Camptothecin prodrug and its pharmaceutical composition

Abstract

Disclosed are compounds of formula (I), stereoisomers of the compounds of formula (I), and cis-trans isomers: [Chemical 1] TIFF2025518808000171.tif106170wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 , R 11 , R 12 , R 13 , R 14 , R 15 are as defined in the present disclosure.

Description

Detailed Description of the Invention

[0001] [Cross - References to Related Applications] This disclosure claims all the benefits of Chinese Patent Application No. 202210602187.7, entitled "Camptothecin Prodrug and Its Pharmaceutical Composition", filed with the State Intellectual Property Office of the People's Republic of China before May 30, 2022, and the entire content thereof is incorporated herein by reference.

[0002] [Field] This disclosure generally relates to the fields of organic chemistry and drug discovery chemistry. [Background] Cancer is a major cause of death to human health. According to the latest global cancer burden data in 2020 published by the International Agency for Research on Cancer (IARC) of the World Health Organization, the number of new cancer patients worldwide in 2020 was 19.29 million, of which 4.57 million were new cancer patients in China. The number of cancer deaths worldwide in 2020 was 9.96 million, of which 3 million were cancer deaths in China. The number of new cancer patients and deaths in China are both at the highest levels in the world. Chemotherapy is still one of the main treatment methods for cancer, but conventional chemotherapy drugs lack tumor cell specificity and have strong toxicity to normal cells while killing tumor cells, which may cause serious systemic toxicity and side effects. In addition, many chemotherapy drugs have problems such as low water solubility and low bioavailability, which limit the clinical application of chemotherapy drugs. Carbohydrates, as one of the basic substances of life, are widely used in the design of prodrugs. Glycosyl modification can not only significantly improve the water solubility of drugs, but also achieve the targeting of chemotherapy drugs to tumor cells through sugar transporters, glycosidases, etc. Prodrug modification is an effective strategy to improve the tumor targeting of chemotherapy drugs, reduce the side effects of drugs, and improve the anti - tumor activity.

[0003] Camptothecin is an alkaloid antitumor drug extracted from the bark and fruits of Camptotheca involucrata by American chemists Wall et al. in 1966. Camptothecin exhibits antitumor activity at nanomolar concentrations and has excellent therapeutic effects on various malignant tumors, such as gastrointestinal tumors, leukemia, and bladder cancer. However, camptothecin has very low water solubility (2.5 μg / ml). Clinically, the treatment with camptothecin causes severe toxic side effects, such as myelosuppression, diarrhea, vomiting, and hematuria, and the clinical use faces problems such as high toxicity, low selectivity, and low water solubility. The development of camptothecin derivatives and prodrugs of camptothecin derivatives is ongoing.

[0004] Prijovich et al. used 5,6-dihydro-4H-benzo[de]quinoline camptothecin (BQC) as a lead compound and conjugated glucuronic acid to the 10-hydroxy group to prepare the saccharide conjugate BQC-G. The water solubility of BQC-G is significantly improved compared to BQC at physiological pH.

[0005] 9ACG is a carbohydrate conjugate of the 9-aminocamptothecin (9AC) lead compound. Toxicity tests indicate that a dose of 50 mg / kg has reached the lethal dose of 9ACG for mice.

[0006] The use of glycosidases to modify camptothecin and prodrugs of camptothecin derivatives continues to improve. [Abstract] In one aspect, the present disclosure relates to a compound of formula (I), as well as stereoisomers and cis-trans isomers of the compound of formula (I):

[0007] [Chemical formula]

[0008] wherein, R1 is hydrogen, C1-C8 hydrocarbyl, -Na, -Li, -K, -Cs, -NH4 + , -NH2 + R 13 R 14 , -NH + R 13 R 14 R 15 , -NH + 3R 13 , and is selected from the group consisting of natural or non-natural amino acids; R2 is selected from the group consisting of hydrogen and C1-C8 hydrocarbyl; R3 is one or more substituents at any substitution position selected from the group consisting of hydrogen, halogen, C1-C8 hydrocarbyl, C1-C8 hydrocarbyloxy, cyano, nitro, amino, aryl, arylhydrocarbyl, and C1-C4 hydrocarbyl-substituted amino; R4 is C1-C9 alkylidene, C1-C8 alkylideneoxy, C1-C8 hydrocarbyl-substituted or unsubstituted C3-C8 heteroaryl, C1-C8 hydrocarbyl-substituted or unsubstituted C3-C 15 aryl, -(CH2R7) n , -(R8) m , C1-C9 alkylidene-arylidene, C1-C9 alkylidene-arylidene-C1-C9 alkyldiene, C1-C9 alkylidene-arylidene-arylidene, C1-C9 alkylidene-heteroarylidene-C1-C9 alkylidene, and an amino acid peptide chain, and is selected from the group consisting of: wherein the amino acid peptide chain is composed of a combination of natural or non-natural amino acids, and the length of the peptide chain is from 1 to 100 peptides, preferably from 1 to 50 peptides, more preferably from 1 to 20 peptides; R5 is selected from the group consisting of hydrogen and C1-C8 hydrocarbyl; R6 is selected from the group consisting of hydrogen, C1-C8 hydrocarbyl, C1-C8 hydrocarbylideneamino(C1-C4 hydrocarbyl)2, C1-C8 hydrocarbylidene thio C1-C8 hydrocarbyl, and C1-C9 alkylidene-oxy-C1-C9 alkyl; R5 and R6 may form a ring, and when R5 and R6 form a ring, the ring may be a 5-membered ring or a 6-membered ring; R7 is selected from hydrogen, C1-C8 hydrocarbylideneoxy, amino C1-C8 hydrocarbylidene, thio C1-C8 hydrocarbylidene, and oxy C1-C8 hydrocarbylidene; n is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, and 9; when n is 0, (CH2R7) n represents a covalent bond; R8 is carbonylamino, where the amino may be substituted with C1-C8 hydrocarbyl or arylhydrocarbyl, C1-C8 hydrocarbylideneamino C1-C8 hydrocarbylidene, C1-C8 hydrocarbylidene thio C1-C8 hydrocarbylidene, or C1-C8 hydrocarbylideneoxy C1-C8 hydrocarbylidene; m is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, and 9; when m is 0, -(R8) m represents a covalent bond; R9 is one or more substituents at any position selected from the group consisting of hydrogen, halogen, cyano, C1-C8 hydrocarbyl, C1-C8 alkoxy, and C5-C 12 aryl; R 10 is one or more substituents at any position selected from the group consisting of hydrogen, halogen, cyano, C1-C8 hydrocarbyl, C1-C8 alkoxy, and C5-C 12 aryl; R 11 is hydrogen, -Na, -Li, -K, -Cs, -NH4 + , -NH2 + R 13 R 14 , -NH + R 13 R 14 R 15 , -NH3 + R 13 and is selected from the group consisting of natural or non-natural amino acids; R 12is hydrogen, -Na, -Li, -K, -Cs, -NH4 + , -NH2 + R 13 R 14 , -NH + R 13 R 14 R 15 , -NH3 + R 13 and is selected from the group consisting of natural or unnatural amino acids; R 13 is hydrogen, C1-C8 hydrocarbyl, C1-C8 cyclo hydrocarbyl, C5-C 18 aryl, and C5-C 18 heteroaryl; R 14 is hydrogen, C1-C8 hydrocarbyl, C1-C8 cyclo hydrocarbyl, C5-C 18 aryl, and C5-C 18 heteroaryl; R 15 is hydrogen, C1-C8 hydrocarbyl, C1-C8 cyclo hydrocarbyl, C5-C 18 aryl, and C5-C 18 heteroaryl; and R1, R 11 , and R 12 the natural or unnatural amino acids in are selected from the group consisting of glycine, alanine, valine, leucine, isoleucine, methionine (methionine), proline, tryptophan, serine, tyrosine, cysteine, phenylalanine, asparagine, glutamine, threonine, aspartic acid, glutamic acid, lysine, arginine, histidine, selenocysteine, sarcosine, pyrrolysine, and homoalanine.

[0009] In other aspects, the present disclosure relates to a pharmaceutical composition comprising a compound of formula (I) or a stereoisomer of a compound of formula (I), and a pharmaceutically acceptable carrier:

[0010]

Chemical formula

[0011] In the formula, R1 is selected from the group consisting of hydrogen, C1-C8 hydrocarbyl, -Na, -Li, -K, -Cs, -NH4 + , -NH2 + R 13 R 14 , -NH + R 13 R 14 R 15 , -NH + 3R 13 , and is selected from the group consisting of natural or non-natural amino acids; R2 is selected from the group consisting of hydrogen and C1-C8 hydrocarbyl; R3 is one or more substituents at any substitution position selected from the group consisting of hydrogen, halogen, C1-C8 hydrocarbyl, C1-C8 hydrocarbyloxy, cyano, nitro, amino, aryl, arylhydrocarbyl, and C1-C4 hydrocarbyl-substituted amino; R4 is selected from the group consisting of C1-C9 alkylidene, C1-C8 alkylideneoxy, C1-C8 hydrocarbyl-substituted or unsubstituted C3-C8 heteroaryl, C1-C8 hydrocarbyl-substituted or unsubstituted C3-C 15 aryl, -(CH2R7) n , -(R8) m , C1-C9 alkylidene-arylidene, C1-C9 alkylidene-arylidene-C1-C9 alkyl diene, C1-C9 alkylidene-arylidene-arylidene, C1-C9 alkylidene-heteroarylidene-C1-C9 alkylidene, and amino acid peptide chains; wherein the amino acid peptide chain is composed of a combination of natural or non-natural amino acids, and the length of the peptide chain is from 1 to 100 peptides, preferably from 1 to 50 peptides, more preferably from 1 to 20 peptides; R5 is selected from the group consisting of hydrogen and C1-C8 hydrocarbyl; R6 is selected from the group consisting of hydrogen, C1-C8 hydrocarbyl, C1-C8 hydrocarbylideneamino(C1-C4 hydrocarbyl)2, C1-C8 hydrocarbylidene thio C1-C8 hydrocarbyl, and C1-C9 alkylidene-oxy-C1-C9 alkyl; R5 and R6 may form a ring, and when R5 and R6 form a ring, the ring may be a 5-membered ring or a 6-membered ring; R7 is selected from the group consisting of hydrogen, C1-C8 hydrocarbylideneoxy, amino C1-C8-hydrocarbylidene, thio C1-C8-hydrocarbylidene, and oxy C1-C8 hydrocarbylidene; n is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, and 9; when n is 0, (CH2R7) n represents a covalent bond; R8 is carbonylamino, where the amino may be substituted with C1-C8 hydrocarbyl or arylhydrocarbyl, C1-C8 hydrocarbylideneamino C1-C8 hydrocarbylidene, C1-C8 hydrocarbylidene thio C1-C8 hydrocarbylidene, or C1-C8 hydrocarbylideneoxy C1-C8 hydrocarbylidene; m is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, and 9; when m is 0, -(R8) m represents a covalent bond; R9 is one or more substituents at any position selected from the group consisting of hydrogen, halogen, cyano, C1-C8 hydrocarbyl, C1-C8 alkoxy, and C5-C 12 aryl; R 10 is one or more substituents at any position selected from the group consisting of hydrogen, halogen, cyano, C1-C8 hydrocarbyl, C1-C8 alkoxy, and C5-C 12 aryl; R 11 is hydrogen, -Na, -Li, -K, -Cs, -NH4 + -NH2 + R 13 R 14 -NH+ R 13 R 14 R 15 、 -NH3 + R 13 、 and selected from the group consisting of natural or non-natural amino acids; R 12 is hydrogen, -Na, -Li, -K, -Cs, -NH4 + 、 -NH2 + R 13 R 14 、 -NH + R 13 R 14 R 15 、 -NH3 + R 13 、 and selected from the group consisting of natural or non-natural amino acids; R 13 is hydrogen, C1-C8 hydrocarbyl, C1-C8 cyclo hydrocarbyl, C5-C 18 aryl, and C5-C 18 heteroaryl selected from the group consisting of; R 14 is hydrogen, C1-C8 hydrocarbyl, C1-C8 cyclo hydrocarbyl, C5-C 18 aryl, and C5-C 18 heteroaryl selected from the group consisting of; R 15 is hydrogen, C1-C8 hydrocarbyl, C1-C8 cyclo hydrocarbyl, C5-C 18 aryl, and C5-C 18 heteroaryl selected from the group consisting of; and R1, R 11 、 and R 12 The natural or non-natural amino acids in are selected from the group consisting of glycine, alanine, valine, leucine, isoleucine, methionine (methionine), proline, tryptophan, serine, tyrosine, cysteine, phenylalanine, asparagine, glutamine, threonine, aspartic acid, glutamic acid, lysine, arginine, histidine, selenocysteine, sarcosine, pyrrolysine, and homoalanine.

[0012] In a further aspect, the present disclosure relates to the use of a compound of formula (I) or a stereoisomer of a compound of formula (I) in the manufacture of a medicament for the treatment of a tumor or cancer, or the use of a pharmaceutical composition comprising a compound of formula (I) or a stereoisomer of a compound of formula (I) and a pharmaceutically acceptable carrier:

[0013]

Chemical formula

[0014] wherein, R1 is hydrogen, C1-C8 hydrocarbyl, -Na, -Li, -K, -Cs, -NH4 + , -NH2 + R 13 R 14 , -NH + R 13 R 14 R 15 , -NH + 3R 13 , and is selected from the group consisting of natural or non-natural amino acids; R2 is selected from the group consisting of hydrogen and C1-C8 hydrocarbyl; R3 is one or more substituents at any substitution position selected from the group consisting of hydrogen, halogen, C1-C8 hydrocarbyl, C1-C8 hydrocarbyloxy, cyano, nitro, amino, aryl, arylhydrocarbyl, and C1-C4 hydrocarbyl-substituted amino; R4 is C1-C9 alkylidene, C1-C8 alkylideneoxy, C1-C8 hydrocarbyl-substituted or unsubstituted C3-C8 heteroaryl, C1-C8 hydrocarbyl-substituted or unsubstituted C3-C 15 aryl, -(CH2R7) n , -(R8) m, selected from the group consisting of C1-C9 alkylidene-arylidene, C1-C9 alkylidene-arylidene-C1-C9 alkyldiene, C1-C9 alkylidene-arylidene-arylidene, C1-C9 alkylidene-heteroarylidene-C1-C9 alkylidene, and amino acid peptide chains; wherein the amino acid peptide chain is composed of a combination of natural or non-natural amino acids, and the length of the peptide chain is from 1 to 100 peptides, preferably from 1 to 50 peptides, more preferably from 1 to 20 peptides; R5 is selected from the group consisting of hydrogen and C1-C8 hydrocarbyl; R6 is selected from the group consisting of hydrogen, C1-C8 hydrocarbyl, C1-C8 hydrocarbylideneamino(C1-C4 hydrocarbyl)2, C1-C8 hydrocarbylidene thio C1-C8 hydrocarbyl, and C1-C9 alkylidene-oxy-C1-C9 alkyl; R5 and R6 may form a ring, and when R5 and R6 form a ring, the ring may be a 5-membered ring or a 6-membered ring; R7 is selected from the group consisting of hydrogen, C1-C8 hydrocarbylideneoxy, amino C1-C8-hydrocarbylidene, thio C1-C8-hydrocarbylidene, and oxy C1-C8 hydrocarbylidene; n is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, and 9; when n is 0, (CH2R7) n represents a covalent bond; R8 is carbonylamino, where the amino may be substituted with C1-C8 hydrocarbyl or arylhydrocarbyl, C1-C8 hydrocarbylideneamino C1-C8 hydrocarbylidene, C1-C8 hydrocarbylidene thio C1-C8 hydrocarbylidene, or C1-C8 hydrocarbylideneoxy C1-C8 hydrocarbylidene; m is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, and 9; when m is 0, -(R8) m represents a covalent bond; R9 is one or more substituents at any position selected from the group consisting of hydrogen, halogen, cyano, C1-C8 hydrocarbyl, C1-C8 alkoxy, and C5-C 12 aryl; R 10 is one or more substituents at any position selected from the group consisting of hydrogen, halogen, cyano, C1-C8 hydrocarbyl, C1-C8 alkoxy, and C5-C 12 aryl; R 11 is hydrogen, -Na, -Li, -K, -Cs, -NH4 + , -NH2 + R 13 R 14 , -NH + R 13 R 14 R 15 , -NH3 + R 13 , and is selected from the group consisting of natural or non-natural amino acids; R 12 is hydrogen, -Na, -Li, -K, -Cs, -NH4 + , -NH2 + R 13 R 14 , -NH + R 13 R 14 R 15 , -NH3 + R 13 , and is selected from the group consisting of natural or non-natural amino acids; R 13 is hydrogen, C1-C8 hydrocarbyl, C1-C8 cyclo hydrocarbyl, C5-C 18 aryl, and C5-C 18 heteroaryl; R 14 is hydrogen, C1-C8 hydrocarbyl, C1-C8 cyclo hydrocarbyl, C5-C 18 aryl, and C5-C 18 heteroaryl; R 15 is hydrogen, C1-C8 hydrocarbyl, C1-C8 cyclo hydrocarbyl, C5-C 18Aryl, and C5-C 18 selected from the group consisting of heteroaryl; and R1, R 11 , and R 12 The natural or non-natural amino acids in are selected from the group consisting of glycine, alanine, valine, leucine, isoleucine, methionine (methionine), proline, tryptophan, serine, tyrosine, cysteine, phenylalanine, asparagine, glutamine, threonine, aspartic acid, glutamic acid, lysine, arginine, histidine, selenocysteine, sarcosine, pyrrolysine, and homoalanine.

[0015] In some embodiments, exemplary examples of tumors or cancers include, but are not limited to, colorectal cancer, lung cancer, cervical cancer, ovarian cancer, gastric cancer, esophageal cancer, breast cancer, pancreatic cancer, bladder cancer, liver cancer, gastric cancer, colon cancer, head and neck cancer, uterine cancer, urothelial cancer, osteosarcoma, sarcoma, kidney cancer, melanoma, prostate cancer, glioma, glioma and leukemia.

[0016] In yet other aspects, the present disclosure relates to a method of treating a tumor or cancer, comprising administering to a subject in need of treatment a therapeutically effective amount of a compound of formula (I) or a stereoisomer of a compound of formula (I), or a compound of formula (I) or a stereoisomer of a compound of formula (I), and a pharmaceutical composition comprising a pharmaceutically acceptable carrier:

[0017]

Chemical formula

[0018] Wherein, R1 is hydrogen, C1-C8 hydrocarbyl, -Na, -Li, -K, -Cs, -NH4 + , -NH2 + R 13 R 14 , -NH + R 13 R 14 R 15 , -NH + 3R 13and is selected from the group consisting of natural or non-natural amino acids; R2 is selected from the group consisting of hydrogen and C1-C8 hydrocarbyl; R3 is one or more substituents at any substitution position selected from the group consisting of hydrogen, halogen, C1-C8 hydrocarbyl, C1-C8 hydrocarbyloxy, cyano, nitro, amino, aryl, arylhydrocarbyl, and C1-C4 hydrocarbyl-substituted amino; R4 is C1-C9 alkylidene, C1-C8 alkylideneoxy, C1-C8 hydrocarbyl-substituted or unsubstituted C3-C8 heteroaryl, C1-C8 hydrocarbyl-substituted or unsubstituted C3-C 15 aryl, -(CH2R7) n , -(R8) m , C1-C9 alkylidene-arylidene, C1-C9 alkylidene-arylidene-C1-C9 alkyldiene, C1-C9 alkylidene-arylidene-arylidene, C1-C9 alkylidene-heteroarylidene-C1-C9 alkylidene, and amino acid peptide chains; wherein the amino acid peptide chain is composed of a combination of natural or non-natural amino acids, and the length of the peptide chain is from 1 to 100 peptides, preferably from 1 to 50 peptides, more preferably from 1 to 20 peptides; R5 is selected from the group consisting of hydrogen and C1-C8 hydrocarbyl; R6 is selected from the group consisting of hydrogen, C1-C8 hydrocarbyl, C1-C8 hydrocarbylideneamino(C1-C4 hydrocarbyl)2, C1-C8 hydrocarbylidene thio C1-C8 hydrocarbyl, and C1-C9 alkylidene-oxy-C1-C9 alkyl; R5 and R6 may form a ring, and when R5 and R6 form a ring, the ring may be a 5-membered ring or a 6-membered ring; R7 is selected from hydrogen, C1-C8 hydrocarbylideneoxy, amino C1-C8-hydrocarbylidene, thio C1-C8-hydrocarbylidene, and oxy C1-C8 hydrocarbylidene; n is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, and 9; when n is 0, (CH2R7) n represents a covalent bond; R8 is carbonylamino, where the amino may be substituted with C1-C8 hydrocarbyl or arylhydrocarbyl, C1-C8 hydrocarbylideneamino C1-C8 hydrocarbylidene, C1-C8 hydrocarbylidene thio C1-C8 hydrocarbylidene, or C1-C8 hydrocarbylideneoxy C1-C8 hydrocarbylidene; m is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, and 9; when m is 0, -(R8) m represents a covalent bond; R9 is one or more substituents at any position selected from the group consisting of hydrogen, halogen, cyano, C1-C8 hydrocarbyl, C1-C8 alkoxy, and C5-C 12 aryl; R 10 is one or more substituents at any position selected from the group consisting of hydrogen, halogen, cyano, C1-C8 hydrocarbyl, C1-C8 alkoxy, and C5-C 12 aryl; R 11 is hydrogen, -Na, -Li, -K, -Cs, -NH4 + -NH2 + R 13 R 14 -NH + R 13 R 14 R 15 -NH3 + R 13 and is selected from the group consisting of natural or non-natural amino acids; R 12 is hydrogen, -Na, -Li, -K, -Cs, -NH4 + -NH2 + R 13 R 14 -NH + R 13 R 14 R 15 -NH3 + R 13and is selected from the group consisting of natural or non-natural amino acids; R 13 is hydrogen, C1-C8 hydrocarbyl, C1-C8 cyclo hydrocarbyl, C5-C 18 aryl, and C5-C 18 heteroaryl, and is selected from the group consisting of; R 14 is hydrogen, C1-C8 hydrocarbyl, C1-C8 cyclo hydrocarbyl, C5-C 18 aryl, and C5-C 18 heteroaryl, and is selected from the group consisting of; R 15 is hydrogen, C1-C8 hydrocarbyl, C1-C8 cyclo hydrocarbyl, C5-C 18 aryl, and C5-C 18 heteroaryl, and is selected from the group consisting of; and R1, R 11 , and R 12 the natural or non-natural amino acids in are selected from the group consisting of glycine, alanine, valine, leucine, isoleucine, methionine (methionine), proline, tryptophan, serine, tyrosine, cysteine, phenylalanine, asparagine, glutamine, threonine, aspartic acid, glutamic acid, lysine, arginine, histidine, selenocysteine, sarcosine, pyrrolysine, and homoalanine.

[0019] In some embodiments, exemplary examples of tumors or cancers include, but are not limited to, colorectal cancer, lung cancer, cervical cancer, ovarian cancer, gastric cancer, esophageal cancer, breast cancer, pancreatic cancer, bladder cancer, liver cancer, gastric cancer, colon cancer, head and neck cancer, uterine cancer, urothelial cancer, osteosarcoma, sarcoma, kidney cancer, melanoma, prostate cancer, glioma, glioblastoma, and leukemia.

[0020] In yet other aspects, the present disclosure relates to a process for preparing a compound of formula (I):

[0021]

Chemical formula

[0022] In the formula, R1 is selected from the group consisting of hydrogen, C1-C8 hydrocarbyl, -Na, -Li, -K, -Cs, -NH4 + , -NH2 + R 13 R 14 , -NH + R 13 R 14 R 15 , -NH + 3R 13 , and is selected from the group consisting of natural or non-natural amino acids; R2 is selected from the group consisting of hydrogen and C1-C8 hydrocarbyl; R3 is one or more substituents at any substitution position selected from the group consisting of hydrogen, halogen, C1-C8 hydrocarbyl, C1-C8 hydrocarbyloxy, cyano, nitro, amino, aryl, arylhydrocarbyl, and C1-C4 hydrocarbyl-substituted amino; R4 is C1-C9 alkylidene, C1-C8 alkylideneoxy, C1-C8 hydrocarbyl-substituted or unsubstituted C3-C8 heteroaryl, C1-C8 hydrocarbyl-substituted or unsubstituted C3-C 15 aryl, -(CH2R7) n , -(R8) m , C1-C9 alkylidene-arylidene, C1-C9 alkylidene-arylidene-C1-C9 alkyldiene, C1-C9 alkylidene-arylidene-arylidene, C1-C9 alkylidene-heteroarylidene-C1-C9 alkylidene, and an amino acid peptide chain; where the amino acid peptide chain is composed of a combination of natural or non-natural amino acids, and the length of the peptide chain is from 1 to 100 peptides, preferably from 1 to 50 peptides, more preferably from 1 to 20 peptides; R5 is selected from the group consisting of hydrogen and C1-C8 hydrocarbyl; R6 is selected from the group consisting of hydrogen, C1-C8 hydrocarbyl, C1-C8 hydrocarbylideneamino(C1-C4 hydrocarbyl)2, C1-C8 hydrocarbylidene thio C1-C8 hydrocarbyl, and C1-C9 alkylidene-oxy-C1-C9 alkyl; R5 and R6 may form a ring, and when R5 and R6 form a ring, the ring may be a 5-membered ring or a 6-membered ring; R7 is selected from the group consisting of hydrogen, C1-C8 hydrocarbylideneoxy, amino C1-C8-hydrocarbylidene, thio C1-C8-hydrocarbylidene, and oxy C1-C8 hydrocarbylidene; n is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, and 9; when n is 0, (CH2R7) n represents a covalent bond; R8 is carbonylamino, where the amino may be substituted with C1-C8 hydrocarbyl or arylhydrocarbyl, C1-C8 hydrocarbylideneamino C1-C8 hydrocarbylidene, C1-C8 hydrocarbylidene thio C1-C8 hydrocarbylidene, or C1-C8 hydrocarbylideneoxy C1-C8 hydrocarbylidene; m is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, and 9; when m is 0, -(R8) m represents a covalent bond; R9 is one or more substituents at any position selected from the group consisting of hydrogen, halogen, cyano, C1-C8 hydrocarbyl, C1-C8 alkoxy, and C5-C 12 aryl; R 10 is one or more substituents at any position selected from the group consisting of hydrogen, halogen, cyano, C1-C8 hydrocarbyl, C1-C8 alkoxy, and C5-C 12 aryl; R 11 is hydrogen, -Na, -Li, -K, -Cs, -NH4 + , -NH2 + R 13 R 14 , -NH + R13 R 14 R 15 、 -NH3 + R 13 、 and selected from the group consisting of natural or non-natural amino acids; R 12 is hydrogen, -Na, -Li, -K, -Cs, -NH4 + 、 -NH2 + R 13 R 14 、 -NH + R 13 R 14 R 15 、 -NH3 + R 13 、 and selected from the group consisting of natural or non-natural amino acids; R 13 is hydrogen, C1 - C8 hydrocarbyl, C1 - C8 cyclo hydrocarbyl, C5 - C 18 aryl, and C5 - C 18 heteroaryl selected from the group consisting of; R 14 is hydrogen, C1 - C8 hydrocarbyl, C1 - C8 cyclo hydrocarbyl, C5 - C 18 aryl, and C5 - C 18 heteroaryl selected from the group consisting of; R 15 is hydrogen, C1 - C8 hydrocarbyl, C1 - C8 cyclo hydrocarbyl, C5 - C 18 aryl, and C5 - C 18 heteroaryl selected from the group consisting of; and R1, R 11 、 and R 12 The natural or non-natural amino acids in are selected from the group consisting of glycine, alanine, valine, leucine, isoleucine, methionine (methionine), proline, tryptophan, serine, tyrosine, cysteine, phenylalanine, asparagine, glutamine, threonine, aspartic acid, glutamic acid, lysine, arginine, histidine, selenocysteine, sarcosine, pyrrolysine, and homoalanine: Here, the process includes the following: (1) Reacting the compound of formula (A-I) with the compound of formula (A-II) to obtain the compound of formula (A-III),

[0023]

Chemical formula

[0024] wherein the groups represented by R4’, R9’, and R 10 ’ in formula (A-I) and formula (A-II) are as defined for R4, R9, and R 10 in formula (I); (2) Reacting the compound of formula (A-III) with sodium azide to obtain the compound of formula (A-IV),

[0025]

Chemical formula

[0026] wherein the groups represented by R4’, R9’, and R 10 ’ in formula (A-III) and formula (A-IV) are as defined for R4, R9, and R 10 in formula (I); (3) Reacting the compound of formula (A-IV) with sodium 4-amino-5-hydroxy-1,3-naphthalenedisulfonate to obtain the compound of formula (A-V),

[0027]

Chemical formula

[0028] wherein the groups represented by R4’, R9’, and R 10 ’ in formula (A-IV) and formula (A-V) are as defined for R4, R9, and R 10 in formula (I); (4) Reacting the compound of formula (B-I) with carbon tetrabromide to obtain the compound of formula (B-II),

[0029] [Chemical formula]

[0030] Here, the groups represented by R1’, R2’, and R3’ in formula (B-I) and formula (B-II) are as defined for R1, R2, and R3 in formula (I); (5) reacting the compound of formula (B-II) with the compound of formula (B-III) to obtain the compound of formula (B-IV)

[0031] [Chemical formula]

[0032] Here, the groups represented by R1’, R2’, R3’, R5’, and R6’ in formula (B-II), formula (B-III), and formula (B-IV) are as defined for R1, R2, R3, R5, and R6 in formula (I); (6) Reacting the compound of formula (B-IV) under basic conditions to obtain the compound of formula (B-V),

[0033] [Chemical formula]

[0034] Here, the groups represented by R1’, R2’, R3’, R5’, and R6’ in formula (B-IV) and formula (B-V) are as defined for R1, R2, R3, R5, and R6 in formula (I); (7) Reacting the compound of formula (A-V) with the compound of formula (B-V) to obtain the compound of formula (I), or reacting the product obtained by reacting the compound of formula (A-V) with the compound of formula (B-V) with the corresponding acid or base to form its pharmaceutically acceptable salt

[0035] [Chemical formula]

[0036] Here, the groups represented by R2’, R3’, R4’, R5’, R6’, R9’, and R 10 ’ in formulas (A-V) and (B-V) are as defined for R2, R3, R4, R5, R6, R9, and R 10 in formula (I).

[0037] In yet another aspect, the present application relates to the following compounds and stereoisomers of the above compounds:

[0038]

Chemical formula

[0039]

Chemical formula

[0040]

Chemical formula

[0041]

Chemical formula

[0042]

Chemical formula

[0043]

Chemical formula

[0044]

Chemical formula

[0045]

Chemical formula

[0046]

Chem.

[0047]

Chem.

[0048]

Chem.

[0049]

Chem.

[0050]

Chem.

[0051]

Chem.

[0052]

Chem.

[0053]

Chem.

[0054]

Chem.

[0055]

Chem.

[0056]

Chem.

[0057]

Chem.

[0058]

Chem.

[0059]

Chem.

[0060]

Chem.

[0061]

Chem.

[0062]

Chem.

[0063]

Chem.

[0064]

Chem.

[0065]

Chem.

[0066]

Chem.

[0067] [Chemistry]

[0068] [Chemistry]

[0069] [Chemistry]

[0070] [Chemistry]

[0071] [Chemistry]

[0072] [Chemistry]

[0073] [Chemistry]

[0074] [Chemistry]

[0075] [Chemistry]

[0076] [Chemistry]

[0077] [Chemistry]

[0078]

Chem.

[0079]

Chem.

[0080]

Chem.

[0081]

Chem.

[0082]

Chem.

[0083]

Chem.

[0084]

Chem.

[0085]

Chem.

[0086]

Chem.

[0087]

Chem.

[0088]

Chem.

[0089]

Chem.

[0090]

Chem.

[0091]

Chem.

[0092]

Chem.

[0093]

Chem.

[0094]

Chem.

[0095]

Chem.

[0096]

Chem.

[0097]

Chem.

[0098]

Chem.

[0099]

Chem.

[0100]

Chem.

[0101]

Chem.

[0102]

Chem.

[0103]

Chem.

[0104]

Chem.

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Chem.

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Chem.

[0107]

Chem.

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Chem.

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Chem.

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Chem.

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Chem.

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Chem.

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Chem.

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Chem.

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Chem.

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Chem.

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Chem.

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Chem.

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Chem.

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Chem.

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Chem.

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Chem.

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Chem.

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Chem.

[0129]

Chem.

[0130]

Chem.

[0131] [Chemistry]

[0132] [Chemistry]

[0133] [Chemistry]

[0134] [Chemistry]

[0135] [Chemistry]

[0136] [Chemistry]

[0137] [Chemistry]

[0138] [Chemistry]

[0139] [Chemistry]

[0140] [Chemistry]

[0141] [Chemistry]

[0142] [Chemistry]

[0143] [Chemistry]

[0144] [Chemistry]

[0145] [Chemistry]

[0146] [Chemistry]

[0147] In some embodiments, the compounds of the present disclosure have good water solubility. In some embodiments, the compounds of the present disclosure have good stability. The compounds of the present disclosure have good storage stability.

[0148] The compounds of the present disclosure have good stability in the blood circulation of organisms. In some embodiments, the compounds of the present disclosure have good anti-cancer activity. In some embodiments, the compounds of the present disclosure have good safety.

[0149] In some embodiments, the compounds of the present disclosure have good tolerance. In some embodiments, the compounds of the present disclosure have good anti-cancer activity against large tumors.

[0150] In some embodiments, the compounds of the present disclosure have good anti-cancer activity against tumors with poor previous therapeutic effects using irinotecan.

Brief Description of the Drawings

[0151]

Figure 1

Modes for Carrying Out the Invention

[0152] [Detailed Description] In the following description, to provide a complete understanding of the various disclosed embodiments, certain specific details are included. However, those skilled in the relevant art will recognize that the embodiments can be practiced without one or more of these specific details, or with other methods, components, materials, etc.

[0153] Unless the context dictates otherwise, throughout this specification and the following claims, the terms "comprising" and its variations, such as "comprises" and "comprising," are to be construed in an open, inclusive sense, i.e., "including, but not limited to."

[0154] References throughout this specification to "one embodiment" or "an embodiment" or "in another embodiment" or "in some embodiments" mean that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment. Thus, the appearances of the phrases "in one embodiment," or "in an embodiment," or "in another embodiment," or "in some embodiments" in various places throughout this specification are not necessarily all referring to the same embodiment. Further, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments.

[0155] As used in this specification and the appended claims, it should be noted that the singular forms "a", "an", and "the" include plural referents unless the context clearly dictates otherwise.

[0156] [Definitions] Accordingly, as used in this specification and the appended claims, unless otherwise defined, the following terms have the meanings set forth below: Preceding a particular chemical group specified in this specification is a shorthand notation indicating the total number of carbon atoms that would be included in the indicated chemical group. For example, C1-C4 alkyl represents an alkyl group having from 1 to 4 carbon atoms in total, as defined below, and C3-C 10 Cycloalkyl represents a cycloalkyl group having from 3 to 10 carbon atoms in total, as defined below. The total number of carbon atoms in the shorthand notation does not include carbon that may be present in substituents of the recited group.

[0157] The term "halogen" as used in this specification refers to fluoro, chloro, bromo, or iodo. The term "hydroxy" as used in this specification refers to an -OH group.

[0158] The term "amino" as used in this specification refers to an -NH2 group. The term "carboxy" as used in this specification refers to a -COOH group. The term "cyano" as used in this specification refers to a -CN group.

[0159] The term "nitro" as used in this specification refers to a -NO2 group. As used herein, the term "hydrocarbyl" refers to an aliphatic hydrocarbon group. The hydrocarbyl moiety may be a "saturated hydrocarbyl" group, which means that it contains no alkene or alkyne moieties. The hydrocarbyl moiety may also be an "unsaturated hydrocarbyl" moiety, which means that it contains at least one alkene or alkyne moiety. An "alkene" moiety consists of 2 to 8 carbon atoms and at least one carbon-carbon double bond, and refers to a straight-chain or branched hydrocarbon chain group that is bonded to the remainder of the molecule by a single bond. For example, ethenyl, prop-1-enyl, but-1-enyl, pent-1-enyl, pent- 1,4-dienyl, etc. An "alkyne" moiety consists of 2 to 8 carbon atoms and at least one carbon-carbon triple bond, and refers to a straight-chain or branched hydrocarbon chain group that is bonded to the remainder of the molecule by a single bond. The alkyl moiety may be branched or straight-chain, whether saturated or unsaturated.

[0160] The hydrocarbyl group may have 1 to 8 carbon atoms (whenever presented herein, a numerical range such as "1 to 8" refers to each integer within the given numerical range; for example, "1 to 8 carbon atoms" means that the hydrocarbyl group may consist of 1 carbon atom, 2 carbon atoms, 3 carbon atoms, etc., and includes up to 8 carbon atoms, but this definition also encompasses occurrences of the term "hydrocarbyl" when no numerical range is specified).

