α,β-unsaturated amide compounds, preparation methods thereof, pharmaceutical compositions and uses

Abstract

The present invention provides an α,β-unsaturated amide compound, a preparation method thereof, a pharmaceutical composition and uses. Specifically, the present invention provides a compound represented by the following formula I, wherein the definition of each group is as described in the specification. The compound can be prepared as a compound for improving cerebral blood flow and as a pharmaceutical composition for treating neurodegenerative diseases such as Alzheimer's disease and vascular dementia, and stroke. General formula I: TIFF2025521917000044.tif22170

Description

Technical Field

[0001] The present invention relates to the fields of pharmaceutical chemistry and medicine, and specifically provides α,β-unsaturated amide compounds, methods for preparing the same, pharmaceutical compositions containing such compounds, and uses of drugs for treating neurodegenerative diseases such as Alzheimer's disease and vascular dementia, and stroke.

Background Art

[0002] Alzheimer's disease (AD) is a degenerative brain disease that accounts for about two-thirds of dementia in the elderly. The main symptoms include progressive memory loss, β-amyloid deposition (β-Amyloid, Aβ), and neurofibrillary tangles (NFT), etc. The pathological mechanism of AD is very complex. Currently, the commercially available drugs can only temporarily relieve or control the symptoms of AD, and an effective treatment pathway targeting the disease mechanism has not yet been found. Aging is the most major risk factor for AD, and more than 95% of AD patients have a late-onset with the onset age of 65 years or older. Less than 5% of AD cases are early-onset, and the main cause of onset is genetic factors. Cardiovascular and cerebrovascular diseases are also major risk factors for AD. In addition to vascular dementia caused by known vascular lesions, vascular changes may also contribute to the onset of AD. Capillaries are the most abundant and smallest vascular units in the brain, and the damage to cerebral blood flow (CBF) or blood-brain barrier (BBB) caused by them is related to the decline in memory in AD.

[0003] Increasingly, many studies have revealed that in the early stages of AD and in mild cognitive impairment (MCI) due to normal aging, there are decreases in cerebral blood flow, cerebral vascular reactivity damage, and disorders of hemodynamic responses. In early studies, according to transcranial Doppler measurements of the middle cerebral artery, it has been found that individuals with high cerebral blood flow velocity are less likely to develop dementia or have atrophy of the hippocampus and amygdala. In arterial spin-labeling MRI of patients with MCI or early AD, it can be seen that cerebral blood flow in the posterior dentate gyrus and the entire frontal cortex is decreased. In the elderly with a high risk of AD disease, a decrease in cerebral blood flow or inadequate regulation of cerebral blood flow precedes cognitive decline, brain atrophy, and the accumulation of β-amyloid. APOE is a major genetic risk factor for AD and, at the same time, a susceptibility gene for vascular lesions. In animal models, in transgenic mice with targeted replacement of mouse apolipoprotein E4 (APOE) with the human APOE4 gene at 125-127, a decrease in cerebral blood flow and vascular insufficiency have also been confirmed, and it has been found that the vascular phenotype of APOE4-expressing mice precedes neuronal and synaptic dysfunction. Insufficient perfusion may cause or exacerbate neurological disorders and neuropathological changes such as Alzheimer's disease. When blood flow is chronically reduced by 50%, significant changes occur in cognitive function, and when human cerebral blood flow is continuously reduced by more than 20%, it may lead to a decrease in concentration. However, when rat cerebral blood flow exceeds 30%, spatial memory is impaired. When cerebral blood flow decreases, Na + / K +The activity of the pump, and all processes dependent thereon (including the maintenance of the resting potential and the uptake of glutamate), is reduced, which also leads to the production of adenosine, which inhibits the release of glutamate and affects neuronal function. Bilateral carotid artery occlusion in rats induces memory impairment, neurological deficits, synaptic changes and β-amyloid, which in turn leads to the accumulation of neurotoxic β-amyloid oligomers. Cerebral ischemia, hypoxia and Aβ deposition interact with each other. Insufficient perfusion may cause acceleration of Aβ deposition. Aβ damages cerebrovascular function, increases arterial vasoconstriction and decreases cerebral blood flow. In rodents, local ischemia leads to the accumulation of hyperphosphorylated Tau within neurons and the formation of fibrils similar to those seen in human neurodegenerative diseases and Alzheimer's disease. Insufficient perfusion affects the structural and functional changes of the brain and provides a promising biomarker that may potentially identify and diagnose preclinical Alzheimer's disease.

[0004] Capillaries are the narrowest blood vessels in the brain, branching from arterioles to form a rich microvascular network. The maximum surface area of capillaries per gram of brain is approximately 120 cm 2It is so. The capillary network is mainly composed of endothelial cells, basement membrane, pericytes, and astrocytes. In animal models, it has been observed that capillary damage is a precursor to dementia-related neurodegeneration. Capillary constriction in AD causes hypoxia in neural tissue, which is thought to be the cause of the decrease in glucose metabolism in AD. Also, ischemia and hypoxia have been shown to upregulate the enzyme β-secretase (BACE1) involved in the production of Aβ. Capillary blood flow is mainly regulated by pericytes, and a large number of studies have shown that pericyte damage is closely related to AD. In autopsy samples of the brains of some AD patients, the level of pericytes can sometimes decrease by more than 50%. In pericyte-deficient transgenic mice, blood flow decreases, microvessels decrease, Aβ expression increases, and the permeability of the blood-brain barrier increases. Many neuropathological studies report morphological changes in cerebral capillaries in AD and lesions in the periventricular white matter similar to ischemic infarcts. Autopsy studies of patients in the late stage of Alzheimer's disease show that a large number of capillary endothelial cells in the brain still fall off, the blood vessel wall collapses, and the density decreases. Capillaries are easily damaged due to their delicate and special structure, and capillary degeneration occurs more frequently and is more common than vascular amyloidosis, suggesting that potentially, the long-term degenerative process of the AD cerebral microvascular system may be partially independent of amyloid toxicity. More and more studies have shown that vascular factors are major risk factors for AD, and damage to the neurovascular unit is associated with AD. Therefore, finding a way to intervene in capillaries to increase cerebral blood flow may be important for the prevention and treatment of AD.

[0005] The present invention provides a target compound that targets capillaries to increase cerebral blood flow, thereby improving the symptoms of AD, and is used in the clinical treatment of neurodegenerative diseases such as Alzheimer's disease and vascular dementia, as well as stroke.

Summary of the Invention

Problems to be Solved by the Invention

[0006] One object of the present invention is to provide an α,β-unsaturated amide compound represented by the general formula I, or a pharmaceutically acceptable salt, racemic compound, R-isomer or S-isomer thereof, or a mixture thereof.

[0007] Another object of the present invention is to provide a method for preparing the α,β-unsaturated amide compound represented by the general formula I.

[0008] Yet another object of the present invention is to provide a method for treating neurodegenerative diseases such as Alzheimer's disease related to cerebral blood flow, vascular dementia, etc., and stroke, which comprises administering to a patient in need of such treatment one or more selected from the group consisting of the α,β-unsaturated amide compound of the general formula I, a pharmaceutically acceptable salt, racemic compound, R-isomer, S-isomer or mixture thereof.

Means for Solving the Problems

[0009] The first aspect of the present invention provides an α,β-unsaturated amide compound having a structure as shown in the following formula I, or a racemic compound, R-isomer, S-isomer, pharmaceutically acceptable salt or mixture thereof, Formula I: TIFF2025521917000002.tif23170 Here, R 1 、R 2 、R 3 and R 4 are each independently hydrogen, deuterium, tritium, halogen, cyano group, amino group, hydroxy group, nitro group, substituted or unsubstituted C1-C6 alkyl group, substituted or unsubstituted C1-C6 alkoxy group, or (CHR 6 ) n R selected from the group consisting of, where said R is a substituted or unsubstituted C6-C10 aryl group, substituted or unsubstituted 5-7 membered heteroaryl group, substituted or unsubstituted 5-7 membered heterocyclic group, substituted or unsubstituted C3-C12 cycloalkyl group or hetero-condensed ring, or R 3 and R 4together with the carbon atom to which they are attached, form a group selected from the group consisting of a carbonyl group, a substituted or unsubstituted 3- to 8-membered cycloalkyl group, or a substituted or unsubstituted 4- to 8-membered heterocyclic group, TIFF2025521917000003.tif10170 ring is selected from the group consisting of a C6-C10 aryl group, a 5- to 12-membered heteroaryl group, a 5- to 12-membered heterocyclic group, a C3-C12 cycloalkyl group or a hetero-fused ring, R 5 is selected from the group consisting of hydrogen, deuterium, tritium, halogen, cyano group, amino group, hydroxy group, nitro group, substituted or unsubstituted C1-C6 alkyl group, substituted or unsubstituted C1-C6 alkoxy group, substituted or unsubstituted C6-C10 aryl group, substituted or unsubstituted C6-C10 aryloxy group, substituted or unsubstituted 5- to 7-membered heteroaryl group, substituted or unsubstituted 5- to 7-membered heteroaryloxy group, substituted or unsubstituted 5- to 7-membered heterocyclic ring, substituted or unsubstituted C3-C12 cycloalkyl group TIFF2025521917000004.tif10170 are 1, 2, 3, 4 or 5 substituents located on the ring, or two adjacent Rs 5 are TIFF2025521917000005.tif10170 are bonded end to end with the atoms on the ring to form a substituted or unsubstituted 4- to 8-membered ring (i.e., form a fused ring structure with the A ring), or TIFF2025521917000006.tif10170 two Rs on the same atom on the ring 5 are bonded end to end to TIFF2025521917000007.tif10170 form a ring and a substituted or unsubstituted 3- to 8-membered ring (i.e., form a spiro ring structure with the A ring), X is N(CH2) n R 6 、O, or S, n is 0, 1, 2, or 3, R 6is independently selected from the group consisting of hydrogen, halogen, cyano group, amino group, hydroxy group, nitro group, substituted or unsubstituted C1-C6 alkyl group, substituted or unsubstituted C1-C6 alkoxy group, substituted or unsubstituted C6-C10 aryl group, oxygen, sulfur, and nitrogen, a substituted or unsubstituted 5-12 membered heterocyclic ring containing 1-3 heteroatoms selected from the group consisting of, a substituted or unsubstituted C2-C10 acyl group, a substituted or unsubstituted C2-C10 ester group, a substituted or unsubstituted C1-C6 amide group, -SO2R5, -COR5, Here, unless otherwise specified, each of the heteroaromatic ring, heterocyclic ring or heterocyclic group independently contains 1-4 heteroatoms selected from oxygen, sulfur and nitrogen, the aromatic ring or heteroaromatic ring includes a monocyclic, fused ring or condensed ring, and the carbocyclic ring or heterocyclic ring includes a monocyclic, fused ring, spiro ring or bridged ring, The substitution means being substituted by one or more (preferably 1-3) substituents selected from the group consisting of halogen, cyano group, nitro group, amino group, hydroxy group, hydroxymethyl group, carboxy group, mercapto group, C1-C6 alkyl group, halogen-substituted C1-C6 alkyl group, C1-C6 alkoxy group, halogen-substituted C1-C6 alkoxy group, C1-C6 alkoxycarbonyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C3-C8 cycloalkyl group, C1-C6 alkylsulfonyl group, substituted or unsubstituted C6-C10 aryl group, substituted or unsubstituted 5-7 membered heteroaryl group, and 3-12 membered heterocyclic group, The halogen is F, Cl, Br or I.

[0010] In another preferred example, the TIFF2025521917000008.tif10170 ring is selected from the group consisting of C6-C10 aryl group, C5-C12 heteroaryl group.

[0011] In another preferred example, the R 1 , R 2 , R 3 and R 4are each independently hydrogen, deuterium, a substituted or unsubstituted C1-C6 alkyl group, or (CHR 6 ) n R, selected from the group consisting of, where said R is selected from the group consisting of a substituted or unsubstituted C6-C10 aryl group, a substituted or unsubstituted 5- to 7-membered heteroaryl group, n is 0, 1 or 2, and R 6 is hydrogen, halogen, or a substituted or unsubstituted C1-C6 alkyl group.

[0012] In another preferred example, said R 1 , R 2 , R 3 and R 4 are each independently hydrogen, deuterium, a substituted or unsubstituted C1-C6 alkyl group, (CHR 6 ) n R, selected from the group consisting of, where said R is selected from the group consisting of a substituted or unsubstituted C6-C10 aryl group, a substituted or unsubstituted 5- to 7-membered heteroaryl group.

[0013] In another preferred example, said R 3 and R 4 are each independently selected from the group consisting of hydrogen, deuterium, a substituted or unsubstituted C1-C6 alkyl group.

[0014] In another preferred example, said R 1 is H or D, and R 2 is selected from the group consisting of hydrogen, deuterium, a substituted or unsubstituted C1-C6 alkyl group, (CHR 6 ) n R, selected from the group consisting of, where said R is selected from the group consisting of a substituted or unsubstituted C6-C10 aryl group, a substituted or unsubstituted 5- to 7-membered heteroaryl group, and said substitution means being substituted by one or more substituents selected from the group consisting of halogen, cyano group, nitro group, amino group, hydroxy group, hydroxymethyl group, carboxy group, mercapto group, C1-C6 alkyl group, halogen-substituted C1-C6 alkyl group, C1-C6 alkoxy group, halogen-substituted C1-C6 alkoxy group, C1-C6 alkoxycarbonyl group.

[0015] In another preferred example, said R 3 and R 4 are each independently deuterium.

[0016] In another preferred example, said R 1 and R 2 are each independently deuterium.

[0017] In another preferred example, the compound of formula I is the compound described in each example.

[0018] The second aspect of the present invention provides a method for preparing a compound of formula I described in the first aspect of the present invention, said method comprising reacting a compound of formula II with a compound of formula III in an inert solvent JPEG2025521917000009.jpg33170 to obtain a compound of formula I.

[0019] In another preferred example, said reaction is carried out in the presence of an organic amine and pivaloyl chloride.

[0020] In another preferred example, said organic amine is triethylamine.

[0021] The third aspect of the present invention provides a pharmaceutical composition, said pharmaceutical composition comprising (1) a compound described in the first aspect of the present invention or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate or solvate thereof, (2) a pharmaceutically acceptable carrier.

[0022] The fourth aspect of the present invention provides the use of a compound described in the first aspect of the present invention or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or the pharmaceutical composition according to claim 9, which is used in the preparation of a pharmaceutical composition for preventing and / or treating neurodegenerative diseases or stroke.

[0023] In another preferred example, the neurodegenerative disease is selected from the group consisting of Alzheimer's disease and vascular dementia.

Advantages of the Invention

[0024] It should be understood that within the scope of the present invention, by combining each of the above technical features of the present invention with the technical features specifically described below (for example, in the embodiments), new or preferred technical solutions can be constituted. Due to space limitations, it will not be repeated here.

Brief Description of the Drawings

[0025]

Figure 1

Figure 2

Modes for Carrying Out the Invention

[0026] As a result of thorough research over a long period of time, the present inventors provide an α,β-unsaturated amide compound that can be used for neurodegenerative diseases such as Alzheimer's disease. The compound can effectively improve cerebral blood flow in capillaries. Based on the above findings, the present inventors completed the present invention.

[0027] Term In the present invention, the halogen is F, Cl, Br or I.

[0028] In the present invention, unless otherwise specified, the terms used have the ordinary meanings known to those skilled in the art.

[0029] In the present invention, the term "C1-C6 alkyl group" refers to a straight-chain or branched-chain alkyl group having 1 to 6 carbon atoms, and includes, without limitation, a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, an s-butyl group, a t-butyl group, a pentyl group, a hexyl group, etc., and preferably includes an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, an s-butyl group, and a t-butyl group.

[0030] In the present invention, the term "C1-C6 alkoxy group" refers to a straight-chain or branched-chain alkoxy group having 1 to 6 carbon atoms, and includes, without limitation, a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, a butoxy group, etc.

[0031] In the present invention, the term "C2-C6 alkenyl group" refers to a straight-chain or branched-chain alkenyl group having 2 to 6 carbon atoms and containing one double bond, and includes, without limitation, a vinyl group, a propenyl group, a butenyl group, an isobutenyl group, a pentenyl group, a hexenyl group, etc.

[0032] In the present invention, the term "C2-C6 alkynyl group" refers to a straight-chain or branched-chain alkynyl group having 2 to 6 carbon atoms and containing one triple bond, and includes, without limitation, an ethynyl group, a propynyl group, a butynyl group, an isobutynyl group, a pentynyl group, a hexynyl group, etc.

[0033] In the present invention, the term "C3-C10 cycloalkyl group" refers to a cyclic alkyl group having 3 to 10 carbon atoms in the ring, and includes, without limitation, a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, a cyclooctyl group, a cyclodecyl group, etc. The terms "C3-C8 cycloalkyl group", "C3-C7 cycloalkyl group", and "C3-C6 cycloalkyl group" have similar meanings.

[0034] In the present invention, the term "C3-C10 cycloalkenyl group" refers to a cyclic alkenyl group having 3 to 10 carbon atoms in the ring, and includes, but is not limited to, cyclopropenyl group, cyclobutenyl group, cyclopentenyl group, cyclohexenyl group, cycloheptenyl group, cyclooctenyl group, cyclodecenyl group, etc. The term "C3-C7 cycloalkenyl group" has the same meaning.

[0035] In the present invention, the terms "aromatic ring" or "aryl group" have the same meaning. Preferably, the "aryl group" is a "C6-C12 aryl group" or a "C6-C10 aryl group". The term "C6-C12 aryl group" refers to an aromatic ring group having 6 to 12 carbon atoms and containing no heteroatoms in the ring such as phenyl group, naphthyl group, etc. The term "C6-C10 aryl group" has the same meaning.

[0036] In the present invention, the terms "aromatic heterocyclic ring" or "heteroaryl group" have the same meaning, and refer to a heteroaromatic group containing one or more heteroatoms. The heteroatoms referred to in this specification include oxygen, sulfur, and nitrogen. For example, furyl group, thienyl group, pyridyl group, pyrazolyl group, pyrrolyl group, N-alkylpyrrolyl group, pyrimidinyl group, pyrazinyl group, imidazolyl group, tetrazolyl group, etc. The heteroaryl group ring can be condensed with an aryl group, a heterocyclic group or a cycloalkyl group ring, where the ring bonded to the parent structure is a heteroaryl group ring. The heteroaryl group may or may not be optionally substituted.

[0037] In the present invention, the term "3- to 12-membered heterocyclic group" refers to a saturated or unsaturated 3- to 12-membered ring group containing 1 to 3 heteroatoms selected from oxygen, sulfur, and nitrogen in the ring, such as dioxolanyl group, etc. The term "3- to 7-membered heterocyclic group" has the same meaning.

