CN108558756B - 2-aryl-2, 3-dihydro-4 (1H) -quinolinone semicarbazone compound and application thereof - Google Patents

2-aryl-2, 3-dihydro-4 (1H) -quinolinone semicarbazone compound and application thereof Download PDF

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CN108558756B
CN108558756B CN201810512297.8A CN201810512297A CN108558756B CN 108558756 B CN108558756 B CN 108558756B CN 201810512297 A CN201810512297 A CN 201810512297A CN 108558756 B CN108558756 B CN 108558756B
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quinolinone
dihydro
semicarbazone
semicarbazide
chloro
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CN108558756A (en
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郭春
苏昕
候壮
宋少杰
杨晓光
徐航
安然
刘小倩
韩长宏
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Shenyang Pharmaceutical University
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    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
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    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
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Abstract

The invention relates to the technical field of medicines, and designs and synthesizes a series of 2-aryl-2, 3-dihydro-4 (1H) -quinolinone semicarbazone derivatives (I) with novel structures and pharmaceutically acceptable salts, solvates, optical isomers or polymorphs thereof. The derivative (I) and pharmaceutically acceptable salts, solvates, optical isomers or polymorphs thereof can be used as active ingredients to be mixed with pharmaceutically acceptable carriers to prepare a pharmaceutical composition. The antifungal activity of the derivative (I) and the pharmaceutically acceptable salt, solvate, optical isomer or polymorph thereof is tested by a double concentration dilution method, and the result shows that the derivative has stronger killing effect on clinically common pathogenic fungi, and is expected to overcome the defects of large toxic and side effects, easy generation of drug resistance and the like of the clinically widely used azole antifungal drugs at present.

Description

2-aryl-2, 3-dihydro-4 (1H) -quinolinone semicarbazone compound and application thereof
Technical Field
The invention relates to the technical field of medicines, in particular to 2-aryl-2, 3-dihydro-4 (1H) -quinolinone semicarbazone derivatives with antifungal activity, pharmaceutically acceptable salts, solvates, optical isomers or polymorphs thereof and application thereof.
Background
Mycoses are a condition that is frequently and intractable. In recent years, the morbidity and mortality of fungal infection are on the trend of increasing year by year, but clinically used antifungal drugs are relatively deficient, and azole antifungal drugs are still the first choice. Therefore, the development of antifungal drugs with high efficiency, low toxicity, new action mechanism and novel structure is still a very significant work.
Natural flavone (flavanone) compounds are metabolites of plant polyphenol compounds, and have a basic structure of 2-phenyl chromone, which comprises two benzene rings and is connected through a heterocyclic pyran ring. The flavonoid compounds have various varieties and complex structures, and have various medicinal functions, such as antioxidation, anti-aging, anti-inflammatory, anti-tumor, anti-allergy, and good biological activity in improving blood vessel circulation and preventing and treating blood vessel diseases. In recent years, there have been a large number of reports in the literature of such compounds having antifungal activity. In the earlier research of the subject group, a series of thiochroman 4-ketone (thiochromanone) semicarbazone compounds with better in vitro antifungal activity are designed and synthesized by utilizing the combination principle of drug design based on the structural characteristics of flavonoid compounds.
Disclosure of Invention
The invention aims to provide a novel 2-aryl-2, 3-dihydro-4 (1H) -quinolinone semicarbazone derivative, a pharmaceutically acceptable salt, a solvate, an optical isomer or a polymorphic substance thereof, a preparation method thereof and application thereof as an antifungal agent.