[0161] The hydrocarbyl group may be optionally substituted, i.e., it may be either substituted or unsubstituted. When substituted, the substituent is independently selected from the group consisting of cyclo-hydrocarbyl, aryl, heteroaryl, heteroaricyclic, hydroxy, hydrocarbyloxy, aryloxy, mercapto, alkylthio, arylthio, cyano, halo, carbonyl, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amide, N-amide, S-sulfinamide, N-sulfinamide, C-carboxyl, O-carboxyl, isocyanate, thiocyano, isothiocyanate, nitro, silyl, trihalomethanesulfonyl, -NR’R’’ (wherein R’ and R’’ are hydrocarbyl groups as defined herein), or amino including mono-substituted amino groups and di-substituted amino groups, and protected derivatives thereof. Typical hydrocarbyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, hexyl, ethenyl, propenyl, butenyl, ethynyl, propynyl, and butynyl. Whenever a substituent is described as “optionally substituted,” the substituent may be substituted with one of the above substituents.

[0162] In some embodiments, “C1-C4 hydrocarbyl” refers to a hydrocarbyl group as defined above containing from 1 to 4 carbon atoms. The C1-C4 hydrocarbyl group may be optionally substituted as defined for hydrocarbyl groups.

[0163] In some embodiments, “C1-C6 hydrocarbyl” refers to a hydrocarbyl group as defined above containing from 1 to 6 carbon atoms. The C1-C6 hydrocarbyl group may be optionally substituted as defined for hydrocarbyl groups.

[0164] In some embodiments, “C1-C 12 hydrocarbyl” refers to a hydrocarbyl group as defined above containing from 1 to 12 carbon atoms. C1-C 12The hydrocarbyl group may be optionally substituted as defined for the hydrocarbyl group.

[0165] In some embodiments, "C2-C6 hydrocarbyl" refers to a hydrocarbyl group as defined above containing from 2 to 6 carbon atoms. The C2-C6 hydrocarbyl group may be optionally substituted as defined for the hydrocarbyl group.

[0166] In some embodiments, "C3-C6 hydrocarbyl" refers to a hydrocarbyl group as defined above containing from 3 to 6 carbon atoms. The C3-C6 hydrocarbyl group may be optionally substituted as defined for the hydrocarbyl group.

[0167] In some embodiments, "C3-C 12 hydrocarbyl" refers to a hydrocarbyl group as defined above containing from 3 to 12 carbon atoms. C3-C 12 The hydrocarbyl group may be optionally substituted as defined for the hydrocarbyl group.

[0168] In some embodiments, "C6-C 12 hydrocarbyl" refers to a hydrocarbyl group as defined above containing from 6 to 12 carbon atoms. C6-C 12 The hydrocarbyl group may be optionally substituted as defined for the hydrocarbyl group.

[0169] In some embodiments, "C7-C 12 hydrocarbyl" refers to a hydrocarbyl group as defined above containing from 7 to 12 carbon atoms. C7-C 12 The hydrocarbyl group may be optionally substituted as defined for the hydrocarbyl group.

[0170] As used herein, "hydrocarbyloxy" refers to the formula -O-hydrocarbyl, where R is a hydrocarbyl group as defined above, for example, methoxy, ethoxy, n-propoxy, 1-methylethoxy (isopropoxy), n-butoxy, iso-butoxy, sec-butoxy, t-butoxy, amoxy, and t-amoxy.

[0171] As used herein, the term "aryl" refers to a carbocyclic ring (entirely carbon) having a fully delocalized π electron system, or two or more fused rings (rings sharing two adjacent carbon atoms). Examples of aryl groups include, but are not limited to, fluorenyl, phenyl, and naphthyl. An aryl group can have, for example, from 5 to 12 carbon atoms. The aryl groups of the present disclosure may be substituted or unsubstituted. When substituted, the hydrogen atom is substituted with one or more substituents independently selected from the group consisting of hydrocarbyl, cyclohydrocarbyl, aryl, heteroaryl, heteroaricyclic, hydroxy, protected hydroxy, hydrocarbyloxy, aryloxy, mercapto, hydrocarbylthio, arylthio, cyano, halo, carbonyl, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amide, N-amide, S-sulfinamide, N-sulfinamide, C-carboxyl, protected C-carboxyl, O-carboxyl, isocyanate, thiocyano, isothiocyanate, nitro, silyl, trihalomethanesulfonyl, -NR’R’’ (where R’ and R’’ are hydrocarbyl groups as defined herein), and protected amino. Whenever a substituent is described as "optionally substituted", the substituent may be substituted with one of the above substituents.

[0172] As used herein, the term "arylidene" refers to a carbocyclic ring (entirely carbon) having a fully delocalized π - electron system, or two or more fused rings (rings sharing two adjacent carbon atoms). Examples of arylidene groups include, but are not limited to, fluorenylidene, phenylidene, and naphthylidene. An arylidene group can have, for example, from 5 to 12 carbon atoms. The arylidene groups of the present disclosure may be substituted or unsubstituted. When substituted, the hydrogen atom is substituted with one or more substituents independently selected from the group consisting of hydrocarbyl, cyclo - hydrocarbyl, aryl, heteroaryl, heteroaricyclic, hydroxy, protected hydroxy, hydrocarbyloxy, aryloxy, mercapto, hydrocarbylthio, arylthio, cyano, halo, carbonyl, thiocarbonyl, O - carbamyl, N - carbamyl, O - thiocarbamyl, N - thiocarbamyl, C - amide, N - amide, S - sulfinamide, N - sulfinamide, C - carboxyl, protected C - carboxyl, O - carboxyl, isocyanate, thiocyano, isothiocyanate, nitro, silyl, trihalomethanesulfonyl, - NR’R’’ (where R’ and R’’ are hydrocarbyl groups as defined herein) and protected amino. Whenever a substituent is described as "optionally substituted", the substituent may be substituted with one of the above - mentioned substituents. The arylidene may be bonded to the remainder of the molecule and the residue via one carbon within the residue, or via any two carbons within the residue.

[0173] As used herein, the term "aromatic ring group" refers to a carbocyclic ring (entirely carbon) having a fully delocalized π - electron system, or two or more fused rings (rings sharing two adjacent carbon atoms). Examples of aryl groups include, but are not limited to, fluorenyl, phenyl, and naphthyl. An aryl group can have, for example, from 5 to 12 carbon atoms. The aromatic ring groups of the present disclosure may be substituted or unsubstituted. When substituted, a hydrogen atom is substituted with one or more substituents independently selected from the group consisting of hydrocarbyl, cyclo - hydrocarbyl, aryl, heteroaryl, heteroaricyclic, hydroxy, protected hydroxy, hydrocarbyloxy, aryloxy, mercapto, hydrocarbylthio, arylthio, cyano, halo, carbonyl, thiocarbonyl, O - carbamyl, N - carbamyl, O - thiocarbamyl, N - thiocarbamyl, C - amide, N - amide, S - sulfinamide, N - sulfinamide, C - carboxyl, protected C - carboxyl, O - carboxyl, isocyanate, thiocyano, isothiocyanate, nitro, silyl, trihalomethanesulfonyl, - NR’R’’ (where R’ and R’’ are hydrocarbyl groups as defined herein), and protected amino. Whenever a substituent is described as "optionally substituted", the substituent may be substituted with one of the above - mentioned substituents.

[0174] As used herein, the term "arylhydrocarbyloxy" refers to the formula - O - hydrocarbylaryl, where hydrocarbyl and aryl are as defined herein, respectively. Exemplary examples of arylhydrocarbyloxy include, but are not limited to, benzyloxy, phenethyloxy, and phenylpropyloxy.

[0175] In some embodiments, "C6 - C 16 arylhydrocarbyloxy" refers to an arylhydrocarbyloxy group as defined above, containing from 6 to 16 carbon atoms. C6 - C 16An arylhydrocarbyloxy group may be optionally substituted as defined for each of the hydrocarbyl group and the aryl group.

[0176] In some embodiments, "C6-C 18 aryhydrocarbyloxy" refers to an arylhydrocarbyloxy group as defined above, containing 6 to 18 carbon atoms. C6-C 18 An arylhydrocarbyloxy group may be optionally substituted as defined for each of the hydrocarbyl group and the aryl group.

[0177] In some embodiments, "C7-C 18 aryhydrocarbyloxy" refers to an arylhydrocarbyloxy group as defined above, containing 7 to 18 carbon atoms. C7-C 18 An arylhydrocarbyloxy group may be optionally substituted as defined for each of the hydrocarbyl group and the aryl group.

[0178] In some embodiments, "C8-C 18 aryhydrocarbyloxy" refers to an arylhydrocarbyloxy group as defined above, containing 8 to 18 carbon atoms. C8-C 18 An arylhydrocarbyloxy group may be optionally substituted as defined for each of the hydrocarbyl group and the aryl group.

[0179] In some embodiments, "C8-C 24 aryhydrocarbyloxy" refers to an arylhydrocarbyloxy group as defined above, containing 8 to 24 carbon atoms. C8-C 24 An arylhydrocarbyloxy group may be optionally substituted as defined for each of the hydrocarbyl group and the aryl group.

[0180] In some embodiments, "C 11 -C 24"Arylhydrocarbyloxy" refers to an arylhydrocarbyloxy group as defined above and containing from 11 to 24 carbon atoms. C 11 ~C 24 The arylhydrocarbyloxy group may be optionally substituted as defined for each of the hydrocarbyl group and the aryl group.

[0181] In some embodiments, "C 12 ~C 24 Arylhydrocarbyloxy" refers to an arylhydrocarbyloxy group as defined above and containing from 12 to 24 carbon atoms. C 12 ~C 24 The arylhydrocarbyloxy group may be optionally substituted as defined for each of the hydrocarbyl group and the aryl group.

[0182] In some embodiments, "C6~C 24 Arylhydrocarbyloxy" refers to an arylhydrocarbyloxy group as defined above and containing from 6 to 24 carbon atoms. C6~C 24 The arylhydrocarbyloxy group may be optionally substituted as defined for each of the hydrocarbyl group and the aryl group.

[0183] As used herein, the term "heteroaryl" refers to an aromatic ring group having from 5 to 18 members, including from 1 to 17 carbon atoms and from 1 to 10 heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur. In some embodiments, heteroaryl may be a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, and may include fused or bridged ring systems. Further, the nitrogen, carbon, or sulfur atoms in the heteroaryl group may be optionally oxidized, and the nitrogen atoms may be optionally quaternized. Representative examples of heteroaryl include, but are not limited to, azepinyl, acridinyl, benzimidazolyl, benzothiazolyl, benzoindolyl, benzodioxolanyl, benzofuranyl, benzoxazolyl, benzothiazolyl, benzothiadiazolyl, benzo[b][1,4]dioxepanyl, 1,4-benzodioxanyl, benzonaphthofuranyl, benzodioxolanyl, benzodioxadienyl, benzopyranyl, benzopyrronyl, benzofuranyl, benzofuranonyl, benzothienyl, benzotriazolyl, benzo[4,6]imidazo[1,2-a]pyridyl, carbazolyl, cinnolinyl, dibenzofuranyl, dibenzothienyl, furanyl, furanonyl, isothiazolyl, imidazolyl, indazolyl, indolyl, indazolyl, isoindolyl, indolinyl, isoindolinyl, isoquinolyl, indolizinyl, isoxazolyl, naphthyl, naphthyridinyl, oxadiazolyl, 2-oxoazepinyl, oxazolyl, oxiranyl, 1-phenyl-1H-pyrrolyl, phenazinyl, phenothiazinyl, phenoxazinyl, phthalazinyl, pteridinyl, purinyl, pyrrolyl, pyrazolyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyrrolyl, quinazolinyl, quinoxalinyl, quinolyl, quinuclidinyl, isoquinolyl, tetrahydroquinolyl, thiazolyl, thiadiazolyl, triazolyl, tetrazolyl, triazinyl, and thiophenyl. The heteroaryl groups of the present disclosure may be optionally substituted or unsubstituted.When replaced, the hydrogen atom is replaced with one or more substituents independently selected from the group consisting of hydrocarbyl, cyclo hydrocarbyl, aryl, heteroaryl, heteroaricyclic, hydroxy, protected hydroxy, hydrocarbyloxy, aryloxy, mercapto, hydrocarbylthio, arylthio, cyano, halo, carbonyl, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amide, N-amide, S-sulfinamide, N-sulfinamide, C-carboxyl, protected C-carboxyl, O-carboxyl, isocyanate, thiocyano, isothiocyanate, nitro, silyl, trihalomethanesulfonyl, -NR’R’’ (wherein R’ and R’’ are hydrocarbyl groups as defined herein) and protected amino. Whenever a substituent is described as being “optionally substituted”, the substituent may be substituted with one of the above substituents.

[0184] As used herein, the term “heteroarylidene” refers to an arylidene group having from 5 to 18 members, including from 1 to 17 carbon atoms and from 1 to 10 heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur. In some embodiments, heteroarylidene may be a monocyclic, bicyclic, tricyclic or tetracyclic ring system, a fused ring system or a bridged It may contain a ring system. Further, the nitrogen, carbon, or sulfur atoms in the heteroaryliden group may optionally be oxidized, and the nitrogen atoms may optionally be quaternized. Representative examples of heteroaryliden include, but are not limited to, azepinylidene, acridinylidene, benzimidazolylidene, benzothiazolylidene, benzoindolylidene, benzodioxolanylidene, benzofuranylidene, benzoxazolylidene, benzothiazolylidene, benzothiadiazolylidene, benzo[b][1,4]dioxepanylidene, 1,4-benzodioxanylidene, benzonaphthofuranylidene, benzodioxolanylidene, benzodioxadienylidene, benzopyranylidene, benzopyrronylidene, benzofuranylidene, benzofuranonylidene, benzothienylidene, benzotriazolylidene, benzo[4,6]imidazo[1,2-a]pyridylidene, carbazolylidene, cinnolinylidene, dibenzofuranylidene, dibenzothienylidene, furanylidene, furanonylidene, isothiazolylidene, imidazolylidene, indazolylidene, indolylidene, indazolylidene, isoindolylidene, indolinylidene, isoindolinylidene, isoquinolinylidene, indolizinylidene, isoxazolylidene, naphthylidene, naphthyridinylidene, oxadiazolylidene, 2-oxoazepinylidene, oxazolylidene, oxiranylidene, 1-phenyl-1H-pyrrolylidene, phenazinylidene, phenothiazinylidene, phenoxazinylidene, phthalazinylidene, pteridinylidene, purinylidene, pyrrolylidene, pyrazolylidene, pyridinylidene, pyrazinylidene, pyrimidinylidene, pyridazinylidene, pyrrolylidene, quinazolinylidene, quinoxalinylidene, quinolinylidene, quinuclidinylidene, isoquinolinylidene, tetrahydroquinolinylidene, thiazolylidene, thiadiazolylidene, triazolylidene, tetrazolylidene, triazinylidene, and thiophenylidene. The heteroaryliden group of the present disclosure may be substituted or unsubstituted.When replaced, the hydrogen atom is replaced with one or more substituents independently selected from the group consisting of hydrocarbyl, cyclo hydrocarbyl, aryl, heteroaryl, heteroaricyclic, hydroxy, protected hydroxy, hydrocarbyloxy, aryloxy, mercapto, hydrocarbylthio, arylthio, cyano, halo, carbonyl, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amide, N-amide, S-sulfinamide, N-sulfinamide, C-carboxyl, protected C-carboxyl, O-carboxyl, isocyanate, thiocyano, isothiocyanate, nitro, silyl, trihalomethanesulfonyl, -NR’R’’ (wherein R’ and R’’ are hydrocarbyl groups as defined herein), and protected amino. Whenever a substituent is described as being “optionally substituted,” the substituent may be substituted with one of the above substituents.

[0185] As used herein, the term "heteroaromatic ring group" refers to an aromatic ring group having from 5 to 18 members, including from 1 to 17 carbon atoms and from 1 to 10 heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur. In some embodiments, the heteroaromatic ring group may be a monocyclic, bicyclic, tricyclic or tetracyclic ring system and may include a fused ring system or a bridged ring system. Further, the nitrogen, carbon, or sulfur atoms in the heteroaryl group may optionally be oxidized and the nitrogen atoms may optionally be quaternized. Exemplary examples of heteroaromatic ring groups are azepinyl, acridinyl, benzimidazolyl, benzothiazolyl, benzoindolyl, benzodioxolanyl, benzofuranyl, benzoxazolyl, benzothiazolyl, benzothiadiazolyl, benzo[b][1,4]dioxepanyl, 1,4-benzodioxanyl, benzonaphthofuranyl, benzodioxolanyl, benzodioxadienyl, benzopyranyl, benzopyrronyl, benzofuranyl, benzofuranonyl, benzothienyl, benzotriazolyl, benzo[4,6]imidazo[1,2-a]pyridyl, carbazolyl, cinnolinyl, dibenzofuranyl, dibenzothienyl, furanyl, furanonyl, isothiazolyl, imidazolyl, indazolyl, indolyl, indazolyl, isoindolyl, indolinyl, isoindolinyl, isoquinolyl, indolizinyl, isoxazolyl, naphthyl, naphthyridinyl, oxadiazolyl, 2-oxoazepinyl, oxa including, but not limited to, thiazolyl, oxiranyl, 1-phenyl-1H-pyrrolyl, phenazinyl, phenothiazinyl, phenoxazinyl, phthalazinyl, pteridinyl, purinyl, pyrrolyl, pyrazolyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyrrolyl, quinazolinyl, quinoxalinyl, quinolyl, quinuclidinyl, isoquinolyl, tetrahydroquinolyl, thiazolyl, thiadiazolyl, triazolyl, tetrazolyl, triazinyl, and thiophenyl. The heteroaromatic ring groups of the present disclosure may be substituted or unsubstituted. When substituted, the hydrogen atom is substituted with one or more substituents independently selected from the group consisting of hydrocarbyl, cyclo hydrocarbyl, aryl, heteroaryl, heteroaricyclic, hydroxy, protected hydroxy, hydrocarbyloxy, aryloxy, mercapto, hydrocarbylthio, arylthio, cyano, halo, carbonyl, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amide, N-amide, S-sulfinamide, N-sulfinamide, C-carboxyl, protected C-carboxyl, O-carboxyl, isocyanate, thiocyano, isothiocyanate, nitro, silyl, trihalomethanesulfonyl, -NR’R’’ (wherein R’ and R’’ are hydrocarbyl groups as defined herein), and protected amino. Whenever a substituent is described as “optionally substituted,” the substituent may be substituted with one of the above substituents.

[0186] As used herein, the term "cyclohydrocarbyl" refers to a stable non-aromatic monocyclic or bicyclic hydrocarbyl composed of only carbon and hydrogen atoms, having from 3 to 15 carbon atoms, and in some embodiments from 3 to 12 carbon atoms, which is saturated or unsaturated and is bonded to the remainder of the molecule via a single bond, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclodecyl, etc. Unless otherwise specified herein, the term "cyclohydrocarbyl" is intended to include cyclohydrocarbyl groups as defined above, and may be optionally substituted with one or more substituents selected from the group consisting of cyclohydrocarbyl, aryl, heteroaryl, heteroaricyclic, hydroxy, hydrocarbyloxy, aryloxy, mercapto, hydrocarbylthio, arylthio, cyano, halo, carbonyl, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amide, N-amide, S-sulfinamide, N-sulfinamide, C-carboxyl, O-carboxyl, isocyanate, thiocyanate, isothiocyanate, nitro, silyl, trihalomethanesulfonyl, -NR’R’’ (wherein R’ and R’’ are hydrocarbyl groups as defined in the present disclosure), or amino including mono-substituted amino groups and di-substituted amino groups, and their protected derivatives.

[0187] In some embodiments, "C3-C6 cyclohydrocarbyl" refers to a cyclohydrocarbyl group as defined above containing from 3 to 6 carbon atoms. The C3-C6 cyclohydrocarbyl group may be optionally substituted as defined above for cyclohydrocarbyl groups.

[0188] In some embodiments, "C3-C 10 cyclohydrocarbyl" refers to a cyclohydrocarbyl group as defined above containing from 3 to 10 carbon atoms. C3-C 10 cyclohydrocarbyl group may be optionally substituted as defined above for cyclohydrocarbyl groups.

[0189] In some embodiments, "C3-C 12 cyclohydrocarbyl" refers to a cyclohydrocarbyl group as defined above containing from 3 to 12 carbon atoms. C3-C 12 cyclohydrocarbyl groups may be optionally substituted as defined above for cyclohydrocarbyl groups.

[0190] As used herein, the terms "alkylidene" or "hydrocarbyldiene" refer to a divalent hydrocarbon chain consisting only of carbon and hydrogen, which may be linear, branched, or cyclic alkyl. That is, a linear or branched divalent hydrocarbon chain bonded to other parts and residues of the molecule, such as methylidene, ethylidene, propylidene, n-butylidene, vinylene, propenylene, and n-butenylene. The chain of the alkylidene group is bonded to the remainder of the molecule and residues by one carbon contained in the chain, or by any two carbons contained in the chain.

[0191] As used herein, the term "C1-C9 alkylidene" refers to a difunctional linear, branched, or cyclic alkyl group containing from 1 to 9 carbon atoms. That is, "C1-C9 alkylidene" consists only of carbon and hydrogen, and refers to a linear or branched divalent hydrocarbon chain containing from 1 to 9 carbon atoms bonded to other parts and residues of the molecule, such as methylidene, ethylidene, propylidene, n-butylidene, vinylene, propenylene, and n-butenylene. The chain of the alkylidene group is bonded to the remainder of the molecule and residues by one carbon contained in the chain, or by any two carbons contained in the chain.

[0192] As used herein, the terms "alkylideneoxy" or "hydrocarbyldieneoxy" refer to the formula alkylidene-O-, where alkylidene or hydrocarbylidene is as defined in this disclosure. Representative examples of alkylideneoxy include, but are not limited to, methylideneoxy, ethylideneoxy, and n-propylideneoxy.

[0193] As used herein, the term "C1-C9 alkylideneoxy" or "C1-C9 hydrocarbyldienoxy" refers to a bifunctional, straight-chain, branched-chain, or cyclic alkoxy group containing from 1 to 9 carbon atoms.

[0194] As used herein, the term "C1-C8 alkylideneoxy" or "C1-C8 hydrocarbyldienoxy" refers to a bifunctional, straight-chain, branched-chain, or cyclic alkoxy group containing from 1 to 8 carbon atoms.

[0195] As used herein, the term "cyclohydrocarbyloxy" refers to -O-cyclohydrocarbyl, where cyclohydrocarbyl is as defined in this disclosure. Representative examples of cyclohydrocarbyloxy include, but are not limited to, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy, and cyclodecyloxy.

[0196] As used herein, the term "hydrocarbylcarbonylamino" refers to an -NHC(=O)-hydrocarbyl group, where hydrocarbyl is as defined in this disclosure. Exemplary examples of hydrocarbylcarbonylamino include, but are not limited to, acetamide, propionamide, butylamide, and valerylamide.

[0197] As used herein, the term "hydrocarbylcarbonyloxy" refers to an -OC(=O)-hydrocarbyl group, where hydrocarbyl is as defined in this disclosure. Exemplary examples of hydrocarbylcarbonyloxy include, but are not limited to, acetoxy, propionyloxy, butyryloxy, and valeryloxy.

[0198] As used herein, the term "hydrocarbyloxycarbonylamino" refers to an -NHC(=O)O-hydrocarbyl group, where hydrocarbyl is as defined in the present disclosure. Exemplary examples of hydrocarbyloxycarbonylamino include, but are not limited to, methoxycarbonylamino, ethoxycarbonylamino, propoxycarbonylamino, and tert-butoxycarbonylamino. Examples include, but are not limited to, methoxycarbonylamino, ethoxycarbonylamino, propoxycarbonylamino, and tert-butoxycarbonylamino.

[0199] As used herein, the term "hydrocarbyloxycarbonyl" refers to -C(=O)O-hydrocarbyl, where hydrocarbyl is as defined in the present disclosure. Exemplary examples of hydrocarbyloxycarbonyl include, but are not limited to, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, and butoxycarbonyl.

[0200] As used herein, the term "carbonylamino" refers to -C(=O)-NH-. As used herein, the term "a compound of the present disclosure, a stereoisomer of a compound of the present disclosure, or a pharmaceutically acceptable salt thereof" refers to a compound of formula (I) of the present disclosure and its stereoisomers.

[0201] As used herein, the term "mammal" means an animal including, for example, dogs, cats, cows, sheep, horses, and humans. In some embodiments, the mammal includes humans.

[0202] As used herein, the term "patient" means an animal such as a human, for example, companion animals such as dogs, cats, and horses, and livestock such as cows, pigs, and sheep. In some embodiments, the patient is a mammal, including both males and females. In some embodiments, the patient is a human.

[0203] As used herein, the term "pharmaceutically acceptable" means that a carrier, vehicle, diluent, excipient and / or salt must be compatible with the other ingredients of the formulation and not be harmful to its recipient.

[0204] As used herein, the term "optional" or "optionally" means that the subsequent described event or circumstance may or may not occur, and this specification includes both the case where the event or circumstance occurs and the case where it does not occur.

[0205] As used herein, the term "pharmaceutically acceptable carrier, diluent or excipient" includes, but is not limited to, any adjuvant, carrier, excipient, glidant, sweetening agent, diluent, preservative, dye / colorant, flavor enhancer, surfactant, wetting agent, dispersing agent, suspending agent, stabilizer, isotonic agent, solvent, or emulsifying agent, etc., which are approved by the US Food and Drug Administration, are acceptable for use in humans or animals, and have no side effects in the preparation of pharmaceutical compositions.

[0206] As used herein, the term "carrier" defines a compound that facilitates the uptake of a compound into cells or tissues. For example, dimethyl sulfoxide (DMSO) is generally used as a carrier because it facilitates the uptake of many organic compounds into the cells or tissues of organisms.

[0207] As used herein, the term "pharmaceutically acceptable salt" includes both "pharmaceutically acceptable acid addition salts" and "pharmaceutically acceptable base addition salts". As used herein, the term "pharmaceutically acceptable acid addition salt" refers to a salt that retains the biological effectiveness and properties of the free base, is not biologically or otherwise undesirable, and includes, but is not limited to, inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and acetic acid, 2,2-dichloroacetic acid, adipic acid, alginic acid, ascorbic acid, aspartic acid, benzenesulfonic acid, benzoic acid, 4-acetamidobenzoic acid, It is formed using organic acids including, but not limited to, camphanic acid, camphor-10-sulfonic acid, capric acid, caproic acid, caprylic acid, carbonic acid, cinnamic acid, citric acid, cyclamic acid, dodecyl sulfuric acid, ethane-1,2-disulfonic acid, ethanesulfonic acid, 2-hydroxyethanesulfonic acid, formic acid, fumaric acid, galactaric acid, gentisic acid, glucoheptonic acid, gluconic acid, glucuronic acid, glutamic acid, glutaric acid, 2-oxo-glutaric acid, glycerophosphoric acid, glycolic acid, hippuric acid, isobutyric acid, lactic acid, lactobionic acid, lauric acid, maleic acid, malic acid, malonic acid, mandelic acid, methanesulfonic acid, mucic acid, naphthalene-1,5-disulfonic acid, naphthalene-2-sulfonic acid, 1-hydroxy-2-naphthoic acid, nicotinic acid, oleic acid, orotic acid, oxalic acid, palmitic acid, pamoic acid, propionic acid, pyroglutamic acid, pyruvic acid, salicylic acid, 4-aminosalicylic acid, sebacic acid, stearic acid, succinic acid, tartaric acid, thiocyanic acid, p-toluenesulfonic acid, trifluoroacetic acid, undecylenic acid, etc.

[0208] As used herein, the term "pharmaceutically acceptable base addition salt" refers to a salt that retains the biological effectiveness and properties of the free acid and is not biologically or otherwise undesirable. These salts are prepared by adding an inorganic base or an organic base to the free acid. Salts derived from inorganic bases include, but are not limited to, sodium salts, potassium salts, lithium salts, ammonium salts, calcium salts, magnesium salts, iron salts, zinc salts, copper salts, manganese salts, aluminum salts, etc. In some embodiments, the inorganic salts are ammonium salts, sodium salts, potassium salts, calcium salts, and magnesium salts. Salts derived from organic bases include salts of primary, secondary, and tertiary amines, salts of substituted amines including naturally occurring substituted amines, salts of cyclic amines, and basic ion exchange resins, such as ammonia, isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, diethanolamine, ethanolamine, 2-dimethylaminoethanol, 2-diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, procaine, hydrabamine, choline, betaine, benethamine, benzathine, ethylenediamine, glucosamine, methylglucosamine, theobromine, triethanolamine, tromethamine, purine, piperazine, piperidine, N-ethylpiperidine, polyamine resins, etc., but are not limited to these. In some embodiments, the organic bases are isopropylamine, diethylamine, ethanolamine, trimethylamine, dicyclohexylamine, choline, and caffeine.

[0209] As used herein, the term "solvent or solvent mixture" refers to any solvent. In some embodiments, the solvent or solvent mixture is an organic solvent and water, including but not limited to water, methanol, ethanol, 2-propanol, n-butanol, isobutanol, acetone, methyl ethyl ketone, ethyl acetate, 1,4-dioxane, diethyl ether, MTBE, THF, acetonitrile, dichloromethane, chloroform, DMF, cyclohexane, cyclopentane, n-hexane, n-heptane, n-pentane, toluene, o-xylene, p-xylene, DMSO, pyridine, acetic acid, anisole, butyl acetate, cumene, ethyl formate, formic acid, isobutyl acetate, isopropyl acetate, methyl acetate, 3-methyl-1-butanol, methyl isobutyl ketone, 2-methyl-1-propanol, 1-pentanol, propyl acetate, ethylene glycol, and 1-methyl-2-pyrrolidone, as well as any mixture of two or more of the foregoing solvents. In some embodiments, the solvent or solvent mixture is a single solvent and a binary mixture. In some embodiments, the solvent or solvent mixture is water, a single solvent of an organic solvent, and a binary mixture of water and an organic solvent.

[0210] As used herein, the term "pharmaceutical composition" refers to a formulation of a compound of the present disclosure with a medium generally acceptable in the art for delivery of a biologically active compound to mammals such as humans. The medium includes all pharmaceutically acceptable carriers, diluents, or excipients. Including.

[0211] As used herein, the term "therapeutically effective amount" refers to an amount of a compound, or combination of compounds, that ameliorates, reduces, or eliminates a particular disease or condition, or symptoms of a particular disease or condition, or prevents or delays the onset of a particular disease or condition, or symptoms of a particular disease or condition. The amount of the compounds of the present disclosure that constitutes a "therapeutically effective amount" will vary depending on the compound, the condition, and the severity thereof, as well as the age of the mammal being treated, and can be routinely determined by one of ordinary skill in the art in view of the knowledge of one of ordinary skill in the art and the present disclosure.

[0212] As used herein, "treating" or "treatment" includes treating a disease or condition in a mammal, such as a human, having the disease or condition of interest, and includes the following: (i) preventing the occurrence of a disease or condition in a mammal, particularly when the mammal is predisposed to the condition but has not yet been diagnosed as having it; (ii) inhibiting a disease or condition, i.e., arresting its progression; or (iii) alleviating a disease or symptom, i.e., causing regression of the disease or condition.

[0213] As used herein, the terms "disease" and "condition" may be used interchangeably, or a particular disease or condition may not have a known causative agent (and thus the etiology has not yet been elucidated), and is not yet recognized as a disease but is only recognized as an undesirable condition or syndrome, in which case, more or less a particular set of syndromes has been identified by a clinician.

[0214] As used herein, the term "physiologically acceptable" defines a carrier or diluent that does not inactivate the biological activity and properties of a compound. The compounds of the present disclosure or pharmaceutically acceptable salts of the compounds of the present disclosure may contain one or more asymmetric centers and, accordingly, can give rise to enantiomers, diastereomers, and other stereoisomeric forms that can be defined as (R)- or (S)-, or (D)- or (L)- for amino acids from the perspective of absolute stereochemistry. The present disclosure is intended to include all possible isomers thereof, as well as their racemic and optically pure forms. The optically active (+) and (-), (R)- and (S)-, or (D)- and (L)- isomers may be prepared using a chiral synthon or chiral reagent, or separated using conventional techniques such as HPLC using a chiral column. When the compounds described herein contain an olefin double bond or other geometrically asymmetric center, unless otherwise specified, the compounds are intended to include both E and Z geometric isomers. Similarly, all tautomers are also intended to be included.

[0215] As used herein, the term "stereoisomer" refers to compounds that are composed of the same atoms bonded by the same bonds but have different three-dimensional structures that are non-interchangeable. The present disclosure contemplates various stereoisomers and mixtures thereof.

[0216] [Specific Embodiments] In one aspect, the present disclosure relates to compounds of formula (I), stereoisomers and cis-trans isomers of compounds of formula (I):

[0217] [Chemical Formula]

[0218] wherein, R1 is hydrogen, C1-C8 hydrocarbyl, -Na, -Li, -K, -Cs, -NH4 + , -NH2 + R 13 R 14 , -NH + R 13 R 14 R 15 , -NH + 3R13 and is selected from the group consisting of natural or non-natural amino acids; R2 is selected from the group consisting of hydrogen and C1-C8 hydrocarbyl; R3 is one or more substituents at any substitution position selected from the group consisting of hydrogen, halogen, C1-C8 hydrocarbyl, C1-C8 hydrocarbyloxy, cyano, nitro, amino, aryl, arylhydrocarbyl, and C1-C4 hydrocarbyl-substituted amino; R4 is C1-C9 alkylidene, C1-C8 alkylideneoxy, C1-C8 hydrocarbyl-substituted or unsubstituted C3-C8 heteroaryl, C1-C8 hydrocarbyl-substituted or unsubstituted C3-C 15 aryl, -(CH2R7) n , -(R8) m , C1-C9 alkylidene-arylidene, C1-C9 alkylidene-arylidene-C1-C9 alkyldiene, C1-C9 alkylidene-arylidene-arylidene, C1-C9 alkylidene-heteroarylidene-C1-C9 alkylidene, and an amino acid peptide chain, where the amino acid peptide chain is composed of a combination of natural or non-natural amino acids, and the length of the peptide chain is from 1 to 100 peptides, preferably from 1 to 50 peptides, more preferably from 1 to 20 peptides; R5 is selected from the group consisting of hydrogen and C1-C8 hydrocarbyl; R6 is selected from the group consisting of hydrogen, C1-C8 hydrocarbyl, C1-C8 hydrocarbylideneamino(C1-C4 hydrocarbyl)2, C1-C8 hydrocarbylidene thio C1-C8 hydrocarbyl, and C1-C9 alkylidene-oxy-C1-C9 alkyl; R5 and R6 may form a ring, and when R5 and R6 form a ring, the ring may be a 5-membered ring or a 6-membered ring; R7 is selected from hydrogen, C1-C8 hydrocarbylideneoxy, amino C1-C8 hydrocarbylidene, thio C1-C8 hydrocarbylidene, and oxy C1-C8 hydrocarbylidene; n is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, and 9; when n is 0, (CH2R7) n represents a covalent bond; R8 is carbonylamino, where the amino may be substituted with C1-C8 hydrocarbyl or arylhydrocarbyl, C1-C8 hydrocarbylideneamino C1-C8 hydrocarbylidene, C1-C8 hydrocarbylidene thio C1-C8 hydrocarbylidene, or C1-C8 hydrocarbylideneoxy C1-C8 hydrocarbylidene; m is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, and 9; when m is 0, -(R8) m represents a covalent bond; R9 is one or more substituents at any position selected from the group consisting of hydrogen, halogen, cyano, C1-C8 hydrocarbyl, C1-C8 alkoxy, and C5-C 12 aryl; R 10 is one or more substituents at any position selected from the group consisting of hydrogen, halogen, cyano, C1-C8 hydrocarbyl, C1-C8 alkoxy, and C5-C 12 aryl; R 11 is hydrogen, -Na, -Li, -K, -Cs, -NH4 + -NH2 + R 13 R 14 -NH + R 13 R 14 R 15 -NH3 + R 13 and is selected from the group consisting of natural or non-natural amino acids; R 12 is hydrogen, -Na, -Li, -K, -Cs, -NH4 + -NH2 + R 13 R 14 -NH + R 13 R 14 R 15 -NH3 + R 13and is selected from the group consisting of natural or unnatural amino acids; R 13 is hydrogen, C1-C8 hydrocarbyl, C1-C8 cyclo hydrocarbyl, C5-C 18 aryl, and C5-C 18 heteroaryl; R 14 is hydrogen, C1-C8 hydrocarbyl, C1-C8 cyclo hydrocarbyl, C5-C 18 aryl, and C5-C 18 heteroaryl; R 15 is hydrogen, C1-C8 hydrocarbyl, C1-C8 cyclo hydrocarbyl, C5-C 18 aryl, and C5-C 18 heteroaryl; and R1, R 11 , and R 12 The natural or unnatural amino acids in are selected from the group consisting of glycine, alanine, valine, leucine, isoleucine, methionine (methionine), proline, tryptophan, serine, tyrosine, cysteine, phenylalanine, asparagine, glutamine, threonine, aspartic acid, glutamic acid, lysine, arginine, histidine, selenocysteine, sarcosine, pyrrolysine, and homoalanine.