[0038] In the present invention, the term "substituted" refers to the substitution of one or more hydrogen atoms of a specific group by a specific substituent. The specific substituent is the corresponding substituent described above, or the substituent appearing in each example. Unless otherwise specified, a certain substituent can have a substituent selected from a specific group at any substitutable position of the group, and the substituents may be the same or different at each position. A cyclic substituent such as a heterocycloalkyl group can be bonded to another ring such as a cycloalkyl group to form a spiro ring system, for example, two rings having a common carbon atom. Those skilled in the art will understand that the combinations of substituents contemplated by the present invention are stable or chemically feasible. The substituents are, for example, a C1-8 alkyl group, a C2-8 alkenyl group, a C2-8 alkynyl group, a C3-8 cycloalkyl group, a 3- to 12-membered heterocyclic group, an aryl group, a heteroaryl group, a halogen, a hydroxyl group, a carboxyl group (-COOH), a C1-8 aldehyde group, a C2-10 acyl group, a C2-10 ester group, an amino group, an alkoxy group, a C1-10 sulfonyl group, etc. (but not limited thereto).

[0039] The compound of formula I The present invention provides an α,β-unsaturated amide compound having a structure represented by the following formula I, or a racemic compound, an R-isomer, an S-isomer, a pharmaceutically acceptable salt thereof, or a mixture thereof: Formula I: TIFF2025521917000010.tif22170 Here, R 1 、R 2 、R 3 and R 4 are each independently hydrogen, deuterium, tritium, halogen, cyano group, amino group, hydroxy group, nitro group, a substituted or unsubstituted C1-C6 alkyl group, a substituted or unsubstituted C1-C6 alkoxy group, or (CHR 6 ) nIt can be selected from the group consisting of R, where said R is selected from the group consisting of a substituted or unsubstituted C6-C10 aryl group, a substituted or unsubstituted 5-7 membered heteroaryl group, a substituted or unsubstituted 5-7 membered heterocyclic group, a substituted or unsubstituted C3-C12 cycloalkyl group or a hetero-condensed ring. TIFF2025521917000011.tif10170 ring is selected from the group consisting of a C6-C10 aryl group, a 5-12 membered heteroaryl group, a 5-12 membered heterocyclic group, a C3-C12 cycloalkyl group or a hetero-condensed ring. R 5 is selected from the group consisting of hydrogen, deuterium, tritium, halogen, cyano group, amino group, hydroxy group, nitro group, substituted or unsubstituted C1-C6 alkyl group, substituted or unsubstituted C1-C6 alkoxy group, substituted or unsubstituted C6-C10 aryl group, substituted or unsubstituted C6-C10 aryloxy group, substituted or unsubstituted 5-7 membered heteroaryl group, substituted or unsubstituted 5-7 membered heteroaryloxy group, substituted or unsubstituted 5-7 membered heterocyclic ring, substituted or unsubstituted C3-C12 cycloalkyl group. TIFF2025521917000012.tif10170 are 1, 2, 3, 4 or 5 substituents located on the ring. or two adjacent Rs 5 are TIFF2025521917000013.tif10170 The atoms on the ring are bonded end to end to form a substituted or unsubstituted 4-8 membered ring (i.e., form a fused ring structure with the A ring). or TIFF2025521917000014.tif10170 Two Rs on the same atom on the ring are bonded end to end to 5 form TIFF2025521917000015.tif10170 a substituted or unsubstituted 3-8 membered ring with the ring (i.e., form a spiro ring structure with the A ring). X is N(CH2) n R 6 O, or S, n is 0, 1, 2, or 3. R 6is independently selected from the group consisting of hydrogen, halogen, cyano group, amino group, hydroxy group, nitro group, substituted or unsubstituted C1-C6 alkyl group, substituted or unsubstituted C1-C6 alkoxy group, substituted or unsubstituted C6-C10 aryl group, oxygen, sulfur and nitrogen-containing 1-3 heteroatoms substituted or unsubstituted 5-12 membered heterocyclic substituted or unsubstituted C2-C10 acyl group, substituted or unsubstituted C2-C10 ester group, substituted or unsubstituted C1-C6 amide group, -SO2R5, -COR5, wherein, unless otherwise specified, each of the heteroaromatic ring, heterocyclic ring or heterocyclic group independently contains 1-4 heteroatoms selected from oxygen, sulfur and nitrogen, the aromatic ring or heteroaromatic ring includes a monocyclic, fused ring or condensed ring, and the carbocyclic ring or heterocyclic ring includes a monocyclic, fused ring, spiro ring or bridged ring, The above-mentioned substitution means being substituted by one or more (preferably 1-3) substituents selected from the group consisting of halogen, cyano group, nitro group, amino group, hydroxy group, hydroxymethyl group, carboxy group, mercapto group, C1-C6 alkyl group, halogen-substituted C1-C6 alkyl group, C1-C6 alkoxy group, halogen-substituted C1-C6 alkoxy group, C1-C6 alkoxycarbonyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C3-C8 cycloalkyl group, C1-C6 alkylsulfonyl group, substituted or unsubstituted C6-C10 aryl group, substituted or unsubstituted 5-7 membered heteroaryl group, and 3-12 membered heterocyclic group, The above-mentioned halogen is F, Cl, Br or I.

[0040] In a preferred embodiment, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , TIFF2025521917000016.tif10170 ring, X, O, S or n is, respectively, a group corresponding to the compound of each example.

[0041] Method for preparing the compound of formula I The present invention further provides a method for preparing a compound represented by general formula I, and the preparation method is carried out according to the following scheme (example).

[0042] The compound of formula (I) can be prepared according to the method shown in Scheme 1 below.

[0043] The structural formulas and R group numbers used in the following schemes are only used in this section. The compounds of formula (II) and formula (III) are commercially available or can also be synthesized using conventional techniques in the art.

[0044] Scheme 1: JPEG2025521917000017.jpg31170

[0045] Pharmaceutical composition Another aspect of the present invention provides a pharmaceutical composition comprising a therapeutically effective amount of one or more selected from the compounds of the above general formula I, pharmaceutically acceptable salts, enantiomers, diastereomers or racemic compounds thereof, and optionally one or more pharmaceutically acceptable carriers, excipients, adjuvants, auxiliary substances and / or diluents. The auxiliary substances are, for example, odorants, flavorants, sweeteners and the like.

[0046] The pharmaceutical composition provided by the present invention preferably contains the active ingredient in a weight ratio of 1 to 99%, and its preferred ratio is that the compound of general formula I occupies 65 wt% to 99 wt% of the total weight as the active ingredient, and the remaining part is a pharmaceutically acceptable carrier, diluent or solution or physiological saline.

[0047] The compounds and pharmaceutical compositions provided by the present invention can be in various forms such as tablets, capsules, powders, syrups, solutions, suspensions and aerosol agents, and can be present in a suitable solid or liquid carrier or diluent and a sterile device suitable for injection or infusion.

[0048] The various dosage forms of the pharmaceutical composition of the present invention can be prepared according to the conventional preparation methods in the pharmaceutical field. The unit dosage of the formulation contains 1 mg to 700 mg of the compound of general formula I, preferably, the unit dosage of the formulation contains 25 mg to 300 mg of the compound of general formula I.

[0049] The compounds and pharmaceutical compositions of the present invention can be clinically used for mammals including humans and animals, and can be administered through administration routes such as oral, nasal, skin, lung or digestive tract, etc. Oral administration is most preferred. The most preferred daily dose is 50 - 1400 mg / kg body weight for a single administration or 25 - 700 mg / kg body weight for divided administrations. Regardless of the administration route, the optimal dose for an individual varies depending on the specific treatment method. Usually, it starts with a small amount initially and gradually increases the amount until the optimal amount for oneself is found.

[0050] Another aspect of the present invention provides for improving cerebral blood flow, which comprises one or more selected from the compounds represented by the above general formula I, pharmaceutically acceptable salts thereof, racemic compounds, R - isomers, S - isomers or mixtures thereof, and optionally one or more pharmaceutically acceptable carriers, excipients, adjuvants, auxiliary substances and / or diluents.

[0051] The compounds and compositions of the present invention are used for the treatment and prevention of cerebral blood flow - related neurodegenerative diseases and strokes, and the diseases include, but are not limited to, Alzheimer's disease, vascular dementia and stroke, etc.

[0052] Hereinafter, the present invention will be further described in conjunction with specific examples. It should be understood that these examples are only used to illustrate the present invention and do not limit the scope of the present invention. In the following examples, the experimental methods without indicating specific conditions usually follow the conventional conditions or the conditions proposed by the manufacturer. Unless otherwise specified, percentages and parts are calculated by weight.

[0053] Example 1 (E)-3-(3-(o-Tolyl)acryloyl)oxazolidin-2-one TIFF2025521917000018.tif28170

[0054] Compound (E)-3-(o-Tolyl)acrylic acid 1a (400.0 mg, 2.47 mmol) and triethylamine (685.6 μL, 4.93 mmol) were dissolved in ultra-dry dichloromethane. Under the protection of argon gas, pivaloyl chloride (364.5 μL, 2.96 mmol) was added at -78 °C. The reaction mixture was transferred to room temperature and stirred for 1 hour. Then, oxazolidin-2-one (214.8 mg, 2.47 mmol) and lithium chloride (104.5 mg, 2.47 mmol) were added at -78 °C. The mixture was stirred at room temperature for 12 hours. After monitoring the completion of the reaction by TLC, water was added to quench the reaction, and the mixture was extracted with dichloromethane. The organic layers were combined, washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated, and the crude product was purified by column chromatography to obtain the target product (E)-3-(3-(o-Tolyl)acryloyl)oxazolidin-2-one (490 mg, white solid) with a yield of 85.9%. 1 1H NMR (400 MHz, DMSO-d6) δ 7.96 (d, J = 15.7 Hz, 1H), 7.73 (d, J = 15.7 Hz, 1H), 7.61 (d, J = 8.7 Hz, 1H), 7.38 - 7.31 (m, 1H), 7.30 (d, J = 3.9 Hz, 2H), 4.47 - 4.37 (m, 2H), 4.06 - 3.97 (m, 2H), 2.41 (s, 3H). LRMS (ESI): 232.09 [M+H] + 。

[0055] Example 2 (E)-3-(3-(m-Tolyl)acryloyl)oxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(m-Tolyl)acrylic acid, and the remaining required raw materials, reagents, and preparation methods were the same as those in Example 1 to obtain (E)-3-(3-(m-Tolyl)acryloyl)oxazolidin-2-one (yield 82.1%). 11H NMR (400 MHz, DMSO-d6) δ 7.81 (d, J = 16.0 Hz, 1H), 7.72 (d, J = 16.0 Hz, 1H), 7.51 - 7.44 (m, 2H), 7.36 (dt, J = 10.2, 5.1 Hz, 1H), 7.28 (d, J = 7.8 Hz, 1H), 4.42 (td, J = 8.1, 2.4 Hz, 2H), 4.00 (td, J = 8.1, 2.6 Hz, 2H), 2.34 (s, 3H). LRMS (ESI): 232.09 [M+H] + 。

[0056] Example 3 (E)-3-(3-(p-Tolyl)acryloyl)oxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(p-tolyl)acrylic acid, and the remaining necessary raw materials, reagents, and preparation methods were the same as those in Example 1 to obtain (E)-3-(3-(p-tolyl)acryloyl)oxazolidin-2-one (yield 85.2%). 1 1H NMR (400 MHz, DMSO-d6) δ 7.77 (d, J = 15.8 Hz, 1H), 7.70 (d, J = 15.9 Hz, 1H), 7.55 (d, J = 8.2 Hz, 2H), 7.26 (d, J = 7.9 Hz, 2H), 4.39 (dd, J = 8.6, 7.4 Hz, 2H), 3.97 (dd, J = 8.6, 7.4 Hz, 2H), 2.32 (s, 3H). LRMS (ESI): 232.09 [M+H] + 。

[0057] Example 4 (E)-3-(3-(2-Methoxyphenyl)acryloyl)oxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(2-methoxyphenyl)acrylic acid, and the remaining necessary raw materials, reagents, and preparation methods were the same as those in Example 1 to obtain (E)-3-(3-(2-methoxyphenyl)acryloyl)oxazolidin-2-one (yield 87.2%). 11H NMR (400 MHz, DMSO-d6) δ 7.97 (d, J = 16.0 Hz, 1H), 7.88 (d, J = 15.9 Hz, 1H), 7.61 (dd, J = 7.7, 1.6 Hz, 1H), 7.45 (ddd, J = 8.5, 7.3, 1.6 Hz, 1H), 7.12 (d, J = 8.4 Hz, 1H), 7.03 (t, J = 7.5 Hz, 1H), 4.41 (t, J = 8.0 Hz, 2H), 3.99 (dd, J = 8.5, 7.4 Hz, 2H), 3.88 (s, 3H). LRMS (ESI): 248.08 [M+H] + .

[0058] Example 5 (E)-3-(3-(3-Methoxyphenyl)acryloyl)oxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(3-methoxyphenyl)acrylic acid, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(3-methoxyphenyl)acryloyl)oxazolidin-2-one (yield 87.6%). 1 1H NMR (400 MHz, DMSO-d6) δ 7.81 (d, J = 15.8 Hz, 1H), 7.73 (d, J = 15.8 Hz, 1H), 7.39 (t, J = 7.9 Hz, 1H), 7.31 - 7.24 (m, 1H), 7.21 (t, J = 2.0 Hz, 1H), 7.08 - 7.02 (m, 1H), 4.42 (dd, J = 8.5, 7.4 Hz, 2H), 4.00 (dd, J = 8.6, 7.3 Hz, 2H), 3.80 (s, 3H). LRMS (ESI): 248.08 [M+H] + .

[0059] Example 6 (E)-3-(3-(4-Methoxyphenyl)acryloyl)oxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(4-methoxyphenyl)acrylic acid, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(4-methoxyphenyl)acryloyl)oxazolidin-2-one (yield 82.7%). 11H NMR (400 MHz, DMSO-d6) δ 7.77 - 7.66 (m, 2H), 7.64 (d, J = 8.7 Hz, 2H), 7.03 (d, J = 8.8 Hz, 2H), 4.41 (dd, J = 8.5, 7.4 Hz, 2H), 3.99 (dd, J = 8.5, 7.4 Hz, 2H), 3.81 (s, 3H). LRMS (ESI): 248.08 [M + H] + 。

[0060] Example 7 (E)-3-(3-(2-(Trifluoromethylphenyl)acryloyl)oxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(2-trifluoromethylphenyl)acrylic acid, and the remaining necessary raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(2-(trifluoromethylphenyl)acryloyl)oxazolidin-2-one (yield 81.5%). 1 1H NMR (400 MHz, DMSO-d6) δ 7.98 - 7.78 (m, 5H), 7.68 (t, J = 7.6 Hz, 1H), 4.43 (dd, J = 8.5, 7.4 Hz, 2H), 4.02 (dd, J = 8.5, 7.4 Hz, 2H). LRMS (ESI): 286.06 [M + H] + 。

[0061] Example 8 (E)-3-(3-(3-(Trifluoromethylphenyl)acryloyl)oxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(3-trifluoromethylphenyl)acrylic acid, and the remaining necessary raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(3-(trifluoromethylphenyl)acryloyl)oxazolidin-2-one (yield 80.3%). 1 1H NMR (400 MHz, DMSO-d6) δ 8.05 - 7.97 (m, 2H), 7.94 - 7.83 (m, 2H), 7.82 (d, J = 7.1 Hz, 1H), 7.71 (t, J = 7.8 Hz, 1H), 4.43 (dd, J = 8.5, 7.4 Hz, 2H), 4.02 (dd, J = 8.5, 7.4 Hz, 2H). LRMS (ESI): 286.06 [M + H] + 。

[0062] Example 9 (E)-3-(3-(4-(Trifluoromethylphenyl)acryloyl)oxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid is replaced with (E)-3-(4-trifluoromethylphenyl)acrylic acid, and the remaining necessary raw materials, reagents and preparation methods are the same as in Example 1 to obtain (E)-3-(3-(4-(trifluoromethylphenyl)acryloyl)oxazolidin-2-one (yield 85.6%). 1 H NMR (400 MHz, DMSO-d6) δ 7.95 - 7.87 (m, 3H), 7.85 - 7.79 (m, 3H), 4.43 (dd, J = 8.5, 7.4 Hz, 2H), 4.01 (dd, J = 8.6, 7.4 Hz, 2H). LRMS (ESI): 286.06 [M+H] + 。

[0063] Example 10 (E)-3-(3-(2-Fluorophenyl)acryloyl)oxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid is replaced with (E)-3-(2-fluorophenyl)acrylic acid, and the remaining necessary raw materials, reagents and preparation methods are the same as in Example 1 to obtain (E)-3-(3-(2-fluorophenyl)acryloyl)oxazolidin-2-one (yield 92.1%). 1 H NMR (400 MHz, DMSO-d6) δ 7.93 (d, J = 16.0 Hz, 1H), 7.77 (d, J = 16.0 Hz, 1H), 7.79 - 7.72 (m, 1H), 7.58 - 7.47 (m, 1H), 7.42 - 7.26 (m, 2H), 4.50 - 4.37 (m, 2H), 4.01 (m, 2H). LRMS (ESI): 236.06 [M+H] + 。

[0064] Example 11 (E)-3-(3-(4-Fluorophenyl)acryloyl)oxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(4-fluorophenyl)acrylic acid, and the remaining necessary raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(4-fluorophenyl)acryloyl)oxazolidin-2-one (yield 89.0%). 1 H NMR(400MHz,DMSO-d6)δ 7.77(s,2H),7.77-7.73(m,2H),7.37-7.25(m,2H),4.42(dd,J=8.6,7.3Hz,2H),4.00(dd,J=8.5,7.4Hz,2H).LRMS(ESI):236.06[M+H] + 。

[0065] Example 12 (E)-3-(3-(4-Chlorophenyl)acryloyl)oxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(4-chlorophenyl)acrylic acid, and the remaining necessary raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(4-chlorophenyl)acryloyl)oxazolidin-2-one (yield 91.1%). 1 H NMR(400MHz,DMSO-d6)δ 7.82(d,J=15.9Hz,1H),7.75(d,J=15.9Hz,1H),7.73-7.68(m,2H),7.53(dd,J=8.4,1.2Hz,2H),4.42(t,J=8.0Hz,2H),4.00(t,J=8.0Hz,2H).LRMS(ESI):252.03[M+H] + 。

[0066] Example 13 (E)-3-(3-(2-Bromophenyl)acryloyl)oxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(2-bromophenyl)acrylic acid, and the remaining necessary raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(2-bromophenyl)acryloyl)oxazolidin-2-one (yield 93.4%). 11H NMR (400 MHz, DMSO-d6) δ 7.96 (dd, J = 15.9, 1.7 Hz, 1H), 7.84 - 7.73 (m, 3H), 7.50 (td, J = 7.5, 1.4 Hz, 1H), 7.39 (td, J = 7.7, 1.8 Hz, 1H), 4.43 (td, J = 7.9, 1.7 Hz, 2H), 4.01 (ddd, J = 8.7, 7.2, 1.7 Hz, 2H). LRMS (ESI): 295.98, 297.98 [M+H] + 。

