7.49 (m, 3H), 7.41 (t, J=7.6 Hz, 1H), 7.33-7.14 (m, 2H), 6.75 (d, J=7.6 Hz, 1H), 4.12 (s, 3H), 3.92 (q, J=7.2 Hz, 2H), 1.34 (t, J=7.2 Hz, 3H).

Example 7: Synthesis of 2-(N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)sulfamoyl)benzoic acid

[0193] ##STR00024##

[0194] The synthesis of methyl 2-(N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)sulfamoyl)benzoate can refer Example 6.

[0195] Methyl 2-(N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)sulfamoyl)benzoate (50 mg, 0.12 mmol) was dissolved in THF (5 mL) and 2 mol/L NaOH aqueous solution (5 mL). The mixture was stirred at room temperature for 2 h. The solvent was removed and diluted hydrochloric acid was added dropwise, and a yellow precipitate was formed. The precipitate was collected by filtration and washed with water (10 mL×2). The resulting crude product was purified by recrystallization with petroleum and ether/ethyl acetate to afford 2-(N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)sulfamoyl)benzoic acid (33 mg, 69%) as a yellow solid. .sup.1H NMR (400 MHz, d-DMSO) δ 10.04 (s, 1H), 8.18 (d, J=8.4 Hz, 1H), 7.98 (d, J=7.2 Hz, 1H), 7.75-7.66 (m, 2H), 7.63 (t, J=7.6 Hz, 1H), 7.57 (d, J=8.0 Hz, 1H), 7.45 (t, J=7.6 Hz, 1H), 7.22 (d, J=7.6 Hz, 1H), 7.10 (d, J=7.6 Hz, 1H), 3.87 (q, J=7.2 Hz, 2H), 1.23 (t, J=7.2 Hz, 3H).

Example 8: Synthesis of N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)benzenesulfonamide

[0196] ##STR00025##

[0197] The synthesis can refer to Example 1. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.00 (d, J=7.2 Hz, 1H), 7.90 (d, J=8.4 Hz, 1H), 7.74 (d, J=7.6 Hz, 2H), 7.60 (t, J=7.6 Hz, 1H), 7.54-7.49 (m, 1H), 7.39 (t, J=7.6 Hz, 2H), 7.21 (d, J=7.6 Hz, 1H), 7.06 (s, 1H), 6.77 (d, J=7.6 Hz, 1H), 3.93 (q, J=7.2 Hz, 2H), 1.34 (t, J=7.2 Hz, 3H).

Example 9: Synthesis of N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-4-fluorobenzenesulfonamide

[0198] ##STR00026##

[0199] The synthesis can refer to Example 1. .sup.1H NMR (400 MHz, d-DMSO) δ 10.29 (s, 1H), 8.03 (dd, J=16.4, 7.6 Hz, 2H), 7.84-7.63 (m, 3H), 7.33 (t, J=8.8 Hz, 2H), 7.13 (s, 2H), 3.87 (q, J=7.2 Hz, 2H), 1.23 (t, J=7.2 Hz, 3H).

Example 10: Synthesis of N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-3-fluorobenzenesulfonamide

[0200] ##STR00027##

[0201] The synthesis can refer to Example 1. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.03 (d, J=7.2 Hz, 1H), 7.91 (d, J=8.4 Hz, 1H), 7.65 (t, J=7.6 Hz, 1H), 7.66-7.45 (m, 2H), 7.38 (dd, J=13.2, 8.0 Hz, 1H), 7.25 (d, J=4.8 Hz, 1H), 7.20 (s, 1H), 6.79 (d, J=7.6 Hz, 1H), 3.94 (q, J=7.2 Hz, 2H), 1.35 (t, J=7.2 Hz, 3H).

Example 11: Synthesis of N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)ethanesulfonamide

[0202] ##STR00028##

[0203] The synthesis can refer to Example 1. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.22 (d, J=8.4 Hz, 1H), 8.10 (d, J=7.2 Hz, 1H), 7.80 (t, J=7.6 Hz, 1H), 7.54 (d, J=7.6 Hz, 1H), 6.93-6.76 (m, 2H), 3.97 (q, J=7.2 Hz, 2H), 3.16 (q, J=7.2 Hz, 2H), 1.43 (t, J=7.2 Hz, 3H), 1.37 (t, J=7.2 Hz, 3H).

Example 12: Synthesis of N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-4-methoxybenzenesulfonamide

[0204] ##STR00029##

[0205] The synthesis can refer to Example 1. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.02 (d, J=7.2 Hz, 1H), 7.95 (d, J=8.4 Hz, 1H), 7.79-7.51 (m, 3H), 7.20 (d, J=7.6 Hz, 1H), 6.89 (s, 1H), 6.84 (d, J=8.8 Hz, 2H), 6.77 (d, J=7.6 Hz, 1H), 3.93 (q, J=7.2 Hz, 2H), 1.35 (t, J=7.2 Hz, 3H).

Example 13: Synthesis of 4-cyano-N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)benzenesulfonamide

[0206] ##STR00030##

[0207] The synthesis can refer to Example 1. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.04 (d, J=7.2 Hz, 1H), 7.89 (d, J=8.4 Hz, 1H), 7.85 (d, J=8.4 Hz, 2H), 7.74-7.57 (m, 3H), 7.17 (d, J=7.6 Hz, 1H), 7.11 (s, 1H), 6.79 (d, J=7.6 Hz, 1H), 3.94 (q, J=7.2 Hz, 2H), 1.35 (t, J=7.2 Hz, 3H).

Example 14: Synthesis of N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-4-nitrobenzenesulfonamide

[0208] ##STR00031##

[0209] The synthesis can refer to Example 1. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.25 (d, J=8.8 Hz, 2H), 8.05 (d, J=7.2 Hz, 1H), 7.92 (d, J=9.2 Hz, 3H), 7.67 (t, J=7.6 Hz, 1H), 7.17 (d, J=7.6 Hz, 1H), 6.95 (s, 1H), 6.79 (d, J=7.6 Hz, 1H), 3.94 (q, J=7.2 Hz, 2H), 1.36 (t, J=7.2 Hz, 3H).

Example 15: Synthesis of 4-(tert-butyl)-N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)benzenesulfonamide

[0210] ##STR00032##

[0211] The synthesis can refer to Example 1. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.99 (d, J=7.2 Hz, 1H), 7.78 (d, J=8.4 Hz, 1H), 7.63 (d, J=8.4 Hz, 2H), 7.60-7.48 (m, 1H), 7.37 (d, J=8.4 Hz, 2H), 7.28 (s, 1H), 6.80 (d, J=7.6 Hz, 2H), 3.94 (q, J=7.2 Hz, 2H), 1.36 (t, J=7.2 Hz, 3H), 1.27 (s, 9H).

Example 16: Synthesis of N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-4-(trifluoromethoxy)benzenesulfonamide

[0212] ##STR00033##

[0213] The synthesis can refer to Example 1. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.05 (d, J=7.2 Hz, 1H), 7.86 (d, J=8.4 Hz, 1H), 7.79 (d, J=8.8 Hz, 2H), 7.71-7.53 (m, 1H), 7.23 (d, J=7.6 Hz, 3H), 6.87 (s, 1H), 6.82 (d, J=7.6 Hz, 1H), 3.97 (q, J=7.2 Hz, 2H), 1.38 (t, J=7.2 Hz, 3H).

Example 17: Synthesis of 3-chloro-N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-2-fluorobenzenesulfonamide

[0214] ##STR00034##

[0215] The synthesis can refer to Example 1. .sup.1H NMR (400 MHz, d-DMSO) δ 10.82 (s, 1H), 8.12 (d, J=8.4 Hz, 1H), 8.03 (d, J=6.8 Hz, 1H), 7.82 (dd, J=17.6, 10.0 Hz, 1H), 7.76 (d, J=7.2 Hz, 1H), 7.59 (t, J=7.2 Hz, 1H), 7.28 (t, J=8.0 Hz, 1H), 7.22 (d, J=7.6 Hz, 1H), 7.13 (d, J=7.6 Hz, 1H), 3.87 (q, J=7.2 Hz, 2H), 1.23 (t, J=7.2 Hz, 3H).

Example 18: Synthesis of N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-4-methylbenzenesulfonamide

[0216] ##STR00035##

[0217] The synthesis can refer to Example 1. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.02 (d, J=7.2 Hz, 1H), 7.93 (d, J=8.4 Hz, 1H), 7.63 (t, J=8.4 Hz, 3H), 7.19 (dd, J=7.6, 5.2 Hz, 3H), 6.85 (s, 1H), 6.77 (d, J=7.6 Hz, 1H), 3.93 (q, J=7.2 Hz, 2H), 2.36 (s, 3H), 1.35 (t, J=7.2 Hz, 3H).

Example 19: Synthesis of N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-2,4-difluorobenzenesulfonamide

[0218] ##STR00036##

[0219] The synthesis can refer to Example 1. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.14 (d, J=8.4 Hz, 1H), 8.05 (d, J=7.2 Hz, 1H), 7.75-7.70 (m, 2H), 7.23 (d, J=7.6 Hz, 1H), 7.07 (s, 1H), 7.01-6.91 (m, 1H), 6.87 (dd, J=11.6, 5.2 Hz, 1H), 6.75 (d, J=7.6 Hz, 1H), 3.92 (q, J=7.2 Hz, 2H), 1.33 (t, J=7.2 Hz, 3H).

Example 20: Synthesis of N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)propane-1-sulfonamide

[0220] ##STR00037##

[0221] The synthesis can refer to Example 1. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.22 (d, J=8.0 Hz, 1H), 8.09 (d, J=6.8 Hz, 1H), 7.79 (t, J=7.2 Hz, 1H), 7.53 (d, J=7.2 Hz, 1H), 6.99 (s, 1H), 6.88 (d, J=7.2 Hz, 1H), 3.97 (q, J=7.2 Hz, 2H), 3.30-2.79 (m, 2H), 1.91 (dd, J=14.8, 7.2 Hz, 2H), 1.37 (t, J=6.8 Hz, 3H), 1.02 (t, J=7.2 Hz, 3H).

Example 21: Synthesis of N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)cyclopentanesulfonamide

[0222] ##STR00038##

[0223] The synthesis can refer to Example 1. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.25 (d, J=8.0 Hz, 1H), 8.08 (d, J=6.8 Hz, 1H), 7.77 (t, J=7.2 Hz, 1H), 7.58 (d, J=7.2 Hz, 1H), 7.16 (s, 1H), 6.86 (d, J=7.2 Hz, 1H), 3.96 (q, J=7.2 Hz, 2H), 3.51-3.46 (m, 1H), 2.13-2.03 (m, 4H), 1.95-1.78 (m, 4H), 1.36 (t, J=7.2 Hz, 3H).

Example 22: Synthesis of N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-4-(trifluoromethyl)benzenesulfonamide

[0224] ##STR00039##

[0225] The synthesis can refer to Example 1. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.04 (d, J=6.8 Hz, 1H), 7.96-7.73 (m, 3H), 7.68-7.62 (m, 3H), 7.18 (d, J=7.6 Hz, 1H), 6.88 (s, 1H), 6.79 (d, J=7.2 Hz, 1H), 3.94 (q, J=7.2 Hz, 2H), 1.36 (t, J=7.2 Hz, 3H).

Example 23: Synthesis of N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-3-(methylsulfonyl)benzenesulfonamide

[0226] ##STR00040##

[0227] The synthesis can refer to Example 1. .sup.1H NMR (400 MHz, d-DMSO) δ 10.49 (s, 1H), 8.14 (d, J=9.6 Hz, 2H), 8.00 (d, J=7.2 Hz, 2H), 7.93 (d, J=7.6 Hz, 1H), 7.77 (t, J=7.6 Hz, 1H), 7.69 (t, J=7.6 Hz, 1H), 7.13 (s, 2H), 3.87 (d, J=7.2 Hz, 2H), 3.17 (s, 3H), 1.23 (t, J=6.8 Hz, 3H).

Example 24: Synthesis of N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)naphthalene-1-sulfonamide

[0228] ##STR00041##

[0229] The synthesis can refer to Example 1. .sup.1H NMR (400 MHz, d-DMSO) δ 10.61 (s, 1H), 8.80 (d, J=8.4 Hz, 1H), 8.15 (d, J=8.0 Hz, 1H), 8.04 (d, J=7.6 Hz, 1H), 7.98 (d, J=7.2 Hz, 1H), 7.92 (t, J=7.6 Hz, 2H), 7.72-7.65 (m, 2H), 7.53-7.49 (m, 2H), 7.09 (d, J=7.6 Hz, 1H), 7.02 (d, J=7.6 Hz, 1H), 3.82 (q, J=7.2 Hz, 2H), 1.18 (t, J=7.2 Hz, 3H).