[0219] In other embodiments, the disclosure relates to compounds of formula (I), stereoisomers and cis-trans isomers of compounds of formula (I):

[0220]

Chemical formula

[0221] wherein, R1 is hydrogen, C1-C4 hydrocarbyl, -Na, -Li, -K, -Cs, -NH4 + , -NH2 + R 13 R 14 , -NH + R 13R 14 R 15 、 -NH + 3R 13 、 and is selected from the group consisting of natural or non-natural amino acids; R2 is selected from the group consisting of hydrogen and C1-C4 hydrocarbyl; R3 is one or more substituents at any position selected from the group consisting of hydrogen, halogen, C1-C4 hydrocarbyl, C1-C4 hydrocarbyloxy, cyano, nitro, amino, aryl, arylhydrocarbyl, and C1-C4 hydrocarbyl-substituted amino; R4 is C1-C6 alkylidene, C1-C6 alkylideneoxy, C1-C6 hydrocarbyl-substituted or unsubstituted C3-C8 heteroaryl, C1-C8 hydrocarbyl-substituted or unsubstituted C3-C 15 aryl, -(CH2R7) n 、 -(R8) m 、 C1-C4 alkylidene-arylidene, C1-C4 alkylidene-arylidene-C1-C4 alkylidene, C1-C4 alkylidene-arylidene-arylidene, C1-C4 alkylidene-heteroarylidene-C1-C4 alkylidene, and an amino acid peptide chain, where the amino acid peptide chain is composed of a combination of natural or non-natural amino acids, and the length of the peptide chain is from 1 to 100 peptides, preferably from 1 to 50 peptides, more preferably from 1 to 20 peptides; R5 is selected from the group consisting of hydrogen and C1-C4 hydrocarbyl; R6 is selected from the group consisting of hydrogen, C1-C4 hydrocarbyl, C1-C4 hydrocarbylideneamino(C1-C4 hydrocarbyl)2, C1-C4 hydrocarbylidene thio C1-C4 hydrocarbyl, and C1-C4 alkylidene-oxy-C1-C4 alkyl; R5 and R6 may form a ring, and when R5 and R6 form a ring, all rings may be 5-membered or 6-membered rings; R7 is selected from the group consisting of hydrogen, C1-C4 alkylideneoxy, amino C1-C4 alkylidene, thio C1-C4 alkylidene, and oxy C1-C4 alkylidene; n is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, and 9; when n is 0, -(CH2R7) n represents a covalent bond; R8 is carbonylamino, where the amino may be substituted with C1-C4 hydrocarbyl or arylhydrocarbyl, C1-C4 hydrocarbylideneamino C1-C4 hydrocarbylidene, C1-C4 hydrocarbylidene thio C1-C4 hydrocarbylidene, or C1-C4 hydrocarbylideneoxy C1-C4 hydrocarbylidene; m is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, and 9; when m is 0, -(R8) m represents a covalent bond; R9 is one or more substituents at any position selected from the group consisting of hydrogen, halogen, cyano, C1-C4 hydrocarbyl, C1-C4 alkoxy, and C5-C 12 aryl; R 10 is one or more substituents at any position selected from the group consisting of hydrogen, halogen, cyano, C1-C4 hydrocarbyl, C1-C4 alkoxy, and C5-C 12 aryl; R 11 is hydrogen, -Na, -Li, -K, -Cs, -NH4 + , -NH2 + R 13 R 14 , -NH + R 13 R 14 R 15 , -NH3 + R 13 , and is selected from the group consisting of natural or non-natural amino acids; R 12 is hydrogen, -Na, -Li, -K, -Cs, -NH4 + , -NH2 + R 13 R 14 , -NH+ R 13 R 14 R 15 、 -NH3 + R 13 、 and selected from the group consisting of natural or non-natural amino acids; R 13 is selected from the group consisting of hydrogen, C1-C4 alkyl, C1-C8 cycloalkyl, C5-C 18 aryl, and C5-C 18 heteroaryl; R 14 is selected from the group consisting of hydrogen, C1-C4 alkyl, C1-C8 cycloalkyl, C5-C 18 aryl, and C5-C 18 heteroaryl; R 15 is selected from the group consisting of hydrogen, C1-C4 alkyl, C1-C8 cycloalkyl, C5-C 18 aryl, and C5-C 18 heteroaryl; and R1, R 11 , and R 12 the natural or non-natural amino acids in are selected from the group consisting of glycine, alanine, valine, leucine, isoleucine, methionine (methionine), proline, tryptophan, serine, tyrosine, cysteine, phenylalanine, asparagine, glutamine, threonine, aspartic acid, glutamic acid, lysine, arginine, histidine, selenocysteine, sarcosine, pyrrolysine, and homoalanine.

[0222] In some embodiments, R1 is hydrogen, -CH3, -CH2CH3, -Na, -Li, -K, -Cs, -NH4 + , -NH2 + R 13 R 14 , -NH + R 13 R 14 R 15 , -NH + 3R 13 , and selected from the group consisting of natural or non-natural amino acids.

[0223] In some embodiments, R2 is selected from the group consisting of hydrogen, -CH3, and -CH2CH3. In some embodiments, R3 is selected from one or more substituents selected from the group consisting of hydrogen, -F, -Cl, -Br, -CN, -CH3, -CH2CH3, -CH2CH2CH3, -CH2CH2CH2CH3, -OCH3, -OCH2CH3, -OCH2CH2CH3, -OCH2CH2CH2CH3, phenyl, benzyl, -NO2, -NH2, and -N(CH3)2, substituted at any position.

[0224] In some embodiments, R4 is -CH2-, -CH2CH2-, -CH2CH2CH2-, -CH2CH2CH2CH2-, -CH2CH2CH2CH2CH2-, -CH2CH2CH2CH2CH2CH2-, -CH2CH2CH2CH2CH2CH2CH2-, -CH2CH2CH2CH2CH2CH2CH2CH2-, -CH2CH2CH2CH2CH2CH2CH2CH2CH2-, -CH2OCH2-, -CH2OCH2CH2-, -CH2OCH2CH2OCH2-, -CH2OCH2CH2OCH2CH2O CH2-, -CH2OCH2CH2OCH2CH2OCH2CH2OCH2-, -CH2CH2OCH2CH2CH2OCH2-, -CH2CH2OCH2CH2CH2OCH2CH2CH2OCH2-, -CH2CH2OCH2CH2CH2OCH2CH2CH2OCH2CH2CH2OCH2-, -CH2CH2OCH2-, -CH2CH2OCH2CH2CH2OCH2CH2-, -CH2CH2OCH2CH2CH2OCH2-, -CH2NHCH2CH2NHCH2CH2NHCH2-

[0225]

Chemical formula

[0226] In some embodiments, R5 is selected from the group consisting of hydrogen, -CH3, and -CH2CH3. In some embodiments, R6 is selected from the group consisting of hydrogen, -CH3, -CH2OCH3, -CH2N(CH3)2, and -CH2SCH(CH3)2.

[0227] In some embodiments, when R5 and R6 form a ring, the ring may be a 5-membered ring or a 6-membered ring. In some embodiments, when R5 and R6 form a ring, the ring may be selected from the group consisting of cyclopentyl and cyclohexyl.

[0228] In some embodiments, R7 is selected from the group consisting of -H, -OCH2-, -OCH2CH2-, -OCH2CH2CH2-, -OCH2CH2CH2CH2-, -NHCH2-, -NHCH2CH2-, -NHCH2CH2CH2-, -NHCH2CH2CH2CH2-, -SCH2-, -SCH2CH2-, -SCH2CH2CH2-, -SCH2CH2CH2CH2-, -CH2O-, -CH2CH2O-, -CH2CH2CH2O-, and -CH2CH2CH2CH2O-.

[0229] In some embodiments, n is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, and 9. In some embodiments, when n is 0, -(CH2R7) n represents a covalent bond.

[0230] In some embodiments, R8 is -CH2OCH2CH2-, -CH2CH2OCH2-, -CH2CH2OCH2CH2-, -CH2CH2OCH2CH2CH2-, -CH2CH2CH2OCH2CH2-, -CH2CH2CH2OCH2CH2CH2-, -CH2SCH2CH2-, -CH2CH2SCH2-, -CH2CH2SCH2CH2-, -CH2CH2SCH2CH2CH2-, -CH2CH2CH2SCH2CH2- , -CH2CH2CH2SCH2CH2CH2-, -CH2NHCH2CH2-, -CH2CH2NHCH2-, -CH2CH2NHCH2CH2-, -CH2CH2NHCH2CH2CH2-, -CH2CH2CH2NHCH2CH2-, -CH2CH2CH2NHCH2CH2CH2-, -CONHCH2-, -CONHCH2CH2-, -CONHCH2CH2CH2-, -CON(CH3)CH2-, -CON(CH3)CH2CH2-, -CON(CH3)CH2CH2CH2-, -CONHCH(CH3)-, -CONHCH(CH3)CH2-, -CONHCH(CH3)CH2CH2-, -CONHCH2CH(CH3)CH2-, -CONHCH(CH3)CONHCH(CH3)CH2C6H5-, and is selected from the group consisting of.

[0231] In some embodiments, m is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, and 9. In some embodiments, when m is 0, -(R8) m represents a covalent bond.

[0232] In some embodiments, R9 is one or more substituents at any position selected from the group consisting of hydrogen, -F-, -Cl, -Br, -CN, -CH3, -CH2CH3, -OCH3, -OCH2CH3, and phenyl.

[0233] In some embodiments, R10 is one or more substituents at any position selected from the group consisting of hydrogen, -F-, -Cl, -Br, -CN, -CH3, -CH2CH3, -OCH3, -OCH2CH3, and phenyl.

[0234] In some embodiments, R 11 is hydrogen, -Na, -Li, -K, -Cs, -NH4 + , -NH2 + R 13 R 14 , -NH + R 13 R 14 R 15 , -NH3 + R 13 , glycine, alanine, valine, leucine, isoleucine, methionine (methionine), proline, tryptophan, serine, tyrosine, cysteine, phenylalanine, asparagine, glutamine, threonine, aspartic acid, glutamic acid, lysine, arginine, histidine, selenocysteine, sarcosine, pyrrolysine, and homoalanine, selected from the group consisting of.

[0235] In some embodiments, R 12 is hydrogen, -Na, -Li, -K, -Cs, -NH4 + , -NH2 + R 13 R 14 , -NH + R 13 R 14 R 15 , -NH3 + R 13 , glycine, alanine, valine, leucine, isoleucine, methionine (methionine), proline, tryptophan, serine, tyrosine, cysteine, phenylalanine, asparagine, glutamine, threonine, aspartic acid, glutamic acid, lysine, arginine, histidine, selenocysteine, sarcosine, pyrrolysine, and homoalanine selected from the group consisting of.

[0236] In some embodiments, R 13is selected from the group consisting of hydrogen, -CH3, -CH2CH3, -CH(CH3)2, -CH2CH2CH3, -CH2CH2CH2CH2CH3, cyclohexyl, phenyl, pyridyl, thienyl, imidazolyl, indolyl, quinolinyl, pyridoimidazolyl, pyridoindolyl, imidazoquinolinyl, imidazoquinoxalinyl, imidazopyridyl, and benzoxazinyl.

[0237] In some embodiments, R 14 is selected from the group consisting of hydrogen, -CH3, -CH2CH3, -CH(CH3)2, -CH2CH2CH3, -CH2CH2CH2CH2CH3, cyclohexyl, phenyl, pyridyl, thienyl, imidazolyl, indolyl, quinolinyl, pyridoimidazolyl, pyridoindolyl, imidazoquinolinyl, imidazoquinoxalinyl, imidazopyridyl, and benzoxazinyl.

[0238] In some embodiments, R 15 is selected from the group consisting of hydrogen, -CH3, -CH2CH3, -CH(CH3)2, -CH2CH2CH3, -CH2CH2CH2CH2CH3, cyclohexyl, phenyl, pyridyl, thienyl, imidazolyl, indolyl, quinolinyl, pyridoimidazolyl, pyridoindolyl, imidazoquinolinyl, imidazoquinoxalinyl, imidazopyridyl, and benzoxazinyl.

[0239] In yet other aspects, the disclosure relates to the following compounds, stereoisomers, cis-trans isomers, or pharmaceutically acceptable salts of the following compounds: (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)2-methylphenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; 4-Amino-6-((E)-(4’-(6-(4-((3-(((2S,3R,4S,5S,6S)-6-carboxy-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)oxy)-6-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-2-tolyloxy)methyl)-1H-1,2,3-triazol-1-yl)hexanamide)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonic acid disodium; 4-Amino-6-((E)-(4’-(6-(4-((6-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazo[1,2-b]quinolin-9-yl)oxy)methyl)-2-methyl-3-(((2S,3R,4S,5S,6S)-3,4,5-trihydroxy-6-(methoxycarbonyl)tetrahydro-2H-pyran-2-yl)oxy)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)hexanamide)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonic acid disodium; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonaphthalen-2-yl)diazenyl)-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-2-methylphenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; 4-Amino-6-((E)-(4’-(6-(4-((5-(((2S,3R,4S,5S,6S)-6-carboxy-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)oxy)-2-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)hexanamide)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonic acid disodium; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonaphthalen-2-yl)diazenyl )-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; Disodium 4-amino-6-((E)-(4'-(6-(4-((2-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-5-(((2S,3R,4S,5S,6S)-3,4,5-trihydroxy-6-(methoxycarbonyl)tetrahydro-2H-pyran-2-yl)oxy)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)hexanamido)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4-ethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; Disodium 4-amino-6-((E)-(4'-(6-(4-((5-(((2S,3R,4S,5S,6S)-6-carboxy-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)oxy)-2-((((S)-4-ethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)hexanamido)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate; Sodium 4-amino-6-((E)-(4'-(6-(4-((2-(((S)-4-ethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)-5-(((2S,3R,4S,5S,6S)-3,4,5-trihydroxy-6-(methoxycarbonyl)tetrahydro-2H-pyran-2-yl)oxy)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)hexanamido)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)-5-methoxyphenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate trisodium; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4-ethyl-4- hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate trisodium; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)-5-methoxyphenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethoxy-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4-ethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; 4-Amino-6-((E)-(4’-(4-((5-(((2S,3R,4S,5S,6S)-6-carboxy-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)oxy)-2-((((S)-4-ethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)hexanamide)-3,3’-dimethoxy-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonic acid disodium; Sodium 4-amino-6-((E)-(4’-(6-(4-((2-(((S)-4-ethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-5-(((2S,3R,4S,5S,6S)-3,4,5-trihydroxy-6-(methoxycarbonyl)tetrahydro-2H-pyran-2-yl)oxy)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)hexanamido)-3,3’-dimethoxy-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-amino-1-hydroxy-5,7-disulfonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-10-((dimethylamino)methyl)-4-ethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(3-((1-(8-((4’-((E)-(8-amino-1-hydroxy-5,7-disulfonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-8-oxooctyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(3-((1-(8-((4’-((E)-(8-amino-1-hydroxy-5,7-disulfonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-8-oxooctyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; Disodium 4-amino-6-((E)-(4'-(8-(4-((5-(((2S,3R,4S,5S,6S)-6-carboxy-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)oxy)-2-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)octanamido)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate; Disodium 4-amino-6-((E)-(4'-(8-(4-((2-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indrazolo[1,2-b]quinolin-9-yl)oxy)methyl)-5-(((2S,3R,4S,5S,6S)-3,4,5-trihydroxy-6-(methoxycarbonyl)tetrahydro-2H-pyran-2-yl)oxy)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)octanamido)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate; (2S,3S,4S,5R,6S)-6-(3-((1-(8-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-[1,1'-biphenyl]-4-yl)amino)-8-oxooctyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(3-((1-(8-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-8-oxooctyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-2-methylphenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(3-((1-(2-(2-(2-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-2-oxoethoxy)ethoxy)ethyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; 4-Amino-6-((E)-(4’-(2-(2-(2-(2-(2-((5-(((2S,3R,4S,5S,6S)-6-carboxy-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)oxy)-2-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)ethoxy)ethoxy)acetamido)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonic acid disodium; Sodium 4-amino-6-((E)-(4'-(2-(2-(2-((2-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indazolo[1,2-b]quinolin-9-yl)oxy)methyl)-5-(((2S,3R,4S,5S,6S)-3,4,5-trihydroxy-6-(methoxycarbonyl)tetrahydro-2H-pyran-2-yl)oxy)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)ethoxy)acetamido)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate; (2S,3S,4S,5R,6S)-6-(3-((1-(2-(2-(2-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonaphthalen-2-yl)diazenyl)-3,3'-dimethoxy-[1,1'-biphenyl]-4-yl)amino)-2-oxoethoxy)ethoxy)ethyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; Sodium 4-amino-6-((E)-(4'-(2-(2-(2-(2-(2-((5-(((2S,3R,4S,5S,6S)-6-carboxy-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)oxy)-2-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)ethoxy)ethoxy)acetamido)-3,3'-dimethoxy-[1,1'-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate; Disodium 4-amino-6-((E)-(4'-(2-(2-(2-((2-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indazolo[1,2-b]quinolin-9-yl)oxy)methyl)-5-(((2S,3R,4S,5S,6S)-3,4,5-trihydroxy-6-(methoxycarbonyl)tetrahydro-2H-pyran-2-yl)oxy)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)ethoxy)acetamido)-3,3’-dimethoxy-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonaphthalen-2-yl)diazenyl)-3,3’-dimethoxy-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium salt; Disodium 4-amino-6-((E)-(4'-(6-(4-((5-(((2S,3R,4S,5S,6S)-6-carboxy-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)oxy)-2-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)hexanamido)-3,3’-dimethoxy-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate; 4-Amino-6-((E)-(4'-(6-(4-((2-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1 H-pyrano[3’,4’:6,7]indazolo[1,2-b]quinolin-9-yl)oxy)methyl)-5-(((2S,3R,4S,5S,6S)-3,4,5-trihydroxy-6-(methoxycarbonyl)tetrahydro-2H-pyran-2-yl)oxy)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)hexanamide)-3,3’-dimethoxy-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxy naphthalene-1,3-disulfonic acid disodium; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-amino-1-hydroxy-5,7-disulfonaphthalene-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxy tetrahydro-2H-pyran-2-carboxylic acid; 1-Amino-7-((E)-(4'-(6-(4-((5-(((2S,3R,4S,5S,6S)-6-carboxy-3,4,5-trihydroxy tetrahydro-2H-pyran-2-yl)oxy)-2-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)hexanamide)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)diazenyl)-8-hydroxy-4-sulfonaphthalene-2-sulfonic acid sodium; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trilithium; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid triammonium; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid tripotassium; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S )-4,11-Diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinoline-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-Diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinoline-9-yl)oxy)methyl)-2-fluorophenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-2-chloro-4-((((S)-4,11-Diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinoline-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-2-bromo-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-2-methoxyphenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-2-ethylphenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(1-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)ethyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-((6-((1-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-5-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)-[1,1’-biphenyl]-2-yl)oxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)-2-nitrophenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; ​(2S,3S,4S,5R,6S)-6-(2-amino-3-((1-(6-((4’-((E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium salt; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-2-(dimethylamino)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium salt; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-5-fluorophenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium salt; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-5-chloro-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-5-bromo-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)-5-methylphenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-5-nitrophenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium salt; (2S,3S,4S,5R,6S)-6-((5-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-6-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)-[1,1’-biphenyl]-3-yl)oxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium salt; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-5-ethylphenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium salt; (2S,3S,4S,5R,6S)-6-(3-amino-5-((1-(6-((4’-((E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)- (8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-5-(dimethylamino)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(5-((1-(6-((4’-((E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)-2-fluorophenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(5-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-2-chloro-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium salt; (2S,3S,4S,5R,6S)-6-(5-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-2-bromo-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium salt; (2S,3S,4S,5R,6S)-6-(5-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-2-methoxyphenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium salt; (2S,3S,4S,5R,6S)-6-(5-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)-2-nitrophenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-((4-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-ox ohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-5-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)-[1,1’-biphenyl]-2-yl)oxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(5-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)-2-ethylphenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(2-Amino-5-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(5-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)-2-(dimethylamino)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-6-fluoro-2-methoxyphenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-6-chloro-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-5-fluoro-2-methylphenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxo hexyl)-1H-1,2,3-triazol-4-yl)methoxy)-6-bromo-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-2-methoxyphenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-9-ethyl-9-hydroxy-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,7]benzo[d]pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-4-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(4-(((S)-4-Acetoxy-4-ethyl-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)-3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)phenoxy)-3, trisodium 4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4-Ethyl-3,14-dioxo-4-(propionyloxy)-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4-Ethyl-4-(glycyloxy)-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((R)-5-Ethyl-5-hydroxy-3,15-dioxo-4,5,13,15-tetrahydro-1H,3H-oxazepino[3’,4’:6,7]indolizino[1,2-b]quinolin-10-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4-Ethyl-4-hydroxy-10-(methoxymethyl)-3,14-dioxo-3, 4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4-Ethyl-4-hydroxy-10-((isopropylthio)methyl)-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-amino-1-hydroxy-5,7-disulfonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4-ethyl-4-hydroxy-3-oxo-14-thia-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(3-((1-((2-((2-((2-((4’-(E)-(8-amino-1-hydroxy-5,7-disulfonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-2-oxoethyl)(methyl)amino)-2-oxoethyl)(methyl)amino)-2-oxoethyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(3-((1-((2-((2-((2-((4’-(E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-2-oxoethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(3-((1-(2-((S)-1-((S)-1-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-1-oxopropan-2-yl)amino)-1-oxopropan-2-yl)amino)-2-oxoethyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(3-((1-(2-((S)-1-((S)-1-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-1-oxo-3-phenylpropan-2-yl)amino)-1-ox ((S)-Propane-2-yl)amino)-2-oxoethyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(3-((1-(2-(2-(2-(2-((4’-((E)-(8-amino-1-hydroxy-5,7-disulfonaphthalene-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-2-oxoethoxy)ethoxy)ethoxy)ethyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(3-((1-((2-((2-((2-((2-((4’-(E)-(8-amino-1-hydroxy-5,7-disulfonaphthalene-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-2-oxoethyl)amino)ethyl)amino)ethyl)amino)ethyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(3-((1-(3-(3-(3-((4’-((E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-3-oxopropoxy)propoxy)propyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium salt; (2S,3S,4S,5R,6S)-6-(3-((1-(4-((4’-((E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)carbamoyl)phenethyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium salt; (2S,3S,4S,5R,6S)-6-(3-((1-(2-(2-((4’-((E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)carbamoyl)naphthalen-2-yl)ethyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium salt; (2S,3S,4S,5R,6S)-6-(3-((1-(2-(4’-((4’-( (E)-(8-amino-1-hydroxy-5,7-disulfonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)carbamoyl)-[1,1’-biphenyl]-4-yl)ethyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxy-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(3-((1-(4-(4-((4’-((E)-(8-amino-1-hydroxy-5,7-disulfonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-4-oxobutyl)phenyl)ethyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxy-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(3-((1-(2-(2-(6-(4-((4’-((E)-(8-amino-1-hydroxy-5,7-disulfonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-4-oxobutyl)pyridin-3-yl)ethyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxy-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(3-((1-(2-(2-(5-(4-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-4-oxobutyl)thiophen-3-yl)ethyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium salt; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’,5,5’-tetramethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium salt; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-2,2’,3,3’,5,5’,6,6’-octamethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium salt ; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-2,2’,3,3’,5,5’,6,6’-octamethoxy-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium salt; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’,5,5’-tetrachloro-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium salt; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-2,2’,3,3’,5,5’,6,6’-octafluoro-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3’-chloro-3-methoxy-5,5’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((6’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-[1,1’:3’,1’’:3’’,1’’’-quaterphenyl]-4’’-yl)-amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-difluoro-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro Trisodium (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-difluoro-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dichloro-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate trisodium salt; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dibromo-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate trisodium salt; (2S,3S,4S,5R,6S)-6-(3-((1-(5-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-5-oxopentyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(3-((1-(2-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-2-oxoethyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(3-((1-(3-(2-((4’-(E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-2-oxoethoxy)propyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; and (2S,3S,4S,5R,6S)-6-(3-((1-(2-(2-((4’-((E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-3-oxopropoxy)ethyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium salt.

[0240] In yet other embodiments, the disclosure relates to a process for preparing a compound of formula (I):

[0241]

Chemical formula

[0242] Wherein, R1 is hydrogen, C1-C8 hydrocarbyl, -Na, -Li, -K, -Cs, -NH4 + , -NH2 + R 13 R 14 , -NH + R 13 R 14 R 15 , -NH + 3R 13 and is selected from the group consisting of natural or non-natural amino acids; R2 is selected from the group consisting of hydrogen and C1-C8 hydrocarbyl; R3 is one or more substituents at any substitution position selected from the group consisting of hydrogen, halogen, C1-C8 hydrocarbyl, C1-C8 hydrocarbyloxy, cyano, nitro, amino, aryl, arylhydrocarbyl, and C1-C4 hydrocarbyl-substituted amino; R4 is selected from the group consisting of C1-C9 alkylidene, C1-C8 alkylideneoxy, C1-C8 hydrocarbyl-substituted or unsubstituted C3-C8 heteroaryl, C1-C8 hydrocarbyl-substituted or unsubstituted C3-C 15 aryl, -(CH2R7) n , -(R8) m , C1-C9 alkylidene-arylidene, C1-C9 alkylidene-arylidene-C1-C9 alkyldiene, C1-C9 alkylidene-arylidene-arylidene, C1-C9 alkylidene-heteroarylidene-C1-C9 alkylidene, and amino acid peptide chains; wherein the amino acid peptide chain is composed of a combination of natural or non-natural amino acids, and the length of the peptide chain is from 1 to 100 peptides, preferably from 1 to 50 peptides, more preferably from 1 to 20 peptides; R5 is selected from the group consisting of hydrogen and C1-C8 hydrocarbyl; R6 is selected from the group consisting of hydrogen, C1-C8 hydrocarbyl, C1-C8 hydrocarbylideneamino(C1-C4 hydrocarbyl)2, C1-C8 hydrocarbylidene thio C1-C8 hydrocarbyl, and C1-C9 alkylidene-oxy-C1-C9 alkyl; R5 and R6 may form a ring, and when R5 and R6 form a ring, the ring may be a 5-membered ring or a 6-membered ring; R7 is selected from hydrogen, C1-C8 hydrocarbylideneoxy, amino C1-C8-hydrocarbylidene, thio C1-C8-hydrocarbylidene, and oxy C1-C8 hydrocarby lidene; n is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, and 9; when n is 0, (CH2R7) n represents a covalent bond; R8 is a carbonylamino, where the amino may be substituted with a C1-C8 hydrocarbyl or arylhydrocarbyl, C1-C8 hydrocarbylideneamino C1-C8 hydrocarbylidene, C1-C8 hydrocarbylidene thio C1-C8 hydrocarbylidene, or C1-C8 hydrocarbylideneoxy C1-C8 hydrocarbylidene; m is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, and 9; when m is 0, -(R8) m represents a covalent bond; R9 is one or more substituents at any position selected from the group consisting of hydrogen, halogen, cyano, C1-C8 hydrocarbyl, C1-C8 alkoxy, and C5-C 12 aryl; R 10 is one or more substituents at any position selected from the group consisting of hydrogen, halogen, cyano, C1-C8 hydrocarbyl, C1-C8 alkoxy, and C5-C 12 aryl; R 11 is hydrogen, -Na, -Li, -K, -Cs, -NH4 + , -NH2 + R 13 R 14 , -NH + R 13 R 14 R 15 , -NH3 + R 13 , and is selected from the group consisting of natural or non-natural amino acids; R 12 is hydrogen, -Na, -Li, -K, -Cs, -NH4 + , -NH2 + R 13 R 14 , -NH + R 13 R 14 R 15 , -NH3 + R 13 , and is selected from the group consisting of natural or non-natural amino acids; R 13 is hydrogen, C1-C8 hydrocarbyl, C1-C8 cyclo hydrocarbyl, C5-C18 Aryl, and C5-C 18 selected from the group consisting of heteroaryl; R 14 is hydrogen, C1-C8 hydrocarbyl, C1-C8 cyclo hydrocarbyl, C5-C 18 aryl, and C5-C 18 selected from the group consisting of heteroaryl; R 15 is hydrogen, C1-C8 hydrocarbyl, C1-C8 cyclo hydrocarbyl, C5-C 18 aryl, and C5-C 18 selected from the group consisting of heteroaryl; and R1, R 11 , and R 12 the natural or non-natural amino acids at are selected from the group consisting of glycine, alanine, valine, leucine, isoleucine, methionine (methionine), proline, tryptophan, serine, tyrosine, cysteine, phenylalanine, asparagine, glutamine, threonine, aspartic acid, glutamic acid, lysine, arginine, histidine, selenocysteine, sarcosine, pyrrolysine, and homoalanine: wherein the process comprises: (1) reacting a compound of formula (A-I) with a compound of formula (A-II) to obtain a compound of formula (A-III),

[0243]

Chemical formula

[0244] wherein the groups represented by R4’, R9’, and R 10 ’ in formula (A-I) and formula (A-II) are as defined for R4, R9, and R 10 in formula (I); (2) reacting a compound of formula (A-III) with sodium azide to obtain a compound of formula (A-IV),

[0245]

Chemical formula

[0246] Here, the groups represented by R4’, R9’, and R 10 ’ in formulas (A-III) and (A-IV) are as defined for R4, R9, and R 10 in formula (I); (3) Reacting the compound of formula (A-IV) with monosodium 4-amino-5-hydroxy-1,3-naphthalenedisulfonate to obtain the compound of formula (A-V),

[0247]

Chemical formula

[0248] Here, the groups represented by R4’, R9’, and R 10 ’ in formulas (A-IV) and (A-V) are as defined for R4, R9, and R 10 in formula (I); (4) Reacting the compound of formula (B-I) with carbon tetrabromide to obtain the compound of formula (B-II),

[0249]

Chemical formula

[0250] Here, the groups represented by R1’, R2’, and R3’ in formulas (B-I) and (B-II) are as defined for R1, R2, and R3 in formula (I); (5) Reacting the compound of formula (B-II) with the compound of formula (B-III) to obtain the compound of formula (B-IV)

[0251]

Chemical formula

[0252] Here, the groups represented by R1’, R2’, R3’, R5’, and R6’ in formula (B-II), formula (B-III), and formula (B-IV) are as defined for R1, R2, R3, R5, and R6 in formula (I); (6) Reacting the compound of formula (B-IV) under basic conditions to obtain the compound of formula (B-V),

[0253]

Chemical formula

[0254] Here, the groups represented by R1’, R2’, R3’, R5’, and R6’ in formula (B-IV) and formula (B-V) are as defined for R1, R2, R3, R5, and R6 in formula (I); (7) Reacting the compound of formula (A-V) with the compound of formula (B-V) to obtain the compound of formula (I), or reacting the product obtained by reacting the compound of formula (A-V) with the compound of formula (B-V) with the corresponding acid or base to form the pharmaceutically acceptable salt

[0255]

Chemical formula

[0256] Here, the groups represented by R2’, R3’, R4’, R5’, R6’, R9’, and R 10 ’ in formula (A-V) and formula (B-V) are as defined for R2, R3, R4, R5, R6, R9, and R 10 as defined.

[0257] In yet another aspect, the present disclosure relates to a compound of formula (I), a stereoisomer of a compound of formula (I), or a cis-trans isomer for use in the manufacture of a medicament for the treatment of cancer or a tumor:

[0258]

Chemical formula

[0259] In the formula, R1 is selected from the group consisting of hydrogen, C1-C8 hydrocarbyl, -Na, -Li, -K, -Cs, -NH4 + , -NH2 + R 13 R 14 , -NH + R 13 R 14 R 15 , -NH + 3R 13 , and is selected from the group consisting of natural or non-natural amino acids; R2 is selected from the group consisting of hydrogen and C1-C8 hydrocarbyl; R3 is one or more substituents at any substitution position selected from the group consisting of hydrogen, halogen, C1-C8 hydrocarbyl, C1-C8 hydrocarbyloxy, cyano, nitro, amino, aryl, arylhydrocarbyl, and C1-C4 hydrocarbyl-substituted amino; R4 is selected from the group consisting of C1-C9 alkylidene, C1-C8 alkylideneoxy, C1-C8 hydrocarbyl-substituted or unsubstituted C3-C8 heteroaryl, C1-C8 hydrocarbyl-substituted or unsubstituted C3-C 15 aryl, -(CH2R7) n , -(R8) m , C1-C9 alkylidene-arylidene, C1-C9 alkylidene-arylidene-C1-C9 alkyldiene, C1-C9 alkylidene-arylidene-arylidene, C1-C9 alkylidene-heteroarylidene-C1-C9 alkylidene, and amino acid peptide chains; wherein the amino acid peptide chain is composed of a combination of natural or non-natural amino acids, and the length of the peptide chain is from 1 to 100 peptides, preferably from 1 to 50 peptides, more preferably from 1 to 20 peptides; R5 is selected from the group consisting of hydrogen and C1-C8 hydrocarbyl; R6 is selected from the group consisting of hydrogen, C1-C8 hydrocarbyl, C1-C8 hydrocarbylideneamino(C1-C4 hydrocarbyl)2, C1-C8 hydrocarbylidene thio C1-C8 hydrocarbyl, and C1-C9 alkylidene-oxy-C1-C9 alkyl; R5 and R6 may form a ring, and when R5 and R6 form a ring, the ring may be a 5-membered ring or a 6-membered ring; R7 is selected from the group consisting of hydrogen, C1-C8 hydrocarbylideneoxy, amino C1-C8 hydrocarbylidene, thio C1-C8 hydrocarbylidene, and oxy C1-C8 hydrocarbylidene; n is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, and 9; when n is 0, (CH2R7) n represents a covalent bond; R8 is carbonylamino, where the amino may be substituted with C1-C8 hydrocarbyl or arylhydrocarbyl, C1-C8 hydrocarbylideneamino C1-C8 hydrocarbylidene, C1-C8 hydrocarbylidene thio C1-C8 hydrocarbylidene, or C1-C8 hydrocarbylideneoxy C1-C8 hydrocarbylidene; m is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, and 9; when m is 0, -(R8) m represents a covalent bond; R9 is one or more substituents at any position selected from the group consisting of hydrogen, halogen, cyano, C1-C8 hydrocarbyl, C1-C8 alkoxy, and C5-C 12 aryl; R 10 is one or more substituents at any position selected from the group consisting of hydrogen, halogen, cyano, C1-C8 hydrocarbyl, C1-C8 alkoxy, and C5-C 12 aryl; R 11 is hydrogen, -Na, -Li, -K, -Cs, -NH4 + -NH2 + R 13 R 14 -NH+ R 13 R 14 R 15 、 -NH3 + R 13 、 and selected from the group consisting of natural or non-natural amino acids; R 12 is hydrogen, -Na, -Li, -K, -Cs, -NH4 + 、 -NH2 + R 13 R 14 、 -NH + R 13 R 14 R 15 、 -NH3 + R 13 、 and selected from the group consisting of natural or non-natural amino acids; R 13 is hydrogen, C1-C8 hydrocarbyl, C1-C8 cyclo hydrocarbyl, C5-C 18 aryl, and C5-C 18 heteroaryl selected from the group consisting of; R 14 is hydrogen, C1-C8 hydrocarbyl, C1-C8 cyclo hydrocarbyl, C5-C 18 aryl, and C5-C 18 heteroaryl selected from the group consisting of; R 15 is hydrogen, C1-C8 hydrocarbyl, C1-C8 cyclo hydrocarbyl, C5-C 18 aryl, and C5-C 18 heteroaryl selected from the group consisting of; and R1, R 11 、 and R 12 The natural or non-natural amino acids in are selected from the group consisting of glycine, alanine, valine, leucine, isoleucine, methionine (methionine), proline, tryptophan, serine, tyrosine, cysteine, phenylalanine, asparagine, glutamine, threonine, aspartic acid, glutamic acid, lysine, arginine, histidine, selenocysteine, sarcosine, pyrrolysine, and homoalanine.

[0260] In some embodiments, a compound of formula (I), or a stereoisomer of a compound of formula (I), can be used in the manufacture of a medicament for the treatment of cancer or a tumor, where the cancer includes, but is not limited to, colorectal cancer, lung cancer, cervical cancer, ovarian cancer, gastric cancer, esophageal cancer, breast cancer, pancreatic cancer, bladder cancer, liver cancer, gastric cancer, colon cancer, head and neck cancer, uterine cancer, urothelial cancer, osteosarcoma, sarcoma, kidney cancer, melanoma, prostate cancer, glioma, glioblastoma, and leukemia.