[0067] Example 14 (E)-3-(3-(4-Bromophenyl)acryloyl)oxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(4-bromophenyl)acrylic acid, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(4-bromophenyl)acryloyl)oxazolidin-2-one (yield 91.1%). 1 1H NMR (400 MHz, DMSO-d6) δ 7.83 (d, J = 15.9 Hz, 1H), 7.73 (d, J = 15.9 Hz, 1H), 7.67 (d, J = 8.7 Hz, 2H), 7.63 (d, J = 8.7 Hz, 2H), 4.42 (dd, J = 8.6, 7.4 Hz, 2H), 4.00 (dd, J = 8.5, 7.4 Hz, 2H). LRMS (ESI): 295.98, 297.98 [M+H] + 。

[0068] Example 15 (E)-3-(3-(2-Phenoxyphenyl)acryloyl)oxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(2-phenoxyphenyl)acrylic acid, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(2-phenoxyphenyl)acryloyl)oxazolidin-2-one (yield 89.3%). 11H NMR (400 MHz, DMSO-d6) δ 7.99 - 7.88 (m, 2H), 7.83 - 7.76 (m, 1H), 7.50 - 7.44 (m, 1H), 7.41 (tq, J = 7.4, 1.2 Hz, 2H), 7.27 (td, J = 7.6, 1.5 Hz, 1H), 7.17 (tt, J = 7.4, 1.2 Hz, 1H), 7.05 - 6.98 (m, 2H), 6.96 (dt, J = 8.2, 1.3 Hz, 1H), 4.40 (td, J = 8.0, 1.4 Hz, 2H), 4.01 - 3.91 (m, 2H). LRMS (ESI): 310.10 [M + H] + 。

[0069] Example 16 (E)-3-(3-(3-Phenoxyphenyl)acryloyl)oxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(3-phenoxyphenyl)acrylic acid, and the remaining necessary raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(3-phenoxyphenyl)acryloyl)oxazolidin-2-one (yield 82.7%). 1 1H NMR (400 MHz, DMSO-d6) δ 7.80 - 7.70 (m, 2H), 7.49 - 7.39 (m, 4H), 7.31 (dd, J = 2.9, 1.4 Hz, 1H), 7.22 - 7.15 (m, 1H), 7.10 - 7.00 (m, 3H), 4.45 - 4.36 (m, 2H), 4.03 - 3.94 (m, 2H). LRMS (ESI): 310.10 [M + H] + 。

[0070] Example 17 (E)-3-(3-(4-Phenoxyphenyl)acryloyl)oxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(4-phenoxyphenyl)acrylic acid, and the remaining necessary raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(4-phenoxyphenyl)acryloyl)oxazolidin-2-one (yield 88.1%). 11H NMR (400 MHz, DMSO-d6) δ 7.81 (d, J = 15.1 Hz, 1H), 7.61 - 7.52 (m, 1H), 7.54 - 7.45 (m, 2H), 7.39 (t, J = 7.5 Hz, 2H), 7.19 - 7.10 (m, 1H), 7.06 (ddd, J = 7.8, 5.7, 1.9 Hz, 4H), 4.40 (t, J = 6.3 Hz, 2H), 4.05 (t, J = 6.4 Hz, 2H). LRMS (ESI): 310.10 [M+H] + 。

[0071] Example 18 (E)-3-(3-([1,1'-Biphenyl]-2-yl)acryloyl)oxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-([1,1'-biphenyl]-2-yl)acrylic acid, and the remaining necessary raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-([1,1'-biphenyl]-2-yl)acryloyl)oxazolidin-2-one (yield 86.7%). 1 1H NMR (400 MHz, DMSO-d6) δ 7.90 - 7.78 (m, 2H), 7.64 (dd, J = 15.8, 1.4 Hz, 1H), 7.60 - 7.39 (m, 6H), 7.33 (dt, J = 7.8, 1.5 Hz, 2H), 4.47 - 4.36 (m, 2H), 3.95 (m, 2H). LRMS (ESI): 294.11 [M+H] + 。

[0072] Example 19 (E)-3-(3-([1,1'-Biphenyl]-3-yl)acryloyl)oxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-([1,1'-biphenyl]-3-yl)acrylic acid, and the remaining necessary raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-([1,1'-biphenyl]-3-yl)acryloyl)oxazolidin-2-one (yield 88.3%). 11H NMR (400 MHz, DMSO-d6) δ 7.94 (s, 1H), 7.88 (d, J = 5.9 Hz, 2H), 7.78 - 7.68 (m, 4H), 7.57 (t, J = 7.7 Hz, 1H), 7.51 (t, J = 7.6 Hz, 2H), 7.42 (t, J = 7.3 Hz, 1H), 4.43 (t, J = 8.0 Hz, 2H), 4.02 (t, J = 7.9 Hz, 2H). LRMS (ESI): 294.11 [M+H] + 。

[0073] Example 20 (E)-3-(3-(4-Fluoro-2-trifluoromethylphenyl)acryloyl)oxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(4-fluoro-2-trifluoromethylphenyl)acrylic acid, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(4-fluoro-2-trifluoromethylphenyl)acryloyl)oxazolidin-2-one (yield 81.0%). 1 1H NMR (400 MHz, Chloroform-d) δ 8.15 (dq, J = 15.6, 2.3 Hz, 1H), 7.91 - 7.78 (m, 2H), 7.42 (dd, J = 8.8, 2.7 Hz, 1H), 7.35 - 7.22 (m, 1H), 4.49 (t, J = 8.0 Hz, 2H), 4.16 (t, J = 8.0 Hz, 2H). LRMS (ESI): 304.05 [M+H] + 。

[0074] Example 21 (E)-3-(3-(Naphthalen-1-yl)acryloyl)oxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(naphthalen-1-yl)acrylic acid, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(naphthalen-1-yl)acryloyl)oxazolidin-2-one (yield 87.1%). 11H NMR (400 MHz, DMSO-d6) δ 8.52 (d, J = 15.6 Hz, 1H), 8.25 (d, J = 8.3 Hz, 1H), 8.09 - 8.00 (m, 2H), 7.95 - 7.86 (m, 2H), 7.69 - 7.58 (m, 3H), 4.45 (dd, J = 8.6, 7.3 Hz, 2H), 4.05 (dd, J = 8.6, 7.3 Hz, 2H). LRMS (ESI): 268.09 [M+H] + 。

[0075] Example 22 (E)-3-(3-(Benzo[d][1,3]dioxolan-5-yl)acryloyl)oxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(benzo[d][1,3]dioxolan-5-yl)acrylic acid, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(benzo[d][1,3]dioxolan-5-yl)acryloyl)oxazolidin-2-one (yield 89.2%). 1 1H NMR (400 MHz, Chloroform-d) δ 7.79 (d, J = 15.7 Hz, 1H), 7.73 (d, J = 15.6 Hz, 1H), 7.15 (d, J = 1.7 Hz, 1H), 7.10 (dd, J = 8.0, 1.8 Hz, 1H), 6.82 (d, J = 8.0 Hz, 1H), 6.02 (s, 2H), 4.45 (dd, J = 8.6, 7.5 Hz, 2H), 4.13 (dd, J = 8.5, 7.4 Hz, 2H); LRMS (ESI): 262.06 [M+H] + 。

[0076] Example 23 (E)-3-(3-(Thiophen-2-yl)acryloyl)oxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(thiophen-2-yl)acrylic acid, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(thiophen-2-yl)acryloyl)oxazolidin-2-one (yield 87.4%). 11H NMR (400 MHz, DMSO-d6) δ 8.03 (dd, J = 2.8, 1.2 Hz, 1H), 7.77 (d, J = 15.8 Hz, 1H), 7.66 (ddd, J = 5.0, 2.9, 0.7 Hz, 1H), 7.61 (d, J = 15.7 Hz, 1H), 7.42 (dd, J = 5.1, 1.2 Hz, 1H), 4.41 (dd, J = 8.5, 7.4 Hz, 2H), 3.99 (dd, J = 8.5, 7.4 Hz, 2H). LRMS (ESI): 224.03 [M+H] + 。

[0077] Example 24 (E)-3-(3-Cyclohexylacryloyl)oxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-cyclohexylacrylic acid, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (E)-3-(3-Cyclohexylacryloyl)oxazolidin-2-one (yield 85.1%). 1 1H NMR (400 MHz, DMSO-d6) δ 7.12 (dd, J = 15.6, 1.3 Hz, 1H), 6.95 (dd, J = 15.6, 6.6 Hz, 1H), 4.37 (dd, J = 8.5, 7.5 Hz, 2H), 3.92 (dd, J = 8.6, 7.4 Hz, 2H), 2.21 (qd, J = 8.0, 7.3, 4.5 Hz, 1H), 1.77 - 1.68 (m, 4H), 1.63 (d, J = 12.5 Hz, 1H), 1.36 - 1.23 (m, 2H), 1.14 (pd, J = 13.3, 12.7, 3.7 Hz, 3H). LRMS (ESI): 224.12 [M+H] + 。

[0078] Example 26 (E)-3-(3-(2-Trifluoromethylphenyl)acryloyl)-4-phenyloxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid is replaced by (E)-3-(2-trifluoromethylphenyl)acrylic acid, oxazolidin-2-one is replaced by 4-phenyloxazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods are the same as in Example 1 to obtain (E)-3-(3-(2-trifluoromethylphenyl)acryloyl)-4-phenyloxazolidin-2-one (yield 89.9%). 1 H NMR(400MHz,DMSO-d6)δ 7.95(d,J=7.8Hz,1H),7.91-7.77(m,4H),7.68(t,J=7.7Hz,1H),7.46-7.33(m,5H),5.59(dd,J=8.6,4.1Hz,1H),4.82(t,J=8.7Hz,1H),4.24(dd,J=8.7,4.1Hz,1H). LRMS(ESI):362.09[M+H] + 。

[0079] Example 27 (S,E)-3-(3-(2-Trifluoromethylphenyl)acryloyl)-4-phenyloxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid is replaced by (E)-3-(2-trifluoromethylphenyl)acrylic acid, oxazolidin-2-one is replaced by (S)-4-phenyloxazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods are the same as in Example 1 to obtain (S,E)-3-(3-(2-trifluoromethylphenyl)acryloyl)-4-phenyloxazolidin-2-one (yield 90.9%). 1 H NMR(400MHz,DMSO-d6)δ 7.95(d,J=7.8Hz,1H),7.91-7.77(m,4H),7.68(t,J=7.7Hz,1H),7.46-7.33(m,5H),5.59(dd,J=8.6,4.1Hz,1H),4.82(t,J=8.7Hz,1H),4.24(dd,J=8.7,4.1Hz,1H). LRMS(ESI):362.09[M+H] + 。

[0080] Example 28 (R,E)-3-(3-(2-Trifluoromethylphenyl)acryloyl)-4-phenyloxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(2-trifluoromethylphenyl)acrylic acid, oxazolidin-2-one was replaced with (R)-4-phenyloxazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (R,E)-3-(3-(2-trifluoromethylphenyl)acryloyl)-4-phenyloxazolidin-2-one (yield 90.4%). 1 H NMR(400MHz,DMSO-d6)δ 7.95(d,J=7.8Hz,1H),7.91-7.77(m,4H),7.68(t,J=7.7Hz,1H),7.46-7.33(m,5H),5.59(dd,J=8.6,4.1Hz,1H),4.82(t,J=8.7Hz,1H),4.24(dd,J=8.7,4.1Hz,1H). LRMS(ESI):362.09[M+H] + 。

[0081] Example 29 (S,E)-4-Phenyl-3-(3-(3-(trifluoromethoxy)phenyl)acryloyl)oxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-(3-(trifluoromethoxy)phenyl)acrylic acid, oxazolidin-2-one was replaced with (S)-4-phenyloxazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (S,E)-4-phenyl-3-(3-(3-(trifluoromethoxy)phenyl)acryloyl)oxazolidin-2-one. 1 H NMR(400MHz,Chloroform-d)δ 7.94(d,J=15.7Hz,1H),7.72(d,J=15.7Hz,1H),7.52(dt,J=7.8,1.3Hz,1H),7.45-7.32(m,7H),7.25(ddd,J=8.2,2.7,1.5Hz,1H),5.56(dd,J=8.7,3.9Hz,1H),4.75(t,J=8.8Hz,1H),4.33(dd,J=8.9,3.9Hz,1H); LRMS(ESI):378.09[M+H] + 。

[0082] Example 30 (S,E)-4-Phenyl-3-(3-(2-(trifluoromethoxy)phenyl)acryloyl)oxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid is replaced with (E)-(2-(trifluoromethoxy)phenyl)acrylic acid, oxazolidin-2-one is replaced with (S)-4-phenyloxazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods are the same as in Example 1 to obtain (S,E)-4-phenyl-3-(3-(2-(trifluoromethoxy)phenyl)acryloyl)oxazolidin-2-one. 1 H NMR(400MHz,Chloroform-d)δ 8.05(d,J=15.8Hz,1H),7.97(d,J=15.9Hz,1H),7.84-7.75(m,1H),7.47-7.25(m,8H),5.56(dd,J=8.8,3.9Hz,1H),4.76(t,J=8.8Hz,1H),4.34(dd,J=8.9,3.9Hz,1H);LRMS(ESI):378.09[M+H] + 。

[0083] Example 31 (S,E)-4-Phenyl-3-(3-(4-(trifluoromethoxy)phenyl)acryloyl)oxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid is replaced with (E)-(4-(trifluoromethoxy)phenyl)acrylic acid, oxazolidin-2-one is replaced with (S)-4-phenyloxazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods are the same as in Example 1 to obtain (S,E)-4-phenyl-3-(3-(4-(trifluoromethoxy)phenyl)acryloyl)oxazolidin-2-one. 1 H NMR(400MHz,Methylene Chloride-d2)δ 7.90(d,J=15.8Hz,1H),7.73(d,J=15.7Hz,1H),7.68-7.63(m,2H),7.44-7.32(m,5H),7.28-7.22(m,2H),5.53(dd,J=8.7,4.1Hz,1H),4.74(t,J=8.8Hz,1H),4.29(dd,J=8.9,4.1Hz,1H);LRMS(ESI):378.09[M+H]+ .

[0084] Example 32 (S,E)-3-(3-(2-Phenoxyphenyl)acryloyl)-4-phenyloxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid is replaced with (E)-3-(2-phenoxyphenyl)acrylic acid, and oxazolidin-2-one is replaced with (S)-4-phenyloxazolidin-2-one. The remaining necessary raw materials, reagents, and preparation methods are the same as in Example 1 to obtain (S,E)-3-(3-(2-phenoxyphenyl)acryloyl)-4-phenyloxazolidin-2-one (yield 90.1%). 1 H NMR(400MHz,DMSO-d6)δ 7.98(d,J=15.9Hz,1H),7.84(d,J=16.0Hz,1H),7.80(dd,J=7.9,1.7Hz,1H),7.47(ddd,J=8.3,7.3,1.7Hz,1H),7.43-7.36(m,4H),7.35-7.25(m,4H),7.18-7.13(m,1H),7.03-6.97(m,2H),6.94(dd,J=8.2,1.1Hz,1H),5.55(dd,J=8.6,3.9Hz,1H),4.79(t,J=8.7Hz,1H),4.20(dd,J=8.7,3.9Hz,1H).LRMS(ESI):386.13[M+H] + .

[0085] Example 33 (R,E)-3-(3-(2-Phenoxyphenyl)acryloyl)-4-phenyloxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid is replaced with (E)-3-(2-phenoxyphenyl)acrylic acid, and oxazolidin-2-one is replaced with (R)-4-phenyloxazolidin-2-one. The remaining necessary raw materials, reagents, and preparation methods are the same as in Example 1 to obtain (R,E)-3-(3-(2-phenoxyphenyl)acryloyl)-4-phenyloxazolidin-2-one (yield 90.5%). 11H NMR (400 MHz, DMSO-d6) δ 7.98 (d, J = 15.9 Hz, 1H), 7.84 (d, J = 16.0 Hz, 1H), 7.80 (dd, J = 7.9, 1.7 Hz, 1H), 7.47 (ddd, J = 8.3, 7.3, 1.7 Hz, 1H), 7.43 - 7.36 (m, 4H), 7.35 - 7.25 (m, 4H), 7.18 - 7.13 (m, 1H), 7.03 - 6.97 (m, 2H), 6.94 (dd, J = 8.2, 1.1 Hz, 1H), 5.55 (dd, J = 8.6, 3.9 Hz, 1H), 4.79 (t, J = 8.7 Hz, 1H), 4.20 (dd, J = 8.7, 3.9 Hz, 1H). LRMS (ESI): 386.13 [M+H] + .

