Novel benzodiazepine compounds, methods for their preparation and uses thereof

Abstract

Provided are a new type of benzodiazepine compound, a preparation method thereof, and a use thereof. The short-acting benzodiazepine derivative has the characteristics of rapid onset, short action time, strong depth, fast metabolism, and fast awakening. In the anesthesia experiments on mice and rats, the short-acting benzodiazepine derivative has an onset time comparable to that of remazepam, but the action time and awakening time are significantly shortened, and the action depth of some compounds is significantly enhanced, and has the characteristics of faster onset, shorter action time, greater action strength, faster metabolism, and faster awakening. In the long-term infusion anesthesia experiment on rats, compared with remazepam, the short-acting benzodiazepine derivative has significantly shortened awakening time and recovery time, and has the characteristics of faster awakening and faster recovery.

Description

[0001] This application claims the patent filed on November 9, 2020 with the China National Intellectual Property Administration, patent application number 202011237945.7, entitled "A Novel Benzodiazepine". Priority is claimed in the prior application concerning "a class of compounds, their preparation methods and uses thereof," the entire contents of which are incorporated herein by reference. Technical Field

[0002] This invention relates to benzodiazepine of formula (I) as a short-acting anesthetic. Derivatives, pharmaceutical compositions comprising them, cassettes comprising them, methods of their preparation, methods of sedation and anesthesia using them, and their use in the preparation of sedative and anesthetic drugs. Background Technology

[0003] Anesthetic drugs can temporarily and reversibly cause loss of sensation and pain in the body or a local area, helping patients reduce pain and other discomfort symptoms. They are an essential adjuvant drug in clinical surgery.

[0004] benzodiazepine Benzodiazepines are GABA derivatives. A GABA receptor (also known as γ-aminobutyric acid type A receptor) activator. A The receptor is a gated receptor for chloride ion channels, consisting of two α and two β subunits (α2β2). The β subunit has a GABA receptor; when GABA binds to it, the chloride ion channel opens, allowing an influx of chloride ions, which hyperpolarizes the nerve cell and produces an inhibitory effect. The α subunit contains benzodiazepines. Acceptor, when benzodiazepine When combined with this, it can increase the frequency of chloride channel opening (rather than prolonging the chloride channel opening time or increasing the chloride ion flux) by promoting the binding of GABA to GABAA receptors, thereby resulting in a greater chloride ion influx. This allows benzodiazepines... These derivatives can enhance GABA neurotransmission and synaptic inhibition, thus exerting various therapeutic effects in clinical practice, such as inducing anesthesia, hypnosis, anti-anxiety, and relieving spasms caused by central nervous system lesions or epilepsy.

[0005] benzodiazepine Benzodiazepines are a rapidly developing class of sedative and anesthetic drugs in recent years. They possess good amnesic, anti-anxiety, and sedative effects, and are therefore widely used in the field of sedation and anesthesia. The first benzodiazepine... Class II drugs chlordiazepoxide (Librium) was introduced to the market in 1960. Since then, new types of benzodiazepines have been continuously developed. The emergence of drug classes includes ultra-short-acting (remazolam), short-acting (triazolam / midazolam), intermediate-acting (lorazepam / eszolam), and long-acting (diazepam), etc. Benzodiazepam is commonly used clinically. There are more than 20 derivatives of GABA, and although they are structurally similar, their clinical indications vary. This is because the binding sites and functions of GABA to GABA receptors are heterogeneous. GABA-gated channels in different nerves are composed of different types of subunits, and the composition of these subunits can lead to subtle changes in the interaction between these channels and allosteric modulators, producing different sedative and anesthetic effects. Midazolam was first developed as a water-soluble benzodiazepine in the early 1980s. This type of compound has been introduced to the market and is used intravenously as a means of sedation and anesthesia for short surgeries or intensive care units. However, midazolam produces active metabolites in the body, resulting in a prolonged recovery time for patients from midazolam-induced sedation. Furthermore, the metabolism of midazolam depends on the liver enzyme cytochrome P400. 450 3A4. Drug interactions may occur after administration to patients with impaired liver function. Remimazolam was approved in December 2019 as a novel, ultra-short-acting GABAergic agonist. A The market launch of receptor agonists was based on benzodiazepines. A methyl propionate side chain, which can be rapidly metabolized, is introduced into the core structure. Because its methyl propionate side chain can be rapidly metabolized by esterases, and its main metabolite, azolamyric acid, has almost no sedative or anesthetic activity, the drug's effect is very short-lived, classifying it as an ultra-short-acting benzodiazepine. This type of drug. However, prolonged infusion can still cause problems such as delayed awakening and drug accumulation, and it is currently only approved for sedation and general anesthesia in gastroscopy.

[0006] In summary, benzodiazepines Narcotic drugs often lead to dependence and addiction, and many of their metabolites retain some efficacy, making it difficult for patients to quickly return to normal. Long-term use can easily lead to drug accumulation, hindering their further development. Therefore, the development of benzodiazepines that have rapid onset of action, short recovery time, and no accumulation is crucial. The availability of such drugs is an urgent problem to be solved. Summary of the Invention

[0007] To address the above problems, this invention provides a novel type of benzodiazepine. Class of compounds, their preparation methods and uses.

[0008] The technical solution of this invention is: a novel type of benzodiazepine Class I compounds, compounds of general formula (I), pharmaceutically acceptable salts, stereoisomers, tautomers, polymorphs, solvates, metabolites, or prodrugs:

[0009]

[0010] in:

[0011] R1 is selected from hydrogen, C l-20 Alkyl, C 2-20 alkenyl, C 2-20 alkynyl, 3-10 membered cycloalkyl or C 1-10 alkylene-3-10 membered cycloalkyl, 3-10 membered heterocyclic or C 1-10 alkylene-3-10-membered heterocyclic, 6-14-membered aryl or C 1-10 alkylene-6-14 aryl, 5-14 heteroaryl or C 1-10 alkylene-5-14-membered heteroaryl,

[0012] The C l-20 Alkyl, C 2-20 alkenyl, C 2-20 alkynyl, 3-10 membered cycloalkyl or C 1-10 alkylene-3-10 membered cycloalkyl, 3-10 membered heterocyclic or C 1-10 alkylene-3-10-membered heterocyclic, 6-14-membered aryl or C 1-10 alkylene-6-14 aryl, 5-14 heteroaryl or C 1-10 Each of the alkylene-5-14 heteroaryl groups is optionally surrounded by one or more (e.g., 1, 2, 3, or 4) independently selected from halogen, hydroxyl, cyano, amino, nitro, C l-20 Alkyl, C l-20 Alkoxy, C 2-20 alkenyl, C 2-20 alkynyl, 3-10 membered cycloalkyl or C 1-10 alkylene-3-10 membered cycloalkyl, 3-10 membered heterocyclic or C 1-10 alkylene-3-10-membered heterocyclic, 6-14-membered aryl or C 1-10 alkylene-6-14 aryl, 5-14 heteroaryl or C 1-10 Alkyl-5-14-membered heteroaryl substitution, preferably, R1 is selected from hydrogen, C l-6 Alkyl or C 1-10 alkylene-5-14-membered heteroaryl, more preferably, R1 is selected from hydrogen or methyl or ethyl or propyl or isopropyl or n-butyl or isobutyl or tert-butyl or n-pentyl or isopentyl or neopentyl or C 1-6 alkylene-morpholinocyclo group;

[0013] R2 is located at any position on the benzene ring and is monosubstituted or polysubstituted, preferably selected from the 6th, 7th, 8th or 9th position of substitution, and more preferably selected from the 7th position of substitution;

[0014] R2 is selected from hydrogen, halogen, hydroxyl, cyano, (R6)(R7)N-(CH2). n -、R6R7N-(CH2) n -, trifluoromethyl, nitro, amino, C l-20 Alkyl, C 2-20 alkenyl, C 2-20 alkynyl, 3-10 membered cycloalkyl or C 1-10 alkylene-3-10 membered cycloalkyl, 3-10 membered heterocyclic or C 1-10 alkylene-3-10-membered heterocyclic, 6-14-membered aryl or C 1-10 alkylene-6-14 aryl, 5-14 heteroaryl or C 1-10 alkylene-5-14-membered heteroaryl,

[0015] The C l-20 Alkyl, C 2-20 alkenyl, C 2-20 alkynyl, 3-10 membered cycloalkyl or C 1-10 alkylene-3-10 membered cycloalkyl, 3-10 membered heterocyclic or C 1-10 alkylene-3-10-membered heterocyclic, 6-14-membered aryl or C 1-10 alkylene-6-14 aryl, 5-14 heteroaryl or C 1-10 Each of the alkylene-5-14 heteroaryl groups is optionally surrounded by one or more (e.g., 1, 2, 3, or 4) independently selected from halogen, hydroxyl, cyano, amino, nitro, C l-20 Alkyl, C l-20 Alkoxy, C 2-20 alkenyl, C 2-20 alkynyl, 3-10 membered cycloalkyl or C 1-10 alkylene-3-10 membered cycloalkyl, 3-10 membered heterocyclic or C 1-10 alkylene-3-10-membered heterocyclic, 6-14-membered aryl or C 1-10 alkylene-6-14 aryl, 5-14 heteroaryl or C 1-10 The alkylene-5-14-membered heteroaryl group is substituted, preferably, R2 is selected from hydrogen, halogen, hydroxyl, or R6R7N-(CH2). 1-10 -or (R6)(R7)N-(CH2) 1-10 -or trifluoromethyl or nitro or cyano or amino or C 1-6 Alkyl or C l-6 Alkoxy or C 2-6 alkenyl or C 2-6The alkynyl group, more preferably, R2 is selected from hydrogen, chlorine, bromine, fluorine, nitro, cyano, or amino, or (R6) or (R7)N-(CH2). 1-6 -or R6R7N-(CH2) 1-6 - or trifluoromethyl; R2 is further preferably hydrogen or chlorine or bromine or fluorine or nitro or trifluoromethyl;

[0016] X is selected from C or N. When X is C, R3 is selected from hydrogen, halogen, hydroxyl, cyano, R6R7N-(CH2). n -、(R6)(R7)N-(CH2) n -, trifluoromethyl, nitro, amino, C l-20 Alkyl, C 2-20 alkenyl, C 2-20 alkynyl, 3-10 membered cycloalkyl or C 1-10 alkylene-3-10 membered cycloalkyl, 3-10 membered heterocyclic or C 1-10 alkylene-3-10-membered heterocyclic, 6-14-membered aryl or C 1-10 alkylene-6-14 aryl, 5-14 heteroaryl or C 1-10 alkylene-5-14-membered heteroaryl,

[0017] The C l-20 Alkyl, C 2-20 alkenyl, C 2-20 alkynyl, 3-10 membered cycloalkyl or C 1-10 alkylene-3-10 membered cycloalkyl, 3-10 membered heterocyclic or C 1-10 alkylene-3-10-membered heterocyclic, 6-14-membered aryl or C 1-10 alkylene-6-14 aryl, 5-14 heteroaryl or C 1-10 Each of the alkylene-5-14 heteroaryl groups is optionally surrounded by one or more (e.g., 1, 2, 3, or 4) independently selected from halogen, hydroxyl, cyano, amino, nitro, C l-20 Alkyl, C l-20 Alkoxy, C 2-20 alkenyl, C 2-20 alkynyl, 3-10 membered cycloalkyl or C 1-10 alkylene-3-10 membered cycloalkyl, 3-10 membered heterocyclic or C 1-10 alkylene-3-10-membered heterocyclic, 6-14-membered aryl or C 1-10 alkylene-6-14 aryl, 5-14 heteroaryl or C 1-10 The alkylene-5-14-membered heteroaryl group is substituted, preferably, R3 is selected from hydrogen, halogen, hydroxyl, or R6R7N-(CH2). 1-10 -or (R6)(R7)N-(CH2) 1-10 -or trifluoromethyl or nitro or cyano or amino or C1-6 Alkyl or C l-6 Alkoxy or C 2-6 alkenyl or C 2-6 The alkynyl group, more preferably, R3 is selected from hydrogen, chlorine, bromine, fluorine, nitro, cyano, or amino, or R6R7N-(CH2). 1-6 -or (R6)(R7)N-(CH2) 1-6 - or trifluoromethyl; when X is N, the R3 substituent is not present;

[0018] R4 is located at any position on the benzene ring or pyridine ring and is monosubstituted or polysubstituted, preferably selected from the 3', 4', and 5' positions of substitution, and more preferably selected from the 4' position of substitution;

[0019] R4 is selected from hydrogen, halogen, hydroxyl, cyano, and R6R7N-(CH2). n -、(R6)(R7)N-(CH2) n -, trifluoromethyl, nitro, amino, C l-20 Alkyl, C 2-20 alkenyl, C 2-20 alkynyl, 3-10 membered cycloalkyl or C 1-10 alkylene-3-10 membered cycloalkyl, 3-10 membered heterocyclic or C 1-10 alkylene-3-10-membered heterocyclic, 6-14-membered aryl or C 1-10 alkylene-6-14 aryl, 5-14 heteroaryl or C 1-10 alkylene-5-14-membered heteroaryl,

[0020] The C l-20 Alkyl, C 2-20 alkenyl, C 2-20 alkynyl, 3-10 membered cycloalkyl or C 1-10 alkylene-3-10 membered cycloalkyl, 3-10 membered heterocyclic or C 1-10 alkylene-3-10-membered heterocyclic, 6-14-membered aryl or C 1-10 alkylene-6-14 aryl, 5-14 heteroaryl or C 1-10 Each of the alkylene-5-14 heteroaryl groups is optionally surrounded by one or more (e.g., 1, 2, 3, or 4) independently selected from halogen, hydroxyl, cyano, amino, nitro, C l-20 Alkyl, C l-20 Alkoxy, C 2-20 alkenyl, C 2-20 alkynyl, 3-10 membered cycloalkyl or C 1-10 alkylene-3-10 membered cycloalkyl, 3-10 membered heterocyclic or C 1-10 alkylene-3-10-membered heterocyclic, 6-14-membered aryl or C 1-10alkylene-6-14 aryl, 5-14 heteroaryl or C 1-10 The alkylene-5-14-membered heteroaryl group is substituted, preferably, R4 is selected from hydrogen, halogen, hydroxyl, or R6R7N-(CH2). 1-10 -or (R6)(R7)N-(CH2) 1-10 -or trifluoromethyl or nitro or cyano or amino or C 1-6 Alkyl or C l-6 Alkoxy or C 2-6 alkenyl or C 2-6 The alkynyl group, more preferably, R4 is selected from hydrogen, chlorine, bromine, fluorine, nitro, cyano, or amino, or (R6) or (R7)N-(CH2). 1-6 -or trifluoromethyl;

[0021] R5 is selected from hydrogen, C l-20 Alkyl, C 1-20 Acyl group, C 2-20 alkenyl, C 2-20 alkynyl group, C 1-10 alkylene phosphate group, P(O)(OH)2-C 1-10 Alkylene, 3-10 membered cycloalkyl or C 1-10 Alkylene-3-10 membered cycloalkyl, R6R7N-(CH2) n -、(R6)(R7)N-(CH2) n - 3-10 membered heterocyclic groups or C 1-10 alkylene-3-10-membered heterocyclic, 6-14-membered aryl or C 1-10 alkylene-6-14 aryl, 5-14 heteroaryl or C 1-10 Alkylene-5-14-membered heteroaryl; those skilled in the art should understand that when R5 is hydrogen, -SH can resonate with the attached triazole ring to form a =S structure;

[0022] The C l-20 Alkyl, C 1-20 Acyl group, C 2-20 alkenyl, C 2-20 alkynyl, 3-10 membered cycloalkyl or C 1-10 Alkylene-3-10 membered cycloalkyl, R6R7N-(CH2) n -、(R6)(R7)N-(CH2) n - 3-10 membered heterocyclic groups or C 1-10 alkylene-3-10-membered heterocyclic, 6-14-membered aryl or C 1-10 alkylene-6-14 aryl, 5-14 heteroaryl or C 1-10 Each of the alkylene-5-14-membered heteroaryl groups is optionally selected independently by one or more (e.g., 1, 2, 3, or 4) halogens, oxo (=O), C 1-10Alkylene halogens, hydroxyl groups, C 1-10 Alkylene-hydroxyl, R6R7N-(CH2) n -、(R6)(R7)N-(CH2) n -, cyano, C 1-10 alkylene-cyano, nitro, C 1-10 alkylene-nitro, amino, C l-20 Alkyl, C l-20 Alkoxy, C 2-20 alkenyl, C 2-20 alkynyl, 3-10 membered cycloalkyl or C 1-10 alkylene-3-10 membered cycloalkyl, 3-10 membered heterocyclic or C 1-10 alkylene-3-10-membered heterocyclic, 6-14-membered aryl or C 1-10 alkylene-6-14 aryl, 5-14 heteroaryl or C 1-10 Substituent substitution of alkylene-5-14-membered heteroaryl groups; preferably, R5 is selected from hydrogen and C. l-10 Alkyl, C 1-10 alkylene phosphate group, P(O)(OH)2-C 1-10 Alkylene, 3-10 membered cycloalkyl or C 1-10 Alkylene-3-10 membered cycloalkyl, R6R7N-(CH2) n -、(R6)(R7)N-(CH2) n - 3-10 membered heterocyclic groups or C 1-10 alkylene-3-10-membered heterocyclic group; more preferably, R5 is selected from hydrogen or methyl or ethyl or methylene-phosphate or P(O)(OH)2-methylene, or C 1-10 alkylene-morpholinocyclo group or C 1-10 alkylene-pyrrole cyclogroup or C 1-10 alkylene-imidazolium cyclogroup or C 1-10 alkylene-piperidine cycloyl or 2-((4-hydroxypiperidine-1-yl)ethyl or C 1-10 alkylene-pyridine cyclogroup or C 1-10alkylene-piperazine cycloyl or 2-(4-methylpiperazin-1-yl)ethyl or 3-(4-(2-hydroxyethyl)piperazin-1-yl)propyl or 2-(4-methylpiperazin-1-yl)2-oxoethyl or 2-(4-methylpiperazin)-1-carbonyl or (4-phenylpiperazin-1-yl)methyl or 2-hydroxyethyl or 2-aminoethyl or acetyl or prop-2-yn-1-yl or dimethylaminomethyl or dimethylaminoethyl or dimethylaminon-propyl Or dimethylaminoisopropyl or dimethylaminon-butyl or dimethylaminoisobutyl or dimethylaminotert-butyl or dimethylaminon-pentyl or dimethylaminoisopentyl or dimethylaminoneopentyl or cyclopropylmethyl or cyclopropylethyl or cyclopropyln-propyl or cyclopropylisopropyl or 1-methylpiperidin-4-yl or 1-ethylcarbamoyl or 1-methylcarbamoyl or (dimethylamino)-3-oxopropyl or (4,5-dihydro-1H-imidazol-2-yl)methyl;

[0023] R6 and R7 are selected from hydrogen and C. l-20 Alkyl, C 2-20 alkenyl, C 2-20 alkynyl, 3-10 membered cycloalkyl or C 1-10 alkylene-3-10 membered cycloalkyl, 3-10 membered heterocyclic or C 1-10 alkylene-3-10-membered heterocyclic, 6-14-membered aryl or C 1-10 alkylene-6-14 aryl, 5-14 heteroaryl or C 1-10 alkylene-5-14-membered heteroaryl,

[0024] The C l-20 Alkyl, C 2-20 alkenyl, C 2-20 alkynyl, 3-10 membered cycloalkyl or C 1-10 alkylene-3-10 membered cycloalkyl, 3-10 membered heterocyclic or C 1-10 alkylene-3-10-membered heterocyclic, 6-14-membered aryl or C 1-10 alkylene-6-14 aryl, 5-14 heteroaryl or C 1-10 Each of the alkylene-5-14-membered heteroaryl groups is optionally selected by one or more (e.g., 1, 2, 3 or 4) independently from halogens, C 1-10 Alkylene halogens, hydroxyl groups, C 1-10 Alkylene-hydroxyl, R6R7N-(CH2) n -、(R6)(R7)N-(CH2) n -, cyano, C 1-10 alkylene-cyano, nitro, C 1-10 alkylene-nitro, amino, C l-20 Alkyl, C l-20 Alkoxy, C 2-20 alkenyl, C 2-20alkynyl, 3-10 membered cycloalkyl or C 1-10 alkylene-3-10 membered cycloalkyl, 3-10 membered heterocyclic or C 1-10 alkylene-3-10-membered heterocyclic, 6-14-membered aryl or C 1-10 alkylene-6-14 aryl, 5-14 heteroaryl or C 1-10 Substituent substitution of alkylene-5-14-membered heteroaryl groups; preferably, R6 and R7 are selected from C6. l-6 Alkyl; more preferably, R6 and R7 are selected from methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, or neopentyl.

[0025] n is selected from 1 to 20, preferably from 1 to 10, and more preferably from 1 to 6;

[0026] W is selected from hydrogen, halogen, hydroxyl, cyano, and R6R7N-(CH2). n -、(R6)(R7)N-(CH2) n -, trifluoromethyl, nitro, amino, C l-20 Alkyl, C 2-20 alkenyl, C 2-20 alkynyl, 3-10 membered cycloalkyl or C 1-10 alkylene-3-10 membered cycloalkyl, 3-10 membered heterocyclic or C 1-10 alkylene-3-10-membered heterocyclic, 6-14-membered aryl or C 1-10 alkylene-6-14 aryl, 5-14 heteroaryl or C 1-10 alkylene-5-14-membered heteroaryl,

[0027] The C l-20 Alkyl, C 2-20 alkenyl, C 2-20 alkynyl, 3-10 membered cycloalkyl or C 1-10 alkylene-3-10 membered cycloalkyl, 3-10 membered heterocyclic or C 1-10 alkylene-3-10-membered heterocyclic, 6-14-membered aryl or C 1-10 alkylene-6-14 aryl, 5-14 heteroaryl or C 1-10 Each of the alkylene-5-14-membered heteroaryl groups is optionally selected by one or more (e.g., 1, 2, 3 or 4) independently from halogens, C 1-10 Alkylene halogens, hydroxyl groups, C 1-10 Alkylene-hydroxyl, (R6)(R7)N-(CH2) n -, cyano, C 1-10 alkylene-cyano, nitro, C 1-10 alkylene-nitro, amino, C l-20 Alkyl, C l-20 Alkoxy, C2-20 alkenyl, C 2-20 alkynyl, 3-10 membered cycloalkyl or C 1-10 alkylene-3-10 membered cycloalkyl, 3-10 membered heterocyclic or C 1-10 alkylene-3-10-membered heterocyclic, 6-14-membered aryl or C 1-10 alkylene-6-14 aryl, 5-14 heteroaryl or C 1-10 Substituents of alkylene-5-14-membered heteroaryl groups; preferably, W is selected from hydrogen, halogen, hydroxyl, or (R6)(R7)N-(CH2). 1-10 -or trifluoromethyl or nitro or cyano or C 1-6 Alkyl or C l-6 Alkoxy or C 2-6 alkenyl or C 2-6 Alkyne group; more preferably, W is selected from hydrogen or hydroxyl or chlorine or bromine or fluorine or nitro or cyano or (R6)(R7)N-(CH2). 1-6 -or trifluoromethyl;

[0028] The hydrogen and the hydrogen contained in the above-mentioned groups are independently selected from protium, deuterium and tritium, preferably protium or deuterium.

[0029] Furthermore, a new type of benzodiazepine Class of compounds, including pharmaceutically acceptable salts, stereoisomers, tautomers, polymorphs, solvates, metabolites, or prodrugs;

[0030] Where X is C; R2 and R3 are halogens; R5 is selected from hydrogen, C l-20 Alkyl, C 1-20 Acyl group, C 2-20 alkenyl, C 2-20 alkynyl group, C 1-10 alkylene phosphate group, P(O)(OH)2-C 1-10 Alkylene, 3-10 membered cycloalkyl or C 1-10 Alkylene-3-10 membered cycloalkyl, R6R7N-(CH2) n -、(R6)(R7)N-(CH2) n - 3-10 membered heterocyclic groups or C 1-10 alkylene-3-10-membered heterocyclic, 6-14-membered aryl or C 1-10 alkylene-6-14 aryl, 5-14 heteroaryl or C 1-10 alkylene-5-14-membered heteroaryl,

[0031] The C l-20 Alkyl, C 1-20 Acyl group, C 2-20 alkenyl, C 2-20 alkynyl, 3-10 membered cycloalkyl or C 1-10Alkylene-3-10 membered cycloalkyl, R6R7N-(CH2) n -、(R6)(R7)N-(CH2) n - 3-10 membered heterocyclic groups or C 1-10 alkylene-3-10-membered heterocyclic, 6-14-membered aryl or C 1-10 alkylene-6-14 aryl, 5-14 heteroaryl or C 1-10 Each of the alkylene-5-14-membered heteroaryl groups is optionally selected by one or more (e.g., 1, 2, 3 or 4) independently from halogens, C 1-10 Alkylene halogens, hydroxyl groups, C 1-10 Alkylene-hydroxyl, R6R7N-(CH2) n -、(R6)(R7)N-(CH2) n -, cyano, C 1-10 alkylene-cyano, nitro, C 1-10 alkylene-nitro, amino, C l-20 Alkyl, C l-20 Alkoxy, C 2-20 alkenyl, C 2-20 alkynyl, 3-10 membered cycloalkyl or C 1-10 alkylene-3-10 membered cycloalkyl, 3-10 membered heterocyclic or C 1-10 alkylene-3-10-membered heterocyclic, 6-14-membered aryl or C 1-10 alkylene-6-14 aryl, 5-14 heteroaryl or C 1-10 Substituent substitution of alkylene-5-14-membered heteroaryl groups; preferably, R5 is selected from hydrogen and C. l-10 Alkyl, C 1-10 alkylene-phosphate group, 3-10 membered cycloalkyl group or C 1-10 Alkylene-3-10 membered cycloalkyl, R6R7N-(CH2) n -、(R6)(R7)N-(CH2) n - 3-10 membered heterocyclic groups or C 1-10 alkylene-3-10-membered heterocyclic group; more preferably, R5 is selected from hydrogen, methyl, ethyl, methylene-phosphate, or C. 1-10 alkylene-morpholinocyclo group or C 1-10 alkylene-pyrrole cyclogroup or C 1-10 alkylene-imidazolium cycloyl or 2-((4-hydroxypiperidin-1-yl)ethyl or C 1-10 alkylene-pyridine cyclogroup or C 1-10alkylene-piperazine cycloyl or 2-(4-methylpiperazin-1-yl)ethyl or 3-(4-(2-hydroxyethyl)piperazin-1-yl)propyl or 2-(4-methylpiperazin-1-yl)2-oxoethyl or 2-(4-methylpiperazin)-1-carbonyl or (4-phenylpiperazin-1-yl)methyl or 2-hydroxyethyl or 2-aminoethyl or acetyl or prop-2-yn-1-yl or dimethylaminomethyl or dimethylaminoethyl or dimethylaminon-propyl Or dimethylaminoisopropyl or dimethylaminon-butyl or dimethylaminoisobutyl or dimethylaminotert-butyl or dimethylaminon-pentyl or dimethylaminoisopentyl or dimethylaminoneopentyl or cyclopropylmethyl or cyclopropylethyl or cyclopropyln-propyl or cyclopropylisopropyl or 1-methylpiperidin-4-yl or 1-ethyl-carbamoyl or 1-methyl-carbamoyl or (dimethylamino)-3-oxopropyl or (4,5-dihydro-1H-imidazol-2-yl)methyl.

[0032] Furthermore, a new type of benzodiazepine Class of compounds, including pharmaceutically acceptable salts, stereoisomers, tautomers, polymorphs, solvates, metabolites, or prodrugs.