[0261] In yet another aspect, the present disclosure relates to a pharmaceutical composition comprising a compound of formula (I), a stereoisomer or cis-trans isomer of a compound of formula (I), and a pharmaceutically acceptable carrier:

[0262]

Chemical formula

[0263] wherein R1 is hydrogen, C1-C8 hydrocarbyl, -Na, -Li, -K, -Cs, -NH4 + , -NH2 + R 13 R 14 , -NH + R 13 R 14 R 15 , -NH + 3R 13 and is selected from the group consisting of natural or non-natural amino acids; R2 is selected from the group consisting of hydrogen and C1-C8 hydrocarbyl; R3 is one or more substituents at any substitutable position selected from the group consisting of hydrogen, halogen, C1-C8 hydrocarbyl, C1-C8 hydrocarbyloxy, cyano, nitro, amino, aryl, arylhydrocarbyl, and C1-C4 hydrocarbyl-substituted amino; R4 is C1-C9 alkylidene, C1-C8 alkylideneoxy, C1-C8 hydrocarbyl-substituted or unsubstituted C3-C8 heteroaryl, C1-C8 hydrocarbyl-substituted or unsubstituted C3-C 15 aryl, -(CH2R7) n, -(R8) m , selected from the group consisting of C1-C9 alkylidene-arylidene, C1-C9 alkylidene-arylidene-C1-C9 alkyldiene, C1-C9 alkylidene-arylidene-arylidene, C1-C9 alkylidene-heteroarylidene-C1-C9 alkylidene, and amino acid peptide chains; wherein the amino acid peptide chain is composed of a combination of natural or non-natural amino acids, and the length of the peptide chain is from 1 to 100 peptides, preferably from 1 to 50 peptides, more preferably from 1 to 20 peptides; R5 is selected from the group consisting of hydrogen and C1-C8 hydrocarbyl; R6 is selected from the group consisting of hydrogen, C1-C8 hydrocarbyl, C1-C8 hydrocarbylideneamino(C1-C4 hydrocarbyl)2, C1-C8 hydrocarbylidene thio C1-C8 hydrocarbyl, and C1-C9 alkylidene-oxy-C1-C9 alkyl; R5 and R6 may form a ring, and when R5 and R6 form a ring, the ring may be a 5-membered ring or a 6-membered ring; R7 is selected from the group consisting of hydrogen, C1-C8 hydrocarbylideneoxy, amino C1-C8 hydrocarbylidene, thio C1-C8 hydrocarbylidene, and oxy C1-C8 hydrocarbylidene; n is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, and 9; when n is 0, (CH2R7) n represents a covalent bond; R8 is carbonylamino, where the amino may be substituted with C1-C8 hydrocarbyl or arylhydrocarbyl, C1-C8 hydrocarbylideneamino C1-C8 hydrocarbylidene, C1-C8 hydrocarbylidene thio C1-C8 hydrocarbylidene, or C1-C8 hydrocarbylideneoxy C1-C8 hydrocarbylidene; m is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, and 9; when m is 0, -(R8) m represents a covalent bond; R9 is one or more substituents at any position selected from the group consisting of hydrogen, halogen, cyano, C1-C8 hydrocarbyl, C1-C8 alkoxy, and C5-C 12 aryl; R 10 is one or more substituents at any position selected from the group consisting of hydrogen, halogen, cyano, C1-C8 hydrocarbyl, C1-C8 alkoxy, and C5-C 12 aryl; R 11 is hydrogen, -Na, -Li, -K, -Cs, -NH4 + , -NH2 + R 13 R 14 , -NH + R 13 R 14 R 15 , -NH3 + R 13 , and is selected from the group consisting of natural or non-natural amino acids; R 12 is hydrogen, -Na, -Li, -K, -Cs, -NH4 + , -NH2 + R 13 R 14 , -NH + R 13 R 14 R 15 , -NH3 + R 13 , and is selected from the group consisting of natural or non-natural amino acids; R 13 is hydrogen, C1-C8 hydrocarbyl, C1-C8 cyclo hydrocarbyl, C5-C 18 aryl, and C5-C 18 heteroaryl; R 14 is hydrogen, C1-C8 hydrocarbyl, C1-C8 cyclo hydrocarbyl, C5-C 18 aryl, and C5-C 18 heteroaryl; R 15 is hydrogen, C1-C8 hydrocarbyl, C1-C8 cyclo hydrocarbyl, C5-C 18Aryl, and C5-C 18 selected from the group consisting of heteroaryl; and R1, R 11 , and R 12 The natural or non-natural amino acids in are selected from the group consisting of glycine, alanine, valine, leucine, isoleucine, methionine (methionine), proline, tryptophan, serine, tyrosine, cysteine, phenylalanine, asparagine, glutamine, threonine, aspartic acid, glutamic acid, lysine, arginine, histidine, selenocysteine, sarcosine, pyrrolysine, and homoalanine.

[0264] In yet another aspect, the present disclosure relates to a pharmaceutical composition comprising a compound of formula (I), a stereoisomer of a compound of formula (I), or a cis-trans isomer, and a pharmaceutically acceptable carrier, solvent, osmotic pressure regulator, pH regulator, solubilizer, co-solvent, antioxidant, bacteriostatic agent, emulsifier, suspending agent, filler, complexing agent, and chelating agent:

[0265]

Chemical formula

[0266] wherein, R1 is hydrogen, C1-C8 hydrocarbyl, -Na, -Li, -K, -Cs, -NH4 + , -NH2 + R 13 R 14 , -NH + R 13 R 14 R 15 , -NH + 3R 13 , and selected from the group consisting of natural or non-natural amino acids; R2 is selected from the group consisting of hydrogen and C1-C8 hydrocarbyl; R3 is one or more substituents at any substitution position selected from the group consisting of hydrogen, halogen, C1-C8 hydrocarbyl, C1-C8 hydrocarbyloxy, cyano, nitro, amino, aryl, arylhydrocarbyl, and C1-C4 hydrocarbyl-substituted amino; R4 is selected from the group consisting of C1-C9 alkylidene, C1-C8 alkylideneoxy, C1-C8 hydrocarbyl-substituted or unsubstituted C3-C8 heteroaryl, C1-C8 hydrocarbyl-substituted or unsubstituted C3-C 15 aryl, -(CH2R7) n 、-(R8) m 、C1-C9 alkylidene-arylidene, C1-C9 alkylidene-arylidene-C1-C9 alkyl diene, C1-C9 alkylidene-arylidene-arylidene, C1-C9 alkylidene-heteroarylidene-C1-C9 alkylidene, and amino acid peptide chains; wherein the amino acid peptide chain is composed of a combination of natural or non-natural amino acids, and the length of the peptide chain is from 1 to 100 peptides, preferably from 1 to 50 peptides, more preferably from 1 to 20 peptides; R5 is selected from the group consisting of hydrogen and C1-C8 hydrocarbyl; R6 is selected from the group consisting of hydrogen, C1-C8 hydrocarbyl, C1-C8 hydrocarbylideneamino(C1-C4 hydrocarbyl)2, C1-C8 hydrocarbylidene thio C1-C8 hydrocarbyl, and C1-C9 alkylidene-oxy-C1-C9 alkyl; R5 and R6 may form a ring, and when R5 and R6 form a ring, the ring may be a 5-membered ring or a 6-membered ring; R7 is selected from hydrogen, C1-C8 hydrocarbylideneoxy, amino C1-C8 hydrocarbylidene, thio C1-C8 hydrocarbylidene, and oxy C1-C8 hydrocarbylidene; n is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, and 9; when n is 0, (CH2R7) n represents a covalent bond; R8 is carbonylamino, where the amino may be substituted with C1-C8 hydrocarbyl or arylhydrocarbyl, C1-C8 hydrocarbylideneamino C1-C8 hydrocarbylidene, C1-C8 hydrocarbylidene thio C1-C8 hydrocarbylidene, or C1-C8 hydrocarbylideneoxy C1-C8 hydrocarbylidene; m is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, and 9; when m is 0, -(R8) m represents a covalent bond; R9 is one or more substituents at any position selected from the group consisting of hydrogen, halogen, cyano, C1-C8 hydrocarbyl, C1-C8 alkoxy, and C5-C 12 aryl; R 10 is one or more substituents at any position selected from the group consisting of hydrogen, halogen, cyano, C1-C8 hydrocarbyl, C1-C8 alkoxy, and C5-C 12 aryl; R 11 is hydrogen, -Na, -Li, -K, -Cs, -NH4 + , -NH2 + R 13 R 14 , -NH + R 13 R 14 R 15 , -NH3 + R 13 , and is selected from the group consisting of natural or unnatural amino acids; R 12 is hydrogen, -Na, -Li, -K, -Cs, -NH4 + , -NH2 + R 13 R 14 , -NH + R 13 R 14 R 15 , -NH3 + R 13 , and is selected from the group consisting of natural or unnatural amino acids; R 13 is hydrogen, C1-C8 hydrocarbyl, C1-C8 cyclo hydrocarbyl, C5-C18 Aryl, and C5-C 18 selected from the group consisting of heteroaryl; R 14 is hydrogen, C1-C8 hydrocarbyl, C1-C8 cyclo hydrocarbyl, C5-C 18 aryl, and C5-C 18 selected from the group consisting of heteroaryl; R 15 is hydrogen, C1-C8 hydrocarbyl, C1-C8 cyclo hydrocarbyl, C5-C 18 aryl, and C5-C 18 selected from the group consisting of heteroaryl; and R1, R 11 , and R 12 The natural or non-natural amino acids at are selected from the group consisting of glycine, alanine, valine, leucine, isoleucine, methionine (methionine), proline, tryptophan, serine, tyrosine, cysteine, phenylalanine, asparagine, glutamine, threonine, aspartic acid, glutamic acid, lysine, arginine, histidine, selenocysteine, sarcosine, pyrrolysine, and homoalanine.

[0267] In yet another aspect, the present disclosure relates to a method for treating a tumor or cancer, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula (I), or a stereoisomer of a compound of formula (I), or a therapeutically effective amount of a pharmaceutical composition comprising a compound of formula (I) or a stereoisomer of a compound of formula (I), wherein the cancer includes, but is not limited to: colorectal cancer, lung cancer, cervical cancer, ovarian cancer, gastric cancer, esophageal cancer, breast cancer, pancreatic cancer, bladder cancer, liver cancer, gastric cancer, colon cancer, head and neck cancer, uterine cancer, urothelial cancer, osteosarcoma, sarcoma, kidney cancer, melanoma, prostate cancer, glioma, glioblastoma, and leukemia:

[0268]

Chemical formula

[0269] wherein, R1 is hydrogen, C1-C8 hydrocarbyl, -Na, -Li, -K, -Cs, -NH4 + , -NH2 + R 13 R 14 , -NH + R 13 R 14 R 15 , -NH + 3R 13 , and is selected from the group consisting of natural or non-natural amino acids; R2 is selected from the group consisting of hydrogen and C1-C8 hydrocarbyl; R3 is one or more substituents at any substitution position selected from the group consisting of hydrogen, halogen, C1-C8 hydrocarbyl, C1-C8 hydrocarbyloxy, cyano, nitro, amino, aryl, arylhydrocarbyl, and C1-C4 hydrocarbyl-substituted amino; R4 is C1-C9 alkylidene, C1-C8 alkylideneoxy, C1-C8 hydrocarbyl-substituted or unsubstituted C3-C8 heteroaryl, C1-C8 hydrocarbyl-substituted or unsubstituted C3-C 15 aryl, -(CH2R7) n , -(R8) m , C1-C9 alkylidene-arylidene, C1-C9 alkylidene-arylidene-C1-C9 alkyl diene, C1-C9 alkylidene-arylidene-arylidene, C1-C9 alkylidene-heteroarylidene-C1-C9 alkylidene, and an amino acid peptide chain; where the amino acid peptide chain is composed of a combination of natural or non-natural amino acids, and the length of the peptide chain is from 1 to 100 peptides, preferably from 1 to 50 peptides, more preferably from 1 to 20 peptides; R5 is selected from the group consisting of hydrogen and C1-C8 hydrocarbyl; R6 is selected from the group consisting of hydrogen, C1-C8 hydrocarbyl, C1-C8 hydrocarbylideneamino(C1-C4 hydrocarbyl)2, C1-C8 hydrocarbylidene thio C1-C8 hydrocarbyl, and C1-C9 alkylidene-oxy-C1-C9 alkyl; R5 and R6 may form a ring, and when R5 and R6 form a ring, the ring may be a 5-membered ring or a 6-membered ring; R7 is selected from hydrogen, C1-C8 hydrocarbylideneoxy, amino C1-C8 hydrocarbylidene, thio C1-C8 hydrocarbylidene, and oxy C1-C8 hydrocarbylidene; n is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, and 9; when n is 0, (CH2R7) n represents a covalent bond; R8 is carbonylamino, where the amino may be substituted with C1-C8 hydrocarbyl or arylhydrocarbyl, C1-C8 hydrocarbylideneamino C1-C8 hydrocarbylidene, C1-C8 hydrocarbylidene thio C1-C8 hydrocarbylidene, or C1-C8 hydrocarbylideneoxy C1-C8 hydrocarbylidene; m is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, and 9; when m is 0, -(R8) m represents a covalent bond; R9 is one or more substituents at any position selected from the group consisting of hydrogen, halogen, cyano, C1-C8 hydrocarbyl, C1-C8 alkoxy, and C5-C 12 aryl; R 10 is one or more substituents at any position selected from the group consisting of hydrogen, halogen, cyano, C1-C8 hydrocarbyl, C1-C8 alkoxy, and C5-C 12 aryl; R 11 is hydrogen, -Na, -Li, -K, -Cs, -NH4 + -NH2 + R 13 R 14 -NH + R 13 R 14 R 15 -NH3 + R 13 and is selected from the group consisting of natural or non-natural amino acids; R 12is hydrogen, -Na, -Li, -K, -Cs, -NH4 + , -NH2 + R 13 R 14 , -NH + R 13 R 14 R 15 , -NH3 + R 13 and is selected from the group consisting of natural or non-natural amino acids; R 13 is hydrogen, C1-C8 hydrocarbyl, C1-C8 cyclo hydrocarbyl, C5-C 18 aryl, and C5-C 18 heteroaryl and is selected from the group consisting of; R 14 is hydrogen, C1-C8 hydrocarbyl, C1-C8 cyclo hydrocarbyl, C5-C 18 aryl, and C5-C 18 heteroaryl and is selected from the group consisting of; R 15 is hydrogen, C1-C8 hydrocarbyl, C1-C8 cyclo hydrocarbyl, C5-C 18 aryl, and C5-C 18 heteroaryl and is selected from the group consisting of; and R1, R 11 , and R 12 The natural or non-natural amino acids in are selected from the group consisting of glycine, alanine, valine, leucine, isoleucine, methionine (methionine), proline, tryptophan, serine, tyrosine, cysteine, phenylalanine, asparagine, glutamine, threonine, aspartic acid, glutamic acid, lysine, arginine, histidine, selenocysteine, sarcosine, pyrrolysine, and homoalanine.

[0270] In some embodiments, a method for treating a tumor or cancer comprises administering to a subject in need thereof from 10 mg to 5 g of a compound of the disclosure, a stereoisomer of a compound of the disclosure, a cis-trans isomer, or a pharmaceutically acceptable salt thereof.

[0271] In some embodiments, a method for treating a tumor or cancer comprises administering to a subject in need thereof a compound of the present disclosure, a stereoisomer of a compound of the present disclosure, a cis-trans isomer, or a pharmaceutically acceptable salt thereof, in an amount from 10 mg to 3000 mg.

[0272] In some embodiments, a method for treating a tumor or cancer comprises administering to a subject in need thereof a compound of the present disclosure, a stereoisomer of a compound of the present disclosure, a cis-trans isomer, or a pharmaceutically acceptable salt thereof, in an amount from 50 mg to 2000 mg.

[0273] In some embodiments, a method for treating a tumor or cancer comprises administering to a subject in need thereof a compound of the present disclosure, a stereoisomer of a compound of the present disclosure, a cis-trans isomer, or a pharmaceutically acceptable salt thereof, in an amount of 50 mg, 100 mg, 200 mg, 250 mg, 300 mg, 2000 mg, 400 mg, 450 mg, 500 mg, 550 mg, 650 mg, 700 mg, 750 mg, 800 mg, 850 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, 1500 mg, 1600 mg, 1900 mg, 1800 mg, 1900 mg, or 2000 mg.

[0274] [Pharmaceutical Composition] In some embodiments, a pharmaceutical composition comprises a compound of the present disclosure, a stereoisomer of a compound of the present disclosure, a cis-trans isomer, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent, or excipient.

[0275] In some embodiments, the route of administration of a compound of the present disclosure, a stereoisomer of a compound of the present disclosure, a cis-trans isomer, or a pharmaceutically acceptable salt thereof for treating a tumor or cancer in a mammal can be gastrointestinal or parenteral.

[0276] The compounds of the present disclosure may be obtained in any suitable form, such as injectable formulations. Exemplary examples of such injectable formulations include, but are not limited to, injection solutions, sterile powders for injection, and concentrated injection solutions. Injection solutions include solution-type, emulsion-type (such as fat emulsion injection solutions), or suspension-type injection solutions (for example, some liposome injection solutions, cortisone acetate injection solutions, etc.), and can be used for intramuscular injection, intravenous injection, intravenous drip, etc. Large-volume injections for intravenous injection (usually 100 ml or more unless otherwise specified) are also called intravenous infusions. Ampoules are generally also called small-volume aqueous injections and are different from large-volume infusions. Sterile powders for injection include freeze-dried powder injections and sterile dispensing. Concentrated injection solutions are sterile concentrated solutions that are diluted before use. Examples of pharmaceutically acceptable carriers that can be used in the pharmaceutical compositions of the present disclosure include any of various forms such as carriers, carriers, carrier materials, solvents, osmotic pressure regulators, pH regulators, solubilizers, co-solvents, antioxidants, bacteriostatic agents, emulsifiers, suspending agents, fillers, complexing agents, chelating agents, etc., but are not limited thereto, and they have been approved by the US Food and Drug Administration for use in humans or animals and do not adversely affect the composition of the pharmaceutical composition. Carriers in various forms do not have side effects on the composition of the pharmaceutical composition. Carriers acceptable for therapeutic use are well known in the pharmaceutical field and are described, for example, in Remington’s Pharmaceutical Sciences, 18th Edition, Mack Publishing Co., Easton, PA (1990). The description thereof is hereby incorporated by reference in its entirety into this specification.

[0277] The pharmaceutical compositions of the present application can be administered by any method that achieves the intended purpose. The pharmaceutical compositions of the present disclosure may be administered by injection, such as intradermal injection, subcutaneous injection, intramuscular injection, intravenous drip, intra-arterial injection, intracardiac injection, intra-articular injection, subcutaneous infusion, etc. The dosage will depend on the age, health status, and weight of the recipient, and in the case of combination therapy, will depend on the type of combination therapy, the frequency of treatment, and the nature of the desired effect.

[0278] Suitable dosage forms include, but are not limited to, injection solutions, sterile powders for injection, and concentrated injection solutions. Injection solutions include solution-type, emulsion-type (e.g., fat emulsion injection solutions, etc.) or suspension-type injection solutions (e.g., some liposome injection solutions, cortisone acetate injection solutions, etc.), and can be used for intramuscular injection, intravenous injection, intravenous drip, etc. Injections for intravenous injection include intravenous infusion and small water needles. Sterile powders for injection include freeze-dried powder injections and sterile dispensing. Concentrated injection solutions are sterile concentrated solutions that are diluted before use and can be prepared according to methods known in the art.

[0279] Appropriate carriers, solvents, osmotic pressure regulators, pH regulators, solubilizers, cosolvents, antioxidants, bacteriostatic agents, emulsifiers, suspending agents, fillers, complexing agents, and chelating agents, etc., can be provided in the pharmaceutical composition as needed. For example, water for injection, vegetable oils such as soybean oil for injection, ethanol, propylene glycol, polyethylene glycol, etc. can be added as solvents, sodium chloride, glucose, etc. can be added as osmotic pressure regulators, inorganic acids or inorganic bases, organic acids or organic bases, such as hydrochloric acid, sodium hydroxide, sodium citrate, and citric acid, etc. can be added as pH regulators, polyoxyethylene castor oil, polysorbate, cyclodextrin, such as hydroxypropyl-β-cyclodextrin, etc. can be added as solubilizers, organic acids and their sodium salts, such as sodium benzoate, etc. can be added as solubilizers, amides, amines, such as meglumine, etc. can be added as cosolvents, ascorbic acid, sodium sulfite, sodium bisulfite, sodium metabisulfite, etc. can be added as antioxidants, phenol, cresol, trichlorobutanol, and thimerosal can be added as antibacterial agents, lecithin, poloxamer, etc. can be added as emulsifiers, polyvinylpyrrolidone, methylcellulose, etc. can be added as suspending agents, mannitol, glucose, etc. can be added as fillers, ethylenediaminetetraacetic acid, etc. can be added as complexing agents, chelating agents, etc.

[0280] Suitable routes of administration may include, for example, oral administration, rectal administration, transmucosal administration, parenteral delivery, transdermal administration, topical administration, or enteral administration, and parenteral delivery includes intramuscular injection, subcutaneous injection, intravenous, intramedullary, and intrathecal, direct intraventricular, intraperitoneal, intranasal, or intraocular. The compounds can also be extended at a predetermined rate and / or in sustained release or controlled release dosage forms including depot injection, osmotic pumps, pills, transdermal (including iontophoresis) patches, timing, pulsed dosing, and the like.

[0281] The pharmaceutical compositions of the present disclosure can be produced by known methods, for example, by conventional methods such as mixing, formulating, filtering, encapsulating, sterilizing, and the like.

[0282] Thus, according to the present disclosure, the pharmaceutical compositions used can be formulated by conventional methods using one or more physiologically acceptable carriers including adjuvants, and the adjuvants facilitate processing the active compounds into pharmaceutically acceptable formulations. Suitable formulations will depend on the selected route of administration. Any well-known techniques, carriers, and excipients can be used as required, as understood in the art.

[0283] Injections can be prepared in the following conventional forms: as solutions or suspensions, suitable solid dosage forms as solutions or suspensions before injection, or as emulsions. Suitable excipients are, for example, water, saline, dextrose, mannitol, lactose, lecithin, albumin, sodium glutamate, cysteine hydrochloride, and the like. Further, if necessary, the pharmaceutical compositions for injection may contain a small amount of non-toxic adjuvants such as wetting agents, pH buffers, and the like. Physiologically suitable buffers include, but are not limited to, Hank's solution, Ringer's solution, or saline buffer. Absorption enhancing formulations (e.g., liposomes) can be used if necessary.

[0284] In some embodiments, the pharmaceutical composition of the present disclosure may contain from 0.1% to 95% of the compound of the present disclosure, a stereoisomer of the compound of the present disclosure, or a pharmaceutically acceptable salt thereof.

[0285] In some embodiments, the pharmaceutical composition of the present disclosure may contain from 1% to 70% of the compound of the present disclosure, a stereoisomer of the compound of the present disclosure, or a pharmaceutically acceptable salt thereof.

[0286] In any case, the composition or formulation to be administered will contain a certain amount of the compound of the present disclosure, a stereoisomer of the compound of the present disclosure, or a pharmaceutically acceptable salt thereof.

[0287] In any case, the administration will involve an effective amount of the compound of the present disclosure, a stereoisomer of the compound of the present disclosure, or a pharmaceutically acceptable salt thereof for treating the disease / condition of the subject being treated.

[0288] [Method of Administration] At least one compound described in the present disclosure, a stereoisomer of at least one compound described in the present disclosure, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising at least one compound described in the present disclosure, a stereoisomer of at least one compound described in the present disclosure, or a pharmaceutically acceptable salt thereof, can undergo appropriate systemic and / or local delivery in any of the compounds described in the present disclosure, stereoisomers of the compounds described in the present disclosure, or pharmaceutically acceptable salts thereof. The method is administered to a patient. Non-limiting examples of the administration method include: (a) administration by the oral route, including administration in the form of capsules, tablets, granules, sprays, syrups, etc.; (b) administration by parenteral administration, such as rectal, vaginal, intraurethral, intraocular, intranasal or intraauricular, etc., and the administration includes aqueous suspensions, oily preparations, etc., or in the form of drops, sprays, suppositories, ointments, creams, etc.; (c) administration by subcutaneous injection, intraperitoneal injection, intravenous injection, intramuscular injection, intradermal injection, intraorbital injection, intracapsular injection, intraspinal injection, intrathoracic injection, etc., including infusion pump delivery; (d) local administration, such as direct injection into the kidney region or heart region, etc., such as by depot implantation; and (e) topical administration; As is known to those skilled in the art, the appropriate administration method is considered to be bringing the compound described in the present disclosure into contact with living tissue.

[0289] The most appropriate route depends on the nature and severity of the condition being treated. Those skilled in the art are also proficient in determining the administration method (oral, intravenous, inhalation, subcutaneous, rectal, etc.), dosage form, appropriate pharmaceutical excipients, and other matters related to the delivery of the compound to the subject in need.

[0290] Pharmaceutical compositions suitable for administration include those containing an effective amount of an active ingredient. The dosage required for a therapeutically effective amount of the pharmaceutical compositions described in the present disclosure depends on the route of administration, the type of animal being treated, including humans, and the physical characteristics of the particular animal in question. The dosage can be adjusted to achieve the desired effect, but this depends on factors such as body weight, diet, concurrent drug therapy, and other factors recognized by those skilled in the medical art. More specifically, a therapeutically effective amount refers to the amount of a compound that is effective in preventing, alleviating, or improving the symptoms of a disease or in prolonging the lifespan of the individual being treated. The actual ability of those skilled in the art can sufficiently determine a therapeutically effective amount, particularly in accordance with the detailed disclosure provided by the present disclosure.

[0291] As will be apparent to those skilled in the art, the dosage and the particular method of administration for in vivo administration will vary depending on the age, body weight and type of the mammal being treated, the particular compound being used, and the particular use for which the compound is used. Those skilled in the art will be able to achieve the objective of determining an effective dosage level, i.e., the dosage level required to achieve the desired effect, using conventional pharmacological methods. Usually, human clinical applications of a product are initiated at lower dosage levels and the dosage level is increased until the desired effect is achieved. Alternatively, established in vitro studies can be used to establish the effective dosage and route of administration of a composition identified by a method using established pharmacological methods.

[0292] In non-human animal studies, the application of a potential product is initiated at higher dosage levels and the dosage is decreased until the desired effect is no longer achieved or the undesirable side effects disappear. The dosage range can be made wider depending on the desired effect and the therapeutic index. Generally, the dosage can be from about 10 μg / kg body weight to 1000 mg / kg body weight, and in certain embodiments, can be from about 100 μg / kg body weight to 300 mg / kg body weight. Alternatively, as will be appreciated by those skilled in the art, the dosage can be calculated based on the patient's body surface area.

[0293] Each physician can select the exact formulation, route of administration and dosage of the pharmaceutical composition described in this disclosure based on the patient's condition. Generally, the dosage of the composition administered to a patient can range from about 0.05 mg / kg to 3000 mg / kg of the patient's body weight. The dosage can be administered once or more than once a day or for several days, depending on the patient's needs. If the human dosage of the compound has been established in at least some conditions, this disclosure will use those same dosages, or dosages in the range of about 0.1% to 500% of the determined human dosage. In certain embodiments, the dosage is in the range of 25% to 250% of the determined human dosage. In the case of newly discovered drug compounds where there is no determined human dosage, an appropriate human dosage can be inferred from the median effective dose, or median infective dose, or other appropriate values from in vitro or in vivo studies, similar to animals. Quantification by a laboratory for toxicity studies and performance.

[0294] It should be noted that due to toxicity and organ dysfunction, the attending physician should know how to end, interrupt, or adjust the administration. Conversely, if the clinical response is insufficient (excluding toxicity), the attending physician will also know to adjust the treatment to a higher level. The size of the dosage in the treatment of the subject's condition will vary depending on the severity of the condition being treated and the route of administration. The severity of the disease state can be partially evaluated, for example, by standard prognostic assessment methods. Further, the dosage and possible dosing frequency also vary depending on the age, weight, and response of the individual patient. Protocols comparable to the above protocols can be used in veterinary medicine.

[0295] Although the correct dosage can be determined for each drug, in most cases, a certain degree of generalization can be made with respect to the drug. The daily dosing schedule for adult patients is, for example, oral administration of 0.1 mg to 2000 mg of each active ingredient, in certain embodiments, 1 mg to 2000 mg of each active ingredient, for example, 5 mg to 1500 mg of each active ingredient. In other embodiments, the intravenous, subcutaneous, or intramuscular dosage of each active ingredient used is from 0.01 mg to 1000 mg, and in certain embodiments, from 0.1 mg to 1000 mg, for example, from 1 mg to 800 mg. In the case of administration of pharmaceutically acceptable salts, the dosage can be calculated as the free base. In certain embodiments, the composition is administered from 1 to 4 times a day. Alternatively, the compositions described in the present disclosure may, in certain embodiments, be administered by continuous intravenous infusion at a dosage of up to 2000 mg of each active ingredient per day. As will be understood by those skilled in the art, in certain cases, it may be necessary to administer the compounds described in the present disclosure in amounts that exceed, or significantly exceed, the above dosage ranges in order to effectively and rapidly treat rapidly progressing diseases or infections. In certain embodiments, the compounds are administered, for example, during continuous treatment for one week or several weeks, or several months or years.

[0296] The dosage and dosing interval can be adjusted individually to provide a plasma level sufficient to maintain the modulating effect, or the active fraction of the minimum effective concentration (MEC). The MEC of each compound is different, but the MEC can be evaluated from in vitro data. The dosage required to achieve the MEC will depend on the individual characteristics and route of administration. However, the plasma concentration can be determined using an HPLC (high performance liquid chromatography) assay or a bioassay.

[0297] The dosing interval can also be determined using the MEC value. A treatment that maintains plasma levels above the MEC should be used for 10% to 90% of the time, in some embodiments for 30% to 90% of the time, and in some embodiments for 50% to 90% of the time. Apply the dosing schedule to the composition.

[0298] In the case of topical administration or selective absorption, the effective local concentration of the drug is independent of the plasma concentration. Of course, the amount of the composition to be administered is determined by the individual being treated, depending on the individual's body weight, the severity of the pain, the method of administration, and the judgment of the prescribing physician.

[0299] The efficacy and toxicity of the compounds described in the present disclosure can be evaluated using known methods. For example, the toxicity of a particular compound, or a subset of the compounds sharing a particular chemical moiety, can be established by measuring, for example, the toxicity of cell lines in mammalian cell lines, and in certain embodiments human cell lines, in vitro. The results of such studies generally predict the toxicity of animals such as mammals, or more specifically humans. Alternatively, the toxicity of a particular compound in an animal model such as a mouse, rat, rabbit, or monkey can be determined using known methods. The effectiveness of a particular compound can be determined using any of several recognized methods such as in vitro methods, animal models, or human clinical trials. There are well-recognized in vitro models for almost all types of disease states, including but not limited to cancer, cardiovascular disease, and various immune dysfunctions. Similarly, acceptable animal models can be used to determine the effectiveness of chemical substances that treat these disease states. When selecting a model for measuring efficacy, a skilled artisan can select an appropriate model, dosage, and route of administration, as well as a treatment plan, in accordance with the guidance of the prior art in the art. Of course, human clinical trials can also be used to determine the efficacy of a compound in the human body.

[0300] Optionally, the composition can be placed in a packing device or a dispenser device, which can contain one or more unit dosage forms containing the active ingredient. The pack can include, for example, a metal foil or a plastic foil such as a blister pack. Instructions regarding administration can be provided for the packing device or the dispenser device. The packing device or the dispenser device may also carry notes related to the container, which are defined by the government agency that regulates the manufacture, use or sale of the drug and which reflect that the drug form is approved for administration to humans or animals. Such considerations may be, for example, the label for a prescription drug approved by the State Food and Drug Administration or the US Food and Drug Administration, or an approved product specification. The composition containing the compound of the present invention can be prepared in a suitable container, placed in a compatible pharmaceutical carrier, and may be labeled for therapeutic use in a defined pathological condition.

[0301] The present disclosure will be described in detail by the following examples in order to better understand the various aspects of the present application and their advantages. However, it should be understood that the following examples are non-limiting and are intended to illustrate only specific embodiments of the present application.

[0302] [Examples] Abbreviations: aq: aqueous solution ml: milliliter g: gram V: volume / weight eq: equivalent ratio L: liter M: mole / liter mg: milligram μl: microliter EDCI: 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride HOBt: 1-hydroxybenzotriazole DIEA: diisopropylethylamine DCM: dichloromethane PE: Petroleum ether EA: Ethyl acetate DMSO: Dimethyl sulfoxide ACN: Acetonitrile MeOH: Methanol DMF: N,N-Dimethylformamide PPh3: Triphenylphosphine THF: Tetrahydrofuran VCNa: Sodium ascorbate NaH: Sodium hydride CuSO4: Anhydrous copper sulfate HCl: Hydrochloric acid NaOH: Sodium hydroxide CBr4: Carbon tetrabromide AcOH: Glacial acetic acid Ar: Argon NaN3: Sodium azide NaCl: Sodium chloride AlCl3: Aluminum chloride K2CO3: Potassium carbonate Na2SO4: Sodium sulfate CHCl3: Chloroform NaBH4: Sodium borohydride IPA: Isopropanol TFA: Trifluoroacetic acid MTBE: Methyl tert-butyl ether HATU: 2-(7-Azabenzotriazol)-N,N,N’,N’-tetramethyluronium hexafluorophosphate NH4Cl: Ammonium chloride MeONa: Sodium methoxide Ag2O: Silver oxide Boc2O: Di-tert-butyl dicarbonate CDCl3: Deuterated chloroform HPLC: High performance liquid chromatography TLC: Thin layer chromatography DMF: N,N-Dimethylformamide EDTA: Ethylenediaminetetraacetic acid mM: mmol / L mm 3 : Cubic centimeter 1 HNMR: Nuclear magnetic resonance spectrum

[0303] Example 1 N-(4’-Amino-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)-6-bromohexanamide To 60 ml of DCM, 2.177 g of ortho-toluidine, 2.359 g of EDCI, 1.663 g of HOBt, and 1.590 g of DIEA were added. The mixture was stirred until completely dissolved under argon and cooled from 0 °C to 5 °C. 2 g of 6-bromohexanoic acid was dissolved in 40 ml of DCM. The resulting solution was added dropwise to the reaction system at 0 °C to 5 °C. After the addition was complete, the reaction was carried out at room temperature overnight. 20 ml of saturated aqueous sodium bicarbonate solution was added to the reaction system, stirred, and suction filtered. The filter cake was stirred in DCM and suction filtered. The filtrate was retained. The above steps were repeated 3 times. The combined DCM phases were dried, suction filtered, concentrated, and purified by column chromatography, and concentrated to obtain 2.047 g of the product. MS(m / e): 389.20 [M+H] + .

[0304] Example 2 N-(4’-Amino-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)-6-azidohexanamide To the reaction flask, 0.73 g of the compound of Example 1 and 5.1 ml of DMSO were added. The mixture was stirred at room temperature until completely dissolved. 0.15 g of NaN3 was added to obtain an orange-red suspension, which was stirred at room temperature overnight. DCM (20 ml) and water (20 ml) were added. The mixture was extracted and separated. The DCM phase was retained, and the aqueous phase was extracted and separated again with DCM (20 ml). The combined DCM phases were washed with saturated aqueous NaCl solution, dried over anhydrous sodium sulfate, suction filtered, concentrated, and purified by column chromatography to obtain 0.28 g of the product. MS(m / e): 352.24 [M+H] + .

[0305] Example 3 (E)-4-Amino-6-((4’-(6-azidohexanamido)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonic acid disodium Step 1: 0.25 g of the compound of Example 2 was added to 4 ml of acetonitrile. The mixture was cooled in an ice-salt bath and stirred under argon until completely dissolved. The ice-salt bath was cooled from 0 °C to 5 °C, and an HCl solution (having 0.18 ml of 12 mol / L hydrogen chloride in 6 ml of deionized water) was added dropwise. After stirring for 5 minutes, a sodium nitrite solution (having 0.1 g of sodium nitrite in 300 ml of deionized water) was added dropwise over about 20 minutes. The addition was completed while stirring for 30 minutes. Step 2: 0.24 g of sodium 4-amino-5-hydroxy-1,3-naphthalenedisulfonate and 5 ml of deionized water were added to the reaction flask. The mixture was cooled in an ice-salt bath and stirred under Ar protection until completely dissolved. The ice-salt bath was cooled from 0 °C to 5 °C. A sodium bicarbonate solution (having 0.24 g of sodium bicarbonate in 5 ml of deionized water) was added dropwise over about 20 minutes.

[0306] The ice-salt bath was maintained at a temperature of 0 °C to 5 °C. The reaction solution of Step 1 was slowly added to the reaction solution of Step 2. The resulting mixture was stirred in an ice-salt bath for 3 hours. 19 mL of 20% aqueous NaCl solution was added. The mixture was stirred at room temperature overnight. The reaction solution was centrifuged to obtain about 1.2 g of a purple solid. The solid was dissolved in H2O:ACN = 10:1 (total 13.2 mL). The resulting mixture was stirred at room temperature overnight. The reaction solution was centrifuged to obtain a crude purple solution. The crude purple solution was purified at medium pressure. The prepared solution was concentrated to remove acetonitrile and freeze-dried to obtain 0.41 g of the product. 1 HNMR (DMSO-d6, 600 MHz) δ: 15.954 (s, 1H), 9.643 (s, 1H), 9.277 (s, 1H), 8.362 (s, 1H), 8.042 - 8.025 (d, 1H), 7.902 - 7.887 (d, 1H), 7.652 - 7.650 (m, 2H), 7.572 (s, 1H), 1.661 - 1.581 (s, 2H), 7.003 - 6.987 (d, 1H), 3.366 - 3.344 (t, 2H), 2.277 (s, 3H), 2.385 - 2.361 (t, 2H), 2.277 (s, 3H), 1.661 - 1.581 (m, 4H), 1.422 - 1.397 (m, 2H).