Example 25: Synthesis of Methyl 4-(N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)sulfamoyl)benzoate

[0230] ##STR00042##

[0231] The synthesis can refer to Example 1. .sup.1H NMR (400 MHz, d-DMSO) δ 10.46 (s, 1H), 8.04 (d, J=8.4 Hz, 3H), 8.00 (d, J=7.2 Hz, 1H), 7.80 (d, J=8.4 Hz, 2H), 7.70 (t, J=7.6 Hz, 1H), 7.11 (s, 2H), 3.87 (q, J=7.2 Hz, 5H), 1.23 (t, J=7.2 Hz, 3H).

Example 26: Synthesis of 4-(N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)sulfamoyl)benzoic acid

[0232] ##STR00043##

[0233] The synthesis can refer to Example 7. .sup.1H NMR (400 MHz, d-DMSO) δ 13.41 (s, 1H), 10.44 (s, 1H), 8.17-7.92 (m, 4H), 7.77 (d, J=8.0 Hz, 2H), 7.70 (t, J=7.6 Hz, 1H), 7.11 (s, 2H), 3.86 (q, J=7.2 Hz, 2H), 1.23 (t, J=7.2 Hz, 3H).

Example 27: Synthesis of methyl 3-(N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)sulfamoyl)benzoate

[0234] ##STR00044##

[0235] The synthesis can refer to Example 1. .sup.1H NMR (400 MHz, d-DMSO) δ 10.43 (s, 1H), 8.22 (s, 1H), 8.12 (d, J=7.6 Hz, 1H), 8.04-7.98 (m, 2H), 7.86 (d, J=7.6 Hz, 1H), 7.70-7.61 (m, 2H), 7.11 (s, 2H), 3.93-3.77 (m, 5H), 1.22 (t, J=7.1 Hz, 3H).

Example 28: Synthesis of 3-(N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)sulfamoyl)benzoic acid

[0236] ##STR00045##

[0237] The synthesis can refer to Example 7. .sup.1H NMR (400 MHz, d-DMSO) δ 13.27 (s, 1H), 10.39 (s, 1H), 8.21 (s, 1H), 8.10 (d, J=7.6 Hz, 1H), 8.01-7.98 (m, 2H), 7.84 (d, J=7.6 Hz, 1H), 7.68 (t, J=7.6 Hz, 1H), 7.61 (t, J=7.6 Hz, 1H), 7.11 (s, 2H), 3.86 (q, J=7.2 Hz, 2H), 1.22 (t, J=7.2 Hz, 3H).

Example 29: Synthesis of N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-2,3-dihydrobenzo[b][1,4]dioxine-6-sulfonamide

[0238] ##STR00046##

[0239] The synthesis can refer to Example 1. .sup.1H NMR (400 MHz, d-DMSO) δ 10.14 (s, 1H), 8.10 (d, J=8.4 Hz, 1H), 8.01 (d, J=6.8 Hz, 1H), 7.73 (t, J=7.6 Hz, 1H), 7.26-7.00 (m, 4H), 6.91 (d, J=8.4 Hz, 1H), 4.25 (d, J=9.2 Hz, 4H), 3.87 (q, J=7.2 Hz, 2H), 1.23 (t, J=7.2 Hz, 3H).

Example 30: Synthesis of 2-bromo-N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)benzenesulfonamide

[0240] ##STR00047##

[0241] The synthesis can refer to Example 1. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.26 (d, J=8.4 Hz, 1H), 8.05 (d, J=7.2 Hz, 1H), 7.87 (d, J=7.6 Hz, 1H), 7.80 (d, J=7.6 Hz, 1H), 7.73 (t, J=7.6 Hz, 1H), 7.40 (t, J=7.6 Hz, 1H), 7.36-7.28 (m, 2H), 7.11 (d, J=7.6 Hz, 1H), 6.69 (d, J=7.6 Hz, 1H), 3.90 (q, J=7.2 Hz, 2H), 1.31 (t, J=7.2 Hz, 3H).

Example 31: Synthesis of 5-bromo-N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-2-methoxybenzenesulfonamide

[0242] ##STR00048##

[0243] The synthesis can refer to Example 1. .sup.1H NMR (400 MHz, d-DMSO) δ 10.29 (s, 1H), 8.24 (d, J=8.4 Hz, 1H), 8.02 (d, J=6.8 Hz, 1H), 7.79 (t, J=7.6 Hz, 1H), 7.71 (d, J=8.8 Hz, 1H), 7.61 (s, 1H), 7.24 (d, J=7.6 Hz, 1H), 7.15 (d, J=8.8 Hz, 1H), 7.10 (d, J=7.6 Hz, 1H), 3.98-3.57 (m, 5H), 1.22 (t, J=7.2 Hz, 3H).

Example 32: Synthesis of 2,6-dichloro-N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)benzenesulfonamide

[0244] ##STR00049##

[0245] The synthesis can refer to Example 1. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.17 (d, J=8.0 Hz, 1H), 8.05 (d, J=7.2 Hz, 1H), 7.73 (t, J=7.6 Hz, 1H), 7.50 (s, 1H), 7.45 (d, J=8.0 Hz, 2H), 7.38-7.29 (m, 1H), 7.22 (d, J=7.6 Hz, 1H), 6.74 (d, J=7.6 Hz, 1H), 3.92 (q, J=7.2 Hz, 2H), 1.33 (t, J=7.2 Hz, 3H).

Example 33: Synthesis of N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-2,5-dimethoxybenzenesulfonamide

[0246] ##STR00050##

[0247] The synthesis can refer to Example 1. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.23 (d, J=8.4 Hz, 1H), 8.04 (d, J=7.2 Hz, 1H), 7.72 (t, J=7.6 Hz, 1H), 7.27 (d, J=4.4 Hz, 1H), 7.22 (s, 1H), 7.11 (d, J=7.6 Hz, 1H), 7.02 (s, 2H), 6.70 (d, J=7.6 Hz, 1H), 4.07 (s, 3H), 3.90 (q, J=7.2 Hz, 2H), 3.67 (s, 3H), 1.31 (t, J=7.2 Hz, 3H).

Example 34: Synthesis of 3,5-dichloro-N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)benzenesulfonamide

[0248] ##STR00051##

[0249] The synthesis can refer to Example 1. .sup.1H NMR (400 MHz, d-DMSO) δ 10.52 (s, 1H), 8.05 (t, J=8.0 Hz, 2H), 7.93 (s, 1H), 7.76 (t, J=7.6 Hz, 1H), 7.60 (s, 2H), 7.29-6.97 (m, 2H), 3.88 (q, J=7.2 Hz, 2H), 1.23 (t, J=7.2 Hz, 3H).

Example 35: Synthesis of 2,3-dichloro-N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)benzenesulfonamide

[0250] ##STR00052##

[0251] The synthesis can refer to Example 1. .sup.1H NMR (400 MHz, d-DMSO) δ 10.77 (s, 1H), 8.24 (d, J=8.0 Hz, 1H), 8.03 (d, J=6.8 Hz, 1H), 7.89 (d, J=8.0 Hz, 1H), 7.80 (dd, J=7.6, 4.0 Hz, 2H), 7.42 (t, J=8.0 Hz, 1H), 7.18 (d, J=7.6 Hz, 1H), 7.09 (d, J=7.6 Hz, 1H), 3.85 (q, J=7.2 Hz, 2H), 1.21 (t, J=7.2 Hz, 3H).

Example 36: Synthesis of methyl4-((N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)sulfamoyl)methyl)benzoate

[0252] ##STR00053##

[0253] The synthesis can refer to Example 1. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.10 (d, J=6.8 Hz, 1H), 7.95 (t, J=8.4 Hz, 3H), 7.74 (t, J=7.6 Hz, 1H), 7.52 (d, J=7.6 Hz, 1H), 7.36 (d, J=8.0 Hz, 2H), 6.87 (d, J=7.6 Hz, 1H), 6.82 (s, 1H), 4.43 (s, 2H), 3.97 (q, J=7.2 Hz, 2H), 3.91 (s, 3H), 1.38 (t, J=7.2 Hz, 3H).

Example 37: Synthesis of 4-((N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)sulfamoyl)methyl)benzoic acid

[0254] ##STR00054##

[0255] The synthesis can refer to Example 1. .sup.1H NMR (400 MHz, d-DMSO) δ 12.92 (s, 1H), 9.96 (s, 1H), 8.31 (d, J=8.4 Hz, 1H), 8.08 (d, J=6.8 Hz, 1H), 7.86-7.80 (m, 3H), 7.48 (d, J=7.6 Hz, 1H), 7.43 (d, J=8.0 Hz, 2H), 7.19 (d, J=7.6 Hz, 1H), 4.59 (s, 2H), 3.92 (q, J=6.8 Hz, 2H), 1.27 (t, J=7.2 Hz, 3H).

Example 38: Synthesis of N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-1-(3-fluorophenyl)methanesulfonamide

[0256] ##STR00055##

[0257] The synthesis can refer to Example 1. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.10 (d, J=7.2 Hz, 1H), 7.96 (d, J=8.4 Hz, 1H), 7.74 (t, J=7.6 Hz, 1H), 7.52 (d, J=7.6 Hz, 1H), 7.32-7.13 (m, 2H), 7.04 (t, J=10.4 Hz, 3H), 6.91-6.66 (m, 2H), 4.37 (s, 2H), 3.98 (q, J=7.2 Hz, 2H), 1.38 (t, J=7.2 Hz, 3H).

Example 39: Synthesis of methyl3-((N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)sulfamoyl)methyl)benzoate

[0258] ##STR00056##

[0259] The synthesis can refer to Example 1. .sup.1H NMR (400 MHz, d-DMSO) δ 9.94 (s, 1H), 8.27 (d, J=8.4 Hz, 1H), 8.07 (d, J=6.8 Hz, 1H), 7.88 (d, J=7.8 Hz, 1H), 7.86-7.82 (m, 2H), 7.60 (d, J=7.6 Hz, 1H), 7.51-7.35 (m, 2H), 7.17 (d, J=7.6 Hz, 1H), 4.61 (s, 2H), 3.92 (d, J=7.2 Hz, 2H), 3.79 (s, 3H), 1.27 (t, J=7.2 Hz, 3H).

Example 40: Synthesis of N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-1-(4-(trifluoromethyl)phenyl)methanesulfonamide

[0260] ##STR00057##

[0261] The synthesis can refer to Example 1. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.09 (d, J=6.8 Hz, 1H), 7.97 (d, J=8.0 Hz, 1H), 7.73 (t, J=7.6 Hz, 1H), 7.51 (t, J=6.4 Hz, 3H), 7.40 (d, J=7.6 Hz, 2H), 6.94 (s, 1H), 6.86 (d, J=7.6 Hz, 1H), 4.44 (s, 2H), 3.97 (q, J=7.2 Hz, 2H), 1.38 (t, J=7.2 Hz, 3H).

Example 41: Synthesis of N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-1-(p-tolyl)methanesulfonamide

[0262] ##STR00058##

[0263] The synthesis can refer to Example 1. .sup.1H NMR (400 MHz, d-DMSO) δ 9.84 (s, 1H), 8.32 (d, J=8.4 Hz, 1H), 8.07 (d, J=6.8 Hz, 1H), 7.82 (t, J=7.6 Hz, 1H), 7.47 (d, J=7.6 Hz, 1H), 7.20-7.18 (m, 3H), 7.11 (d, J=7.6 Hz, 2H), 4.42 (s, 2H), 3.92 (q, J=7.2 Hz, 2H), 2.28 (s, 3H), 1.27 (t, J=7.2 Hz, 3H).

Example 42: Synthesis of N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-1-(2-fluorophenyl)methanesulfonamide

[0264] ##STR00059##

[0265] The synthesis can refer to Example 1. .sup.1H NMR (400 MHz, d-DMSO) δ 10.03 (s, 1H), 8.34 (d, J=8.4 Hz, 1H), 8.08 (d, J=6.8 Hz, 1H), 7.84 (t, J=7.6 Hz, 1H), 7.50 (d, J=7.6 Hz, 1H), 7.41 (t, J=7.2 Hz, 2H), 7.20-7.16 (m, 3H), 4.53 (s, 2H), 3.93 (q, J=7.2 Hz, 2H), 1.27 (t, J=7.2 Hz, 3H).