[0033] Where X is N; R5 is selected from hydrogen and C. l-20 Alkyl, C 1-20 Acyl group, C 2-20 alkenyl, C 2-20 alkynyl group, C 1-10 alkylene phosphate group, P(O)(OH)2-C 1-10 Alkylene, 3-10 membered cycloalkyl or C 1-10 Alkylene-3-10 membered cycloalkyl, R6R7N-(CH2) n -、(R6)(R7)N-(CH2) n - 3-10 membered heterocyclic groups or C 1-10 alkylene-3-10-membered heterocyclic, 6-14-membered aryl or C 1-10 alkylene-6-14 aryl, 5-14 heteroaryl or C 1-10 alkylene-5-14-membered heteroaryl, wherein C l-20 Alkyl, C 1-20 Acyl group, C 2-20 alkenyl, C 2-20 alkynyl, 3-10 membered cycloalkyl or C 1-10 Alkylene-3-10 membered cycloalkyl, R6R7N-(CH2) n -、(R6)(R7)N-(CH2) n - 3-10 membered heterocyclic groups or C 1-10 alkylene-3-10-membered heterocyclic, 6-14-membered aryl or C 1-10 alkylene-6-14 aryl, 5-14 heteroaryl or C 1-10Each of the alkylene-5-14-membered heteroaryl groups is optionally selected by one or more (e.g., 1, 2, 3 or 4) independently from halogens, C 1-10 Alkylene halogens, hydroxyl groups, C 1-10 Alkylene-hydroxyl, R6R7N-(CH2) n -、(R6)(R7)N-(CH2) n -, cyano, C 1-10 alkylene-cyano, nitro, C 1-10 alkylene-nitro, amino, C l-20 Alkyl, C l-20 Alkoxy, C 2-20 alkenyl, C 2-20 alkynyl, 3-10 membered cycloalkyl or C 1-10 alkylene-3-10 membered cycloalkyl, 3-10 membered heterocyclic or C 1-10 alkylene-3-10-membered heterocyclic, 6-14-membered aryl or C 1-10 alkylene-6-14 aryl, 5-14 heteroaryl or C 1-10 Substituent substitution of alkylene-5-14-membered heteroaryl groups; preferably, R5 is selected from hydrogen and C. l-10 Alkyl, C 1-10 alkylene-phosphate group, 3-10 membered cycloalkyl group or C 1-10 Alkylene-3-10 membered cycloalkyl, R6R7N-(CH2) n -、(R6)(R7)N-(CH2) n - 3-10 membered heterocyclic groups or C 1-10 alkylene-3-10-membered heterocyclic group; more preferably, R5 is selected from hydrogen, methyl, ethyl, methylene-phosphate, or C. 1-10 alkylene-morpholinocyclo group or C 1-10 alkylene-pyrrole cyclogroup or C 1-10 alkylene-imidazolium cycloyl or 2-((4-hydroxypiperidin-1-yl)ethyl or C 1-10 alkylene-pyridine cyclogroup or C 1-10alkylene-piperazine cycloyl or 2-(4-methylpiperazin-1-yl)ethyl or 3-(4-(2-hydroxyethyl)piperazin-1-yl)propyl or 2-(4-methylpiperazin-1-yl)2-oxoethyl or 2-(4-methylpiperazin)-1-carbonyl or (4-phenylpiperazin-1-yl)methyl or 2-hydroxyethyl or 2-aminoethyl or acetyl or prop-2-yn-1-yl or dimethylaminomethyl or dimethylaminoethyl or dimethylaminon-propyl Or dimethylaminoisopropyl or dimethylaminon-butyl or dimethylaminoisobutyl or dimethylaminotert-butyl or dimethylaminon-pentyl or dimethylaminoisopentyl or dimethylaminoneopentyl or cyclopropylmethyl or cyclopropylethyl or cyclopropyln-propyl or cyclopropylisopropyl or 1-methylpiperidin-4-yl or 1-ethylcarbamoyl or 1-methylcarbamoyl or (dimethylamino)-3-oxopropyl or (4,5-dihydro-1H-imidazol-2-yl)methyl;

[0034] Furthermore, the compound is selected from:

[0035] (S)-3-(8-chloro-6-(2-fluorophenyl)-1-mercapto-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 1)

[0036] (S)-3-(8-chloro-6-(2-fluorophenyl)-1-thio-2,4-dihydro-1H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (tautomer of compound 1),

[0037] (S)-3-(8-chloro-6-(2-chlorophenyl)-1-mercapto-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 2)

[0038] (S)-3-(8-chloro-6-(2-chlorophenyl)-1-thio-2,4-dihydro-1H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (tautomer of compound 2),

[0039] (S)-3-(8-bromo-6-(pyridin-2-yl)-1-mercapto-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 3)

[0040] (S)-3-(8-bromo-6-(pyridin-2-yl)-1-thio-2,4-dihydro-1H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 3 tautomer),

[0041] (S)-3-(8-bromo-6-(2-fluorophenyl)-1-mercapto-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza methyl 4-yl)propionate (compound 4)

[0042] (S)-3-(8-bromo-6-(2-fluorophenyl)-1-thio-2,4-dihydro-1H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 4 tautomer),

[0043] (S)-3-(6-phenyl-1-mercapto-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza) Methyl 4-yl)propionate (compound 5)

[0044] (S)-3-(6-phenyl-1-thio-2,4-dihydro-1H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza) Methyl 4-yl)propionate (tautomer of compound 5),

[0045] (S)-3-(6-(4-fluorophenyl)-1-mercapto-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza methyl 4-yl)propionate (compound 6)

[0046] (S)-3-(6-(4-fluorophenyl)-1-thio-2,4-dihydro-1H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 6 tautomer),

[0047] (S)-3-(8-chloro-6-phenyl-1-mercapto-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza) methyl 4-yl)propionate (compound 7)

[0048] (S)-3-(8-chloro-6-phenyl-1-thio-2,4-dihydro-1H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza) Methyl 4-yl)propionate (tautomer of compound 7),

[0049] (S)-3-(8-chloro-6-(2-fluorophenyl)-1-(methylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 8)

[0050] (S)-3-(8-bromo-6-(2-fluorophenyl)-1-(methylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza 4-yl)methyl propionate (compound 9)

[0051] (S)-3-(8-nitro-6-(2-fluorophenyl)-1-(methylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 10)

[0052] (S)-3-(8-chloro-6-(2-fluorophenyl)-1-(ethio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 11)

[0053] (S)-3-(8-bromo-6-(2-fluorophenyl)-1-(ethio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 12)

[0054] (S)-3-(8-nitro-6-(2-fluorophenyl)-1-(ethylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 13)

[0055] (S)-3-(8-chloro-6-(2-fluorophenyl)-1-(propylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 14)

[0056] (S)-3-(8-bromo-6-(2-fluorophenyl)-1-(propylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 15)

[0057] (S)-3-(8-nitro-6-(2-fluorophenyl)-1-(propylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 16)

[0058] (S)-3-(8-chloro-6-(2-fluorophenyl)-1-((2-hydroxyethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 17)

[0059] (S)-3-(8-bromo-6-(2-fluorophenyl)-1-((2-hydroxyethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 18)

[0060] (S)-3-(8-nitro-6-(2-fluorophenyl)-1-((2-hydroxyethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 19)

[0061] (S)-3-(8-chloro-6-(2-fluorophenyl)-1-((2-aminoethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 20)

[0062] (S)-3-(8-bromo-6-(2-fluorophenyl)-1-((2-aminoethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 21)

[0063] (S)-3-(8-nitro-6-(2-fluorophenyl)-1-((2-aminoethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 22)

[0064] (S)-3-(8-chloro-6-(2-chlorophenyl)-1-(methylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 23)

[0065] (S)-3-(8-bromo-6-(2-chlorophenyl)-1-(methylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 24)

[0066] (S)-3-(8-nitro-6-(2-chlorophenyl)-1-(methylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 25)

[0067] (S)-3-(8-chloro-6-(2-chlorophenyl)-1-(ethio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 26)

[0068] (S)-3(8-bromo-6-(2-chlorophenyl)-1-(ethio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 27)

[0069] (S)-3-(8-nitro-6-(2-chlorophenyl)-1-(ethio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 28)

[0070] (S)-3-(8-chloro-6-(2-chlorophenyl)-1-(propylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza methyl 4-yl)propionate (compound 29)

[0071] (S)-3-(8-bromo-6-(2-chlorophenyl)-1-(propylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 30)

[0072] (S)-3-(8-nitro-6-(2-chlorophenyl)-1-(propylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 31)

[0073] (S)-3-(8-chloro-6-(2-chlorophenyl)-1-((2-hydroxyethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 32)

[0074] (S)-3-(8-bromo-6-(2-chlorophenyl)-1-((2-hydroxyethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 33)

[0075] (S)-3-(8-nitro-6-(2-chlorophenyl)-1-((2-hydroxyethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 34)

[0076] (S)-3-(8-chloro-6-(2-chlorophenyl)-1-((2-aminoethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 35)

[0077] (S)-3-(8-bromo-6-(2-chlorophenyl)-1-((2-aminoethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 36)

[0078] (S)-3-(8-nitro-6-(2-chlorophenyl)-1-((2-aminoethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza methyl 4-yl)propionate (compound 37)

[0079] (S)-3-(8-chloro-6-(2-chlorophenyl)-1-(acetylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 38)

[0080] (S)-3-(8-bromo-6-(2-chlorophenyl)-1-(acetylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza methyl 4-yl)propionate (compound 39)

[0081] (S)-3-(8-nitro-6-(2-chlorophenyl)-1-(acetylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 40)

[0082] (S)-3-(8-chloro-6-(2-chlorophenyl)-1-mercapto-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza ethyl 4-yl)propionate (compound 41)

[0083] (S)-3-(8-chloro-6-(2-chlorophenyl)-1-thio-2,4-dihydro-1H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza ethyl 4-yl)propionate (compound 41 tautomer),

[0084] (S)-3-(8-chloro-6-(2-chlorophenyl)-1-(methylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza ethyl 4-yl)propionate (compound 42)

[0085] (S)-3-(8-bromo-6-(2-chlorophenyl)-1-(methylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza ethyl 4-yl)propionate (compound 43)

[0086] (S)-3-(8-nitro-6-(2-chlorophenyl)-1-(methylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza ethyl 4-yl)propionate (compound 44)

[0087] (S)-3-(8-chloro-6-(2-fluorophenyl)-1-((cyclopropylmethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 45)

[0088] (S)-3-(8-bromo-6-(2-fluorophenyl)-1-((cyclopropylmethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 46)

[0089] (S)-3-(8-nitro-6-(2-fluorophenyl)-1-((cyclopropylmethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 47)

[0090] (S)-3-(8-chloro-6-(2-fluorophenyl)-1-(propynylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 48)

[0091] (S)-3-(8-bromo-6-(2-fluorophenyl)-1-(propynylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza methyl 4-yl)propionate (compound 49)

[0092] (S)-3-(8-nitro-6-(2-fluorophenyl)-1-(propynylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 50)

[0093] (S)-3-(8-chloro-6-(2-fluorophenyl)-1-((2-morpholinoethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 51)

[0094] (S)-3-(8-bromo-6-(2-fluorophenyl)-1-((2-morpholinoethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 52)

[0095] (S)-3-(8-nitro-6-(2-fluorophenyl)-1-((2-morpholinoethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 53)

[0096] (S)-3-(8-chloro-6-(2-fluorophenyl)-1-((2-(diethylamino)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 54)

[0097] (S)-3-(8-bromo-6-(2-fluorophenyl)-1-((2-(diethylamino)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 55)

[0098] (S)-3-(8-nitro-6-(2-fluorophenyl)-1-((2-(diethylamino)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 56)

[0099] (S)-3-(8-chloro-6-(2-fluorophenyl)-1-((3-(dimethylamino)propyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 57)

[0100] (S)-3-(8-bromo-6-(2-fluorophenyl)-1-((3-(dimethylamino)propyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 58)

[0101] (S)-3-(8-nitro-6-(2-fluorophenyl)-1-((3-(dimethylamino)propyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 59)

[0102] (S)-3-(8-chloro-6-(2-fluorophenyl)-1-((2-(4-methylpiperazin-1-yl)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 60)

[0103] (S)-3-(8-bromo-6-(2-fluorophenyl)-1-((2-(4-methylpiperazin-1-yl)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 61)

[0104] (S)-3-(8-nitro-6-(2-fluorophenyl)-1-((2-(4-methylpiperazin-1-yl)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 62)

[0105] (S)-3-(8-chloro-6-(2-fluorophenyl)-1-((1-methylpiperidin-4-yl)thio)-4H-benzo[f][1,2,4]triazol[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 63)

[0106] (S)-3-(8-bromo-6-(2-fluorophenyl)-1-((1-methylpiperidin-4-yl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 64)

[0107] (S)-3-(8-nitro-6-(2-fluorophenyl)-1-((1-methylpiperidin-4-yl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 65)

[0108] (S)-3-(8-chloro-6-(2-fluorophenyl)-1-((3-(4-(2-hydroxyethyl)piperazin-1-yl)propyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 66)

[0109] (S)-3-(8-bromo-6-(2-fluorophenyl)-1-((3-(4-(2-hydroxyethyl)piperazin-1-yl)propyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 67)

[0110] (S)-3-(8-nitro-6-(2-fluorophenyl)-1-((3-(4-(2-hydroxyethyl)piperazin-1-yl)propyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 68)

[0111] (S)-3-(8-chloro-6-(2-fluorophenyl)-1-((morpholinomethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 69)

[0112] (S)-3-(8-bromo-6-(2-fluorophenyl)-1-((morpholinomethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 70)

[0113] (S)-3-(8-nitro-6-(2-fluorophenyl)-1-((morpholinomethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 71)

[0114] (S)-3-(8-chloro-6-(2-fluorophenyl)-1-(((4-phenylpiperazin-1-yl)methyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 72)

[0115] (S)-3-(8-bromo-6-(2-fluorophenyl)-1-(((4-phenylpiperazin-1-yl)methyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 73)

[0116] (S)-3-(8-nitro-6-(2-fluorophenyl)-1-(((4-phenylpiperazin-1-yl)methyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 74)

[0117] (S)-3-(8-chloro-6-(2-chlorophenyl)-1-((cyclopropylmethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 75)

[0118] (S)-3-(8-bromo-6-(2-chlorophenyl)-1-((cyclopropylmethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 76)

[0119] (S)-3-(8-nitro-6-(2-chlorophenyl)-1-((cyclopropylmethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 77)

[0120] (S)-3-(8-chloro-6-(2-chlorophenyl)-1-(propynylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 78)

[0121] (S)-3-(8-bromo-6-(2-chlorophenyl)-1-(propynylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 79)

[0122] (S)-3-(8-nitro-6-(2-chlorophenyl)-1-(propynylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 80)

[0123] (S)-3-(8-chloro-6-(2-chlorophenyl)-1-((2-morpholinoethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 81)

[0124] (S)-3-(8-bromo-6-(2-chlorophenyl)-1-((2-morpholinoethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 82)

[0125] (S)-3-(8-nitro-6-(2-chlorophenyl)-1-((2-morpholinoethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 83)

[0126] (S)-3-(8-chloro-6-(2-chlorophenyl)-1-((2-(diethylamino)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 84)

[0127] (S)-3-(8-bromo-6-(2-chlorophenyl)-1-((2-(diethylamino)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 85)

[0128] (S)-3-(8-nitro-6-(2-chlorophenyl)-1-((2-(diethylamino)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 86)

[0129] (S)-3-(8-chloro-6-(2-chlorophenyl)-1-((3-(dimethylamino)propyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 87)

[0130] (S)-3-(8-bromo-6-(2-chlorophenyl)-1-((3-(dimethylamino)propyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 88)

[0131] (S)-3-(8-nitro-6-(2-chlorophenyl)-1-((3-(dimethylamino)propyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 89)

[0132] (S)-3-(8-chloro-6-(2-chlorophenyl)-1-((2-(4-methylpiperazin-1-yl)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 90)

[0133] (S)-3-(8-bromo-6-(2-chlorophenyl)-1-((2-(4-methylpiperazin-1-yl)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 91)

[0134] (S)-3-(8-nitro-6-(2-chlorophenyl)-1-((2-(4-methylpiperazin-1-yl)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 92)

[0135] (S)-3-(8-chloro-6-(2-chlorophenyl)-1-((1-methylpiperidin-4-yl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza 4-yl)methyl propionate (compound 93)

[0136] (S)-3-(8-bromo-6-(2-chlorophenyl)-1-((1-methylpiperidin-4-yl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 94)

[0137] (S)-3-(8-nitro-6-(2-chlorophenyl)-1-((1-methylpiperidin-4-yl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 95)

[0138] (S)-3-(8-chloro-6-(2-chlorophenyl)-1-((3-(4-(2-hydroxyethyl)piperazin-1-yl)propyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 96)

[0139] (S)-3-(8-bromo-6-(2-chlorophenyl)-1-((3-(4-(2-hydroxyethyl)piperazin-1-yl)propyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 97)

[0140] (S)-3-(8-nitro-6-(2-chlorophenyl)-1-((3-(4-(2-hydroxyethyl)piperazin-1-yl)propyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 98)

[0141] (S)-3-(8-chloro-6-(2-chlorophenyl)-1-((morpholinomethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 99)

[0142] (S)-3-(8-bromo-6-(2-chlorophenyl)-1-((morpholinomethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 100)

[0143] (S)-3-(8-nitro-6-(2-chlorophenyl)-1-((morpholinomethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 101),

[0144] (S)-3-(8-chloro-1-(methylthio)-6-phenyl-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 102),

[0145] (S)-3-(8-bromo-1-(methylthio)-6-phenyl-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 103),

[0146] (S)-3-(8-nitro-1-(methylthio)-6-phenyl-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 104),

[0147] (S)-3-(8-chloro-1-((2-morpholinoethyl)thio)-6-phenyl-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 105),

[0148] (S)-3-(8-bromo-1-((2-morpholinoethyl)thio)-6-phenyl-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 106)

[0149] (S)-3-(8-nitro-1-((2-morpholinoethyl)thio)-6-phenyl-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 107)

[0150] (S)-3-(8-chloro-1-((3-(dimethylamino)propyl)thio)-6-phenyl-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 108)

[0151] (S)-3-(8-bromo-1-((3-(dimethylamino)propyl)thio)-6-phenyl-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 109)

[0152] (S)-3-(8-nitro-1-((3-(dimethylamino)propyl)thio)-6-phenyl-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 110)

[0153] (S)-3-(8-chloro-6-(2-chlorophenyl)-1-(((phosphono)methyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 111)

[0154] (S)-3-(8-bromo-6-(2-chlorophenyl)-1-(((phosphono)methyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 112)

[0155] (S)-3-(8-nitro-6-(2-chlorophenyl)-1-(((phosphono)methyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 113)

[0156] (S)3-(8-bromo-6-(pyridin-2-yl)-1-methylthio-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 114)

[0157] (S)3-(8-bromo-6-(pyridin-2-yl)-1-ethylthio-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 115)

[0158] (S)3-(8-bromo-6-(pyridin-2-yl)-1-((cyclopropylmethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 116)

[0159] (S)3-(8-bromo-6-(pyridin-2-yl)-1-((2-morpholinoethyl)thio)-4H-benzo[f][1,2,4]triazol[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 117)

[0160] (S)3-(8-bromo-6-(pyridin-2-yl)-1-(3-((dimethylamino)propyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 118)

[0161] (S)3-(8-chloro-6-(2-chlorophenyl)-1-(2-((pyrrolidin-1-yl)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 119)

[0162] (S)3-(8-bromo-6-(2-fluorophenyl)-1-(2-((pyrrolid-1-yl)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 120)

[0163] (S)3-(8-bromo-6-(2-chlorophenyl)-1-((2-(pyrrolid-1-yl)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 121)

[0164] (S)3-(8-chloro-6-(2-chlorophenyl)-1-(2-((piperidin-1-yl)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 122)

[0165] (S)3-(8-bromo-6-(2-fluorophenyl)-1-(2-((piperidin-1-yl)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 123)

[0166] (S)3-(8-chloro-6-(2-chlorophenyl)-1-(2-((pyridin-4-yl)methyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 124)

[0167] (S)3-(8-bromo-6-(2-fluorophenyl)-1-(2-((pyridin-4-yl)methyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 125)

[0168] (S)3-(8-bromo-6-(pyridin-2-yl)-1-(((pyridin-4-yl)methyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 126)

[0169] (S)3-(8-chloro-6-(2-chlorophenyl)-1-(2-((4,4-difluoropiperidin-1-yl)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 127)

[0170] (S)3-(8-bromo-6-(2-fluorophenyl)-1-(2-((4,4-difluoropiperidin-1-yl)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 128)

[0171] (S)3-(8-chloro-6-(2-chlorophenyl)-1-((2-(4-methylpiperazin-1-yl)2-oxoethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 129)

[0172] (S)3-(8-chloro-6-(2-chlorophenyl)-1-(2-(4-methylpiperazine-1-carbonyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 130)

[0173] (S)3-(8-bromo-6-(2-fluorophenyl)-1-(2-(4-methylpiperazine-1-carbonyl)thio))-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 131)

[0174] (S)3-(8-chloro-6-(2-chlorophenyl)-1-(3-((diethylamino)propyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 132)

[0175] (S)3-(8-chloro-6-(2-chlorophenyl)-1-(2-((dimethylamino)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 133)

[0176] (S)3-(8-bromo-6-(2-fluorophenyl)-1-(2-((dimethylamino)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 134)

[0177] (S)3-(8-chloro-6-(2-chlorophenyl)-1-(2-((4-hydroxypiperidin-1-yl)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 135)

[0178] (S)3-(8-chloro-6-(2-chlorophenyl)-1-(2-((4-methylpiperidin-2-carbonyl)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 136)

[0179] (S)3-(8-chloro-6-(2-chlorophenyl)-1-thio-2,4-dihydro-1H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza 2-morpholinoethyl 4-yl)propionic acid (compound 137)

[0180] (S)3-(8-chloro-6-(2-chlorophenyl)-1-(2-((1H-imidazol-1-yl)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 138)

[0181] (S)3-(8-bromo-6-(2-fluorophenyl)-1-(2-((1H-imidazol-1-yl)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 139)

[0182] (S)3-(8-chloro-6-(2-chlorophenyl)-1-(2-((1H-pyrrolo-1-yl)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 140)

[0183] (S)3-(8-chloro-6-(2-chlorophenyl)-1-((1-methyl-1H-imidazol-4-yl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 141)

[0184] (S)3-(8-chloro-6-(2-chlorophenyl)-1-((ethyl(methyl)carbamoyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 142)

[0185] (S)3-(8-chloro-6-(2-chlorophenyl)-1-(3-((dimethylamino)-3-oxopropyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 143)

[0186] (S)3-(8-chloro-6-(2-chlorophenyl)-1-(((4,5-dihydro-1H-imidazol-2-yl)methyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 144), and the structures of some compounds are as follows:

[0187]

[0188]

[0189]

[0190]

[0191]

[0192]

[0193] Furthermore, the content or amount of the compound of the present invention in the pharmaceutical composition may be from about 10 mg to about 3000 mg, suitably 25-3000 mg, preferably 60-2700 mg, more preferably 60-1500 mg, particularly preferably 60-1000 mg, for example 60 mg, 80 mg, 100 mg, 150 mg, 200 mg, 300 mg or 500 mg.

[0194] The pharmaceutically acceptable carrier is selected from water, oil, and other injectable solvents.

[0195] The pharmaceutical excipients used are selected from starch, glucose, lactose, brown sugar, gelatin, maltose, acetic acid, silica gel, sodium stearate, glyceryl monostearate, talc, sodium oxide, skim milk powder, glycerin, propylene glycol, ethanol, lecithin, glycine, mannitol, Tween 80, polysorbate, sodium carboxymethyl cellulose, gelatin, pectin, albumin, trehalose, and dextran.

[0196] Furthermore, its pharmaceutically acceptable salts are selected from acetates, adipates, aspartates, benzoates, benzenesulfonates, bicarbonates / carbonates, bisulfates / sulfates, borates, camphor sulfonates, citrates, cyclohexanesulfonates, ethanedisulfonates, ethanesulfonates, formates, fumarates, glucohepanoates, glucuronates, glucuronates, hexafluorophosphates, hydrochlorides / oxides, hydrobromates / bromines, hydroiodates / iodides, hydroxyethyl sulfonates, lactates, malates, maleic anhydride, malonate, and methanesulfonates. Methyl sulfate, naphthate, 2-naphthalenesulfonate, nicotinate, nitrate, orotate, oxalate, palmitate, dihydronaphthalate, phosphate / hydrogen phosphate / dihydrogen phosphate, pyroglutamate, glycoside, stearate, succinate, tannic acid, tartrate, toluenesulfonate, trifluoroacetate and sine, aluminum salt, arginine salt, benzathine penicillin salt, calcium salt, choline salt, diethylamine salt, diethanolamine salt, glycine salt, lysine salt, magnesium salt, meglumine salt, ethanolamine salt, sodium salt, potassium salt, ammonium salt, tromethamine salt and zinc salt.

[0197] Furthermore, the method for preparing the compound follows the reaction route as follows:

[0198]

[0199] Where R1, R2, R3, R4, R5, and W are as defined in any of technical solutions 1 and 3.

[0200] The method includes the following steps:

[0201] (1) React A with a chiral amino acid or its derivative protected by N2 in a condensation reaction to obtain intermediate C.

[0202] The reaction is preferably carried out in the presence of a base and a condensing agent; the base is, for example, but not limited to, DIPEA, N-methylmorpholine, or TEA; the condensing agent is, for example, but not limited to, HATU, DCC, EDCI, PyBOP, BOP-Cl, or T3P; the reaction is preferably carried out in a suitable solvent; the suitable solvent is, for example, but not limited to, THF, DMF, or DCM; the reaction is preferably carried out under ice bath conditions, at room temperature, or under solvent reflux conditions; the free amino acid or its derivative is, for example, but not limited to, L-glutamic acid-5-methyl ester or L-glutamic acid-5-ethyl ester.

[0203] (2) Remove the protecting group from intermediate C to obtain benzodiazepine. Intermediate class D,

[0204] The reaction is preferably carried out under acidic conditions; such acidic conditions are, for example, but not limited to, trifluoroacetic acid or hydrochloric acid.

[0205] (3) Make the benzodiazepine Intermediate D reacts with Lawson's reagent or phosphorus pentasulfide under reflux to give reactive intermediate E. The reaction is preferably carried out in a suitable solvent, such as, but not limited to, toluene or THF.

[0206] (4) The active intermediate E is subjected to a substitution reaction with hydrazine hydrate to obtain intermediate F.

[0207] The reaction is preferably carried out in a suitable solvent; the suitable solvent is, for example, but not limited to, toluene or THF, and the reaction is preferably carried out under ice bath conditions, at room temperature, or under solvent reflux conditions.

[0208] (5) The intermediate F is reacted with sulfur phosgene to close the ring and obtain the target product G.

[0209] The reaction is preferably carried out in a suitable solvent; the suitable solvent is, for example, but not limited to, DCM, DMF, or THF; the reaction is preferably carried out under ice bath conditions, or at room temperature, or under solvent reflux conditions; the reaction is preferably carried out under alkaline conditions, the alkaline conditions being, for example, but not limited to, triethylamine, DIPEA, or K2CO3.

[0210] (6) The intermediate G is reacted with a sodium salt in an aqueous solution to obtain the target product H.

[0211] The reaction is preferably carried out in a suitable solvent, such as, but not limited to, DCM, CH3OH, CH3CH2OH, CH3CH(OH)CH3, or THF. The reaction is preferably carried out under ice bath conditions, at room temperature, or under solvent reflux conditions. The reaction is preferably carried out under alkaline conditions, such as, but not limited to, sodium isopropoxide, sodium tert-butoxide, sodium methoxide, or sodium ethoxide.

[0212] (7) The intermediate H is subjected to a substitution reaction to obtain the target product I.

[0213] The reaction is preferably carried out in a suitable solvent; the suitable solvent is, for example, but not limited to, DCM, DMF or THF, and the reaction is preferably carried out under ice bath conditions or at room temperature or under solvent reflux conditions.

[0214] Furthermore, the use of the compound or composition in the preparation of sedative and anesthetic drugs includes conscious sedation during short-term diagnostic, surgical, or endoscopic procedures, induction and maintenance of general anesthesia, and ICU sedation.

[0215] Furthermore, a method of sedation and anesthesia includes administering an effective amount of the compound of any one of claims 1-7 or the pharmaceutical composition of claim 8 via intravenous, intra-arterial, subcutaneous, intraperitoneal, intramuscular, or transdermal routes.

[0216] Furthermore, a pharmaceutical preparation comprising a compound of general formula (I) or a pharmaceutically acceptable salt thereof as an active agent and a pharmaceutically acceptable carrier. A pharmaceutically acceptable carrier refers to one or more inert, non-toxic solid or liquid fillers, diluents, adjuvants, etc., which do not react adversely with the active compound or the patient.

[0217] Furthermore, the dosage form can be a commonly used pharmaceutical dosage form such as a suspension, emulsion, injection, or lyophilized powder for injection.

[0218] Furthermore, the dosing regimen can be adjusted to provide the optimal required response. For example, a single bolus injection can be administered, several fractions can be administered over time, or the dose can be proportionally reduced or increased as indicated by the urgency of the treatment situation. It should be noted that dosage values ​​can vary depending on the type and severity of the condition to be alleviated, and may include single or multiple doses. To further understand, for any given individual, the specific dosing regimen should be adjusted over time based on individual needs and the professional judgment of the person administering the composition or supervising its administration.

[0219] The object of this invention is to provide a pharmaceutical composition comprising an effective amount of the compound of this invention and one or more pharmaceutically acceptable carriers.

[0220] Pharmaceutically acceptable carriers that can be used in the pharmaceutical compositions of the present invention include, but are not limited to, sterile liquids such as water, oils, and other injectable solvents, including those of petroleum, animal, plant, or synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil, etc.; water is an exemplary carrier when the pharmaceutical composition is administered intravenously; physiological saline, glucose, aqueous glycerol, ethanol, propylene glycol, polyethylene glycol, and glycerin can also be used as liquid carriers, particularly for injections or emulsions. Suitable pharmaceutical excipients include starch, glucose, lactose, brown sugar, gelatin, maltose, acetic acid, silica gel, sodium stearate, glyceryl monostearate, talc, sodium oxide, skim milk powder, glycerin, propylene glycol, ethanol, lecithin, glycine, mannitol, Tween 80, polysorbate, sodium carboxymethyl cellulose, gelatin, pectin, albumin, trehalose, dextran, etc. The compositions may also contain small amounts of wetting agents, emulsifiers, or pH buffers as needed.

[0221] The pharmaceutical compositions of the present invention can be administered via suitable routes. Preferably, the pharmaceutical compositions of the present invention are administered via intravenous, intra-arterial, subcutaneous, intraperitoneal, intramuscular, or transdermal routes.

[0222] Another object of the present invention is to provide a medicine box containing the compounds or pharmaceutical compositions of the present invention.

[0223] Another object of the present invention is to provide a method of sedation and anesthesia, comprising administration, preferably by intravenous, intra-arterial, subcutaneous, intraperitoneal, intramuscular, or percutaneous route, of an effective amount of the compound or pharmaceutical composition of the present invention, said sedation and anesthesia method preferably for the following clinical treatment regimens: preoperative sedation during surgery; conscious sedation during short-term diagnostic, surgical, or endoscopic procedures; induction and maintenance of general anesthesia before and / or simultaneously with the administration of other anesthetics and analgesics; ICU sedation; and use in the preparation of sedative-hypnotic and anti-anxiety drugs, including sedation, hypnosis, anti-anxiety, and amnesia for early awakening-type insomnia caused by dysfunction of excitation and inhibition of the brain.