[0086] Example 34 (E)-3-(3-([1,1'-Biphenyl]-3-yl)acryloyl)-4-phenyloxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-([1,1'-biphenyl]-3-yl)acrylic acid, and oxazolidin-2-one was replaced with 4-phenyloxazolidin-2-one. The remaining necessary raw materials, reagents, and preparation methods were the same as in Example 1, and (E)-3-(3-([1,1'-biphenyl]-3-yl)acryloyl)-4-phenyloxazolidin-2-one (yield 86.9%) was obtained. 1 1H NMR (400 MHz, DMSO-d6) δ 7.96 - 7.89 (m, 2H), 7.81 - 7.67 (m, 5H), 7.56 (t, J = 7.7 Hz, 1H), 7.50 (dd, J = 8.2, 6.9 Hz, 2H), 7.44 - 7.32 (m, 6H), 5.61 (dd, J = 8.6, 3.9 Hz, 1H), 4.82 (t, J = 8.7 Hz, 1H), 4.23 (dd, J = 8.6, 3.9 Hz, 1H). LRMS (ESI, m / z): 370.14 [M+H] + Example 35 (S,E)-3-(3-([1,1'-Biphenyl]-3-yl)acryloyl)-4-phenyloxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-([1,1'-biphenyl]-3-yl)acrylic acid, oxazolidin-2-one was replaced with (S)-4-phenyloxazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (S,E)-3-(3-([1,1'-biphenyl]-3-yl)acryloyl)-4-phenyloxazolidin-2-one (yield 89.6%). 1 H NMR(400MHz,DMSO-d6)δ 8.00-7.88(m,2H),7.81-7.66(m,5H),7.56(t,J=7.7Hz,1H),7.53-7.47(m,2H),7.45-7.33(m,6H),5.61(dd,J=8.6,3.9Hz,1H),4.87-4.78(m,1H),4.27-4.20(m,1H).LRMS(ESI):370.14[M+H] + 。

[0087] Example 36 (R,E)-3-(3-([1,1'-biphenyl]-3-yl)acryloyl)-4-phenyloxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-([1,1'-biphenyl]-3-yl)acrylic acid, oxazolidin-2-one was replaced with (R)-4-phenyloxazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (R,E)-3-(3-([1,1'-biphenyl]-3-yl)acryloyl)-4-phenyloxazolidin-2-one (yield 88.9%). 1 H NMR(400MHz,DMSO-d6)δ 8.00-7.88(m,2H),7.81-7.66(m,5H),7.56(t,J=7.7Hz,1H),7.53-7.47(m,2H),7.45-7.33(m,6H),5.61(dd,J=8.6,3.9Hz,1H),4.87-4.78(m,1H),4.27-4.20(m,1H).LRMS(ESI):370.14[M+H] + 。

[0088] (S,E)-3-(3-(4'-Fluoro-[1,1'-biphenyl]-3-yl)acryloyl)-4-phenyloxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(4'-fluoro-[1,1'-biphenyl]-3-yl)acrylic acid, oxazolidin-2-one was replaced with (S)-4-phenyloxazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (S,E)-3-(3-(4'-fluoro-[1,1'-biphenyl]-3-yl)acryloyl)-4-phenyloxazolidin-2-one (yield 78.1%). 1 H NMR(400MHz,DMSO-d6)δ 7.94-7.87(m,2H),7.80-7.70(m,4H),7.68(dt,J=7.9,1.3Hz,1H),7.55(t,J=7.7Hz,1H),7.43-7.39(m,1H),7.39-7.36(m,2H),7.36-7.28(m,4H),5.61(dd,J=8.6,3.9Hz,1H),4.82(t,J=8.7Hz,1H),4.23(dd,J=8.6,3.9Hz,1H). LRMS(ESI):409.9[M+Na] + 。

[0089] (S,E)-4-Phenyl-3-(3-(3-(pyridin-3-yl)phenyl)acryloyl)oxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(3-(pyridin-3-yl)phenyl)acrylic acid, oxazolidin-2-one was replaced with (S)-4-phenyloxazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (S,E)-4-phenyl-3-(3-(3-(pyridin-3-yl)phenyl)acryloyl)oxazolidin-2-one (yield 67.1%). 11H NMR (400 MHz, DMSO-d6) δ 8.95 (d, J = 2.4 Hz, 1H), 8.61 (dd, J = 4.8, 1.6 Hz, 1H), 8.13 (dt, J = 8.0, 2.0 Hz, 1H), 8.01 (t, J = 1.7 Hz, 1H), 7.93 (d, J = 15.9 Hz, 1H), 7.85 - 7.72 (m, 3H), 7.61 (t, J = 7.8 Hz, 1H), 7.52 (dd, J = 8.0, 4.8 Hz, 1H), 7.45 - 7.31 (m, 5H), 5.61 (dd, J = 8.6, 3.9 Hz, 1H), 4.82 (t, J = 8.6 Hz, 1H), 4.23 (dd, J = 8.6, 3.9 Hz, 1H). LRMS (ESI): 393.01 [M+Na] + 。

[0090] Example 39 (S,E)-4-Phenyl-3-(3-(3-(pyridin-4-yl)phenyl)acryloyl)oxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(3-(pyridin-4-yl)phenyl)acrylic acid, oxazolidin-2-one was replaced with (S)-4-phenyloxazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (S,E)-4-phenyl-3-(3-(3-(pyridin-4-yl)phenyl)acryloyl)oxazolidin-2-one (yield 65.5%). 1 1H NMR (400 MHz, DMSO-d6) δ 8.70 - 8.65 (m, 2H), 8.07 (s, 1H), 7.97 - 7.90 (m, 1H), 7.89 (d, J = 7.4 Hz, 1H), 7.82 - 7.73 (m, 4H), 7.62 (t, J = 7.6 Hz, 1H), 7.45 - 7.31 (m, 5H), 5.61 (dd, J = 8.6, 3.9 Hz, 1H), 4.82 (t, J = 8.6 Hz, 1H), 4.23 (dd, J = 8.6, 3.9 Hz, 1H). LRMS (ESI): 392.92 [M+Na] + 。

[0091] Example 40 (S,E)-4-Phenyl-3-(3-(3-(thiophen-2-yl)phenyl)acryloyl)oxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(3-(thiophen-2-yl)phenyl)acrylic acid, oxazolidin-2-one was replaced with (S)-4-phenyloxazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (S,E)-4-phenyl-3-(3-(3-(thiophen-2-yl)phenyl)acryloyl)oxazolidin-2-one (yield 87.8%). 1 H NMR(400MHz,DMSO-d6)δ 7.81(d,J=15.0Hz,1H),7.78-7.66(m,2H),7.62(q,J=1.7Hz,1H),7.55(d,J=15.2Hz,1H),7.55-7.43(m,2H),7.45-7.35(m,3H),7.36-7.26(m,2H),7.29-7.19(m,1H),7.13(t,J=7.5Hz,1H),5.29(t,J=7.0Hz,1H),5.08(dd,J=11.5,7.0Hz,1H),4.80(dd,J=11.5,7.0Hz,1H). LRMS(ESI):376.09[M+H] + 。

[0092] Example 41 (S,E)-4-Phenyl-3-(3-(5-phenylthiophen-2-yl)acryloyl)oxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(5-phenylthiophen-2-yl)acrylic acid, oxazolidin-2-one was replaced with (S)-4-phenyloxazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (S,E)-4-phenyl-3-(3-(5-phenylthiophen-2-yl)acryloyl)oxazolidin-2-one (yield 91.3%). 11H NMR (400 MHz, DMSO-d6) δ 7.89 (d, J = 7.6 Hz, 1H), 7.87 - 7.77 (m, 3H), 7.71 (d, J = 7.4 Hz, 1H), 7.55 (d, J = 15.1 Hz, 1H), 7.52 - 7.44 (m, 3H), 7.47 - 7.38 (m, 2H), 7.31 (t, J = 7.3 Hz, 2H), 7.29 - 7.19 (m, 1H), 5.29 (t, J = 7.0 Hz, 1H), 5.07 (dd, J = 11.5, 7.0 Hz, 1H), 4.81 (dd, J = 11.4, 6.9 Hz, 1H). LRMS (ESI): 376.09 [M+H] + 。

[0093] Example 42 (S,E)-4-Phenyl-3-(3-(4-phenylthiophen-2-yl)acryloyl)oxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(4-phenylthiophen-2-yl)acrylic acid, oxazolidin-2-one was replaced with (S)-4-phenyloxazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (S,E)-4-phenyl-3-(3-(4-phenylthiophen-2-yl)acryloyl)oxazolidin-2-one (yield 92.1%). 1 1H NMR (400 MHz, DMSO-d6) δ 7.86 - 7.77 (m, 3H), 7.63 - 7.53 (m, 3H), 7.42 (dtdd, J = 9.3, 7.1, 4.5, 3.0 Hz, 5H), 7.31 (t, J = 7.3 Hz, 2H), 7.29 - 7.19 (m, 1H), 5.31 (t, J = 6.9 Hz, 1H), 5.08 (dd, J = 11.4, 6.9 Hz, 1H), 4.81 (dd, J = 11.5, 7.0 Hz, 1H). LRMS (ESI): 376.09 [M+H] + 。

[0094] Example 43 (S,E)-3-(3-(4-Fluoro-2-(trifluoromethyl)phenyl)acryloyl)-4-phenyloxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid is replaced by (E)-4-fluoro-2-(trifluoromethyl)phenyl)acrylic acid, oxazolidin-2-one is replaced by (S)-4-phenyloxazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods are the same as those in Example 1 to obtain (S,E)-3-(3-(4-fluoro-2-(trifluoromethyl)phenyl)acryloyl)-4-phenyloxazolidin-2-one. 1 H NMR(400MHz,Chloroform-d)δ 8.08(d,J=15.4Hz,1H),7.95-7.80(m,2H),7.39(dt,J=15.8,7.4Hz,6H),7.32-7.22(m,1H),5.55(dd,J=8.7,3.9Hz,1H),4.76(t,J=8.8Hz,1H),4.35(dd,J=8.9,3.9Hz,1H);LRMS(ESI):380.24[M+H] + 。

[0095] Example 44 (S,E)-3-(3-(Benzo[d][1,3]dioxolan-5-yl)acryloyl)-4-phenyloxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid is replaced by (E)-3-(benzo[d][1,3]dioxolan-5-yl)acrylic acid, oxazolidin-2-one is replaced by (S)-4-phenyloxazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods are the same as those in Example 1 to obtain (S,E)-3-(3-(benzo[d][1,3]dioxolan-5-yl)acryloyl)-4-phenyloxazolidin-2-one. 1 H NMR(400MHz,Chloroform-d)δ 7.84-7.64(m,2H),7.44-7.29(m,5H),7.13(d,J=1.7Hz,1H),7.05(dd,J=8.1,1.7Hz,1H),6.80(d,J=8.0Hz,1H),6.01(s,2H),5.55(dd,J=8.7,3.9Hz,1H),4.73(t,J=8.8Hz,1H),4.31(dd,J=8.8,3.8Hz,1H);LRMS(ESI):338.10[M+H] + 。

[0096] (S,E)-3-(3-(2-Chloroquinolin-4-yl)acryloyl)-4-phenyloxazolidin-2-one Replace (E)-3-(o-tolyl)acrylic acid with (E)-3-(2-chloroquinolin-4-yl)acrylic acid, replace oxazolidin-2-one with (S)-4-phenyloxazolidin-2-one, and use the same necessary raw materials, reagents and preparation methods as in Example 1 to obtain (S,E)-3-(3-(2-chloroquinolin-4-yl)acryloyl)-4-phenyloxazolidin-2-one. 1 H NMR(400MHz,Chloroform-d)δ 8.38(dd,J=15.6,0.8Hz,1H),8.13-8.05(m,3H),7.77(ddd,J=8.4,6.9,1.4Hz,1H),7.64(s,1H),7.63-7.58(m,1H),7.40(m,5H),5.59(dd,J=8.8,4.0Hz,1H),4.81(t,J=8.8Hz,1H),4.43-4.35(m,1H);LRMS(ESI):379.08[M+H] + 。

[0097] (S,E)-3-(3-(Benzofuran-2-yl)acryloyl)-4-phenyloxazolidin-2-one Replace (E)-3-(o-tolyl)acrylic acid with (E)-3-(benzofuran-2-yl)acrylic acid, replace oxazolidin-2-one with (S)-4-phenyloxazolidin-2-one, and use the same necessary raw materials, reagents and preparation methods as in Example 1 to obtain (S,E)-3-(3-(benzofuran-2-yl)acryloyl)-4-phenyloxazolidin-2-one. 11H NMR (400 MHz, Methylene Chloride-d2) δ 7.95 (d, J = 15.4 Hz, 1H), 7.67 - 7.58 (m, 2H), 7.55 (dt, J = 8.4, 1.0 Hz, 1H), 7.45 - 7.32 (m, 6H), 7.30 - 7.22 (m, 1H), 7.03 (d, J = 4.6 Hz, 1H), 5.54 (dd, J = 8.8, 4.1 Hz, 1H), 4.75 (t, J = 8.8 Hz, 1H), 4.29 (dd, J = 8.9, 4.1 Hz, 1H); LRMS (ESI): 334.10 [M+H] + 。

[0098] Example 47 (S,E)-3-(3-(Benzofuran-7-yl)acryloyl)-4-phenyloxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(benzofuran-7-yl)acrylic acid, and oxazolidin-2-one was replaced with (S)-4-phenyloxazolidin-2-one. The remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (S,E)-3-(3-(benzofuran-7-yl)acryloyl)-4-phenyloxazolidin-2-one. 1 1H NMR (400 MHz, Chloroform-d) δ 7.97 (d, J = 15.7 Hz, 1H), 7.92 (d, J = 15.7 Hz, 1H), 7.86 (d, J = 1.7 Hz, 1H), 7.67 (d, J = 2.2 Hz, 1H), 7.60 (dd, J = 8.6, 1.8 Hz, 1H), 7.52 (d, J = 8.6 Hz, 1H), 7.46 - 7.35 (m, 5H), 6.82 (dd, J = 2.3, 0.9 Hz, 1H), 5.60 (dd, J = 8.7, 3.9 Hz, 1H), 4.78 (t, J = 8.8 Hz, 1H), 4.35 (dd, J = 8.8, 3.9 Hz, 1H); LRMS (ESI): 334.10 [M+H] + 。

[0099] Example 48 (S,E)-3-(3-(Naphthalen-1-yl)acryloyl)-4-phenyloxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(naphthalen-1-yl)acrylic acid, oxazolidin-2-one was replaced with (S)-4-phenyloxazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (S,E)-3-(3-(naphthalen-1-yl)acryloyl)-4-phenyloxazolidin-2-one. 1 H NMR(400MHz,Chloroform-d)δ 8.68(d,J=15.5Hz,1H),8.20(d,J=8.1Hz,1H),8.05(dt,J=15.5,0.9Hz,1H),7.97-7.91(m,2H),7.91-7.86(m,1H),7.60-7.50(m,3H),7.48-7.35(m,5H),5.63(dd,J=8.7,3.9Hz,1H),4.80(ddt,J=9.7,8.8,1.0Hz,1H),4.41-4.34(m,1H);LRMS(ESI):344.12[M+H] + 。

[0100] Example 49 (S,E)-3-(3-(Benzo[b]thiophen-2-yl)acryloyl)-4-phenyloxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(benzo[b]thiophen-2-yl)acrylic acid, oxazolidin-2-one was replaced with (S)-4-phenyloxazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (S,E)-3-(3-(benzothiophen-2-yl)acryloyl)-4-phenyloxazolidin-2-one. 1 H NMR(400MHz,DMSO-d6)δ 8.05-7.95(m,2H),7.93-7.82(m,2H),7.69(d,J=15.5Hz,1H),7.39(dp,J=21.3,8.2,7.0Hz,7H),5.59(dd,J=8.7,3.9Hz,1H),4.81(t,J=8.7Hz,1H),4.22(dd,J=8.7,3.9Hz,1H);LRMS(ESI):350.08[M+H] + 。

[0101] Example 50 (E)-4-(4'-fluorophenyl)-3-(3-(2-(trifluoromethylphenyl)acryloyl)oxazolidin-2-one (E)-3-(o-tolyl)acrylic acid is replaced with (E)-3-(2-trifluoromethylphenyl)acrylic acid, oxazolidin-2-one is replaced with 4-(4'-fluorophenyl)oxazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods are the same as in Example 1 to obtain (E)-4-(4'-fluorophenyl)-3-(3-(2-(trifluoromethylphenyl)acryloyl)oxazolidin-2-one. LRMS(ESI): 380.08 [M+H] + .

[0102] Example 51 (S,E)-4-(4'-fluorophenyl)-3-(3-(2-(trifluoromethylphenyl)acryloyl)oxazolidin-2-one (E)-3-(o-tolyl)acrylic acid is replaced with (E)-3-(2-trifluoromethylphenyl)acrylic acid, oxazolidin-2-one is replaced with (S)-4-(4'-fluorophenyl)oxazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods are the same as in Example 1 to obtain (S,E)-4-(4'-fluorophenyl)-3-(3-(2-(trifluoromethylphenyl)acryloyl)oxazolidin-2-one. LRMS(ESI): 380.08 [M+H] + .

[0103] Example 52 (E)-4-(4'-fluorophenyl)-3-(3-(2-(trifluoromethoxyphenyl)acryloyl)oxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(2-trifluoromethoxyphenyl)acrylic acid, oxazolidin-2-one was replaced with 4-(4'-fluorophenyl)oxazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (E)-4-(4'-fluorophenyl)-3-(3-(2-(trifluoromethoxyphenyl)acryloyl)oxazolidin-2-one. LRMS(ESI): 396.08 [M+H] + .

[0104] Example 53 (S,E)-4-(4'-fluorophenyl)-3-(3-(2-(trifluoromethoxyphenyl)acryloyl)oxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(2-trifluoromethoxyphenyl)acrylic acid, oxazolidin-2-one was replaced with (S)-4-(4'-fluorophenyl)oxazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (S,E)-4-(4'-fluorophenyl)-3-(3-(2-(trifluoromethoxyphenyl)acryloyl)oxazolidin-2-one. LRMS(ESI): 396.08 [M+H] + .

[0105] Example 54 (E)-4-(4'-fluorophenyl)-3-(3-(2-phenoxyphenyl)acryloyl)oxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(2-phenoxyphenyl)acrylic acid, oxazolidin-2-one was replaced with 4-(4'-fluorophenyl)oxazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (E)-4-(4'-fluorophenyl)-3-(3-(2-phenoxyphenyl)acryloyl)oxazolidin-2-one. LRMS(ESI): 404.12 [M+H] + .

[0106] (S,E)-4-(4'-Fluorophenyl)-3-(3-(2-phenoxyphenyl)acryloyl)oxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(2-phenoxyphenyl)acrylic acid, oxazolidin-2-one was replaced with (S)-4-(4'-fluorophenyl)oxazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (S,E)-4-(4'-fluorophenyl)-3-(3-(2-phenoxyphenyl)acryloyl)oxazolidin-2-one. LRMS(ESI): 404.12 [M+H] + .

[0107] (E)-3-(3-([1,1'-Biphenyl]-3-yl)acryloyl)-4-(4'-fluorophenyl)oxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-([1,1'-biphenyl]-3-yl)acrylic acid, oxazolidin-2-one was replaced with 4-(4'-fluorophenyl)oxazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (E)-3-(3-([1,1'-biphenyl]-3-yl)acryloyl)-4-(4'-fluorophenyl)oxazolidin-2-one. LRMS(ESI): 388.13 [M+H] + .

[0108] (E)-4-Benzyl-3-(3-(2-trifluoromethylphenyl)acryloyl)oxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(2-trifluoromethylphenyl)acrylic acid, oxazolidin-2-one was replaced with 4-benzyloxazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (E)-4-benzyl-3-(3-(2-trifluoromethylphenyl)acryloyl)oxazolidin-2-one (yield 86.9%). 11H NMR (400 MHz, DMSO-d6) δ 7.91 - 7.82 (m, 2H), 7.76 (td, J = 7.4, 2.0 Hz, 1H), 7.64 (d, J = 15.0 Hz, 1H), 7.49 (td, J = 7.5, 2.1 Hz, 1H), 7.33 - 7.23 (m, 3H), 7.24 - 7.14 (m, 3H), 4.64 (p, J = 7.0 Hz, 1H), 4.56 (dd, J = 11.3, 7.0 Hz, 1H), 4.33 (dd, J = 11.3, 6.8 Hz, 1H), 3.17 (dd, J = 12.4, 6.9 Hz, 1H), 2.91 (dd, J = 12.4, 6.9 Hz, 1H). LRMS (ESI): 376.11 [M+H] + .