Example 43: Synthesis of 1-(4-chlorophenyl)-N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)methanesulfonamide

[0266] ##STR00060##

[0267] The synthesis can refer to Example 1. .sup.1H NMR (400 MHz, d-DMSO) δ 9.92 (s, 1H), 8.31 (d, J=8.4 Hz, 1H), 8.07 (d, J=6.8 Hz, 1H), 7.83 (t, J=7.6 Hz, 1H), 7.48 (d, J=7.6 Hz, 1H), 7.35 (q, J=8.4 Hz, 4H), 7.18 (d, J=7.6 Hz, 1H), 4.51 (s, 2H), 3.92 (q, J=7.2 Hz, 2H), 1.27 (t, J=7.2 Hz, 3H).

Example 44: Synthesis of 1-(4-cyanophenyl)-N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)methanesulfonamide

[0268] ##STR00061##

[0269] The synthesis can refer to Example 1. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 10.01 (s, 1H), 8.29 (d, J=8.0 Hz, 1H), 8.08 (d, J=6.8 Hz, 1H), 7.83 (t, J=7.6 Hz, 1H), 7.78 (d, J=8.0 Hz, 2H), 7.52-7.46 (m, 3H), 7.19 (d, J=7.6 Hz, 1H), 4.64 (s, 2H), 3.92 (q, J=6.8 Hz, 2H), 1.27 (t, J=7.2 Hz, 3H).

Example 45: Synthesis of N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-1-(4-fluorophenyl)methanesulfonamide

[0270] ##STR00062##

[0271] The synthesis can refer to Example 1. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.10 (d, J=7.2 Hz, 1H), 7.96 (d, J=8.4 Hz, 1H), 7.84-7.68 (m, 1H), 7.51 (d, J=7.6 Hz, 1H), 7.25 (d, J=9.2 Hz, 1H), 6.98 (t, J=8.4 Hz, 2H), 6.87 (d, J=7.6 Hz, 1H), 6.71 (s, 1H), 4.36 (s, 2H), 3.98 (q, J=7.2 Hz, 2H), 1.39 (t, J=7.2 Hz, 3H).

[0272] The synthesis of formula II:

Example 46: Synthesis of N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-4-fluorobenzamide

[0273] ##STR00063##

[0274] 6-amino-1-ethylbenzo[cd]indol-2(1H)-one can refer to Example 1.

[0275] A reaction mixture of 6-amino-1-ethylbenzo[cd]indol-2(1H)-one (100 mg, 0.47 mmol) and 4-fluorobenzoic acid (98 mg, 0.7 mmol) in DCM (20 mL) was stirred at rt for 5 m in. HATU (269 mg, 0.71 mmol) and DIPEA (183 mg, 1.41 mmol) was added to the re action mixture. After the reaction was completed, the reaction mixture was stirred at rt f or overnight. The reaction mixture was extracted with ethyl acetate (150 mL×2). The organic layer was washed with brine and dried over Na.sub.2SO.sub.4. The solid was filtered off, and the filtrate was concentrated under reduced pressure. The resulting crude product was purified by silica gel chromatography with petroleum ether/ethyl acetate (3/1, v/v) to yield N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-4-fluorobenzamide (90 mg, 57%) as a yellow solid. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.20 (s, 1H), 8.03-7.96 (m, 4H), 7.81 (d, J=7.6 Hz, 1H), 7.68 (t, J=7.6 Hz, 1H), 7.20 (t, J=8.4 Hz, 2H), 6.87 (d, J=7.6 Hz, 1H), 3.96 (q, J=7.2 Hz, 2H), 1.37 (t, J=7.2 Hz, 3H).

Example 47: Synthesis of 2-(4-chlorophenyl)-N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)acetamide

[0276] ##STR00064##

[0277] The synthesis can refer to Example 46. .sup.1H NMR (400 MHz, d-DMSO) δ 10.23 (s, 1H), 8.28 (d, J=8.0 Hz, 1H), 8.06 (d, J=6.8 Hz, 1H), 7.83 (t, J=7.6 Hz, 1H), 7.76 (d, J=7.6 Hz, 1H), 7.61-7.26 (m, 4H), 7.16 (d, J=7.6 Hz, 1H), 3.90 (q, J=7.2 Hz, 2H), 3.82 (s, 2H), 1.25 (t, J=7.2 Hz, 3H).

Example 48: Synthesis of 2-(3,4-dimethoxyphenyl)-N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)acetamide

[0278] ##STR00065##

[0279] The synthesis can refer to Example 46. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.01 (d, J=6.8 Hz, 1H), 7.87 (d, J=7.6 Hz, 1H), 7.62 (t, J=7.6 Hz, 1H), 7.55 (s, 1H), 7.50 (d, J=8.0 Hz, 1H), 6.98-6.94 (m, 3H), 6.85 (d, J=7.6 Hz, 1H), 3.96-3.92 (m, 8H), 3.82 (s, 2H), 1.34 (t, J=7.2 Hz, 3H).

Example 49: Synthesis of 2-(2,4-dichlorophenyl)-N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)acetamide

[0280] ##STR00066##

[0281] The synthesis can refer to Example 46. .sup.1H NMR (400 MHz, d-DMSO) δ 10.29 (s, 1H), 8.33 (d, J=8.0 Hz, 1H), 8.07 (d, J=6.8 Hz, 1H), 7.84 (t, J=7.6 Hz, 1H), 7.74 (d, J=7.6 Hz, 1H), 7.63 (s, 1H), 7.52 (d, J=8.4 Hz, 1H), 7.43 (d, J=8.4 Hz, 1H), 7.17 (d, J=7.6 Hz, 1H), 4.01 (s, 2H), 3.91 (q, J=7.2 Hz, 2H), 1.26 (t, J=7.2 Hz, 3H).

Example 50: Synthesis of N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-3-phenylpropanamide

[0282] ##STR00067##

[0283] The synthesis can refer to Example 46. .sup.1H NMR (400 MHz, d-DMSO) δ 9.95 (s, 1H), 8.11 (d, J=8.4 Hz, 1H), 8.05 (d, J=7.2 Hz, 1H), 7.86-7.73 (m, 1H), 7.71 (d, J=7.6 Hz, 1H), 7.31 (d, J=4.0 Hz, 3H), 7.23 (s, 1H), 7.16 (d, J=7.6 Hz, 1H), 3.91 (q, J=7.2 Hz, 2H), 2.98 (t, J=7.6 Hz, 2H), 2.79 (t, J=7.6 Hz, 2H), 1.26 (t, J=7.2 Hz, 3H).

Example 51: Synthesis of N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-4,4,4-trifluorobutanamide

[0284] ##STR00068##

[0285] The synthesis can refer to Example 46. .sup.1H NMR (400 MHz, d-DMSO) δ 10.14 (s, 1H), 8.32 (d, J=8.4 Hz, 1H), 8.07 (d, J=6.8 Hz, 1H), 7.83 (t, J=7.6 Hz, 1H), 7.77 (d, J=7.6 Hz, 1H), 7.18 (d, J=7.6 Hz, 1H), 3.91 (q, J=7.2 Hz, 2H), 2.88-2.71 (m, 2H), 2.71-2.51 (m, 2H), 1.26 (t, J=7.2 Hz, 3H).

Example 52: Synthesis of N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)propionamide

[0286] ##STR00069##

[0287] The synthesis can refer to Example 46. .sup.1H NMR (400 MHz, d-DMSO) δ 9.92 (s, 1H), 8.30 (d, J=8.4 Hz, 1H), 8.06 (d, J=6.8 Hz, 1H), 7.89-7.62 (m, 2H), 7.16 (d, J=7.6 Hz, 1H), 3.91 (q, J=7.2 Hz, 2H), 2.46 (q, J=7.6 Hz, 2H), 1.26 (t, J=7.2 Hz, 3H), 1.16 (t, J=7.6 Hz, 3H).

Example 53: Synthesis of 4-chloro-N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)benzamide

[0288] ##STR00070##

[0289] The synthesis can refer to Example 46. .sup.1H NMR (400 MHz, d-DMSO) δ 10.55 (s, 1H), 8.20 (d, J=8.0 Hz, 1H), 8.09 (t, J=8.8 Hz, 3H), 7.81 (t, J=7.6 Hz, 1H), 7.65 (d, J=8.4 Hz, 3H), 7.23 (d, J=7.6 Hz, 1H), 3.94 (q, J=7.2 Hz, 2H), 1.29 (t, J=7.2 Hz, 3H).

Example 54: Synthesis of N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-2-(p-tolyl)acetamide

[0290] ##STR00071##

[0291] The synthesis can refer to Example 46. .sup.1H NMR (400 MHz, d-DMSO) d 10.19 (s, 1H), 8.27 (d, J=8.0 Hz, 1H), 8.06 (d, J=6.8 Hz, 1H), 7.82 (t, J=7.6 Hz, 1H), 7.75 (d, J=7.6 Hz, 1H), 7.30 (d, J=7.6 Hz, 2H), 7.16 (d, J=7.6 Hz, 3H), 3.90 (q, J=7.2 Hz, 2H), 3.75 (s, 2H), 2.29 (s, 3H), 1.25 (t, J=7.2 Hz, 3H).

Example 55: Synthesis of (E)-N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-3-(furan-2-yl)acrylamide

[0292] ##STR00072##

[0293] The synthesis can refer to Example 46. .sup.1H NMR (400 MHz, d-DMSO) δ 10.24 (s, 1H), 8.43 (d, J=8.0 Hz, 1H), 8.07 (t, J=7.6 Hz, 2H), 7.84 (d, J=11.2 Hz, 2H), 7.45 (d, J=11.2 Hz, 1H), 7.20 (d, J=7.6 Hz, 1H), 7.04-6.75 (m, 2H), 6.64 (s, 1H), 3.92 (q, J=6.8 Hz, 2H), 1.27 (t, J=7.2 Hz, 3H).

[0294] The synthesis of formula III:

Example 56: Synthesis of I-ethyl-6-((3-phenylpropyl)amino)benzo[cd]indol-2(1H)-one

[0295] ##STR00073##

[0296] 6-amino-1-ethylbenzo[cd]indol-2(1H)-one can refer to Example 1.

[0297] A reaction mixture of 6-amino-1-ethylbenzo[cd]indol-2(1H)-one (100 mg, 0.47 mmol) and (3-chloropropyl)benzene (73 mg, 0.47 mmol) in CH.sub.3CN (20 mL) was stirred at rt. K.sub.2CO.sub.3 (195 mg, 1.41 mmol) was added to the reaction mixture, and stirred at 70° C. for overnight. The reaction mixture was extracted with ethyl acetate (150 mL×2). The organic layer was washed with brine and dried over Na.sub.2SO.sub.4. The solid was filtered off, and the filtrate was concentrated under reduced pressure. The resulting crude product was purified by silica gel chromatography with petroleum ether/ethyl acetate (5/1, v/v) to yield 1-ethyl-6-((3-phenylpropyl)amino)benzo[cd]indol-2(1H)-one (60 mg, 38%) as a yellow solid. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.06 (d, J=7.2 Hz, 11H), 7.84 (d, J=8.0 Hz, 1H), 7.63 (t, J=7.6 Hz, 1H), 7.32 (t, J=7.6 Hz, 2H), 7.26-7.04 (m, 3H), 6.77 (d, J=7.6 Hz, 1H), 6.34 (d, J=7.2 Hz, 1H), 4.24 (s, 1H), 3.94 (q, J=7.2 Hz, 2H), 3.30 (t, J=6.8 Hz, 2H), 2.83 (t, J=7.2 Hz, 2H), 2.21-2.03 (m, 2H), 1.36 (t, J=7.2 Hz, 3H).

Example 56: Synthesis of 1-ethyl-6-((3-morpholinopropyl)amino)benzo[cd]indol-2(1H)-one

[0298] ##STR00074##

[0299] The synthesis can refer to Example 56. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.07 (d, J=7.6 Hz, 2H), 7.66 (t, J=7.6 Hz, 1H), 6.79 (d, J=7.6 Hz, 1H), 6.35 (d, J=7.6 Hz, 1H), 5.81 (s, 1H), 3.95 (q, J=7.2 Hz, 2H), 3.82 (t, J=4.4 Hz, 4H), 3.35 (t, J=6.0 Hz, 2H), 2.60-2.54 (m, 6H), 2.02-1.87 (m, 2H), 1.36 (t, J=7.2 Hz, 3H).

Example 58: Synthesis of 1-ethyl-6-((4-methoxybenzyl)amino)benzo[cd]indol-2(1H)-one

[0300] ##STR00075##

[0301] The synthesis can refer to Example 56. .sup.1H NMR (400 MHz, d-DMSO) δ 8.51 (d, J=8.0 Hz, 1H), 7.98 (d, J=7.2 Hz, 1H), 7.71 (t, J=7.6 Hz, 1H), 7.33 (d, J=8.4 Hz, 2H), 7.05 (s, 1H), 6.88 (d, J=8.4 Hz, 3H), 6.21 (d, J=7.6 Hz, 1H), 4.40 (d, J=4.4 Hz, 2H), 3.82 (q, J=7.2 Hz, 2H), 3.70 (d, J=8.8 Hz, 3H), 1.20 (t, J=7.2 Hz, 3H).