[0224] Another object of the present invention is to provide the compounds of the invention for use as sedative and anesthetic drugs, wherein the sedation and anesthesia methods are preferably used for intravenous administration in the following clinical treatment regimens: preoperative sedation during surgery; conscious sedation during short-term diagnostic, surgical, or endoscopic procedures; induction and maintenance of general anesthesia before and / or simultaneously with the administration of other anesthetics and analgesics; ICU sedation; and use in the preparation of sedative-hypnotic and anti-anxiety drugs, including for sedation, hypnosis, anti-anxiety, and amnesia in early-morning insomnia caused by dysfunction of the brain's excitation and inhibition mechanisms.

[0225] Another object of the present invention is to provide the use of the compounds or pharmaceutical compositions of the present invention in the preparation of sedative and anesthetic drugs, wherein the sedation and anesthesia methods are preferably used for intravenous administration in the following clinical treatment regimens: preoperative sedation during surgery; conscious sedation during short-term diagnostic, surgical, or endoscopic procedures; induction and maintenance of general anesthesia before and / or simultaneously with the administration of other anesthetics and analgesics; ICU sedation; and use in the preparation of sedative-hypnotic and anti-anxiety drugs, including sedation, hypnosis, anti-anxiety, and amnesia for early awakening-type insomnia caused by dysfunction of excitation and inhibition of the brain.

[0226] The amount of the compound of the present invention administered will depend on the individual being treated, the rate of administration, the disposal of the compound, and the judgment of the prescribing physician. Generally, the effective dose is about 0.0001 to about 50 mg per kg of body weight per day, for example, about 0.01 to about 10 mg / kg / day (single or divided doses). For a 70 kg person, this would total about 0.007 mg / day to about 3500 mg / day, for example, about 0.7 mg / day to about 700 mg / day. In some cases, dose levels below the lower limit of the foregoing range may be sufficient, while in other cases, larger doses may still be used without causing any harmful side effects, provided that the larger dose is first divided into several smaller doses administered throughout the day.

[0227] Beneficial effects

[0228] The beneficial effects of this invention are: the short-acting benzodiazepine of this invention... The derivatives of this invention are characterized by rapid onset of action, short duration of action, strong depth of action, rapid metabolism, and rapid recovery. In anesthesia experiments on mice and rats, the short-acting benzodiazepine of this invention... The onset time of this derivative is comparable to that of remimazolam, but both the duration of action and recovery time are significantly shortened. Furthermore, some compounds exhibit a markedly enhanced depth of action, demonstrating faster onset, shorter duration of action, greater potency, faster metabolism, and faster recovery. In long-term infusion anesthesia experiments on rats, compared to remimazolam, the short-acting benzodiazepine of this invention... The awakening and recovery times of the derivatives are significantly shortened, exhibiting characteristics such as faster awakening and faster recovery; the benzodiazepine of this invention... These compounds not only retain their affinity for GABA A The high affinity and selectivity of the receptor, and through benzodiazepines The structural modification and adjustment of the carboxylic acid ester group have the following advantages: predictable rapid onset time of sedation and anesthesia, short effective duration, strong depth of action, and short recovery time, thereby reducing adverse inhibitory reactions on the cardiovascular and respiratory systems, and reducing side effects on the patient's nervous system, including drowsiness, dizziness, and other problems.

[0229] Terminology Definitions and Explanations

[0230] Unless otherwise stated, the definitions of groups and terms recorded in this application specification and claims, including definitions as examples, exemplary definitions, preferred definitions, definitions recorded in tables, and definitions of specific compounds in the examples, can be arbitrarily combined and combined with each other. Such combinations and combinations of group definitions and compound structures should be understood as being within the scope of this application specification and / or claims.

[0231] Unless otherwise stated, the numerical ranges described in this specification and claims are equivalent to describing at least each specific integer value therein. For example, the numerical range "1-20" is equivalent to describing each integer value in the numerical range "1-10", namely 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and each integer value in the numerical range "11-20", namely 11, 12, 13, 14, 15, 16, 17, 18, 19, 20.

[0232] The term "halogen" refers to fluorine, chlorine, bromine, and iodine.

[0233] Term "C" 1-20 "Alkyl" should be understood as referring to a straight-chain or branched saturated monovalent hydrocarbon group having 1 to 20 carbon atoms. For example, "C 1-10 "Alkyl" refers to straight-chain and branched alkyl groups having 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 carbon atoms. 1-8 "Alkyl" refers to straight-chain and branched alkyl groups having 1, 2, 3, 4, 5, 6, 7, or 8 carbon atoms. 1-6 "Alkyl" means a straight-chain or branched alkyl group having 1, 2, 3, 4, 5, or 6 carbon atoms. The alkyl group is, for example, methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, isobutyl, sec-butyl, tert-butyl, isopentyl, 2-methylbutyl, 1-methylbutyl, 1-ethylpropyl, 1,2-dimethylpropyl, neopentyl, 1,1-dimethylpropyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 1-methylpentyl, 2-ethylbutyl, 1-ethylbutyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 2,3-dimethylbutyl, 1,3-dimethylbutyl, or 1,2-dimethylbutyl, or their isomers.

[0234] Term "C" 2-20 "Alkenyl" should be understood as representing a straight-chain or branched monovalent hydrocarbon group containing one or more double bonds and having 2 to 20 carbon atoms, preferably "C". 2-10 "Alkenyl". "C" 2-10"Alkenyl" should be understood to preferably represent a straight or branched monovalent hydrocarbon group containing one or more double bonds and having 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, more preferably "C 2-8 "Alkenyl". "C" 2-10 "Alkenyl" should be understood to preferably represent a straight or branched monovalent hydrocarbon group containing one or more double bonds and having 2, 3, 4, 5, 6, 7 or 8 carbon atoms, for example, having 2, 3, 4, 5 or 6 carbon atoms (i.e., C... 2-6 alkenyl), having 2 or 3 carbon atoms (i.e., C24, C34, C4 ... 2-3 Alkenyl). It should be understood that when the alkenyl group contains more than one double bond, the double bonds may be separable or conjugated. The alkenyl group is, for example, vinyl, allyl, (E)-2-methylvinyl, (Z)-2-methylvinyl, (E)-but-2-enyl, (Z)-but-2-enyl, (E)-but-1-enyl, (Z)-but-1-enyl, pent-4-enyl, (E)-pent-3-enyl, (Z)-pent-3-enyl, (E)-pent-2-enyl, (Z)-pent-2-enyl, (E)- Pentyl-1-enyl, (Z)-pentyl-1-enyl, hex-5-enyl, (E)-hex-4-enyl, (Z)-hex-4-enyl, (E)-hex-3-enyl, (Z)-hex-3-enyl, (E)-hex-2-enyl, (Z)-hex-2-enyl, (E)-hex-1-enyl, (Z)-hex-1-enyl, isopropenyl, 2-methylprop-2-enyl, 1-methylprop-2-enyl 2-Methylprop-1-enyl, (E)-1-methylprop-1-enyl, (Z)-1-methylprop-1-enyl, 3-methylbut-3-enyl, 2-methylbut-3-enyl, 1-methylbut-3-enyl, 3-methylbut-2-enyl, (E)-2-methylbut-2-enyl, (Z)-2-methylbut-2-enyl, (E)-1-methylbut-2-enyl, (Z)-1-methyl But-2-enyl, (E)-3-methylbut-1-enyl, (Z)-3-methylbut-1-enyl, (E)-2-methylbut-1-enyl, (Z)-2-methylbut-1-enyl, (E)-1-methylbut-1-enyl, (Z)-1-methylbut-1-enyl, 1,1-dimethylprop-2-enyl, 1-ethylprop-1-enyl, 1-propylvinyl, 1-isopropylvinyl.

[0235] Term "C" 2-20 "Alkyne group" should be understood as representing a straight or branched monovalent hydrocarbon group containing one or more triple bonds and having 2 to 20 carbon atoms, preferably "C". 2-10 "Alkyne group". The term "C" 2-10"Alkyne" should be understood to preferably represent a straight or branched monovalent hydrocarbon group containing one or more triple bonds and having 2, 3, 4, 5, 6, 7, 8, 9, or 10 carbon atoms, for example, having 2, 3, 4, 5, 6, 7, or 8 carbon atoms (i.e., "C"). 2-8 "Alkyne group" has 2, 3, 4, 5 or 6 carbon atoms (i.e., "C"). 2-6 The alkynyl group ("C") has 2 or 3 carbon atoms ("C") 2-3 The alkynyl group is, for example, ethynyl, prop-1-alkynyl, prop-2-alkynyl, but-1-alkynyl, but-2-alkynyl, but-3-alkynyl, pent-1-alkynyl, pent-2-alkynyl, pent-3-alkynyl, pent-4-alkynyl, hex-1-alkynyl, hex-2-alkynyl, hex-3-alkynyl, hex-4-alkynyl, hex-5-alkynyl, 1-methylprop-2-alkynyl, 2-methylbut-3-alkynyl, 1-methylbut-3-alkynyl, 1-methylbut-2-alkynyl, 3-methylbut-1-alkynyl, 1-ethylprop-2-alkynyl, 3-methylpent-4-alkynyl, 2-methylpent-4-alkynyl, 1-methylpent-4-alkynyl -Alynyl, 2-methylpentan-3-ynyl, 1-methylpentan-3-ynyl, 4-methylpentan-2-ynyl, 1-methylpentan-2-ynyl, 4-methylpentan-1-ynyl, 3-methylpentan-1-ynyl, 2-ethylbutan-3-ynyl, 1-ethylbutan-3-ynyl, 1-ethylbutan-2-ynyl, 1-propylpropan-2-ynyl, 1-isopropylpropan-2-ynyl, 2,2-dimethylbutan-3-ynyl, 1,1-dimethylbutan-3-ynyl, 1,1-dimethylbutan-2-ynyl, or 3,3-dimethylbutan-1-ynyl. In particular, the ynyl group is ethynyl, propan-1-ynyl, or propan-2-ynyl.

[0236] Term "C" 3-10 "Cycloalkyl" should be understood to refer to a saturated monovalent monocyclic, bicyclic (e.g., bridged, spirocyclic) hydrocarbon ring or tricyclic alkane having 3, 4, 5, 6, 7, 8, 9, or 10 carbon atoms. The C... 3-10 Cycloalkyl groups can be monocyclic hydrocarbon groups, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, or cyclodecyl; or bicyclic hydrocarbon groups, such as borneolyl, indolyl, hexahydroindolyl, tetrahydronaphthyl, decahydronaphthyl, bicyclo[2.1.1]hexyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.1]heptenyl, 6,6-dimethylbicyclo[3.1.1]heptyl, 2,6,6-trimethylbicyclo[3.1.1]heptyl, bicyclo[2.2.2]octyl, 2,7-diazaspiro[3,5]nonyl, 2,6-diazaspiro[3,4]octyl; or tricyclic hydrocarbon groups, such as adamantyl.

[0237] The term "3-10 membered heterocyclic group" refers to a saturated or unsaturated non-aromatic ring or ring system containing at least one heteroatom selected from O, S, and N. The heterocyclic group can be connected to the remainder of the molecule via any one of the carbon atoms or a nitrogen atom (if present). The heterocyclic group can include fused or bridged rings and spirocyclic rings. Specifically, the heterocyclic group can include, but is not limited to: 4-membered rings, such as azirrobutyl or oxobutyl; 5-membered rings, such as tetrahydrofuranyl, dioxacyclopentenyl, pyrrolyl, imidazoalkyl, pyrazolyl, or pyrrololinyl; or 6-membered rings, such as tetrahydropyranyl, piperidinyl, morpholinyl, dithiaalkyl, thiomorpholinyl, piperazinyl, or trithiaalkyl; or 7-membered rings, such as diazacycloheptyl. Optionally, the heterocyclic group can be benzofused. The heterocyclic group can be bicyclic, such as, but not limited to, a 5,5-membered ring, like a hexahydrocyclopentano[c]pyrrole-2(1H)-yl ring, or a 5,6-membered bicyclic ring, like a hexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl ring. The heterocyclic group can be partially unsaturated, meaning it can contain one or more double bonds, such as, but not limited to, dihydrofuranyl, dihydropyranyl, 2,5-dihydro-1H-pyrroleyl, 4H-[1,3,4]thiadiazinyl, 1,2,3,5-tetrahydrooxazolyl, or 4H-[1,4]thiazinyl, or it can be benzofused, such as, but not limited to, dihydroisoquinolinyl. When the 3-10-membered heterocyclic group is linked to other groups to form the compounds of the present invention, the carbon atom on the 3-10-membered heterocyclic group can be linked to other groups, or the heterocyclic atom on the 3-10-membered heterocyclic ring can be linked to other groups. For example, when the 3-10 membered heterocyclic group is selected from piperazine, the nitrogen atom on the piperazine group can be attached to other groups. Or when the 3-10 membered heterocyclic group is selected from piperidinium, the nitrogen atom on the piperidinium ring and the carbon atom at its para position can be attached to other groups.

[0238] Term "C" 6-14 "Aryl" should be understood to preferably represent a monovalent aromatic or partially aromatic monocyclic, bicyclic, or tricyclic hydrocarbon ring ("C") having 6, 7, 8, 9, 10, 11, 12, 13, or 14 carbon atoms. 6-14 Aryl), particularly a ring with 6 carbon atoms (“C6 aryl”), such as phenyl; or biphenyl, or a ring with 9 carbon atoms (“C9 aryl”), such as indenyl or indenyl, or a ring with 10 carbon atoms (“C9 aryl”). 10 Aryl groups, such as tetrahydronaphthyl, dihydronaphthyl, or naphthyl, or rings with 13 carbon atoms (“C”). 13 Aryl groups, such as fluorene groups, or rings with 14 carbon atoms (“C”). 14 Aryl), for example, anthracene. When the C 6-14When the aryl group is substituted, it can be monosubstituted or polysubstituted. Furthermore, there are no restrictions on the substitution site; for example, it can be ortho, para, or meta substituted.

[0239] The term "5-14-membered heteroaryl" should be understood to include monocyclic, bicyclic (e.g., fused, bridged, spirocyclic), or tricyclic aromatic ring systems having 5 to 14 ring atoms and containing one or more (e.g., 1 to 5) heteroatoms independently selected from N, O, and S, such as "5-14-membered heteroaryl". "5-14-membered heteroaryl" should also be understood to include monovalent monocyclic, bicyclic, or tricyclic aromatic ring systems having 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14 ring atoms, particularly 5, 6, 9, or 10 carbon atoms, and containing 1 to 5, preferably 1 to 3, heteroatoms independently selected from N, O, and S, and in each case, may be benzo-fused. "Heteroaryl" also refers to a group in which the heteroaryl ring is fused with one or more aryl, alicyclic, or heterocyclic rings, wherein the root or point of the connection is on the heteroaryl ring. When the 5-14 membered heteroaryl group is linked with other groups to form the compound of the present invention, the carbon atom on the 5-14 membered heteroaryl ring may be linked with other groups, or the heteroatom on the 5-14 membered heteroaryl ring may be linked with other groups. When the 5-14 membered heteroaryl group is substituted, it may be monosubstituted or polysubstituted. Furthermore, there are no restrictions on the substitution site; for example, the hydrogen atom on the heteroaryl ring linked with a carbon atom may be substituted, or the hydrogen atom on the heteroaryl ring linked with a heteroatom may be substituted.

[0240] The term "spirocycle" refers to a ring system in which two rings share a single ring atom.

[0241] The term "fused ring" refers to a ring system in which two rings share two cyclic atoms.

[0242] The term "bridged ring" refers to a ring system in which two rings share three or more cyclic atoms.

[0243] The term "oxo" refers to the substitution of a carbon, nitrogen, or sulfur atom in a substituent with an oxygen atom (=O) formed by oxidation. Detailed Implementation

[0244] To make the objectives and technical solutions of this invention clearer, the invention is further described below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Furthermore, specific experimental methods not mentioned in the following embodiments were performed according to conventional experimental methods.

[0245] The abbreviations used in this article have the following meanings:

[0246]

[0247] The structure of the compound was determined by nuclear magnetic resonance spectroscopy (NMR).1 H NMR, 13 The reaction was confirmed by C NMR and mass spectrometry (MS); the reaction was monitored by thin-layer chromatography (TLC) or LCMS, and the developing solvent systems used were: dichloromethane and methanol system, n-hexane and ethyl acetate system, and petroleum ether and ethyl acetate system.

[0248] Column chromatography typically uses 200-300 mesh silica gel as the stationary phase; the eluent systems include: dichloromethane and methanol system, n-hexane and ethyl acetate system, and the volume ratio of the solvent is adjusted according to the polarity of the compound.

[0249] In the following examples, unless otherwise specified, the reaction temperature is room temperature (20°C to 30°C).

[0250] Example 1: (S)-3-(8-chloro-6-(2-fluorophenyl)-1-mercapto-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 1) (compound 1 tautomer)

[0251]

[0252] Step 1: Preparation of methyl (S)-5-((2-fluoro-benzoyl-4-chlorophenyl)amino)-4-((tert-butoxycarbonyl)amino)-5-oxovalerate (compound 1c):

[0253] 2-Amino-5-chloro-2'-fluorobenzophenone (compound 1a, 11.48 g, 0.046 mol) and compound N-tert-butoxycarbonyl-L-glutamic acid-5-methyl ester (compound 1b, 10 g, 0.038 mol) were dissolved in DCM (300 mL). The mixture was cooled to 0 °C, DCC (9.49 g, 0.046 mmol) was added, and the mixture was stirred for 24 hours. LC-MS showed that the reaction was complete. The filtrate was collected, and the reaction solvent was removed under reduced pressure. The remaining product was purified by column chromatography (petroleum ether / ethyl acetate, 4:1, v / v) to give a white solid (S)-5-((2-fluoro-benzoyl-4-chlorophenyl)amino)-4-((tert-butoxycarbonyl)amino)-5-oxovalerate methyl ester (compound 1c, 10.56 g, yield: 56.4%).

[0254] Step 2: Preparation of (S)-4-amino-5-((2-fluorobenzoyl-4-chlorophenyl)amino)-5-oxovalerate methyl ester (compound 1d):

[0255] Methyl (S)-5-((2-fluorobenzoyl-4-chlorophenyl)amino)-4-((tert-butoxycarbonyl)amino)-5-oxovalerate (compound 1c, 10.56 g) was dissolved in DCM (50 mL). TFA (50 mL) was added, and the mixture was stirred for 20 minutes until LCMS showed the end of the reaction. The reaction solution was concentrated, and the residue obtained was crude methyl (S)-4-amino-5-((2-fluorobenzoyl-4-chlorophenyl)amino)-5-oxovalerate (compound 1d, 8.4 g), which was used directly in the next reaction.

[0256] Step 3: (S)-3-(7-chloro-2-oxo-5-(2-fluorophenyl)-2,3-dihydro-1H-benzo[e][l,4]diaza Preparation of methyl 3-yl)propionate (compound 1e):

[0257] Methyl (S)-4-amino-5-((2-fluorobenzoyl-4-chlorophenyl)amino)-5-oxovalerate (compound 1d, 8.4 g) was dissolved in MeOH (100 mL), and the pH was adjusted to approximately 10 with NaHCO3. The mixture was stirred for 24 hours. LCMS showed the reaction was complete. The reaction solution was filtered, and the filtrate was poured into ice water and extracted with ethyl acetate. The organic phase was washed three times with water, dried, and concentrated. The residue was purified by column chromatography (petroleum ether / ethyl acetate, 2:1, v / v) to give a white (S)-3-(7-chloro-2-oxo-5-(2-fluorophenyl)-2,3-dihydro-1H-benzo[e][l,4]diaza)- Methyl 3-yl)propionate (compound 1e, 7.5g)

[0258] Step 4: (S)-3-(7-chloro-5-(2-fluorophenyl)-2-thio-2-3,3-dihydro-1H-benzo[e][1,4]diaza Preparation of methyl 3-yl)propionate (compound 1f):

[0259] (S)-3-(7-chloro-2-oxo-5-(2-fluorophenyl)-2,3-dihydro-1H-benzo[e][l,4]diaza Methyl (-3-yl)propionate (compound 1e, 7.5 g) was dissolved in toluene (200 mL), and Lawson's reagent (4.86 g, 0.012 mol) was added. The compound was heated to 100 °C and stirred for 1.5 hours until the reaction was complete as indicated by LCMS. Excess Lawson's reagent was removed by adding saturated sodium bicarbonate solution, and the mixture was extracted with ethyl acetate (20 mL × 3). The organic layers were combined and dried over anhydrous sodium sulfate. The reaction solvent was removed under reduced pressure. The residual product was purified by column chromatography (petroleum ether / ethyl acetate, 7:1, v / v) to give a pale yellow solid (S)-3-(7-chloro-5-(2-fluorophenyl)-2-thio-2-3,3-dihydro-1H-benzo[e][1,4]diaza Methyl 3-yl)propionate (compound 1f, 4.07 g, yield: 52.1%)

[0260] Step 5: (S)-3-(7-chloro-5-(2-fluorophenyl)-2-hydrazino-2,3-dihydro-1H-benzo[e][1,4]diaza) Preparation of methyl 3-yl)propionate (compound 1g)

[0261] (S)-3-(7-chloro-5-(2-fluorophenyl)-2-thio-2-3,3-dihydro-1H-benzo[e][1,4]diaza Methyl (-3-yl)propionate (compound 1f, 4.07 g) was dissolved in 50 mL THF. The mixture was cooled to 0 °C, and 80% hydrazine hydrate (1.56 g, 0.031 mol) was added. The mixture was stirred for 30 minutes until the reaction was complete as indicated by LCMS. Excess hydrazine hydrate was removed with saturated NaCl, and the organic phases were extracted with DCM. The combined organic phases were dried and concentrated to give crude (S)-3-(7-chloro-5-(2-fluorophenyl)-2-hydrazino-2,3-dihydro-1H-benzo[e][1,4]diaza Methyl 3-yl)propionate (1 g of compound, 3.1 g of compound) was used directly in the next reaction.

[0262] Step 6: (S)-3-(8-bromo-6-(pyridin-2-yl)-1-thio-2-2,4-dihydro-1H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Preparation of methyl 4-yl)propionate (tautomer of compound 1)

[0263] (S)-3-(7-chloro-5-(2-fluorophenyl)-2-hydrazino-2,3-dihydro-1H-benzo[e][1,4]diaza Methyl (-3-yl)propionate (1 g of compound, 3.1 g) was dissolved in 80 mL of THF, and TEA (1.77 g, 0.018 mol) was added. The mixture was cooled to 0 °C, and sulfur phosgene (1.0 g, 0.009 mol) was added. The mixture was stirred for 2 h until the LCMS showed the end of the reaction. The filtrate was collected and the reaction solvent was removed under reduced pressure. The residual product was purified by column chromatography (petroleum ether / ethyl acetate, 4:1, v / v) to give a white solid (S)-3-(8-bromo-6-(pyridin-2-yl)-1-thio-2-2,4-dihydro-1H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza) Methyl 4-yl)propionate (compound 1 tautomer, 1.46 g, yield: 42.5%)

[0264] 1 H NMR (300MHz, DMSO-d6) δ: 14.17 (s, 1H), 8.46 (d, J = 8.7Hz, 1H), 7.90-7.28 (m, 6H), 4.26 (t, J = 6.1Hz, 1H), 3.62 (s, 3H), 2.70-2.45 (m, 4H); 13 C NMR(75MHz,DMSO-d6)δ:173.58,166.94,164.32,161.78,158.47,153.86,133.56,132.55,132.23,131.91, 131.18,129.03,127.87,127.02,125.27,116.78,55.15,51.85,30.19,26.26; LC-MS(ESI)m / z:430.5[M+H] + .

[0265] Examples 2-7 were synthesized according to the corresponding methods in the above examples. The specific NMR and CMR characterization data are as follows:

[0266] Example 2: (S)-3-(8-chloro-6-(2-chlorophenyl)-1-thio-2,4-dihydro-1H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Preparation of methyl 4-yl)propionate (the tautomer of compound 2):

[0267] 1H NMR(300MHz,DMSO-d6)δ:14.15(s,1H),8.46(d,J=8.8Hz,1H),7.87(d,J=7.4Hz,1H),7 .66-7.50(m,4H),7.16(s,1H),4.34(t,J=5.8Hz,1H),3.62(s,3H),2.70-2.45(m,4H); 13 C NMR(75MHz,DMSO-d6)δ:173.54,167.16,167.00,153.68,138.23,132.42,132.28,132.12,131.94,131.73, 131.64,131.07,130.21,128.52,127.99,127.96,55.30,51.85,30.22,26.16; LC-MS(ESI)m / z:447.2[M+H] + .

[0268] Example 3: (S)-3-(8-bromo-6-(pyridin-2-yl)-1-thio-2,4-dihydro-1H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Preparation of methyl 4-yl)propionate (compound 3 tautomer)

[0269] 1 H NMR(300MHz, DMSO-d6)δ:14.17(s,1H),8.59(d,J=4.3Hz,1H),8.37(d,J=8.8Hz,1H),8.13(d,J=7.9H z,1H),8.03-7.98(m,2H),7.60-7.54(m,2H),4.34(t,J=5.8Hz,1H),3.65(s,3H),2.70-2.45(m,4H); 13 C NMR(75MHz, CDCl3-d1)δ:173.70,167.81,166.51,157.68,155.34,149.03,136.91,134.69,134.01,132 .24,130.18,126.91,125.28,124.90,123.99,55.09,51.71,30.17,26.18; LC-MS(ESI)m / z:457.8[M+H] + .

[0270] Example 4: (S)-3-(8-bromo-6-(2-fluorophenyl)-1-thio-2,4-dihydro-1H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Preparation of methyl 4-yl)propionate (compound 4 tautomer)

[0271] 1 H NMR(300MHz, DMSO-d6)δ:11.14(s,1H),8.38(d,J=9.1Hz,1H),7.97(d,J=8.9Hz,1H),7.66-7.54(m,2H),7.43 (s,1H),7.36(t,J=7.5Hz,1H),7.24(t,J=9.8Hz,1H),4.27(t,J=6.7Hz,1H),3.60(s,3H),2.70-2.45(m,4H); 13 C NMR(75MHz,DMSO-d6)δ:173.60,166.91,164.26,161.78,158.48,153.87,134.09,133.46,132.45,131.93, 131.60,128.02,127.05,125.28,120.85,116.80,55.14,51.87,30.20,26.27; LC-MS(ESI)m / z:475.1[M+H] + .

[0272] Example 5: (S)-3-(6-phenyl-1-thio-2,4-dihydro-1H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza) Preparation of methyl 4-yl)propionate (the tautomer of compound 5):

[0273] 1 H NMR (400MHz, DMSO-d6) δ: 14.06 (s, 1H), 8.43 (d, J = 8.0Hz, 1H), 7.80 (t, J = 7.3Hz ,1H),7.60-7.40(m,7H),4.17(t,J=5.7Hz,1H),3.62(s,3H),2.70-2.40(m,4H); 13 CNMR(75MHz, CDCl3-d1)δ:173.89,169.62,167.15,154.17,138.77,133.17,131.38,131.10,131.00,129 .80(2C),129.57,128.35(2C),127.88,125.67,54.78,51.87,30.25,26.21; LC-MS(ESI)m / z:379.5[M+H] + .

[0274] Example 6: (S)-3-(6-(4-fluorophenyl)-1-thio-2,4-dihydro-1H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Preparation of methyl 4-yl)propionate (compound 6 tautomer):

[0275] 1 H NMR(400MHz, DMSO-d6)δ:14.06(s,1H),8.43(d,J=8.3Hz,1H),7.81(t,J=8.8Hz,1H),7.60-7.55(m,3H ),7.43(d,J=9.0Hz,1H),7.28(t,J=7.7Hz,2H),4.17(t,J=7.6Hz,1H),3.62(s,3H),2.70-2.40(m,4H); 13 C NMR(75MHz, CDCl3-d1)δ:173.84,168.39,167.18,166.24,162.90,154.14,134.90,133.16,131.98,131 .18,129.31,127.98,125.80,115.58,115.29,54.77,51.88,30.22,26.17; LC-MS(ESI)m / z:397.3[M+H] + .

[0276] Example 7: (S)-3-(8-chloro-6-phenyl)-1-thio-2,4-dihydro-1H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Preparation of methyl 4-yl)propionate (the tautomer of compound 7):

[0277] 1 H NMR (300MHz, CDCl3-d1) δ: 11.34 (s, 1H), 8.57 (d, J = 8.8Hz, 1H), 7.71-7.41 (m, 7H), 4.17 (t, J = 5.8Hz, 1H), 3.73 (s, 3H), 2.81-2.60 (m, 4H); 13 C NMR(75MHz,DMSO-d6)δ:173.62,167.25,166.82,154.07,138.40,132.31,132.24,131.44,131.20, 130.96,130.45,129.54,128.91,127.86,55.36,51.84,30.23,26.34; LC-MS(ESI)m / z:412.7[M+H] + .

[0278] Example 8: (S)-3-(8-chloro-6-(2-fluorophenyl)-1-(methylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Preparation of methyl 4-yl)propionate (compound 8)

[0279]

[0280] (S)-3-(8-chloro-6-(2-fluorophenyl)-1-mercapto-4H-benzo[f][1,2,4]triazolo[4,3-a][1,4]diaza Methyl 4-(8-chloro-6-(2-fluorophenyl)-1-(methylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza) was dissolved in 8 ml of THF, cooled in an ice bath, and 20% sodium isopropoxide in tetrahydrofuran solution was added dropwise. After the addition was complete, the mixture was stirred at room temperature for 30 minutes. The solvent was removed by rotary evaporation to obtain the corresponding sodium salt. Iodomethane (0.049 g, 0.35 mmol) was added, and the mixture was heated to reflux at 68 °C for 8 h. After concentration by reduced pressure column chromatography (PE:EA = 1:1), a white solid (S)-3-(8-chloro-6-(2-fluorophenyl)-1-(methylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 8, 0.075 g, yield: 72.8%).