[0307] Example 4 (2S,3R,4S,5S,6S)-2-(4-(Bromomethyl)-3-(prop-2-ynyloxy)phenoxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triacetate To 7 mL of DCM, 1 g of (2S,3R,4S,5S,6S)-2-(4-(hydroxymethyl)-3-(prop-2-ynyloxy)phenoxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triacetate (see the preparation method of PCT international application, 2012153193, on November 15, 2012) and 1.6 g of carbon tetrabromide were added. The mixture was stirred until dissolved. The resulting mixture was cooled in an ice-salt bath and stirred. The reaction system was cooled from 6 °C to 8 °C. 0.8 g of triphenylphosphine was weighed and added little by little to the reaction flask. The mixture was stirred in the ice-salt bath for 5 minutes. The reaction system was cooled to about 10 °C. The ice-salt bath was removed and the reaction was stirred at room temperature for 2 hours. Silica gel was added directly to the reaction solution and 0.74 g of the product was obtained by column chromatography. 1 H NMR (CDCl3, 400 MHz) δ: 7.277 - 7.263 (d, 1H), 6.752 - 6.721 (d, 1H), 6.640 - 6.586 (dd, 1H), 2.051 (m, 2H), 5.292 - 5.263 (m, 1H), 5.159 - 5.146 (d, 1H), 4.758 - 4.754 (d, 2H), 4.542 - 4.506 (d, 2H), 4.189 - 4.173 (m, 1H), 3.730 (s, 3H), 2.043 (t, 1H), 2.064 (s, 3H), 2.051 (s, 3H), 2.043 (s, 3H). MS (m / e): 579.65 [M+Na] + .

[0308] Example 5 (2S,3R,4S,5S,6S)-2-(4-(((S)-4,11-Diethyl-4-hydroxy-3,14-dioxy-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-3-(prop-2-ynyloxy)phenoxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triacetate To a reaction flask, 0.74 g of (2S,3R,4S,5S,6S)-2-(4-(bromomethyl)-3-(prop-2-ynyloxy)phenoxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triacetate and 43.3 g of (S)-4,11-diethyl-4,9-dihydroxy-1,12-dihydro-14H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-3,14(4H)-dione were added. The mixture was shielded from light and dissolved in 600 mL of DMF. The resulting mixture was stirred in an ice-salt bath for 2 minutes. 0.04 g of sodium hydride was slowly added little by little. The resulting substance was stirred under argon for 1 minute. The ice-salt bath was removed, and after 20 minutes, the reaction system was dissolved and became transparent, and stirred at room temperature for 1 hour. 0.06 ml of AcOH was added to the reaction. The mixture was stirred for 1 minute. DMF was removed by concentration on silica gel. 1.2 g of the product was obtained by column chromatography. 12 ml of EA was added. The mixture was sonicated, stirred at room temperature for 16 hours, and suction filtered. The filter cake was washed with EA to obtain 0.73 g of the product. HPLC purity 96.5%. 1 HNMR(DMSO-d6,400MHz)δ:8.076-8.053(d,1H),7.561-7.468(m,3H),3.634(s,1H),2.010(s,1H),3.586(d,1H),2.028(s,1H),5.731-5.711(d,1H),2.000(t,1H),3.178-3.160(s,2H),0.895-0.8 59 (s, 2H), 1.883 - 1.845 (s, 2H), 5.136 - 5.050 (m, 2H), 4.925 (s, 2H), s (d, 1H), 3.634 (s, 3H), 3.586 (s, 1H), 3.178 - 3.160 (d, 2H), 2.028 (s, 3H), 2.010 (s, 3H), 2.000 (s, 3H), 1.883 - 1.845 (m, 2H), 1.297 - 1.260 (t, 3H), 0.895 - 0.859 (t, 3H). MS (m / e): 869.98 [M + H] + .

[0309] Example 6 (2S,3S,4S,5R,6S)-6-(4-(((S)-4,11-Diethyl-4-hydroxy-3,14-dioxy-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-3-(prop-2-ynyloxy)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid 0.72 g of (2S,3R,4S,5S,6S)-2-(4-(((S)-4,11-Diethyl-4-hydroxy-3,14-dioxy-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indrazino[1,2-b]quinolin-9-yl)oxy)methyl)-3-(prop-2-ynyloxy)phenoxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triacetate and 7.2 ml of THF were added to a reaction flask. The mixture was stirred and cooled in an ice-ethanol bath. The mixture was stirred for about 30 minutes. 0.2 g of sodium hydroxide was dissolved in 7.2 ml of deionized water. The solution was added dropwise to the mixture. The sample was gradually dissolved. The ice-ethanol was removed. The resulting mixture was stirred at room temperature for 1 hour and cooled with ice-cold ethanol for about 10 minutes. 5 ml of 1N·HCl was added dropwise over about 20 minutes. The THF was removed by concentration. The resulting substance was filtered under reduced pressure using a water pump. 0.57 g of the product was obtained by column chromatography. 1HNMR (DMSO-d6, 400 MHz) δ: 8.050 - 8.035 (d, 1H), 3.164 - 3.153 (s, 1H), 7.519 - 7.503 (d, 1H), t(d, 1H), 3.310 - 3.256 (s, 1H), 6.863 (s, 1H), 6.720 - 6.707 (d, 1H), 6.495 (s, 1H), 1.301 - 1.276 (m, 0.890 - 0.865), 4.997 - 4.985 (d, 1H), 1.905 - 1.833 (s, 2H), 3.686 (s, 1H), 3.585 (s, 1H), 3.310 - 3.256 (m, 3H), 3.164 - 3.153 (d, 2H), 1.905 - 1.833 (m, 2H), 1.301 - 1.276 (t, 3H), 0.890 - 0.865 (t, 3H). MS (m / e): 729.74 [M+H] + .

[0310] Example 7 (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium Under room temperature conditions, 0.54 g of the compound of Example 6 and 0.5 g of disodium (E)-4-amino-6-((4’-(6-azidohexanamido)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate were added to a reaction flask. The mixture was dissolved in 11 ml of THF while shielding from light and stirring. 0.02 g of CuSO4 was dissolved in 0.3 ml of deionized water, and 0.06 g of VCNa was dissolved using 0.3 ml of deionized water. While protecting with argon, the above solutions and 10 ml of deionized water were successively added to the reaction system. The mixture was stirred at room temperature for 1 hour and suction filtered to obtain a purple filtrate. THF was removed by concentration at 38 °C. After concentration, 10 ml of water was added and stirred for 5 to 10 minutes. 4 ml of a 20% aqueous NaCl solution was added to prepare the crude product as an approximately 5% aqueous NaCl solution and salted out overnight at room temperature. The reaction product was centrifuged and separated to obtain a solid. The solid was dissolved in 210 ml of deionized water and mechanically stirred at room temperature for 1 hour. 4 ml of a 20% aqueous NaCl solution was added to prepare the crude product as a 3% aqueous NaCl solution and salted out overnight at room temperature. The reaction product was centrifuged and separated to obtain a solid. The solid was dissolved in 15 ml of deionized water and stirred overnight at room temperature. The resulting substance was suction filtered to obtain a purple filtrate. The filtrate was purified under medium pressure. The prepared solution was concentrated to remove acetonitrile, freeze-dried and pulverized to obtain 0.73 g of the product. 1HNMR (DMSO-d6, 400 MHz) δ: 15.907 (s, 1H), 9.638 (s, 1H), 9.378 (s, 1H), 8.413 (s, 1H), 8.281 (s, 1H), 8.029 - 8.013 (d, 1H), 7.984 - 7.970 (d, 1H), 7.816 - 7.804 (d, 1H), 7.580 (s, 2H), 7.493 - 7.432 (m, 5H), 7.372 - 7.358 (d, 1H), 7.243 (s, 1H), 7.033 (s, 1H), 6.979 - 6.963 (d, 1H), 6.681 - 6.668 (d, 1H), 6.506 (s, 1H), 5.424 - 5.184 (m, 10H), 4.980 - 4.970 (d, 1H), 4.348 (s, 2H), 3.623 (s, 1H), 3.337 - 3.247 (m, 3H), 3.073 (s, 2H), 2.455 (s, 3H), 2.315 (s, 2H), 2.211 (s, 3H), 1.821 - 1.810 (m, 4H), 1.578 (s, 2H), 1.233 - 1.223 (m, 5H), 0.884 - 0.860 (t, 3H).

[0311] Example 8 (2S,3R,4S,5S,6S)-2-(4-Formyl-3-hydroxy-2-methylphenoxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triacetate 1.686 g of 2,4-dihydroxy-3-methylbenzaldehyde, 4 g of (2S,3R,4S,5S,6S)-2-bromo-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triacetate, 1.292 g of silver oxide, and 1.6 g of 4A molecular sieve were weighed and successively added to a reaction flask. 80 ml of acetonitrile was added to the reaction flask. The mixture was protected with argon and stirred at room temperature for 1 hour. The resulting substance was suction filtered. Celite was added. The filter cake was washed with dichloromethane. The filtrate was concentrated to dryness. After purification by column chromatography, 2.935 g of the product was obtained. MS (m / e): 491.11 [M+Na] + . 1HNMR (DMSO-d6, 600 MHz) δ: 11.348 (s, 1H), 9.895 (s, 1H), 7.674 - 7.660 (d, 1H), 6.806 - 6.792 (d, 1H), 5.772 - 5.759 (d, 1H), 5.531 - 5.499 (t, 1H), 5.222 - 5.193 (dd, 1H), 5.120 - 5.087 (t, 1H), 4.796 - 4.779 (d, 1H), 3.649 (s, 3H), 2.034 - 2.020 (t, 9H), 1.950 (s, 3H).

[0312] Example 9 (2S,3R,4S,5S,6S)-2-(4-Formyl-2-methyl-3-(prop-2-ynyloxy)phenoxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triacetate 2.83 g of (2S,3R,4S,5S,6S)-2-(4-formyl-3-hydroxy-2-methylphenoxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triacetate was weighed and added to 28 ml of dry DMF. The mixture was stirred until completely dissolved at room temperature. Potassium carbonate (2.505 g) and bromopropyne (1.078 g) were successively weighed and slowly added to the reaction system little by little. The reaction was carried out at room temperature for 4 hours. The reaction system was extracted with ethyl acetate. The organic phase was washed twice with saturated ammonium chloride solution, washed with saturated sodium chloride, and dried over anhydrous sodium sulfate. The filtrate was concentrated to dryness by suction. After purification by column chromatography, 2.588 g of the product was obtained. MS (m / e): 507.15 [M + H] + . 1 HNMR (6H, 600 MHz) δ: 10.183 (s, 1H), 7.691 - 7.677 (d, 1H), 7.066 - 7.051 (d, 1H), 5.782 - 5.769 (d, 1H), 2.027 - 2.021 (t, 1H), 5.225 - 5.196 (dd, 1H), 5.120 - 5.087 (t, 1H), 4.795 - 4.779 (m, 3H), 3.660 - 3.652 (t, 1H), 3.611 (s, 3H), 2.060 (s, 3H), 2.047 (s, 3H), 2.027 - 2.021 (d, 6H).

[0313] Example 10 (2S,3R,4S,5S,6S)-2-(4-Hydroxymethyl)-2-methyl-3-(prop-2-ynyloxy)phenoxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triacetate 2.367 g of (2S,3R,4S,5S,6S)-2-(4-formyl-2-methyl-3-(prop-2-ynyloxy)phenoxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triacetate was weighed and added to 23.7 ml of chloroform. The mixture was stirred until completely dissolved and cooled to 0 °C - 5 °C in an ice-salt bath. 11.835 g of silica gel and 4.7 ml of isopropanol were successively added. 442 mg of sodium borohydride was weighed and added little by little. The reaction was maintained at 0 °C - 5 °C for 1 hour. The reaction was quenched by the addition of 1 ml of glacial acetic acid. The resulting substance was suction filtered. Diatomaceous earth was added. The filter cake was washed with dichloromethane. The filtrate was concentrated to dryness. After purification by column chromatography, 2.038 g of the product was obtained. MS(m / e): 531.20[M+Na] + . 1 HNMR(DMSO-d6,600MHz)δ: 7.223 - 7.209(2.025 - 2.010,1H), 6.868 - 6.854(2.025 - 2.010,1H), 5.556 - 5.543(2.025 - 2.010,1H), 5.504 - 5.472(t,1H), 5.159 - 5.130(dd,1H), 5.091 - 5.058(t,1H), 5.027 - 5.009(t,1H), 4.727 - 4.711(2.025 - 2.010,1H), 4.569 - 4.565(2.025 - 2.010,2H), 4.501 - 4.491(2.025 - 2.010,2H), 3.652(s,3H), 3.571 - 5.562(t,1H), 2.040(s,3H), 2.025 - 2.010(t,9H).

[0314] Example 11 (2S,3R,4S,5S,6S)-2-(4-(Bromomethyl)-2-methyl-3-(prop-2-ynyloxy)phenoxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triacetate 1.99 g of the product was prepared by the preparation method of Example 4 using (2S,3R,4S,5S,6S)-2-(4-hydroxymethyl)-2-methyl-3-(prop-2-ynyloxy)phenoxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triacetate. 1 HNMR(DMSO-d6,600 MHz) δ: 7.248 - 7.234 (d, 1H), 6.839 - 6.825 (d, 1H), 5.375 - 5.359 (m, 3H), 5.141 - 5.129 (dd, 1H), 4.676 - 4.659 (m, 3H), 4.614 - 4.596 (d, 1H), 4.216 - 4.201 (dd, 1H), 3.756 (s, 3H), 2.585 - 2.577 (t, 1H), 2.163 (s, 3H), 2.088 - 2.070 (t, 9H).

[0315] Example 12 (2S,3R,4S,5S,6S)-2-(4-(((S)-4,11-diethyl-4- (hydroxy-3,14-dioxy-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)-2-methyl-3-(prop-2-ynyloxy)phenoxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triacetate 2.6 g of the product (2S,3R,4S,5S,6S)-2-(4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)-2-methyl-3-(prop-2-ynyloxy)phenoxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triacetate was prepared using (2S,3R,4S,5S,6S)-2-(4-(bromomethyl)-2-methyl-3-(prop-2-ynyloxy)phenoxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triacetate and the compound (S)-4,11-diethyl-4,9-dihydroxy-1,12-dihydro-14H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-3,14(4H)-dione obtained by the preparation method of Example 5. MS (m / e): 883.49 [M+H] + . 1 1H NMR (DMSO-d6, 600 MHz) δ: 8.086 - 8.071 (d, 1H), 7.603 - 7.598 (d, 1H), 7.541 - 7.521 (dd, 1H), 7.421 - 7.406 (d, 1H), 7.272 (s, 1H), 6.937 - 6.923 (d, 1H), 6.502 (s, 1H), 5.610 - 5.597 (d, 1H), 5.507 - 5.460 (t, 1H), 5.432 (s, 2H), 5.350 - 5.323 (d, 2H), 5.297 (s, 2H), 5.179 - 5.150 (q, 1H), 5.097 - 5.059 (t, 1H), 4.745 - 4.734 (d, 1H), 4.700 - 4.696 (d, 2H), 3.652 - 3.635 (s, 3H), 3.609 - 3.601 (t, 1H), 3.196 - 3.159 (dd, 2H), 2.086 (s, 3H), 2.039 (s, 3H), 2.013 - 2.011 (d, 6H), 1.915 - 1.829 (m, 2H), 1.294 - 1.268 (t, 3H), 0.896 - 0.872 (t, 3H).

[0316] Example 13 (2S,3S,4S,5R,6S)-6-(4-(((S)-4,11-Diethyl-4-hydroxy-3,14-dioxy-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)-2-methyl-3-(prop-2-ynyloxy)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid 1.5 g of the product was prepared by the method of Preparation Example 6 using (2S,3R,4S,5S,6S)-2-(4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxy-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)-2-methyl-3-(prop-2-ynyloxy)phenoxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triacetate. MS (m / e): 743.38 [M+H] + . 1 HNMR (DMSO-d6, 600 MHz) δ: 8.064 - 8.049 (d, 1H), 7.608 (s, 1H), 1.913 - 1.830 (d, 1H), 1.315 - 1.290 (d, 1H), 7.265 (s, 1H), 6.969 - 6.955 (d, 1H), 6.497 (s, 1H), 5.454 - 5.398 (t, 2H), 3.345 - 3.291 (m, 6H), 5.134 (s, 1H), 0.897 - 0.873 (d, 1H), 4.680 - 4.677 (d, 2H), 3.591 - 3.583 (t, 2H), 3.345 - 3.291 (d, 3H), s(d, 2H), 2.209 (s, 3H), 1.913 - 1.830 (m, 2H), 1.315 - 1.290 (t, 3H), 0.897 - 0.873 (t, 3H).

[0317] Example 14 (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)-2-methylphenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium 248 mg of the product was prepared by the preparation method of Example 7 using (2S,3S,4S,5R,6S)-6-(4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)-2-methyl-3-(prop-2-ynyloxy)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid, and (E)-4-amino-6-((4’-(6-azidohexanamido)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonic acid disodium. MS(m / e): 1424.70 [M - 3Na + 4H] + . 1HNMR (DMSO-d6, 600 MHz) δ: 15.915 (s, 1H), 9.253 (s, 1H), 8.370 (s, 1H), 8.186 (s, 1H), 8.063 - 8.032 (t, 2H), 7.887 - 7.872 (d, 1H), 7.629 - 7.619 (d, 3H), 7.535 - 7.504 (m, 2H), 7.469 (s, 2H), 7.331 - 7.317 (d, 1H), 7.268 (s, 1H), 7.008 - 6.956 (dd, 2H), 6.483 (s, 1H), 5.419 - 5.414 (d, 2H), 5.292 (s, 2H), 5.253 - 5.180 (m, 3H), 5.055 - 5.016 (q, 2H), 4.979 (s, 1H), 4.817 - 4.805 (d, 1H), 4.342 - 4.319 (t, 2H), 3.402 - 3.385 (d, 1H), 3.271 - 3.255 (m, 2H), 3.171 - 3.148 (t, 3H), 2.511 - 2.502 (m, 3H), 2.311 - 2.288 (t, 2H), 2.243 - 2.235 (d, 6H), 1.893 - 1.823 (m, 2H), 1.811 - 1.772 (m, 2H), 1.588 - 1.564 (m, 2H), 1.264 - 1.251 (m, 5H), 0.885 - 0.860 (t, 3H).

[0318] Example 15 4-Amino-6-((E)-(4'-(6-(4-((3-(((2S,3R,4S,5S,6S)-6-carboxy-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)oxy)-6-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxy-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)-2-tolyloxy)methyl)-1H-1,2,3-triazol-1-yl)hexanamide)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonic acid disodium At room temperature, 49 mg of the compound of Example 14 was dissolved in 1 ml of ionized water. To the mixture, 0.33 ml of 0.1 M hydrochloric acid was added with stirring. The resulting substance was stirred at room temperature for 1 hour. A purple reaction solution was prepared and purified under medium pressure. The prepared solution was concentrated to remove acetonitrile and freeze-dried to obtain 10 mg of the product. MS (m / e): 1424.53 [M - 2Na + 3H] + .

[0319] Example 16 Methyl (2S,3S,4S,5R,6S)-6-(4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxy-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy) methyl)-2-methyl-3-(prop-2-ynyloxy)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate 126 mg of the product was prepared by the preparation method of Example 20 using (2S,3R,4S,5S,6S)-2-(4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxy-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)-2-methyl-3-(prop-2-ynyloxy)phenoxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triacetate. MS (m / e): 757.58 [M + H] + .

[0320] Example 17 Sodium 4-amino-6-((E)-(4'-(6-(4-((6-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indazolo[1,2-b]quinolin-9-yl)oxy)methyl)-2-methyl-3-((((2S,3R,4S,5S,6S)-3,4,5-trihydroxy-6-(methoxycarbonyl)tetrahydro-2H-pyran-2-yl)oxy)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)hexanamido)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate 24 mg of the product was prepared by the preparation method of Example 7 using methyl (2S,3S,4S,5R,6S)-6-(4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indazolo[1,2-b]quinolin-9-yl)oxy)methyl)-2-methyl-3-(prop-2-ynyloxy)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate, and disodium (E)-4-amino-6-((4'-(6-azidohexanamido)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate. MS (m / e): 1438.57 [M - 2Na + 3H] + .

[0321] Example 18 (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,7]quinolin-9-yl)oxy)methyl)-2-methylphenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium 135 mg of the product was prepared by the preparation method of Example 7 using (2S,3S,4S,5R,6S)-6-(4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indrazolo[1,2-b]quinolin-9-yl)oxy)methyl)-2-methyl-3-(prop-2-ynyloxy)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid and (E)-4-amino-6-((4’-(6-azidohexanamido)-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonic acid disodium. MS (m / e): 1397.04 [M - 3Na + 4H] + . 1 HNMR (DMSO-d6, 600 MHz) δ: 15.644 (s, 1H), 10.036 (s, 1H), 8.353 (s, 1H), 8.150 (s, 1H), 8.061 - 8.046 (d, 1H), 8.009 - 7.992 (d, 1H), 7.719 - 7.705 (d, 2H), 7.669 - 7.649 (dd, 4H) , 7.626 - 7.611 (d, 3H), 7.514 - 7.495 (d, 1H), 7.286 - 7.262 (t, 2H), 6.960 - 6.928 (t, 2H), 6.472 (s, 1H), 5.438 - 5.378 (q, 2H), 5.296 (s, 2H), 5.230 - 5.211 (d, 2H), 5.161 - 5.142 (d, 1H), 5.052 - 5.002 (q, 2H), 4.969 - 4.963 (d, 1H), 4.808 (d, 1H), 4.332 - 4.309 (t, 2H), 3.403 - 3.388 (d, 1H), 3.259 (s, 2H), 3.166 - 3.154 (d, 3H), 2.270 - 2.246 (t, 2H), 2.211 (s, 3H), 1.874 - 1.797 (m, 2H), 1.775 - 1.727 (m, 2H), 1.555 - 1.531 (m, 2H), 1.282 - 1.256 (t, 3H), 1.192 (m, 2H), 0.878 - 0.853 (t, 3H).

[0322] Example 19 4 - Amino - 6 - ((E)-(4’-(6-(4-((5-(((2S,3R,4S,5S,6S)-6 - carboxy - 3,4,5 - trihydroxytetrahydro - 2H - pyran - 2 - yl)oxy)-2 - ((((S)-4,11 - diethyl - 4 - hydroxy - 3,14 - dioxo - 3,4,12,14 - tetrahydro - 1H - pyrano[3’,4’:6,7]indolizino[1,2 - b]quinolin - 9 - yl)oxy)methyl)phenoxy)methyl)-1H - 1,2,3 - triazol - 1 - yl)hexanamide)-3,3’ - dimethyl - [1,1’ - biphenyl]-4 - yl)diazenyl)-5 - hydroxynaphthalene - 1,3 - disulfonic acid disodium The 15 mg product was prepared by the preparation method of Example 15 using trisodium (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate. MS (m / e): 1410.57 [M-2Na+3H] + .

[0323] Example 20 Methyl (2S,3S,4S,5R,6S)-6-(4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-3-(prop-2-ynyloxy)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate 1 g of (2S,3R,4S,5S,6S)-2-(4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indazolo[1,2-b]quinolin-9-yl)oxy)methyl)-3-(prop-2-ynyloxy)phenoxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triacetate, 120 ml of methanol, and 120 ml of tetrahydrofuran are dissolved at room temperature with stirring. 180 mg of sodium methoxide is added. The mixture is stirred at room temperature for 1 hour. 5 drops of glacial acetic acid are added to the reaction. The mixture is evaporated to dryness. The result is dissolved in methanol. The mixture is stirred until clear. After purification by column chromatography, 670 mg of the product is obtained. MS (m / e): 743.34 [M+H] + .1H NMR (DMSO-d6, 600 MHz) δ: 8.083 - 8.068 (m, 1H), 0.899 - 0.848 (m, 1H), 4.091 - 4.068 (1.310 - 1.284, 1H), 7.443 - 7.429 (m, 1H), 3.661 (s, 1H), 4.918 - 4.914 (m, 1H), 3.572 - 3. 564 (1.310 - 1.284, 1H), 1.915 - 1.832 (s, 1H), 5.495 - 5.487 (m, 1H), 5.430 - 5.421 (m, 3H), 5.301 (s, 2H), t (m, 1H), 5.235 (s, 2H), 5.170 - 5.158 (m, 1H), 4.918 - 4.914 (m, 2H), 4.091 - 4.068 (1.310 - 1.284, 1H), 3.661 (s, 3H), 3.572 - 3.564 (t, 1H), 3.437 - 3.305 (m, 3H), 3.190 - 3.165 (m, 2H), 1.915 - 1.832 (m, 2H), 1.310 - 1.284 (t, 3H), 0.899 - 0.848 (m, 3H).

[0324] Example 21 4-Amino-6-((E)-(4'-(6-(4-((2-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxy-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indrazolo[1,2-b]quinolin-9-yl)oxy)methyl)-5-(((2S,3R,4S,5S,6S)-3,4,5-trihydroxy-6-(methoxycarbonyl)tetrahydro-2H-pyran-2-yl)oxy)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)hexanamido)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonic acid disodium 223 mg of the product was prepared by the preparation method of Example 7 using methyl (2S,3S,4S,5R,6S)-6-(4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxy-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indrazino[1,2-b]quinolin-9-yl)oxy)methyl)-3-(prop-2-ynyloxy)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate and (E)-4-amino-6-((4'-(6-azidohexanamido)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonic acid disodium. MS (m / e): 1424.91 [M - 2Na + 3H] + . 1HNMR (DMSO-d6, 600 MHz) δ: 15.945 (s, 1H), 9.217 (s, 1H), 8.368 (s, 1H), 8.182 (s, 1H), 8.065 - 8.050 (d, 1H), 8.040 - 8.024 (d, 1H), 7.881 - 7.866 (d, 1H), 7.625 - 7.616 (d, 2H), 7.533 (s, 3H), 7.465 (s, 2H), 7.413 - 7.398 (d, 1H), 7.264 (s, 1H), 7.005 - 6.978 (m, 2H), 6.688 - 6.670 (dd, 1H), 6.504 (s, 1H), 5.533 - 5.525 (d, 1H), 5.474 - 5.465 (d, 1H), 5.415 (s, 2H), 5.329 - 5.320 (d, 1H), 5.292 - 5.272 (t, 3H), 5.225 - 5.195 (t, 4H), 4.354 - 4.330 (t, 2H), 4.132 - 4.116 (d, 1H), 3.654 (s, 3H), 3.438 - 3.398 (m, 1H), 3.328 (s, 2H), 3.139 - 3.127 (dd, 2H), 2.514 - 2.505 (s, 3H), 2.306 - 2.284 (t, 2H), 2.226 (s, 3H), 1.876 - 1.792 (m, 4H), 1.593 - 1.569 (m, 2H), 1.266 - 1.219 (m, 5H), 0.883 - 0.858 (t, 3H).

[0325] Example 22 (2S,3R,4S,5S,6S)-2-(4-(((S)-4-Ethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)-3-(prop-2-ynyloxy)phenoxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triacetate 700 mg of the product was prepared by the method of Example 5 from (2S,3R,4S,5S,6S)-2-(4-(bromomethyl)-3-(prop-2-ynyloxy)phenoxy)- It was prepared using 6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triacetate and (S)-4-ethyl-4,9-dihydroxy-1,12-dihydro-14H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinoline-3,14(4H)-dione. MS (m / e): 841.88 [M+H] + .

[0326] Example 23 (2S,3S,4S,5R,6S)-6-(4-(((S)-4-ethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-3-(prop-2-ynyloxy)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid 220 mg of the product was prepared by the preparation method of Example 6 using (2S,3R,4S,5S,6S)-2-(4-((((S)-4-ethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indazol[1,2-b]quinolin-9-yl)oxy)methyl)-3-(prop-2-ynyloxy)phenoxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triacetate. MS (m / e): 701.51 [M+H] + . 11H NMR (DMSO-d6, 600 MHz) δ: 8.551 (s, 1H), 8.075 - 8.059 (1.917 - 1.822, 1H), m (s, 1H), 7.554 - 7.538 (1.917 - 1.822, 1H), 7.418 - 7.404 (1.917 - 1.822, 1H), 0.802 - 0.878 (s, 1H), 6.891 (s, 1H), 3.185 - 3.154 (1.917 - 1.822, 1H), 5.450 - 5.394 (t, 2H), 5.273 (s, 2H), 5.182 (s, 2H), 4.889 (s, 3H), 3.596 (s, 1H), 3.446 - 3.430 (1.917 - 1.822, 1H), 3.296 - 3.227 (m, 2H), 3.185 - 3.154 (t, 1H), 1.917 - 1.822 (m, 2H), 0.802 - 0.878 (t, 3H).

[0327] Example 24 (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4-ethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium The 68 mg product was prepared by the preparation method of Example 7 using (2S,3S,4S,5R,6S)-6-(4-(((S)-4-ethyl-4-hydroxy-3,14-dioxy-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indazolo[1,2-b]quinolin-9-yl)oxy)methyl)-3-(prop-2-ynyloxy)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid and disodium (E)-4-amino-6-((4’-(6-azidohexanamido)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate. MS (m / e): 1380.59 [M - 3Na + 2H] - . 1 1H NMR (DMSO-d6, 600 MHz) δ: 15.956 (s, 1H), 9.529 (s, 1H), 8.526 (s, 1H), 8.371 - 8.357 (d, 2H), 8.062 - 8.027 (t, 2H), 7.889 - 7.871 (d, 1H), 7.631 (s, 2H), 7.583 - 7.579 (d, 1H), 7.531 - 7.513 (dd, 2H), 7.480 - 7.446 (t, 2H), 7.368 - 7.355 (d, 1H), 7.239 (s, 1H), 7.041 (s, 1H), 7. 011 - 6.991 (d, 1H), 6.646 (s, 1H), 6.501 (s, 1H), 5.441 - 5.385 (t, 2H), 5.343 - 5.322 (d, 1H), 5.262 (s, 4H), 5.142 (t, 2H), 5.038 (d, 1H), 4.962 (s, 1H), 4.375 - 4.367 (d, 2H), 3.582 (s, 1H), 3.295 - 3.189 (m, 3H), 2.511 - 2.502 (m, 3H), 2.352 (t, 2H), 2.234 (s, 3H), 1.896 - 1.815 (m, 4H), 1.606 (s, 2H), 1.281 - 1.260 (t, 2H), 0.891 - 0.867 (t, 3H).

[0328] Example 25 Disodium 4-amino-6-((E)-(4'-(6-(4-((5-(((2S,3R,4S,5S,6S)-6-carboxy-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)oxy)-2-((((S)-4-ethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)hexanamido)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate A 12 mg product was prepared by the preparation method of Example 15 using trisodium (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-amino-1-hydroxy-5,7-disulfonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4-ethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate. MS (m / e): 1382.44 [M-2Na+3H] + 。

[0329] Example 26 Methyl (2S,3S,4S,5R,6S)-6-(4-(((S)-4-ethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)-3-(prop-2-ynyloxy)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate A 108 mg product was prepared by the preparation method of Example 20 using (2S,3R,4S,5S,6S)-2-(4-((((S)-4-ethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indazolo[1,2-b]quinolin-9-yl)oxy)methyl)-3-(prop-2-ynyloxy)phenoxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triacetate. MS (m / e): 715.23 [M+H] + 。

[0330] Example 27 4-Amino-6-((E)-(4’-(6-(4-((2-(((S)-4-ethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)-5-(((2S,3R,4S,5S,6S)-3,4,5-trihydroxy-6-(methoxycarbonyl)tetrahydro-2H-pyran-2-yl)oxy)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)hexanamido)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonic acid disodium A 19 mg product was prepared by the preparation method of Example 7 using methyl (2S,3S,4S,5R ,6S)-6-(4-(((S)-4-ethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indazolo[1,2-b]quinolin-9-yl)oxy)methyl)-3-(prop-2-ynyloxy)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate, and (E)-4-amino-6-((4’-(6-azidohexanamido)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonic acid disodium. MS (m / e): 1396.37 [M-2Na+3H] + 。

[0331] Example 28 (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-Diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-5-methoxyphenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium 7 mg of the product was prepared by the preparation method of Example 7 using (2S,3S,4S,5R,6S)-6-(4-(((S)-4,11-Diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-3-methoxy-5-(prop-2-ynyloxy)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid, and (E)-4-Amino-6-((4’-(6-azidohexanamido)-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonic acid disodium. MS (m / e): 1412.11 [M - 3Na + 4H] + .

[0332] Example 29 (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonaphthalen-2-yl)diazenyl)-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4-ethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium 82 mg of the product was prepared by the preparation method of Example 7 using (2S,3S,4S,5R,6S)-6-(4-(((S)-4-ethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indrazolo[1,2-b]quinolin-9-yl)oxy)methyl)-3-(prop-2-ynyloxy)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid, and disodium (E)-4-amino-6-((4’-(6-azidohexanamido)-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate. MS (m / e): 1354.57 [M - 3Na + 4H] + .

[0333] Example 30 (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonaphthalen-2-yl)diazenyl) Trisodium (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4'-((E)-(8-amino-1-hydroxy-5,7-disulfonaphthalen-2-yl)diazenyl)-3,3'-dimethoxy-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4-ethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate 5 mg of the product was prepared by the method of Preparation Example 7 using (2S,3S,4S,5R,6S)-6-(4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-3-methoxy-5-(prop-2-ynyloxy)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid and disodium (E)-4-amino-6-((4'-(6-azidohexanamido)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate. MS (m / e): 1440.2 [M - 3Na + 4H] + 。

[0334] Example 31 (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4'-((E)-(8-amino-1-hydroxy-5,7-disulfonaphthalen-2-yl)diazenyl)-3,3'-dimethoxy-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4-ethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium The 82 mg product was prepared by the preparation method of Example 7 using (2S,3S,4S,5R,6S)-6-(4-(((S)-4-ethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indazolo[1,2-b]quinolin-9-yl)oxy)methyl)-3-(prop-2-ynyloxy)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid and disodium (E)-4-amino-6-((4’-(6-azidohexanamido)-3,3’-dimethoxy-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate. MS (m / e): 1414.80 [M - 3Na + 4H] + 。

[0335] Example 32 Disodium 4-amino-6-((E)-(4’-(6-(4-((5-(((2S,3R,4S,5S,6S)-6-carboxy-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)oxy)-2-((((S)-4-ethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)hexanamido)-3,3’-dimethoxy-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate The 15 mg product was prepared by the preparation method of Example 15 using (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-amino-1-hydroxy-5,7-disulfonaphthalen-2-yl)diazenyl)-3,3’-dimethoxy-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4-ethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’ :6,7]Indolizino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium was used for the preparation. MS(m / e): 1414.56[M-2Na+3H] + 。

[0336] Example 33 4-Amino-6-((E)-(4’-(6-(4-((2-(((S)-4-Ethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)-5-(((2S,3R,4S,5S,6S)-3,4,5-trihydroxy-6-(methoxycarbonyl)tetrahydro-2H-pyran-2-yl)oxy)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)hexanamide)-3,3’-dimethoxy-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonic acid disodium 11 mg of the product was prepared by the preparation method of Example 7 using (2S,3S,4S,5R,6S)-6-(4-(((S)-4-Ethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazo[1,2-b]quinolin-9-yl)oxy)methyl)-3-(prop-2-ynyloxy)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid methyl ester, and (E)-4-amino-6-((4’-(6-azidohexanamide)-3,3’-dimethoxy-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonic acid disodium. MS(m / e): 1428.33[M-2Na+3H] + 。

[0337] Example 34 (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-10-((dimethylamino)methyl)-4-ethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium The 5 mg product was prepared by the preparation method of Example 7 using (2S,3S,4S,5R,6S)-6-(4-(((S)-10-((dimethylamino)methyl)-4-ethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)-3-(prop-2-ynyloxy)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid, and disodium (E)-4-amino-6-((4’-(6-azidohexanamido)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate. MS (m / e): 1439.21 [M - 3Na + 4H] + .

[0338] Example 35 tert-Butyl (4’-amino-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)carbamate 5g of 3,3'-dimethyl-[1,1'-biphenyl]-4,4'-diamine was weighed and added to 75 ml of 1,4-dioxane. The mixture was stirred at room temperature under an argon atmosphere. 5.14 g of Boc2O was weighed and diluted with 25 ml of 1,4-dioxane. The resulting substance was added dropwise to the reaction solution. The resulting mixture was stirred at room temperature overnight. The resulting substance was concentrated to dryness. After purification by column chromatography, 4.485 g of the product was obtained.

[0339] Example 36 tert-Butyl (4'-(8-bromooctanamido)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl) carbamate 2.4 g of tert-butyl (4'-amino-3,3'-dimethyl-[1,1'-biphenyl]-4-yl) carbamate and 2 g of 8-bromooctanoic acid were weighed and added to 40 ml of dichloromethane and dissolved. 2.1 g of EDCI and 1 g of HOBT were successively added to the mixture. 1.3 ml of DIEA was added dropwise. The mixture was stirred under argon at room temperature overnight and concentrated to dryness with water. After purification by column chromatography, 1.247 g of the product was obtained. MS (m / e): 517.25 [M+H] + .

[0340] Example 37 N-(4'-Amino-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)-8-bromooctanamide 1.147 g of tert-butyl (4'-(8-bromooctanamido)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl) carbamate was weighed and dissolved in 14 ml of dichloromethane. 1.4 ml of trifluoroacetic acid was added dropwise to the mixture at room temperature for 2 hours. The resulting substance was dried and purified by column chromatography to obtain 1.159 g of the product. MS (m / e): 417.24 [M+H] + .