Example 59: Synthesis of 1-ethyl-6-((4-methylbenzyl)amino)benzo[cd]indol-2(1H)-one

[0302] ##STR00076##

[0303] The synthesis can refer to Example 56. .sup.1H NMR (400 MHz, d-DMSO) δ 8.52 (d, J=8.0 Hz, 1H), 7.99 (d, J=6.8 Hz, 1H), 7.71 (t, J=7.6 Hz, 1H), 7.29 (d, J=7.6 Hz, 2H), 7.12 (d, J=7.6 Hz, 3H), 6.87 (d, J=7.6 Hz, 1H), 6.17 (d, J=7.6 Hz, 1H), 4.42 (s, 2H), 3.81 (q, J=7.2 Hz, 2H), 2.26 (s, 3H), 1.20 (t, J=7.2 Hz, 3H).

Example 60: Synthesis of 1-ethyl-6-((4-(trifluoromethyl)benzyl)amino)benzo[cd]indol-2(1H)-one

[0304] ##STR00077##

[0305] The synthesis can refer to Example 56. .sup.1H NMR (400 MHz, d-DMSO) δ 8.52 (d, J=8.0 Hz, 1H), 8.00 (d, J=6.8 Hz, 1H), 7.74 (t, J=7.6 Hz, 1H), 7.69 (d, J=8.0 Hz, 2H), 7.63 (d, J=8.0 Hz, 2H), 7.26 (s, 1H), 6.87 (d, J=7.6 Hz, 1H), 6.14 (d, J=7.6 Hz, 1H), 4.58 (d, J=5.2 Hz, 2H), 3.81 (q, J=7.2 Hz, 2H), 1.20 (t, J=7.2 Hz, 3H).

Example 61: Synthesis of 6-((4-chlorobenzyl)amino)-1-ethylbenzo[cd]indol-2(1H)-one

[0306] ##STR00078##

[0307] The synthesis can refer to Example 56. .sup.1H NMR (400 MHz, d-DMSO) δ 8.51 (d, J=8.4 Hz, 1H), 8.00 (d, J=6.8 Hz, 1H), 7.73 (t, J=7.6 Hz, 1H), 7.43 (d, J=8.4 Hz, 2H), 7.37 (d, J=8.4 Hz, 2H), 7.18 (t, J=6.0 Hz, 1H), 6.88 (d, J=7.6 Hz, 1H), 6.15 (d, J=7.6 Hz, 1H), 4.47 (d, J=6.0 Hz, 2H), 3.82 (q, J=7.2 Hz, 2H), 1.20 (t, J=7.2 Hz, 3H).

Example 62: Synthesis of 1-ethyl-6-((4-fluorobenzyl)amino)benzo[cd]indol-2(1H)-one

[0308] ##STR00079##

[0309] The synthesis can refer to Example 56. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.07 (d, J=7.2 Hz, 1H), 8.00 (d, J=8.2 Hz, 1H), 7.66 (t, J=7.6 Hz, 1H), 7.41 (dd, J=8.4, 5.6 Hz, 2H), 7.06 (t, J=8.4 Hz, 2H), 6.75 (d, J=7.6 Hz, 1H), 6.38 (d, J=7.6 Hz, 1H), 4.66 (s, 1H), 4.45 (s, 2H), 3.94 (q, J=7.2 Hz, 2H), 1.35 (t, J=7.2 Hz, 3H).

[0310] The synthesis of formula IV:

Example 63: Synthesis of N-((1-acetylpiperidin-4-yl)methyl)-1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide

[0311] ##STR00080##

[0312] The synthesis of 1-ethylbenzo[cd]indol-2(1H)-one can refer to Example 1.

Step 1. Synthesis of 1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonyl chloride

[0313] ##STR00081##

[0314] To a solution of 1-ethylbenzo[cd]indol-2(1H)-one (6.46 g, 0.03 mol) in chloroform (100 mL) was added batches of chlorosulfonic (11.5 g, 0.1 mol) at 0° C. for 10 min. The reaction mixture was heated at 50° C. for 6 h. The mixture was then poured into ice water and extracted with DCM (150 mL×2). The organic layer was washed with brine and dried over Na.sub.2SO.sub.4. The solid was filtered off, and the filtrate was concentrated under reduced pressure. The resulting crude product was purified by silica gel chromatography with petroleum ether/ethyl acetate (5/1, v/v) to yield 1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonyl chloride (5.75 g, 59%) as a yellow solid. MS (ESI), m/z: M.sup.+ 297.1.

[0315] A reaction mixture of 1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonyl chloride (100 mg, 0.34 mmol) and 1-(4-(aminomethyl)piperidin-1-yl)ethan-1-one (64 mg, 0.41 mmol) in pyridine (5 mL) was stirred at 80° C. for 1 h. Dilute HCl was added, the aqueous layer was extracted with ethyl acetate (50 mL×3), and the organic layer was washed with water and brine, dried with Na.sub.2SO.sub.4 and evaporated. The residue was purified by silica gel chromatography with petroleum and ether/ethyl acetate (4/1, v/v) to afford N-((1-acetylpiperidin-4-yl)methyl)-1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide (92 mg, 65%). .sup.1H-NMR (400 MHz, d-DMSO) δ 8.69 (d, J=8.4 Hz, 1H), 8.16 (d, J=6.8 Hz, 1H), 8.07 (d, J=7.6 Hz, 1H), 7.96 (t, J=7.2 Hz, 1H), 7.86 (t, J=6.0 Hz, 1H), 7.31 (d, J=7.6 Hz, 1H), 4.24 (d, J=8.0 Hz, 1H), 3.93 (q, J=6.8 Hz, 2H), 3.69 (d, J=12.4 Hz, 1H), 2.87 (t, J=13.2 Hz, 1H), 2.64 (t, J=6.0 Hz, 2H), 2.36 (t, J=12.0 Hz, 1H). 1.92 (s, 3H), 1.56-1.51 (m, 3H), 1.28 (t, J=7.2 Hz, 3H). MS (ESI), m/z: M.sup.+ 417.0; M.sup.− 415.0.

Example 64: Synthesis of N-(1-acetylcyclohexyl)-1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide

[0316] ##STR00082##

[0317] The synthesis can refer to Example 63. .sup.1H-NMR (400 MHz, d-DMSO) d 8.58 (d, J=8.4 Hz, 1H), 8.15 (d, J=7.2 Hz, 1H), 8.09 (d, J=7.6 Hz, 1H), 7.96 (t, J=8.0 Hz, 1H), 7.31 (d, J=7.6 Hz, 1H), 3.92 (q, J=6.8 Hz, 2H), 3.26-3.21 (m, 4H), 1.25 (t, J=7.2 Hz, 3H), 1.01-0.98 (m, 6H). MS (ESI), m/z: M.sup.− 400.8.

Example 65: Synthesis of 1-ethyl-N-((3-isopropyl-4,5-dihydroisoxazol-5-yl)methyl)-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide

[0318] ##STR00083##

[0319] The synthesis can refer to Example 63. .sup.1H-NMR (400 MHz, d-DMSO) δ 8.70 (d, J=8.0 Hz, 1H), 8.14-8.09 (m, 2H), 8.06 (d, J=7.6 Hz, 1H), 7.94 (t, J=7.6 Hz, 1H), 7.29 (d, J=7.2 Hz, 1H), 4.43-4.39 (m, 1H), 3.93 (q, J=6.8 Hz, 2H), 2.84-2.83 (m, 2H), 2.48 (s, 3H), 1.26 (t, J=6.8 Hz, 1H), 0.98 (s, 6H). MS (ESI), m/z: M.sup.− 400.0.

Example 66: Synthesis of N-((3,5-dimethyl-4,5-dihydroisoxazol-5-yl)methyl)-1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide

[0320] ##STR00084##

[0321] The synthesis can refer to Example 63. .sup.1H-NMR (400 MHz, d-DMSO) δ 8.72 (d, J=8.4 Hz, 1H), 8.15-8.10 (m, 2H), 8.07 (d, J=7.6 Hz, 1H), 7.94 (t, J=7.2 Hz, 1H), 7.30 (d, J=7.6 Hz, 1H), 3.93 (q, J=7.2 Hz, 2H), 2.85-2.82 (m, 3H), 2.58 (s, 1H), 1.75 (s, 3H), 1.27-1.22 (m, 4H), 1.17 (s, 2H). MS (ESI), m/z: M.sup.− 386.0.

Example 67: Synthesis of N-(4-acetylphenyl)-1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide

[0322] ##STR00085##

[0323] The synthesis of 1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonyl chloride can refer to Example 63.

[0324] A reaction mixture of I-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonyl chloride (100 mg, 0.34 mmol) and 1-(4-aminophenyl)ethan-1-one (55 mg, 0.41 mmol) in pyridine (3 m L) was stirred at rt for overnight. Dilute HCl was added, the aqueous layer was extracted with ethyl acetate (50 mL×3), and the organic layer was washed with water and brine, dried with Na.sub.2SO.sub.4 and evaporated. The residue was purified by silica gel chromatography with petroleum and ether/ethyl acetate (4/1, v/v) to afford N-((1-acetylpiperidin-4-yl)methyl)-1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide (80 mg, 60%). .sup.1H-NMR (400 MHz, d-DMSO) δ10.82 (s, 1H), 8.69 (d, J=8.4 Hz, 1H), 8.19 (d, J=7.6 Hz, 1H), 8.09 (d, J=7.2 Hz, 1H), 7.94 (t, J=8.0 Hz, 1H), 7.58-7.53 (m, 2H), 7.31 (d, J=5.6 Hz, 2H), 7.25 (d, J=7.6 Hz, 1H), 3.86 (q, J=6.8 Hz, 2H), 2.43 (s, 3H), 1.22 (t, J=6.8 Hz, 3H). MS (ESI), m/z: M+395.0; M.sup.−393.0.

Example 68: Synthesis of N-(2-chlorobenzyl)-1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide

[0325] ##STR00086##

[0326] The synthesis can refer to Example 63. .sup.1H-NMR (400 MHz, d-DMSO) δ 8.68 (d, J=8.0 Hz, 1H), 8.13 (d, J=7.2 Hz, 1H), 8.04 (d, J=7.6 Hz, 1H), 7.92 (t, J=7.2 Hz, 1H), 7.27-7.29 (m, 3H), 7.12-7.02 (m, 2H), 4.12 (s, 2H), 3.93 (q, J=7.2 Hz, 1H), 1.27 (t, J=7.2 Hz, 3H). MS (ESI), m/z: M.sup.− 399.0.

Example 69: Synthesis of 1-ethyl-N-(2-fluorobenzyl)-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide

[0327] ##STR00087##

[0328] The synthesis can refer to Example 63. .sup.1H-NMR (400 MHz, d-DMSO) δ 8.64 (d, J=8.4 Hz, 1H), 8.41 (s, 1H), 8.12 (d, J=6.8 Hz, 1H), 8.03 (d, J=8.0 Hz, 1H), 7.91 (t, J=7.2 Hz, 1H), 7.21 (d, J=7.6 Hz, 1H), 7.15 (t, J=8.0 Hz, H), 7.07-7.05 (m, 1H), 7.91-7.83 (m, 2H), 4.06 (s, 2H), 3.92 (q, J=7.2 Hz, 2H), 1.29 (t, J=7.2 Hz, 3H). MS (ESI), m/z: M.sup.− 383.0.

Example 70: Synthesis of N-(1-acetylpiperidin-4-yl)-1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide

[0329] ##STR00088##

[0330] The synthesis can refer to Example 63. .sup.1H-NMR (400 MHz, d-DMSO) δ 8.70 (d, J=8.4 Hz, 1H), 8.16-8.11 (m, 2H), 8.02 (d, J=7.6 Hz, 1H), 7.94 (q, J=7.2 Hz, 1H), 7.30 (d, J=8.0 Hz, 1H), 4.01 (q, J=6.8 Hz, 1H), 3.93 (q, J=7.2 Hz, 2H), 3.58 (d, J=14.0 Hz, 1H), 3.33-3.19 (m, 1H), 2.97-2.90 (m, 1H), 2.62-2.55 (m, 1H), 1.88 (s, 3H), 1.49 (d, J=10.0 Hz, 2H), 1.28 (t, J=7.2 Hz, 3H), 1.27-1.22 (m, 2H). MS (ESI), m/z: M.sup.+ 402.1; M.sup.− 400.1.