[0281] 1 H NMR(300MHz, CDCl3-d1)δ:7.78-7.61(m,3H),7.48(q,J=6.1Hz,1H),7.34-7.24(m, 2H),7.05(t,J=9.6Hz,1H),4.23(t,J=5.7Hz,1H),3.68(s,3H),2.90-2.72(m,7H); 13 CNMR(75MHz, CDCl3-d1)δ173.88,163.67,161.96,158.65,157.58,151.07,133.73,132.71,132.60,131.62,13 1.27,130.35,129.78,127.05,124.63,116.46,55.06,51.63,30.18,26.55,15.28; LC-MS(ESI)m / z:445.3[M+H] + .

[0282] Examples 9-144 (compounds 9-144) were all synthesized according to the corresponding methods in the above examples. Specific NMR and CMR characterization data are as follows:

[0283] Example 9: (S)-3-(8-bromo-6-(2-fluorophenyl)-1-(methylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza 4-yl)methyl propionate (compound 9):

[0284] 1 H NMR (300MHz, CDCl3-d1) δ7.67(dd,J=7.3,2.2Hz,1H),7.59(d,J=2.0Hz,1H),7.55-7.31(m,5H),7.22(dd,J=7 .2,2.2Hz,1H),5.22(s,1H),3.68(s,3H),2.53(d,J=28.9Hz,4H),2.45-2.26(m,2H),2.25(d,J=12.4Hz,1H); 13 C NMR (75MHz, CDCl3-d1) δ173.78,160.03,150.29,147.02,140.17,138.02,131.75,129.62,129.44,129.40,125 .51,125.40,122.44,118.85,117.15,115.82,54.38,51.46,32.25,27.63,14.05; LC-MS(ESI)m / z:490.3[M+H] + .

[0285] Example 10: (S)3-(8-nitro-6-(2-fluorophenyl)-1-(methylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza -4-yl)propionic acid (compound 10):

[0286] 1 H NMR (300MHz, CDCl3-d1) δ8.30(dd,J=7.5,2.0Hz,1H),8.15(d,J=2.0Hz,1H),7.75(d,J=7.5Hz,1H),7.64(dd,J=7.2,2.3Hz,1H),7.50–7.31(m, 2H),7.27(dd,J=7.2,2.4Hz,1H),5.15(s,1H),3.68(s,3H),2.56(s,3H),2.53(d,J=12.4Hz,1H),2.40(d,J=12.4Hz,1H),2.24(d,J=1.5Hz,2H); 13C NMR (75MHz, CDCl3-d1) δ173.68,160.03,150.29,148.47,146.96,143.52,141.28,129.83,129.75,128.39,124 .87,124.15,123.29,122.44,120.52,115.88,57.87,51.40,32.25,27.60,14.05; LC-MS(ESI)m / z:456.4[M+H] + .

[0287] Example 11: (S)3-(8-chloro-6-(2-fluorophenyl)-1-(ethylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza 4-yl)methyl propionate (compound 11):

[0288] 1 H NMR(300MHz, CDCl3-d1)δ:7.78-7.61(m,5H),7.48(q,J=5.4Hz,1H),7.34-7.24(m,2H),7.05(t,J=9.4Hz, 1H),4.23(t,J=5.7Hz,1H),3.68(s,3H),3.25(q,J=7.2Hz,2H),2.90-2.72(m,4H),1.39(t,J=7.2Hz,3H); 13 C NMR(75MHz, CDCl3-d1)δ:173.88,163.70,162.02,158.68,157.41,150.20,133.69,132.71,131.51,131.26,130.4 0,129.65,127.06,125.08,124.56,116.45,55.10,51.63,30.20,27.81,26.54,14.66; LC-MS(ESI)m / z:458.9[M+H] + .

[0289] Example 12: (S)3-(8-bromo-6-(2-fluorophenyl)-1-(ethylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 12)

[0290] 1H NMR (300MHz, CDCl3-d1) δ7.67(dd,J=7.1,2.4Hz,1H),7.59(d,J=2.0Hz,1H),7.55-7.29(m,4H),7.22(dd,J=7.0,2.5Hz,1H ),5.22(s,1H),3.68(s,3H),3.18(s,2H),2.50(d,J=12.4Hz,1H),2.39(d,J=12.4Hz,1H),2.37-2.19(m,2H),1.39(s,3H); 13 C NMR (75MHz, CDCl3-d1) δ173.78,160.03,147.02,144.40,140.17,138.02,131.75,129.69,129.44,129.40,127.05 ,124.20,122.44,119.90,116.44,115.82,54.38,51.46,32.25,28.40,27.60,14.23; LC-MS(ESI)m / z:504.4[M+H] + .

[0291] Example 13: (S)3-(8-nitro-6-(2-fluorophenyl)-1-(ethylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 13)

[0292] 1 H NMR(300MHz, CDCl3-d1)δ8.30(dd,J=7.5,2.0Hz,1H),8.17(d,J=2.0Hz,1H),7.75(d,J=7.5Hz,1H),7.66-7.56(m,1H),7.47–7.31(m,2H), 7.32-7.22(m,1H),5.15(s,1H),3.68(s,3H),3.18(s,2H),2.53(d,J=12.4Hz,1H),2.45-2.33(m,2H),2.23(d,J=12.4Hz,1H),1.40(s,3H); 13C NMR (75MHz, CDCl3-d1) δ173.90,160.03,148.47,146.96,144.00,143.52,141.28,129.50,129.44,128.71,124.87 ,124.15,122.86,122.44,120.52,115.88,54.38,51.43,32.25,28.40,27.60,14.23; LC-MS(ESI)m / z:470.5[M+H] + .

[0293] Example 14: (S)3-(8-chloro-6-(2-fluorophenyl)-1-(propylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 14)

[0294] 1 H NMR(300MHz, CDCl3-d1)δ:7.78-7.61(m,3H),7.48(q,J=8.3Hz,1H),7.34-7.24(m,2H),7.05(t,J=9.0Hz,1H),4.23( t,J=6.2Hz,1H),3.68(s,3H),3.22(t,J=7.0Hz,2H),2.90-2.72(m,4H),1.77(q,J=7.1Hz,2H),1.01(t,J=7.2Hz,3H); 13 C NMR(75MHz, CDCl3-d1)δ:173.89,163.69,162.02,158.68,157.40,150.42,133.67,132.70,131.50,131.27,130.42,1 29.65,127.06,125.11,124.57,116.45,55.11,51.63,35.33,30.21,26.54,22.68,13.17; LC-MS(ESI)m / z:473.1[M+H] + .

[0295] Example 15: (S)3-(8-bromo-6-(2-fluorophenyl)-1-(propylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 15)

[0296] 1H NMR (300MHz, CDCl3-d1) δ7.67(dd,J=7.0,2.4Hz,1H),7.62-7.29(m,6H),7.21(dd,J=6.9,2.5Hz,1H),5.17(s ,1H),3.68(s,3H),3.24(s,2H),2.50(d,J=12.4Hz,1H),2.452.19(m,3H),1.80(d,J=0.4Hz,3H),1.01(s,3H); 13 C NMR (75MHz, CDCl3-d1) δ173.78,160.03,147.02,145.70,140.80,138.02,131.75,129.84,129.69,129.44,127.05,12 4.20,122.44,121.80,116.44,115.82,54.38,51.45,32.86,32.25,27.67,27.60,14.10; LC-MS(ESI)m / z:518.4[M+H] + .

[0297] Example 16: (S)3-(8-nitro-6-(2-fluorophenyl)-1-(propylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 16)

[0298] 1 H NMR (300MHz, CDCl3-d1) δ8.28 (dd, J=7.5, 2.0Hz, 1H), 8.17 (d, J=1.9Hz, 1H), 7.7 5(d,J=7.5Hz,1H),7.64(dd,J=5.7,3.8Hz,1H),7.40(dd,J=5.6,3.9Hz,2H),7.2 8(dd,J=5.6,3.9Hz,1H),5.15(s,1H),3.68(s,3H),3.28(s,2H),2.53(d,J=12.4 Hz,1H),2.40(d,J=12.4Hz,1H),2.24(d,J=1.5Hz,2H),1.79(s,2H),1.03(s,3H); 13C NMR (75MHz, CDCl3-d1) δ173.90,160.03,148.47,145.70,144.82,143.03,142.03,129.44,128.90,128.71,124.87,12 4.15,122.86,122.44,120.52,115.82,54.33,51.46,33.02,32.86,27.67,27.60,14.09; LC-MS(ESI)m / z:484.5[M+H] + .

[0299] Example 17: (S)3-(8-chloro-6-(2-fluorophenyl)-1-((2-hydroxyethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 17)

[0300] 1 H NMR (300MHz, CDCl3-d1)δ:7.78-7.61(m,3H),7.48(q,J=7.3Hz,1H),7.34-7.24(m,2H),7.05(t,J=10. 0Hz,1H),4.25-4.13(m,2H),3.99(q,J=5.6Hz,2H),3.68(s,3H),3.49-3.35(m,2H),2.90-2.72(m,4H); 13 C NMR(75MHz, CDCl3-d1)δ:173.81,163.79,162.01,158.67,157.51,150.84,133.95,132.78,131.69,131.27,130.1 7,129.77,126.92,125.06,124.58,116.50,61.90,54.99,51.66,36.08,30.13,26.46; LC-MS(ESI)m / z:475.1[M+H] + .

[0301] Example 18: (S)3-(8-bromo-6-(2-fluorophenyl)-1-((2-hydroxyethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diazide Methyl hetero-4-yl)propionate (compound 18)

[0302] 1H NMR (300MHz, CDCl3-d1) δ7.67(dd,J=7.0,2.4Hz,1H),7.62–7.46(m,2H),7.47-7.29(m,2H),7.21(dd,J=6.9,2.5Hz,1H),7.11(d,J=7.5Hz,1H),5. 15(s,1H),4.58(t,J=5.5Hz,1H),3.71-3.49(m,6H),3.43(d,J=12.4Hz,1 H),2.50(d,J=12.4Hz,1H),2.39(d,J=12.4Hz,1H),2.24(d,J=1.6Hz,2H); 13 C NMR (75MHz, CDCl3-d1) δ173.78,160.03,147.02,145.12,140.80,138.02,131.75,129.84,129.65,129.44,127.05 ,124.20,122.44,121.80,116.44,115.82,61.40,54.38,51.45,34.93,32.03,27.60; LC-MS(ESI)m / z:520.4[M+H] + .

[0303] Example 19: (S)3-(8-nitro-6-(2-fluorophenyl)-1-((2-hydroxyethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diazide Methyl hetero-4-yl)propionate (compound 19)

[0304] 1 H NMR (300MHz, CDCl3-d1) δ8.28 (dd, J=7.5, 2.0Hz, 1H), 8.17 (d, J=2.0Hz, 1H), 7.75 (d,J=7.5Hz,1H),7.64(dd,J=5.7,3.8Hz,1H),7.40(dd,J=5.6,3.9Hz,2H),7.41- 7.23(m,1H),5.15(s,1H),4.27(t,J=5.5Hz,1H),3.71-3.54(m,6H),3.51(d,J=12 .4Hz,1H),2.53(d,J=12.4Hz,1H),2.40(d,J=12.4Hz,1H),2.24(d,J=1.6Hz,2H); 13C NMR (75MHz, CDCl3-d1) δ173.90,160.03,148.47,145.70,144.82,143.03,142.03,129.44,128.90,128.71,124.87 ,124.15,122.86,122.44,121.02,115.82,61.63,54.33,51.46,35.01,33.02,27.60; LC-MS(ESI)m / z:486.5[M+H] + .

[0305] Example 20: (S)3-(8-chloro-6-(2-fluorophenyl)-1-((2-aminoethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 20)

[0306] 1 H NMR(300MHz, CDCl3-d1)δ:7.78-7.61(m,3H),7.48(q,J=5.4Hz,1H),7.34-7.24(m,2H),7. 05(t,J=9.0Hz,1H),4.38-4.21(m,3H),3.68(s,3H),3.46-3.22(m,4H),2.90-2.72(m,4H); 13 C NMR(75MHz, CDCl3-d1)δ:173.84,163.79,162.00,158.65,157.61,150.05,133.93,132.74,131.74,131.24,130.0 9,129.69,126.95,125.11,124.56,116.48,54.98,51.65,40.72,31.58,30.15,26.45; LC-MS(ESI)m / z:474.0[M+H] + .

[0307] Example 21: (S)3-(8-bromo-6-(2-fluorophenyl)-1-((2-aminoethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 21)

[0308] 1H NMR (300MHz, CDCl3-d1) δ7.67 (dd, J = 7.0, 2.5Hz, 1H), 7.62-7.46 (m, 2H), 7. 47-7.29(m,2H),7.21(dd,J=6.9,2.5Hz,1H),7.04(d,J=7.5Hz,1H),5.15(s, 1H),4.49(d,J=0.7Hz,1H),4.37(d,J=0.7Hz,1H),3.71-3.51(m,5H),2.95(s ,2H),2.50(d,J=12.4Hz,1H),2.39(d,J=12.4Hz,1H),2.24(d,J=1.5Hz,2H); 13 C NMR (75MHz, CDCl3-d1) δ173.78,160.03,147.02,145.12,140.80,138.02,131.75,129.84,129.69,129.44,127.05 ,124.20,122.44,121.80,116.44,115.82,54.38,51.45,39.99,34.13,32.03,27.60; LC-MS(ESI)m / z:519.4[M+H] + .

[0309] Example 22: (S)3-(8-nitro-6-(2-fluorophenyl)-1-((2-aminoethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 22)

[0310] 1 H NMR (300MHz, CDCl3-d1) δ8.29(dd,J=7.5,2.0Hz,1H),8.17(d,J=2.0Hz,1H),7.75(d,J =7.5Hz,1H),7.64(dd,J=5.7,3.8Hz,1H),7.40(dd,J=5.6,3.9Hz,2H),7.41-7.23(m,1H ),5.15(s,1H),4.49(d,J=0.7Hz,1H),4.37(d,J=0.7Hz,1H),3.65(d,J=17.9Hz,5H),3. 00-2.82(m,2H),2.53(d,J=12.4Hz,1H),2.40(d,J=12.4Hz,1H),2.24(d,J=1.6Hz,2H); 13C NMR (75MHz, CDCl3-d1) δ173.90,160.03,148.47,145.70,144.82,143.03,142.03,129.44,128.90,128.71,124.87 ,124.15,122.86,122.44,120.52,115.82,54.33,51.46,39.99,34.37,33.02,27.60; LC-MS(ESI)m / z:485.5[M+H] + .

[0311] Example 23: (S)3-(8-chloro-6-(2-chlorophenyl)-1-(methylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 23)

[0312] 1 H NMR(300MHz, CDCl3-d1)δ:7.74(d,J=8.6Hz,1H),7.64-7.54(m,2H),7.43-7.3 3(m,3H),7.19(s,1H),4.28(t,J=6.4Hz,1H),3.68(s,3H),2.90-2.76(m,7H); 13 C NMR(75MHz, CDCl3-d1)δ:173.83,166.45,157.49,151.12,138.02,133.68,132.84,131.57,131.35,131.30,13 1.00,130.94,130.25,129.49,127.19,124.62,55.10,51.63,30.18,26.50,15.25; LC-MS(ESI)m / z:461.1[M+H] + .

[0313] Example 24: (S)3-(8-bromo-6-(2-chlorophenyl)-1-(methylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 24)

[0314] 1H NMR(300MHz, CDCl3-d1)δ7.66(dd,J=7.4,1.9Hz,1H),7.62-7.44(m,3H),7.51-7.27(m,3H),7.34-7.2 4(m,1H),5.32(s,1H),3.68(s,3H),2.53(d,J=28.9Hz,4H),2.45-2.26(m,2H),2.25(d,J=12.4Hz,1H); 13 C NMR (75MHz, CDCl3-d1) δ173.78,150.29,149.26,147.02,140.80,133.13,132.57,131.75,130.86,129.62,128 .97,128.62,125.51,124.07,118.85,118.19,54.38,51.46,32.25,27.63,14.05; LC-MS(ESI)m / z:506.8[M+H] + .

[0315] Example 25: (S)3-(8-nitro-6-(2-chlorophenyl)-1-(methylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 25)

[0316] 1 H NMR(300MHz, CDCl3-d1)δ8.33(dd,J=7.5,2.0Hz,1H),8.17(d,J=2.1Hz,1H),7.68-7.54(m,2H),7.54-7.31(m, 3H),5.22(s,1H),3.68(s,3H),2.56(s,3H),2.53(d,J=12.4Hz,1H),2.40(d,J=12.4Hz,1H),2.35-2.17(m,2H); 13 C NMR (75MHz, CDCl3-d1) δ173.78,150.96,150.29,148.47,143.37,141.28,134.20,130.98,130.35,129.35,128 .71,128.62,124.17,123.83,122.86,121.02,54.38,51.43,32.25,27.60,14.05; LC-MS(ESI)m / z:472.9[M+H] + .

[0317] Example 26: (S)3-(8-chloro-6-(2-chlorophenyl)-1-(ethylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 26)

[0318] 1 H NMR(300MHz, CDCl3-d1)δ:7.74(d,J=8.5Hz,1H),7.64-7.54(m,2H),7.43-7.33(m,3H),7.19(s,1H), 4.28(t,J=6.2Hz,1H),3.68(s,3H),3.34(q,J=7.6Hz,2H),2.90-2.72(m,4H),1.42(t,J=7.1Hz,3H); 13 C NMR(75MHz, CDCl3-d1)δ:173.83,166.46,157.23,150.27,138.05,133.63,132.82,131.46,131.32,131.30,130.9 8,130.95,130.21,129.36,127.19,125.04,55.14,51.63,30.20,27.68,26.49,14.77; LC-MS(ESI)m / z:475.1[M+H] + .

[0319] Example 27: (S)3-(8-bromo-6-(2-chlorophenyl)-1-(ethylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 27)

[0320] 1 H NMR(300MHz, CDCl3-d1)δ7.71-7.61(m,1H),7.60(d,J=2.0Hz,1H),7.57-7.25(m,6H),5.32(s,1H),3.6 8(s,3H),3.18(s,2H),2.50(d,J=12.4Hz,1H),2.45-2.26(m,2H),2.25(d,J=12.4Hz,1H),1.39(s,3H); 13C NMR (75MHz, CDCl3-d1) δ173.78,149.26,147.02,144.40,140.17,133.47,132.57,131.75,130.98,129.65,128.97 ,128.62,127.05,124.07,122.26,116.44,54.38,51.48,32.03,29.80,28.40,14.23; LC-MS(ESI)m / z:520.8[M+H] + .

[0321] Example 28: (S)3-(8-nitro-6-(2-chlorophenyl)-1-(ethylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 28)

[0322] 1 H NMR (300MHz, CDCl3-d1) δ8.30(dd,J=7.5,2.0Hz,1H),8.19(d,J=2.0Hz,1H),7.75(d,J=7.5Hz,1H),7.61(dd,J=7.4,2.0Hz,1H),7.54-7 .31(m,3H),5.22(s,1H),3.68(s,3H),3.18(s,2H),2.53(d,J=12.4Hz,1H),2.40(d,J=12.4Hz,1H),2.24(d,J=1.5Hz,2H),1.40(s,3H); 13 C NMR (75MHz, CDCl3-d1) δ173.90,150.96,147.02,144.00,143.37,141.28,133.92,130.98,130.35,129.31,128.71 ,128.54,124.07,123.83,122.86,121.02,54.38,51.46,32.25,28.40,27.60,14.23; LC-MS(ESI)m / z:486.9[M+H] + .

[0323] Example 29: (S)3-(8-chloro-6-(2-chlorophenyl)-1-(propylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 29)

[0324] 1H NMR(300MHz, CDCl3-d1)δ:7.76-7.19(m,7H),4.28(t,J=5.7Hz,1H),3.68(s,3H),3.3 0(t,J=13.8Hz,2H),2.90-2.72(m,4H),1.81(q,J=6.7Hz,2H),1.04(t,J=6.9Hz,3H); 13 C NMR(75MHz, CDCl3-d1)δ:173.85,166.46,157.22,150.50,138.06,133.61,132.84,131.47,131.35,131.29,130.99,1 30.95,130.22,129.35,127.18,125.09,55.19,51.64,35.17,30.23,26.52,22.73,13.23; LC-MS(ESI)m / z:488.9[M+H] + .

[0325] Example 30: (S)3-(8-bromo-6-(2-chlorophenyl)-1-(propylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 30)

[0326] 1 H NMR(300MHz, CDCl3-d1)δ7.99-7.88(m,2H),7.79(dd,J=8.4,2.5Hz,1H),7.59-7 .49(m,1H),7.51-7.39(m,2H),7.41-7.27(m,1H),6.06-5.90(m,1H),3.62(s,2H ),3.32(dt,J=14.5,6.4Hz,1H),3.17(dt,J=14.5,6.4Hz,1H),2.79-2.62(m,1H) ,2.58-2.40(m,2H),2.44-2.24(m,1H),1.93-1.58(m,2H),1.02(t,J=7.6Hz,3H); 13C NMR (75MHz, CDCl3-d1) δ173.45,162.53,154.57,153.88,138.65,136.35,134.47,133.31,132.86,130.41,129.64,12 9.59,128.37,126.63,122.44,119.72,55.11,51.90,34.69,29.81,29.59,22.63,13.16; LC-MS(ESI)m / z:532.03[M+H] + .

[0327] Example 31: (S)3-(8-nitro-6-(2-chlorophenyl)-1-(propylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 31)

[0328] 1 H NMR (300MHz, CDCl3-d1) δ8.46 (dd, J=8.5, 2.1Hz, 1H), 8.36 (d, J=2.1Hz, 1H), 8.25(d,J=8.5Hz,1H),7.57(dd,J=7.8,1.5Hz,1H),7.54-7.36(m,2H),7.35( td,J=7.6,1.5Hz,1H),5.12-4.94(m,1H),3.61(s,2H),3.38-3.13(m,2H),2. 70-2.46(m,3H),2.35-2.17(m,1H),1.92-1.58(m,2H),1.03(t,J=7.6Hz,3H); 13 C NMR (75MHz, CDCl3-d1) δ173.50,162.06,154.57,153.88,146.01,138.70,137.82,134.63,130.41,129.65,128.42,12 8.36,128.20,126.67,125.98,123.39,55.11,51.90,34.69,29.70,29.62,22.63,13.16; LC-MS(ESI)m / z:499.11[M+H] + .

[0329] Example 32: (S)3-(8-chloro-6-(2-chlorophenyl)-1-((2-hydroxyethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 32)

[0330] 1 H NMR(300MHz, CDCl3-d1)δ:7.75(d,J=8.6Hz,1H),7.64-7.55(m,2H),7.45-7.33(m,3H),7.19(s,1 H),4.28(t,J=5.3Hz,1H),4.11-3.96(m,3H),3.68(s,3H),3.51-3.42(m,2H),2.90-2.72(m,4H); 13 C NMR(75MHz, CDCl3-d1)δ:173.79,166.57,157.42,150.92,137.91,133.98,132.83,131.65,131.39,131.29,130.9 8,130.71,130.27,129.48,127.22,125.07,62.20,55.08,51.68,36.05,30.15,26.42; LC-MS(ESI)m / z:491.4[M+H] + .

[0331] Example 33: (S)3-(8-bromo-6-(2-chlorophenyl)-1-((2-hydroxyethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 33)

[0332] 1 H NMR (300MHz, CDCl3-d1) δ7.99-7.88 (m, 2H), 7.81 (dd, J = 8.4, 2.5Hz, 1H), 7.59 -7.48(m,1H),7.51-7.39(m,2H),7.39-7.27(m,1H),6.07-5.90(m,1H),4.40(t ,J=7.2Hz,1H),3.75(q,J=7.0Hz,2H),3.62(s,3H),3.67–3.51(m,1H),3.39(dt ,J=15.0,6.8Hz,1H),2.78-2.60(m,1H),2.60-2.38(m,2H),2.41-2.22(m,1H); 13C NMR (75MHz, CDCl3-d1) δ173.42,162.52,154.54,153.87,138.65,136.35,134.89,133.44,132.85,130.33,129.69 ,129.62,128.28,126.66,122.43,119.94,60.25,55.10,51.89,35.35,29.70,29.59; LC-MS(ESI)m / z:534.01[M+H] + .

[0333] Example 34: (S)3-(8-nitro-6-(2-chlorophenyl)-1-((2-hydroxyethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 34)

[0334] 1 H NMR (300MHz, CDCl3-d1) δ8.49-8.35(m,2H),8.26(d,J=8.4Hz,1H),7.57(dd,J=7.8,1.4Hz,1H),7.54-7.38(m,2H),7.34(td,J=7.5,1.5Hz,1H),5.0 9-4.93(m,1H),4.40(t,J=7.2Hz,1H),3.82-3.63(m,2H),3.61(s,3H),3. 68-3.40(m,2H),2.77-2.60(m,1H),2.61-2.42(m,2H),2.35-2.16(m,1H); 13 C NMR (75MHz, CDCl3-d1) δ173.40,162.06,154.59,153.87,146.02,138.70,137.80,134.47,130.33,129.69,128.29 ,128.18,127.85,126.71,125.90,123.39,60.27,55.10,51.90,35.34,29.65,29.60; LC-MS(ESI)m / z:501.09[M+H] + .

[0335] Example 35: (S)3-(8-chloro-6-(2-chlorophenyl)-1-((2-aminoethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 35)

[0336] 1 H NMR(300MHz, CDCl3-d1)δ:7.79(d,J=8.7Hz,1H),7.62-7.51(m,2H),7.41-7.31(m,3H), 7.15(s,1H),6.46(s,2H),4.24(t,J=7.8Hz,1H),3.77-3.52(m,7H),2.82-2.73(m,4H); 13 C NMR(75MHz, CDCl3-d1)δ:173.80,166.72,157.62,150.17,137.84,134.11,132.82,131.95,131.37,131.23,130.9 3,130.39,130.27,129.39,127.18,125.15,54.93,51.71,40.16,31.60,30.15,26.31; LC-MS(ESI)m / z:490.2[M+H] + .

[0337] Example 36: (S)3-(8-bromo-6-(2-chlorophenyl)-1-((2-aminoethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 36)

[0338] 1 H NMR(300MHz, CDCl3-d1)δ7.98-7.88(m,2H),7.81(dd,J=8.3,2.5Hz,1H),7.59-7 .49(m,1H),7.51-7.39(m,2H),7.39-7.27(m,1H),6.06-5.89(m,1H),3.74(t,J= 6.1Hz,2H),3.62(s,2H),3.48(dt,J=15.6,5.8Hz,1H),3.34(dt,J=15.6,5.9Hz, 1H),3.18-2.88(m,2H),2.79-2.61(m,1H),2.59-2.37(m,2H),2.41-2.22(m,1H); 13C NMR (75MHz, CDCl3-d1) δ173.42,162.53,154.45,153.86,138.65,136.35,134.80,133.38,132.85,130.33,129.69 ,129.62,128.28,126.66,122.43,119.94,55.10,51.89,40.95,35.18,29.70,29.59; LC-MS(ESI)m / z:533.03[M+H] + .

[0339] Example 37: (S)3-(8-nitro-6-(2-chlorophenyl)-1-((2-aminoethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 37)

[0340] 1 H NMR (300MHz, CDCl3-d1) δ8.47(dd,J=8.5,2.1Hz,1H),8.37(d,J=2.1Hz,1H),8.27(d,J=8.4H z,1H),7.56(dd,J=7.7,1.5Hz,1H),7.56-7.38(m,2H),7.34(td,J=7.5,1.5Hz,1H),5.08-4.9 0(m,1H),3.74(t,J=6.1Hz,2H),3.64-3.33(m,4H),3.14(dp,J=14.6,6.0Hz,1H),2.98(dp,J =14.6,5.9Hz,1H),2.74-2.57(m,1H),2.62-2.42(m,2H),2.26(dtd,J=11.0,8.4,7.7Hz,1H); 13 C NMR (75MHz, CDCl3-d1) δ173.39,162.06,154.50,153.88,146.02,138.70,137.80,134.48,130.33,129.69,128.29 ,128.17,127.79,126.71,125.90,123.39,55.10,51.90,40.95,35.19,29.65,29.60; LC-MS(ESI)m / z:500.10[M+H] + .

[0341] Example 38: (S)3-(8-chloro-6-(2-chlorophenyl)-1-(acetylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 38)

[0342] 1 H NMR(300MHz, CDCl3-d1)δ:8.49(d,J=8.8Hz,1H),7.64(d,J=9.5Hz,1H),7.51-7.39(m,4H), 7.15(d,J=3.2Hz,1H),4.28(t,J=5.8Hz,1H),3.68(s,3H),2.80-2.62(m,4H),2.30(s,3H); 13 C NMR(75MHz, CDCl3-d1)δ:173.46,168.18,167.82,166.20,151.61,141.72,137.59,134.00,133.16,132.08,131.51 ,131.07,130.85,130.49,129.00,127.37,127.07,54.77,51.81,29.81,25.73,20.63; LC-MS(ESI)m / z:489.4[M+H] + .

[0343] Example 39: (S)3-(8-bromo-6-(2-chlorophenyl)-1-(acetylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 39)

[0344] 1 H NMR (300MHz, CDCl3-d1) δ8.10(d,J=8.3Hz,1H),7.96(d,J=2.5Hz,1H),7.79(dd,J=8.4,2.5Hz,1H),7.57 -7.27(m,4H),6.06-5.93(m,1H),3.62(s,3H),2.71-2.44(m,3H),2.45-2.22(m,4H); 13C NMR (75MHz, CDCl3-d1) δ185.25,173.42,162.53,154.37,148.67,138.65,136.35,134.79,133.71,132.84,130.33, 129.63,129.62,128.28,126.66,122.42,119.94,55.10,51.89,30.14,29.65,29.59; LC-MS(ESI)m / z:532.00[M+H] + .