[0109] Example 58 (S,E)-4-Benzyl-3-(3-(2-trifluoromethylphenyl)acryloyl)oxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(2-trifluoromethylphenyl)acrylic acid, oxazolidin-2-one was replaced with (S)-4-benzyloxazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (S,E)-4-benzyl-3-(3-(2-trifluoromethylphenyl)acryloyl)oxazolidin-2-one (yield 86.9%). 1 1H NMR (400 MHz, DMSO-d6) δ 7.91 - 7.82 (m, 2H), 7.76 (td, J = 7.4, 2.0 Hz, 1H), 7.64 (d, J = 15.0 Hz, 1H), 7.49 (td, J = 7.5, 2.1 Hz, 1H), 7.33 - 7.23 (m, 3H), 7.24 - 7.14 (m, 3H), 4.64 (p, J = 7.0 Hz, 1H), 4.56 (dd, J = 11.3, 7.0 Hz, 1H), 4.33 (dd, J = 11.3, 6.8 Hz, 1H), 3.17 (dd, J = 12.4, 6.9 Hz, 1H), 2.91 (dd, J = 12.4, 6.9 Hz, 1H). LRMS (ESI): 376.11 [M+H] + .

[0110] Example 59 (R,E)-4-Benzyl-3-(3-(2-trifluoromethylphenyl)acryloyl)oxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(2-trifluoromethylphenyl)acrylic acid, oxazolidin-2-one was replaced with (R)-4-benzyloxazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (R,E)-4-benzyl-3-(3-(2-trifluoromethylphenyl)acryloyl)oxazolidin-2-one (yield 86.4%). 1 H NMR(400MHz,DMSO-d6)δ 7.91-7.82(m,2H),7.76(td,J=7.4,2.0Hz,1H),7.64(d,J=15.0Hz,1H),7.49(td,J=7.5,2.1Hz,1H),7.33-7.23(m,3H),7.24-7.14(m,3H),4.64(p,J=7.0Hz,1H),4.56(dd,J=11.3,7.0Hz,1H),4.33(dd,J=11.3,6.8Hz,1H),3.17(dd,J=12.4,6.9Hz,1H),2.91(dd,J=12.4,6.9Hz,1H). LRMS(ESI):376.11[M+H] + 。

[0111] Example 60 (E)-3-(3-([1,1'-Biphenyl]-3-yl)acryloyl)-4-benzyloxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-([1,1'-biphenyl]-3-yl)acrylic acid, oxazolidin-2-one was replaced with 4-benzyloxazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (E)-3-(3-([1,1'-biphenyl]-3-yl)acryloyl)-4-benzyloxazolidin-2-one (yield 79.0%). 11H NMR (400 MHz, DMSO-d6) δ 7.95 (s, 1H), 7.93 (d, J = 15.8 Hz, 1H), 7.87 (d, J = 15.8 Hz, 1H), 7.78 - 7.74 (m, 1H), 7.74 - 7.68 (m, 3H), 7.57 (t, J = 7.7 Hz, 1H), 7.50 (dd, J = 8.2, 7.0 Hz, 2H), 7.44 - 7.38 (m, 1H), 7.36 - 7.30 (m, 2H), 7.29 - 7.21 (m, 3H), 4.79 (td, J = 7.7, 3.8 Hz, 1H), 4.40 (t, J = 8.5 Hz, 1H), 4.24 (dd, J = 8.7, 2.9 Hz, 1H), 3.11 (dd, J = 13.6, 3.4 Hz, 1H), 3.02 (dd, J = 13.6, 7.5 Hz, 1H). LRMS (ESI): 384.0 [M + H] + 。

[0112] Example 61 (S,E)-4-Isopropyl-3-(3-(2-(trifluoromethyl)phenyl)acryloyl)oxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(2-trifluoromethylphenyl)acrylic acid, oxazolidin-2-one was replaced with (S)-4-isopropyloxazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (S,E)-4-isopropyl-3-(3-(2-(trifluoromethyl)phenyl)acryloyl)oxazolidin-2-one. 1 1H NMR (400 MHz, Chloroform-d) δ 8.22 (dq, J = 15.5, 2.3 Hz, 1H), 7.92 (d, J = 15.5 Hz, 1H), 7.86 (d, J = 7.8 Hz, 1H), 7.71 (dd, J = 7.8, 1.3 Hz, 1H), 7.58 (td, J = 7.8, 1.5 Hz, 1H), 7.49 (tt, J = 7.6, 1.0 Hz, 1H), 4.60 - 4.54 (m, 1H), 4.34 (dd, J = 9.2, 8.3 Hz, 1H), 4.27 (dd, J = 9.1, 3.2 Hz, 1H), 2.49 (pd, J = 7.0, 3.9 Hz, 1H), 0.95 (dd, J = 15.0, 7.0 Hz, 6H); LRMS (ESI): 328.11 [M + H] + 。

[0113] (S,E)-4-Isopropyl-3-(3-(4-(trifluoromethyl)phenyl)acryloyl)oxazolidin-2-one Replace (E)-3-(o-tolyl)acrylic acid with (E)-3-(4-trifluoromethylphenyl)acrylic acid, replace oxazolidin-2-one with (S)-4-isopropyloxazolidin-2-one, and use the remaining necessary raw materials, reagents and preparation methods in the same manner as in Example 1 to obtain (S,E)-4-isopropyl-3-(3-(4-(trifluoromethyl)phenyl)acryloyl)oxazolidin-2-one. LRMS(ESI): 328.11 [M+H] + 。

[0114] (S,E)-4-Isopropyl-3-(3-(3-(trifluoromethyl)phenyl)acryloyl)oxazolidin-2-one Replace (E)-3-(o-tolyl)acrylic acid with (E)-3-(3-trifluoromethylphenyl)acrylic acid, replace oxazolidin-2-one with (S)-4-isopropyloxazolidin-2-one, and use the remaining necessary raw materials, reagents and preparation methods in the same manner as in Example 1 to obtain (S,E)-4-isopropyl-3-(3-(3-(trifluoromethyl)phenyl)acryloyl)oxazolidin-2-one. LRMS(ESI): 328.11 [M+H] + 。

[0115] (S,E)-4-Isopropyl-3-(3-(3-trifluoromethoxyphenyl)acryloyl)oxazolidin-2-one Replace (E)-3-(o-tolyl)acrylic acid with (E)-3-(3-trifluoromethoxyphenyl)acrylic acid, replace oxazolidin-2-one with (S)-4-isopropyloxazolidin-2-one, and use the remaining necessary raw materials, reagents and preparation methods in the same manner as in Example 1 to obtain (S,E)-4-isopropyl-3-(3-(3-trifluoromethoxyphenyl)acryloyl)oxazolidin-2-one. 11H NMR (400 MHz, Chloroform-d) δ 7.96 (d, J = 15.7 Hz, 1H), 7.80 (d, J = 15.7 Hz, 1H), 7.56 (dt, J = 7.8, 1.2 Hz, 1H), 7.47 - 7.40 (m, 2H), 7.29 - 7.21 (m, 1H), 4.57 (ddd, J = 8.3, 4.0, 3.2 Hz, 1H), 4.34 (dd, J = 9.1, 8.3 Hz, 1H), 4.27 (dd, J = 9.1, 3.2 Hz, 1H), 2.46 (pt, J = 7.0, 3.5 Hz, 1H), 0.94 (dd, J = 17.4, 7.0 Hz, 6H); LRMS (ESI): 344.10 [M+H] + 。

[0116] Example 65 (S,E)-4-Isopropyl-3-(3-(2-trifluoromethoxyphenyl)acryloyl)oxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(2-trifluoromethoxyphenyl)acrylic acid, oxazolidin-2-one was replaced with (S)-4-isopropyloxazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (S,E)-4-isopropyl-3-(3-(2-trifluoromethoxyphenyl)acryloyl)oxazolidin-2-one. 1 1H NMR (400 MHz, Chloroform-d) δ 8.11 (d, J = 15.9 Hz, 1H), 7.99 (d, J = 15.8 Hz, 1H), 7.81 (dd, J = 7.8, 1.7 Hz, 1H), 7.44 (ddd, J = 8.2, 7.4, 1.7 Hz, 1H), 7.36 - 7.28 (m, 2H), 4.57 (ddd, J = 8.2, 3.9, 3.1 Hz, 1H), 4.34 (dd, J = 9.1, 8.3 Hz, 1H), 4.27 (dd, J = 9.1, 3.1 Hz, 1H), 2.48 (heptd, J = 7.0, 3.9 Hz, 1H), 0.97 (d, J = 7.0 Hz, 3H), 0.93 (d, J = 7.0 Hz, 3H); LRMS (ESI): 344.10 [M+H] + 。

[0117] (S,E)-4-Isopropyl-3-(3-(4-trifluoromethoxyphenyl)acryloyl)oxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(4-trifluoromethoxyphenyl)acrylic acid, oxazolidin-2-one was replaced with (S)-4-isopropyloxazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (S,E)-4-isopropyl-3-(3-(4-trifluoromethoxyphenyl)acryloyl)oxazolidin-2-one. LRMS(ESI): 344.10[M+H] + .

[0118] (S,E)-3-(3-([1,1'-Biphenyl]-3-yl)acryloyl)-4-isopropyloxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-([1,1'-biphenyl]-3-yl)acrylic acid, oxazolidin-2-one was replaced with (S)-4-isopropyloxazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (S,E)-3-(3-([1,1'-biphenyl]-3-yl)acryloyl)-4-isopropyloxazolidin-2-one. LRMS(ESI): 336.15[M+H] + .

[0119] (S,E)-3-(3-(4-Fluoro-2-(trifluoromethyl)phenyl)acryloyl)-4-isopropyloxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(4-fluoro-2-(trifluoromethyl)phenyl)acrylic acid, oxazolidin-2-one was replaced with (S)-4-isopropyloxazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (S,E)-3-(3-(4-fluoro-2-(trifluoromethyl)phenyl)acryloyl)-4-isopropyloxazolidin-2-one. 11H NMR (400 MHz, Chloroform-d) δ 8.14 (d, J = 15.5 Hz, 1H), 7.88 (d, J = 14.7 Hz, 2H), 7.60 - 7.36 (m, 1H), 7.30 (d, J = 8.5 Hz, 1H), 4.57 (dd, J = 8.0, 3.9 Hz, 1H), 4.40 - 4.18 (m, 2H), 2.64 - 2.34 (m, 1H), 0.95 (dd, J = 16.0, 7.0 Hz, 8H); LRMS (ESI): 346.10 [M+H] + 。

[0120] Example 69 (S,E)-3-(3-(Benzofuran-2-yl)acryloyl)-4-isopropyloxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(benzofuran-2-yl)acrylic acid, and oxazolidin-2-one was replaced with (S)-4-isopropyloxazolidin-2-one. The remaining necessary raw materials, reagents and preparation methods were the same as those in Example 1 to obtain (S,E)-3-(3-(benzofuran-2-yl)acryloyl)-4-isopropyloxazolidin-2-one. 1 1H NMR (400 MHz, Methylene Chloride-d2) δ 7.96 (dd, J = 15.4, 0.6 Hz, 1H), 7.70 (d, J = 15.4 Hz, 1H), 7.62 (ddd, J = 7.8, 1.3, 0.7 Hz, 1H), 7.54 (dq, J = 8.4, 0.9 Hz, 1H), 7.42 - 7.36 (m, 1H), 7.26 (ddd, J = 8.1, 7.2, 1.0 Hz, 1H), 7.05 (s, 1H), 4.55 (ddd, J = 8.2, 4.0, 3.2 Hz, 1H), 4.33 (dd, J = 9.1, 8.2 Hz, 1H), 4.26 (dd, J = 9.1, 3.2 Hz, 1H), 2.00 (s, 1H), 0.95 (d, J = 7.0 Hz, 3H), 0.91 (d, J = 6.9 Hz, 3H); LRMS (ESI): 300.12 [M+H] + 。

[0121] Example 70 (S,E)-3-(3-(Benzo[b]thiophen-2-yl)acryloyl)-4-isopropyloxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(benzo[b]thiophen-2-yl)acrylic acid, oxazolidin-2-one was replaced with (S)-4-isopropyloxazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (S,E)-3-(3-(benzo[b]thiophen-2-yl)acryloyl)-4-isopropyloxazolidin-2-one. 1 H NMR(400MHz,DMSO-d6)δ 8.09-8.03(m,1H),8.02-7.98(m,1H),7.92-7.87(m,2H),7.69(d,J=15.4Hz,1H),7.44(pd,J=7.1,1.4Hz,2H),4.49(dt,J=7.4,3.7Hz,1H),4.41-4.33(m,2H),1.32-1.19(m,1H),0.86(dd,J=26.2,6.9Hz,6H);LRMS(ESI):316.09[M+H] + 。

[0122] Example 71 (S,E)-4-Isopropyl-3-(3-(naphthalen-1-yl)acryloyl)oxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(naphthalen-1-yl)acrylic acid, oxazolidin-2-one was replaced with (S)-4-isopropyloxazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (S,E)-4-isopropyl-3-(3-(naphthalen-1-yl)acryloyl)oxazolidin-2-one. 11H NMR (400 MHz, Chloroform-d) δ 8.74 (d, J = 15.5 Hz, 1H), 8.28 (d, J = 8.4 Hz, 1H), 8.06 (d, J = 15.5 Hz, 1H), 7.95 (dd, J = 7.7, 3.5 Hz, 2H), 7.91 (dd, J = 7.7, 1.3 Hz, 1H), 7.61 (ddd, J = 8.5, 6.8, 1.5 Hz, 1H), 7.58 - 7.51 (m, 2H), 4.63 (dt, J = 8.3, 3.5 Hz, 1H), 4.37 (t, J = 8.7 Hz, 1H), 4.30 (dd, J = 9.1, 3.1 Hz, 1H), 2.54 (pd, J = 7.0, 4.0 Hz, 1H), 1.01 (d, J = 7.0 Hz, 3H), 0.98 (d, J = 6.9 Hz, 3H); LRMS (ESI): 310.10 [M+H] + 。

[0123] Example 72 (S,E)-3-(3-(Benzo[d][1,3]dioxolan-5-yl)acryloyl)-4-isopropyloxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(benzo[d][1,3]dioxolan-5-yl)acrylic acid, oxazolidin-2-one was replaced with (S)-4-isopropyloxazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (S,E)-3-(3-(benzo[d][1,3]dioxolan-5-yl)acryloyl)-4-isopropyloxazolidin-2-one. 1 1H NMR (400 MHz, Chloroform-d) δ 7.77 (d, J = 0.9 Hz, 2H), 7.15 (d, J = 1.7 Hz, 1H), 7.10 (dd, J = 8.0, 1.7 Hz, 1H), 6.82 (d, J = 8.0 Hz, 1H), 6.02 (s, 2H), 4.56 (ddd, J = 8.2, 4.0, 3.1 Hz, 1H), 4.31 (dd, J = 9.1, 8.3 Hz, 1H), 4.25 (dd, J = 9.0, 3.2 Hz, 1H), 2.46 (pd, J = 7.0, 3.9 Hz, 1H), 0.96 (d, J = 7.0 Hz, 3H), 0.91 (d, J = 6.9 Hz, 3H); LRMS (ESI): 304.11 [M+H] + 。

[0124] Example 73 (E)-3-(3-(Benzo[d][1,3]dioxolan-5-yl)acryloyl)-4,4-dimethyloxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid is replaced with (E)-3-(benzo[d][1,3]dioxolan-5-yl)acrylic acid, and oxazolidin-2-one is replaced with 4,4-dimethyloxazolidin-2-one. The remaining necessary raw materials, reagents, and preparation methods are the same as in Example 1 to obtain (E)-3-(3-(benzo[d][1,3]dioxolan-5-yl)acryloyl)-4,4-dimethyloxazolidin-2-one. 1 H NMR (400 MHz, Chloroform-d) δ 7.71 (d, J = 15.6 Hz, 1H), 7.56 (d, J = 15.5 Hz, 1H), 7.12 (d, J = 1.7 Hz, 1H), 7.07 (dd, J = 8.0, 1.7 Hz, 1H), 6.81 (d, J = 8.0 Hz, 1H), 6.01 (s, 2H), 4.05 (s, 2H), 1.64 (s, 6H); LRMS (ESI): 290.10 [M+H] + 。

[0125] Example 74 (E)-4,4-Dimethyl-3-(3-(2-(trifluoromethyl)phenyl)acryloyl)oxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid is replaced with (E)-3-(2-trifluoromethylphenyl)acrylic acid, and oxazolidin-2-one is replaced with 4,4-dimethyloxazolidin-2-one. The remaining necessary raw materials, reagents, and preparation methods are the same as in Example 1 to obtain (E)-4,4-dimethyl-3-(3-(2-(trifluoromethyl)phenyl)acryloyl)oxazolidin-2-one. 1 H NMR (400 MHz, Chloroform-d) δ 8.15 (d, J = 15.4 Hz, 1H), 7.83 (d, J = 7.8 Hz, 1H), 7.79 - 7.65 (m, 2H), 7.53 (dt, J = 37.3, 7.7 Hz, 2H), 4.08 (s, 2H), 1.66 (s, 6H); LRMS (ESI): 314.09 [M+H] + 。

[0126] (E)-4,4-Dimethyl-3-(3-(3-(trifluoromethoxy)phenyl)acryloyl)oxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid is replaced with (E)-3-(3-trifluoromethoxyphenyl)acrylic acid, oxazolidin-2-one is replaced with 4,4-dimethyloxazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods are the same as in Example 1 to obtain (E)-4,4-dimethyl-3-(3-(3-(trifluoromethoxy)phenyl)acryloyl)oxazolidin-2-one. 1 H NMR(400MHz,Chloroform-d)δ 7.73(s,2H),7.53(dt,J=7.7,1.2Hz,1H),7.45-7.38(m,2H),7.25-7.22(m,1H),4.08(s,2H),1.65(s,6H);LRMS(ESI):330.09[M+H] + 。

[0127] (E)-4,4-Dimethyl-3-(3-(2-(trifluoromethoxy)phenyl)acryloyl)oxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid is replaced with (E)-3-(2-trifluoromethoxyphenyl)acrylic acid, oxazolidin-2-one is replaced with 4,4-dimethyloxazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods are the same as in Example 1 to obtain (E)-4,4-dimethyl-3-(3-(2-(trifluoromethoxy)phenyl)acryloyl)oxazolidin-2-one. 1 H NMR(400MHz,Chloroform-d)δ 8.04(d,J=15.8Hz,1H),7.88-7.66(m,2H),7.47-7.38(m,1H),7.38-7.20(m,2H),4.08(s,2H),1.66(s,6H);LRMS(ESI):330.09[M+H] + 。