Example 71: Synthesis of tert-butyl4-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamido)piperidine-1-carboxylate

[0331] ##STR00089##

[0332] The synthesis can refer to Example 63. .sup.1H-NMR (400 MHz, d-DMSO) δ 8.68 (d, J=8.4 Hz, 1H), 8.15-8.10 (m, 2H), 7.98-7.92 (m, 2H), 7.29 (d, J=7.6 Hz, 1H), 3.93 (d, J=7.2 Hz, 2H), 3.67-3.64 (m, 2H), 3.18 (s, 1H), 2.69 (s, 2H), 1.47-1.44 (m, 2H), 1.32 (s, 9H), 1.32-1.25 (m, 3H), 1.17-1.51 (m, 2H). MS (ESI), m/z: M 458.0.

Example 72: Synthesis of N-cyclopentyl-1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide

[0333] ##STR00090##

[0334] The synthesis can refer to Example 63. .sup.1H-NMR (400 MHz, d-DMSO) δ 8.72 (d, J=8.4 Hz, 1H), 8.14 (d, J=6.8 Hz, 1H), 8.09 (d, J=7.6 Hz, H), 7.95 (t, J=7.6 Hz, 1H), 7.80 (d, J=7.2 Hz, 1H), 7.26 (d, J=7.6 Hz, 1H), 3.95 (q, J=7.2 Hz, 2H), 3.44 (q, J=6.4 Hz, 1H), 1.51-1.46 (m, 4H), 1.28-1.22 (m, 7H). MS (ESI), m/z: M 343.0.

Example 73: Synthesis of ethyl 1-((1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamido)methyl)cyclopentanecarboxylate

[0335] ##STR00091##

[0336] The synthesis can refer to Example 63. .sup.1H-NMR (400 MHz, d-DMSO) δ 8.63 (d, J=8.4 Hz, 1H), 8.17 (d, J=7.6 Hz, 1H), 8.11 (d, J=7.2 Hz, 1H), 7.86 (t, J=8.0 Hz, 1H), 6.93 (d, J=7.6 Hz, 1H), 5.36 (t, J=6.8 Hz, 1H), 4.04-3.96 (m, 4H), 2.92 (d, J=7.2 Hz, 2H), 1.93-1.89 (m, 2H), 1.71 (s, 2H), 1.58-1.54 (m, 6H), 1.39 (t, J=7.2 Hz, 3H), 1.16 (t, J=7.2 Hz, 3H). MS (ESI), m/z: M.sup.− 429.0.

Example 74: Synthesis of 1-((1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamido)methyl)cyclopentanecarboxylic acid

[0337] ##STR00092##

[0338] The synthesis of ethyl 1-((1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamido)meth yl)cyclopentanecarboxylate can refer to Example 73.

[0339] Ethyl1-((1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamido)methyl)cyclopentanecarboxylate (100 mg, 0.23 mmol) was dissolved in THF (5 mL) and 2 mol/L NaOH aqueous solution (5 mL). The mixture was stirred at room temperature for 2 h. The solvent w as removed and diluted hydrochloric acid was added dropwise, and a yellow precipitate was formed. The precipitate was collected by filtration and washed with water (10 mL×2). The resulting crude product was purified by recrystallization with petroleum and ether/ethyl acetate to afford 1-((1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamido)methyl)cyclopentanecarboxylic acid (86 mg, 93%) as a yellow solid. .sup.1H-NMR (400 MHz, d-DMSO) δ 8.63 (d, J=8.4 Hz, 1H), 8.17 (d, J=7.6 Hz, 1H), 8.11 (d, J=7.2 Hz, 1H), 7.86 (t, J=8.0 Hz, 1H), 6.93 (d, J=7.6 Hz, 1H), 5.36 (t, J=6.8 Hz, 1H), 3.92 (m, 3H), 2.83 (s, 2H), 1.81 (m, 2H), 1.45 (m, 6H), 1.25 (m, 4H).

Example 75: Synthesis of N-(4-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamido)phenyl)acetamide

[0340] ##STR00093##

[0341] The synthesis can refer to Example 67. .sup.1H NMR (400 MHz, d-DMSO) δ 10.33 (s, 1H), 9.79 (s, 1H), 8.68 (d, J=8.0 Hz, 1H), 8.10 (dd, J=14.4, 6.8 Hz, 2H), 7.92 (t, J=7.2 Hz, 1H), 7.34 (d, J=7.6 Hz, 2H), 7.23 (d, J=7.6 Hz, 1H), 6.94 (d, J=7.6 Hz, 2H), 3.88 (d, J=6.8 Hz, 2H), 1.95 (s, 3H), 1.23 (t, J=7.2 Hz, 3H).

Example 76: Synthesis of 2-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamido)benzoic acid

[0342] ##STR00094##

[0343] The synthesis can refer to Example 74. .sup.1H NMR (400 MHz, d-DMSO) δ 11.96 (s, 1H), 8.52 (d, J=8.4 Hz, 1H), 8.26 (d, J=7.6 Hz, 1H), 8.13 (d, J=7.2 Hz, 1H), 8.02-7.84 (m, 1H), 7.80 (d, J=7.2 Hz, 1H), 7.63-7.41 (m, 2H), 7.28 (d, J=7.6 Hz, 1H), 7.02 (t, J=7.6 Hz, 1H), 3.89 (q, J=7.2 Hz, 2H), 1.23 (t, J=7.2 Hz, 3H).

Example 77: Synthesis of 1-ethyl-N-(4-fluorophenyl)-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide

[0344] ##STR00095##

[0345] The synthesis can refer to Example 67. .sup.1H NMR (400 MHz, d-DMSO) δ 10.48 (s, 1H), 8.64 (d, J=8.4 Hz, 1H), 8.13-8.07 (m, 2H), 8.00-7.79 (m, 1H), 7.25 (d, J=7.6 Hz, 1H), 7.17-6.83 (m, 4H), 3.89 (q, J=7.2 Hz, 2H), 1.25 (t, J=7.2 Hz, 3H).

Example 78: Synthesis of N-butyl-1-ethyl-2-oxo-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide

[0346] ##STR00096##

[0347] The synthesis can refer to Example 67. .sup.1H NMR (400 MHz, d-DMSO) δ 8.69 (d, J=8.4 Hz, 1H), 8.15 (d, J=7.2 Hz, 1H), 8.08 (d, J=7.6 Hz, 1H), 8.01-7.85 (m, 1H), 7.77 (t, J=6.0 Hz, 1H), 7.31 (d, J=7.6 Hz, 1H), 3.94 (q, J=7.2 Hz, 2H), 2.75 (dd, J=13.2, 6.8 Hz, 2H), 1.35-1.21 (m, 5H), 1.19-1.12 (m, 2H), 0.70 (t, J=7.2 Hz, 3H).

Example 79: Synthesis of N-(2-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamido)ethyl)acetamide

[0348] ##STR00097##

[0349] The synthesis can refer to Example 67. .sup.1H NMR (400 MHz, d-DMSO) δ 8.65 (d, J=8.2 Hz, 1H), 8.14 (d, J=6.4 Hz, 1H), 8.06 (d, J=7.2 Hz, 1H), 7.94 (t, J=7.2 Hz, 1H), 7.87 (s, 1H), 7.76 (s, 1H), 7.30 (d, J=7.2 Hz, 1H), 3.93 (d, J=6.8 Hz, 2H), 3.01 (d, J=5.6 Hz, 2H), 2.77 (s, 2H), 1.65 (s, 3H), 1.26 (t, J=6.4 Hz, 3H).

Example 80: Synthesis of 1-ethyl-N-(2-(methyl sulfonyl)ethyl)-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide

[0350] ##STR00098##

[0351] The synthesis can refer to Example 67. .sup.1H NMR (400 MHz, d-DMSO) δ 8.64 (d, J=8.4 Hz, 1H), 8.16-8.10 (m, 3H), 7.96 (t, J=7.6 Hz, 1H), 7.33 (d, J=7.6 Hz, 1H), 3.94 (q, J=6.8 Hz, 2H), 3.23 (t, J=6.8 Hz, 2H), 3.14 (t, J=6.8 Hz, 2H), 2.97 (s, 3H), 1.27 (t, J=7.2 Hz, 3H).

Example 81: Synthesis of 1-ethyl-2-oxo-N-(2-(2-oxoimidazolidin-1-yl)ethyl)-1,2-dihydrobenzo[cd]indole-6-sulfonamide

[0352] ##STR00099##

[0353] The synthesis can refer to Example 67. .sup.1H NMR (400 MHz, d-DMSO) δ 8.66 (d, J=8.0 Hz, 1H), 8.14 (d, J=6.4 Hz, 1H), 8.08 (d, J=7.2 Hz, 1H), 7.92 (d, J=6.4 Hz, 2H), 7.29 (d, J=7.2 Hz, 1H), 6.23 (s, 1H), 3.93 (d, J=6.4 Hz, 2H), 3.18 (d, J=7.2 Hz, 2H), 3.09-3.02 (m, 4H), 2.86-2.84 (m, 2H), 1.26 (t, J=7.2 Hz, 3H).

Example 82: Synthesis of tert-butyl(4-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamido)butyl)carbamate

[0354] ##STR00100##

[0355] The synthesis can refer to Example 67. .sup.1H NMR (400 MHz, d-DMSO) δ 8.67 (d, J=8.4 Hz, 1H), 8.13 (d, J=6.8 Hz, 1H), 8.06 (d, J=7.6 Hz, 1H), 7.93 (t, J=7.6 Hz, 1H), 7.76 (s, 1H), 7.29 (d, J=7.6 Hz, 1H), 6.67 (s, 1H), 3.92 (d, J=7.2 Hz, 2H), 2.91-2.64 (m, 4H), 1.26 (s, 9H), 1.25-1.24 (m, 4H), 1.24 (t, J=7.2 Hz, 3H).

Example 83: Synthesis of N-(5-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamido)pyridin-2-yl)acetamide

[0356] ##STR00101##

[0357] The synthesis can refer to Example 67. .sup.1H NMR (400 MHz, d-DMSO) δ 10.48 (s, 1H), 10.34 (s, 1H), 8.62 (d, J=8.4 Hz, 1H), 8.12 (d, J=7.6 Hz, 1H), 8.06 (d, J=7.6 Hz, 1H), 7.99-7.70 (m, 3H), 7.41 (d, J=8.8 Hz, 1H), 7.23 (d, J=7.6 Hz, 1H), 3.88 (q, J=6.8 Hz, 2H), 1.98 (d, J=8.4 Hz, 3H), 1.22 (t, J=7.2 Hz, 3H).

Example 84: Synthesis of tert-butyl3-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamido)pyrrolidine-1-carboxylate

[0358] ##STR00102##

[0359] The synthesis can refer to Example 67. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.62 (d, J=8.4 Hz, 1H), 8.23 (d, J=7.6 Hz, 1H), 8.13 (d, J=7.2 Hz, 1H), 7.85 (t, J=7.6 Hz, 1H), 6.95 (d, J=7.6 Hz, 1H), 5.10 (d, J=7.2 Hz, 1H), 4.00 (q, J=7.2 Hz, 2H), 3.86 (d, J=4.8 Hz, 1H), 3.48-3.30 (m, 2H), 3.29-3.26 (m, 1H), 3.07-3.03 (m, 1H), 1.94-1.87 (m, 2H), 1.48-1.29 (m, 12H).

Example 85: Synthesis of tert-butyl3-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamido)azetidine-1-carboxylate

[0360] ##STR00103##

[0361] The synthesis can refer to Example 67. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.60 (d, J=8.4 Hz, 1H), 8.14 (d, J=7.6 Hz, 1H), 8.12 (d, J=6.8 Hz, 1H) 7.85 (t, J=7.6 Hz, 1H), 6.92 (d, J=7.6 Hz, 1H), 5.31 (d, J=8.8 Hz, 1H), 4.11 (d, J=8.0 Hz, 1H), 4.01-3.95 (m, 4H), 3.56 (s, 2H), 1.44-1.30 (m, 12H).

Example 86: Synthesis of N-(2-cyclohexylethyl)-1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide

[0362] ##STR00104##

[0363] The synthesis can refer to Example 67. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.64 (d, J=8.4 Hz, 1H), 8.19 (d, J=7.6 Hz, 1H), 8.12 (d, J=7.2 Hz, 1H), 7.84 (t, J=7.2 Hz, 1H), 6.93 (d, J=7.5 Hz, 1H), 4.41 (t, J=6.0 Hz, 1H), 3.99 (q, J=7.2 Hz, 2H), 2.97 (dd, J=13.2, 6.8 Hz, 2H), 1.39-1.37 (m, 4H), 1.28-1.25 (m, 6H), 1.13-1.08 (m, 2H), 1.02-0.97 (m, 2H), 0.96-0.89 (m, 2H).