[0345] Example 40: (S)3-(8-nitro-6-(2-chlorophenyl)-1-(acetylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 40)

[0346] 1 H NMR (300MHz, CDCl3-d1) δ8.54-8.36(m,2H),8.34(d,J=2.0Hz,1H),7.55(ddd,J=7.7,6.0,1.8Hz,2H),7.53-7. 32(m,2H),5.99(ddd,J=8.2,7.4,0.8Hz,1H),3.61(s,2H),2.71-2.40(m,3H),2.42(s,3H),2.44-2.25(m,1H); 13 C NMR (75MHz, CDCl3-d1) δ185.25,173.39,162.06,154.37,148.19,146.02,138.70,138.07,134.47,130.33,129.69, 128.29,128.21,128.17,126.71,125.90,123.40,55.10,51.90,30.14,29.65,29.60; LC-MS(ESI)m / z:499.07[M+H] + .

[0347] Example 41: (S)3-(8-chloro-6-(2-chlorophenyl)-1-mercapto-4H-benzo[f][1,2,4]triazolo[4,3-a][1,4]diaza ethyl 4-yl)propionate (compound 41)

[0348] 1H NMR(300MHz, CDCl3-d1)δ:12.39(s,1H),8.52(d,J=8.7Hz,1H),7.62(d,J=8.6Hz,1H),7.64-7.38(m,4H ),7.14(s,1H),4.28(t,J=6.3Hz,1H),4.14(q,J=7.0Hz,2H),2.76-2.57(m,4H),1.23(t,J=7.1Hz,3H); 13 C NMR(75MHz, CDCl3-d1)δ:173.32,168.00,167.13,153.25,137.67,133.88,133.07,131.81,131.39,131.17 ,130.91,130.82,130.40,129.14,127.01,60.70,54.92,30.18,25.84,14.19; LC-MS(ESI)m / z:461.0[M+H] + .

[0349] Example 42: (S)3-(8-chloro-6-(2-chlorophenyl)-1-(methylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza ethyl 4-yl)propionate (compound 42)

[0350] 1 H NMR(300MHz, CDCl3-d1)δ:7.75(d,J=8.5Hz,1H),7.64-7.56(m,2H),7.43-7.31(m,3H),7.19( s,1H),4.28(t,J=5.6Hz,1H),4.14(q,J=7.0Hz,2H),2.90-2.76(m,7H)1.24(t,J=6.6Hz,3H); 13 C NMR(75MHz, CDCl3-d1)δ:173.44,166.45,157.55,151.14,138.05,133.70,132.88,131.60,131.38,131.0 2,130.28,129.51,127.22,124.63,60.43,55.14,30.46,26.54,15.27,14.24; LC-MS(ESI)m / z:475.1[M+H] + .

[0351] Example 43: (S)3-(8-bromo-6-(2-chlorophenyl)-1-(methylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza ethyl 4-yl)propionate (compound 43)

[0352] 1 H NMR (300MHz, CDCl3-d1) δ7.99-7.87(m,2H),7.80(dd,J=8.4,2.5Hz,1H),7.53(dd,J=8.0,1.6Hz,1H),7.51-7.39(m,2H),7.3 9-7.27(m,1H),5.02(ddd,J=8.3,7.6,0.7Hz,1H),4.21-3.97(m,2H),2.64(s,3H),2.73–2.26(m,4H),1.18(t,J=6.9Hz,3H); 13 CNMR(75MHz, CDCl3-d1)δ172.72,162.53,154.47,153.45,138.65,136.35,134.56,133.15,132.85,130.33,129.69 ,129.62,128.28,126.67,122.44,119.73,60.67,55.10,30.27,29.68,16.53,14.18; LC-MS(ESI)m / z:518.02[M+H] + .

[0353] Example 44: (S)3-(8-nitro-6-(2-chlorophenyl)-1-(methylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza ethyl 4-yl)propionate (compound 44)

[0354] 1 H NMR (300MHz, CDCl3-d1) δ8.52-8.35(m,2H),8.25(d,J=8.4Hz,1H),7.56(dd,J=7.7,1.5Hz,1H),7.53-7.39(m,2H),7.33(td,J=7.5,1.5Hz ,1H),5.02-4.87(m,1H),4.21-3.97(m,2H),2.75-2.58(m,1H),2.64(s,3H),2.61-2.39(m,2H),2.33-2.15(m,1H),1.18(t,J=6.9Hz,3H); 13C NMR (75MHz, CDCl3-d1) δ172.77,161.98,154.47,153.47,146.09,138.70,137.56,134.51,130.33,129.67,128.29 ,128.17,127.79,126.66,125.92,123.39,60.68,55.10,30.29,29.68,16.53,14.17; LC-MS(ESI)m / z:485.09[M+H] + .

[0355] Example 45: (S)-3-(8-chloro-1-((cyclopropylmethyl)thio)-6-(2-fluorophenyl)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 45)

[0356] 1 H NMR(300MHz, CDCl3-d1)δ:7.90(s,2H),7.62(dt,J=25.3,7.0Hz,2H),7.37(d,J=14.2Hz,2H),7.22(t,J=9.6Hz,1H),4.28(t, J=6.4Hz,1H),3.62(s,3H),3.07(d,J=7.2Hz,2H),2.77-2.57(m,4H),1.05(s,1H),0.45(d,J=7.9Hz,2H),0.24-0.12(m,2H); 13 CNMR(75MHz, CDCl3-d1)δ:173.57,163.45,161.94,161.87,161.44,156.52 ,153.90,134.08,133.03,132.44,132.38,131.36,130.59,130.53,129.90, 127.85,127.79,127.77,127.69,124.73,124.71,122.90,116.37,116.21,5 5.18,51.94,38.04,29.44,29.28,11.77,6.27; LC-MS(ESI)m / z:486.1[M+H] + .

[0357] Example 46: (S)-3-(8-bromo-1-((cyclopropylmethyl)thio)-6-(2-fluorophenyl)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 46)

[0358] 1 H NMR (300MHz, CDCl3-d1) δ7.97-7.83 (m, 2H), 7.80 (dd, J = 8.4, 2.5Hz, 1H), 7.53 (dddd,J=15.6,7.6,5.0,1.6Hz,2H),7.28(dtd,J=16.5,7.7,1.4Hz,2H),4.70- 4.53(m,1H),3.61(s,2H),3.36-3.21(m,1H),3.09-2.96(m,1H),2.71-2.53(m, 1H),2.58-2.42(m,2H),2.36(dtd,J=10.9,8.4,7.6Hz,1H),1.40-1.20(m,5H); 13 C NMR (75MHz, CDCl3-d1) δ173.43,163.16,162.00,161.89,159.80,154.35,1 53.86,136.35,133.54,132.91,131.57,131.46,130.46,130.36,128.86,12 8.82,126.92,126.66,124.26,124.22,122.43,119.98,115.98,115.71,55 .26,51.89,37.41,29.65,29.60,13.37,6.76; LC-MS(ESI)m / z:528.06[M+H] + .

[0359] Example 47: (S)-3-(8-nitro-1-((cyclopropylmethyl)thio)-6-(2-fluorophenyl)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 47)

[0360] 1 H NMR(300MHz, CDCl3-d1)δ8.46(dd,J=8.5,2.1Hz,1H),8.35–8.19(m,2H),7.63-7.44(m,2H),7.30(dtd,J=13.2,7.7,1.4Hz,2H),4 .93(t,J=8.1Hz,1H),3.61(s,2H),3.42-3.29(m,1H),3.05-2.91(m,1H),2.71-2.50(m,2H),2.55-2.27(m,2H),1.39-1.20(m,5H); 13C NMR (75MHz, CDCl3-d1) δ173.39,163.12,161.47,161.36,159.76,154.35,1 53.88,146.14,137.98,131.60,131.49,130.48,130.37,128.16,127.31,12 7.25,127.07,126.81,126.00,124.32,124.28,123.39,115.95,115.68,55 .26,51.90,37.41,29.65,29.61,13.37,6.76; LC-MS(ESI)m / z:495.14[M+H] + .

[0361] Example 48: (S)-3-(8-chloro-6-(2-fluorophenyl)-1-(prop-2-yn-1-ylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 48)

[0362] 1 H NMR(400MHz, CDCl3-d1)δ:7.95-7.85(m,2H),7.68-7.53(m,2H),7.42-7.30(m,2H),7.28-7.18(m,1H),4.30 (dd,J=8.0,5.5Hz,1H),3.98(qd,J=16.4,2.6Hz,2H),3.62(s,3H),3.17(t,J=2.6Hz,1H),2.80-2.54(m,4H); 13 CNMR(75MHz, CDCl3-d1)δ:173.35,163.77,161.57,161.23,161.14,156.64, 153.26,134.21,133.16,132.95,132.63,131.36,130.71,130.55,129.34,1 27.76,127.65,127.58,127.39,124.83,124.53,123.25,116.64,116.33,79 .82,72.44,55.37,51.62,29.43,29.30,20.68; LC-MS(ESI)m / z:469.2[M+H] + .

[0363] Example 49: (S)-3-(8-bromo-6-(2-fluorophenyl)-1-(prop-2-yn-1-ylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 49)

[0364] 1 H NMR(300MHz, CDCl3-d1)δ7.91(d,J=8.4Hz,1H),7.88-7.74(m,2H),7.63-7.44(m,2H),7.37-7.19(m,2H),4.90 (t,J=8.0Hz,1H),4.07(dd,J=12.4,3.0Hz,1H),3.85(dd,J=12.4,3.0Hz,1H),3.62(s,2H),2.71-2.27(m,5H); 13 C NMR (75MHz, CDCl3-d1) δ173.39,163.17,162.00,161.89,159.80,154.01,1 53.86,136.35,133.51,132.85,131.57,131.46,130.43,130.33,128.86,12 8.82,126.93,126.66,124.29,124.25,122.43,119.81,115.98,115.71,79. 08,72.66,55.26,51.89,29.65,29.59,20.39; LC-MS(ESI)m / z:512.03[M+H] + .

[0365] Example 50: (S)-3-(8-nitro-6-(2-fluorophenyl)-1-(prop-2-yn-1-ylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 50)

[0366] 1H NMR (300MHz, CDCl3-d1) δ8.48(dd,J=8.5,2.1Hz,1H),8.33(d,J=2.1Hz,1H),8.22(d,J=8.5Hz,1H),7.63-7.45(m,2H),7.29(dtd,J=16 .4,7.7,1.4Hz,2H),4.90(t,J=8.1Hz,1H),4.08(dd,J=12.3,3.0Hz,1H),3.87(dd,J=12.3,3.0Hz,1H),3.61(s,2H),2.73-2.26(m,5H); 13 C NMR (75MHz, CDCl3-d1) δ173.41,163.13,161.47,161.36,159.77,154.02,1 53.88,146.14,137.89,131.58,131.46,130.43,130.33,128.17,127.36,12 7.32,127.07,126.81,126.05,124.33,124.29,123.39,115.98,115.71,79. 07,72.67,55.26,51.90,29.65,29.61,20.39; LC-MS(ESI)m / z:479.11[M+H] + .

[0367] Example 51: (S)-3-(8-chloro-6-(2-fluorophenyl)-1-((2-morpholinoethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 51)

[0368] 1 H NMR(300MHz, CDCl3-d1)δ:7.93(s,2H),7.75-7.52(m,2H),7.45-7.31(m,2H),7.30-7.18(m,1H),4.31( d,J=5.9Hz,1H),3.63(s,3H),3.55-3.45(m,4H),3.35(d,J=6.7Hz,2H),2.86-2.55(m,6H),2.36(s,4H); 13C NMR(75MHz, CDCl3-d1)δ:173.54,163.45,161.75,161.42,161.17,156.34,15 3.67,134.62,133.22,132.15,132.07,131.46,130.36,130.22,129.77,127. 83,127.72,127.68,127.61,124.84,124.71,122.83,116.41,116.33,66.57, 55.24,53.94,53.56,51.78,30.26,29.56,29.35; LC-MS(ESI)m / z:547.1[M+H] + .

[0369] Example 52: (S)-3-(8-bromo-6-(2-fluorophenyl)-1-((2-morpholinoethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 52)

[0370] 1 H NMR (300MHz, CDCl3-d1) δ: 8.06 (dd, J=8.7, 2.2Hz, 1H), 7.85 (d, J=8.7Hz, 1H), 7.74-7.47 (m, 3H), 7.37 (t, J=7.5Hz, 1H), 7.25 (dd, J=10.6,8.6Hz,1H),4.30(t,J=6.6Hz,1H),3.64(s,3H),3.53-3.46(m,4H),3.35(d,J=6.8Hz,2H),2.89-2.56(m,6H),2.36(s,4H); 13 C NMR (75MHz, CDCl3-d1) δ173.40,163.21,162.00,161.89,159.85,154.56,153 .86,136.19,133.51,132.95,131.61,131.50,130.38,130.28,128.98,128.9 4,126.92,126.66,124.32,124.28,122.44,119.83,115.98,115.71,65.42,5 5.26,53.50,52.67,51.93,30.41,29.65,29.61; LC-MS(ESI)m / z:591.90[M+H] + .

[0371] Example 53: (S)-3-(8-nitro-6-(2-fluorophenyl)-1-((2-morpholinoethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 53)

[0372] 1 H NMR (300MHz, CDCl3-d1) δ8.52(dd,J=8.5,2.1Hz,1H),8.38(d,J=2.1Hz,1H),8.22(d,J=8.4Hz,1H),7.64-7.46(m,2H),7.37-7.20(m,2H),6 .05-5.91(m,1H),3.66-3.50(m,7H),3.37(dt,J=14.3,5.2Hz,1H),2.81(dt,J=12.0,5.2Hz,1H),2.71–2.40(m,6H),2.42-2.22(m,3H).13C NMR (75MHz, CDCl3-d1) δ173.37,163.30,161.48,161.38,159.94,154.57,153 .88,146.17,137.95,131.60,131.49,130.54,130.43,128.17,127.60,127.5 6,127.08,126.81,125.94,124.26,124.22,123.35,115.98,115.71,65.46,5 5.26,53.55,52.62,51.89,30.41,29.67,29.61; LC-MS(ESI)m / z:555.60[M+H] + .

[0373] Example 54: (S)-3-(8-chloro-1-((2-(diethylamino)ethyl)thio)-6-(2-fluorophenyl)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 54)

[0374] 1H NMR (300MHz, CDCl3-d1) δ: 7.90 (d, J = 1.8 Hz, 2H), 7.69-7.53 (m, 2H), 7.41-7.31 (m, 2H), 7.29-7.17 (m, 1H), 4.27 (dd, J = 7.7, 5. 5Hz,1H),3.61(s,3H),3.30-3.22(m,2H),2.80-2.68(m,3H),2.68-2.52(m,4H),2.45(q,J=7.1Hz,6H),0.90(t,J=7.1Hz,6H); 13 CNMR(75MHz, CDCl3-d1)δ:173.49,163.48,161.84,161.77,161.52,156.36,1 53.37,134.73,133.25,132.58,132.39,131.41,130.67,130.46,129.73,127. 74,127.62,127.58,127.39,124.68,124.51,122.76,116.45,116.26,55.22, 51.83,51.53,47.82,30.37,29.51,29.33,11.51; LC-MS(ESI)m / z:531.6[M+H] + .

[0375] Example 55: (S)-3-(8-bromo-1-((2-(diethylamino)ethyl)thio)-6-(2-fluorophenyl)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 55)

[0376] 1 H NMR(300MHz, CDCl3-d1)δ7.96-7.84(m,2H),7.79(dd,J=8.4,2.5Hz,1H),7.53(dddd,J=16.9 ,7.6,5.0,1.6Hz,2H),7.28(dtd,J=16.4,7.7,1.4Hz,2H),6.05-5.89(m,1H),3.62(s,2H),3. 51(dt,J=14.1,5.2Hz,1H),3.35(dt,J=14.1,5.2Hz,1H),2.84(dt,J=12.2,5.2Hz,1H),2.77- 2.60(m,2H),2.66-2.47(m,4H),2.53-2.40(m,2H),2.43-2.24(m,1H),1.01(t,J=7.2Hz,6H); 13C NMR (75MHz, CDCl3-d1) δ173.41,163.21,162.00,161.89,159.85,154.56,153 .86,136.19,133.43,132.95,131.62,131.52,130.53,130.42,128.86,128.8 2,126.92,126.66,124.26,124.22,122.42,119.83,115.98,115.71,55.26,5 1.93,50.88,47.11,30.42,29.65,29.61,11.17; LC-MS(ESI)m / z:575.51[M+H] + .

[0377] Example 56: (S)-3-(8-nitro-1-((2-(diethylamino)ethyl)thio)-6-(2-fluorophenyl)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 56)

[0378] 1 H NMR (300MHz, CDCl3-d1) δ8.49 (dd, J=8.5, 2.1Hz, 1H), 8.32 (d, J=2.1Hz, 1H), 8.21 (d, J=8.5Hz,1H),7.54(dddd,J=20.4,7.6,5.0,1.7Hz,2H),7.37-7.20(m,2H),4.89(ddd ,J=8.2,7.5,0.6Hz,1H),3.62(s,2H),3.47(dt,J=14.1,5.2Hz,1H),3.33(dt,J=14.1 ,5.2Hz,1H),2.87(dt,J=12.1,5.2Hz,1H),2.79-2.26(m,9H),1.01(t,J=7.2Hz,6H); 13C NMR (75MHz, DMSO-d6) δ173.42,163.09,161.48,161.38,159.73,154.51,153. 88,146.17,137.95,131.60,131.49,130.49,130.38,128.17,127.60,127.56 ,127.08,126.81,126.00,124.26,124.22,123.37,115.98,115.71,55.26,51 .91,50.88,47.11,30.42,29.67,29.61,11.17; LC-MS(ESI)m / z:541.61[M+H] + .

[0379] Example 57: (S)-3-(8-chloro-1-((3-(dimethylamino)propyl)thio)-6-(2-fluorophenyl)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 57)

[0380] 1 H NMR(300MHz, CDCl3-d1)δ:7.92-7.84(m,2H),7.65(td,J=7.6,1.8Hz,1H),7 .58(tdd,J=7.5,5.2,1.8Hz,1H),7.42-7.31(m,2H),7.22(dd,J=10.9,8.3H z,1H),4.28(dd,J=7.7,5.5Hz,1H),3.61(s,3H),3.24-3.06(m,2H),2.78-2 .52(m,4H),2.39(tt,J=6.9,4.3Hz,2H),2.18(s,6H),1.79(q,J=7.1Hz,2H); 13 C NMR(75MHz, CDCl3-d1)δ:173.72,163.68,161.90,161.82,161.54,156.38,15 3.73,134.21,133.12,132.51,132.36,131.73,130.66,130.48,129.41,127.8 8,127.60,127.47,127.39,124.63,124.49,122.88,116.47,116.28,58.73,5 5.48,51.63,45.28,31.91,29.53,29.33,26.74; LC-MS(ESI)m / z:517.14[M+H] + .

[0381] Example 58: (S)-3-(8-bromo-1-((3-(dimethylamino)propyl)thio)-6-(2-fluorophenyl)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 58)

[0382] 1 H NMR (300MHz, CDCl3-d1) δ7.97-7.83 (m, 2H), 7.79 (dd, J = 8.4, 2.5Hz, 1H), 7.5 3(dddd,J=16.9,7.6,4.9,1.6Hz,2H),7.28(dtd,J=13.1,7.7,1.4Hz,2H),6.0 6-5.91(m,1H),3.62(s,3H),3.37-3.12(m,2H),2.70-2.53(m,2H),2.58-2.40 (m,2H),2.45-2.24(m,2H),2.21(s,5H),1.94(ddq,J=21.9,13.0,6.5Hz,2H), 13 C NMR (75MHz, CDCl3-d1) δ173.41,163.21,162.00,161.89,159.85,154.56,153 .86,136.19,133.43,132.95,131.57,131.46,130.53,130.42,128.86,128.8 2,126.92,126.66,124.26,124.22,122.42,119.83,115.98,115.72,57.69,5 5.26,51.89,44.74,30.52,29.65,29.61,27.44; LC-MS(ESI)m / z:560.49[M+H] + .

[0383] Example 59: (S)-3-(8-nitro-1-((3-(dimethylamino)propyl)thio)-6-(2-fluorophenyl)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 59)

[0384] 1H NMR (300MHz, CDCl3-d1) δ8.48 (dd, J=8.5, 2.1Hz, 1H), 8.31 (d, J=2.1Hz, 1H) ,8.22(d,J=8.5Hz,1H),7.63-7.45(m,2H),7.37-7.20(m,2H),4.95(t,J=8. 1Hz,1H),3.62(s,3H),3.30(dt,J=14.4,6.4Hz,1H),3.15(dt,J=14.4,6.4H z,1H),2.71-2.26(m,6H),2.21(s,5H),1.91(ddq,J=20.6,13.0,6.5Hz,2H); 13 C NMR (75MHz, CDCl3-d1) δ173.43,163.12,161.48,161.38,159.76,154.59,153 .88,146.17,137.96,131.60,131.49,130.51,130.41,128.17,127.29,127.2 5,127.08,126.81,126.00,124.26,124.22,123.37,115.95,115.68,57.69,5 5.26,51.91,44.74,30.52,29.65,29.61,27.43; LC-MS(ESI)m / z:527.59[M+H] + .

[0385] Example 60: (S)-3-(8-chloro-6-(2-fluorophenyl)-1-((2-(4-methylpiperazin-1-yl)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 60)

[0386] 1 H NMR(300MHz, CDCl3-d1)δ:7.96-7.83(m,3H),7.71-7.55(m,3H),7.43-7.32(m,3H),7.2 3(dd,J=11.0,8.3Hz,2H),4.28(dd,J=7.7,5.5Hz,2H),3.62(s,3H),2.78-2.56(m,11H); 13C NMR(75MHz, CDCl3-d1)δ:173.69,163.57,161.84,161.73,161.56,156.48,153. 38,134.67,133.55,132.47,132.34,131.73,130.35,130.13,129.57,127.65,1 27.58,127.37,127.29,124.67,124.61,122.48,116.37,116.24,55.32,53.46, 52.78,52.55,51.78,45.84,30.26,29.74,29.36; LC-MS(ESI)m / z:557.18[M+H] + .

[0387] Example 61: (S)-3-(8-bromo-6-(2-fluorophenyl)-1-((2-(4-methylpiperazin-1-yl)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 61)

[0388] 1 H NMR(300MHz, CDCl3-d1)δ7.96-7.84(m,2H),7.80(dd,J=8.3,2.4Hz,1H),7.54(dd dd,J=15.2,7.6,5.0,1.6Hz,2H),7.28(dtd,J=17.6,7.7,1.4Hz,2H),6.06-5.90( m,1H),3.66–3.50(m,4H),3.31(dt,J=14.1,5.2Hz,1H),2.93(dt,J=12.1,5.2Hz, 1H),2.72-2.60(m,2H),2.65-2.49(m,4H),2.55-2.40(m,2H),2.43-2.21(m,7H). 13C NMR (75MHz, CDCl3-d1) δ173.36,163.19,162.00,161.89,159.83,154.56,153. 86,136.38,133.51,132.95,131.61,131.50,130.38,130.28,128.98,128.94,1 26.92,126.66,124.32,124.28,122.44,119.83,115.98,115.71,55.26,53.62, 52.88,52.57,51.93,45.16,30.41,29.67,29.59; LC-MS(ESI)m / z:602.54[M+H] + .

[0389] Example 62: (S)-3-(8-nitro-6-(2-fluorophenyl)-1-((2-(4-methylpiperazin-1-yl)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 62)

[0390] 1 H NMR (300MHz, CDCl3-d1) δ8.52 (dd, J=8.4, 2.1Hz, 1H), 8.37 (d, J=2.1Hz, 1H), 8. 20(d,J=8.5Hz,1H),7.64-7.46(m,2H),7.28(dtd,J=18.3,7.7,1.4Hz,2H),5.98 (ddd,J=8.2,7.5,0.6Hz,1H),3.66-3.49(m,4H),3.29(dt,J=14.1,5.2Hz,1H),2 .84(dt,J=12.1,5.2Hz,1H),2.80-2.45(m,8H),2.52-2.29(m,5H),2.25(s,3H); 13C NMR (75MHz, CDCl3-d1) δ173.36,163.30,161.48,161.38,159.94,154.51,153. 88,146.17,138.11,131.60,131.49,130.54,130.43,128.17,127.60,127.56,1 27.08,126.81,125.94,124.26,124.22,123.35,115.98,115.71,55.26,53.62, 52.88,52.57,51.93,45.16,30.41,29.67,29.61; LC-MS(ESI)m / z:568.64[M+H] + .

[0391] Example 63: (S)-3-(8-chloro-6-(2-fluorophenyl)-1-((1-methylpiperidin-4-yl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 63)

[0392] 1 H NMR(300MHz, CDCl3-d1)δ:7.94-7.71(m,3H),7.62(tdd,J=7.6,5.3,1.9Hz,1H),7.50-7.25(m,3H),2.63(dt,J=17.0,8 .0Hz,2H),2.15-2.09(m,3H),1.94(d,J=15.2Hz,6H),1.86-1.74(m,1H),1.61-1.42(m,2H),1.26(p,J=4.6,3.6Hz,2H); 13 C NMR(75MHz, CDCl3-d1)δ:173.62,163.43,161.72,161.63,161.53,154.68,15 3.31,133.68,133.10,132.42,132.23,131.41,130.63,130.48,129.88,127.8 2,127.79,127.73,127.45,124.68,124.56,123.36,116.38,116.23,55.16,5 3.81,51.92,45.91,39.48,31.55,29.39,29.25; LC-MS(ESI)m / z:528.63[M+H] + .

[0393] Example 64: (S)-3-(8-bromo-6-(2-fluorophenyl)-1-((1-methylpiperidin-4-yl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 64)

[0394] 1 H NMR (300MHz, CDCl3-d1) δ7.95-7.85 (m, 2H), 7.80 (dd, J = 8.4, 1.9Hz, 1H), 7.64-7. 45(m,2H),7.28(dtd,J=16.4,7.7,1.3Hz,2H),6.05-5.91(m,1H),3.62(s,2H),3.2 7(p,J=5.8Hz,1H),2.74(ddd,J=12.2,7.8,5.9Hz,2H),2.68-2.51(m,1H),2.58-2 .42(m,3H),2.48-2.32(m,2H),2.37-2.29(m,0H),2.29(s,3H),2.04-1.79(m,4H). 13 C NMR (75MHz, CDCl3-d1) δ173.41,163.21,162.00,161.89,159.85,153.44,153 .01,136.19,133.07,132.95,131.60,131.49,130.53,130.42,128.86,128.8 2,126.92,126.66,124.26,124.22,122.42,119.83,115.98,115.71,55.26,5 4.28,51.93,45.68,34.94,31.76,29.65,29.61; LC-MS(ESI)m / z:573.50[M+H] + .

[0395] Example 65: (S)-3-(8-nitro-6-(2-fluorophenyl)-1-((1-methylpiperidin-4-yl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 65)

[0396] 1H NMR (300MHz, CDCl3-d1) δ8.51 (dd, J=8.4, 1.9Hz, 1H), 8.40 (d, J=1.9Hz, 1H), 8. 22(d,J=8.5Hz,1H),7.55(dddd,J=17.0,7.6,5.0,1.7Hz,2H),7.29(dtd,J=14.3 ,7.7,1.4Hz,2H),6.06-5.90(m,1H),3.62(s,2H),3.28(p,J=5.8Hz,1H),2.77(d dd,J=12.2,7.8,5.8Hz,2H),2.71-2.24(m,6H),2.29(s,3H),2.06-1.80(m,4H). 13 C NMR (75MHz, CDCl3-d1) δ173.37,163.09,161.48,161.38,159.73,153.42,153 .03,146.17,137.52,131.60,131.49,130.51,130.41,128.17,127.60,127.5 6,127.08,126.81,126.05,124.26,124.22,123.35,115.98,115.71,55.26,5 4.28,51.91,45.68,34.92,31.67,29.67,29.61; LC-MS(ESI)m / z:539.60[M+H] + .

[0397] Example 66: (S)-3-(8-chloro-6-(2-fluorophenyl)-1-((3-(4-(2-hydroxyethyl)piperazin-1-yl)propyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 66)

[0398] 1 H NMR(300MHz, CDCl3-d1)δ:7.89(s,2H),7.70-7.53(m,2H),7.42-7.31(m,2H),7.22(dd,J=10.9,8.3Hz,1H),4.35(s,1H),4.27(dd,J= 7.8,5.5Hz,1H),3.45(q,J=6.0Hz,2H),3.33(s,4H),3.21-3.03(m,2H),2.80-2.57(m,4H),2.41-2.21(m,10H),1.74(q,J=6.9Hz,2H); 13C NMR(75MHz, CDCl3-d1)δ:173.51,163.39,161.74,161.67,161.24,156.51,153.86 ,134.09,133.33,132.18,132.28,131.50,130.54,130.47,129.88,127.75,127.58 ,127.72,127.61,124.72,124.66,122.55,116.36,116.02,59.79,57.51,55.23,55 .12,52.68,52.08,51.89,31.15,29.43,29.18,27.65; LC-MS(ESI)m / z:602.3[M+H] + .

[0399] Example 67: (S)-3-(8-bromo-6-(2-fluorophenyl)-1-((3-(4-(2-hydroxyethyl)piperazin-1-yl)propyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 67)

[0400] 1 H NMR(300MHz, CDCl3-d1)δ7.94-7.77(m,3H),7.54(dddd,J=8.5,7.5,5.0,1.4Hz,2H), 7.37-7.18(m,2H),6.07-5.90(m,1H),4.26(t,J=7.3Hz,1H),3.66–3.45(m,4H),3.36 -3.12(m,2H),2.87(t,J=5.3Hz,3H),2.72-2.53(m,7H),2.54(dt,J=3.6,1.8Hz,1H), 2.56-2.42(m,2H),2.49-2.31(m,1H),2.36-2.22(m,1H),1.88(pd,J=6.5,4.1Hz,2H). 13C NMR (75MHz, CDCl3-d1) δ173.40,163.37,162.00,161.89,160.00,154.56,153.86, 136.38,133.59,132.95,131.61,131.50,130.39,130.28,128.98,128.94,126.93, 126.66,124.21,124.17,122.44,119.76,115.91,115.64,59.24,58.71,55.29,55. 11,52.38,52.36,51.93,30.47,29.67,29.59,27.31; LC-MS(ESI)m / z:645.59[M+H] + .