The invention is realized by the following technical scheme:
Figure BDA0001672662320000011
the invention provides 2-aryl-2, 3-dihydro-4 (1H) -quinolinone semicarbazone derivatives with a structure shown as a general formula (I) and pharmaceutically acceptable salts, solvates, optical isomers or polymorphs thereof:
Figure BDA0001672662320000021
wherein:
R1is H atom, halogen, C1-C6 alkyl, C1-C6 alkoxy, nitro, cyano, halogenated C1-C6 alkyl;
R2,R3is H atom, halogen, cyano, nitro, halogenated C1-C6 alkyl, C1-C6 alkyl, C1-C6 alkoxy, C6-C10 aryl, C4-C6 aromatic heterocyclic group; r2，R3May be the same or different;
ar is substituted or unsubstituted C6-C10 aryl, C4-C6 aromatic heterocyclic radical, the substituent is halogen, cyano, nitryl, halogenated C1-C6 alkyl, C1-C6 alkyl, C1-C6 alkoxy;
the invention preferably relates to 2-aryl-2, 3-dihydro-4 (1H) -quinolinone semicarbazone derivatives with the structure of general formula (I) and pharmaceutically acceptable salts, solvates, optical isomers or polymorphs thereof:
wherein:
R1is H atom, halogen, C1-C4 alkyl, C1-C4 alkoxy, nitro, cyano, halogenated C1-C4 alkyl;
R2,R3is a hydrogen atom, a halogen, a cyano group,nitro, halogenated C1-C4 alkyl, C1-C4 alkyl, C1-C4 alkoxy, C6-C10 aryl, C4-C6 aromatic heterocyclic group; r2，R3May be the same or different;
ar is substituted or unsubstituted C6-C10 aryl, C4-C6 aromatic heterocyclic radical, the substituent is halogen, cyano, nitryl, halogenated C1-C4 alkyl, C1-C4 alkyl, C1-C4 alkoxy;
the invention preferably relates to 2-aryl-2, 3-dihydro-4 (1H) -quinolinone semicarbazone derivatives with the structure of general formula (I) and pharmaceutically acceptable salts, solvates, optical isomers or polymorphs thereof:
wherein:
R1is H atom, halogen, C1-C4 alkyl, C1-C4 alkoxy, nitro, cyano, halogenated C1-C4 alkyl;
R2,R3is H atom, halogen, cyano, nitro, halogenated C1-C4 alkyl, C1-C4 alkyl, C1-C4 alkoxy, C6-C10 aryl, C4-C6 aromatic heterocyclic group; r2，R3May be the same or different;
ar is substituted or unsubstituted phenyl, furyl or thienyl, and the substituent is halogen, cyano, nitro, halogenated C1-C4 alkyl, C1-C4 alkyl or C1-C4 alkoxy;
the invention preferably relates to 2-aryl-2, 3-dihydro-4 (1H) -quinolinone semicarbazone derivatives with the structure of general formula (I) and pharmaceutically acceptable salts, solvates, optical isomers or polymorphs thereof:
wherein:
R1h atom, halogen, nitro, cyano, trifluoromethyl, methyl, methoxy;
R2,R3h atom, halogen, cyano, nitro, trifluoromethyl, C1-C4 alkyl, C1-C4 alkoxy; r2，R3May be the same or different;
ar ═ furyl, thienyl, phenyl containing 1 to 4 substituents such as halogen, cyano, nitro, trifluoromethyl, C1 to C4 alkyl, and C1 to C4 alkoxy;
the invention preferably relates to 2-aryl-2, 3-dihydro-4 (1H) -quinolinone semicarbazone derivatives with the structure of general formula (I) and pharmaceutically acceptable salts, solvates, optical isomers or polymorphs thereof:
R1is H atom, halogen, nitryl, cyano, trifluoromethyl, methyl, methoxyl;
R2,R3is H atom, halogen, nitro, trifluoromethyl, methyl, methoxy, R2，R3May be the same or different;
ar is thienyl, 1-4 halogens, cyano, nitro, trifluoromethyl, methyl and methoxy substituted phenyl;
preferred Ar is 4-halophenyl, 4-methylphenyl, 4-trifluoromethylphenyl, 4-methoxyphenyl, 2, 4-dichlorophenyl, 3, 5-dichlorophenyl, 2, 4-dimethylphenyl, 3, 4-dimethylphenyl;
according to the invention, particularly preferred 2-aryl-2, 3-dihydro-4 (1H) -quinolinone semicarbazone derivatives of formula I above are selected from:
Figure BDA0001672662320000031
Figure BDA0001672662320000032
Figure BDA0001672662320000041
Figure BDA0001672662320000051
Figure BDA0001672662320000061
Figure BDA0001672662320000071
Figure BDA0001672662320000081
the 2-aryl-2, 3-dihydro-4 (1H) -quinolinone semicarbazone derivative of the formula I can form pharmaceutically acceptable salts with acid or alkali, and particularly can form pharmaceutically acceptable carboxylate with carboxylic acid.