Example 87: Synthesis of I-ethyl-2-oxo-N-(pyrrolidin-3-yl)-1,2-dihydrobenzo[cd]indole-6-sulfonamide

[0364] ##STR00105##

[0365] The synthesis of tert-butyl3-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamido) pyrrolidine-1-carboxylate can refer to 84.

[0366] Tert-butyl3-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamido)pyrrolidine-1-carboxylate (50 mg, 0.112 mmol) was dissolved in DCM (20 mL) and trifluoroacetic acid (0.5 mL). The mixture was stirred at room temperature for 2 h. The solvent was removed and was purified by recrystallization with petroleum and ether/ethyl acetate to afford 1-ethyl-2-oxo-N-(pyrrolidin-3-yl)-1,2-dihydrobenzo[cd]indole-6-sulfonamide (37 mg, 95%) as a yellow solid. .sup.1H NMR (400 MHz, d-DMSO) δ 8.74 (s, 1H), 8.65 (d, J=8.4 Hz, 1H), 8.29 (d, J=6.0 Hz, 1H), 8.18 (d, J=7.2 Hz, 1H), 8.13 (d, J=7.6 Hz, 1H), 8.03-7.86 (m, 1H), 7.34 (d, J=7.6 Hz, 1H), 3.94 (q, J=7.2 Hz, 1H), 3.74 (dd, J=12.0, 6.0 Hz, 1H), 3.18-3.12 (m, 1H), 3.11-2.99 (m, 1H), 2.93-2.89 (m, 1H), 1.90-1.83 (m, 1H), 1.69-1.66 (m, 1H), 1.27 (t, J=7.2 Hz, 2H).

Example 88: Synthesis of N-(azetidin-3-yl)-1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide

[0367] ##STR00106##

[0368] The synthesis can refer to Example 87. .sup.1H NMR (400 MHz, d-DMSO) δ 8.78 (d, J=7.6 Hz, 1H), 8.61 (d, J=8.4 Hz, 2H), 8.18 (d, J=7.2 Hz, 1H), 8.10 (d, J=7.6 Hz, 1H), 7.99 (t, 7.2 Hz, 1H), 7.33 (d, J=7.6 Hz, 1H), 3.94 (q, J=7.2 Hz, 2H), 3.86 (t, J=9.2 Hz, 2H), 3.66 (s, 2H), 1.27 (t, J=7.2 Hz, 3H).

Example 89: Synthesis of 1-ethyl-N-hexyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide

[0369] ##STR00107##

[0370] The synthesis can refer to Example 67. .sup.1H NMR (400 MHz, d-DMSO) δ 8.68 (d, J=8.4 Hz, 1H), 8.14 (d, J=7.2 Hz, 1H), 8.07 (d, J=7.6 Hz, 1H), 8.00-7.83 (m, 1H), 7.76 (t, J=6.0 Hz, 1H), 7.29 (d, J=7.6 Hz, 1H), 3.93 (q, J=7.2 Hz, 2H), 2.75 (dd, J=12.8, 6.4 Hz, 2H), 1.35-1.12 (m, 6H), 1.09-0.88 (m, 6H), 0.67 (t, J=6.8 Hz, 3H).

Example 90: Synthesis of I-ethyl-2-oxo-N-(2-(pyrrolidin-1-yl)ethyl)-1,2-dihydrobenzo[cd]indole-6-sulfonamide

[0371] ##STR00108##

[0372] The synthesis can refer to Example 67. .sup.1H NMR (400 MHz, d-DMSO) δ 8.68 (d, J=8.2 Hz, 1H), 8.17 (d, J=6.8 Hz, 1H), 8.12 (d, J=7.6 Hz, 1H), 7.96 (t, J=7.6 Hz, 1H), 7.33 (d, J=7.6 Hz, 1H), 4.00-3.88 (m, 2H), 3.18-3.02 (m, 3H), 2.85 (s, 4H), 1.73 (s, 3H), 1.28 (t, J=7.2 Hz, 3H).

Example 91: Synthesis of 1-ethyl-2-oxo-N-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-1,2-dihydrobenzo[cd]indole-6-sulfonamide

[0373] ##STR00109##

[0374] The synthesis can refer to Example 67. .sup.1H NMR (400 MHz, d-DMSO) δ 8.69 (d, J=8.4 Hz, 1H), 8.16 (d, J=7.2 Hz, 1H), 8.08 (d, J=7.6 Hz, 1H), 7.96 (t, J=7.6 Hz, 1H), 7.78 (s, 1H), 7.30 (d, J=7.6 Hz, 1H), 3.93 (t, J=7.2 Hz, 2H), 3.63 (dd, J=11.2, 3.6 Hz, 2H), 2.89 (t, J=11.2 Hz, 2H), 2.80 (d, J=4.8 Hz, 2H), 1.35-1.10 (m, 8H), 0.90-0.86 (m, 2H).

Example 92: Synthesis of 1-ethyl-2-oxo-N-(tetrahydrofuran-3-yl)-1,2-dihydrobenzo[cd]indole-6-sulfonamide

[0375] ##STR00110##

[0376] The synthesis can refer to Example 67. .sup.1H NMR (400 MHz, d-DMSO) δ 8.69 (d, J=8.4 Hz, 1H), 8.16 (d, J=6.0 Hz, 2H), 8.11 (d, J=7.6 Hz, 1H), 7.95 (t, J=7.6 Hz, 1H), 7.32 (d, J=7.6 Hz, 1H), 3.94 (q, J=7.2 Hz, 2H), 3.72 (s, 1H), 3.64 (dd, J=14.4, 7.2 Hz, 1H), 3.59-3.44 (m, 2H), 1.81-1.76 (m, 1H), 1.53 (dd, J=12.4, 6.0 Hz, 1H), 1.27 (t, J=7.2 Hz, 3H).

Example 93: Synthesis of N-(2-(4-chlorophenoxy)ethyl)-1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide

[0377] ##STR00111##

[0378] The synthesis can refer to Example 67. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.61 (d, J=8.4 Hz, 1H), 8.19 (d, J=7.6 Hz, 1H), 8.09 (d, J=7.2 Hz, 1H), 7.82 (t, J=7.6 Hz, 1H), 7.10 (d, J=8.8 Hz, 2H), 6.88 (d, J=7.6 Hz, 1H), 6.51 (d, J=8.8 Hz, 2H), 5.08 (t, J=6.0 Hz, 1H), 3.97 (q, J=7.2 Hz, 2H), 3.88 (t, J=5.2 Hz, 2H), 3.37 (dd, J=10.8, 5.2 Hz, 2H), 1.38 (t, J=7.2 Hz, 3H).

Example 94: Synthesis of N,1-diethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide

[0379] ##STR00112##

[0380] The synthesis can refer to Example 67. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.65 (d, J=8.4 Hz, 1H), 8.20 (d, J=7.6 Hz, 1H), 8.12 (d, J=6.8 Hz, 1H), 7.84 (t, J=7.6 Hz, 1H), 6.93 (d, J=7.6 Hz, 1H), 4.52 (s, 1H), 3.99 (q, J=7.2 Hz, 2H), 3.02 (t, J=7.2 Hz, 2H), 1.39 (t, J=7.2 Hz, 3H), 1.08 (t, J=7.2 Hz, 3H).

Example 95: Synthesis of 1-ethyl-2-oxo-N-pentyl-1,2-dihydrobenzo[cd]indole-6-sulfonamide

[0381] ##STR00113##

[0382] The synthesis can refer to Example 67. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.64 (d, J=8.4 Hz, 1H), 8.18 (d, J=7.6 Hz, 1H), 8.11 (d, J=6.8 Hz, 1H), 7.84 (t, J=7.6 Hz, 1H), 6.92 (d, J=7.6 Hz, 1H), 4.54 (d, J=6.0 Hz, 1H), 3.99 (q, J=7.2 Hz, 2H), 2.94 (q, J=6.8 Hz, 2H), 1.40 (q, J=7.2 Hz, 5H), 1.16 (d, J=6.4 Hz, 4H), 0.75 (t, J=7.2 Hz, 3H).

Example 96: Synthesis of 1-ethyl-N-methyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide

[0383] ##STR00114##

[0384] The synthesis can refer to Example 67. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.64 (d, J=8.4 Hz, 1H), 8.19 (d, J=7.6 Hz, 1H), 8.12 (d, J=7.2 Hz, 1H), 7.83 (t, J=7.6 Hz, 1H), 6.94 (d, J=7.6 Hz, 1H), 4.49 (d, J=5.2 Hz, 1H), 3.99 (q, J=7.2 Hz, 2H), 2.65 (d, J=5.2 Hz, 3H), 1.39 (t, J=7.2 Hz, 3H).

Example 97: Synthesis of N-cyclohexyl-1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide

[0385] ##STR00115##

[0386] The synthesis can refer to Example 67. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.61 (d, J=8.4 Hz, 1H), 8.20 (d, J=7.6 Hz, 1H), 8.11 (d, J=7.2 Hz, 1H), 7.84 (t, J=7.2 Hz, 1H), 6.92 (d, J=7.6 Hz, 1H), 4.52 (d, J=7.6 Hz, 1H), 3.99 (q, J=7.2 Hz, 2H), 3.29-2.92 (m, 1H), 1.75-1.63 (m, 2H), 1.58-1.50 (m, 1H), 1.49-1.46 (m, 1H), 1.40 (t, J=7.2 Hz, 3H), 1.25-1.05 (m, 6H).

Example 98: Synthesis of tert-butyl3-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamido)piperidine-1-carboxylate

[0387] ##STR00116##

[0388] The synthesis can refer to Example 67. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.60 (d, J=8.4 Hz, 1H), 8.21 (d, J=7.6 Hz, 1H), 8.11 (d, J=7.2 Hz, 1H), 7.84 (t, J=7.6 Hz, 1H), 6.92 (d, J=7.6 Hz, 1H), 4.87 (s, 1H), 3.98 (q, J=7.2 Hz, 2H), 3.47-3.16 (m, 4H), 3.02 (dd, J=13.2, 7.2 Hz, 1H), 1.67-1.53 (m, 2H), 1.47-1.25 (m, 14H).

Example 99: Synthesis of 1-ethyl-N-isobutyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfon amide

[0389] ##STR00117##

[0390] The synthesis can refer to Example 67. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.64 (d, J=8.4 Hz, 1H), 8.18 (d, J=7.6 Hz, 1H), 8.11 (d, J=7.2 Hz, 1H), 7.84 (t, J=7.6 Hz, 1H), 6.92 (d, J=7.6 Hz, 1H), 4.61 (t, J=6.4 Hz, 1H), 3.99 (q, J=7.2 Hz, 2H), 2.75 (t, J=6.4 Hz, 2H), 1.67 (dt, J=13.2, 6.8 Hz, 1H), 1.39 (t, J=7.2 Hz, 3H), 0.81 (d, J=6.8 Hz, 6H).

Example 10: Synthesis of 1-ethyl-2-oxo-N-propyl-1,2-dihydrobenzo[cd]indole-6-sulfonamide

[0391] ##STR00118##

[0392] The synthesis can refer to Example 67. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.65 (d, J=8.4 Hz, 1H), 8.18 (d, J=7.6 Hz, 1H), 8.10 (d, J=7.2 Hz, 1H), 7.92-7.68 (m, 1H), 6.92 (d, J=7.6 Hz, 1H), 4.66 (t, J=6.0 Hz, 1H), 3.98 (q, J=7.2 Hz, 2H), 2.91 (dd, J=13.2, 6.8 Hz, 2H), 1.46 (dt, J=14.4, 7.2 Hz, 2H), 1.39 (t, J=7.2 Hz, 3H), 0.80 (t, J=7.2 Hz, 3H).

Example 101: Synthesis of 1-ethyl-N-(3-(4-methylpiperazin-1-yl)propyl)-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide

[0393] ##STR00119##

[0394] The synthesis can refer to Example 67. .sup.1H NMR (400 MHz, d-DMSO) δ 8.68 (d, J=8.4 Hz, 1H), 8.16 (d, J=6.8 Hz, 1H), 8.08 (d, J=7.2 Hz, 1H), 7.95 (t, J=7.6 Hz, 1H), 7.78 (s, 1H), 7.31 (d, J=7.6 Hz, 1H), 3.94 (q, J=7.2 Hz, 2H), 2.79 (d, J=5.6 Hz, 2H), 2.23-1.86 (m, 11H), 1.48-1.33 (m, 2H), 1.28 (t, J=7.2 Hz, 3H).