[0128] (E)-3-(3-(4-Fluoro-2-(trifluoromethyl)phenyl)acryloyl)-4,4-dimethyloxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(4-fluoro-2-trifluoromethylphenyl)acrylic acid, oxazolidin-2-one was replaced with 4,4-dimethyloxazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(4-fluoro-2-(trifluoromethyl)phenyl)acryloyl)-4,4-dimethyloxazolidin-2-one. 1 H NMR(400MHz,Chloroform-d)δ 8.07(d,J=15.6Hz,1H),7.84(dd,J=8.8,5.4Hz,1H),7.67(d,J=15.5Hz,1H),7.45-7.38(m,1H),7.27(d,J=6.5Hz,1H),4.08(s,2H),1.66(s,6H);LRMS(ESI):332.12[M+H] + 。

[0129] (E)-3-(3-([1,1'-Biphenyl]-3-yl)acryloyl)thiazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-([1,1'-biphenyl]-3-yl)acrylic acid, oxazolidin-2-one was replaced with thiazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (E)-3-(3-([1,1'-biphenyl]-3-yl)acryloyl)thiazolidin-2-one (yield 89.0%). 1 H NMR(400MHz,DMSO-d6)δ 7.81(d,J=15.0Hz,1H),7.73(dd,J=7.5,2.0Hz,2H),7.66-7.44(m,7H),7.44-7.34(m,1H),3.70(t,J=6.1Hz,2H),3.55(t,J=6.0Hz,2H).LRMS(ESI):310.08[M+H] + 。

[0130] Example 79 (E)-3-(3-(2-Phenoxyphenyl)acryloyl)thiazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(2-phenoxyphenyl)acrylic acid, oxazolidin-2-one was replaced with thiazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(2-phenoxyphenyl)acryloyl)thiazolidin-2-one (yield 89.6%). 1 H NMR (400 MHz, DMSO-d6) δ 7.94 (dd, J = 15.0, 0.9 Hz, 1H), 7.68 - 7.60 (m, 2H), 7.46 (td, J = 7.5, 2.0 Hz, 1H), 7.44 - 7.34 (m, 2H), 7.23 - 7.09 (m, 2H), 7.12 - 7.01 (m, 3H), 3.70 (t, J = 6.1 Hz, 2H), 3.55 (t, J = 6.0 Hz, 2H). LRMS (ESI): 326.08 [M+H] + 。

[0131] Example 80 (E)-3-(3-(2-Trifluoromethylphenyl)acryloyl)thiazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(2-trifluoromethylphenyl)acrylic acid, oxazolidin-2-one was replaced with thiazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(2-trifluoromethylphenyl)acryloyl)thiazolidin-2-one (yield 90.6%). 1 H NMR (400 MHz, DMSO-d6) δ 7.86 - 7.79 (m, 1H), 7.76 (td, J = 7.5, 2.0 Hz, 1H), 7.69 - 7.55 (m, 2H), 7.47 (td, J = 7.4, 2.1 Hz, 1H), 7.30 - 7.23 (m, 1H), 3.70 (t, J = 6.2 Hz, 2H), 3.55 (t, J = 6.2 Hz, 2H). LRMS (ESI): 302.04 [M+H] + 。

[0132] Example 81 (E)-3-(3-(Thiophen-2-yl)acryloyl)thiazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(thiophen-2-yl)acrylic acid, oxazolidin-2-one was replaced with thiazolidin-2-one, and the remaining necessary raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(thiophen-2-yl)acryloyl)thiazolidin-2-one (yield 85.1%). 1 H NMR(400MHz,DMSO-d6)δ 7.86-7.75(m,2H),7.70(dd,J=7.4,1.6Hz,1H),7.60(d,J=15.0Hz,1H),7.20(t,J=7.4Hz,1H),3.70(t,J=6.1Hz,2H),3.55(t,J=6.0Hz,2H).LRMS(ESI):240.01[M+H] + 。

[0133] Example 83 (S,E)-4-Phenyl-3-(3-(2-trifluoromethylphenyl)acryloyl)oxazolidin-2-one-5,5-d2 (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(2-trifluoromethylphenyl)acrylic acid, oxazolidin-2-one was replaced with (S)-4-phenyloxazolidin-2-one-5,5-d2, and the remaining necessary raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S,E)-4-phenyl-3-(3-(2-trifluoromethylphenyl)acryloyl)oxazolidin-2-one-5,5-d2. 1 H NMR(400MHz,DMSO-d6)δ 7.94(d,J=7.8Hz,1H),7.89-7.77(m,4H),7.67(t,J=7.6Hz,1H),7.44-7.30(m,5H),5.57(s,1H).LRMS(ESI):364.11[M+H] + 。

[0134] Example 84 (S,E)-4-Phenyl-3-(3-(2-trifluoromethoxyphenyl)acryloyl)oxazolidin-2-one-5,5-d2 (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(2-trifluoromethoxyphenyl)acrylic acid, oxazolidin-2-one was replaced with (S)-4-phenyloxazolidin-2-one-5,5-d2, and the remaining necessary raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S,E)-4-phenyl-3-(3-(2-trifluoromethoxyphenyl)acryloyl)oxazolidin-2-one-5,5-d2. 1 H NMR(400MHz,DMSO-d6)δ 7.95(d,J=15.0Hz,1H),7.70-7.60(m,2H),7.39-7.28(m,4H),7.28-7.18(m,2H),7.02(t,J=7.1Hz,2H),5.50(s,1H). LRMS(ESI):380.11[M+H] + 。

[0135] Example 85 (S,E)-4-Phenyl-3-(3-(2-phenoxyphenyl)acryloyl)oxazolidin-2-one-5,5-d2 (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(2-phenoxyphenyl)acrylic acid, oxazolidin-2-one was replaced with (S)-4-phenyloxazolidin-2-one-5,5-d2, and the remaining necessary raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S,E)-4-phenyl-3-(3-(2-phenoxyphenyl)acryloyl)oxazolidin-2-one-5,5-d2. 1 H NMR(400MHz,DMSO-d6)δ 7.95(d,J=15.0Hz,1H),7.68-7.58(m,2H),7.46(td,J=7.4,2.0Hz,1H),7.42-7.19(m,7H),7.19-7.09(m,1H),7.09-7.01(m,2H),5.50(s,1H). LRMS(ESI):388.14[M+H] + 。

[0136] Example 86 (S,E)-3-(3-([1,1'-Biphenyl]-3-yl)acryloyl)-4-phenyloxazolidin-2-one-5,5-d2 (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-([1,1'-biphenyl]-3-yl)acrylic acid, oxazolidin-2-one was replaced with (S)-4-isopropyloxazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (S,E)-3-(3-([1,1'-biphenyl]-3-yl)acryloyl)-4-phenyloxazolidin-2-one-5,5-d2. 1 H NMR(400MHz,DMSO-d6)δ 7.81(d,J=15.0Hz,1H),7.73(dd,J=7.6,2.0Hz,3H),7.62(dt,J=7.6,2.1Hz,1H),7.54-7.47(m,3H),7.47-7.32(m,7H),7.32-7.25(m,1H),7.24(ddt,J=5.3,3.9,1.6Hz,1H),5.50(s,1H). LRMS(ESI):372.15[M+H] + 。

[0137] Example 87 (S,E)-4-Phenyl-3-(3-(3-phenoxyphenyl)acryloyl)oxazolidin-2-one-5,5-d2 (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(3-phenoxyphenyl)acrylic acid, oxazolidin-2-one was replaced with (S)-4-phenyloxazolidin-2-one-5,5-d2, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (S,E)-4-phenyl-3-(3-(3-phenoxyphenyl)acryloyl)oxazolidin-2-one-5,5-d2. 1 H NMR(400MHz,DMSO-d6)δ 7.81(d,J=15.1Hz,1H),7.44-7.29(m,9H),7.29-7.20(m,2H),7.14(tt,J=7.4,2.0Hz,1H),7.05(dd,J=7.5,2.0Hz,2H),6.88(dp,J=4.1,2.1Hz,2H),5.50(s,1H). LRMS(ESI):388.14[M+H] + 。

[0138] Example 88 (E)-4-Phenyl-3-(3-(2-trifluoromethylphenyl)acryloyl)oxazolidin-2-one-5,5-d2 (E)-3-(o-Tolyl)acrylic acid is replaced with (E)-3-(2-trifluoromethylphenyl)acrylic acid, oxazolidin-2-one is replaced with 4-phenyloxazolidin-2-one-5,5-d2, and the remaining necessary raw materials, reagents and preparation methods are the same as in Example 1 to obtain (E)-4-phenyl-3-(3-(2-trifluoromethylphenyl)acryloyl)oxazolidin-2-one-5,5-d2. 1 H NMR (400 MHz, DMSO-d6) δ 7.94 (d, J = 7.8 Hz, 1H), 7.89 - 7.77 (m, 4H), 7.67 (t, J = 7.6 Hz, 1H), 7.44 - 7.30 (m, 5H), 5.57 (s, 1H). LRMS (ESI): 364.11 [M + H] + 。

[0139] Example 89 (E)-3-(3-(2-Trifluoromethylphenyl)acryloyl)oxazolidin-2-one-4,4,5,5-d4 (E)-3-(o-Tolyl)acrylic acid is replaced with (E)-3-(2-trifluoromethylphenyl)acrylic acid, oxazolidin-2-one is replaced with oxazolidin-2-one-4,4,5,5-d4, and the remaining necessary raw materials, reagents and preparation methods are the same as in Example 1 to obtain (E)-3-(3-(2-trifluoromethylphenyl)acryloyl)oxazolidin-2-one-4,4,5,5-d4. 1 H NMR (400 MHz, DMSO-d6) δ 8.00 - 7.89 (m, 2H), 7.76 (td, J = 7.5, 2.1 Hz, 1H), 7.64 (d, J = 15.0 Hz, 1H), 7.35 (td, J = 7.5, 2.0 Hz, 1H), 7.27 - 7.19 (m, 1H). LRMS (ESI): 290.09 [M + H] + 。

[0140] Example 90 (E)-3-(3-(2-Methoxyphenyl)acryloyl)oxazolidin-2-one-4,4,5,5-d4 (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(2-methoxyphenyl)acrylic acid, oxazolidin-2-one was replaced with oxazolidin-2-one-4,4,5,5-d4, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(2-methoxyphenyl)acryloyl)oxazolidin-2-one-4,4,5,5-d4. 1 H NMR(400MHz,DMSO-d6)δ 7.95(dd,J=15.0,1.0Hz,1H),7.70-7.60(m,2H),7.49(td,J=7.5,2.0Hz,1H),7.11-6.97(m,2H),3.91(s,3H). LRMS(ESI):252.11[M+H] + 。

[0141] Example 91 (E)-3-(3-(3-Methoxyphenyl)acryloyl)oxazolidin-2-one-4,4,5,5-d4 (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(3-methoxyphenyl)acrylic acid, oxazolidin-2-one was replaced with oxazolidin-2-one-4,4,5,5-d4, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(3-methoxyphenyl)acryloyl)oxazolidin-2-one-4,4,5,5-d4. 1 H NMR(400MHz,DMSO-d6)δ 7.81(d,J=15.0Hz,1H),7.41-7.27(m,3H),7.04(t,J=1.6Hz,1H),6.86-6.77(m,1H),3.73(s,3H). LRMS(ESI):252.11[M+H] + 。

[0142] Example 92 (E)-3-(3-(4-Methoxyphenyl)acryloyl)oxazolidin-2-one-4,4,5,5-d4 (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(4-methoxyphenyl)acrylic acid, oxazolidin-2-one was replaced with oxazolidin-2-one-4,4,5,5-d4, and the remaining necessary raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(4-methoxyphenyl)acryloyl)oxazolidin-2-one-4,4,5,5-d4. 1 H NMR(400MHz,DMSO-d6)δ 7.81(d,J=15.0Hz,1H),7.72-7.64(m,2H),7.37(dt,J=15.2,1.0Hz,1H),7.10-7.02(m,2H),3.79(s,3H).LRMS(ESI):252.11[M+H] + 。

[0143] Example 93 (E)-3-(3-([1,1'-Biphenyl]-3-yl)acryloyl)oxazolidin-2-one-4,4,5,5-d4 (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-([1,1'-biphenyl]-3-yl)acrylic acid, oxazolidin-2-one was replaced with oxazolidin-2-one-4,4,5,5-d4, and the remaining necessary raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-([1,1'-biphenyl]-3-yl)acryloyl)oxazolidin-2-one-4,4,5,5-d4. 1 H NMR(400MHz,DMSO-d6)δ 7.81(d,J=15.0Hz,1H),7.73(dd,J=7.6,2.0Hz,3H),7.62(dt,J=7.6,2.1Hz,1H),7.54-7.43(m,4H),7.43-7.32(m,2H).LRMS(ESI):298.13[M+H] + 。

[0144] Example 94 (E)-3-(3-(3-Phenoxyphenyl)acryloyl)oxazolidin-2-one-4,4,5,5-d4 (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(3-phenoxyphenyl)acrylic acid, oxazolidin-2-one was replaced with oxazolidin-2-one-4,4,5,5-d4, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(3-phenoxyphenyl)acryloyl)oxazolidin-2-one-4,4,5,5-d4. 1 H NMR(400MHz,DMSO-d6)δ 7.81(d,J=15.1Hz,1H),7.44-7.31(m,4H),7.29(t,J=7.7Hz,1H),7.14(tt,J=7.5,2.0Hz,1H),7.09-7.01(m,2H),6.88(dp,J=4.1,2.1Hz,2H). LRMS(ESI):314.13[M+H] + 。

[0145] Example 95 (E)-3-(3-(4-Methoxyphenyl)acryloyl)oxazolidin-2-one-4,4-d2 (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(4-methoxyphenyl)acrylic acid, oxazolidin-2-one was replaced with oxazolidin-2-one-4,4-d2, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(4-methoxyphenyl)acryloyl)oxazolidin-2-one-4,4-d2. 1 H NMR(400MHz,DMSO-d6)δ 7.81(d,J=15.0Hz,1H),7.72-7.64(m,2H),7.37(dt,J=15.2,1.0Hz,1H),7.10-7.02(m,2H),4.30(s,2H),3.79(s,3H). LRMS(ESI):250.10[M+H] + 。

[0146] Example 96 (E)-3-(3-(4-Methoxyphenyl)acryloyl)oxazolidin-2-one-5,5-d2 (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(4-methoxyphenyl)acrylic acid, oxazolidin-2-one was replaced with oxazolidin-2-one-5,5-d2, and the remaining necessary raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(4-methoxyphenyl)acryloyl)oxazolidin-2-one-5,5-d2. 1 H NMR(400MHz,DMSO-d6)δ 7.81(d,J=15.0Hz,1H),7.72-7.64(m,2H),7.37(dt,J=15.1,1.0Hz,1H),7.10-7.02(m,2H),3.80(s,2H),3.79(s,3H).LRMS(ESI):250.10[M+H] + 。

[0147] Example 97 (E)-3-(3-(3-Phenoxyphenyl)acryloyl)oxazolidin-2-one-4,4-d2 (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(3-phenoxyphenyl)acrylic acid, oxazolidin-2-one was replaced with oxazolidin-2-one-4,4-d2, and the remaining necessary raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(3-phenoxyphenyl)acryloyl)oxazolidin-2-one-4,4-d2. 1 H NMR(400MHz,DMSO-d6)δ 7.81(d,J=15.1Hz,1H),7.44-7.31(m,4H),7.29(t,J=7.7Hz,1H),7.14(tt,J=7.5,2.0Hz,1H),7.09-7.01(m,2H),6.88(dp,J=5.7,2.1Hz,2H),4.30(s,2H).LRMS(ESI):312.12[M+H] + 。

[0148] Example 98 (E)-3-(3-(3-Phenoxyphenyl)acryloyl)oxazolidin-2-one-5,5-d2 (E)-3-(o-Tolyl)acrylic acid is replaced with (E)-3-(3-phenoxyphenyl)acrylic acid, oxazolidin-2-one is replaced with oxazolidin-2-one-5,5-d2, and the remaining necessary raw materials, reagents and preparation methods are the same as in Example 1 to obtain (E)-3-(3-(3-phenoxyphenyl)acryloyl)oxazolidin-2-one-5,5-d2. 1 H NMR(400MHz,DMSO-d6)δ 7.81(d,J=15.1Hz,1H),7.44-7.31(m,4H),7.29(t,J=7.7Hz,1H),7.14(tt,J=7.5,2.0Hz,1H),7.09-7.01(m,2H),6.88(dp,J=5.7,2.1Hz,2H),3.80(s,2H). LRMS(ESI):312.12[M+H] + 。

[0149] Example 99 (E)-3-(3-(2-Trifluoromethylphenyl)acryloyl)oxazolidin-2-one-5,5-d2 (E)-3-(o-Tolyl)acrylic acid is replaced with (E)-3-(2-trifluoromethylphenyl)acrylic acid, oxazolidin-2-one is replaced with oxazolidin-2-one-5,5-d2, and the remaining necessary raw materials, reagents and preparation methods are the same as in Example 1 to obtain (E)-3-(3-(2-trifluoromethylphenyl)acryloyl)oxazolidin-2-one-5,5-d2. 1 H NMR(400MHz,DMSO-d6)δ 8.00-7.89(m,2H),7.76(td,J=7.5,2.1Hz,1H),7.64(d,J=15.0Hz,1H),7.35(td,J=7.5,2.0Hz,1H),7.23(ddd,J=7.6,2.1,1.0Hz,1H),3.80(s,2H). LRMS(ESI):288.07[M+H] + 。

[0150] Example 100 (E)-3-(3-([1,1’-Biphenyl]-3-yl)acryloyl)oxazolidin-2-one-5,5-d2 (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-([1,1'-biphenyl]-3-yl)acrylic acid, oxazolidin-2-one was replaced with oxazolidin-2-one-5,5-d2, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (E)-3-(3-([1,1'-biphenyl]-3-yl)acryloyl)oxazolidin-2-one-5,5-d2. 1 H NMR(400MHz,DMSO-d6)δ 7.81(d,J=15.0Hz,1H),7.73(dq,J=8.3,2.1Hz,3H),7.62(dt,J=7.6,2.1Hz,1H),7.54-7.43(m,4H),7.39(s,1H),7.44-7.32(m,1H),3.80(s,2H). LRMS(ESI):296.12[M+H] + 。

[0151] Example 101 (E)-4,4-Dimethyl-3-(3-(2-(trifluoromethyl)phenyl)acryloyl)oxazolidin-2-one-5,5-d2 (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(2-trifluoromethylphenyl)acrylic acid, oxazolidin-2-one was replaced with 4,4-dimethyloxazolidin-2-one-5,5-d2, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (E)-4,4-dimethyl-3-(3-(2-(trifluoromethyl)phenyl)acryloyl)oxazolidin-2-one-5,5-d2. 1 H NMR(400MHz,DMSO-d6)δ 8.00-7.89(m,2H),7.76(td,J=7.5,2.0Hz,1H),7.64(d,J=15.0Hz,1H),7.35(td,J=7.5,2.1Hz,1H),7.23(ddd,J=7.5,2.1,1.0Hz,1H),1.29(s,6H). LRMS(ESI):316.12[M+H] + 。