[0401] Example 68: (S)-3-(8-nitro-6-(2-fluorophenyl)-1-((3-(4-(2-hydroxyethyl)piperazin-1-yl)propyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 68)

[0402] 1 H NMR(300MHz, CDCl3-d1)δ8.52(dd,J=8.4,1.9Hz,1H),8.41(d,J=1.8Hz,1H),8.22(d,J=8.3Hz,1H) ,7.63-7.48(m,2H),7.28(dtd,J=21.6,7.7,1.4Hz,2H),6.04-5.89(m,1H),4.27(t,J=7.3Hz,1H), 3.66-3.49(m,4H),3.35(dt,J=14.4,6.4Hz,1H),3.19(dt,J=14.4,6.4Hz,1H),2.87(t,J=5.3Hz,3 H),2.72-2.58(m,4H),2.64-2.44(m,6H),2.47-2.23(m,2H),1.85(ddq,J=29.5,13.0,6.5Hz,2H). 13C NMR (75MHz, CDCl3-d1) δ173.36,163.30,161.56,161.45,159.94,154.60,153.88, 146.16,138.12,131.61,131.50,130.46,130.35,128.16,127.78,127.74,127.08, 126.81,125.94,124.35,124.31,123.35,115.91,115.64,59.24,58.71,55.26,55. 11,52.44,52.41,51.94,30.45,29.67,29.59,27.31; LC-MS(ESI)m / z:612.69[M+H] + .

[0403] Example 69: (S)-3-(8-chloro-6-(2-fluorophenyl)-1-((morpholinomethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 69)

[0404] 1 H NMR(300MHz, CDCl3-d1)δ:8.47(d,J=8.9Hz,1H),7.87(dd,J=8.9,2.5Hz,1H),7.69-7.42(m,3H),7.41-7.31(m,2H),7.25(dd,J=10.8,8.3Hz,1H ),5.19(d,J=13.4Hz,1H),5.03(d,J=13.4Hz,1H),4.33(dd,J=8.7,5.1Hz,1H),3.32(s,1H),2.88-2.54(m,7H),2.49-2.39(m,1H),1.24(s,1H); 13 C NMR(75MHz, CDCl3-d1)δ:173.44,163.43,161.90,161.83,161.34,153.79, 153.74,134.22,133.01,132.43,132.37,131.35,130.53,130.46,129.92,1 27.75,127.65,127.51,127.49,124.71,124.61,123.02,116.42,116.01,66 .71,58.33,55.58,51.74,43.81,29.41,29.17; LC-MS(ESI)m / z:531.2[M+H] + .

[0405] Example 70: (S)-3-(8-bromo-6-(2-fluorophenyl)-1-((morpholinomethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 70)

[0406] 1 H NMR(300MHz, CDCl3-d1)δ:7.97-7.83(m,2H),7.81(dd,J=8.4,2.5Hz,1H),7.53(dddd,J=16.9,7.6,5.0,1.6Hz,2H),7.36-7.19(m,2H),6.04-5.90( m,1H),4.24(d,J=13.4Hz,1H),3.99(d,J=13.4Hz,1H),3.75-3.56(m,7H), 2.93(ddd,J=12.7,6.5,5.5Hz,2H),2.80-2.40(m,5H),2.41-2.23(m,1H). 13 C NMR (75MHz, CDCl3-d1) δ173.41,163.21,162.00,161.89,159.85,153.86,1 49.17,136.19,133.62,132.95,131.62,131.52,130.53,130.42,128.86,12 8.82,126.92,126.66,124.26,124.22,122.42,119.83,115.98,115.71,66. 31,58.28,55.26,52.38,51.93,29.65,29.61; LC-MS(ESI)m / z:575.47[M+H] + .

[0407] Example 71: (S)-3-(8-nitro-6-(2-fluorophenyl)-1-((morpholinomethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 71)

[0408] 1H NMR(300MHz, CDCl3-d1)δ8.50(dd,J=8.4,2.1Hz,1H),8.33(d,J=2.1Hz,1H),8.23(d,J=8 .5Hz,1H),7.65-7.46(m,2H),7.29(dtd,J=14.4,7.7,1.4Hz,2H),4.75(t,J=8.2Hz,1H), 4.20(d,J=13.4Hz,1H),4.06(d,J=13.4Hz,1H),3.74-3.54(m,7H),2.93(ddd,J=12.7,6. 8,5.3Hz,2H),2.73(ddd,J=12.7,6.9,5.2Hz,2H),2.72–2.48(m,2H),2.53-2.27(m,2H). 13 C NMR (75MHz, CDCl3-d1) δ173.37,163.09,161.48,161.38,159.73,153.86,1 49.17,146.17,137.95,131.60,131.49,130.51,130.41,128.17,127.65,12 7.61,127.08,126.81,126.05,124.26,124.22,123.35,115.98,115.71,66. 32,58.28,55.26,52.43,51.91,29.67,29.61; LC-MS(ESI)m / z:541.57[M+H] + .

[0409] Example 72: (S)-3-(8-chloro-6-(2-fluorophenyl)-1-(((4-phenylpiperazin-1-yl)methyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 72)

[0410] 1H NMR(300MHz, CDCl3-d1)δ:8.47(d,J=8.9Hz,1H),7.92-7.83(m,1H),7.68-7.51(m,2H ),7.40-7.30(m,2H),7.29-7.14(m,3H),6.93(t,J=9.3Hz,2H),6.76(t,J=7.2Hz,1H), 5.28(d,J=13.4Hz,1H),5.10(d,J=13.4Hz,1H),4.37-4.23(m,1H),3.33(s,2H),3.13 (t,J=4.9Hz,3H),3.02-2.85(m,4H),2.82-2.56(m,4H),2.45(dd,J=10.1,6.7Hz,1H); 13 CNMR(75MHz, CDCl3-d1)δ:173.46,163.40,161.84,161.81,161.33,153.79,153.34, 150.64,134.18,133.22,132.16,132.12,131.39,130.49,130.33,129.94,129.11,1 27.75,127.63,127.53,127.49,124.63,124.45,123.18,118.61,116.59,116.44,11 6.31,58.36,55.28,51.91,51.72,48.41,29.39,29.19; LC-MS(ESI)m / z:605.22[M+H] + .

[0411] Example 73: (S)-3-(8-bromo-6-(2-fluorophenyl)-1-(((4-phenylpiperazin-1-yl)methyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 73)

[0412] 1H NMR(300MHz, CDCl3-d1)δ:7.87(d,J=2.4Hz,1H),7.80-7.62(m,2H),7.57(dddd,J=7.6,6.7,3.9,1 .4Hz,2H),7.29(td,J=7.5,1.4Hz,1H),7.23-7.11(m,3H),6.90-6.81(m,3H),6.02-5.87(m,1H),4 .34-4.09(m,2H),3.76(s,2H),3.34(ddd,J=11.8,6.4,4.2Hz,2H),3.22(ddd,J=11.8,6.5,4.2Hz, 2H),2.76(ddd,J=11.7,6.4,4.2Hz,2H),2.61-2.52(m,1H),2.60-2.32(m,4H),2.41-2.15(m,1H); 13 C NMR(75MHz, CDCl3-d1)δ:173.34,163.22,162.45,161.76,160.45,153.56,151.31,1 49.21,136.45,133.70,132.32,131.37,131.67,130.78,130.43,129.23,128.68,12 8.45,126.57,126.34,124.23,124.12,122.45,119.56,118.50,116.12,115.91,115 .64,58.79,55.33,51.53,51.74,48.44,29.32,29.52; LC-MS(ESI)m / z:649.58[M+H] + .

[0413] Example 74: (S)-3-(8-nitro-6-(2-fluorophenyl)-1-(((4-phenylpiperazin-1-yl)methyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 74)

[0414] 1H NMR(300MHz, CDCl3-d1)δ:8.48-8.37(m,2H),8.00(d,J=8.2Hz,1H),7.56-7.38(m,2H),7.23(td,J=7.6,1.3Hz,1 H),7.14-7.01(m,3H),6.88-6.73(m,3H),4.56(ddd,J=8.2,7.2,0.7Hz,1H),4.13(d,J=13.4Hz,1H),4.01(d,J=13 .3Hz,1H),3.43(s,2H),3.21(ddd,J=11.8,6.3,4.2Hz,2H),3.01(ddd,J=11.8,6.5,4.2Hz,2H),2.74(ddd,J=11.8 ,6.4,4.2Hz,2H),2.65-2.54(m,1H),2.60-2.47(m,2H),2.53-2.42(m,1H),2.48-2.33(m,1H),2.34-2.16(m,1H); 13 C NMR(75MHz, CDCl3-d1)δ:173.34,163.54,161.56,161.36,160.78,153.98,151.45,1 49.54,146.16,137.22,131.51,131.65,130.54,130.76,129.17,128.20,127.55,12 7.12,127.01,126.71,126.02,124.43,124.23,123.45,118.08,116.11,115.87,115 .45,58.56,55.68,51.45,51.67,48.44,29.78,29.68; LC-MS(ESI)m / z:615.68[M+H] + .

[0415] Example 75: (S)-3-(8-chloro-6-(2-chlorophenyl)-1-((cyclopropylmethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 75)

[0416] 1H NMR(300MHz, CDCl3-d1)δ:7.93-7.81(m,2H),7.66(dd,J=6.0,3.3Hz,1H),7.53(dq,J=6.1,4.0,3.4Hz,2H),7.51-7.42(m,1H),7.19(d,J=2.3Hz, 1H),4.31(dd,J=7.9,5.5Hz,1H),3.26-3.07(m,2H),2.79-2.57(m,3H),1 .11(ddt,J=10.7,7.5,3.7Hz,1H),0.58-0.45(m,2H),0.34-0.21(m,2H); 13 C NMR(75MHz, CDCl3-d1)δ:173.43,162.78,156.44,153.88,137.85,134.75,133.44,133.26,131.45,131.39,129.69,1 29.45,128.57,128.38,127.21,122.56,54.73,51.82,38.13,29.58,29.14,11.63,6.31; LC-MS(ESI)m / z:503.0[M+H] + .

[0417] Example 76: (S)-3-(8-bromo-6-(2-chlorophenyl)-1-((cyclopropylmethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 76)

[0418] 1 H NMR(300MHz, CDCl3-d1)δ:7.81(d,J=2.4Hz,1H),7.74(d,J=8.4Hz,1H),7.70- 7.55(m,2H),7.53-7.41(m,2H),7.32(ddd,J=7.8,5.1,3.8Hz,1H),4.79-4.50( m,1H),3.70(s,2H),3.43(dd,J=13.5,4.8Hz,1H),3.13(dd,J=13.6,4.8Hz,1H ),2.71-2.43(m,3H),2.53-2.28(m,1H),1.50-1.33(m,1H),1.42-1.14(m,4H); 13C NMR(75MHz, CDCl3-d1)δ:173.45,162.31,154.35,153.57,138.87,136.17,134.12,133.45,132.28,130.98,129.34,1 29.47,128.38,126.68,122.44,119.76,55.43,51.67,37.43,29.81,29.62,13.54,6.60; LC-MS(ESI)m / z:545.88[M+H] + .

[0419] Example 77: (S)-3-(8-nitro-6-(2-chlorophenyl)-1-((cyclopropylmethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 77)

[0420] 1 H NMR(300MHz, CDCl3-d1)δ:8.49(d,J=2.1Hz,1H),8.37(dd,J=8.5,2.1Hz,1H),8.02(d,J=8.5Hz,1H),7.67-7.48(m,3H),7.30(ddd,J=8.0,6.9,1.7Hz,1 H),4.67-4.43(m,1H),3.34(s,2H),3.10-3.01(m,1H),2.90-2.85(m,1H),2 .59-2.33(m,2H),2.39-2.23(m,1H),2.20-2.05(m,1H),1.46-1.21(m,5H); 13 C NMR(75MHz, CDCl3-d1)δ:173.50,162.65,154.76,153.55,146.81,138.09,137.32,134.46,130.71,129.98,128.12,1 28.23,128.46,126.87,125.67,123.75,55.43,51.56,37.56,29.65,29.23,13.45,6.76; LC-MS(ESI)m / z:511.98[M+H] + .

[0421] Example 78: (S)-3-(8-chloro-6-(2-chlorophenyl)-1-(prop-2-yn-1-thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 78)

[0422] 1 H NMR(300MHz, CDCl3-d1)δ:7.94-7.80(m,2H),7.69-7.60(m,1H),7.58-7.48(m,2H),7.45(qd,J=5.5,2.5Hz,1H),7.20( d,J=2.4Hz,1H),4.33(dd,J=7.9,5.4Hz,1H),4.15-3.96(m,2H),3.60(s,3H),3.21(t,J=2.5Hz,1H),2.78-2.54(m,4H); 13 C NMR(75MHz, CDCl3-d1)δ:173.25,162.95,156.03,153.88,137.76,134.79,133.90,133.0 6,131.54,131.29,129.88,129.65,128.82,128.67,127.31,123.03,79.13,72.19,54.94 51.94,29.57,29.24,20.22; LC-MS(ESI)m / z:485.1[M+H] + .

[0423] Example 79: (S)-3-(8-bromo-6-(2-chlorophenyl)-1-(prop-2-yn-1-ylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 79)

[0424] 1 H NMR(300MHz, CDCl3-d1)δ:7.97(d,J=2.5Hz,1H),7.76(d,J=8.4Hz,1H),7.55(dd,J=8.5,2.4Hz,1H),7.48-7.31(m,3H),7.18(ddd,J=7.8,5.7, 3.2Hz,1H),4.67-4.52(m,1H),4.01(dd,J=12.3,3.0Hz,1H),3.89(dd,J=12.4,3.0Hz,1H),3.71(s,2H),2.65-2.32(m,3H),2.29-2.05(m,2H); 13C NMR(75MHz, CDCl3-d1)δ:173.12,162.65,154.30,153.09,138.23,136.76,134.09,133.19,132.65,130.65,129.45,12 9.76,128.78,126.13,122.56,119.73,79.01,72.66,55.11,51.70,29.57,29.76,20.41; LC-MS(ESI)m / z:529.87[M+H] + .

[0425] Example 80: (S)-3-(8-nitro-6-(2-chlorophenyl)-1-(prop-2-yn-1-ylthio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 80)

[0426] 1 H NMR(300MHz, CDCl3-d1)δ:8.49-8.34(m,2H),8.09(d,J=8.4Hz,1H),7.55-7.40(m,3H),7.30(ddd,J=7.7,7.2,1.7Hz,1H),4.89(t,J=8.0Hz,1H),4.1 2(dd,J=12.4,3.0Hz,1H),3.89(dd,J=12.4,3.0Hz,1H),3.60(s,2H),2.87 -2.63(m,2H),2.49-2.33(m,1H),2.37-2.29(m,1H),2.21(t,J=3.0Hz,1H); 13 C NMR(75MHz, CDCl3-d1)δ:173.50,162.06,154.02,153.88,146.01,138.70,137.82,134.63,130.41,129.65,128.39,12 8.36,128.20,126.67,125.98,123.39,79.06,72.67,55.11,51.90,29.70,29.62,20.40; LC-MS(ESI)m / z:495.97[M+H] + .

[0427] Example 81: (S)-3-(8-chloro-6-(2-chlorophenyl)-1-((2-morpholinoethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 81)

[0428] 1 H NMR(300MHz, CDCl3-d1)δ:7.92(d,J=1.8Hz,2H),7.72-7.64(m,1H),7.58-7.46(m,3H),7.27-7.16(m,1H),4.34(t,J =6.6Hz,1H),3.62(s,3H),3.55(t,J=4.5Hz,4H),3.43(s,2H),2.81-2.67(m,2H),2.63(t,J=6.6Hz,4H),2.40(s,4H); 13 C NMR(75MHz, CDCl3-d1)δ:173.34,162.85,156.47,153.39,137.34,134.56,133.33,133.10,131.49,131.36,129.24,129. 11,128.87,128.59,127.39,122.55,66.23,54.88,53.99,53.54,51.78,30.35,29.88,29.68; LC-MS(ESI)m / z:564.1[M+H] + .

[0429] Example 82: (S)-3-(8-bromo-6-(2-chlorophenyl)-1-((2-morpholinoethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza 4-yl)methyl propionate (compound 82)

[0430] 1 H NMR(300MHz, CDCl3-d1)δ:8.04(dd,J=8.7,2.3Hz,1H),7.83(d,J=8.7Hz,1H),7.68(dd,J=6.0,3.3Hz,1H),7.60-7.45(m,3H),7.33(d,J=2.2Hz, 1H),4.33(t,J=6.6Hz,1H),3.62(s,3H),3.56-3.51(m,4H),3.39(d,J=6 .2Hz,2H),2.82-2.66(m,2H),2.62(t,J=6.7Hz,4H),2.45-2.32(m,4H); 13C NMR(75MHz, CDCl3-d1)δ:173.54,162.56,154.86,153.45,138.96,136.11,134.57,133.69,132.98,130.01,129.24,129. 30,128.45,126.35,122.57,119.97,65.12,55.45,53.55,52.57,51.98,30.65,29.80,29.89; LC-MS(ESI)m / z:606.7[M+H] + .

[0431] Example 83: (S)-3-(8-nitro-6-(2-chlorophenyl)-1-((2-morpholinoethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 83)

[0432] 1 H NMR(300MHz, CDCl3-d1)δ:8.56-8.43(m,2H),8.13(d,J=8.3Hz,1H),7.59-7.47(m,1H),7.52-7.38(m,2H),7.37-7.25(m,1H), 5.11-4.96(m,1H),3.54-3.33(m,8H),3.19(dt,J=14.1,5.2Hz,1H),2.89-2.65(m,3H),2.57-2.32(m,6H),2.20-2.11(m,1H); 13 C NMR(75MHz, CDCl3-d1)δ:173.11,162.45,154.44,153.90,146.22,138.67,137.48,135.92,130.33,129.68,128.45,128.8 5,128.68,126.15,125.68,123.42,65.82,55.15,53.47,52.98,51.75,30.09,29.61,29.01; LC-MS(ESI)m / z:571.05[M+H] + .

[0433] Example 84: (S)-3-(8-chloro-6-(2-chlorophenyl)-1-((2-(diethylamino)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 84)

[0434] 1 H NMR(300MHz, CDCl3-d1)δ:8.06-7.74(m,2H),7.66(s,1H),7.49(d,J=27.1Hz,3H),7.19(s,1H),3.60(s,3H),3.32(s,2H),2.69(s,5H),0.93(s,6H); 13 C NMR(75MHz, CDCl3-d1)δ:173.45,162.23,156.68,153.44,137.88,134.21,133.45,133.88,131.73,131.46,129.96,129. 78,128.75,128.53,127.38,122.45,54.59,51.83,51.67,47.65,30.57,29.99,29.43,11.87; LC-MS(ESI)m / z:548.1[M+H] + .

[0435] Example 85: (S)-3-(8-bromo-6-(2-chlorophenyl)-1-((2-(diethylamino)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 85)

[0436] 1 H NMR(300MHz, CDCl3-d1)δ:7.95(d,J=2.4Hz,1H),7.79-7.61(m,2H),7.55-7.40 (m,3H),7.28(ddd,J=7.7,6.4,2.4Hz,1H),4.76-4.62(m,1H),3.68-3.51(m,3H) ,3.43(dt,J=14.2,5.2Hz,1H),2.87(dt,J=12.1,5.2Hz,1H),2.79-2.56(m,3H), 2.63-2.46(m,4H),2.52-2.39(m,1H),2.43-2.24(m,1H),1.03(t,J=7.2Hz,6H); 13C NMR(75MHz, CDCl3-d1)δ:173.47,162.55,154.56,153.88,138.65,136.19,134.57,133.30,132.51,130.41,129.80,129.3 1,128.32,126.70,122.48,119.74,55.12,51.92,50.90,47.11,30.42,29.81,29.62,11.17; LC-MS(ESI)m / z:590.97[M+H] + .

[0437] Example 86: (S)-3-(8-nitro-6-(2-chlorophenyl)-1-((2-(diethylamino)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 86)

[0438] 1 H NMR(300MHz, CDCl3-d1)δ:8.54(dd,J=8.5,2.1Hz,1H),8.41(d,J=2.1Hz,1H),8.29(d,J =8.3Hz,1H),7.60(dd,J=7.7,1.5Hz,1H),7.56-7.39(m,2H),7.31(td,J=7.5,1.4Hz,1H) ,5.98(ddd,J=8.2,7.3,0.7Hz,1H),3.76-3.56(m,4H),3.33(dt,J=14.3,5.2Hz,1H),2. 81(dt,J=12.1,5.2Hz,1H),2.63-2.49(m,8H),2.32-2.14(m,1H),1.01(t,J=7.3Hz,6H); 13 C NMR(75MHz, CDCl3-d1)δ:173.23,162.11,154.63,153.23,146.87,138.86,137.98,134.58,130.23,129.96,128.42,128.1 8,128.49,126.26,125.86,123.14,55.75,51.87,50.97,47.31,30.65,29.43,29.61,11.32; LC-MS(ESI)m / z:557.07[M+H] + .

[0439] Example 87: (S)-3-(8-chloro-6-(2-chlorophenyl)-1-((3-(dimethylamino)propyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 87)

[0440] 1 H NMR(300MHz, CDCl3-d1)δ:7.93-7.80(m,2H),7.66(dd,J=5.9,3.4Hz,1H),7 .53(dq,J=6.1,3.9,3.5Hz,2H),7.50-7.42(m,1H),7.19(d,J=2.3Hz,1H),4. 31(dd,J=7.9,5.5Hz,1H),3.60(s,3H),3.31-3.23(m,1H),3.16(dt,J=13.4, 7.2Hz,1H),2.78-2.57(m,4H),2.36(s,2H),2.17(s,6H),1.86-1.73(m,2H); 13 C NMR(75MHz, CDCl3-d1)δ:173.98,162.36,156.78,153.43,137.67,134.84,133.56,133.42,131.86,131.46,129.86,129.0 8,128.68,128.49,127.17,122.98,58.03,54.10,51.27,45.55,31.36,29.71,29.59,26.59; LC-MS(ESI)m / z:534.07[M+H] + .

[0441] Example 88: (S)-3-(8-bromo-6-(2-chlorophenyl)-1-((3-(dimethylamino)propyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 88)

[0442] 1H NMR(300MHz, CDCl3-d1)δ:7.99(d,J=8.4Hz,1H),7.87-7.70(m,2H),7.67(dd,J=7.6,1 .8Hz,1H),7.56(dd,J=7.6,1.6Hz,1H),7.39(dtd,J=23.1,7.4,1.7Hz,2H),6.01-5.91 (m,1H),3.65(s,3H),3.38(dt,J=14.4,6.4Hz,1H),3.10(dt,J=14.4,6.5Hz,1H),2.67 -2.34(m,6H),2.22(s,5H),2.01(dp,J=12.9,6.4Hz,1H),1.88(dp,J=12.8,6.4Hz,1H); 13 C NMR(75MHz, CDCl3-d1)δ:173.14,162.23,154.50,153.43,138.22,136.18,134.79,133.26,132.96,130.16,129.09,129.3 4,128.98,126.12,122.43,119.21,57.64,55.86,51.43,44.53,30.15,29.70,29.34,27.78; LC-MS(ESI)m / z:576.92[M+H] + .

[0443] Example 89: (S)-3-(8-nitro-6-(2-chlorophenyl)-1-((3-(dimethylamino)propyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza 4-yl)methyl propionate (compound 89)

[0444] 1 H NMR (300MHz, CDCl3-d1)δ:8.58(dd,J=8.5,2.1Hz,1H),8.43(d,J=2.1Hz,1H),8.34(d,J=8.5Hz,1H),7.55(dd,J=7.7,1.4Hz,1H),7.50–7.38(m,2H),7. 32(td,J=7.5,1.5Hz,1H),4.99(t,J=8.1Hz,1H),3.61(s,3H),3.26–3.04(m ,2H),2.83–2.37(m,6H),2.31(s,5H),1.95(ddt,J=17.5,12.8,6.3Hz,2H); 13C NMR(75MHz, CDCl3-d1)δ:173.14,162.40,154.60,153.77,146.41,138.33,137.69,134.87,130.44,129.82,128.58,128.6 9,127.77,126.86,125.93,123.39,57.73,55.26,51.98,44.99,30.58,29.88,29.09,27.54; LC-MS(ESI)m / z:543.09[M+H] + .

[0445] Example 90: (S)-3-(8-chloro-6-(2-chlorophenyl)-1-((2-(4-methylpiperazin-1-yl)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 90)

[0446] 1 H NMR (300MHz, CDCl3-d1)δ:7.91(dd,J=8.7,2.4Hz,1H),7.84(d,J=8.7Hz,1H),7.71-7.63(m,1H),7.59-7.50(m ,2H),7.50-7.41(m,1H),7.21(d,J=2.4Hz,1H),4.32(dd,J=7.9,5.5Hz,1H),3.60(s,3H),2.92-2.56(m,10H); 13 C NMR(75MHz, CDCl3-d1)δ:173.76,162.91,156.09,153.49,137.91,134.24,133.76,133.42,131.90,131.11,129.46,129.36,1 28.87,128.71,127.90,122.23,54.29,53.70,52.40,52.22,51.53,45.66,30.98,29.56,29.29; LC-MS(ESI)m / z:573.19[M+H] + .

[0447] Example 91: (S)-3-(8-bromo-6-(2-chlorophenyl)-1-((2-(4-methylpiperazin-1-yl)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 91)

[0448] 1 H NMR(300MHz, CDCl3-d1)δ:8.03-7.87(m,2H),7.86(dd,J=8.3,2.4Hz,1H),7 .60(ddd,J=7.7,5.3,1.6Hz,2H),7.42(td,J=7.5,1.7Hz,1H),7.32(td,J=7. 6,1.5Hz,1H),6.10-5.98(m,1H),3.69-3.56(m,4H),3.33(dt,J=14.2,5.2H z,1H),2.90(dt,J=12.1,5.2Hz,1H),2.78-2.33(m,13H),2.36-2.26(s,3H); 13 C NMR(75MHz, CDCl3-d1)δ:173.23,162.76,154.34,153.67,138.98,136.34,134.59,133.16,132.90,130.46,129.51,129.33,1 28.40,126.10,122.21,119.70,55.37,53.48,52.69,52.16,51.95,45.17,30.34,29.11,29.60; LC-MS(ESI)m / z:617.99[M+H] + .

[0449] Example 92: (S)-3-(8-nitro-6-(2-chlorophenyl)-1-((2-(4-methylpiperazin-1-yl)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 92)

[0450] 1 H NMR (300MHz, CDCl3-d1)δ:8.56(dd,J=7.2,1.5Hz,1H),8.33(d,J=1.5Hz,1H),7.87(d,J=7.7Hz,1H),7.69-7.59(m,1H),7.56-7.33(m,3H),5.95-5.83 (m,1H),3.56(s,3H),3.50-3.28(m,2H),2.88-2.60(m,2H),2.67-2.49(m, 7H),2.55-2.45(m,4H),2.50-2.42(m,1H),2.42-2.29(m,0H),2.30(s,3H); 13C NMR(75MHz, CDCl3-d1)δ:173.36,162.07,154.51,153.88,146.14,138.72,137.95,134.98,130.33,129.65,128.27,128.25,1 28.17,126.71,125.83,123.35,55.10,53.62,52.88,52.57,51.93,45.16,30.41,29.67,29.61; LC-MS(ESI)m / z:584.19[M+H] + .

[0451] Example 93: (S)-3-(8-chloro-6-(2-chlorophenyl)-1-((1-methylpiperidin-4-yl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 93)

[0452] 1 H NMR(300MHz, CDCl3-d1)δ:7.92-7.78(m,2H),7.70-7.60(m,1H),7.58-7.41(m,3H),7 .18(d,J=2.4Hz,1H),4.31(dd,J=7.8,5.5Hz,1H),3.36(d,J=18.0Hz,4H),2.79-2.54 (m,5H),2.13(s,3H),2.10-1.92(m,3H),1.90-1.79(m,1H),1.66(dtd,J=13.2,10.2, 9.7,3.5Hz,1H),1.51(dtd,J=13.8,10.3,3.8Hz,1H),1.24(s,1H),1.19-0.97(m,1H); 13 CNMR(75MHz, CDCl3-d1)δ:173.56,162.78,154.34,153.98,137.09,134.34,133.39,133.14,131.98,131.01,129.84,129. 37,128.81,128.58,127.23,123.67,54.45,53.76,51.43,45.98,39.09,31.34,29.71,29.01; LC-MS(ESI)m / z:544.17[M+H] + .

[0453] Example 94: (S)-3-(8-bromo-6-(2-chlorophenyl)-1-((1-methylpiperidin-4-yl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 94)

[0454] 1 H NMR(300MHz, CDCl3-d1)δ8.02-7.93(m,1H),7.87-7.74(m,2H),7.68-7.57(m, 1H),7.53-7.37(m,3H),5.75(t,J=8.3Hz,1H),3.74(p,J=4.3Hz,1H),2.95(dd d,J=12.6,7.7,5.0Hz,2H),2.81-2.69(m,2H),2.72-2.64(m,1H),2.67-2.52( m,1H),2.38-2.22(m,2H),2.25(s,2H),2.11-1.94(m,2H),1.76-1.60(m,2H); 13 C NMR (75MHz, CDCl3-d1) δ173.44,162.92,154.83,153.07,136.68,136.32,134.54,132.69,130.92,129.67,129.29,12 8.62,126.95,122.39,118.51,55.15,52.59,51.85,45.28,39.32,30.13,29.31,29.03; LC-MS(ESI)m / z:589.07[M+H] + .