Experimental results show that the 2-aryl-2, 3-dihydro-4 (1H) -quinolinone semicarbazone derivative of the formula I and pharmaceutically acceptable salts, solvates, optical isomers or polymorphs thereof have potential antifungal effects, and therefore, the 2-aryl-2, 3-dihydro-4 (1H) -quinolinone semicarbazone derivative can be clinically used for preparing antifungal agents.
The compounds according to the invention are useful as active ingredients in the treatment or prevention of fungal infections and the invention also provides methods for the treatment or prevention of the above-mentioned diseases which comprise administering to a patient suffering from or susceptible to such a disease a therapeutically effective amount of a compound of the invention.
The present invention includes pharmaceutical compositions containing as an active ingredient a 2-aryl-2, 3-dihydro-4 (1H) -quinolinone semicarbazone derivative of formula i above and pharmaceutically acceptable salts, solvates, optical isomers or polymorphs thereof. The derivatives of the invention may be administered as such or as a pharmaceutical composition comprising the derivatives of the invention in admixture with pharmaceutically acceptable diluents, adjuvants and/or carriers, particularly preferably in the absence of substances which may cause adverse effects such as allergic reactions.
When the pharmaceutical composition of the present invention is clinically used, it can be formulated into several dosage forms containing some excipients commonly used in the pharmaceutical field; for example, oral formulations (e.g., tablets, capsules, lozenges, solutions or suspensions); injectable formulations (e.g., injectable solutions or suspensions, or injectable dry powders, which are immediately ready for use by addition of water for injection prior to injection); topical formulations (e.g. ointments or solutions).
Carriers for the pharmaceutical compositions of the present invention are of the usual type available in the pharmaceutical art and include: binders, lubricants, disintegrants, solubilizing agents, diluents, stabilizers, suspending agents, non-coloring agents, flavoring agents, etc. for oral preparations; preservatives, solubilizers, stabilizers and the like for injectable preparations; bases for topical formulations, diluents, lubricants, preservatives, and the like. Pharmaceutical formulations may be administered orally or parenterally (e.g., intravenously, subcutaneously, intraperitoneally, or topically), and if certain drugs are unstable under gastric conditions, they may be formulated as enteric coated tablets.
Furthermore, the clinical dosage of the 2-aryl-2, 3-dihydro-4 (1H) -quinolinone semicarbazone derivatives of formula I above and the pharmaceutically acceptable salts, solvates, optical isomers or polymorphs thereof for a patient may be based on: the therapeutic efficacy and bioavailability of the active ingredients in the body, their metabolism and excretion rates and the age, sex, disease stage of the patient are suitably adjusted, although the daily dose for an adult should generally be 10-500mg, preferably 50-300 mg. Therefore, when the pharmaceutical composition of the present invention is formulated into a unit dosage form, each unit preparation should contain 10 to 500mg of the above 2-aryl-2, 3-dihydro-4 (1H) -quinolinone semicarbazone derivative of the formula I and a pharmaceutically acceptable salt, solvate, optical isomer or polymorph thereof, preferably 50 to 300mg, in consideration of the above effective dose. These formulations may be administered in several doses (preferably one to six times) at regular intervals, according to the guidance of a doctor or pharmacist.
The following synthetic schemes describe the preparation of the compounds of formula I of this invention, all starting materials are prepared by the methods described in these synthetic schemes, by methods well known to those of ordinary skill in the art of organic chemistry or are commercially available. All of the final compounds of the present invention are prepared by the methods described in these synthetic routes or by methods analogous thereto, which are well known to those of ordinary skill in the art of organic chemistry. All variables used in these synthetic routes are as defined below or in the claims.
Compounds of the formula I according to the invention, in the synthesis of the object compounds described below, the substituent R1、R2、R3And Ar is as previously defined.
Figure BDA0001672662320000091
Substituted o-nitroacetophenone is used as a starting material, nitro reduction is carried out to obtain o-aminoacetophenone (A1-A4), acetyl protected o-aminoacetophenone (B1-B4) is obtained after acetylation, aldol condensation reaction is carried out on the intermediate B and various substituted benzaldehydes (thiophenecarboxaldehyde and furaldehyde) under alkaline conditions to obtain intermediate C1-C34, the intermediate C is subjected to hydrochloric acid deacetylation protection group and cyclization to obtain intermediate D1-CD 34, and the intermediate D and 4-substituted semicarbazide are condensed in hydrochloric acid ethanol to obtain the target compound.