[0152] Example 102 (E)-4-(4'-Fluorophenyl)-3-(3-(2-(trifluoromethylphenyl)acryloyl)oxazolidin-2-one-5,5-d2 Replace (E)-3-(o-tolyl)acrylic acid with (E)-3-(2-trifluoromethylphenyl)acrylic acid, replace oxazolidin-2-one with 4-(4'-fluorophenyl)oxazolidin-2-one-5,5-d2, and use the remaining necessary raw materials, reagents and preparation methods in the same manner as in Example 1 to obtain (E)-4-(4'-fluorophenyl)-3-(3-(2-(trifluoromethylphenyl)acryloyl)oxazolidin-2-one-5,5-d2). 1 H NMR (400 MHz, DMSO-d6) δ 8.00 - 7.89 (m, 2H), 7.76 (td, J = 7.5, 2.1 Hz, 1H), 7.64 (d, J = 15.0 Hz, 1H), 7.35 (td, J = 7.5, 2.1 Hz, 1H), 7.27 - 7.12 (m, 5H), 5.50 (s, 1H). LRMS (ESI): 382.10 [M+H] + 。

[0153] Example 103 (S,E)-4-(4'-fluorophenyl)-3-(3-(2-(trifluoromethylphenyl)acryloyl)oxazolidin-2-one-5,5-d2 Replace (E)-3-(o-tolyl)acrylic acid with (E)-3-(2-trifluoromethylphenyl)acrylic acid, replace oxazolidin-2-one with (S)-4-(4'-fluorophenyl)oxazolidin-2-one-5,5-d2, and use the remaining necessary raw materials, reagents and preparation methods in the same manner as in Example 1 to obtain (S,E)-4-(4'-fluorophenyl)-3-(3-(2-(trifluoromethylphenyl)acryloyl)oxazolidin-2-one-5,5-d2). 1 H NMR (400 MHz, DMSO-d6) δ 8.00 - 7.89 (m, 2H), 7.76 (td, J = 7.5, 2.1 Hz, 1H), 7.64 (d, J = 15.0 Hz, 1H), 7.35 (td, J = 7.5, 2.1 Hz, 1H), 7.27 - 7.12 (m, 5H), 5.50 (s, 1H). LRMS (ESI): 382.10 [M+H] + 。

[0154] Example 104 (E)-4-Benzyl-3-(3-(2-trifluoromethylphenyl)acryloyl)oxazolidin-2-one-5,5-d2 (E)-3-(o-Tolyl)acrylic acid is replaced with (E)-3-(2-trifluoromethylphenyl)acrylic acid, oxazolidin-2-one is replaced with 4-benzyloxazolidin-2-one-5,5-d2, and the remaining necessary raw materials, reagents and preparation methods are the same as in Example 1 to obtain (E)-4-benzyl-3-(3-(2-trifluoromethylphenyl)acryloyl)oxazolidin-2-one-5,5-d2. 1 H NMR (400 MHz, DMSO-d6) δ 8.00-7.89 (m, 2H), 7.76 (td, J = 7.5, 2.1 Hz, 1H), 7.64 (d, J = 15.0 Hz, 1H), 7.35 (td, J = 7.5, 2.1 Hz, 1H), 7.33-7.14 (m, 6H), 4.60 (t, J = 5.3 Hz, 1H), 3.04 (dd, J = 12.4, 5.3 Hz, 1H), 2.78 (dd, J = 12.4, 5.3 Hz, 1H). LRMS (ESI): 378.12 [M+H] + .

[0155] Example 105 (S,E)-4-Benzyl-3-(3-(2-trifluoromethylphenyl)acryloyl)oxazolidin-2-one-5,5-d2 (E)-3-(o-Tolyl)acrylic acid is replaced with (E)-3-(2-trifluoromethylphenyl)acrylic acid, oxazolidin-2-one is replaced with (S)-4-benzyloxazolidin-2-one-5,5-d2, and the remaining necessary raw materials, reagents and preparation methods are the same as in Example 1 to obtain (S,E)-4-benzyl-3-(3-(2-trifluoromethylphenyl)acryloyl)oxazolidin-2-one-5,5-d2. 11H NMR (400 MHz, DMSO-d6) δ 8.00 - 7.89 (m, 2H), 7.76 (td, J = 7.5, 2.1 Hz, 1H), 7.64 (d, J = 15.0 Hz, 1H), 7.35 (td, J = 7.5, 2.1 Hz, 1H), 7.33 - 7.14 (m, 6H), 4.60 (t, J = 5.3 Hz, 1H), 3.04 (dd, J = 12.4, 5.3 Hz, 1H), 2.78 (dd, J = 12.4, 5.3 Hz, 1H). LRMS (ESI): 378.12 [M+H] + 。

[0156] Example 106 (S,E)-4-(4'-fluorophenyl)-3-(3-(2-(trifluoromethoxyphenyl)acryloyl)oxazolidin-2-one-5,5-d2 (E)-3-(o-tolyl)acrylic acid was replaced with (E)-3-(2-trifluoromethoxyphenyl)acrylic acid, and oxazolidin-2-one was replaced with (S)-4-(4'-fluorophenyl)oxazolidin-2-one-5,5-d2. The remaining necessary raw materials, reagents and preparation methods were the same as in Example 1, and (S,E)-4-(4'-fluorophenyl)-3-(3-(2-(trifluoromethoxyphenyl)acryloyl)oxazolidin-2-one-5,5-d2 was obtained. 1 1H NMR (400 MHz, DMSO-d6) δ 7.95 (dd, J = 15.0, 0.9 Hz, 1H), 7.70 - 7.60 (m, 2H), 7.28 - 7.12 (m, 5H), 7.02 (t, J = 7.1 Hz, 2H), 5.50 (s, 1H). LRMS (ESI): 398.09 [M+H] + 。

[0157] Example 107 (S,E)-4-(4'-fluorophenyl)-3-(3-(2-(phenoxyphenyl)acryloyl)oxazolidin-2-one-5,5-d2 (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(2-phenoxyphenyl)acrylic acid, oxazolidin-2-one was replaced with (S)-4-(4'-fluorophenyl)oxazolidin-2-one-5,5-d2, and the remaining necessary raw materials, reagents and preparation methods were the same as those in Example 1 to obtain (S,E)-4-(4'-fluorophenyl)-3-(3-(2-(phenoxyphenyl)acryloyl)oxazolidin-2-one-5,5-d2). 1 H NMR(400MHz,DMSO-d6)δ 7.95(dd,J=15.0,0.9Hz,1H),7.68-7.58(m,2H),7.46(td,J=7.4,2.0Hz,1H),7.44-7.34(m,2H),7.31-7.18(m,3H),7.21-7.10(m,3H),7.14-7.01(m,3H),5.50(s,1H). LRMS(ESI):406.13[M+H] + 。

[0158] Example 108 (S,E)-3-(3-([1,1'-Biphenyl]-3-yl)acryloyl)-4-(4'-fluorophenyl)oxazolidin-2-one-5,5-d2 (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-([1,1'-biphenyl]-3-yl)acrylic acid, oxazolidin-2-one was replaced with (S)-4-(4'-fluorophenyl)oxazolidin-2-one-5,5-d2, and the remaining necessary raw materials, reagents and preparation methods were the same as those in Example 1 to obtain (S,E)-3-(3-([1,1'-biphenyl]-3-yl)acryloyl)-4-(4'-fluorophenyl)oxazolidin-2-one-5,5-d2. 1 H NMR(400MHz,DMSO-d6)δ 7.81(d,J=15.0Hz,1H),7.73(dd,J=7.5,2.0Hz,3H),7.62(dt,J=7.6,2.1Hz,1H),7.54-7.43(m,4H),7.44-7.33(m,2H),7.26-7.12(m,4H),5.50(s,1H). LRMS(ESI):390.13[M+H] + 。

[0159] Example 109 (S,E)-4-(4'-fluorophenyl)-3-(3-(3-(phenoxyphenyl)acryloyl)oxazolidin-2-one-5,5-d2 (E)-3-(o-tolyl)acrylic acid was replaced with (E)-3-(3-phenoxyphenyl)acrylic acid, oxazolidin-2-one was replaced with (S)-4-(4'-fluorophenyl)oxazolidin-2-one-5,5-d2, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (S,E)-4-(4'-fluorophenyl)-3-(3-(3-(phenoxyphenyl)acryloyl)oxazolidin-2-one-5,5-d2. 1 H NMR (400 MHz, DMSO-d6) δ 7.81 (d, J = 15.1 Hz, 1H), 7.44 - 7.09 (m, 11H), 7.09 - 7.01 (m, 2H), 6.88 (dp, J = 4.1, 2.1 Hz, 2H), 5.50 (s, 1H). LRMS (ESI): 406.13 [M+H] + .

[0160] Example 110 (R,E)-5,5-dimethyl-4-phenyl-3-(3-(2-(trifluoromethyl)phenyl)acryloyl)oxazolidin-2-one (E)-3-(o-tolyl)acrylic acid was replaced with (E)-3-(o-trifluoromethylphenyl)acrylic acid, oxazolidin-2-one was replaced with (R)-5,5-dimethyl-4-phenyloxazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (R,E)-5,5-dimethyl-4-phenyl-3-(3-(2-(trifluoromethyl)phenyl)acryloyl)oxazolidin-2-one (yield 64.2%). 11H NMR (500 MHz, Chloroform-d) δ 8.16 (dq, J = 15.5, 2.3 Hz, 1H), 8.00 (d, J = 15.6 Hz, 1H), 7.89 (d, J = 7.8 Hz, 1H), 7.69 (d, J = 7.8 Hz, 1H), 7.59 (t, J = 7.6 Hz, 1H), 7.51 - 7.47 (m, 1H), 7.42 - 7.33 (m, 3H), 7.22 - 7.19 (m, 2H), 5.20 (s, 1H), 1.65 (s, 3H), 1.04 (s, 3H). HRMS (ESI): 390.1315 [M+H] + 。

[0161] Example 111 (S,E)-5,5-Dimethyl-4-phenyl-3-(3-(2-(trifluoromethyl)phenyl)acryloyl)oxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(o-trifluoromethylphenyl)acrylic acid, oxazolidin-2-one was replaced with (S)-5,5-dimethyl-4-phenyloxazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (S,E)-5,5-dimethyl-4-phenyl-3-(3-(2-(trifluoromethyl)phenyl)acryloyl)oxazolidin-2-one (yield 71.5%). 1 1H NMR (500 MHz, Chloroform-d) δ 8.19 (ddd, J = 7.4, 1.5, 0.6 Hz, 1H), 8.02 (td, J = 7.4, 1.6 Hz, 1H), 7.96 (dd, J = 7.5, 1.6 Hz, 1H), 7.90 (td, J = 7.5, 1.6 Hz, 1H), 7.88 - 7.82 (m, 1H), 7.62 (d, J = 15.0 Hz, 1H), 7.36 - 7.24 (m, 5H), 5.25 - 5.21 (m, 1H), 1.46 (d, J = 1.6 Hz, 3H), 1.41 (d, J = 1.5 Hz, 3H). LRMS (ESI): 390.20 [M+H] + 。

[0162] Example 112 (R,E)-7-Phenyl-6-(3-(2-(trifluoromethyl)phenyl)acryloyl)-4-oxa-6-azaspiro[2.4]heptan-5-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(o-trifluoromethylphenyl)acrylic acid, oxazolidin-2-one was replaced with (R)-7-phenyl-4-oxa-6-azaspiro[2.4]heptan-5-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (R,E)-7-phenyl-6-(3-(2-(trifluoromethyl)phenyl)acryloyl)-4-oxa-6-azaspiro[2.4]heptan-5-one (yield 49.2%). 1 H NMR(500MHz,Chloroform-d)δ 8.18-8.13(m,1H),7.94(d,J=15.4Hz,1H),7.86(d,J=7.8Hz,1H),7.68(dd,J=7.9,1.3Hz,1H),7.58(t,J=7.7Hz,1H),7.48(t,J=7.6Hz,1H),7.43-7.32(m,5H),5.32(s,1H),1.40-1.33(m,1H),1.21-1.13(m,1H),0.98-0.89(m,1H),0.48(d,J=345.4Hz,1H). HRMS(ESI):388.1156[M+H] + 。

[0163] Example 113 (S,E)-7-Phenyl-6-(3-(2-(trifluoromethyl)phenyl)acryloyl)-4-oxa-6-azaspiro[2.4]heptan-5-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(o-trifluoromethylphenyl)acrylic acid, oxazolidin-2-one was replaced with (S)-7-phenyl-4-oxa-6-azaspiro[2.4]heptan-5-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (S,E)-7-phenyl-6-(3-(2-(trifluoromethyl)phenyl)acryloyl)-4-oxa-6-azaspiro[2.4]heptan-5-one (yield 47.2%). 11H NMR (500 MHz, Chloroform-d) δ 8.19 (ddd, J = 7.4, 1.6, 0.6 Hz, 1H), 8.02 (td, J = 7.4, 1.6 Hz, 1H), 7.96 (dd, J = 7.5, 1.6 Hz, 1H), 7.90 (td, J = 7.5, 1.6 Hz, 1H), 7.88 - 7.82 (m, 1H), 7.62 (d, J = 15.0 Hz, 1H), 7.37 - 7.24 (m, 5H), 5.20 (d, J = 0.7 Hz, 1H), 1.66 - 1.55 (m, 2H), 1.55 - 1.44 (m, 2H). LRMS (ESI): 388.12 [M+H] + 。

[0164] Example 114 (E)-5-Phenyl-1-(3-(2-(trifluoromethyl)phenyl)acryloyl)imidazolidine-2,4-dione (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(m-methoxyphenyl), oxazolidin-2-one was replaced with 5-phenylimidazolidine-2,4-dione, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (E)-5-phenyl-1-(3-(2-(trifluoromethyl)phenyl)acryloyl)imidazolidine-2,4-dione (yield 62.8%). 1 1H NMR (400 MHz, DMSO-d6) δ 11.95 (s, 1H), 7.99 - 7.92 (m, 2H), 7.91 - 7.84 (m, 1H), 7.82 - 7.76 (m, 2H), 7.67 - 7.62 (m, 1H), 7.41 (d, J = 4.3 Hz, 4H), 7.39 - 7.34 (m, 1H), 5.67 (s, 1H). HRMS (ESI): 375.0952 [M+H] + 。

[0165] Example 115 (R,E)-6-(3-(3-Methoxyphenyl)acryloyl)-7-phenyl-4-oxa-6-azaspiro[2.4]heptan-5-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(methoxyphenyl)acrylic acid, oxazolidin-2-one was replaced with (R)-7-phenyl-4-oxa-6-azaspiro[2.4]heptan-5-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (R,E)-6-(3-(3-methoxyphenyl)acryloyl)-7-phenyl-4-oxa-6-azaspiro[2.4]heptan-5-one (yield 43.2%). 1 H NMR(500MHz,Chloroform-d)δ 7.93(d,J=15.7Hz,1H),7.75(d,J=15.8Hz,2H),7.40-7.25(m,8H),7.19(dt,J=7.8,1.4Hz,1H),7.09(dd,J=2.6,1.6Hz,1H),6.97-6.91(m,2H),5.32(s,1H),1.41-1.32(m,1H),1.20-1.10(m,1H),0.96-0.87(m,1H),0.51-0.42(m,1H). HRMS(ESI):350.1384[M+H] + 。

[0166] Example 116 (S,E)-6-(3-(3-Methoxyphenyl)acryloyl)-7-phenyl-4-oxa-6-azaspiro[2.4]heptan-5-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(methoxyphenyl)acrylic acid, oxazolidin-2-one was replaced with (S)-7-phenyl-4-oxa-6-azaspiro[2.4]heptan-5-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (S,E)-6-(3-(3-methoxyphenyl)acryloyl)-7-phenyl-4-oxa-6-azaspiro[2.4]heptan-5-one (yield 48.2%). 11H NMR (500 MHz, Chloroform-d) δ 7.77 (d, J = 15.0 Hz, 1H), 7.72 - 7.65 (m, 1H), 7.37 - 7.23 (m, 7H), 7.15 (t, J = 1.5 Hz, 1H), 7.06 (ddt, J = 7.5, 3.1, 1.6 Hz, 2H), 5.20 (d, J = 0.7 Hz, 1H), 3.80 (s, 2H), 1.66 - 1.55 (m, 2H), 1.55 - 1.44 (m, 2H). LRMS (ESI): 350.15 [M+H] + 。

[0167] Example 117 (R,E)-6-(3-(3-Phenoxyphenyl)acryloyl)-7-phenyl-4-oxa-6-azaspiro[2.4]heptan-5-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(phenoxyphenyl)acrylic acid, and oxazolidin-2-one was replaced with (R)-7-phenyl-4-oxa-6-azaspiro[2.4]heptan-5-one. The remaining necessary raw materials, reagents and preparation methods were the same as in Example 1, and (R,E)-6-(3-(3-phenoxyphenyl)acryloyl)-7-phenyl-4-oxa-6-azaspiro[2.4]heptan-5-one (yield 51.1%) was obtained. 1 1H NMR (500 MHz, Chloroform-d) δ 7.91 (d, J = 15.7 Hz, 1H), 7.72 (d, J = 15.7 Hz, 1H), 7.42 - 7.30 (m, 9H), 7.24 - 7.21 (m, 1H), 7.13 (t, J = 7.4 Hz, 1H), 7.04 - 6.99 (m, 3H), 5.31 (s, 1H), 1.39 - 1.32 (m, 1H), 1.19 - 1.11 (m, 1H), 0.96 - 0.88 (m, 1H), 0.52 - 0.42 (m, 1H). HRMS (ESI): 421.1542 [M+H] + 。

[0168] Example 118 (S,E)-6-(3-(3-Phenoxyphenyl)acryloyl)-7-phenyl-4-oxa-6-azaspiro[2.4]heptan-5-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(phenoxyphenyl)acrylic acid, oxazolidin-2-one was replaced with (S)-7-phenyl-4-oxa-6-azaspiro[2.4]heptan-5-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (S,E)-6-(3-(3-phenoxyphenyl)acryloyl)-7-phenyl-4-oxa-6-azaspiro[2.4]heptan-5-one (yield 48.1%). 1 H NMR(500MHz,Chloroform-d)δ 7.77(d,J=15.0Hz,1H),7.72-7.65(m,1H),7.40-7.24(m,10H),7.20-7.15(m,1H),7.18-7.00(m,6H),5.19(s,1H),1.66-1.44(m,5H).LRMS(ESI):421.10[M+H] + 。