[0341] Example 38 N-(4'-Amino-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)-8-azidooctanamide 1.159 g of N-(4'-amino-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)-8-bromooctanamide was weighed and added to a reaction flask. 8 ml of dimethyl sulfoxide was added to the reaction flask to dissolve it, and 271 mg of sodium azide was added. The reaction mixture was transferred to an oil bath and stirred for 6 hours. The reaction mixture was quenched with 40 ml of water and stirred, stirred for 10 minutes, and adjusted from pH 7 to pH 8 using an aqueous sodium bicarbonate solution. The reaction system was extracted 5 times with dichloromethane. The organic phase was washed with saturated sodium chloride and dried over anhydrous sodium sulfate. The filtrate was concentrated and dried by suction. After purification by column chromatography, 640 mg of the product was obtained. MS(m / e): 380.30 [M+H] + 。

[0342] Example 39 (E) Disodium 4-amino-6-((4'-(8-azidooctanamido)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate 212 mg of the product was prepared using N-(4'-amino-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)-8-azidooctanamide and sodium 4-amino-5-hydroxy-1,3-naphthalenedisulfonate by the preparation method of Example 3. MS(m / e): 710.28 [M - 2Na + 3H] + . 1 HNMR(DMSO-d6, 600 MHz) δ: 15.962(s, 1H), 9.278(s, 1H), 6H(s, 1H), 8.031(d, 1H), 7.896(d, 1H), 7.654(s, 2H), 7.578(s, 1H), 1.352(t, 2H), 7.013(d, 1H), 3.337(s, 2H), 2.528 - 2.508(s, 3H), 1.556(t, 2H), 2.281(s, 3H), 1.630(s, 2H), 1.556(t, 2H), 1.352(s, 6H).

[0343] Example 40 (2S,3S,4S,5R,6S)-6-(3-((1-(8-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-8-oxooctyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxy-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium 103 mg of the product was prepared by the preparation method of Example 7 using disodium (E)-4-amino-6-((4’-(8-azidooctanamido)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate and (2S,3S,4S,5R,6S)-6-(4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxy-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,7]quinolin-9-yl)oxy)methyl)-3-(prop-2-ynyloxy)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid. MS (m / e): 1438.40 [M - 3Na + 4H] + 。

[0344] Example 41 4-Amino-6-((E)-(4'-(8-(4-((5-(((2S,3R,4S,5S,6S)-6-carboxy-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)oxy)-2-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxy-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)octanamido)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonic acid disodium 18 mg of the product was prepared by the preparation method of Example 15 using trisodium (2S,3S,4S,5R,6S)-6-(3-((1-(8-((4'-((E)-(8-amino-1-hydroxy-5,7-disulfonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-8-oxooctyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxy-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,7]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate. MS (m / e): 1438.32 [M - 2Na + 3H] + 。

[0345] Example 42 Sodium 4-amino-6-((E)-(4'-(8-(4-((2-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indazolo[1,2-b]quinolin-9-yl)oxy)methyl)-5-(((2S,3R,4S,5S,6S)-3,4,5-trihydroxy-6-(methoxycarbonyl)tetrahydro-2H-pyran-2-yl)oxy)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)octanamido)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate 9 mg of the product was prepared by the preparation method of Example 7 using methyl (2S,3S,4S,5R,6S)-6-(4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano [3',4':6,7]indazolo[1,2-b]quinolin-9-yl)oxy)methyl)-3-(prop-2-ynyloxy)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate and (E)-4-amino-6-((4'-(8-azidooctanamido)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonic acid disodium. MS (m / e): 1452.61 [M - 2Na + 3H] + .

[0346] Example 43 tert-Butyl (4'-(8-bromooctanamido)-[1,1'-biphenyl]-4-yl)carbamate 942 mg of 8-bromooctanoic acid, 1 g of tert-butyl (4’-amino-[1,1’-biphenyl]-4-yl)carbamate, and 1.605 g of HATU were weighed and dissolved in 20 ml of DMF. 697 μl of DIEA was added dropwise to the mixture. The resulting substance was stirred at room temperature for 1 hour. The reaction was dried and 20 ml of dichloromethane was added to the slurry at room temperature overnight. The solid was suction filtered and dried to obtain 1.43 g of the product tert-butyl (4’-(8-bromooctanamido)-[1,1’-biphenyl]-4-yl)carbamate. MS (m / e): 489.25 [M+H] + 。

[0347] Example 44 N-(4’-amino-[1,1’-biphenyl]-4-yl)-8-bromooctanamide 714 mg of tert-butyl (4’-(8-bromooctanamido)-[1,1’-biphenyl]-4-yl)carbamate was weighed and dissolved in 8.6 ml of dichloromethane. The mixture was stirred at room temperature overnight and 860 μl of trifluoroacetic acid was added dropwise. The reaction was dried and 10 ml of methyl tert-butyl ether was added at room temperature overnight. The solid was suction filtered and dried to obtain 709 mg of the product. MS (m / e): 389.15 [M+H] + . 1 HNMR (DMSO-d6, 600 MHz) δ: 9.948 (s, 1H), 7.677 - 7.662 (d, 2H), 7.634 - 7.620 (d, 2H), 7.581 - 7.567 (d, 2H), 7.176 - 7.163 (d, 2H), 3.541 - 3.518 (t, 2H), 2.330 - 2.306 (t, 2H), 1.810 - 1.786 (m, 2H), 1.612 - 1.588 (t, 2H), 1.394 - 1.381 (m, 2H), 1.323 - 1.312 (t, 4H).

[0348] Example 45 N-(4’-amino-[1,1’-biphenyl]-4-yl)-8-azocinamide 140 mg of N-(4’-amino-[1,1’-biphenyl]-4-yl)-8-bromooctanamide was prepared by the preparation method of Example 2 using N-(4’-amino-[1,1’-biphenyl]-4-yl)-8-bromooctanamide. MS (m / e): 352.22 [M+H] + 。

[0349] Example 46 (E)-4-amino-6-((4’-(8-azidooctanamido)-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonic acid disodium 170 mg of the product (E)-4-amino-6-((4’-(8-azidooctanamido)-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonic acid disodium was prepared by the preparation method of Example 3 using N-(4’-amino-[1,1’-biphenyl]-4-yl)-8-azidooctanamide and sodium 4-amino-5-hydroxy-1,3-naphthalenedisulfonate. MS (m / e): 682.31 [M-2Na+3H]+. 1 HNMR(DM SO-d6, 600 MHz) δ: 15.656 (s, 1H), 9.966 (s, 1H), 8.351 (s, 1H), 8.015 - 7.998 (d, 1H), 7.752 - 7.738 (d, 2H), 7.705 - 7.656 (m, 6H), 6.953 - 6.937 (d, 1H), 3.341 - 3.330 (d, 2H), 2.346 - 2.321 (t, 2H), 1.629 - 1.605 (t, 2H), 1.557 - 1.534 (t, 2H), 1.339 - 1.333 (d, 6H).

[0350] Example 47 (2S,3S,4S,5R,6S)-6-(3-((1-(8-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-[1,1’-biphenyl]-4-yl)amino)-8-oxooctyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium 95 mg of the product (2S,3S,4S,5R,6S)-6-(3-((1-(8-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-[1,1’-biphenyl]-4-yl)amino)-8-oxooctyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium was prepared by the preparation method of Example 7 using disodium (E)-4-amino-6-((4’-(8-azidooctanamido)-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate and (2S,3S,4S,5R,6S)-6-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-3-(prop-2-ynyloxy)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid. MS (m / e): 1410.01 [M - 3Na + 4H] + 。

[0351] Example 48 (2S,3S,4S,5R,6S)-6-(3-((1-(8-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-8-oxooctyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-2-methylphenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium The 125 mg product was prepared by the preparation method of Example 7 using (2S,3S,4S,5R,6S)-6-(4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indrazolo[1,2-b]quinolin-9-yl)oxy)methyl)-2-methyl-3-(prop-2-ynyloxy)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid, and disodium (E)-4-amino-6-((4’-(8-azidooctylamido)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate. M S(m / e): 1452.97 [M - 3Na + 4H] + .

[0352] Example 49 2-(2-(2-Bromoethoxy)ethoxy)acetic acid 400 mg of tert-butyl 2-(2-(2-bromoethoxy)ethoxy)acetate was weighed and added to a reaction flask. 8 ml of dichloromethane and 480 μl of trifluoroacetic acid were added dropwise to the reaction flask. The mixture was stirred overnight at room temperature. The resulting substance was concentrated to dryness. The solid was dissolved in dichloromethane and the mixture was concentrated to dryness. The above procedure was carried out 3 times. The solid was dissolved in ethyl acetate and the mixture was concentrated to dryness. The above procedure was carried out 3 times. 10 ml of methyl tert-butyl ether was added and the mixture was stirred at room temperature for 3 hours. The reaction solution was concentrated to dryness and the compound was obtained in 100% yield.

[0353] Example 50 tert-butyl (4’-(2-(2-(2-bromoethoxy)ethoxy)acetamido)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)carbamate 321 mg of tert-butyl 2-(2-(2-bromoethoxy)ethoxy)acetate, 368 mg of (4’-amino-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)carbamate, and 538 mg of HATU were weighed and dissolved in 6.5 ml of DMF. The mixture was stirred overnight at room temperature. The reaction was quenched by adding 80 ml of water and the reaction system was extracted 3 times with dichloromethane. The organic phase was washed with saturated sodium chloride, dried over anhydrous sodium sulfate, and the filtrate was concentrated to dryness by suction. After purification by column chromatography, 412 mg of the product was obtained. MS (m / e): 521.20 [M+H] + . 1 HNMR (DMSO-d6, 600 MHz) δ: 9.073 (s, 1H), 8.553 (s, 1H), 7.636 - 7.622 (d, 1H), 7.527 - 7.524 (d, 1H), 7.476 - 7.439 (m, 2H), 7.425 - 7.406 (m, 2H), 4.146 (s, 2H), 1.482 (t, 2H), 3.748 - 3.734 (m, 2H), 3.705 - 3.688 (m, 2H), 3.618 - 3.599 (t, 2H), 2.286 - 2.266 (d, 9H), 1.482 (s, 9H).

[0354] Example 51 N-(4’-Amino-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)-2-(2-(2-bromoethoxy)ethoxy)acetamide 389 mg of the product N-(4’-amino-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)-2-(2-(2-bromoethoxy)ethoxy)acetamide was prepared by the preparation method of Example 37 using tert-butyl (4’-(2-(2-(2-bromoethoxy)ethoxy)acetamido)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)carbamate. MS(m / e): 421.23 [M+H] + .

[0355] Example 52 N-(4’-Amino-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)-2-(2-(2-azidoethoxy)ethoxy)acetamide 216 mg of the product N-(4’-amino-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)-2-(2-(2-bromoethoxy)ethoxy)acetamide was prepared by the preparation method of Example 2 using N-(4’-amino-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)acetamide. MS(m / e): 384.24 [M+H] + . 1 HNMR(DMSO-d6, 400 MHz) δ: 9.001(s, 1H), 7.530 - 7.509(d, 1H), 7.415 - 7.411(d, 1H), 7.360 - 7.335(dd, 1H), 7.262 - 7.205(m, 2H), 2.123(d, 1H), 4.947(s, 2H), 4.124(s, 2H), 3.748 - 3.726(t, 2H), 3.695 - 3.645(m, 4H), 3.429 - 3.440(t, 2H), 2.250(s, 3H), 2.123(s, 3H).

[0356] Example 53 (E)-4-Amino-6-((4’-(2-(2-(2-azidoethoxy)ethoxy)acetamido)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonic acid disodium salt 137 mg of the product was prepared by the preparation method of Example 3 using N-(4’-amino-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)-2-(2-(2-azidoethoxy)ethoxy)acetamide and sodium 4-amino-5-hydroxy-1,3-naphthalenedisulfonate. MS(m / e): 714.24 [M - 2Na + 3H] + .

[0357] Example 54 (2S,3S,4S,5R,6S)-6-(3-((1-(2-(2-(2-((4’-((E)-(8-amino-1-hydroxy-5,7-disulfonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-2-oxoethoxy)ethoxy)ethyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium salt A 130 mg product was prepared by the preparation method of Example 7 using disodium (E)-4-amino-6-((4’-(2-(2-(2-azidoethoxy)ethoxy)acetamido)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate and (2S,3S,4S,5R,6S)-6-(4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-3-(prop-2-ynyloxy)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid. MS (m / e): 1442.45 [M - 3Na + 4H] + .

[0358] Example 55 Disodium 4-amino-6-((E)-(4’-(2-(2-(2-(2-((5-(((2S,3R,4S,5S,6S)-6-carboxy-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)oxy)-2-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)ethoxy)acetamido)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate The 12 mg product was prepared by the preparation method of Example 15 using trisodium (2S,3S,4S,5R,6S)-6-(3-((2-(2-(2-((4’-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-2-oxoethoxy)ethoxy)ethyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate. MS (m / e): 1442.39 [M-2Na+3H] + 。

[0359] Example 56 Disodium 4-amino-6-((E)-(4’-(2-(2-((2-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazo[1,2-b]quinolin-9-yl)oxy)methyl)-5-(((2S,3R,4S,5S,6S)-3,4,5-trihydroxy-6-(methoxycarbonyl)tetrahydro-2H-pyran-2-yl)oxy)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)ethoxy)acetamido)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate The 20 mg product was prepared by the preparation method of Example 7 using methyl (2S,3S,4S,5R,6S)-6-(4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)-3-(prop-2-ynyloxy)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate and disodium (E)-4-amino-6-((4’-(2-(2-(2-azidoethoxy)ethoxy)acetamido)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)diazinyl)-5-hydroxynaphthalene-1,3-disulfonate. MS (m / e): 1456.53 [M - 2Na + 3H] + .

[0360] Example 57 tert-Butyl (4’-(2-(2-(2-bromoethoxy)ethoxy)acetamido)-3,3’-dimethoxy-[1,1’-biphenyl]-4-yl)carbamate The 458 mg product was prepared by the preparation method of Example 36 using 2-(2-(2-bromoethoxy)ethoxy)acetic acid and the compound tert-butyl (4’-amino-3,3’-dimethoxy-[1,1’-biphenyl]-4-yl)carbamate. MS (m / e): 553.21 [M + H] + . 1 HNMR (DMSO-d6, 600 MHz) δ: 9.002 (s, 1H), 8.235 - 8.221 (d, 1H), 7.936 (s, 1H), 7.780 - 7.767 (d, 1H), 7.323 - 7.319 (d, 1H), 7.272 - 7.228 (m, 3H), 1.479 (s, 2H), 3.980 (s, 3H), 3.920 (s, 3H), 3.813 - 3.793 (t, 2H), 3.748 - 3.731 (m, 2H), 9H (m, 2H), 3.627 - 3.608 (t, 2H), 1.479 (s, 9H).

[0361] Example 58 N-(4'-Amino-3,3'-dimethoxy-[1,1'-biphenyl]-4-yl)-2-(2-(2-bromoethoxy)ethoxy)acetamide 432 mg of the product was prepared by the preparation method of Example 37 using tert-butyl (4'-(2-(2-(2-bromoethoxy)ethoxy)acetamido)-3,3'-dimethoxy-[1,1'-biphenyl]-4-yl)carbamate. MS (m / e): 453.20 [M+H] + . 1 HNMR (DMSO-d6, 600 MHz) δ: 9.000 (s, 1H), 8.227 - 8.213 (d, 1H), 7.306 - 7.292 (dd, 2H), 7.257 - 7.240 (dd, 1H), 7.224 - 7.207 (dd, 1H), 7.078 - 7.065 (d, 1H), 4.144 (s, 2H), 3.973 - 3.934 (d, 3.607 - 3.608), 3.811 - 3.792 (t, 2H), 3.746 - 3.729 (m, 2H), 3.704 - 3.687 (m, 2H), 3.607 - 3.608 (t, 2H).

[0362] Example 59 N-(4'-Amino-3,3'-dimethoxy-[1,1'-biphenyl]-4-yl)-2-(2-(2-azidoethoxy)ethoxy)acetamide 252 mg of the product was prepared by the preparation method of Example 2 using N-(4'-amino-3,3'-dimethoxy-[1,1'-biphenyl]-4-yl)-2-(2-(2-bromoethoxy)ethoxy)acetamide. MS (m / e): 416.27 [M+H] + . 1 HNMR (DMSO-d6, 600 MHz) δ: 8.951 (s, 1H), 8.169 - 8.155 (d, 1H), 7.230 - 7.226 (d, 1H), 7.171 - 7.154 (m, 1H), 7.102 - 7.099 (d, 1H), 7.057 - 7.041 (m, 1H), 6.709 - 6.696 (d, 1H), 4.853 (s, 2H), 3.432 - 3.416 (s, 2H), 3.956 (s, 3H), 3.865 (s, 3H), t(q, 2H), 3.692 - 3.662 (m, 4H), 3.432 - 3.416 (t, 2H).

[0363] Example 60 (E)-4-Amino-6-((4'-(2-(2-(2-azidoethoxy)ethoxy)acetamido)-3,3'-dimethoxy-[1,1'-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonic acid disodium 147 mg of the product (E)-4-amino-6-((4'-(2-(2-(2-azidoethoxy)ethoxy)acetamido)-3,3'-dimethoxy-[1,1'-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonic acid disodium was prepared by the preparation method of Example 3 using N-(4'-amino-3,3'-dimethoxy-[1,1'-biphenyl]-4-yl)-2-(2-(2-azidoethoxy)ethoxy)acetamide and 4-amino-5-hydroxy-1,3-naphthalenedisulfonic acid monosodium. MS (m / e): 746.40 [M - 2Na + 3H] + . 1 HNMR (DMSO-d6, 600 MHz) δ: 15.697 (s, 1H), 9.636 (s, 1H), 9.042 (s, 1H), t (s, 1H), 3.441 - 3.425 (4.012, 1H), 8.015 - 7.998 (4.012, 1H), 7.860 - 7.846 (4.012, 1H), 3.702 - 3.670 (s, 1H), q (m, 3H), 7.365 - 7.348 (3.757 - 3.742, 1H), 6.979 - 6.962 (4.012, 1H), 4.153 (s, 2H), 4.121 (s, 3H), 4.012 (s, 3H), 3.757 - 3.742 (q, 2H), 3.702 - 3.670 (m, 4H), 3.441 - 3.425 (t, 2H).

[0364] Example 61 (2S,3S,4S,5R,6S)-6-(3-((1-(2-(2-(2-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethoxy-[1,1’-biphenyl]-4-yl)amino)-2-oxoethoxy)ethoxy)ethyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium 128 mg of the product was prepared by the preparation method of Example 7 using disodium (E)-4-amino-6-((4’-(2-(2-(2-azidoethoxy)ethoxy)acetamido)-3,3’-dimethoxy-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate and (2S,3S,4S,5R,6S)-6-(4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-3-(prop-2-ynyloxy)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carbo nic acid. MS (m / e): 1474.63 [M - 3Na + 4H] + .1H NMR (DMSO-d6, 600 MHz) δ: 15.697 (s, 1H), 9.636 (s, 1H), 9.042 (s, 1H), 8.352 (s, 1H), 8.278 - 8.264 (d, 1H), 8.015 - 7.998 (d, 1H), 7.860 - 7.846 (d, 1H), 7.651 (s, 1H), 7.456 - 7.411 (m, 3H), 7.365 - 7.348 (dd, 1H), 6.979 - 6.962 (d, 1H), 4.153 (s, 2H), 4.121 (s, 3H), 4.012 (s, 3H), 3.757 - 3.742 (q, 2H), 3.702 - 3.670 (m, 4H), 3.441 - 3.425 (t, 2H).

[0365] Example 62 4-Amino-6-((E)-(4’-(2-(2-(2-(2-(4-((5-(((2S,3R,4S,5S,6S)-6-carboxy-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)oxy)-2-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxy-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)ethoxy)ethoxy)acetamido)-3,3’-dimethoxy-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonic acid disodium The 20 mg product was prepared by the preparation method of Example 15 using trisodium (2S,3S,4S,5R,6S)-6-(3-((2-(2-(2-((4’-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethoxy-[1,1’-biphenyl]-4-yl)amino)-2-oxoethoxy)ethoxy)ethyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate. MS (m / e): 1474.55 [M-2Na+3H] + 。

[0366] Example 63 Disodium 4-amino-6-((E)-(4’-(2-(2-(2-((2-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazo[1,2-b]quinolin-9-yl)oxy)methyl)-5-(((2S,3R,4S,5S,6S)-3,4,5-trihydroxy-6-(methoxycarbonyl)tetrahydro-2H-pyran-2-yl)oxy)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)ethoxy)acetamido)-3,3’-dimethoxy-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate The 16 mg product was prepared by the preparation method of Example 7 using methyl (2S,3S,4S,5R,6S)-6-(4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)-3-(prop-2-ynyloxy)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate and disodium (E)-4-amino-6-((4’-(2-(2-(2-(2-azidoethoxy)ethoxy)acetamido)-3,3’-dimethoxy-[1,1’-biphenyl]-4-yl)diazinyl)-5-hydroxynaphthalene-1,3-disulfonate. MS(m / e): 1488.69 [M-2Na+3H] + .

[0367] Example 64 tert-butyl (4’-amino-3,3’-dimethoxy-[1,1’-biphenyl]-4-yl)carbamate 4.879 g of the product tert-butyl (4’-amino-3,3’-dimethoxy-[1,1’-biphenyl]-4-yl)carbamate was prepared by the preparation method of Example 35 using 3,3’-dimethoxy-[1,1’-biphenyl]-4,4’-diamine. MS(m / e): 345.19 [M+H] + . 1 HNMR(DMSO-d6,400MHz) δ: 7.835(s,1H), 7.688 - 7.668(d,1H), 7.153 - 7.010(m,4H), 6.706 - 6.686(d,1H), 4.809(s,2H), 3.892 - 3.860(d,6H), 1.473(s,9H).

[0368] Example 65 tert-butyl (4’-(6-bromohexanamido)-3,3’-dimethoxy-[1,1’-biphenyl]-4-yl)carbamate 1.735 g of the product tert-butyl (4'-(6-bromohexanamido)-3,3'-dimethoxy-[1,1'-biphenyl]-4-yl)carbamate was prepared by the preparation method of Example 50 using tert-butyl (4'-amino-3,3'-dimethoxy-[1,1'-biphenyl]-4-yl)carbamate and 6-bromohexanoic acid. MS(m / e): 521.24 [M+H] + . 1 HNMR(DMSO-d6,600MHz)δ: 9.108(s,1H), 8.034 - 8.020(d,1H), 7.931(s,1H), 7.774 - 7.761(d,1H), 7.272 - 7.259(dd,2H), 7.233 - 7.204(1.478,2H), 3.939 - 3.917(d,6H), 9H(t,2H), 1.265 - 1.240(t,2H), 1.859 - 1.823(t,2H), 1.630 - 1.592(t,2H), 1.478(s,9H), 1.265 - 1.240(t,2H).

[0369] Example 66 N-(4'-amino-3,3'-dimethoxy-[1,1'-biphenyl]-4-yl)-6-bromohexanamide 1.412 g of the product N-(4'-amino-3,3'-dimethoxy-[1,1'-biphenyl]-4-yl)-6-bromohexanamide was prepared by the preparation method of Example 37 using tert-butyl (4'-(6-bromohexanamido)-3,3'-dimethoxy-[1,1'-biphenyl]-4-yl)carbamate. MS(m / e): 421.23 [M+H] + . 1 HNMR(DMSO-d6,400MHz)δ: 9.090(s,1H), 8.022 - 8.001(d,1H), 7.275 - 7.186(dd,4H), 7.075 - 7.057(m,1H), 3.947(s,6H), 3.570 - 3.537(t,2H), 2.436 - 4.400(t,2H), 1.883 - 1.812(m,2H), 1.637 - 1.581(m,2H), 1.477 - 1.402(m,2H).

[0370] Example 67 N-(4’-Amino-3,3’-dimethoxy-[1,1’-biphenyl]-4-yl)-6-azidohexanamide 959 mg of the product was prepared by the preparation method of Example 2 using N-(4’-amino-3,3’-dimethoxy-[1,1’-biphenyl]-4-yl)-6-bromohexanamide. MS(m / e): 384.24[M+H] + . 1 HNMR(DMSO-d6, 600 MHz) δ: 1.385 - 1.360(m, 1H), 7.943 - 7.929(d, 1H), 7.179 - 7.176(d, 1H), 7.121 - 7.104(dd, 1H), 7.089 - 7.086(d, 1H), 7.044 - 7.027(dd, 1H), 6.705 - 6.692(d, 1H), 4.832(m, 2H), 3.913(m, 3 H), 3.862(m, 3H), 3.355 - 3.332(t, 2H), 2.415 - 4.390(t, 2H), 1.624 - 1.566(m, 4H), 1.385 - 1.360(t, 2H).

[0371] Example 68 (E)4-Amino-6-((4’-(6-azidohexanamide)-3,3’-dimethoxy-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonic acid disodium 171 mg of the product was prepared by the preparation method of Example 3 using N-(4’-amino-3,3’-dimethoxy-[1,1’-biphenyl]-4-yl)-6-azidohexanamide and sodium 4-amino-5-hydroxy-1,3-naphthalenedisulfonate. MS(m / e): 714.25[M - 2Na + 3H] + . 1HNMR (DMSO-d6, 600 MHz) δ: 15.707 (s, 1H), 9.638 (s, 1H), 9.154 (s, 1H), 8.355 (s, 1H), 8.087 - 8.073 (d, 1H), 8.013 - 7.997 (d, 1H), 7.855 - 7.842 (d, 1H), 7.648 (s, 1H), dt (d, 2H), 7.361 - 7.358 (d, 1H), 1.391 - 1.366 (3.384 - 3.344, 1H), m (d, 1H), 4.118 (s, 3H), t (s, 3H), 3.384 - 3.344 (t, 2H), 2.449 - 2.425 (t, 2H), 1.634 - 1.571 (dt, 4H), 1.391 - 1.366 (m, 2H).

[0372] Example 69 (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethoxy-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,7]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium A 129 mg product was prepared by the preparation method of Example 7 using disodium (E)-4-amino-6-((4'-(6-azidohexanamido)-3,3'-dimethoxy-[1,1'-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate and (2S,3S,4S,5R,6S)-6-(4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxy-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-3-(prop-2-ynyloxy)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid. MS (m / e): 1442.04 [M - 3Na + 4H] + . 1 1H NMR (DMSO-d6, 600 MHz) δ: 15.692 (s, 1H), 9.638 (s, 1H), 9.153 (s, 1H), 8.355 (s, 1H), 8.309 (s, 1H), 8.069 - 8.001 (m, 3H), 7.838 - 7.824 (d, 1H), 7.646 (s, 1H), 7.569 - 7.565 (d, 1H), 7.539 - 7.520 (dd, 1H), 7.423 - 7.403 (m, 2H), 7.379 - 7.365 (d, 1H), 7.321 - 7.318 (d, 1H), 7.270 - 7.256 (t, 2H), 7.035 - 7.032 (d, 1H), 6.973 - 6.957 (d, 1H), 6.661 - 6.644 (dd, 1H), 6.482 (s, 1H), 5.413 - 5.407 (d, 2H), 5.317 - 5.265 (q, 4H), 5.244 - 5.188 (m, 4H), 4.995 (d, 1H), 4.933 - 4.921 (d, 1H), 4.359 - 4.336 (t, 2H), 4.111 (s, 3H), 3.934 (s, 3H), 3.528 - 3.511 (d, 1H), 3.286 - 3.233 (m, 2H), 3.168 - 3.148 (m, 3H), 2.392 - 2.362 (t, 2H), 1.894 - 1.782 (m, 4H), 1.560 - 1.535 (t, 2H), 1.279 - 1.219 (m, 5H), 0.887 - 0.863 (t, 3H).

[0373] Example 70 4-Amino-6-((E)-(4’-(6-(4-((5-(((2S,3R,4S,5S,6S)-6-carboxy-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)oxy)-2-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxy-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)hexanamido)-3,3’-dimethoxy-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonic acid disodium A 10 mg product was prepared using trisodium (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-amino-1-hydroxy-5,7-disulfonaphthalen-2-yl)diazenyl)-3,3’-dimethoxy-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxy-3,4,12,14-tetrahydro-1H-pyrano[3,4’:6,7]indolizino[1,7]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate by the preparation method of Example 15. MS (m / e): 1442.69 [M-2Na+3H] + 。

[0374] Example 71 Sodium 4-amino-6-((E)-(4'-(6-(4-((2-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indazolo[1,2-b]quinolin-9-yl)oxy)methyl)-5-(((2S,3R,4S,5S,6S)-3,4,5-trihydroxy-6-(methoxycarbonyl)tetrahydro-2H-pyran-2-yl)oxy)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)hexanamido)-3,3'-dimethoxy-[1,1'-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate The 12 mg product was prepared by the preparation method of Example 7 using methyl (2S,3S,4S,5R,6S)-6-(4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)-3-(prop-2-ynyloxy)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate and disodium (E)-4-amino-6-((4'-(6-azidohexanamido)-3,3'-dimethoxy-[1,1'-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate. MS (m / e): 1456.63 [M - 2Na + 3H] + 。

[0375] Example 72 6-Bromohexanoyl chloride 10 g of 6-bromohexanoic acid was weighed and dissolved in 100 ml of DCM with stirring. 1 drop of DMF was added and 8.75 ml of oxalyl chloride was added dropwise. The mixture was stirred at room temperature for 1 hour under argon. After concentration to dryness, 11.09 g of the product was obtained. The yield was calculated to be 100%.

[0376] Example 73 tert-Butyl (4'-amino-[1,1'-biphenyl]-4-yl)carbamate 6.5 g of the product tert-butyl (4’-amino-[1,1’-biphenyl]-4-yl) carbamate was prepared using p-diaminobiphenyl by the preparation method of Example 35.

[0377] Example 74 tert-butyl (4’-(6-bromohexanamido)-[1,1’-biphenyl]-4-yl) carbamate 4.7 g of tert-butyl (4’-amino-[1,1’-biphenyl]-4-yl) carbamate was weighed and added to a reaction flask. 50 ml of dichloromethane and 4.7 g of DIEA were added to the reaction flask. The mixture was stirred at room temperature and cooled to 0 °C with ice ethanol. A solution of 4.587 g of 6-bromohexanoyl chloride in 10 ml of dichloromethane was added to the reaction flask. The reaction became a white suspension. The ice ethanol was removed and the reaction was stirred at room temperature for 2 hours. The reaction was quenched with 20 ml of water, stirred for 10 minutes, and filtered by suction and dried. 5.524 g of the product was obtained. MS (m / e): 461.23 [M+H] + . 1 HNMR (DMSO-d6, 600 MHz) δ: 9.936 (s, 1H), 9.406 (s, 1H), 7.662 - 7.847 (d, 2H), 7.568 - 7.511 (m, 6H), 3.565 - 3.542 (t, 2H), 2.346 - 2.321 (t, 2H), 1.868 - 1.820 (t, 2H), 1.658 - 1.608 (t, 2H), 1.493 (s, 9H), 1.451 - 1.426 (t, 2H).

[0378] Example 75 N-(4’-amino-[1,1’-biphenyl]-4-yl)-6-bromohexanamide 5.5 g of tert-butyl (4’-(6-bromohexanamido)-[1,1’-biphenyl]-4-yl) carbamate was weighed and added to a reaction flask. 66 ml of dichloromethane and 6.6 ml of trifluoroacetic acid were added to the reaction flask. The mixture was stirred at room temperature for 6 hours, concentrated to dryness. The solid was dissolved in dichloromethane and the mixture was concentrated to dryness. The above procedure was repeated 3 times. The solid was dissolved in ethyl acetate and the mixture was concentrated to dryness. The above procedure was repeated 2 times. 30 ml of methyl tert-butyl ether was added. The mixture was stirred at room temperature overnight and filtered by suction. The solid was washed with methyl tert-butyl ether to obtain a white filter cake. The filter cake was dried to obtain 5.624 g of the product. 1 HNMR (DMSO-d6, 600 MHz) δ: 9.991 (s, 1H), 7.686 - 7.672 (d, 2H), 7.631 - 7.617 (d, 2H), 7.586 - 7.572 (d, 2H), 7.174 - 7.160 (d, 2H), 3.562 - 3.539 (t, 2H), 2.352 - 2.328 (t, 2H), 1.854 - 1.829 (t, 2H), 1.646 - 1.621 (t, 2H), 1.450 - 1.425 (t, 2H).

[0379] Example 76 N-(4’-Amino-[1,1’-biphenyl]-4-yl)-6-azidohexanamide 1.352 g of the product was prepared by the preparation method of Example 2 using N-(4’-amino-[1,1’-biphenyl]-4-yl)-6-bromohexanamide. MS (m / e): 324.22 [M+H] + . 1 HNMR (DMSO-d6, 600 MHz) δ: 9.853 (s, 1H), 7.597 - 7.582 (d, 2H), 7.463 - 7.449 (d, 2H), 7.324 - 7.310 (d, 2H), 6.626 - 6.612 (d, 2H), 5.158 (s, 2H), 3.357 - 3.334 (t, 2H), 2.330 - 2.306 (t, 2H), 1.637 - 1.612 (t, 2H), 1.587 - 1.5 62 (t, 2H), 1.386 - 1.357 (t, 2H).

[0380] Example 77 (E)-4-Amino-6-((4’-(6-azidohexanamido)-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonic acid disodium 206 mg of the product was prepared by the preparation method of Example 3 using N-(4’-amino-[1,1’-biphenyl]-4-yl)-6-azidohexanamide and sodium 4-amino-5-hydroxy-1,3-naphthalenedisulfonate. MS(m / e): 654.25 [M-2Na+3H] + . 1 HNMR(DMSO-d6, 600 MHz) δ: 15.658(s, 1H), 9.986(s, 1H), 8.354(s, 1H), 8.014 - 7.998(d, 1H), 7.754 - 7.739(d, 2H), 7.708 - 7.659(m, 6H), 6.957 - 6.940(d, 1H), 3.365 - 3.342(t, 2H), 2.362 - 2.337(t, 2H), 1.655 - 1.630(t, 2H), 1.597 - 1.572(t, 2H), 1.385 - 1.370(t, 2H).

[0381] Example 78 (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-amino-1-hydroxy-5,7-disulfonaphthalen-2-yl)diazenyl)-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium The 150 mg product was prepared by the preparation method of Example 7 using disodium (E)-4-amino-6-((4'-(6-azidohexanamido)-[1,1'-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate and (2S,3S,4S,5R,6S)-6-(4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxy-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-3-(prop-2-ynyloxy)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid. MS (m / e): 1382.48 [M - 3Na + 4H] + 。 1 HNMR (DMSO-d6, 600 MHz) δ: 15.664 (s, 1H), 10.332 (s, 1H), 8.361 (s, 2H), 8.065 - 8.050 (d, 1H), 8.008 - 7.994 (d, 1H), 7.733 - 7.718 (d, 2H), 7.690 - 7.662 (t, 4H), 7.626 - 7.612 (d, 2H), 7.564 - 7.560 (d, 1H), 7.531 - 7.511 (dd, 1H), 7.366 - 7.352 (d, 1H), 7.272 (s, 1H), 7.048 (s, 1H), 6.962 - 6.944 (d, 1H), 6.644 - 6.632 (d, 1H), 6.485 (s, 1H), 5.415 - 5.408 (d, 2H), 5.381 - 5.343 (d, 1H), 5.289 (s, 2H), 5.264 - 5.256 (d, 2H), 5.234 - 5.228 (d, 1H), 5.209 - 5.175 (t, 2H), 5.033 - 5.025 (d, 1H), 4.966 - 4.956 (d, 1H), 4.381 - 4.314 (m, 2H), 3.617 - 3.600 (d, 1H), 3.290 - 3.203 (s, 3H), 3.158 - 3.145 (m, 2H), 2.355 - 2.279 (m, 2H), 1.897 - 1.774 (m, 4H), 1.599 - 1.566 (m, 2H), 1.279 - 1.231 (m, 5H), 0.890 - 0.865 (t, 3H).

[0382] Example 79 4-Amino-6-((E)-(4’-(6-(4-((5-(((2S,3R,4S,5S,6S)-6-carboxy-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)oxy)-2-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxy-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)hexanamido)-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonic acid disodium 18 mg of the product was prepared using trisodium (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4’-((E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-[1,1’-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxy-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,7]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate by the preparation method of Example 15. MS (m / e): 1382.42 [M - 2Na + 3H] + 。

[0383] Example 80 Sodium 4-amino-6-((E)-(4'-(6-(4-((2-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-5-(((2S,3R,4S,5S,6S)-3,4,5-trihydroxy-6-(methoxycarbonyl)tetrahydro-2H-pyran-2-yl)oxy)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)hexanamido)-[1,1'-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate 19 mg of the product was prepared by the preparation method of Example 7 using (2S,3S,4S,5R,6S)-6-(4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-3-(prop-2-ynyloxy)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid methyl ester, and disodium (E)-4-amino-6-((4'-(6-azidohexanamido)-[1,1'-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate. MS (m / e): 1396.10 [M - 2Na + 3H] + .

[0384] Example 81 tert-Butyl (4'-(5-bromopentanamido)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)carbamate The product tert-butyl (4'-(5-bromopentanamido)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)carbamate was prepared by the preparation method of Example 74 using tert-butyl (4'-amino-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)carbamate and 5-bromopentanoyl chloride, and obtained as 763 mg of a white solid. MS (m / e): 475.52 [M + H] + .