Example 102: Synthesis of 1-ethyl-2-oxo-N-(2-(piperidin-1-yl)ethyl)-1,2-dihydrobenzo[cd]indole-6-sulfonamide

[0395] ##STR00120##

[0396] The synthesis can refer to Example 67. .sup.1H NMR (400 MHz, d-DMSO) δ 8.68 (d, J=8.4 Hz, 1H), 8.15 (d, J=6.8 Hz, 1H), 8.10 (d, J=7.6 Hz, 1H), 7.94 (t, J=7.6 Hz, 1H), 7.67 (s, 1H), 7.30 (d, J=7.6 Hz, 1H), 3.94 (q, J=7.2 Hz, 2H), 2.88 (t, J=6.4 Hz, 2H), 2.23-2.11 (m, 2H), 2.10-2.01 (m, 3H), 1.30-1.22 (m, 7H), 0.94-0.65 (m, 2H).

Example 103: Synthesis of N-(4,4-diethoxybutyl)-1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide

[0397] ##STR00121##

[0398] The synthesis can refer to Example 67. .sup.1H NMR (400 MHz, d-DMSO) δ 8.67 (d, J=8.4 Hz, 1H), 8.14 (d, J=6.8 Hz, 1H), 8.06 (d, J=7.6 Hz, 1H), 7.93 (t, J=7.6 Hz, 1H), 7.79 (t, J=5.2 Hz, 1H), 7.29 (d, J=7.6 Hz, 1H), 4.18 (s, 1H), 3.92 (q, J=6.8 Hz, 2H), 3.42-3.31 (m, 2H), 3.23-3.17 (m, 2H), 2.78 (d, J=5.2 Hz, 2H), 1.35-1.21 (m, 7H), 0.95 (t, J=6.8 Hz, 6H).

Example 104: Synthesis of ethyl 3-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamido)propanoate

[0399] ##STR00122##

[0400] The synthesis can refer to Example 67. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.61 (d, J=8.4 Hz, 1H), 8.19 (d, J=7.6 Hz, 1H), 8.12 (d, J=7.2 Hz, 1H), 7.96-7.69 (m, 1H), 6.93 (d, J=7.6 Hz, 1H), 5.35 (t, J=6.4 Hz, 1H), 4.01-3.96 (m, 4H), 3.19 (dd, J=12.4, 6.4 Hz, 2H), 2.48 (t, J=6.0 Hz, 2H), 1.39 (t, J=7.2 Hz, 3H), 1.18 (t, J=7.2 Hz, 3H).

Example 105: Synthesis of 1-ethyl-N-((1-ethylpyrrolidin-2-yl)methyl)-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide

[0401] ##STR00123##

[0402] The synthesis can refer to Example 67. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.68 (d, J=8.4 Hz, 1H), 8.12 (dd, J=10.4, 7.2 Hz, 2H), 7.96-7.78 (m, 1H), 6.90 (d, J=7.6 Hz, 1H), 3.98 (q, J=7.2 Hz, 2H), 3.67 (d, J=5.6 Hz, 1H), 3.46 (s, 1H), 3.37 (dd, J=14.4, 7.6 Hz, 2H), 3.19 (dd, J=14.4, 3.2 Hz, 1H), 2.87 (s, 1H), 2.76 (s, 1H), 2.15-1.80 (m, 5H), 1.38 (t, J=7.2 Hz, 6H).

Example 106: Synthesis of 1-ethyl-N-(1-methylpiperidin-4-yl)-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide

[0403] ##STR00124##

[0404] The synthesis can refer to Example 67. .sup.1H NMR (400 MHz, d-DMSO) δ 8.68 (d, J=8.4 Hz, 1H), 8.14 (d, J=7.2 Hz, 1H), 8.09 (d, J=7.6 Hz, 1H), 7.93 (dd, J=12.4, 5.6 Hz, 2H), 7.29 (d, J=7.6 Hz, 1H), 3.93 (q, J=7.2 Hz, 2H), 2.93 (s, 1H), 2.58 (d, J=11.2 Hz, 2H), 2.06 (s, 3H), 1.82 (s, 2H), 1.44 (d, J=10.4 Hz, 2H), 1.38-1.35 (m, 2H), 1.27 (t, J=7.2 Hz, 3H).

Example 107: Synthesis of N-cycloheptyl-1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide

[0405] ##STR00125##

[0406] The synthesis can refer to Example 67. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.63 (d, J=8.4 Hz, 1H), 8.21 (d, J=7.6 Hz, 1H), 8.13 (d, J=7.2 Hz, 1H), 7.93-7.60 (m, 1H), 6.94 (d, J=7.6 Hz, 1H), 4.55 (d, J=8.0 Hz, 1H), 4.01 (q, J=7.2 Hz, 2H), 3.50-3.20 (m, 1H), 1.73-1.69 (m, 2H), 1.55-0.99 (m, 15H).

Example 108: Synthesis of 1-ethyl-2-oxo-N-(tetrahydro-2H-pyran-4-yl)-1,2-dihydrobenzo[cd]indole-6-sulfonamide

[0407] ##STR00126##

[0408] The synthesis can refer to Example 67. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.61 (d, J=8.4 Hz, 1H), 8.21 (d, J=7.6 Hz, 1H), 8.12 (d, J=7.2 Hz, 1H), 7.93-7.77 (m, 1H), 6.92 (d, J=7.6 Hz, 1H), 4.65 (d, J=8.0 Hz, 1H), 3.99 (q, J=7.2 Hz, 2H), 3.82 (d, J=12.0 Hz, 2H), 3.44-3.34 (m, 1H), 3.30 (t, J=10.8 Hz, 2H), 1.69 (d, J=13.2 Hz, 2H), 1.51-1.35 (m, 5H).

Example 64: Synthesis of tert-butyl4-(2-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamido)ethyl)piperazine-1-carboxylate

[0409] ##STR00127##

[0410] The synthesis can refer to Example 67. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.63 (d, J=8.4 Hz, 1H), 8.19 (d, J=7.6 Hz, 1H), 8.12 (d, J=7.2 Hz, 1H), 7.93-7.75 (m, 1H), 6.93 (d, J=7.6 Hz, 1H), 5.35 (s, 1H), 3.99 (q, J=7.2 Hz, 2H), 3.28-3.10 (m, 4H), 2.98 (s, 2H), 2.41-2.23 (m, 2H), 2.16-2.04 (m, 4H), 1.47-1.30 (m, 12H).

Example 110: Synthesis of N-cyclohexyl-1-methyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide

[0411] ##STR00128##

[0412] The synthesis can refer to Example 67. .sup.1H NMR (400 MHz, d-DMSO) δ 8.70 (d, J=8.4 Hz, 1H), 8.14 (d, J=7.6 Hz, 1H), 8.11 (d, J=7.2 Hz, 1H), 8.02-7.89 (m, 1H), 7.85 (d, J=7.6 Hz, 1H), 7.23 (d, J=7.6 Hz, 1H), 3.38 (s, 3H), 2.94 (s, 1H), 1.57-1.33 (m, 5H), 1.04-0.88 (m, 5H).

Example 64: Synthesis of N-butyl-1-methyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide

[0413] ##STR00129##

[0414] The synthesis can refer to Example 67. .sup.1H NMR (400 MHz, d-DMSO) δ 8.68 (d, J=8.4 Hz, 1H), 8.15 (d, J=7.2 Hz, 1H), 8.08 (d, J=7.6 Hz, 1H), 7.99-7.83 (m, 1H), 7.77 (s, 1H), 7.25 (d, J=7.6 Hz, 1H), 3.39 (s, 3H), 2.74 (d, J=3.2 Hz, 2H), 1.27 (dd, J=14.8, 7.2 Hz, 2H), 1.15 (dd, J=14.8, 7.2 Hz, 2H), 0.70 (t, J=7.2 Hz, 3H).

Example 112: Synthesis of N-cyclohexyl-2-oxo-1-propyl-1,2-dihydrobenzo[cd]indole-6-sulfonamide

[0415] ##STR00130##

[0416] The synthesis can refer to Example 67. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.62 (d, J=8.4 Hz, 1H), 8.18 (d, J=7.2 Hz, 1H), 8.11 (d, J=7.2 Hz, 1H), 7.83 (t, 7.2 Hz, 1H), 6.91 (d, J=7.6 Hz, 1H), 4.57 (d, J=7.6 Hz, 1H), 3.89 (t, J=7.2 Hz, 2H), 3.31-3.03 (m, 1H), 1.82 (dt, J=14.8, 7.2 Hz, 2H), 1.74-1.64 (m, 2H), 1.57-1.56 (m, 2H), 1.48 (d, J=12.4 Hz, 1H), 1.17-1.08 (m, 4H), 1.02 (t, J=7.2 Hz, 3H).

Example 113: Synthesis of 2-oxo-N,1-dipropyl-1,2-dihydrobenzo[cd]indole-6-sulfonamide

[0417] ##STR00131##

[0418] The synthesis can refer to Example 67. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.64 (d, J=8.4 Hz, 1H), 8.18 (d, J=7.6 Hz, 1H), 8.11 (d, J=7.2 Hz, 1H), 7.94-7.66 (m, 1H), 6.92 (d, J=7.6 Hz, 1H), 4.60 (t, J=6.0 Hz, 1H), 3.89 (t, J=7.2 Hz, 2H), 2.92 (d d, J=13.6, 6.8 Hz, 2H), 1.78 (dt, J=14.4, 7.2 Hz, 2H), 1.44 (dt, J=14.4, 7.2 Hz, 2H), 1.01 (t, J=7.2 Hz, 3H), 0.81 (t, J=7.2 Hz, 3H).

Example 114: Synthesis of N-butyl-2-oxo-1-propyl-1,2-dihydrobenzo[cd]indole-6-sulfonamide

[0419] ##STR00132##

[0420] The synthesis can refer to Example 67. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.64 (d, J=8.4 Hz, 1H), 8.18 (d, J=7.6 Hz, 1H), 8.12 (d, J=7.2 Hz, 1H), 7.84 (dd, J=8.2, 7.2 Hz, 1H), 6.92 (d, J=7.6 Hz, 1H), 4.51 (t, J=6.0 Hz, 1H), 3.90 (t, J=7.2 Hz, 2H), 2.94 (dd, J=13.2, 6.8 Hz, 2H), 1.88-1.70 (m, 2H), 1.50-1.33 (m, 2H), 1.23 (dt, J=14.4, 7.2 Hz, 3H), 1.01 (t, J=7.2 Hz, 3H), 0.78 (t, J=7.2 Hz, 3H).

Example 115: Synthesis of N-butyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide

[0421] ##STR00133##

[0422] The synthesis can refer to Example 67. .sup.1H NMR (400 MHz, d-DMSO) δ 11.13 (s, 1H), 8.68 (d, J=8.4 Hz, 1H), 8.11 (d, J=7.2 Hz, 1H), 8.03 (d, J=7.6 Hz, 1H), 7.98-7.87 (m, 1H), 7.74 (t, J=5.6 Hz, 1H), 7.06 (d, J=7.6 Hz, 1H), 2.74 (dd, J=13.2, 6.8 Hz, 2H), 1.35-1.19 (m, 2H), 1.19-0.98 (m, 2H), 0.69 (t, J=7.2 Hz, 3H).

Example 116: Synthesis of N-butyl-1-isobutyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide

[0423] ##STR00134##

[0424] The synthesis can refer to Example 67. .sup.1H NMR (400 MHz, d-DMSO) δ 8.69 (d, J=8.4 Hz, 1H), 8.16 (d, J=7.2 Hz, 1H), 8.06 (d, J=7.6 Hz, 1H), 8.03-7.83 (m, 1H), 7.77 (t, J=6.0 Hz, 1H), 7.30 (d, J=7.6 Hz, 1H), 3.72 (d, J=7.2 Hz, 2H), 2.76 (dd, J=12.8, 6.8 Hz, 2H), 2.15 (dt, J=13.2, 6.8 Hz, 1H), 1.37-1.21 (m, 2H), 1.18-1.10 (m, 2H), 0.93 (s, 3H), 0.91 (s, 3H), 0.68 (t, J=7.2 Hz, 3H).

Example 117: Synthesis of N-cyclohexyl-1-isobutyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide

[0425] ##STR00135##

[0426] The synthesis can refer to Example 67. .sup.1H NMR (400 MHz, d-DMSO) 8.70 (d, J=8.4 Hz, 1H), 8.12 (d, J=7.2 Hz, 1H), 8.08 (d, J=7.6 Hz, 1H), 8.08-7.93 (m, 1H), 7.85 (t, J=6.0 Hz, 1H), 7.30 (d, J=7.6 Hz, 1H), 3.71 (d, J=7.2 Hz, 2H), 2.94 (s, 1H), 2.08-1.96 (m, 1H), 1.47-1.36 (m, 5H), 1.05-0.90 (m, 5H).