[0169] Example 119 (R,E)-7-Phenyl-6-(3-(2-(trifluoromethoxy)phenyl)acryloyl)-4-oxa-6-azaspiro[2.4]heptan-5-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(trifluoromethoxyphenyl)acrylic acid, oxazolidin-2-one was replaced with (R)-7-phenyl-4-oxa-6-azaspiro[2.4]heptan-5-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (R,E)-7-phenyl-6-(3-(2-(trifluoromethoxy)phenyl)acryloyl)-4-oxa-6-azaspiro[2.4]heptan-5-one (yield 34.2%). 1 H NMR(500MHz,Chloroform-d)δ 8.08-7.96(m,2H),7.80(dd,J=7.8,1.7Hz,1H),7.45-7.24(m,8H),5.32(s,1H),1.41-1.32(m,1H),1.19-1.12(m,1H),0.97-0.90(m,1H),0.51-0.43(m,1H).HRMS(ESI):404.1105[M+H] + 。

[0170] Example 120 (S,E)-7-Phenyl-6-(3-(2-(trifluoromethoxy)phenyl)acryloyl)-4-oxa-6-azaspiro[2.4]heptan-5-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(trifluoromethoxyphenyl)acrylic acid, oxazolidin-2-one was replaced with (S)-7-phenyl-4-oxa-6-azaspiro[2.4]heptan-5-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (S,E)-7-phenyl-6-(3-(2-(trifluoromethoxy)phenyl)acryloyl)-4-oxa-6-azaspiro[2.4]heptan-5-one (yield 36.5%). 1 H NMR(500MHz,Chloroform-d)δ 7.81-7.75(m,1H),7.63(d,J=15.2Hz,1H),7.56(ddd,J=7.5,1.5,0.6Hz,1H),7.38-7.26(m,6H),7.23(dd,J=7.5,1.6Hz,1H),6.99(td,J=7.5,1.6Hz,1H),5.19(s,1H),1.66-1.55(m,2H),1.55-1.44(m,2H). LRMS(ESI):404.13[M+H] + 。

[0171] Example 121 (R,E)-6-(3-(4-Methoxyphenyl)acryloyl)-7-phenyl-4-oxa-6-azaspiro[2.4]heptan-5-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-4-(methoxyphenyl)acrylic acid, oxazolidin-2-one was replaced with (R)-7-phenyl-4-oxa-6-azaspiro[2.4]heptan-5-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (R,E)-6-(3-(4-methoxyphenyl)acryloyl)-7-phenyl-4-oxa-6-azaspiro[2.4]heptan-5-one (yield 41.9%). 11H NMR (600 MHz, Chloroform-d) δ 7.85 - 7.73 (m, 2H), 7.54 (d, J = 8.5 Hz, 2H), 7.40 - 7.30 (m, 5H), 6.89 (d, J = 8.6 Hz, 2H), 5.31 (s, 1H), 3.83 (s, 3H), 1.39 - 1.31 (m, 1H), 1.17 - 1.09 (m, 1H), 0.95 - 0.86 (m, 1H), 0.50 - 0.43 (m, 1H). LRMS (ESI): 350.40 [M+H] + 。

[0172] Example 122 (S,E)-6-(3-(4-Methoxyphenyl)acryloyl)-7-phenyl-4-oxa-6-azaspiro[2.4]heptan-5-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-4-(methoxyphenyl)acrylic acid, oxazolidin-2-one was replaced with (S)-7-phenyl-4-oxa-6-azaspiro[2.4]heptan-5-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (S,E)-6-(3-(4-Methoxyphenyl)acryloyl)-7-phenyl-4-oxa-6-azaspiro[2.4]heptan-5-one (yield 41.9%). 1 1H NMR (600 MHz, Chloroform-d) δ 7.85 - 7.73 (m, 2H), 7.54 (d, J = 8.5 Hz, 2H), 7.40 - 7.30 (m, 5H), 6.89 (d, J = 8.6 Hz, 2H), 5.31 (s, 1H), 3.83 (s, 3H), 1.39 - 1.31 (m, 1H), 1.17 - 1.09 (m, 1H), 0.95 - 0.86 (m, 1H), 0.50 - 0.43 (m, 1H). LRMS (ESI): 350.40 [M+H] + 。

[0173] Example 123 (R,E)-6-(3-([1,1'-Biphenyl]-4-yl)acryloyl)-7-phenyl-4-oxa-6-azaspiro[2.4]heptan-5-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-([1,1'-biphenyl]-4-yl)acrylic acid, oxazolidin-2-one was replaced with (R)-7-phenyl-4-oxa-6-azaspiro[2.4]heptan-5-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (R,E)-6-(3-([1,1'-biphenyl]-4-yl)acryloyl)-7-phenyl-4-oxa-6-azaspiro[2.4]heptan-5-one (yield 33.2%). 1 H NMR(500MHz,Chloroform-d)δ 7.97(d,J=15.7Hz,1H),7.80(d,J=15.7Hz,1H),7.68-7.56(m,6H),7.47-7.28(m,8H),5.30(s,1H),1.39-1.31(m,1H),1.18-1.09(m,1H),0.96-0.87(m,1H),0.50-0.42(m,1H). HRMS(ESI):396.1599[M+H] + 。

[0174] Example 124 (S,E)-6-(3-([1,1'-biphenyl]-4-yl)acryloyl)-7-phenyl-4-oxa-6-azaspiro[2.4]heptan-5-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-([1,1'-biphenyl]-4-yl)acrylic acid, oxazolidin-2-one was replaced with (S)-7-phenyl-4-oxa-6-azaspiro[2.4]heptan-5-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (S,E)-6-(3-([1,1'-biphenyl]-4-yl)acryloyl)-7-phenyl-4-oxa-6-azaspiro[2.4]heptan-5-one (yield 33.2%). 11H NMR (500 MHz, Chloroform-d) δ 7.97 (d, J = 15.7 Hz, 1H), 7.80 (d, J = 15.7 Hz, 1H), 7.68 - 7.56 (m, 6H), 7.47 - 7.28 (m, 8H), 5.30 (s, 1H), 1.39 - 1.31 (m, 1H), 1.18 - 1.09 (m, 1H), 0.96 - 0.87 (m, 1H), 0.50 - 0.42 (m, 1H). LRMS (ESI): 396.16 [M+H] + 。

[0175] Example 125 (S,E)-3-(3-(4-Methoxyphenyl)acryloyl)-4-phenyloxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-4-(methoxyphenyl)acrylic acid, oxazolidin-2-one was replaced with (R)-4-phenyloxazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (S,E)-3-(3-(4-Methoxyphenyl)acryloyl)-4-phenyloxazolidin-2-one (yield 48.2%). 1 1H NMR (600 MHz, Chloroform-d) δ 7.86 - 7.76 (m, 2H), 7.59 - 7.56 (m, 2H), 7.43 - 7.40 (m, 2H), 7.39 - 7.34 (m, 3H), 6.94 - 6.90 (m, 2H), 5.58 (dd, J = 8.7, 3.9 Hz, 1H), 4.75 (t, J = 8.8 Hz, 1H), 4.32 (dd, J = 8.8, 3.9 Hz, 1H), 3.86 (s, 3H). HRMS (ESI): 324.1232 [M+H] + 。

[0176] Example 126 (S,E)-3-(3-(3-Methoxyphenyl)acryloyl)-4-phenyloxazolidin-2-one (E)-3-(o-Tolyl)acrylic acid was replaced with (E)-3-(methoxyphenyl)acrylic acid, oxazolidin-2-one was replaced with (R)-4-phenyloxazolidin-2-one, and the remaining necessary raw materials, reagents and preparation methods were the same as in Example 1 to obtain (S,E)-3-(3-(3-methoxyphenyl)acryloyl)-4-phenyloxazolidin-2-one (yield 46.2%). 1 H NMR(600MHz,Chloroform-d)δ 7.95(d,J=15.7Hz,1H),7.77(d,J=15.7Hz,1H),7.46-7.29(m,6H),7.21(d,J=7.6Hz,1H),7.12(s,1H),6.96(d,J=8.2Hz,1H),5.56(d,J=8.5Hz,1H),4.73(t,J=8.8Hz,1H),4.31(d,J=8.8Hz,1H),3.84(s,3H).HRMS(ESI):324.1233[M+H] + 。

[0177] Examples of Pharmacological Activity Tests Example 1. Measurement of the Activity of the Compounds of the Present Invention against Blood Flow Improvement Using a laser speckle test blood flow model, the activity of compounds that improve cerebral blood flow in mice is tested. The principle is to measure the change in light intensity of flowing blood by laser speckle technology and reflect the real-time cerebral blood flow. By comparing the degree of change in blood flow before and after administration to mice, the blood flow improvement effect of the compound can be detected.

[0178] The experimental process is as shown in Figure 1. After anesthetizing the experimental mice with gas for 30 seconds, they are fixed on a stand. After 2 minutes, when the baseline of the light intensity data is stable, the light intensity data of the cerebral blood flow when the mice are not administered is recorded for 10 minutes. Then the test compound is injected intraperitoneally, and the light intensity data of the cerebral blood flow of the mice within 60 minutes after administration is recorded. By comparing the change in light intensity before and after administration, the degree of change in the cerebral blood flow of the mice can be understood.

[0179] Using the above laser speckle model, a preliminary test was conducted on the activity of the compounds in the examples to improve cerebral blood flow in mice. In this test, ferulic acid (FA) was used as a positive control. The blood flow improvement effect of the compounds is shown in Figure 2. In this model, multiple compounds showed a significant improvement effect on cerebral blood flow. At a dose of 5 mg / kg, Compound 9 could increase the cerebral blood flow of mice by about 10%, and Compound 16 could increase it by about 20%. At a dose of 20 mg / kg, Compounds 30 and 59 could increase the cerebral blood flow of mice by about 10%, Compounds 5, 6, 26, 28, 29, 35, 43, and 58 could increase the cerebral blood flow of mice by about 20%, Compounds 16, 57, and 86 could increase the cerebral blood flow of mice by about 30%, Compounds 27, 84, and 104 could increase it by about 40%, and Compound 83 could increase the cerebral blood flow of mice by 50% - 60%. In summary, this patented compound has good development prospects.

[0180] Example 2. Measurement of in vivo pharmacokinetic parameters of the compounds of the present invention Male ICR (CD-1) mice were divided into two groups of three each. Each group was force-fed a test substance at a dose of 20 mg / kg or injected with a test substance at a dose of 5 mg / kg intravenously. Blood samples were collected before administration, 0.25 hours, 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, and 24 hours after administration, respectively. Plasma was immediately obtained by centrifugation, and the drug concentration in plasma was measured by liquid chromatography-tandem mass spectrometry.

[0181] The pharmacokinetic parameters in mice are as shown in the following table. In mice, the oral bioavailabilities of Compounds 27 and 83 are 14.7% and 17.4%, respectively, and they have good pharmacokinetic properties.

[0182] TIFF2025521917000019.tif138170

[0183] Furthermore, by measuring the drug of the compound in the brain tissue, it was found that the compound has good blood-brain barrier permeability. As shown in Table 3, Compound 27 showed good brain tissue drug distribution after oral administration to mice, and the B / P was about 0.7.

[0184] TIFF2025521917000020.tif144170

[0185] All documents mentioned in the present invention are cited as references in this application as if each document was individually cited as a reference. Furthermore, after reading the above teachings of the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms are also included in the scope defined by the appended claims of this application.

Claims

1. An α,β-unsaturated amide compound having a structure represented by the following formula I, or a racemic compound, R-isomer, S-isomer, pharmaceutically acceptable salt thereof, or a mixture thereof, wherein: Formula I: Wherein: R １ , R ２ , R ３ and R ４ are each independently selected from the group consisting of hydrogen, deuterium, tritium, halogen, cyano group, amino group, hydroxy group, nitro group, substituted or unsubstituted C1-C6 alkyl group, substituted or unsubstituted C1-C6 alkoxy group, or (CHR ６ ), ｎ wherein said R is selected from the group consisting of a substituted or unsubstituted C6-C10 aryl group, a substituted or unsubstituted 5-7 membered heteroaryl group, a substituted or unsubstituted 5-7 membered heterocyclic group, a substituted or unsubstituted C3-C12 cycloalkyl group or a hetero-condensed ring, or R ３ and R ４ together with the carbon atom to which they are attached form a group selected from the group consisting of a carbonyl group, a substituted or unsubstituted 3-8 membered cycloalkyl group, or a substituted or unsubstituted 4-8 membered heterocyclic group. The ring is selected from the group consisting of a C6-C10 aryl group, a 5- to 12-membered heteroaryl group, a 5- to 12-membered heterocyclic group, a C3-C12 cycloalkyl group, or a hetero-condensed ring; R ５ is selected from the group consisting of hydrogen, deuterium, tritium, halogen, cyano group, amino group, hydroxy group, nitro group, substituted or unsubstituted C1-C6 alkyl group, substituted or unsubstituted C1-C6 alkoxy group, substituted or unsubstituted C6-C10 aryl group, substituted or unsubstituted C6-C10 aryloxy group, substituted or unsubstituted 5-7 membered heteroaryl group, substituted or unsubstituted 5-7 membered heteroaryloxy group, substituted or unsubstituted 5-7 membered heterocyclic ring, and substituted or unsubstituted C3-C12 cycloalkyl group 1, 2, 3, 4, or 5 substituents located on the ring; or two adjacent Rs ５ is The atoms on the ring are bonded end to end to form a substituted or unsubstituted 4- to 8-membered ring (i.e., form a fused ring structure with ring A); Or Two Rs on the same atom on the ring ５ are joined end to end to form The ring forms a substituted or unsubstituted 3- to 8-membered ring with the ring (i.e., forms a spiro ring structure with ring A); X is N(CH ２ ) ｎ R ６ , O, or S, and n is 0, 1, 2, or 3; R ６ is independently selected from the group consisting of hydrogen, halogen, cyano group, amino group, hydroxy group, nitro group, substituted or unsubstituted C1-C6 alkyl group, substituted or unsubstituted C1-C6 alkoxy group, substituted or unsubstituted C6-C10 aryl group, oxygen, sulfur, and a substituted or unsubstituted 5- to 12-membered heterocyclic ring containing 1 to 3 heteroatoms selected from nitrogen, substituted or unsubstituted C2-C10 acyl group, substituted or unsubstituted C2-C10 ester group, substituted or unsubstituted C1-C6 amide group, -SO ２ R ５ , -COR ５ and is independently selected from the group consisting of Herein, unless otherwise specified, each of the heteroaromatic ring, heterocyclic ring, or heterocyclic group independently contains 1 to 4 heteroatoms selected from oxygen, sulfur, and nitrogen, the aromatic ring or heteroaromatic ring includes a monocyclic, fused ring, or condensed ring, and the carbocyclic ring or heterocyclic ring includes a monocyclic, fused ring, spiro ring, or bridged ring; Said substitution means being substituted by one or more (preferably 1 to 3) substituents selected from the group consisting of halogen, cyano group, nitro group, amino group, hydroxy group, hydroxymethyl group, carboxy group, mercapto group, C1-C6 alkyl group, halogen-substituted C1-C6 alkyl group, C1-C6 alkoxy group, halogen-substituted C1-C6 alkoxy group, C1-C6 alkoxycarbonyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C3-C8 cycloalkyl group, C1-C6 alkylsulfonyl group, substituted or unsubstituted C6-C10 aryl group, substituted or unsubstituted 5- to 7-membered heteroaryl group, and 3- to 12-membered heterocyclic group; The halogen is F, Cl, Br, or I, and is characterized by the α,β-unsaturated amide compound having a structure represented by the above formula I, or a racemic compound, R-isomer, S-isomer, pharmaceutically acceptable salt thereof, or a mixture thereof.

2. The above The ring is characterized by being selected from the group consisting of a C6-C10 aryl group and a C5-C12 heteroaryl group The α,β-unsaturated amide compound according to Claim 1.

3. Said R １ , R ２ , R ３ and R ４ are each independently hydrogen, deuterium, a substituted or unsubstituted C1-C6 alkyl group, or (CHR ６ ), ｎ selected from the group consisting of R, where said R is selected from the group consisting of a substituted or unsubstituted C6-C10 aryl group, a substituted or unsubstituted 5-7 membered heteroaryl group, n is 0, 1 or 2, and R ６ is hydrogen, halogen, or a substituted or unsubstituted C1-C6 alkyl group, characterized in that The α,β-unsaturated amide compound according to Claim 1.

4. Said R １ , R ２ , R ３ and R ４ are each independently selected from the group consisting of hydrogen, deuterium, a substituted or unsubstituted C1-C6 alkyl group, (CHR ６ ), ｎ R, wherein said R is selected from the group consisting of a substituted or unsubstituted C6-C10 aryl group, a substituted or unsubstituted 5-7 membered heteroaryl group The α,β-unsaturated amide compound according to Claim 1 or 2.

5. Said R １ is H or D, and R ２ is selected from the group consisting of hydrogen, deuterium, a substituted or unsubstituted C1-C6 alkyl group, (CHR ６ ), ｎ R, wherein said R is selected from the group consisting of a substituted or unsubstituted C6-C10 aryl group, a substituted or unsubstituted 5- to 7-membered heteroaryl group, and said substitution means being substituted by one or more substituents selected from the group consisting of a halogen, a cyano group, a nitro group, an amino group, a hydroxy group, a hydroxymethyl group, a carboxy group, a mercapto group, a C1-C6 alkyl group, a halogen-substituted C1-C6 alkyl group, a C1-C6 alkoxy group, a halogen-substituted C1-C6 alkoxy group, and a C1-C6 alkoxycarbonyl group The α,β-unsaturated amide compound according to claim 1 or 2.

6. Said R ３ and R ４ are each independently characterized by being deuterium The α,β-unsaturated amide compound according to claim 1 or 2.

7. The compound of formula I is characterized by being selected from the following table The α,β-unsaturated amide compound according to claim 1.

8. A method for preparing the compound of formula I according to claim 1, wherein The method comprises reacting a compound of formula II with a compound of formula III in an inert solvent to obtain a compound of formula I, and the method for preparing the compound of formula I according to claim 1.

9. A pharmaceutical composition, wherein the pharmaceutical composition comprises (1) the compound according to claim 1 or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate or solvate thereof, and (2) a pharmaceutically acceptable carrier, and the pharmaceutical composition is characterized thereby.

10. Use of the compound according to claim 1 or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or the pharmaceutical composition according to claim 9, wherein it is used for the preparation of a pharmaceutical composition for preventing and / or treating neurodegenerative diseases or stroke, and preferably, the neurodegenerative disease is selected from the group consisting of Alzheimer's disease and vascular dementia, and the use of the compound according to claim 1 or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or the pharmaceutical composition according to claim 9 is characterized thereby.

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