[0385] Example 82 N-(4’-Amino-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)-5-bromopentanamide The product N-(4’-amino-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)-5-bromopentanamide was prepared by the preparation method of Example 75 using tert-butyl (4’-(5-bromopentanamide)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)carbamate and obtained as 665 mg of a brown solid. MS(m / e): 375.20 [M+H] + 。

[0386] Example 83 N-(4’-Amino-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)-5-azidopentanamide The product N-(4’-amino-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)-5-azidopentanamide was prepared by the preparation method of Example 2 using the compound N-(4’-amino-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)-5-bromopentanamide and obtained as 347 mg of a yellow solid. MS(m / e): 338.31 [M+H] + 。

[0387] Example 84 (E)-4-Amino-6-((4’-(5-azidopentanamide)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonic acid disodium The title compound (E)-4-amino-6-((4'-(5-azidopentanamido)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)-5-hydroxynaphthalene-1,3-disulfonic acid disodium was prepared by the preparation method of Example 3 using the compound disodium N-(4'-amino-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)-5-hydroxynaphthalene-1,3-disulfonic acid and the compound sodium 4-amino-5-hydroxy-1,3-naphthalenedisulfonate, and obtained as 233 mg of a purple solid. MS (m / e): 668.46 [M - 2Na + 3H] + 。

[0388] Example 85 (2S,3S,4S,5R,6S)-6-(3-((1-(5-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-5-oxopentyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxy-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium Trisodium (2S,3S,4S,5R,6S)-6-(3-((1-(5-((4’-((E)-(8-amino-1-hydroxy-5,7-disulfonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-5-oxopentyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxy-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate was prepared using disodium (E)-4-amino-6-((4’-(5-azidopentanamido)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate and (2S,3S,4S,5R,6S)-6-(4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxy-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,7]quinolin-9-yl)oxy)methyl)-3-(prop-2-ynyloxy)phenoxy)-3 ,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid. MS (m / e): 1396.84 [M - 3Na + 4H] + .

[0389] Example 86 tert-Butyl (4’-(2-bromoacetamido)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)carbamate The product tert-butyl (4’-(2-bromoacetamido)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)carbamate was prepared by the method of Preparation of Example 74 using tert-butyl 4’-amino-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)carbamate and 2-bromoacetyl chloride, and obtained as 390 mg of a white solid. MS (m / e): 433.10 [M + H] + .

[0390] Example 87 N-(4’-Amino-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)-2-bromoacetamide The product N-(4’-amino-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)-2-bromoacetamide was prepared by the preparation method of Example 75 using tert-butyl (4’-(2-bromoacetamido)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)carbamate and obtained as 263 mg of a yellow solid. MS(m / e): 333.18 [M+H] + 。

[0391] Example 88 N-(4’-Amino-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)-2-azidoacetamide The product N-(4’-amino-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)-2-bromoacetamide was prepared by the preparation method of Example 2 using the compound N-(4’-amino-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)-2-azidoacetamide and obtained as 180 mg of a yellow solid. MS(m / e): 296.24 [M+H] + 。

[0392] Example 89 (E)-4-Amino-6-((4’-(2-azidoacetamido)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonic acid disodium The title compound (E)-4-amino-6-((4'-(2-azidoacetamido)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)-5-hydroxynaphthalene-1,3-disulfonic acid disodium was prepared by the preparation method of Example 3 using the compound N-(4'-amino-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)-2-azidoacetamide and the compound disodium 4-amino-5-hydroxy-1,3-naphthalenedisulfonate, and obtained as 271 mg of a purple solid. MS (m / e): 626.57 [M - 2Na + 3H] + 。

[0393] Example 90 (2S,3S,4S,5R,6S)-6-(3-((1-(2-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-2-oxoethyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxy-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro- 2H-pyran-2-carboxylic acid trisodium Trisodium (2S,3S,4S,5R,6S)-6-(3-((1-((2-((4’-((E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-2-oxoethyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate was prepared by the preparation method of Example 7 using disodium (E)-4-amino-6-((4’-(2-azidoacetamido)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate and (2S,3S,4S,5R,6S)-6-(4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-3-(prop-2-ynyloxy)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid. MS (m / e): 1354.73 [M - 3Na + 4H] + 。

[0394] Example 91 2-(3-chloropropoxy)acetic acid The compound ethyl 2-(3-chloropropoxy)acetate (1.0 g) was dissolved in tetrahydrofuran (10.0 ml). The mixture was stirred at room temperature. Sodium hydroxide (266 mg) was dissolved in water (10.0 ml). The solution was added dropwise. The mixture was stirred at room temperature for 1.5 hours. Tetrahydrofuran was concentrated and dried. 1 mol / L hydrochloric acid (6.64 ml) was added dropwise to adjust the pH. The reaction system was extracted three times with ethyl acetate. The organic phase was washed with a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and suction filtered. The filtrate was concentrated and dried to obtain the product 2-(3-chloropropoxy)acetic acid as a 723 mg yellow oil. MS (m / e): 153.75 [M+H] + .

[0395] Example 92 tert-Butyl (4’-(2-(3-chloropropoxy)acetamido)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)carbamate The product tert-butyl (4’-(2-(3-chloropropoxy)acetamido)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)carbamate was prepared by the preparation method of Example 50 using the compound tert-butyl 4’-amino-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)carbamate and 2-(3-chloropropoxy)acetic acid, and obtained as a 1.61 g white solid. MS (m / e): 447.40 [M+H] + .

[0396] Example 93 N-(4’-Amino-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)-2-(3-chloropropoxy)acetamide The product N-(4’-amino-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)-2-(3-chloropropoxy)acetamide was prepared by the preparation method of Example 37 using tert-butyl (4’-(2-(3-chloropropoxy)acetamido)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)carbamate, and obtained as a 1.315 g yellow solid. MS (m / e): 347.32 [M+H]+ .

[0397] Example 94 N-(4’-Amino-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)-2-(3-azidopropoxy)acetamide The starting material N-(4’-amino-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)-2-(3-chloropropoxy)acetamide (1.315 g) was weighed and added to dimethyl sulfoxide (10 ml). The mixture was stirred at room temperature and dissolved completely. Sodium azide (287 mg) and sodium iodide (441 mg) were added. The reaction was carried out at 80 °C for 17 hours. The reaction was quenched with water and extracted with dichloromethane (200 ml). The aqueous phase was extracted with dichloromethane (200 ml) and separated. The dichloromethane phases were combined and washed 4 times with a saturated aqueous sodium chloride solution (100 ml). The organic phase was dried over anhydrous sodium sulfate and filtered by suction. The filtrate was concentrated to obtain a crude product. The crude product was subjected to column chromatography (eluent: dichloromethane:ethyl acetate = 10:1) to obtain 914 mg of a yellow oil. MS (m / e): 354.32 [M+H] + .

[0398] Example 95 (E)-4-Amino-6-((4’-(2-(3-azidopropoxy)acetamide)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonic acid disodium salt 345 mg of the product was prepared by the preparation method of Example 3 using the compound N-(4’-amino-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)-2-(3-azidopropoxy)acetamide and the compound disodium 4-amino-5-hydroxy-1,3-naphthalenedisulfonate. MS (m / e): 684.39 [M-2Na+3H] + .

[0399] Example 96 (2S,3S,4S,5R,6S)-6-(3-((1-(3-(2-((4’-(E)-(8-Amino-1-hydroxy-5,7-disulfonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-2-oxoethoxy)propyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxy-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,7]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium 234 mg of the product was prepared by the preparation method of Example 7 using disodium (E)-4-amino-6-((4’-(2-(3-azidopropoxy)acetamido)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate and (2S,3S,4S,5R,6S)-6-(4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxy-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-3-(prop-2-ynyloxy)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid. MS (m / e): 1412.27 [M - 3Na + 4H] + 。

[0400] Example 97 tert-Butyl (4’-(3-(2-bromoethoxy)propionamido)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)carbamate 1.6 g of the product was prepared by the preparation method of Example 50 using tert-butyl (4’-amino-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)carbamate and 3-(2-bromoethoxy)propionic acid. MS (m / e): 491.35 [M + H] + 。

[0401] Example 98 N-(4’-Amino-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)-3-(2-bromoethoxy)propanamide 1.2 g of the product was prepared by the preparation method of Example 37 using the compound tert-butyl (4’-(3-(2-bromoethoxy)propanamide)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)carbamate. MS(m / e): 391.30 [M+H] + .

[0402] Example 99 N-(4’-Amino-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)-3-(2-azidoethoxy)propanamide 770 mg of the product was prepared by the preparation method of Example 2 using the compound N-(4’-amino-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)-3-(2-bromoethoxy)propanamide. MS(m / e): 354.32 [M+H] + .

[0403] Example 100 (E)-4-Amino-6-((4’-(3-(2-azidoethoxy)propanamide)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonic acid disodium 379 mg of the product was prepared by the preparation method of Example 3 using the compounds N-(4’-amino-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)-3-(2-azidoethoxy)propanamide and 4-amino-5-hydroxy-1,3-naphthalenedisulfonic acid monosodium. MS(m / e): 684.63 [M-2Na+3H] + .

[0404] Example 101 (2S,3S,4S,5R,6S)-6-(3-((1-(2-(2-((4’-(E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)amino)-3-oxopropoxy)ethyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium 129 mg of the product was prepared by the preparation method of Example 7 using disodium (E)-4-amino-6-((4’-(3-(2-azidoethoxy)propanamido)-3,3’-dimethyl-[1,1’-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate and (2S,3S,4S,5R,6S)-6-(4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)-3-(prop-2-ynyloxy)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid. MS (m / e): 1412.55 [M-3Na+4H] + 。

[0405] Biological Examples Biological Example 1 In Vitro Inhibitory Study Test against Human Tumor Cells 1.1 Test Method 1.1.1 The additives in the cell culture preparation (complete medium) were usually adjusted in combination with the basic medium preparation according to the preparations provided by the Cell Bank of the Chinese Academy of Sciences and ATCC (American Type Culture Collection). 1.1.2 Cell culture method: Cells were cultured in complete medium at 37 °C, 5% CO2, and saturated humidity until the logarithmic growth phase (adherent cells usually reach complete confluence), and the cells were harvested for subsequent experiments (adherent cells were first digested with trypsin / ethylenediaminetetraacetic acid (EDTA) to remove adhesion). 1.1.3 A certain number of cells were inoculated into a 96-well cell culture plate (hereinafter referred to as a 96-well plate) (see Table 1 for details). The cells were allowed to adhere overnight. Different concentrations of the compound were added and co-cultured for a certain period (usually 3 days). Finally, the total amount of cellular protein in the assay wells was measured by the SRB method, or the cell viability was measured by the MTT method. 1.1.3.1 Measurement of the total amount of cellular protein by the SRB method: The culture medium was aspirated from the wells, and the cells were fixed for over 1 hour by adding 10% trichloroacetic acid. The trichloroacetic acid was removed. The resulting substance was washed with H2O and stained with 0.4% SRB for 15 to 30 minutes. The excess SRB was removed. The resulting substance was washed with 1% acetic acid. The protein-bound SRB was dissolved by adding 100 μl of 10 mM Tris (tris(hydroxymethyl)aminomethane). The test was carried out at a wavelength of 570 nm. 1.1.3.2 The cell viability was determined by the MTT assay: Adherent cells: The culture medium was aspirated, and 100 μl / well of basal medium containing 0.5 mg / ml MTT (usually referring to a medium without fetal bovine serum (FBS) and other additives) was added. The cells were cultured for 3 hours. The MTT-containing basal medium was aspirated, and 100 μl / well of DMSO was added to dissolve the formazan. The test was carried out at a wavelength of 490 nm.

[0406] Unstable adherent cells: Unstable adherent cells were directly added to the MTT solution to a concentration of 0.5 mg / ml and cultured for 3 hours. An equal volume of ternary solution was added to the system to dissolve the formazan. The test was carried out at a wavelength of 570 nm. 1.1.3.3 Selection criteria for SRB method and MTT method: The SRB method and the MTT method revealed the number of cells in the assay wells at different time points, and overall, better revealed the cell inhibitory activity in the reaction compounds. The SRB method was highly sensitive and required fewer cells, while the MTT method was simpler. However, the MTT reduction ability in different cells was quite different. The main principle for the selection of the SRB method and the MTT method was that when the cells had sufficient MTT reduction ability, for example, the OD value (optical density) of the positive solvent control group after the co-culture ended was 0.4 or more, etc., the MTT method was preferentially selected. 1.1.4 Dilution and addition of β-glucuronidase: 1 mg to 2 mg of β-glucuronidase was weighed and dissolved in PBS to obtain a 2 mg / ml storage solution. A 12.5 μg / ml enzyme working solution was diluted with complete medium. 80 μl of the enzyme working solution was added to the enzyme-containing assay wells. The amount of β-glucuronidase was 1 μg / well. The enzyme-containing assay wells were not added to 80 μl of complete medium. 1.1.5 Dilution and addition of compounds: 1 mg to 3 mg of the test compound was weighed and dissolved in DMSO to obtain a 20 mM storage solution. The initial concentration was adjusted according to the test requirements, and then diluted in a 3-fold gradient with DMSO, and then diluted 100-fold with RPMI1640 basal medium to obtain a 10× working solution with a total of 8 concentrations. The assay wells were charged with 20 μl of the 10× compound working solution. The final volume was 200 μl per well. The DMSO concentration was 0.1%. 1.1.6 Calculation of compound inhibitory activity: The test included a compound test group, a positive solvent control group without the compound (PC), and a negative solvent control group without the compound (NC). The inhibition rate was [1 - (test value - NC average) / (PC average - NC average)] × 100%. The average inhibition rate and the standard deviation (SD) were obtained from the repeated test wells. The average inhibition rate was plotted based on the compound concentration on the horizontal axis and distributed in logarithmic form. The curve fit the logistic 4-parameter equation. The compound concentration corresponding to the 50% inhibition rate on the curve was IC The compounds were plotted based on the concentration and distributed in logarithmic form. The curve fit the logistic 4-parameter equation. The compound concentration corresponding to the 50% inhibition rate on the curve was IC 50It was a value. Usually, the test was repeated and three valid results were obtained.

[0407]

Table 1

[0408] 1.2 Test Results IC for the inhibition of various tumor cell lines 50 value (see Tables 2 to 4).

[0409]

Table 2

[0410]

Table 3

[0411]

Table 4-1

[0412]

Table 4-2

[0413] Biological Example 2 Efficacy Evaluation Experiment Effect on the growth of human colorectal cancer LoVo in a xenograft model 2.1 Test Method Using the tumor block inoculation method, a xenograft model of human colorectal cancer LoVo was established subcutaneously in nude mice. When the tumor volume of the xenograft was about 100 mm 3 to 300 mm 3When in a stable state, the experimental animals were randomly grouped using the surplus method according to the tumor volume (day 0). The tumor volume was measured two to three times a week. At the end of the administration period, the experimental animals were sacrificed. The subcutaneous tumors were dissected and weighed. The antitumor activity of the drug against the model was evaluated based on tumor volume and tumor weight-related data. 2.1.1 Grouping and Administration Plan

[0414]

Table 5

[0415] The calculation formula for tumor volume was as follows: Volume = 0.5 × major axis × minor axis × minor axis. Relative Tumor Volume (RTV): RTV = Vt / V0. V0 is the tumor volume obtained as a result of measurement at the time of administration (i.e., d0) in the group, and Vt is the tumor volume at each measurement time.

[0416] Relative Tumor Growth Rate T / C: T / C = TRTV / CRTV × 100%. T is the subject, and C is the model control. TRTV is the average RTV of the subject, and CRTV is the average RTV of the model control group.

[0417] Tumor Inhibition Rate (%) = (Average Tumor Weight of Model Control Group - Average Tumor Weight of Treatment Group) / Average Tumor Weight of Model Control Group × 100%. Change Rate of Body Weight = Wn / W0 × 100%.

[0418] Wn: Average body weight of each experimental animal group on day n, and W0: Average body weight of each experimental animal group on day 0. 2.3 Experimental Results

[0419]

Table 6

[0420] Biological Example 3 Efficacy Evaluation Experiment Effect on the Growth of Human Colorectal Cancer SW620 in a Syngeneic Transplantation Model 3.1 Test Method Using the tumor block inoculation method, a syngeneic transplantation model of human colorectal cancer SW620 was established subcutaneously in nude mice. When the tumor volume of the syngeneic transplantation was about 100 mm 3 to 300 mm 3 and a stable state was maintained, the experimental animals were randomly grouped using the residual method according to the size of the tumor volume (day 0). The tumor volume was measured two to three times a week. At the end of the administration period, the experimental animals were sacrificed. The subcutaneous tumors were dissected and weighed. The antitumor activity of the drug against the model was evaluated based on tumor volume and tumor weight-related data. 3.1.1 Grouping and Administration Plan

[0421]

Table 7

[0422] The calculation formula for tumor volume was as follows: Volume = 0.5 × major axis × minor axis × minor axis. Relative Tumor Volume (RTV): RTV = Vt / V0. V0 was the tumor volume obtained as a result of measurement at the time of administration (i.e., d0) in the group, and Vt was the tumor volume at each measurement time.

[0423] Relative Tumor Growth Rate T / C: T / C = TRTV / CRTV × 100%. T is the subject, and C is the model control. TRTV was the average RTV of the subject, and CRTV was the average RTV of the model control group.

[0424] Tumor Inhibition Rate (%) = (Average Tumor Weight of the Model Control Group - Average Tumor Weight of the Treatment Group) / Average Tumor Weight of the Model Control Group × 100%. Rate of Change in Body Weight = Wn / W0 × 100%.

[0425] Wn: Average body weight of each experimental animal group on the nth day, and W0: Average body weight of each experimental animal group on the 0th day. 3.3 Experimental results

[0426]

Table 8

[0427] Biological Example 4 Efficacy evaluation experiment Effect on the growth of human colorectal cancer HCT116 in a syngeneic transplantation model 4.1 Test method Using the tumor block inoculation method, a syngeneic transplantation model of human colorectal cancer HCT116 was established subcutaneously in nude mice. When the tumor volume of the syngeneic transplantation was about 100 mm 3 to 300 mm 3 and it maintained a stable state, the experimental animals were randomly grouped by using the remainder method according to the size of the tumor volume (on the 0th day). The tumor volume was measured two to three times a week. At the end of the administration period, the experimental animals were sacrificed. The subcutaneous tumors were dissected and weighed. The antitumor activity of the drug against the model was evaluated based on tumor volume and tumor weight-related data. 4.1.1 Grouping and administration plan

[0428]

Table 9

[0429] The calculation formula for tumor volume was as follows: Volume = 0.5 × major axis × minor axis × minor axis. Relative tumor volume (RTV): RTV = Vt / V0. V0 is the tumor volume obtained as a result of measurement at the time of administration (i.e., d0) in the group, and Vt is the tumor volume at each measurement time.

[0430] Relative tumor growth rate T / C: T / C = TRTV / CRTV × 100%. T is the subject, and C is the model control. TRTV is the average RTV of the subject, and CRTV was the average RTV of the model control group.

[0431] Tumor suppression rate (%) = (Average tumor weight of the model control group - Average tumor weight of the treatment group) / Average tumor weight of the model control group × 100%. Rate of change in body weight = Wn / W0 × 100%.

[0432] Wn: Average body weight of each experimental animal group on the nth day, and W0: Average body weight of each experimental animal group on the 0th day. 4.3 Experimental results

[0433]

Table 10

[0434] Biological Example 5 Efficacy evaluation experiment Effect on the growth of human pancreatic cancer BxPC-36 in a syngeneic transplantation model 5.1 Test method Using the tumor block inoculation method, a syngeneic transplantation model of human pancreatic cancer BxPC-3 was established subcutaneously in nude mice. When the tumor volume of the syngeneic transplantation was about 100 mm 3 to 300 mm 3 and maintained a stable state, the experimental animals were randomly grouped by using the remainder method according to the size of the tumor volume (on the 0th day). The tumor volume was measured two to three times a week. At the end of the administration period, the experimental animals were sacrificed. The subcutaneous tumors were dissected and weighed. The antitumor activity of the drug against the model was evaluated based on tumor volume and tumor weight-related data. 5.1.1 Grouping and administration plan

[0435]

Table 11

[0436] After two administrations, the animals in group G5 were re - divided into four groups, namely, the model control group (G6.1) and three experimental groups (G6.2, G6.3, G6.4). After the tumor volume of the animals in group G5 continuously increased to exceed an average of 600 mm 3 5.2 Evaluation indicators and statistical methods The calculation formula for tumor volume was as follows: Volume = 0.5×long diameter×short diameter×short diameter.

[0437] Relative tumor volume (RTV): RTV = Vt / V0. V0 was the tumor volume obtained as a result of measurement at the time of administration (i.e., d0) in the group, and Vt was the tumor volume at each measurement time.

[0438] Relative tumor growth rate T / C: T / C = TRTV / CRTV×100%. T was the subject, and C was the model control. TRTV was the average RTV of the subject, and CRTV was the average RTV of the model control group.

[0439] Tumor inhibition rate (%)=(Average tumor weight of the model control group - Average tumor weight of the treatment group Amount) / Average tumor weight of the model control group×100%. Change rate of body weight = Wn / W0×100%.

[0440] Wn: Average body weight of each experimental animal group on the nth day, and W0: Average body weight of each experimental animal group on the 0th day. On D17 (the 17th day), it was administered to two groups of group G5. Therefore, the test end data of group G5 in the main test were d17 data. The tumors were not removed in group G5. Therefore, there was no tumor inhibition rate data. In the large - tumor efficacy test after the second grouping of group G5, since the number of samples in each of the groups G6.1 and G6.4 was less than 3, the relevant data of the large - tumor efficacy test were statistically analyzed between groups using the T - test method. 5.3 Experimental results

[0441]

Table 12

[0442]

Table 13

[0443] Biological Example 6 Efficacy Evaluation Experiment Effect on the Growth of Human Small Cell Lung Cancer NCI-H446 in a Syngeneic Transplantation Model 6.1 Test Method Using the tumor block inoculation method, a syngeneic transplantation model of human small cell lung cancer NCI-H446 was established subcutaneously in nude mice. When the volume of the syngeneic transplanted tumor was about 100 mm 3 to 300 mm 3 and it maintained a stable state, the experimental animals were randomly grouped by the remainder method according to the size of the tumor volume (day 0, i.e., d0). The tumor volume was measured two to three times a week. At the end of the administration period, the experimental animals were sacrificed. The subcutaneous tumors were dissected and weighed. The antitumor activity of the drug against the model was evaluated based on tumor volume and tumor weight-related data. 6.1.1 Grouping and Administration Plan

[0444]

Table 14

[0445] The calculation formula for tumor volume was as follows: Volume = 0.5 × major axis × minor axis × minor axis. Relative Tumor Volume (RTV): RTV = Vt / V0. V0 was the tumor volume obtained as a result of measurement at the time of administration (i.e., d0) in the group, and Vt was the tumor volume at each measurement.

[0446] Relative Tumor Growth Rate T / C: T / C = TRTV / CRTV × 100%. T was the subject, and C was the model control. TRTV was the average RTV of the subject, and CRTV was the average RTV of the model control group.

[0447] Tumor suppression rate (%) = (Average tumor weight of the model control group - Average tumor weight of the treatment group) / Average tumor weight of the model control group × 100%. Rate of change in body weight = Wn / W0 × 100%.

[0448] Wn: Average body weight of each experimental animal group on the nth day, and W0: Average body weight of each experimental animal group on the 0th day. 6.3 Experimental results

[0449]

Table 15

[0450] Biological Example 7 Efficacy evaluation experiment Effect on the growth of human gastric cancer NCI-N87 in an orthotopic transplantation model 7.1 Test method Using the tumor block inoculation method, an orthotopic transplantation model of human gastric cancer NCI-N87 was established subcutaneously in nude mice. When the orthotopic transplanted tumor volume was about 100 mm 3 to 300 mm 3 and maintained a stable state, the experimental animals were randomly grouped and administered by using the surplus method according to the size of the tumor volume (day 0, i.e., d0). The tumor volume was measured two to three times a week. At the end of the administration period, the experimental animals were sacrificed. The subcutaneous tumors were dissected and weighed. The antitumor activity of the drug against the model was evaluated based on tumor volume and tumor weight-related data. 7.1.1 Grouping and administration plan

[0451]

Table 16

[0452] Calculation formula for tumor volume: Volume = 0.5 × long diameter × short diameter × short diameter. Relative tumor volume (RTV): RTV = Vt / V0. V0 is the tumor volume obtained as a result of measurement at the time of administration (i.e., d0) in the group, and Vt is the tumor volume at each measurement time.

[0453] Relative tumor growth rate T / C: T / C = TRTV / CRTV × 100%. T is the subject, and C is the model control. TRTV is the average RTV of the subject, and CRTV is the average RTV of the model control group.

[0454] Tumor inhibition rate (%) = (average tumor weight of the model control group - average tumor weight of the treatment group) / average tumor weight of the model control group × 100%. Change rate of body weight = Wn / W0 × 100%.

[0455] Wn: average body weight of each experimental animal group on the nth day, and W0: average body weight of each experimental animal group on the 0th day. 7.3 Experimental results

[0456]

Table 17

[0457] Biological Example 8 Efficacy evaluation experiment Effect of irinotecan on the growth of human colorectal cancer HCT116 in a syngeneic transplantation model 8.1 Test method Using the tumor block inoculation method, a syngeneic transplantation model of human colorectal cancer HCT116 was established subcutaneously in nude mice. When the tumor volume of the syngeneic transplantation was about 100 mm 3 to 300 mm 3 and maintained a stable state, 15 experimental animals were selected and administered irinotecan (100 mg / kg qw × 2). When the tumor volume reached 600 mm 3When the growth exceeded and was maintained at a stable level, the experimental animals were randomly divided by the surplus method and administered according to the size of the tumor volume. The tumor volume was measured two to three times a week. At the end of the administration period, the experimental animals were sacrificed. The subcutaneous tumors were dissected and weighed. After irinotecan treatment in the model, the antitumor activity of the drug against large tumors was evaluated based on tumor volume and tumor weight-related data. 8.1.1 Grouping and Administration Schedule

[0458]

Table 18

[0459] The calculation formula for tumor volume was as follows: Volume = 0.5 × major axis × minor axis × minor axis. Relative Tumor Volume (RTV): RTV = Vt / V0. V0 was the tumor volume obtained as a result of measurement at the time of administration (i.e., d0) in the group, and Vt was the tumor volume at each measurement time.

[0460] Relative Tumor Growth Rate T / C: T / C = TRTV / CRTV × 100%. T was the subject, and C was the model control. TRTV was the average RTV of the subject, and CRTV was the average RTV of the model control group.

[0461] Tumor Inhibition Rate (%) = (Average Tumor Weight of Model Control Group - Average Tumor Weight of Treatment Group) / Average Tumor Weight of Model Control Group × 100%. Rate of Change in Body Weight = Wn / W0 × 100%.

[0462] Wn: Average body weight of each experimental animal group on the nth day, and W0: Average body weight of each experimental animal group on the 0th day. 8.3 Experimental Results 8.3.1 Model Tumor Growth Curve Before Grouping On D18 (the 18th day) after modeling, the tumor volume was 90.36 mm 3From 187.06 mm 3 (with an average of 142.55 mm 3 , SD 31.36), 15 experimental animals were selected. After measuring the tumor volume, irinotecan (100 mg / kg qw×2) was administered. After the administration was completed, the increase in tumor volume was observed regularly. The tumor growth curve is shown in Figure 1. On d53 (the 53rd day) after modeling, the model tumor volume recovered significantly after irinotecan administration and had an average of 689.82 mm 3 . Therefore, the experimental animals were grouped, and the compound of the present application was administered to continue the treatment. 8.3.2 Effect on the growth of human colorectal cancer HCT116 large tumors in a syngeneic transplantation model after irinotecan administration

[0463]

Table 19

[0464] Biological Example 9 Toxicity evaluation experiment in mice after multiple administrations 9.1 Test method The experimental animals were randomly divided according to body weight. At the time of the experiment, the corresponding dose of the compound was administered to the test animals via the tail vein (i.v.). The grouping and administration plan are shown in detail in Table 2. The administration plan may be appropriately adjusted during the course of the test according to the toxicity of the animals. After the administration, the performance of the experimental animals was observed regularly, and the body weight and necropsy of each experimental animal group were recorded. After the end of the observation period, each animal group was sacrificed and dissected. The changes in the main organs were observed. The toxic effects and toxicity recovery of the compound were evaluated. 9.1.1 Grouping and administration plan

[0465]

Table 20

[0466] Change rate of body weight = Wn / W0×100% (Wn: Average body weight of each experimental animal group on the nth day, W0: Average body weight of each experimental animal group on the 0th day) The animal body weight-related data were statistically analyzed using the general linear model test of SPSS 22.0 software. First, the sphericity test was performed using the repeated measures analysis of variance method. When P > 0.05, it was considered that there was no correlation between the repeated measures data, and one-way analysis of variance (One-Way Anova test) was used to perform the statistical analysis between groups. When P ≤ 0.05, it was considered that there was a correlation between the repeated measures data, and multivariate analysis of variance (multivariate) was used for the statistical analysis between groups. 9.3 Experimental results By the end of the test, no death or near-death occurred in each treatment group. The maximum tolerated dose (MTD) of a single administration of the compound of the present application exceeded 150 mg / kg, and the maximum tolerated dose (MTD) of the total administered dose exceeded 300 mg / kg. This suggested that the compound of the present application had good safety and good tolerance.

[0467] In the present disclosure, relational terms such as first and second are used only to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any actual relationship or order between the entity or operation.

[0468] From the foregoing, although specific embodiments of the present application are described herein for illustrative purposes, it will be understood that various modifications or improvements can be made by those skilled in the art without departing from the spirit and scope of the present disclosure. Such changes or modifications are intended to be included within the scope of the claims appended hereto.

Claims

1. A compound of formula (I), 【Chemical 1】 wherein, R １ is hydrogen, C １ to C ８ hydrocarbyl, -Na, -Li, -K, -Cs, -NH ４ ＋ , -NH ２ ＋ R １３ R １４ , -NH ＋ R １３ R １４ R １５ , -NH ＋ ３ R １３ , and is selected from the group consisting of natural or non-natural amino acids; R ２ is hydrogen, and is selected from the group consisting of C １ to C ８ hydrocarbyl; R ３ is hydrogen, halogen, C １ to C ８ hydrocarbyl, C １ to C ８ hydrocarbyloxy, cyano, nitro, amino, aryl, arylhydrocarbyl, and C １ to C ４ one or more substituents at any substitution position selected from the group consisting of hydrocarbyl-substituted amino; R ４ is C １ to C ９ alkylidene, C １ to C ８ alkylideneoxy, C １ to C ８ hydrocarbyl-substituted or unsubstituted C ３ to C ８ heteroaryl, C １ to C ８ hydrocarbyl-substituted or unsubstituted C ３ to C １５ aryl, -(CH ２ R ７ ) ｎ, -(R ８ ) ｍ , C １ ~C ９ alkylidene-arylidene, C １ ~C ９ alkylidene-arylidene-C １ ~C ９ alkyldiene, C １ ~C ９ alkylidene-arylidene-arylidene, C １ ~C ９ alkylidene-heteroarylidene-C １ ~C ９ alkylidene, and selected from the group consisting of amino acid peptide chains; wherein said amino acid peptide chain is composed of a combination of natural or non-natural amino acids, and the length of said peptide chain is from 1 to 100 peptides, preferably from 1 to 50 peptides, more preferably from 1 to 20 peptides; R ５ is selected from the group consisting of hydrogen and C １ ~C ８ hydrocarbyl; R ６ is selected from the group consisting of hydrogen, C １ ~C ８ hydrocarbyl, C １ ~C ８ hydrocarbylideneamino(C １ ~C ４ hydrocarbyl), ２ , C １ ~C ８ hydrocarbylidene thio C １ ~C ８ hydrocarbyl, and C １ ~C ９ alkylidene-oxy-C １ ~C ９ alkyl; R ５ and R ６ may form a ring, and when R ５ and R ６ form a ring, said ring may be a 5-membered or 6-membered ring; R ７ is selected from the group consisting of hydrogen, C １ ~C ８ Hydrocarbylideneoxy, amino C １ -C ８ Hydrocarbyl ridene, thio C １ -C ８ Hydrocarbylidene, and oxy C １ -C ８ selected from hydrocarbylidene; n is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, and 9; when n is 0, (CH ２ R ７ ) ｎ represents a covalent bond; R ８ is carbonylamino, where the amino is C １ -C ８ hydrocarbyl or arylhydrocarbyl, C １ -C ８ hydrocarbylideneamino C １ -C ８ hydrocarbylidene, C １ -C ８ hydrocarbylidene thio C １ -C ８ hydrocarbylidene, or C １ -C ８ hydrocarbylideneoxy C １ -C ８ may be substituted with hydrocarbylidene; m is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, and 9; when m is 0, -(R ８ ) ｍ represents a covalent bond; R ９ is hydrogen, halogen, cyano, C １ -C ８ hydrocarbyl, C １ -C ８ alkoxy, and C ５ -C １２ one or more substituents at any position selected from the group consisting of aryl; R １０ is hydrogen, halogen, cyano, C １ -C ８ hydrocarbyl, C １ ~C ８ alkoxy, and C ５ ~C １２ one or more substituents at any position selected from the group consisting of; R １１ is hydrogen, -Na, -Li, -K, -Cs, -NH ４ ＋ 、-NH ２ ＋ R １３ R １４ 、-NH ＋ R １３ R １４ R １５ 、-NH ３ ＋ R １３ 、and selected from the group consisting of natural or non-natural amino acids; R １２ is hydrogen, -Na, -Li, -K, -Cs, -NH ４ ＋ 、-NH ２ ＋ R １３ R １４ 、-NH ＋ R １３ R １４ R １５ 、-NH ３ ＋ R １３ 、and selected from the group consisting of natural or non-natural amino acids; R １３ is hydrogen, C １ ~C ８ hydrocarbyl, C １ ~C ８ cyclohydrocarbyl, C ５ ~C １８ aryl, and C ５ ~C １８ heteroaryl; R １４ is hydrogen, C １ ~C ８ hydrocarbyl, C １ ~C ８ cyclohydrocarbyl, C ５ ~C １８ aryl, and C ５ ~C １８ selected from the group consisting of heteroaryl; R １５ is hydrogen, C １ -C ８ hydrocarbyl, C １ -C ８ cyclohydrocarbyl, C ５ -C １８ aryl, and C ５ -C １８ heteroaryl; and R １ R １１ and R １２ the natural or non-natural amino acid at is selected from the group consisting of glycine, alanine, valine, leucine, isoleucine, methionine (methionine), proline, tryptophan, serine, tyrosine, cysteine, phenylalanine, asparagine, glutamine, threonine, aspartic acid, glutamic acid, lysine, arginine, histidine, selenocysteine, sarcosine, pyrrolysine, and homoalanine, a compound of formula (I), and stereoisomers and cis-trans isomers of the compound of formula (I).