The specific implementation mode is as follows:
the compounds of the present invention and their preparation will be better understood in connection with the following examples, which are intended to be illustrative
And are not intended to limit the scope of the present invention.
Example 1:
preparation of 2-aminoacetophenone (A1)
50ml of water, 50ml of ethanol, 8.00g (0.14mol) of reduced iron powder were charged in a 250ml reaction flask using NH4Adjusting the pH value of the solution to 4 by Cl, dripping 2 drops of glacial acetic acid, heating to 55, reacting for 1H, adding 5.00g (0.03mol) of o-nitroacetophenone, heating to 80 ℃, refluxing for 3H, filtering to remove iron mud while the solution is hot, extracting the filtrate by dichloromethane (30ml multiplied by 3), combining organic phases, washing until the organic phase is colorless and transparent, drying the organic phase by anhydrous sodium sulfate, filtering out a drying agent, concentrating under reduced pressure to obtain A1 which is a light yellow transparent liquid with the yield of 3.44g, the yield of 84.11 percent, mp:18 ℃ -20 ℃, LC-MS (M/z):134.2[ M-H ]: 134.2]-。
Example 2:
preparation of 2-acetamidoacetophenone (B1)
Dissolving 4.05g (0.03mol) of 2-aminoacetophenone (A1) in100 ml of dichloromethane, adding 5.3ml (0.04mol) of triethylamine, dropwise adding 3.5ml (0.05mol) of acetyl chloride under stirring at 0-10 ℃, heating to room temperature, and stirringAdding 100ml ethyl acetate to dilute the reaction solution for 3H, separating out an organic phase, washing the organic phase with water until an organic layer is colorless, washing the organic layer with 30ml saturated salt for 1 time, drying the organic phase with anhydrous magnesium sulfate, filtering out a drying agent, and concentrating under reduced pressure to obtain B1 as a white solid with the yield of 4.50g, the yield of 84.7 percent, mp: 80-82 ℃, LC-MS (M/z):176.8[ M-H]-.
Preparation of 2-acetamido-4-chloroacetophenone (B2)
2-acetamido-5-chloroacetophenone (B2) was prepared in 69.2% yield as a white-like solid from 2-amino-4-chloroacetophenone by the method described in B1 (LC-MS (M/z):212.04[ M + H ])]+。
Preparation of 2-acetamido-4-methylacetophenone (B3)
2-acetamido-5-methylacetophenone (B3) was prepared as a white solid in 70.6% yield according to the preparation method of B1 using 2-amino-5-methylacetophenone as a starting material (LC-MS (M/z):192.03[ M + H ])]+。
Preparation of 2-acetamido-4-methoxyacetophenone (B4)
2-acetamido-5-methoxyacetophenone (B4) was prepared as a white solid in 70.6% yield from 2-amino-5-methoxyacetophenone by reference to the preparation method of B1 (LC-MS (m/z): 206.09).
Example 3:
(E) preparation of (E) -N- [2- (3-phenylpropenoyl) phenyl ] acetamide (C1)
Dissolving 5.31g (0.03mol) of 2-acetamidoacetophenone (B1) in100 ml of methanol, adding 3.18(0.03mol) of benzaldehyde, dropwise adding 30ml of 5% sodium hydroxide solution under ice bath cooling, reacting at 0 ℃ for 8h, pouring the reaction solution into 250ml of ice water, separating out a large amount of light yellow solid, performing suction filtration, washing a filter cake with water, and drying to obtain the C1 light yellow solid, wherein the yield is 5.09g, the yield is 64.4%, mp is 159-161 ℃, and LC-MS (m/z) is 265.31.
Intermediates C2-C34 were prepared by reacting intermediates B1-B4 with various aromatic aldehydes, respectively, as the starting materials, in accordance with the preparation method of C1, and the results are shown in Table 1.