[0455] Example 95: (S)-3-(8-nitro-6-(2-chlorophenyl)-1-((1-methylpiperidin-4-yl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (Compound 95)

[0456] 1H NMR(300MHz, CDCl3-d1)δ8.65(dd,J=8.9,2.0Hz,1H),8.44(d,J=2.0Hz,1H),8.20(d,J =8.9Hz,1H),7.68-7.52(m,1H),7.53-7.35(m,3H),5.75(t,J=8.3Hz,1H),3.76(p,J=4. 3Hz,1H),2.92(ddd,J=12.6,7.7,5.0Hz,2H),2.82-2.63(m,2H),2.73-2.64(m,1H),2. 67-2.52(m,1H),2.41-2.32(m,2H),2.24(s,2H),2.11-1.95(m,2H),1.76-1.60(m,2H). 13 C NMR (75MHz, CDCl3-d1) δ173.44,162.54,154.39,153.21,145.72,137.91,137.16,134.54,130.92,129.44,129.27,128.6 1,128.47,126.86,125.17,123.04,55.05,52.59,51.85,45.22,39.42,30.26,29.38,29.04; LC-MS(ESI)m / z:556.15[M+H] + .

[0457] Example 96: (S)-3-(8-chloro-6-(2-chlorophenyl)-1-((3-(4-(2-hydroxyethyl)piperazin-1-yl)propyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 96)

[0458] 1 H NMR(300MHz, CDCl3-d1)δ:7.93-7.84(m,2H),7.74-7.65(m,1H),7.58-7.50(m ,2H),7.50-7.47(m,1H),7.15(d,J=2.3Hz,1H),4.33-4.26(m,2H),3.47(q,J= 5.9Hz,2H),3.43-3.35(m,0H),3.31(s,2H),3.26(dt,J=13.8,7.0Hz,1H),3.1 2(dt,J=13.4,7.2Hz,1H),2.78-2.57(m,3H),2.32(s,10H),1.90-1.71(m,2H); 13C NMR(75MHz, CDCl3-d1)δ:173.23,162.34,156.65,153.22,137.74,134.46,133.56,133.06,131.88,131.72,129.74,129.36,128.80, 128.55,127.38,122.21,59.43,57.76,55.63,54.52,52.37,52.27,51.28,31.15,29.36,29.27,27.46; LC-MS(ESI)m / z:617.23[M+H] + .

[0459] Example 97: (S)-3-(8-bromo-6-(2-chlorophenyl)-1-((3-(4-(2-hydroxyethyl)piperazin-1-yl)propyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 97)

[0460] 1 H NMR(300MHz, CDCl3-d1)δ8.02-7.92(m,1H),7.87-7.73(m,2H),7.68-7.57(m,1H),7.53 -7.37(m,3H),5.75(t,J=8.3Hz,1H),4.11(t,J=6.3Hz,1H),3.62(s,2H),3.60-3.45(m,2 H),3.24(td,J=6.9,1.9Hz,2H),2.78-2.54(m,2H),2.60-2.52(m,1H),2.56-2.43(m,2H ),2.52-2.45(m,1H),2.29-2.35(m,6H),2.40-2.21(m,2H),1.85(tt,J=6.9,5.8Hz,2H); 13 C NMR (75MHz, CDCl3-d1) δ173.41,162.97,156.25,153.66,136.68,136.32,134.34,134.42,132.59,130.92,129.67,129.26,128.51, 126.45,122.37,118.53,59.43,57.28,55.15,54.51,52.52,51.92,51.75,30.28,29.37,29.07,27.65; LC-MS(ESI)m / z:662.13[M+H] + .

[0461] Example 98: (S)-3-(8-nitro-6-(2-chlorophenyl)-1-((3-(4-(2-hydroxyethyl)piperazin-1-yl)propyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (Compound 98)

[0462] 1 H NMR (300MHz, CDCl3-d1) δ8.65(dd,J=8.9,2.0Hz,1H),8.46(d,J=2.0Hz,1H),8.20(d,J=8.9Hz,1H ),7.67-7.66(m,1H),7.53-7.34(m,3H),5.75(t,J=8.3Hz,1H),4.11(t,J=6.3Hz,1H),3.65(s,2H ),3.63–3.55(m,2H),3.24(td,J=6.9,1.9Hz,2H),2.78-2.56(m,2H),2.60-2.51(m,1H),2.56-2. 42(m,3H),2.49-2.34(m,7H),2.44-2.35(m,1H),2.39-2.18(m,2H),1.81(tt,J=6.9,5.8Hz,2H); 13 C NMR (75MHz, CDCl3-d1) δ173.44,162.54,156.32,153.82,145.72,138.32,137.06,134.54,130.92,129.41,129.27,128.61,128.42, 126.96,125.17,123.04,59.43,57.27,55.05,54.51,52.52,51.92,51.85,30.28,29.37,29.07,27.55; LC-MS(ESI)m / z:629.20[M+H] + .

[0463] Example 99: (S)-3-(8-chloro-6-(2-chlorophenyl)-1-((morpholinomethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (Compound 99)

[0464] 1H NMR(300MHz, CDCl3-d1)δ:8.42(d,J=8.8Hz,1H),7.86(dd,J=8.8,2.5Hz,1H),7.70-7.60(m,1H),7.58-7.51(m,2H),7.51-7.42(m,1H), 7.16(d,J=2.4Hz,1H),5.21-5.08(m,2H),4.38(dd,J=8.6,5.2Hz,1H),3.60(s,3H),3.32(s,1H),2.88-2.54(m,7H),2.48-2.38(m,1H); 13 C NMR(75MHz, CDCl3-d1)δ:173.36,162.28,153.47,153.28,137.19,134.03,133.47,133.19,131.63,131.57,129.72,12 9.56,128.86,128.55,127.05,123.53,66.32,58.17,54.59,51.73,43.82,29.47,29.18; LC-MS(ESI)m / z:547.34[M+H] + .

[0465] Example 100: (S)-3-(8-bromo-6-(2-chlorophenyl)-1-((morpholinomethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza 4-yl)methyl propionate (compound 100)

[0466] 1 H NMR (300MHz, CDCl3-d1) δ7.93(dd,J=1.9,0.7Hz,1H),7.87-7.74(m,2H),7.64-7.51(m,1H),7.53-7.37(m,3H),5.75(t,J=8.3Hz,1H) ,4.08(d,J=3.6Hz,2H),3.53(s,3H),3.69-3.52(m,4H),2.68-2.52(m,2H),2.48-2.46(m,4H),2.38-2.29(m,1H),2.33-2.21(m,1H). 13C NMR (75MHz, CDCl3-d1) δ173.44,162.92,153.77,153.55,137.68,136.38,134.61,134.54,132.69,130.92,129.73,12 9.21,128.61,126.95,122.30,118.53,66.63,56.98,55.05,51.65,46.16,29.48,29.27; LC-MS(ESI)m / z:591.01[M+H] + .

[0467] Example 101: (S)-3-(8-nitro-6-(2-chlorophenyl)-1-((morpholinomethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 101)

[0468] 1 H NMR (300MHz, CDCl3-d1) δ8.65(dd,J=9.0,2.1Hz,1H),8.46(d,J=2.2Hz,1H),8.20(d,J=8.9Hz,1H),7.67-7.56(m,1H),7.53-7.37(m,3H),5.72(t, J=8.3Hz,1H),4.08(d,J=3.6Hz,2H),3.63(s,3H),3.69-3.54(m,4H),2.7 2-2.57(m,2H),2.58-2.42(m,4H),2.38-2.25(m,1H),2.33-2.18(m,1H); 13 C NMR (75MHz, CDCl3-d1) δ173.44,162.54,153.83,153.78,145.72,138.23,137.06,134.57,130.82,129.44,129.37,12 8.64,128.47,126.96,125.17,123.04,66.63,56.91,55.05,51.82,46.16,29.38,29.06; LC-MS(ESI)m / z:558.13[M+H] + .

[0469] Example 102: (S)-3-(8-chloro-1-(methylthio)-6-phenyl-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 102)

[0470] 1 H NMR (300MHz, CDCl3-d1)δ:7.97-7.83(m,2H),7.57-7.40(m,6H),4.23(dd,J=7.6,5.5Hz,1H),3.63(s,3H),2.82-2.53(m,7H); 13 C NMR(75MHz, CDCl3-d1)δ:173.47,166.48,153.48,153.37,139.58,133.75,133.42,132.62,130.46,130 .27,128.69,128.43,128.12,122.65,55.63,51.73,29.83,29.07,16.74; LC-MS(ESI)m / z:427.06[M+H] + .

[0471] Example 103: (S)-3-(8-bromo-1-(methylthio)-6-phenyl-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 103)

[0472] 1 H NMR(300MHz, CDCl3-d1)δ7.82-7.70(m,2H),7.66-7.54(m,2H),7.53(d,J=8.1Hz,1H),7.52–7.43(m,2H),7.4 8–7.39(m,1H),5.64(t,J=8.3Hz,1H),2.72(s,3H),2.74-2.51(m,2H),2.38-2.24(m,1H),2.33-2.18(m,1H); 13 CNMR(75MHz, CDCl3-d1)δ:173.44,166.20,153.33,152.80,138.56,136.32,133.69,133.29,129.80,12 9.08,128.49,128.41,122.38,118.45,55.26,51.82,29.38,29.06,16.60; LC-MS(ESI)m / z:472.04[M+H] + .

[0473] Example 104: (S)-3-(8-nitro-1-(methylthio)-6-phenyl-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 104)

[0474] 1 H NMR (300MHz, CDCl3-d1) δ8.61(dd,J=8.9,2.1Hz,1H),8.59(d,J=2.2Hz,1H),8.12(d,J=9.0Hz,1H),7.69-7.66(m,2H),7.55- 7.43(m,2H),7.48-7.34(m,1H),5.64(t,J=8.3Hz,1H),2.72(s,3H),2.78-2.52(m,2H),2.38-2.23(m,1H),2.33-2.18(m,1H); 13 C NMR(75MHz, CDCl3-d1)δ:173.44,166.07,153.35,153.07,145.66,138.78,137.34,129.81,128.93,128 .42,128.42,128.42,125.72,123.07,55.32,51.81,29.34,29.16,16.62; LC-MS(ESI)m / z:438.12[M+H] + .

[0475] Example 105: (S)-3-(8-chloro-1-((2-morpholinoethyl)thio)-6-phenyl-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 105)

[0476] 1 H NMR(300MHz, CDCl3-d1)δ:7.92(d,J=2.5Hz,2H),7.52-7.42(m,6H),4.23(t,J=6.4Hz,1H ),3.63(s,3H),3.43(t,J=4.6Hz,4H),2.75-2.53(m,6H),2.33-2.27(m,3H),2.09(s,1H); 13 C NMR(75MHz, CDCl3-d1)δ:172.36,166.71,156.82,153.23,139.62,133.81,133.53,132.55,130.71,130.52,128.6 4,128.37,128.10,122.51,66.73,55.87,53.44,53.31,51.34,30.36,29.52,29.37; LC-MS(ESI)m / z:526.19[M+H] + .

[0477] Example 106: (S)-3-(8-bromo-1-((2-morpholinoethyl)thio)-6-phenyl-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 106)

[0478] 1 H NMR(300MHz, CDCl3-d1)δ:8.09(d,J=10.9Hz,1H),7.87(d,J=8.7Hz,1H),7.61-7.48(m,6H ),4.25(t,J=6.5Hz,1H),3.65(s,3H),3.56-3.39(m,6H),2.81-2.58(m,6H),2.34(s,4H); 13 C NMR (75MHz, CDCl3-d1) δ173.34,165.99,155.26,153.74,138.36,136.51,134.19,133.09,129.84,129.04,128.5 9,128.40,122.38,118.45,66.51,55.23,54.17,52.82,51.81,30.47,29.32,29.08; LC-MS(ESI)m / z:572.00[M+H] + .

[0479] Example 107: (S)-3-(8-nitro-1-((2-morpholinoethyl)thio)-6-phenyl-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 107)

[0480] 1 H NMR (300MHz, CDCl3-d1) δ8.61(dd,J=8.9,2.1Hz,1H),8.49(d,J=2.2Hz,1H),8.12(d,J=9.0Hz,1H),7.69-7.56(m,2H),7.55-7.43(m,2H),7.48 -7.39(m,1H),5.61(t,J=8.3Hz,1H),3.64-3.43(m,7H),3.35(td,J=6. 3,0.8Hz,2H),2.73-2.76(m,3H),2.61-2.41(m,4H),2.41-2.14(m,2H); 13C NMR(75MHz, CDCl3-d1)δ:173.44,166.04,155.51,153.77,145.66,138.78,137.67,129.60,128.98,128.49,128.4 6,128.42,125.71,123.07,66.23,55.42,54.12,52.79,51.85,30.47,29.35,29.07; LC-MS(ESI)m / z:537.19[M+H] + .

[0481] Example 108: (S)-3-(8-chloro-1-((3-(dimethylamino)propyl)thio)-6-phenyl-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza 4-yl)methyl propionate (compound 108)

[0482] 1 H NMR(300MHz, CDCl3-d1)δ:7.97-7.85(m,2H),7.57-7.40(m,6H),4.23(dd,J=7.6,5.5Hz,1H),3.61(s,2H),3.11(td,J =7.2,2.7Hz,2H),2.82-2.54(m,4H),2.24-2.16(m,2H),2.02(s,6H),1.69(dq,J=14.5,7.1Hz,2H),1.27-1.11(m,1H); 13 C NMR(75MHz, CDCl3-d1)δ:173.57,166.82,156.35,153.86,139.08,133.50,133.02,132.63,130.71,130.21,128.6 6,128.68,128.42,122.91,58.46,55.26,51.91,45.36,31.13,29.46,29.28,26.47; LC-MS(ESI)m / z:499.56[M+H] + .

[0483] Example 109: (S)-3-(8-bromo-1-((3-(dimethylamino)propyl)thio)-6-phenyl-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 109)

[0484] 1H NMR (300MHz, CDCl3-d1) δ7.82-7.70(m,2H),7.66-7.39(m,7H),5.64(t,J=8.3Hz,1H),3.62(s,3H),3.23(d,J=12.4Hz,1H ),2.78–2.61(m,1H),2.67-2.57(m,1H),2.57(t,J=5.7Hz,2H),2.38-2.29(m,1H),2.33-2.14(m,1H),1.92-1.74(m,2H); 13 C NMR (75MHz, CDCl3-d1) δ173.44,165.99,156.25,153.75,138.56,136.31,134.08,133.09,129.80,129.05,128.4 9,128.40,122.32,118.45,58.21,55.26,51.85,44.82,30.04,29.35,29.08,26.61; LC-MS(ESI)m / z:543.11[M+H] + .

[0485] Example 110: (S)-3-(8-nitro-1-((3-(dimethylamino)propyl)thio)-6-phenyl-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 110)

[0486] 1 H NMR (300MHz, CDCl3-d1) δ8.63 (dd, J=8.9, 2.1Hz, 1H), 8.49 (d, J=2.2Hz, 1H), 8. 11(d,J=9.0Hz,1H),7.69-7.56(m,2H),7.55-7.39(m,3H),5.64(t,J=8.3Hz,1H ),3.63(s,3H),3.23(d,J=12.4Hz,1H),2.78-2.64(m,1H),2.67-2.55(m,1H),2 .57(t,J=5.7Hz,2H),2.38-2.23(m,1H),2.33-2.28(m,1H),1.92-1.74(m,2H); 13C NMR (75MHz, CDCl3-d1) δ173.44,166.04,156.33,153.75,145.66,138.78,137.81,129.81,128.98,128.49,128.4 3,128.42,125.61,123.07,58.21,55.42,51.85,44.72,30.08,29.33,29.07,26.61; LC-MS(ESI)m / z:509.19[M+H] + .

[0487] Example 111: (S)-3-(8-chloro-6-(2-chlorophenyl)-1-(((phosphono)methyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 111)

[0488] 1 H NMR(300MHz, CDCl3-d1)δ:7.82(d,J=8.2Hz,1H),7.87(s,2H),7.67-7.60(m,2H),7.51-7.40 (m,4H),5.83(d,J=8.5Hz,2H),5.75(t,J=8.3Hz,1H),2.74-2.56(m,2H),2.39-2.23(m,2H); 13 C NMR(75MHz, CDCl3-d1)δ:173.42,161.14,157.56,157.13,154.10,137.57,134.72,134.19,132.66,131.29,131.26,12 9.70,129.62,128.68,128.46,127.31,123.05,66.32,66.28,58.25,51.94,29.93,29.01; LC-MS(ESI)m / z:557.34[M+H] + .

[0489] Example 112: (S)-3-(8-bromo-6-(2-chlorophenyl)-1-(((phosphono)methyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 112)

[0490] 1H NMR (300MHz, CDCl3-d1) δ7.99 (dd, J = 1.9, 0.7Hz, 1H), 7.87 (s, 2H), 7.84-7.64 (m, 2H), 7.67-7.53 (m, 1H), 7.53-7. 35(m,3H),5.83(d,J=8.4Hz,2H),5.75(t,J=8.3Hz,1H),2.78-2.51(m,2H),2.38-2.29(m,1H),2.33-2.21(m,1H); 13 C NMR (75MHz, CDCl3-d1) δ173.30,161.23,157.01,156.93,153.98,136.52,136.24,135.16,133.90,132.76,130.92,129 .32,128.64,128.61,126.95,122.23,118.29,66.01,65.93,58.26,51.55,29.53,29.22; LC-MS(ESI)m / z:601.96[M+H] + .

[0491] Example 113: (S)-3-(8-nitro-6-(2-chlorophenyl)-1-(((phosphono)methyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 113)

[0492] 1 H NMR (300MHz, CDCl3-d1) δ8.65(dd,J=9.0,2.1Hz,1H),8.41(d,J=2.2Hz,1H),8.29(d,J=8.9Hz,1H),7.87(s,2H),7.67 -7.57(m,1H),7.53–7.37(m,3H),5.81(d,J=8.4Hz,2H),5.75(t,J=8.3Hz,1H),2.77-2.52(m,2H),2.38-2.18(m,2H). 13C NMR(75MHz, CDCl3-d1)δ:173.30,160.78,157.01,157.04,154.03,145.72,137.80,136.97,133.90,130.72,129.30,12 8.61,128.46,128.44,126.75,124.61,123.23,66.11,65.82,58.24,51.72,29.53,29.52; LC-MS(ESI)m / z:567.04[M+H] + .

[0493] Example 114: (S)3-(8-bromo-6-(pyridin-2-yl)-1-methylthio-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 114)

[0494] 1 H NMR(300MHz, CDCl3-d1)δ:8.79(dd,J=3.5,1.2Hz,1H),7.86–7.75(m,3H),7.70–7.65(m,1H),7.54(dd,J=7.8,1.5Hz,1 H),7.33-7.30(m,1H),6.13(t,J=5.3Hz,1H),3.66(s,2H),2.72(s,3H),2.66(td,J=7.8,1.2Hz,3H),2.62–2.51(m,2H). 13 C NMR (75MHz, CDCl3-d1) δ173.38,162.32,155.83,153.99,150.80,147.41,137.47,136.64,136.60,134.48 ,127.86,125.25,122.80,122.65,120.45,57.05,52.01,29.61,29.27,16.69.LC-MS(ESI)m / z:472.3[M+H] + .

[0495] Example 115: (S)3-(8-bromo-6-(pyridin-2-yl)-1-ethylthio-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 115)

[0496] 1H NMR(300MHz, CDCl3-d1)δ:8.78(dd,J=3.5,1.3Hz,1H),7.85–7.74(m,3H),7.67(t,J=1.3Hz,1H),7.54(dd,J=7.9,1.3Hz, 1H),7.33-7.30(m,1H),6.13(t,J=5.2Hz,1H),3.65(s,3H),3.29–3.18(m,2H),2.70–2.52(m,4H),1.40(t,J=7.2Hz,3H). 13 C NMR (75MHz, CDCl3-d1) δ173.72,160.73,157.51,153.83,151.63,147.12,137.61,137.47,136.40,134.75,12 5.25,124.56,123.44,122.65,120.39,66.22,57.42,52.01,29.61,29.23,14.70.LC-MS(ESI)m / z:486.1[M+H] + .

[0497] Example 116: (S)3-(8-bromo-6-(pyridin-2-yl)-1-((cyclopropylmethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 116)

[0498] 1 H NMR(300MHz, CDCl3-d1)δ:8.79(dd,J=3.6,1.3Hz,1H),7.82(td,J=7.6,1.2Hz,1H),7.80–7.71(m,2H),7.67(d,J=2.2Hz,1H),7.56(dd, J=7.9,1.4Hz,1H),7.33-7.31(m,1H),6.13(t,J=5.2Hz,1H),3.66(s,3H),3.02(d,J=4.8Hz,2H),2.70–2.51(m,4H),1.40–1.24(m,5H). 13C NMR (75MHz, CDCl3-d1) δ173.58,162.37,156.38,154.59,149.57,147.13,137.57,137.28,136.60,134.78,127.9 3,125.30,122.76,122.64,120.55,59.05,51.80,39.41,29.45,29.28,10.89,6.19.LC-MS(ESI)m / z:512.4[M+H] + .

[0499] Example 117: (S)3-(8-bromo-6-(pyridin-2-yl)-1-((2-morpholinoethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 117)

[0500] 1 H NMR(300MHz, CDCl3-d1)δ:8.58(d,J=4.2Hz,1H),8.18(d,J=7.9Hz,1H),7.85( dd,J=7.2,1.3Hz,1H),7.79(dd,J=6.5,4.2Hz,1H),7.66(d,J=8.8Hz,2H),7.41 -7.37(m,1H),4.27(t,J=5.1Hz,1H),3.69(s,3H),3.64(t,J=4.8Hz,4H),3.52 -3.41(m,2H),2.91-2.82(m,4H),2.74(t,J=6.7Hz,2H),2.46(t,J=4.5Hz,4H). 13 C NMR (75MHz, CDCl3-d1) δ173.62,162.11,156.69,154.59,148.12,147.31,137.47,137.09,136.60,135.16,128.24,1 25.26,122.73,122.59,120.96,65.69,58.05,54.45,53.31,51.93,32.18,29.54,29.28.LC-MS(ESI)m / z:571.1[M+H] + .

[0501] Example 118: (S)3-(8-bromo-6-(pyridin-2-yl)-1-(3-((dimethylamino)propyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 118)

[0502] 1 H NMR (300MHz, CDCl3-d1) δ: 8.79 (dd, J=3.6, 1.2Hz, 1H), 7.81 (td, J=7.6, 1.2Hz, 1H),7.78–7.72(m,2H),7.67(dd,J=1.7,0.9Hz,1H),7.56(dd,J=7.9,1.4Hz,1H) ,7.33-7.30(m,1H),6.13(t,J=5.4Hz,1H),3.65(s,3H),3.27(t,J=6.4Hz,2H), 2.73–2.62(m,2H),2.60–2.48(m,4H),2.25(s,6H),1.93(pd,J=6.5,1.1Hz,2H). 13 C NMR (75MHz, CDCl3-d1) δ173.33,162.11,156.72,154.49,147.89,146.31,137.30,137.09,136.67,135.32,128.24,1 25.26,122.74,122.32,120.94,58.49,58.05,51.96,44.90,32.55,29.54,29.28,26.44.LC-MS(ESI)m / z:543.2[M+H] + .

[0503] Example 119: (S)3-(8-chloro-6-(2-chlorophenyl)-1-(2-((pyrrolidine-1-yl)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 119)

[0504] 1 H NMR(300MHz, CDCl3-d1)δ:7.91(d,J=2.0Hz,1H),7.61(dd,J=7.1,2.2Hz,1H),7.51–7.37(m,4H),7.29(d,J=7.5Hz,1H),5.22(s,1H) ,3.68(s,3H),3.48(d,J=0.9Hz,2H),2.68–2.58(m,4H),2.49(s,2H),2.44–2.31(m,2H),2.30–2.19(m,2H),1.80(d,J=12.5Hz,4H). 13C NMR (75MHz, CDCl3-d1) δ173.30,160.77,154.13,148.12,138.12,135.83,134.71,132.61,130.82,130.51,130.43,129.2 9,129.04,128.19,126.36,122.81,57.76,55.23,54.02,51.98,32.51,29.56,29.39,23.39.LC-MS(ESI)m / z:544.1[M+H] + .

[0505] Example 120: (S)3-(8-bromo-6-(2-fluorophenyl)-1-(2-((pyrrolidine-1-yl)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 120)

[0506] 1 H NMR(300MHz, CDCl3-d1)δ:7.72(dd,J=8.4,2.6Hz,1H),7.61–7.56(m,2H),7.55–7.43(m,2H),7.28(td,J=7.5,1.5Hz,1H),7.21(dd,J= 7.8,1.5Hz,1H),6.10(t,J=5.2Hz,1H),3.64(s,3H),3.45(t,J=5.1Hz,2H),2.74(t,J=4.9Hz,4H),2.65–2.51(m,6H),1.89-182(m,4H). 13 C NMR (75MHz, CDCl3-d1) δ173.65,163.32,159.17,154.22,147.98,136.64,136.54,132.59,131.54,130.23,128.57,127.7 0,124.00,121.79,120.47,115.76,58.29,55.23,54.02,51.93,32.18,29.54,29.30,23.40.LC-MS(ESI)m / z:572.1[M+H] + .

[0507] Example 121: (S)3-(8-bromo-6-(2-chlorophenyl)-1-((2-(pyrrolidine-1-yl)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 121)

[0508] 1 H NMR(300MHz, CDCl3-d1)δ:7.75(dd,J=8.4,2.6Hz,1H),7.68–7.58(m,2H),7.55 (dd,J=7.7,1.6Hz,1H),7.49(dd,J=7.8,1.6Hz,1H),7.40(td,J=7.6,1.6Hz,1H) ,7.33(td,J=7.5,1.5Hz,1H),6.11(t,J=5.2Hz,1H),3.64(s,3H),3.45(t,J=5. 1Hz,2H),2.74(t,J=4.9Hz,4H),2.65–2.51(m,6H),1.86(td,J=4.9,2.7Hz,4H). 13 C NMR (75MHz, CDCl3-d1) δ173.57,160.33,154.78,149.12,137.49,136.40,136.44,134.71,133.11,131.17,130.63,129.3 6,128.19,126.09,121.84,120.47,57.87,55.33,54.02,51.93,32.14,29.54,29.39,23.33.LC-MS(ESI)m / z:588.0[M+H] + .

[0509] Example 122: (S)3-(8-chloro-6-(2-chlorophenyl)-1-(2-((piperidin-1-yl)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 122)

[0510] 1 H NMR(300MHz, CDCl3-d1)δ:7.77(d,J=8.7Hz,1H),7.61(dd,J=2.4Hz,8.7Hz,1H), 7.57–7.53(m,1H),7.41(dd,J=5.6,3.0Hz,2H),7.37(d,J=3.6Hz,1H),7.17(d,J= 2.4Hz,1H),4.26(t,J=6.9Hz,1H),3.67(s,3H),3.50(t,J=7.1Hz,2H),2.83(t,J =3.7Hz,4H),2.74(t,J=7.1Hz,2H),2.47(s,4H),1.62–1.56(m,4H),1.45(s,2H). 13C NMR (75MHz, CDCl3-d1) δ173.63,160.77,154.20,148.15,138.23,135.93,134.66,132.61,130.83,130.54,130.43,129.22,1 29.10,128.13,126.35,122.71,57.76,54.95,54.06,51.97,32.18,29.54,29.39,26.64,23.96.LC-MS(ESI)m / z:558.2[M+H] + .

[0511] Example 123: (S)3-(8-bromo-6-(2-fluorophenyl)-1-(2-((piperidin-1-yl)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 123)

[0512] 1 H NMR(300MHz, CDCl3-d1)δ:7.73(dd,J=8.4,2.6Hz,1H),7.62–7.56(m,2H),7.53–7.43(m,2H),7.29(td,J=7.5,1.5Hz,1H),7.17(dd,J= 7.9,1.5Hz,1H),6.10(t,J=5.2Hz,1H),3.64(s,3H),3.45(t,J=5.1Hz,2H),2.68–2.51(m,10H),1.58-1.54(m,4H),1.48–1.37(m,2H). 13 C NMR (75MHz, CDCl3-d1) δ173.60,163.21,159.19,154.15,148.12,136.35,136.54,132.44,131.52,130.23,128.53,127.70,1 24.00,121.85,120.25,115.78,58.29,54.90,54.06,51.93,32.18,29.54,29.30,26.83,24.03.LC-MS(ESI)m / z:586.1[M+H] + .

[0513] Example 124: (S)3-(8-chloro-6-(2-chlorophenyl)-1-(2-((pyridin-4-yl)methyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 124)

[0514] 1 H NMR(300MHz, CDCl3-d1)δ:8.47(d,J=5.2Hz,2H),7.93–7.83(m,1H),7.78(d,J=8.7Hz,1H),7.67–7.56(m,1H),7.56–7.47 (m,2H),7.46–7.34(m,3H),7.23–7.09(m,1H),4.64–4.43(m,2H),4.30(t,J=6.2Hz,1H),3.59(s,3H),2.67–2.57(m,4H). 13 C NMR (75MHz, CDCl3-d1) δ173.65,161.70,154.16,149.79,147.48,146.26,138.07,135.66,134.71,132.61,130.82,130.51 ,130.43,129.36,129.04,128.19,126.36,124.08,122.76,57.76,51.96,39.84,29.54,29.39.LC-MS(ESI)m / z:538.1[M+H] + .