2. a compound of formula (I), wherein 【Chemical formula 2】 in the formula, R １ is hydrogen, C １ -C ４ hydrocarbyl, -Na, -Li, -K, -Cs, -NH ４ ＋ -NH ２ ＋ R １３ R １４ -NH ＋ R １３ R １４ R １５ -NH ＋ ３ R １３ and is selected from the group consisting of hydrogen and natural or non-natural amino acids; R ２ is hydrogen, and C １ -C ４Selected from the group consisting of hydrocarbyls; R ３ is one or more substituents at any position selected from the group consisting of hydrogen, halogen, C １ to C ４ hydrocarbyls, C １ to C ４ hydrocarbyloxy, cyano, nitro, amino, aryl, arylhydrocarbyl, and C １ to C ４ hydrocarbyl-substituted amino; R ４ is C １ to C ６ alkylidene, C １ to C ６ alkylideneoxy, C １ to C ６ hydrocarbyl-substituted or unsubstituted C ３ to C ８ heteroaryl, C １ to C ８ hydrocarbyl-substituted or unsubstituted C ３ to C １５ aryl, -(CH ２ R ７ ) ｎ , -(R ８ ) ｍ , C １ to C ４ alkylidene-arylidene, C １ to C ４ alkylidene-arylidene-C １ to C ４ alkylidene, C １ to C ４ alkylidene-arylidene-arylidene, C １ to C ４ alkylidene-heteroarylidene-C １ to C ４ alkylidene, and an amino acid peptide chain; wherein the amino acid peptide chain is composed of a combination of natural or non-natural amino acids, and the length of the peptide chain is from 1 to 100 peptides, preferably from 1 to 50 peptides, more preferably from 1 to 20 peptides; R ５ is hydrogen, and C １ to C ４ selected from the group consisting of hydrocarbyl; R ６ is hydrogen, C １ to C ４ hydrocarbyl, C １ to C ４ hydrocarbylideneamino (C １ to C ４ hydrocarbyl), ２ C １ to C ４ hydrocarbylidene thio C １ to C ４ hydrocarbyl, and C １ to C ４ alkylidene-oxy-C １ to C ４ alkyl selected from the group consisting of; R ５ and R ６ may form a ring, and R ５ and R ６ when forming a ring, all rings may be 5-membered or 6-membered rings; R ７ is hydrogen, C １ to C ４ alkylideneoxy, amino C １ to C ４ -alkylidene, thio C １ to C ４ -alkylidene, and oxy C １ to C ４ alkylidene selected from the group consisting of; n is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, and 9; when n is 0, -(CH ２ R ７ ) ｎ represents a covalent bond; R ８ is carbonylamino, where the amino is C １ to C ４ hydrocarbyl or arylhydrocarbyl, C １ to C ４ hydrocarbylideneamino C １ to C ４Hydrocarbylidene, C １ to C ４ Hydrocarbylidene thio C １ to C ４ Hydrocarbylidene, or C １ to C ４ Hydrocarbylidene oxy C １ to C ４ may be substituted with hydrocarbylidene; m is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, and 9; when m is 0, -(R ８ ) ｍ represents a covalent bond; R ９ is one or more substituents at any position selected from the group consisting of hydrogen, halogen, cyano, C １ to C ４ hydrocarbyl, C １ to C ４ alkoxy, and C ５ to C １２ aryl; R １０ is one or more substituents at any position selected from the group consisting of hydrogen, halogen, cyano, C １ to C ４ hydrocarbyl, C １ to C ４ alkoxy, and C ５ to C １２ aryl; R １１ is selected from the group consisting of hydrogen, -Na, -Li, -K, -Cs, -NH ４ ＋ , -NH ２ ＋ R １３ R １４ , -NH ＋ R １３ R １４ R １５ , -NH ３ ＋ R １３ , and is selected from the group consisting of natural or non-natural amino acids; R １２ is selected from the group consisting of hydrogen, -Na, -Li, -K, -Cs, -NH ４ ＋ , -NH ２ ＋ R １３ R １４ 、 -NH ＋ R １３ R １４ R １５ 、 -NH ３ ＋ R １３ 、 and is selected from the group consisting of natural or non-natural amino acids; R １３ is hydrogen, C １ ~C ４ alkyl, C １ ~C ８ cycloalkyl, C ５ ~C １８ aryl, and C ５ ~C １８ heteroaryl; R １４ is hydrogen, C １ ~C ４ alkyl, C １ ~C ８ cycloalkyl, C ５ ~C １８ aryl, and C ５ ~C １８ heteroaryl; R １５ is hydrogen, C １ ~C ４ alkyl, C １ ~C ８ cycloalkyl, C ５ ~C １８ aryl, and C ５ ~C １８ heteroaryl; and R １ 、 R １１ 、 and R １２The natural or non-natural amino acid in [description] is selected from the group consisting of glycine, alanine, valine, leucine, isoleucine, methionine, proline, tryptophan, serine, tyrosine, cysteine, phenylalanine, asparagine, glutamine, threonine, aspartic acid, glutamic acid, lysine, arginine, histidine, selenocysteine, sarcosine, pyrrolysine, and homoalanine. The compound of formula (I) according to claim 1, and stereoisomers and cis-trans isomers of the compound of formula (I).

3. A compound of formula (I), 【Chemical formula 3】 Wherein, R １ is hydrogen, -CH ３ , -CH ２ CH ３ , -Na, -Li, -K, -Cs, -NH ４ ＋ , -NH ２ ＋ R １３ R １４ , -NH ＋ R １３ R １４ R １５ , -NH ＋ ３ R １３ , and is selected from the group consisting of natural or non-natural amino acids; R ２ is hydrogen, -CH ３ , and -CH ２ CH ３ , and is selected from the group consisting of; R ３ is hydrogen, -F-, -Cl, -Br, -CN, -CH ３ , -CH ２ CH ３ , -CH ２ CH ２ CH ３ , -CH ２ CH ２ CH ２ CH ３ , -OCH ３ , -OCH ２CH ３ 、 - OCH ２ CH ２ CH ３ 、 - OCH ２ CH ２ CH ２ CH ３ 、 phenyl, benzyl, - NO ２ 、 - NH ２ 、 and - N(CH ３ ) ２ selected from one or more substituents replaced at any position selected from; R ４ is, - CH ２ -, - CH ２ CH ２ -, - CH ２ CH ２ CH ２ -, - CH ２ CH ２ CH ２ CH ２ -, - CH ２ CH ２ CH ２ CH ２ CH ２ -, - CH ２ CH ２ CH ２ CH ２ CH ２ CH ２ -, - CH ２ CH ２ CH ２ CH ２ CH ２ CH ２ CH ２ -, - CH ２ CH ２ CH ２ CH ２ CH ２ CH ２ CH ２ CH ２ -, - CH ２ CH ２ CH ２ CH ２ CH ２ CH ２ CH ２ CH ２ CH ２ -, - CH ２ OCH ２-, -CH ２ OCH ２ CH ２ -, -CH ２ OCH ２ CH ２ OCH ２ -, -CH ２ OCH ２ CH ２ OCH ２ CH ２ OCH ２ -, -CH ２ OCH ２ CH ２ OCH ２ CH ２ OCH ２ CH ２ OCH ２ -, -CH ２ CH ２ OCH ２ CH ２ CH ２ OCH ２ -, -CH ２ CH ２ OCH ２ CH ２ CH ２ OCH ２ CH ２ CH ２ OCH ２ -, -CH ２ CH ２ OCH ２ CH ２ CH ２ OCH ２ CH ２ CH ２ OCH ２ CH ２ CH ２ OCH ２ -, -CH ２ CH ２ OCH ２ -, -CH ２ CH ２ OCH ２ CH ２ CH ２ OCH ２ CH ２ -, -CH ２ CH ２ OCH ２ CH ２ CH ２ OCH ２ -, -CH ２ NHCH ２ CH ２ NHCH ２ CH ２ NHCH ２ -, 【Chemical Formula 4】 selected from the group consisting of, and peptides, wherein the peptide is composed of, for example, combinations of natural or non-natural amino acids such as glycine, alanine, valine, leucine, isoleucine, methionine (methionine), proline, tryptophan, serine, tyrosine, cysteine, phenylalanine, asparagine, glutamine, threonine, aspartic acid, glutamic acid, lysine, arginine, histidine, selenocysteine, sarcosine, pyrrolysine, homoalanine, or any combination thereof; the length of the peptide chain is from 1 to 100 peptides, preferably from 1 to 50 peptides, more preferably from 1 to 20 peptides; R ５ is selected from the group consisting of hydrogen, -CH ３ and -CH ２ CH ３ ; R ６ is selected from the group consisting of hydrogen, -CH ３ , -CH ２ OCH ３ , -CH ２ N(CH ３ ) ２ and -CH ２ SCH(CH ３ ) ２ ; R ５ and R ６ form a ring, the ring may be a 5-membered ring or a 6-membered ring; R ７ is -H, -OCH ２ -, -OCH ２ CH ２ -, -OCH ２ CH ２ CH ２ -, -OCH ２ CH ２ CH ２ CH ２ -, -NHCH ２ -, -NHCH ２ CH ２ -, -NHCH ２ CH ２ CH ２ -, -NHCH ２ CH ２ CH ２ CH ２ -, -SCH ２ -, -SCH ２ CH ２ -, -SCH ２ CH ２ CH ２ -, -SCH ２ CH ２ CH ２ CH ２ -, -CH ２ O-, -CH ２ CH ２ O-, -CH ２ CH ２ CH ２ O-, and -CH ２ CH ２ CH ２ CH ２ O-, selected from the group consisting of; n is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, and 9; when n is 0, -(CH ２ R ７ ) ｎ represents a covalent bond; R ８ is, -CH ２ OCH ２ CH ２ -, -CH ２ CH ２ OCH ２ -, -CH ２ CH ２ OCH ２ CH ２ -, -CH ２ CH ２ OCH ２ CH ２ CH ２ -, -CH ２ CH ２ CH ２ OCH ２ CH ２ -, -CH ２ CH ２ CH ２ OCH ２ CH ２ CH ２ —, —CH ２ SCH ２ CH ２ —, —CH ２ CH ２ SCH ２ —, —CH ２ CH ２ SCH ２ CH ２ —, —CH ２ CH ２ SCH ２ CH ２ CH ２ —, —CH ２ CH ２ CH ２ SCH ２ CH ２ —, —CH ２ CH ２ CH ２ SCH ２ CH ２ CH ２ —, —CH ２ NHCH ２ CH ２ —, —CH ２ CH ２ NHCH ２ —, —CH ２ CH ２ NHCH ２ CH ２ —, —CH ２ CH ２ NHCH ２ CH ２ CH ２ —, —CH ２ CH ２ CH ２ NHCH ２ CH ２ —, —CH ２ CH ２ CH ２ NHCH ２ CH ２ CH ２ —, —CONHCH ２ —, —CONHCH ２ CH ２ —, —CONHCH ２CH ２ CH ２ -, -CON(CH ３ )CH ２ -, -CON(CH ３ )CH ２ CH ２ -, -CON(CH ３ )CH ２ CH ２ CH ２ -, -CONHCH(CH ３ )-, -CONHCH(CH ３ )CH ２ -, -CONHCH(CH ３ )CH ２ CH ２ -, -CONHCH ２ CH(CH ３ )CH ２ -, -CONHCH(CH ３ )CONHCH(CH ３ )CH ２ C ６ H ５ -, selected from the group consisting of; m is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, and 9; when m is 0, -(R ８ ) ｍ represents a covalent bond; R ９ is one or more substituents at any position selected from the group consisting of hydrogen, -F-, -Cl, -Br, -CN, -CH ３ 、-CH ２ CH ３ 、-OCH ３ 、-OCH ２ CH ３ 、and phenyl; R １０ is one or more substituents at any position selected from the group consisting of hydrogen, -F-, -Cl, -Br, -CN, -CH ３ 、-CH ２ CH ３ 、-OCH ３ 、-OCH ２ CH ３ 、and phenyl; R １１ is hydrogen, -Na, -Li, -K, -Cs, -NH ４ ＋ ,-NH ２ ＋ R １３ R １４ ,-NH ＋ R １３ R １４ R １５ ,-NH ３ ＋ R １３ , selected from the group consisting of glycine, alanine, valine, leucine, isoleucine, methionine (methionine), proline, tryptophan, serine, tyrosine, cysteine, phenylalanine, asparagine, glutamine, threonine, aspartic acid, glutamic acid, lysine, arginine, histidine, selenocysteine, sarcosine, pyrrolysine, and homoalanine; R １２ is hydrogen, -Na, -Li, -K, -Cs, -NH ４ ＋ , -NH ２ ＋ R １３ R １４ , -NH ＋ R １３ R １４ R １５ , -NH ３ ＋ R １３ , selected from the group consisting of glycine, alanine, valine, leucine, isoleucine, methionine (methionine), proline, tryptophan, serine, tyrosine, cysteine, phenylalanine, asparagine, glutamine, threonine, aspartic acid, glutamic acid, lysine, arginine, histidine, selenocysteine, sarcosine, pyrrolysine, and homoalanine; R １３ is hydrogen, -CH ３ , -CH ２ CH ３ , -CH(CH ３ ) ２ , -CH ２ CH ２ CH ３ , -CH ２ CH ２ CH ２ CH ２ CH ３ selected from the group consisting of cyclohexyl, phenyl, pyridyl, thienyl, imidazolyl, indolyl, quinolinyl, pyridoimidazolyl, pyridoindolyl, imidazoquinolinyl, imidazoquinoxalinyl, imidazopyridyl, and benzoxazinyl; R １４ is hydrogen, -CH ３ -, -CH ２ CH ３ -, -CH(CH ３ ) ２ -, -CH ２ CH ２ CH ３ -, -CH ２ CH ２ CH ２ CH ２ CH ３ selected from the group consisting of cyclohexyl, phenyl, pyridyl, thienyl, imidazolyl, indolyl, quinolinyl, pyridoimidazolyl, pyridoindolyl, imidazoquinolinyl, imidazoquinoxalinyl, imidazopyridyl, and benzoxazinyl; and R １５ is hydrogen, -CH ３ -, -CH ２ CH ３ -, -CH(CH ３ ) ２ -, -CH ２ CH ２ CH ３ -, -CH ２ CH ２ CH ２ CH ２ CH ３ selected from the group consisting of cyclohexyl, phenyl, pyridyl, thienyl, imidazolyl, indolyl, quinolinyl, pyridoimidazolyl, pyridoindolyl, imidazoquinolinyl, imidazoquinoxalinyl, imidazopyridyl, and benzoxazinyl, The compound of formula (I) according to claim 1 or claim 2, and stereoisomers and cis-trans isomers of the compound of formula (I).

4. Compounds, stereoisomers and cis-trans isomers of compounds selected from the group consisting of Trisodium (2S,3S,4S,5R,6S)-6-((3-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-2-methylphenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; Disodium 4-amino-6-((E)-(4'-(6-(4-((3-(((2S,3R,4S,5S,6S)-6-carboxy-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)oxy)-6-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-2-tolyloxy)methyl)-1H-1,2,3-triazol-1-yl)hexanamide)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate; 4-amino-6-((E)-(4'-(6-(4-((6-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1 Disodium 4-amino-6-((E)-(4'-(6-(4-((6-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-2-methyl-3-(((2S,3R,4S,5S,6S)-3,4,5-trihydroxy-6-(methoxycarbonyl)tetrahydro-2H-pyran-2-yl)oxy)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)hexanamide)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonaphthalen-2-yl)diazenyl)-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-2-methylphenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; 4-amino-6-((E)-(4'-(6-(4-((5-(((2S,3R,4S,5S,6S)-6-carboxy-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)oxy)-2-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)hexanamide)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonic acid disodium; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; Disodium 4-amino-6-((E)-(4'-(6-(4-(((2-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-5-((((2S,3R,4S,5S,6S)-3,4,5-trihydroxy-6-(methoxycarbonyl)tetrahydro-2H-pyran-2-yl)oxy)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)hexanamido)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate; Trisodium (2S,3S,4S,5R,6S)-6-(3-(((1-(6-((4'-( (E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4-ethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; Disodium 4-amino-6-((E)-(4'-(6-(4-(((5-((((2S,3R,4S,5S,6S)-6-carboxy-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)oxy)-2-((((S)-4-ethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)hexanamido)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate; Disodium 4-amino-6-((E)-(4'-(6-(4-(((5-((((2S,3R,4S,5S,6S)-6-carboxy-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)oxy)-2-((((S)-4-ethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)hexanamido)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate; Sodium 4-amino-6-((E)-(4'-(6-(4-(((2-(((S)-4-ethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)-5-((((2S,3R,4S,5S,6S)-3,4,5-trihydroxy-6-(methoxycarbonyl)tetrahydro-2H-pyran-2-yl)oxy)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)hexanamido)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate; Trisodium (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)-5-methoxyphenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; Trisodium (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4-ethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; Trisodium (2S,3S,4S,5R,6S)-6-((3-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-5-methoxyphenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; Trisodium (2S,3S,4S,5R,6S)-6-((3-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethoxy-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4-ethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; Disodium 4-amino-6-((E)-(4'-(4-((5-(((2S,3R,4S,5S,6S)-6-carboxy-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)oxy)-2-(((S)-4-ethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)hexanamide)-3,3'-dimethoxy- [1,1'-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate; 4-Amino-6-((E)-(4'-(6-(4-((2-(((S)-4-Ethyl-4-hydroxy-3,14-dioxy-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-5-(((2S,3R,4S,5S,6S)-3,4,5-trihydroxy-6-(methoxycarbonyl)tetrahydro-2H-pyran-2-yl)oxy)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)hexanamido)-3,3'-dimethoxy-[1,1'-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonic acid disodium; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4'-(E)-(8-Amino-1-hydroxy-5,7-disulfonaphthalene-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-10-((dimethylamino)methyl)-4-ethyl-4-hydroxy-3,14-dioxy-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(3-((1-(8-((4'-(E)-(8-Amino-1-hydroxy-5,7-disulfonaphthalene-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-8-oxooctyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-Diethyl-4-hydroxy-3,14-dioxy-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; Sodium 4-amino-6-((E)-(4'-(8-(4-((5-(((2S,3R,4S,5S,6S)-6-carboxy-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)oxy)-2-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)octanamido)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate; Sodium 4-amino-6-((E)-(4'-(8-(4-((2-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazo[1,2-b]quinolin-9-yl)oxy)methyl)-5-((((2S,3R,4S,5S,6S)-3,4,5-trihydroxy-6-(methoxycarbonyl)tetrahydro-2H-pyran-2-yl)oxy)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)octanamido)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate; Trisodium (2S,3S,4S,5R,6S)-6-(3-((1-(8-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-[1,1'-biphenyl]-4-yl)amino)-8-oxooctyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; (2S,3S,4S,5R,6S)-6-(3-((1-(8-((4'-(E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-8-oxooctyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-2-methylphenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(3-((1-(2-(2-(2-((4'-(E)-(8-Amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-2-oxoethoxy)ethoxy)ethyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3R,4S,5S,6S)-6-carboxy-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)oxy)-2-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)ethoxy)ethoxy)acetamide)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonic acid disodium; Sodium 4-amino-6-((E)-(4'-(2-(2-(2-(2-(((2-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indazolo[1,2-b]quinolin-9-yl)oxy)methyl)-5-((((2S,3R,4S,5S,6S)-3,4,5-trihydroxy-6-(methoxycarbonyl)tetrahydro-2H-pyran-2-yl)oxy)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)ethoxy)acetamido)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate; Trisodium (2S,3S,4S,5R,6S)-6-(3-((1-(2-(2-(2-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethoxy-[1,1'-biphenyl]-4-yl)amino)-2-oxoethoxy)ethoxy)ethyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; Sodium 4-amino-6-((E)-(4'-(2-(2-(2-(2-(2-((((5-((((2S,3R,4S,5S,6S)-6-carboxy-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)oxy)-2-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)ethoxy)ethoxy)acetamido)-3,3'-dimethoxy-[1,1'-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate; 4-Amino-6-((E)-(4'-(2-(2-(2-((2-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro -1H-pyrano[3',4':6,7]indazolo[1,2-b]quinolin-9-yl)oxy)methyl)-5-((((2S,3R,4S,5S,6S)-3,4,5-trihydroxy-6-(methoxycarbonyl)tetrahydro-2H-pyran-2-yl)oxy)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)ethoxy)acetamido)-3,3'-dimethoxy-[1,1'-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonic acid disodium; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4'-( (E)-(8-amino-1-hydroxy-5,7-disulfonaphthalen-2-yl)diazenyl)-3,3'-dimethoxy-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; 4-Amino-6-((E)-(4'-(6-(4-((5-((((2S,3R,4S,5S,6S)-6-carboxy-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)oxy)-2-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)hexanamido)-3,3'-dimethoxy-[1,1'-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonic acid disodium; Sodium 4-amino-6-((E)-(4'-(6-(4-(((2-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indazolo[1,2-b]quinolin-9-yl)oxy)methyl)-5-((((2S,3R,4S,5S,6S)-3,4,5-trihydroxy-6-(methoxycarbonyl)tetrahydro-2H-pyran-2-yl)oxy)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)hexanamido)-3,3'-dimethoxy-[1,1'-biphenyl]-4-yl)diazenyl)-5-hydroxynaphthalene-1,3-disulfonate; (2S,3S,4S,5R,6S)-6-(3-(((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid; Sodium 1-amino-7-((E)-(4'-(6-(4-(((5-((((2S,3R,4S,5S,6S)-6-carboxy-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)oxy)-2-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)hexanamido)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)diazenyl)-8-hydroxy-4-sulfonatonaphthalene-2-sulfonate; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S )-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate trilithium; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate triammonium; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate tripotassium; Tricesium (2S,3S,4S,5R,6S)-6-((3-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; Trisodium (2S,3S,4S,5R,6S)-6-((3-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)-2-fluorophenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; Trisodium (2S,3S,4S,5R,6S)-6-((3-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-2-chloro-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; (2S,3S,4S,5R,6S)-6-((3-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-2-bromo-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2 -b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium salt; (2S,3S,4S,5R,6S)-6-((3-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-2-methoxyphenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium salt; (2S,3S,4S,5R,6S)-6-((3-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-2-ethylphenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium salt; Trisodium (2S,3S,4S,5R,6S)-6-((3-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((1-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl)oxy)ethyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; Trisodium (2S,3S,4S,5R,6S)-6-((6-((1-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-5-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)-[1,1'-biphenyl]-2-yl)oxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; Trisodium (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-2-nitrophenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; Trisodium (2S,3S,4S,5R,6S)-6-((2-amino-3-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; Trisodium (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-2-(dimethylamino)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; Trisodium (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-5-fluorophenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; Trisodium (2S,3S,4S,5R,6S)-6-((3-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-5-chloro-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; Trisodium (2S,3S,4S,5R,6S)-6-((3-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-5-bromo-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; Trisodium (2S,3S,4S,5R,6S)-6-((3-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)-5-methylphenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4'-((E)-(8-amino-1-hydroxy-5,7-disulfonnaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxy-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-5-nitrophenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate trisodium; (2S,3S,4S,5R,6S)-6-((5-((1-(6-((4'-((E)-(8-amino-1-hydroxy-5,7-disulfonato-2-yl)diazenyl) trisodium (((S)-4,11-diethyl-4-hydroxy-3,14-dioxy-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)-[1,1'-biphenyl]-3-yl)oxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4'-((E)-(8-amino-1-hydroxy-5,7-disulfonnaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxy-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-5-ethylphenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate trisodium; Trisodium (2S,3S,4S,5R,6S)-6-((3-amino-5-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; Trisodium (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-5-(dimethylamino)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; Trisodium (2S,3S,4S,5R,6S)-6-(5-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)-2-fluorophenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; (2S,3S,4S,5R,6S)-6-(5-((1-(6-((4'-((E)-(8-amino-1-hydroxy-5,7-disulfonnaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-2-chloro-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxy-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate trisodium; (2S,3S,4S,5R,6S)-6-(5-((1-(6-((4'-((E)-(8-amino-1-hydroxy-5,7-disulfonnaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxo hexyl)-1H-1,2,3-triazol-4-yl)methoxy)-2-bromo-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxy-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate trisodium; (2S,3S,4S,5R,6S)-6-(5-((1-(6-((4'-((E)-(8-amino-1-hydroxy-5,7-disulfonnaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxy-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-2-methoxyphenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate trisodium; Trisodium (2S,3S,4S,5R,6S)-6-((5-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)-2-nitrophenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; Trisodium (2S,3S,4S,5R,6S)-6-((4-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-5-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)-[1,1'-biphenyl]-2-yl)oxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; Trisodium (2S,3S,4S,5R,6S)-6-(5-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)-2-ethylphenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; Trisodium (2S,3S,4S,5R,6S)-6-((2-amino-5-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3,4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; (2S,3S,4S,5R,6S)-6-(5-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S )-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)-2-(dimethylamino)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate trisodium; Trisodium (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-6-fluoro-2-methoxyphenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; Trisodium (2S,3S,4S,5R,6S)-6-((3-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-6-chloro-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-5-fluoro-2-methylphenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; Trisodium (2S,3S,4S,5R,6S)-6-((3-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-6-bromo-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)-2-methoxyphenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; Trisodium (2S,3S,4S,5R,6S)-6-((3-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-9-ethyl-9-hydroxy-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,7]benzo[d]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-4-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; (2S,3S,4S,5R,6S)-6-((4-(((S)-4-acetoxy-4-ethyl-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)-3-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)phenoxy)-3, trisodium 4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4-ethyl-3,14-dioxo-4-(propionyloxy)-3,4,12,1 4-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4-ethyl-4-(glycyloxy)-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium; Trisodium (2S,3S,4S,5R,6S)-6-(3-(((1-(6-(((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((R)-5-ethyl-5-hydroxy-3,15-dioxo-4,5,13,15-tetrahydro-1H,3H-oxazepino[3',4':6,7]indolizino[1,2-b]quinolin-10-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; Trisodium (2S,3S,4S,5R,6S)-6-(3-(((1-(6-(((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4-ethyl-4-hydroxy-10-(methoxymethyl)-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; Trisodium (2S,3S,4S,5R,6S)-6-(3-(((1-(6-(((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4-ethyl-4-hydroxy-10-((isopropylthio)methyl)-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; Trisodium (2S,3S,4S,5R,6S)-6-((3-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4-ethyl-4-hydroxy-3-oxo-14-thia-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; Trisodium (2S,3S,4S,5R,6S)-6-(3-((1-((2-((2-((2-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-2-oxoethyl)(methyl)amino)-2-oxoethyl)(methyl)amino)-2-oxoethyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2- b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; Trisodium (2S,3S,4S,5R,6S)-6-(3-((1-((2-((2-((2-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-2-oxoethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; Trisodium (2S,3S,4S,5R,6S)-6-((3-((1-(2-((S)-1-((S)-1-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-1-oxopropan-2-yl)amino)-1-oxopropan-2-yl)amino)-2-oxoethyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; Trisodium (2S,3S,4S,5R,6S)-6-((3-((1-(2-((S)-1-((S)-1-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-1-oxo-3-phenylpropan-2-yl)amino)-1-oxopropan-2-yl)amino)-2-oxoethyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; (2S,3S,4S,5R,6S)-6-(3-((1-(2-(2-(2-(2-(((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-2-oxoethoxy)ethoxy)ethoxy)ethyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium salt; (2S,3S,4S,5R,6S)-6-(3-((1-((2-((2-((2-((2-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-2-oxoethyl)amino)ethyl)amino)ethyl)amino)ethyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium salt; (2S,3S,4S,5R,6S)-6-(3-((1-(3-(3-(3-(((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonaphthalen-2-yl )diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-3-oxopropoxy)propoxy)propyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium salt; Trisodium (2S,3S,4S,5R,6S)-6-((3-((1-(4-(((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)carbamoyl)phenethyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; Trisodium (2S,3S,4S,5R,6S)-6-((3-((1-(2-(2-(((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)carbamoyl)naphthalen-2-yl)ethyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; Trisodium (2S,3S,4S,5R,6S)-6-((3-((1-(2-(4'-(4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)carbamoyl)-[1,1'-biphenyl]-4-yl)ethyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; (2S,3S,4S,5R,6S)-6-(3-((1-(4-(4-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-4-oxobutyl)phenethyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium salt; (2S,3S,4S,5R,6S)-6-(3-((1-(2-(2-(6-(4-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-4-oxobutyl)pyridin-3-yl)ethyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium salt; (2S,3S,4S,5R,6S)-6-(3-((1-(2-(2-(5-(4-( (4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-4-oxobutyl)thiophen-3-yl)ethyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium salt; Trisodium (2S,3S,4S,5R,6S)-6-((3-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3',5,5'-tetramethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; Trisodium (2S,3S,4S,5R,6S)-6-((3-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-2,2',3,3',5,5',6,6'-octamethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; Trisodium (2S,3S,4S,5R,6S)-6-((3-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-2,2',3,3',5,5',6,6'-octamethoxy-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; Trisodium (2S,3S,4S,5R,6S)-6-((3-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3',5,5'-tetrachloro-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; Trisodium (2S,3S,4S,5R,6S)-6-((3-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-2,2',3,3',5,5',6,6'-octafluoro-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; m; Trisodium (2S,3S,4S,5R,6S)-6-((3-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3'-chloro-3-methoxy-5,5'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3,4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; Trisodium (2S,3S,4S,5R,6S)-6-((3-((1-(6-((6'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-[1,1':3',1'':3'',1'''-quaterphenyl]-4''-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; Trisodium (2S,3S,4S,5R,6S)-6-((3-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-difluoro-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; Trisodium (2S,3S,4S,5R,6S)-6-((3-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dichloro-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-((((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate; (2S,3S,4S,5R,6S)-6-(3-((1-(6-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dibromo-[1,1'-biphenyl]-4-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium salt; (2S,3S,4S,5R,6S)-6-(3-((1-(5-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-5-oxopentyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium salt; (2S,3S,4S,5R,6S)-6-(3-((1-(2-((4'-(E)- (8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-2-oxoethyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium salt; (2S,3S,4S,5R,6S)-6-(3-((1-(3-(2-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-2-oxoethoxy)propyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium;and (2S,3S,4S,5R,6S)-6-(3-((1-(2-(2-((4'-(E)-(8-amino-1-hydroxy-5,7-disulfonatonaphthalen-2-yl)diazenyl)-3,3'-dimethyl-[1,1'-biphenyl]-4-yl)amino)-3-oxopropoxy)ethyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-(((S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolazino[1,2-b]quinolin-9-yl)oxy)methyl)phenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid trisodium.

5. A pharmaceutical composition comprising the compound according to any one of claims 1 to 4, a stereoisomer or a cis-trans isomer of the compound, and a pharmaceutically acceptable carrier.

6. The pharmaceutical composition according to claim 5, which is prepared as a preparation for injection.

7. The pharmaceutical composition according to claim 6, wherein the preparation for injection is an injection, a sterile powder for injection, or a concentrated solution for injection.

8. A method for treating a tumor or cancer, comprising administering a therapeutically effective amount of the compound according to any one of claims 1 to 4, a stereoisomer or a cis-trans isomer of the compound, or the pharmaceutical composition according to any one of claims 5 to 7 to a subject in need of treatment.

9. The method according to claim 8, wherein the tumor or cancer is selected from the group consisting of colorectal cancer, lung cancer, cervical cancer, ovarian cancer, gastric cancer, esophageal cancer, breast cancer, pancreatic cancer, bladder cancer, liver cancer, gastric cancer, colon cancer, head and neck cancer, uterine cancer, urothelial cancer, osteosarcoma, sarcoma, kidney cancer, melanoma, prostate cancer, glioma, glioblastoma, and leukemia.

10. A process for preparing the compound of formula (I) according to claim 1, a stereoisomer, a cis-trans isomer, or a pharmaceutically acceptable salt of the compound of formula (I), comprising: 【Chemical Formula 5】 wherein R １ is hydrogen, C １ ~ C ８ hydrocarbyl, -Na, -Li, -K, -Cs, -NH ４ ＋ 、-NH ２ ＋ R １３ R １４ 、-NH ＋ R １３ R １４ R １５, -NH ＋ ３ R １３ and is selected from the group consisting of natural or non-natural amino acids; R ２ is hydrogen, and C １ -C ８ hydrocarbyl selected from the group consisting of; R ３ is hydrogen, halogen, C １ -C ８ hydrocarbyl, C １ -C ８ hydrocarbyloxy, cyano, nitro, amino, aryl, arylhydrocarbyl, and C １ -C ４ one or more substituents at any substitution position selected from the group consisting of hydrocarbyl-substituted amino; R ４ is C １ -C ９ alkylidene, C １ -C ８ alkylideneoxy, C １ -C ８ hydrocarbyl-substituted or unsubstituted C ３ -C ８ heteroaryl, C １ -C ８ hydrocarbyl-substituted or unsubstituted C ３ -C １５ aryl, -(CH ２ R ７ ) ｎ -(R ８ ) ｍ C １ -C ９ alkylidene-arylidene, C １ -C ９ alkylidene-arylidene-C １ -C ９ alkyldiene, C １ -C ９ alkylidene-arylidene-arylidene, C １ -C ９ alkylidene-heteroarylidene-C １ -C ９selected from the group consisting of an alkylidene and an amino acid peptide chain; wherein the amino acid peptide chain is composed of a combination of natural or non-natural amino acids, and the length of the peptide chain is from 1 to 100 peptides, preferably from 1 to 50 peptides, more preferably from 1 to 20 peptides; R ５ is selected from the group consisting of hydrogen and C １ - C ８ hydrocarbyl; R ６ is selected from the group consisting of hydrogen, C １ - C ８ hydrocarbyl, C １ - C ８ hydrocarbylideneamino (C １ - C ４ hydrocarbyl), ２ C １ - C ８ hydrocarbylidene thio C １ - C ８ hydrocarbyl, and C １ - C ９ alkylidene-oxy-C １ - C ９ alkyl; R ５ and R ６ may form a ring, and when R ５ and R ６ form a ring, the ring may be a 5-membered or 6-membered ring; R ７ is selected from the group consisting of hydrogen, C １ - C ８ hydrocarbylideneoxy, amino C １ - C ８ hydrocarbylidene, thio C １ - C ８ hydrocarbylidene, and oxy C １ - C ８ hydrocarbylidene; n is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, and 9; when n is 0, (CH ２ R ７ ) ｎrepresents a covalent bond; R ８ is carbonylamino, where the amino is C １ ~C ８ hydrocarbyl or arylhydrocarbyl, C １ ~C ８ hydrocarbylideneamino C １ ~C ８ hydrocarbylidene, C １ ~C ８ hydrocarbylidene thio C １ ~C ８ hydrocarbylidene, or C １ ~C ８ hydrocarbylideneoxy C １ ~C ８ hydrocarbylidene and may be substituted; m is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, and 9; when m is 0, -(R ８ ) ｍ represents a covalent bond; R ９ is hydrogen, halogen, cyano, C １ ~C ８ hydrocarbyl, C １ ~C ８ alkoxy, and C ５ ~C １２ aryl and is one or more substituents at any position selected from the group; R １０ is hydrogen, halogen, cyano, C １ ~C ８ hydrocarbyl, C １ ~C ８ alkoxy, and C ５ ~C １２ aryl and is one or more substituents at any position selected from the group; R １１ is hydrogen, -Na, -Li, -K, -Cs, -NH ４ ＋ , -NH ２ ＋ R １３ R １４ -NH ＋ R １３ R １４ R １５ 、 -NH ３ ＋ R １３ 、 and selected from the group consisting of natural or non-natural amino acids; R １２ is hydrogen, -Na, -Li, -K, -Cs, -NH ４ ＋ 、 -NH ２ ＋ R １３ R １４ 、 -NH ＋ R １３ R １４ R １５ 、 -NH ３ ＋ R １３ 、 and selected from the group consisting of natural or non-natural amino acids; R １３ is hydrogen, C １ ~C ８ hydrocarbyl, C １ ~C ８ cycloalkyl, C ５ ~C １８ aryl, and C ５ ~C １８ heteroaryl; and selected from the group consisting of R １４ is hydrogen, C １ ~C ８ hydrocarbyl, C １ ~C ８ cycloalkyl, C ５ ~C １８ aryl, and C ５ ~C １８ heteroaryl; and selected from the group consisting of R １５ is hydrogen, C １ ~C ８ hydrocarbyl, C １ ~C ８ cycloalkyl, C ５ ~C １８ aryl, and C ５ ~C １８ heteroaryl; and selected from the group consisting of; and R １ 、 R １１, and R １２ The natural or non-natural amino acids in are selected from the group consisting of glycine, alanine, valine, leucine, isoleucine, methionine (methionine), proline, tryptophan, serine, tyrosine, cysteine, phenylalanine, asparagine, glutamine, threonine, aspartic acid, glutamic acid, lysine, arginine, histidine, selenocysteine, sarcosine, pyrrolysine, and homoalanine; Here, the process includes the following: (1) Reacting a compound of formula (A-I) with a compound of formula (A-II) to obtain a compound of formula (A-III), [Chemical formula 6] Here, R in the formula (A-I) and the formula (A-II) ４ ’, R ９ ’, and R １０ ’ are the same as defined for R in the formula (I) ４ , R ９ , and R １０ ; (2) Reacting the compound of formula (A-III) with sodium azide to obtain a compound of formula (A-IV), [Chemical formula 7] Here, R in the formula (A-III) and the formula (A-IV) ４ ’, R ９ ’, and R １０ ’ are the same as defined for R in the formula (I) ４ , R ９ , and R １０ ; (3) Reacting the compound of formula (A-IV) with sodium 4-amino-5-hydroxy-1,3-naphthalenedisulfonate to obtain a compound of formula (A-V), [Chemical formula 8] Here, R in the formula (A-IV) and the formula (A-V) ４ ’, R ９ ’, and R １０ ’ are the same as defined for R in the formula (I) ４ , R ９ , and R １０ are as defined for (4) Reacting the compound of formula (B-I) with carbon tetrabromide to obtain a compound of formula (B-II), [Chemical Formula 9] wherein the groups represented by R １ ', R ２ ', and R ３ ' in the formula (B-I) and the formula (B-II) are as defined for R １ , R ２ , and R ３ in the formula (I); (5) Reacting the compound of formula (B-II) with a compound of formula (B-III) to obtain a compound of formula (B-IV) [Chemical Formula 10] wherein the groups represented by R １ ', R ２ ', R ３ ', R ５ ', and R ６ ' in the formula (B-II), the formula (B-III) and the formula (B-IV) are as defined for R １ , R ２ , R ３ , R ５ , and R ６ in the formula (I); (6) Reacting the compound of formula (B-IV) under basic conditions to obtain a compound of formula (B-V), [Chemical Formula 11] wherein the groups represented by R １ ', R ２ ', R ３ ', R ５ ', and R ６ ' in the formula (B-IV) and the formula (B-V) are as defined for R １ , R ２ , R ３ , R ５ , and R ６ in the formula (I); (7) Reacting the compound of formula (A-V) with the compound of formula (B-V) to obtain the compound of formula (I), or reacting the product obtained by reacting the compound of formula (A-V) with the compound of formula (B-V) with the corresponding acid or base to form its pharmaceutically acceptable salt [Chemical Formula 12] Herein, the groups represented by R ２ ’, R ３ ’, R ４ ’, R ５ ’, R ６ ’, R ９ ’, and R １０ ’ are as defined for R ２ , R ３ , R ４ , R ５ , R ６ , R ９ , and R １０ in formula (I). Preparation process.

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