Example 118: Synthesis of N-cyclohexyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide

[0427] ##STR00136##

[0428] The synthesis can refer to Example 67. .sup.1H NMR (400 MHz, d-DMSO) δ 11.10 (s, 1H), 8.69 (d, J=8.4 Hz, 1H), 8.09 (d, J=6.8 Hz, 1H), 8.04 (d, J=7.6 Hz, 1H), 7.96-7.87 (m, 1H), 7.81 (d, J=7.6 Hz, 1H), 7.04 (d, J=7.6 Hz, 1H), 2.93 (s, 1H), 1.58-1.30 (m, 5H), 1.06-0.98 (m, 5H).

Example 119: Synthesis of N-(3-acetylphenyl)-1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide

[0429] ##STR00137##

[0430] The synthesis can refer to Example 67. .sup.1H NMR (400 MHz, d-DMSO) δ 10.82 (s, 1H), 8.70 (d, J=8.4 Hz, 1H), 8.19 (d, J=7.6 Hz, 1H), 8.13 (d, J=6.8 Hz, 1H), 7.95 (t, J=7.6 Hz, 1H), 7.65-7.46 (m, 2H), 7.39-7.24 (m, 3H), 3.88 (q, J=6.8 Hz, 2H), 2.45 (s, 3H), 1.22 (t, J=7.2 Hz, 3H). .sup.13C NMR (500 MHz, d-DMSO) δ 197.1, 166.6, 143.4, 138.0, 137.5, 133.5, 130.7, 129.6, 128.9, 127.4, 126.0, 125.2, 124.8, 123.9, 123.8, 123.2, 117.7, 103.9, 34.6, 26.5, 13.5.

Example 120: Synthesis of N-(4-chlorophenyl)-1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide

[0431] ##STR00138##

[0432] The synthesis can refer to Example 67. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.54 (d, J=8.4 Hz, 1H), 8.09 (d, J=7.6 Hz, 2H), 7.79 (t, J=7.6 Hz, 1H), 7.13 (d, J=8.4 Hz, 2H), 6.94 (d, J=8.4 Hz, 2H), 6.90 (s, 1H), 6.85 (d, J=7.6 Hz, 1H), 3.95 (q, J=7.2 Hz, 2H), 1.36 (t, J=7.2 Hz, 3H).

Example 121: Synthesis of 1-ethyl-2-oxo-N-phenyl-1,2-dihydrobenzo[cd]indole-6-sulfonamide

[0433] ##STR00139##

[0434] The synthesis can refer to Example 67. .sup.1H NMR (400 MHz, d-DMSO) δ 10.56 (s, 1H), 8.69 (d, J=8.4 Hz, 1H), 8.16-8.11 (m, 2H), 7.93 (t, J=7.6 Hz, 1H), 7.26 (d, J=7.6 Hz, 1H), 7.16 (t, J=7.6 Hz, 2H), 7.04 (d, J=7.6 Hz, 2H), 6.94 (t, J=7.2 Hz, 1H), 3.89 (q, J=7.2 Hz, 2H), 1.23 (t, J=7.2 Hz, 3H).

Example 122: Synthesis of N-(2-chlorophenyl)-1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide

[0435] ##STR00140##

[0436] The synthesis can refer to Example 67. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.51 (d, J=8.4 Hz, 1H), 8.14 (d, J=7.6 Hz, 1H), 8.07 (d, J=7.2 Hz, 1H), 7.77 (t, J=7.6 Hz, 1H), 7.66 (d, J=8.4 Hz, 1H), 7.22 (t, J=7.6 Hz, 1H), 7.13 (d, J=7.6 Hz, 2H), 6.99 (t, J=7.6 Hz, 1H), 6.84 (d, J=7.6 Hz, 1H), 3.94 (q, J=7.2 Hz, 2H), 1.35 (t, J=7.2 Hz, 3H).

Example 123: Synthesis of N-(3-chlorophenyl)-1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide

[0437] ##STR00141##

[0438] The synthesis can refer to Example 67. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.55 (d, J=8.4 Hz, 1H), 8.16 (d, J=7.6 Hz, 1H), 8.10 (d, J=7.2 Hz, 1H), 7.80 (t, J=7.6 Hz, 1H), 7.16-7.01 (m, 3H), 6.93-6.82 (m, 2H), 3.96 (d, J=7.2 Hz, 2H), 1.37 (t, J=7.2 Hz, 3H).

Example 124

[0439] Activity test in vitro: the compounds of the present invention were conducted the AlphaScreen assay to confirm the ability of a ligand to disrupt the interaction of BRD(1) and its SRC1-4 peptide.

[0440] 1. Purpose of AlphaScreen Assay

[0441] To test the ability of the compounds of the present invention inhibit BRD(1) protein.

[0442] 2. Experimental Materials

[0443] BRD4(1) protein, 500 nM; buffer, (10×) MOPS (500 mM), CHAPS (0.5 mM), NaF (500 mM), BSA (1 mg/mL), PH (7.4); streptavidin donor beads 50 μg/mL, nickel acceptor beads 50 μg/mL, BRD4(1) ligand, biotinylated SRC1-4 peptide, H4KAc4-botin (SGRG{Lys-Ac}GG{Lys-Ac}GLG{Lys-Ac}GGA{Lys-Ac} RHR{Lys(biotin)}) 50 nM. 150 μL mix system: BRD4(1) protein, 15 μL; buffer, 15 μL; ddH.sub.2O, 15 μL; compound, 15 μL; streptavidin donor beads, 15 μL; nickel acceptor beads, 15 μL; positive compound, (+)-JQ1.

[0444] 3. Protocol

[0445] The BRD4(1) protein and biotinylated SRC1-4 peptide were added in ddH2O and buffer. The reaction mixture was incubated at 20° C. for 1.5 h, streptavidin donor beads and nickel acceptor beads was added. The reaction mixture was incubated at 20° C. in dark for 1 h. The reaction mixture (40 μL) was transferred to 384 well plates, and tested by PE Envison2104 multifunctional detection of microplate reader. Excitation wavelength, 680 nM; Emission wavelength, 520-620 nM.

Example 125

[0446] Activity test in vitro: the compounds of the present invention were conducted the TSA assay to determine the thermodynamic stability of BRD4(1).

[0447] 1. Purpose of TSA Assay

[0448] To test the ability of the compounds of the present invention inhibit BRD(1) protein.

[0449] 2. Experimental Materials

[0450] BRD4(1) protein, 100 μM; compounds, 400 μM, buffer, (10×) MOPS (50 mM), NaCl (150 mM), glycerin 10%, PH (7.5); Sypro Orange Protein Gel Stain (500×). Mix system: BRD4(1) protein, 2 μL; Sypro Orange Protein Gel Stain (500×), 2 μL; compound, 10 μL; buffer, 2 μL; ddH.sub.2O, 2 μL, positive compound, (+)-JQ1.

[0451] 3. Protocol

[0452] The 10 μL reaction mix was added to 96-well PCR plates. SYPRO Orange (Sigma) was added as a fluorescence probe at a dilution of 1:1000 and incubated with compounds on ice for 30 min. The total DMSO concentration was less than 2%. The TSA was carried out using the Bio-Rad CFX96 Real-Time PCR System. The temperature was raised at a step of 0.5° C. per minute from 30° C. to 80° C. The fluorescence readings were recorded at a 0.5° C. interval, and obtained the ΔTm.

[0453] The results come from the AlphaScreen assay and TSA assay in table 1-4.

TABLE-US-00001 TABLE 1 The activities of compounds of formula I AlphaScreen TSA Compounds (μM) ΔTm (° C.) (+)-JQ1 0.18 11.5 Example 1 0.53 7.4 Example 2 0.51 7.1 Example 3 1.08 7.5 Example 4 0.52 8.5 Example 5 0.14 10 Example 6 1.70 6.5 Example 7 0.84 6.0 Example 8 0.24 9.5 Example 9 0.41 9.5 Example 10 1.68 8 Example 11 2.08 5.5 Example 12 5.59 6.5 Example 13 6.29 6.0 Example 14 5.71 6.5 Example 15 6.05 3.0 Example 16 4.00 5.0 Example 17 2.27 7.0 Example 18 0.56 9.0 Example 19 0.47 9.5 Example 20 1.25 7.0 Example 21 0.34 8.1 Example 22 2.56 5.7 Example 23 3.7 2.4 Example 24 1.84 4.2 Example 25 8.17 4.2 Example 26 12.97 3 Example 27 3.13 4.2 Example 28 3.51 5.7 Example 29 2.73 6.3 Example 30 0.97 7.2 Example 31 0.41 9 Example 32 3.53 4 Example 33 3.87 5 Example 34 >20 2.4 Example 35 2.55 4.5 Example 36 7.31 1.2 Example 37 10.71 2.1 Example 38 >20 3.9 Example 39 >20 3.3 Example 40 >20 1.8 Example 41 5.64 4.5 Example 42 4.15 6 Example 43 4.81 3.6 Example 44 >20 3 Example 45 0.85 4.5

TABLE-US-00002 TABLE 2 The activities of compounds of formula II Alphascreen TSA(° C.) Compounds (μM) ΔTm (° C.) Example 46 >20 3 Example 47 >20 0 Example 48 >20 3.6 Example 49 >20 0 Example50 >20 1 Example 51 >20 2.4 Example 52 14.51 4 Example 53 >20 0 Example 54 >20 0 Example 55 >20 0

TABLE-US-00003 TABLE 3 The activities of compounds of formula III Alphascreen TSA(° C.) Compounds (μM) ΔTm (° C.) Example 56 >20 0 Example 57 11.18 4 Example 58 2.7 2 Example 59 >20 1 Example 60 1.77 2 Example 61 >20 2 Example 62 2.49 2

TABLE-US-00004 TABLE 4 The activities of compounds of formula IV Alphascreen TSA(° C.) Compounds (μM) ΔTm (° C.) Example 63 3.18 5 Example 64 1.94 5 Example 65 20.7 2.5 Example 66 5.90 4 Example 67 6.69 3 Example 68 14.45 3.5 Example 69 13.92 3.5 Example 70 7.55 3.5 Example 71 1.69 5.5 Example 72 0.21 7 Example 73 7.70 2 Example 74 2.58 4 Example 75 4.7 3.5 Example 76 1.04 6.8 Example 77 1.53 4.5 Example 78 0.44 8 Example 79 >20 2.4 Example 80 >20 1.7 Example 81 >20 2.4 Example 82 1.16 6.2 Example 83 12.03 2.4 Example 84 4.10 3.5 Example 85 4.84 3.4 Example 86 2.47 1.8 Example 87 >20 1.8 Example 88 >20 0.5 Example 89 >20 3.5 Example 90 >20 0.7 Example 91 3.44 3.9 Example 92 1.67 6.1 Example 93 >20 0.2 Example 94 1.09 6.1 Example 95 1.50 5.5 Example 96 >20 1 Example 97 0.13 9 Example 98 1.12 6 Example 99 0.60 8 Example 100 0.31 9 Example 101 4.17 5 Example 102 >20 2 Example 103 >20 3 Example 104 >20 3 Example 105 >20 1.7 Example 106 >20 2 Example 107 0.45 7 Example 108 1.21 7 Example 109 8.27 1 Example 110 >20 1 Example 111 15.49 5 Example 112 5.21 4 Example 113 >20 3 Example 114 >20 3 Example 115 >20 1 Example 116 >20 0 Example 117 >20 0 Example 118 >20 2 Example 119 5.50 3 Example 120 3.38 3.3 Example 121 1.09 7.5 Example 122 1.89 5.1 Example 123 3.52 3.3

[0454] The compounds of the present invention, especially Examples 1, 2, 3, 4, 5, 8, 9, 10, 17, 18, 19, 20, 21, 30, 31, 78, 97, 99 and 100, showed similar potent when compared (+)-JQ1. The compounds of the present invention were chemically stable and easily prepared when compared positive compound. The use of a compound according to any one of Examples 1-123 in the manufacture of a medicament for the treatment of a disease or a condition for which a BET bromodomain inhibitor is indicated. These data indicated the compounds of the present invention may lead to a new therapeutics to treat cancera, cellar proliferative disorders, inflammatory conditions, autoimmune disorders, sepsis, or viral infections.

[0455] The embodiments above described illustrative of several embodiments of the invention, and these illusion are specific and detailed, but not to be construed as limiting the scope of the invention. It should be noted that various modifications and improvements can be made by those skilled in the art without departing from the spirit of the invention, which are within the scope of the present invention. Accordingly, the scope of protection of the present invention should be determined by the appended claims.