[0515] Example 125: (S)3-(8-bromo-6-(2-fluorophenyl)-1-(2-((pyridin-4-yl)methyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 125)

[0516] 1 H NMR(300MHz, CDCl3-d1)δ:8.62–8.57(m,2H),7.73(dd,J=8.4,2.6Hz,1H),7.59(d,J=2.5Hz,1H),7.58–7.51(m,2H),7.47(td,J=7.7,1. 6Hz,1H),7.33–7.26(m,3H),7.26–7.20(m,1H),6.10(t,J=5.2Hz,1H),4.53(s,2H),3.64(s,3H),2.67–2.57(m,2H),2.57–2.51(m,2H). 13C NMR (75MHz, CDCl3-d1) δ173.62,163.35,159.17,154.16,149.79,147.48,146.26,136.60,136.54,132.67,131.51,130.23 ,128.53,127.70,124.09,124.00,121.79,120.47,115.76,58.29,51.92,39.84,29.54,29.30.LC-MS(ESI)m / z:566.4[M+H] + .

[0517] Example 126: (S)3-(8-bromo-6-(pyridin-2-yl)-1-(((pyridin-4-yl)methyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 126)

[0518] 1 H NMR(300MHz, CDCl3-d1)δ:8.62–8.58(m,1H),8.53–8.46(m,2H),8.18(d,J=7.9Hz,1H),7.84(td,J=7.8,1.7Hz,1H),7.75(dd,J=8.7,2.2Hz,1H),7.67 (d,J=2.2Hz,1H),7.54(d,J=8.7Hz,1H),7.42-7.38(m,1H),7.36–7.32(m, 2H),4.55–4.37(m,2H),4.30–4.21(m,1H),3.69(s,3H),2.93–2.77(m,4H). 13 C NMR (75MHz, CDCl3-d1) δ173.41,161.93,156.42,154.52,149.59,147.48,147.33,146.06,137.37,137.19,136.60,135 .48,128.31,125.25,124.08,122.76,122.61,120.94,58.05,51.96,39.84,29.54,29.34.LC-MS(ESI)m / z:549.4[M+H] + .

[0519] Example 127: (S)3-(8-chloro-6-(2-chlorophenyl)-1-(2-((4,4-difluoropiperidin-1-yl)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 127)

[0520] 1 H NMR(300MHz, CDCl3-d1)δ:7.68–7.59(m,2H),7.62–7.52(m,2H),7.53–7.45(m,1H),7.41–7.32(m,2H),6.11( t,J=5.2Hz,1H),3.66(s,3H),3.46(t,J=5.2Hz,2H),2.74–2.62(m,6H),2.65–2.51(m,4H),2.25–2.12(m,4H). 13 C NMR (75MHz, CDCl3-d1) δ172.98,160.92,154.16,148.12,137.98,135.93,134.65,132.65,131.03,130.83,130.56,129.18,1 29.10,128.07,126.30,122.69,118.58,57.87,54.60,51.78,48.83,32.57,31.95,9.54,29.49.LC-MS(ESI)m / z:594.4[M+H] + .

[0521] Example 128: (S)3-(8-bromo-6-(2-fluorophenyl)-1-(2-((4,4-difluoropiperidin-1-yl)ethyl)thio))-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 128)

[0522] 1 H NMR(300MHz, CDCl3-d1)δ:7.74(dd,J=8.4,2.4Hz,1H),7.62–7.54(m,2H),7.54–7.44(m,2H),7.33–7.21(m,2H),4.32(t,J=5.3,6.8Hz,1H),3. 66(s,3H),3.46(t,J=5.2,7.4Hz,2H),2.74–2.68(m,3H),2.68–2.62(m, 4H), 2.61 (dd, J=1.9, 1.2Hz, 1H), 2.61–2.51 (m, 2H), 2.25–2.12 (m, 4H). 13C NMR (75MHz, CDCl3-d1) δ173.33,163.02,159.33,154.16,148.12,136.55,136.54,132.67,131.53,130.23,128.58,127.70,1 23.91,121.85,120.45,118.58,115.77,58.29,54.60,51.94,48.71,32.61,32.23,29.34,29.63.LC-MS(ESI)m / z:622.5[M+H] + .

[0523] Example 129: (S)3-(8-chloro-6-(2-chlorophenyl)-1-((2-(4-methylpiperazin-1-yl)2-oxoethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 129)

[0524] 1 H NMR(300MHz, CDCl3-d1)δ:7.72(d,J=8.4Hz,1H),7.64–7.57(m,2H),7.55(d,J=2.4Hz,1H),7.53–7.45(m,1H),7.41–7.32 (m,2H),6.11(t,J=5.2Hz,1H),4.08(d,J=2.7Hz,2H),3.66(s,3H),3.49(t,J=5.3Hz,4H),2.65–2.50(m,8H),2.23(s,3H). 13 C NMR (75MHz, CDCl3-d1) δ173.37,171.54,160.92,154.17,147.98,137.98,136.05,134.72,132.65,131.16,130.83,130.56,1 29.18,129.10,128.33,126.44,122.74,56.97,54.43,51.80,46.07,45.25,35.71,29.47,29.78.LC-MS(ESI)m / z:587.5[M+H] + .

[0525] Example 130: (S)3-(8-chloro-6-(2-chlorophenyl)-1-(2-(4-methylpiperazin-1-carbonyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 130)

[0526] 1 H NMR(300MHz, CDCl3-d1)δ:7.69(d,J=8.3Hz,1H),7.61–7.54(m,2H),7.54–7.45(m,2H),7.41–7.30( m,2H),6.12(t,J=5.4Hz,1H),3.77–3.62(m,7H),2.74–2.63(m,2H),2.60–2.45(m,6H),2.29(s,3H). 13 C NMR (75MHz, CDCl3-d1) δ173.22,164.87,160.77,154.72,143.84,137.98,136.55,134.71,132.60,130.83,130.54,130.4 3,129.20,129.10,128.16,126.36,122.85,57.81,54.27,52.08,47.39,45.36,29.54,29.57.LC-MS(ESI)m / z:573.1[M+H] + .

[0527] Example 131: (S)3-(8-bromo-6-(2-fluorophenyl)-1-(2-(4-methylpiperazine-1-carbonyl)thio))-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 131)

[0528] 1 H NMR (300MHz, CDCl3-d1)δ:7.75(dd,J=8.4,2.6Hz,1H),7.59(d,J=2.5Hz,1H),7.56–7.44(m,3H),7.28(td,J=7.6,1.4Hz,1H),7.22(dd,J=7.7,1.3Hz,1 H),6.12(t,J=5.4Hz,1H),3.77–3.68(m,2H),3.68–3.63(m,5H),2.74–2.63 (m,2H),2.57(ddd,J=7.9,5.5,1.0Hz,2H),2.55–2.45(m,4H),2.29(s,3H). 13C NMR(75MHz, CDCl3-d1)δ:173.61,167.58,160.70,148.74,143.80,143.14,132.49,131.38,131.10,129.83,129.44,129.4 0,124.54,124.20,121.80,115.88,115.73,54.33,54.18,51.71,51.50,44.98,33.02,31.91.LC-MS(ESI)m / z:601.10[M+H] + .

[0529] Example 132: (S)3-(8-chloro-6-(2-chlorophenyl)-1-(3-((diethylamino)propyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 132)

[0530] 1 H NMR(300MHz, CDCl3-d1)δ:7.91(d,J=1.6Hz,1H),7.62(dd,J=7.2,2.2Hz,1H),7.51–7.37(m,5H),5.32(s,1H), 3.68(s,3H),3.25(d,J=2.5Hz,2H),2.65–2.49(m,6H),2.44–2.28(m,4H),1.99(d,J=2.2Hz,2H),0.99(s,6H). 13 C NMR(75MHz, CDCl3-d1)δ:173.62,145.70,144.01,141.27,138.92,132.79,130.73,130.17,129.99,129.43,129.37,128.94,1 28.72,128.62,124.77,120.33,54.20,53.56,51.40,47.08,33.51,33.02,31.91,30.11,11.83.LC-MS(ESI)m / z:560.16[M+H] + .

[0531] Example 133: (S)3-(8-chloro-6-(2-chlorophenyl)-1-(2-((dimethylamino)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 133)

[0532] 1H NMR(300MHz, CDCl3-d1)δ:7.75(d,J=8.7Hz,1H),7.59(dd,J=8.7,2.4Hz,1H),7.55(dd,J=5.8,3.4Hz,1H),7.45–7.39(m,2H),7.37–7.32(m ,1H),7.17(d,J=2.3Hz,1H),4.26(t,J=6.0Hz,1H),3.67(s,3H),3.62–3.40(m,2H),2.91–2.78(m,4H),2.72(h,J=6.1Hz,2H),2.30(s,6H). 13 C NMR(75MHz, CDCl3-d1)δ:173.88,145.68,144.42,143.87,138.88,133.17,130.68,130.54,129.82,129.72,129.4 6,129.41,128.74,124.66,122.11,54.20,52.83,51.40,42.92,37.46,33.02,31.93.LC-MS(ESI)m / z:518.11[M+H] + .

[0533] Example 134: (S)3-(8-bromo-6-(2-fluorophenyl)-1-(2-((dimethylamino)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 134)

[0534] 1 H NMR(300MHz, CDCl3-d1)δ:7.73(dd,J=8.5,2.5Hz,1H),7.61–7.55(m,2H),7.54–7.43(m,2H),7.29(td,J=7.7,1.5Hz,1H),7.23(dd,J=7.9,1.5Hz ,1H),4.30(t,J=5.2Hz,1H),3.64(s,3H),3.46(t,J=5.2Hz,2H),2.71(dt ,J=12.4,5.2Hz,1H),2.69–2.57(m,3H),2.60–2.51(m,2H),2.29(s,6H). 13C NMR(75MHz, CDCl3-d1)δ:173.78,160.38,145.61,144.39,143.49,134.16,131.97,130.87,130.41,130.05,129.44,12 4.54,124.20,122.40,115.82,115.55,54.33,52.69,51.40,42.92,37.46,33.02,30.26.LC-MS(ESI)m / z:546.09[M+H] + .

[0535] Example 135: (S)3-(8-chloro-6-(2-chlorophenyl)-1-(2-((4-hydroxypiperidin-1-yl)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 135)

[0536] 1 H NMR(300MHz, CDCl3-d1)δ:7.91(d,J=2.0Hz,1H),7.66(dd,J=7.0,2.4Hz,1H), 7.50–7.35(m,4H),7.29(d,J=7.5Hz,1H),5.25(s,1H),3.68(s,3H),3.63–3.5 1(m,2H),3.48(d,J=0.9Hz,2H),2.62(d,J=2.4Hz,4H),2.55(s,2H),2.44–2.3 2(m,2H),2.33(d,J=7.0Hz,1H),2.25(d,J=12.5Hz,1H),1.79(d,J=7.5Hz,4H). 13 C NMR(75MHz, CDCl3-d1)δ:173.61,145.63,145.00,143.04,138.86,132.79,130.72,130.15,129.99,129.37,128.72,128. 60,128.19,124.67,119.77,67.85,54.33,51.50,50.74,50.54,33.99,33.02,32.94,31.92.LC-MS(ESI)m / z:574.14[M+H] + .

[0537] Example 136: (S)3-(8-chloro-6-(2-chlorophenyl)-1-(2-((4-methylpiperidin-2-carbonyl)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 136)

[0538] 1 H NMR(300MHz, CDCl3-d1)δ:7.98(d,J=2.0Hz,1H),7.66–7.59(m,1H),7.50–7.44(m, 1H),7.46–7.33(m,3H),7.29(d,J=7.5Hz,1H),5.25(s,1H),4.42(s,1H),3.68(s,3H ),2.62(d,J=10.6Hz,2H),2.49(d,J=12.3Hz,1H),2.41–2.30(m,5H),2.25(d,J=12 .5Hz,1H),2.02(d,J=21.1Hz,2H),1.65(s,1H),1.59(d,J=4.6Hz,2H),1.53(s,1H). 13 C NMR(75MHz, CDCl3-d1)δ:175.67,173.61,148.74,145.69,143.49,138.91,132.79,130.71,130.16,129.99,129.84,129.37,128.72, 128.60,128.19,124.68,122.11,62.34,54.53,54.33,51.45,41.64,33.02,31.91,28.57,26.60,22.95.LC-MS(ESI)m / z:571.12[M+H] + .

[0539] Example 137: (S)3-(8-chloro-6-(2-chlorophenyl)-1-thio-2,4-dihydro-1H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza -4-yl)propionic acid-2-morpholinoethyl ester (compound 137)

[0540] 1H NMR(300MHz, CDCl3-d1)δ:13.8(s,1H),7.80(d,J=8.5Hz,1H),7.58–7.50(m,2H),7.50–7.45(m,1H),7.45–7.36(m,2H),7.34(d,J=2.4Hz,1H),4.5 6(t,J=6.0Hz,1H),4.22(t,J=6.5Hz,2H),3.60–3.48(m,4H),2.85(t,J=6 .4,8.2Hz,2H),2.72–2.57(m,4H),2.53–2.45(m,2H),2.43–2.28(m,2H). 13 C NMR(75MHz, CDCl3-d1)δ:173.82,172.99,145.29,143.07,143.02,132.79,130.64,130.52,129.38,129.37,129.30,12 8.94,128.72,128.62,124.74,122.85,66.04,65.90,55.35,54.26,53.77,30.86,30.56.LC-MS(ESI)m / z:546.11[M+H] + .

[0541] Example 138: (S)3-(8-chloro-6-(2-chlorophenyl)-1-(2-((1H-imidazol-1-yl)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 138)

[0542] 1 H NMR(300MHz, CDCl3-d1)δ:7.85(s,1H),7.63(d,J=8.3Hz,1H),7.59–7.51(m,3H),7.47(dd,J=7.7,1.7Hz,1H),7.38(td,J=2 3.6,7.4,1.6Hz,2H),7.03(s,2H),6.10(t,J=5.2Hz,1H),4.27(td,J=5.0,1.6Hz,2H),3.66–3.60(m,5H),2.66–2.51(m,4H). 13C NMR(75MHz, CDCl3-d1)δ:173.87,145.66,145.05,143.04,139.39,138.93,133.92,132.79,130.68,130.55,129.71,129.46,12 9.44,129.37,129.31,128.94,128.62,124.73,120.33,54.20,51.40,49.21,36.04,33.07,31.90.LC-MS(ESI)m / z:541.09[M+H] + .

[0543] Example 139: (S)3-(8-bromo-6-(2-fluorophenyl)-1-(2-((1H-imidazol-1-yl)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 139)

[0544] 1 H NMR(300MHz, CDCl3-d1)δ:7.85(s,1H),7.72(dd,J=8.4,2.6Hz,1H),7.61–7 .54(m,2H),7.52(dd,J=7.9,1.5Hz,1H),7.47(td,J=7.7,1.6Hz,1H),7.28(t d,J=7.5,1.5Hz,1H),7.21(dd,J=7.8,1.5Hz,1H),7.03(s,2H),6.10(t,J=5. 2Hz,1H),4.27(td,J=5.0,1.7Hz,2H),3.66–3.60(m,5H),2.67–2.51(m,4H). 13 C NMR (75MHz, CDCl3-d1) δ172.39,160.89,154.16,148.42,137.37,136.33,136.43,134.20,132.08,131.13,130.83,129.1 3,128.19,126.39,121.84,120.47,57.37,55.24,54.02,51.93,32.18,28.94,29.34,23.27.LC-MS(ESI)m / z:569.1[M+H] + .

[0545] Example 140: (S)3-(8-chloro-6-(2-chlorophenyl)-1-(2-((1H-pyrrolo-1-yl)ethyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza 4-yl)methyl propionate (compound 140)

[0546] 1 H NMR(300MHz, CDCl3-d1)δ:7.87(dd,J=8.7,2.4Hz,1H),7.78(d,J=8.7Hz,1H), 7.65(dd,J=5.9,3.3Hz,1H),7.55–7.49(m,2H),7.49–7.42(m,1H),7.18(d,J=2 .3Hz,1H),6.76(t,J=2.1Hz,2H),5.99(t,J=2.1Hz,2H),4.32(t,J=6.4Hz,1H) ,4.24(t,J=6.5Hz,2H),3.60(s,3H),2.68(t,J=6.4Hz,2H),2.52-2.50(m,4H). 13 C NMR(75MHz, CDCl3-d1)δ:173.90,145.62,145.01,143.04,138.89,132.79,130.67,130.54,129.72,129.46,129.44,129.37 ,128.94,128.62,125.93,124.70,120.33,119.18,54.20,53.61,51.39,36.04,33.00,31.89.LC-MS(ESI)m / z:540.09[M+H] + .

[0547] Example 141: (S)3-(8-chloro-6-(2-chlorophenyl)-1-((1-methyl-1H-imidazol-4-yl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 141)

[0548] 1 H NMR(300MHz, CDCl3-d1)δ:8.03(s,1H),7.97–7.90(m,2H),7.61(dd,J=7.5,2.0Hz,1H ),7.53–7.34(m,5H),5.17(s,1H),3.68(s,6H),2.56–2.45(m,2H),2.30–2.19(m,2H). 13C NMR(75MHz, CDCl3-d1)δ:173.94,156.53,145.64,145.36,144.40,138.85,137.66,133.15,132.20,130.65,130.54,129.82 ,129.70,129.46,129.44,128.94,128.70,124.72,122.11,54.20,51.40,33.80,33.05,30.26; LC-MS(ESI)m / z:527.07[M+H] + .

[0549] Example 142: (S)3-(8-chloro-6-(2-chlorophenyl)-1-((ethyl(methyl)carbamoyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 142)

[0550] 1H NMR (300MHz, CDCl3-d1) δ7.75(d,J=8.4Hz,1H),7.60–7.51(m,3H),7.50(dd,J=7.8,1.4Hz,1H),7.41(td,J=7.7,1.8Hz,1H),7.34(td,J=7.5,1 .4Hz,1H),4.30(t,J=8.2Hz,1H),3.64(s,3H),3.45(q,J=7.2Hz,2H),3. 02(s,3H),2.75–2.59(m,2H),2.59-2.53(m,2H),1.22(t,J=7.2Hz,3H). 13 C NMR(75MHz, CDCl3-d1)δ:173.90,162.05,148.74,146.39,143.80,138.87,133.16,130.61,130.53,129.82,129.75,129.4 6,129.45,129.25,128.74,124.69,124.25,54.19,51.41,43.61,34.27,32.98,30.26,12.47.LC-MS(ESI)m / z:532.09[M+H] + .

[0551] Example 143: (S)3-(8-chloro-6-(2-chlorophenyl)-1-(3-((dimethylamino)-3-oxopropyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza Methyl 4-yl)propionate (compound 143)

[0552] 1 H NMR(300MHz, CDCl3-d1)δ:7.89(d,J=1.9Hz,1H),7.61(dd,J=7.1,2.2Hz,1H),7.54–7.37(m,6H),5.32(s, 1H),3.68(s,3H),3.39(s,2H),2.86(s,5H),2.80–2.69(m,2H),2.44–2.28(m,3H),2.25(d,J=12.5Hz,1H). 13 C NMR(75MHz, CDCl3-d1)δ:173.78,172.42,145.67,144.02,143.04,138.84,132.79,130.60,130.55,129.74,129.46,129.3 7,129.02,128.93,128.62,124.74,120.33,54.22,51.42,36.42,35.74,33.03,31.88,31.67.LC-MS(ESI)m / z:546.1[M+H] + .

[0553] Example 144: (S)3-(8-chloro-6-(2-chlorophenyl)-1-(((4,5-dihydro-1H-imidazol-2-yl)methyl)thio)-4H-benzo[f][1,2,4]triazole[4,3-a][1,4]diaza 4-yl)methyl propionate (compound 144)

[0554] 1 H NMR(300MHz, CDCl3-d1)δ:7.91(d,J=2.0Hz,1H),7.61(dd,J=7.2,2.3Hz,1H),7.54–7.37(m,4H),7.31(d,J=7.5Hz,1H),6.83(s,1 H),5.17(s,1H),4.32(s,2H),3.68(s,3H),3.59–3.50(m,4H),2.49(d,J=12.5Hz,1H),2.40(d,J=12.5Hz,1H),2.30–2.19(m,2H). 13C NMR(75MHz, CDCl3-d1)δ:173.87,159.44,145.60,143.90,141.65,138.93,133.18,130.69,130.56,129.82,129.73,129.4 6,129.44,128.91,128.70,124.73,122.11,54.18,51.38,44.30,44.27,41.81,33.04,31.95.LC-MS(ESI)m / z:529.1[M+H] + .

[0555] Pharmacological activity experiments:

[0556] In anesthetic drug experiments, the latency period generally refers to the time from the start of drug administration to the loss of consciousness in the subject. A shorter latency period is better, indicating a rapid onset of action. The duration of anesthesia generally refers to the time from loss of consciousness to regained consciousness in the subject. The duration of anesthesia varies depending on the animal model or species. An excessively long duration of anesthesia may cause adverse inhibitory effects on the cardiovascular and respiratory systems, such as neurological side effects including drowsiness and dizziness. Conversely, an excessively short duration of anesthesia may affect the anesthetic effect, leading to problems such as increased intraoperative anesthetic dosage.

[0557] Example 145. Experiment on drug-induced loss of righting reflex in mice:

[0558] KM mice (female, 18-25g) were randomly divided into groups. After a single rapid intravenous injection of the drug via the tail vein, the latency and duration of loss of the righting reflex were recorded. The experimental results are shown in Table 1 below.

[0559] Table 1. Tests showing drug-induced loss of righting reflex in mice

[0560]

[0561]

[0562]

[0563]

[0564] As shown in Table 1, in mouse experiments, the compounds of the present invention have an anesthetic effect with rapid onset and even faster recovery.

[0565] Example 146. Test on drug-induced loss of righting reflex in rats

[0566] SD rats (male, 200-280g) were randomly divided into groups. After a single rapid bolus injection of the drug via the tail vein, the latency and duration of the righting reflex were recorded.

[0567] Table 2. Tests showing drug-induced loss of righting reflex in rats

[0568]

[0569]

[0570] Table 2 above shows that, in rat experiments, the compounds of the present invention have a rapid onset and rapid recovery anesthetic effect.

[0571] Example 147. Rat anesthesia induction experiment with continuous drug infusion for 20 minutes

[0572] SD rats (male, 200-280g) were randomly divided into groups. The initial dose was rapidly injected via the tail vein, followed by a maintenance dose. After 20 minutes, the duration of the righting reflex and the time from awakening to recovery were recorded.

[0573] Table 3. Rat anesthesia induced by continuous drug infusion for 20 minutes

[0574]

[0575]

[0576] Table 3 above shows that the compounds of the present invention can maintain anesthesia in animals during continuous infusion, and once the continuous infusion ends, they have the characteristics of faster awakening and faster recovery.

[0577] Example 148. Effect of drugs on cellular GABA activation currents detected by patch-clamp assay

[0578] The test compounds were dissolved in different concentrations in external solutions (NaCl 140mM, KCl 4.7mM, HEPES 10mM, CaCl2 2mM, glucose 10mM, MgCl2 1mM, pH 7.4). HEK 293T cells were seeded on coverslips and cultured in DMEM medium at 37°C and 5% CO2 for 24 h. GABA Cl - Whole-cell recordings were performed using a HEKA EPC 10USB patch-clamp amplifier. 2 μM GABA was used to excite Cl... - Current and membrane potential were clamped at -60 mV. Cells were simultaneously treated with the analyte compound and 2 μM GABA, and the effect on Cl- in the same cells was recorded. - The induction effect of current and E max .

[0579] Table 4. Effects on cellular GABA activation current

[0580]

[0581] Maximum enhancement percentage E of 2μM GABA current max And its corresponding concentration (μM): 100% for normal individuals. The higher the percentage, the lower the corresponding concentration, and the stronger the depth of anesthesia.

[0582] Table 5. Effects on cellular GABA activation current

[0583]

[0584] Note: The positive enhancement of EC induced by 2μM GABA 50 (μM): The concentration of the drug required to achieve a certain depth of anesthesia; the lower the value, the better.

[0585] As shown in Tables 4 and 5 above, the compounds of the present invention have a suitable depth of anesthesia, indicating that the compounds of the present invention have excellent anesthetic effects.

[0586] Example 149. Rate of drug crossing the blood-brain barrier in vitro

[0587] Place a Transwell apparatus (5.0 μm pore size) into a 24-well cell culture well, then add 1×10 5 hCMEC / D3 cells per ml were transferred to the upper wells of a Transwell microwell at a rate of 150 μL / well, and cell culture medium was added to the lower wells. Once the cells had formed a complete monolayer, the medium was replaced with EBM-2 complete medium containing 1% FBS, and the cells were cultured in a CO2 incubator for 10 days until a completely dense monolayer was formed. After the cell monolayer was formed, 0.1 mg / ml of the compound was added to the lower culture medium, and the compound concentration in the upper culture medium was measured after 5 minutes to calculate the permeability.

[0588] P 化合物 % = C 上层化合物 / C 下层化合物 ×100%

[0589] Table 6. Tests on the rate of drug crossing the blood-brain barrier

[0590]

[0591]

[0592] Table 6 above shows that this compound has the ability to rapidly cross the blood-brain barrier.

[0593] Example 150. In vitro plasma half-life test of drugs

[0594] Plasma preparation: After fasting for 12 hours with unlimited access to water, SD rats were fed and blood was collected via the orbital venous plexus. The freshly collected blood was placed in centrifuge tubes containing heparin sodium and centrifuged at 5000 rpm for 10 minutes at 4°C. The supernatant was slowly aspirated and aliquoted. Finally, the collected SD rat plasma was sealed, labeled, and stored at -20°C for later use.

[0595] Prepare the target compound sample: Accurately weigh the target compound using an analytical balance and prepare a stock solution with a concentration of 2 mg / mL (solvent is V acetone: V Tween 80: V physiological saline = 1:1:3) for later use.

[0596] Determination of the in vitro half-life of the target compound sample: Take 20 μL of the mother solution of the test compound and 80 μL of rat plasma, respectively, mix well, and take 9 parallel EP tubes, labeled as corresponding test tubes for 0, 1, 2, 3, 5, 10, 15, 20, and 30 min. Incubate in a 37℃ water bath for 0, 1, 2, 3, 5, 10, 15, 20, and 30 min. At each time point, take 50 μL of the mixture from the corresponding EP tube, add 100 mL of acetonitrile to precipitate the protein, vortex for 10 min, centrifuge at 12000 rpm for 15 min, take the supernatant and centrifuge again at 12000 rpm for 10 min. Use Intellistat software in UPLC-MS / MS to determine the optimal detection method of the MRM mode of the target compound, integrate the corresponding mass spectrometry peak areas, and calculate its plasma half-life.

[0597] Table 7. Results of in vitro plasma half-life test for drugs

[0598]

[0599] Table 7 above shows that this compound has the ability to rapidly cross the blood-brain barrier.

[0600] Example 151. Detection of whether a drug has a potential inhibitory effect on voltage-gated potassium ion channels (hERG) using fluorescence polarization technology.

[0601] This experiment calculated the IC by detecting the effect of eight compound concentrations on the hERG channel current. 50 Strictly follow the Predictor TM The hERG fluorescence polarization analysis kit was used. Before measuring fluorescence polarization, the assay plate was covered to protect the reagents from light and evaporation. After incubation at room temperature for 2-4 hours, the sample plate was centrifuged, and the fluorescence polarization values ​​were read. The excitation light was 540 nm, and the emission light was 573 nm. Data showed that the cardiotoxicity of the compound of this invention was significantly lower than that of the marketed drug midazolam.

[0602] Table 8. Results of the effect of drugs on hERG channel currents

[0603] #imgpt361#

[0604] The above pharmacological data show that the compounds of general formula (I) of this invention have the characteristics of rapid onset of action, strong depth of action, and rapid recovery, and the preferred compounds have almost no accumulation.

[0605] Lyophilized powder for injection:

[0606] Example 152. Lyophilized powder for injection containing active agent compound 32:

[0607] Compound 32 (10g) and glycine (100g) were added to a vial, and water for injection was added to a final volume of 1L. The pH of the solution was adjusted to 3.5. The solution was dispensed into 1000 vials and then lyophilized into a lyophilized powder for injection using conventional lyophilization methods.

[0608] It should be understood that after reading the above teachings of this invention, those skilled in the art can make various modifications or alterations to this invention, and these equivalent forms also fall within the scope defined by the appended claims.

Claims

1. The following compounds or their pharmaceutically acceptable salts: 。 2. A pharmaceutical composition comprising an effective amount of the compound of claim 1 or a pharmaceutically pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers, wherein the effective amount is from 10 mg to 3000 mg.

3. The compound of claim 1 or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 2, wherein the pharmaceutically acceptable salt is selected from acetate, adipic acid salt, aspartate, benzoate, benzenesulfonate, bicarbonate, carbonate, bisulfate, sulfate, borate, camphor sulfonate, citrate, cyclohexanesulfonate, ethanedisulfonate, ethanesulfonate, formate, fumarate, glucohepanoate, glucuronate, hexafluorophosphate, hydrochloride, oxide, hydrobromide, bromide, hydroiodate, iodide, hydroxyethyl sulfonate, lactate, malate, cis... Butenedioic acid salts, malonate salts, methanesulfonates, methyl sulfates, naphthates, 2-naphthalenesulfonates, nicotinates, nitrates, orotates, oxalates, palmitates, dihydronaphthalates, phosphates, hydrogen phosphates, dihydrogen phosphates, pyroglutamates, glycosides, stearates, succinates, tannins, tartrates, toluenesulfonates, trifluoroacetates and sine, aluminum salts, arginine salts, benzathine penicillin salts, calcium salts, choline salts, diethylamine salts, diethanolamine salts, glycine salts, lysine salts, magnesium salts, meglumine salts, ethanolamine salts, sodium salts, potassium salts, ammonium salts, tromethamine salts and zinc salts.

4. The use of the compound of claim 1 or a pharmaceutically acceptable salt thereof or the composition of claim 2 in the preparation of sedative and anesthetic drugs.

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