Figure BDA0001672662320000111
Figure BDA0001672662320000112
Example 4:
synthesis of 2-phenyl-2, 3-dihydro-4 (1H) -quinolinone (D1)
7.9g (0.03mol) (E) -N- [2- (3-phenylpropenoyl) phenyl ] acetamide (C1) was dissolved in 80ml ethanol, 40ml 5% hydrochloric acid was added, the mixture was refluxed for 8 hours, the reaction mixture was poured into 200ml ice water, the pH was adjusted to 9 with ammonia water, a large amount of white solid was precipitated, and the mixture was filtered under suction, and recrystallized from ethanol to give 2-phenyl-2, 3-dihydro-4 (1H) -quinolinone (D1) as a white solid, 4.75g was obtained, yield 71.1%, mp:124 ℃ to 126 ℃, LC-MS (m/z): 223.3.
Intermediates D2-D34 were prepared from intermediates C2-C34, respectively, according to the preparation method of D1, and the results are shown in Table 2.
Figure BDA0001672662320000121
Figure BDA0001672662320000122
Figure BDA0001672662320000131
Example 5:
preparation of 2-phenyl-2, 3-dihydro-4 (1H) -quinolinone (4-phenyl) semicarbazide (I01)
0.11g (0.50mmol) of 2-phenyl-2, 3-dihydro-4 (1H) -quinolinone (D1) and 0.09g (0.6mmol) of 4-phenylsemicarbazone are added into 30ml of absolute ethyl alcohol, stirred to be dissolved, then 0.05ml of hydrochloric acid is added, the mixture is heated to reflux reaction for 5 hours, white solid is precipitated, the mixture is filtered by suction when the mixture is hot, and I01 is obtained after drying, the amount of the I01 is 0.11g, the yield is 57.1 percent, and the mp:156 ℃ 158 ℃. LC-MS (M/z):357.2[ M + H]+,1H-NMR(600MHz,DMSO-d6)δ9.67(s,1H),8.83(s,1H),8.11(m,1H),7.60(m,4H),7.42(m,2H),7.29(m,2H),7.12(m,2H),7.06(m,3H),6.49(s,1H),4.48-4.38(m,1H),3.13(dd,J＝16.3,3.6Hz,1H),2.55(dd,J＝16.2,3.4Hz,1H)。
Example 6:
preparation of 2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (4-chlorophenyl) ] semicarbazone (I02)
2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (4-chlorophenyl) ketal ] was prepared from intermediate D1 and 4- (4-chloro) phenylsemicarbazone, according to the preparation method of Compound I01]Semicarbazide (I02): white solid, yield 53.1%, LC-MS (M/z):391.1[ M + H]+,1H-NMR(600MHz,DMSO-d6)δ9.67(s,1H),8.89(s,1H),8.13(d,J＝7.7Hz,1H),7.76-7.66(m,2H),7.59(d,J＝8.4Hz,2H),7.45(m,3H),7.11-7.04(m,3H),6.79(d,J＝8.0Hz,1H),6.72-6.62(m,1H),6.48(s,1H),4.44(dd,J＝10.8,3.9Hz,1H),3.10(dd,J＝16.3,3.6Hz,1H),2.57(dd,J＝16.3,10.9Hz,1H)。
Example 7:
preparation of 2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (4-bromophenyl) ] semicarbazide (I03)
2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (4-bromophenyl) ketal ] was prepared starting from intermediate D1 and 4- (4-bromo) phenylsemicarbazone, according to the preparation method of Compound I01]Semicarbazide (I03): off-white solid, yield 50.4%, LC-MS (M/z):435.3[ M + H]+,1H-NMR(600MHz,DMSO-d6)δ9.67(s,1H),8.90(s,1H),8.11(d,J＝7.6Hz,1H),7.88-7.76(m,2H),7.59-7.55(m,2H),7.43(m,4H),7.20-7.15(m,2H),6.79(d,J＝8.0Hz,1H),6.70-6.59(m,1H),6.43(s,1H),4.42(dd,J＝10.4,3.9Hz,1H),3.11(dd,J＝16.3,3.5Hz,1H),2.57(dd,J＝16.3,10.7Hz,1H)。
Example 8:
preparation of 2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (4-methylphenyl) ] semicarbazide (I04)
2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (4-methylphenyl) quinolinone-ketal ] was prepared starting from intermediate D1 and 4- (4-methyl) phenylsemicarbazone according to the preparation method of Compound I01]Semicarbazide (I04): off-white solid, yield 64.9%, LC-MS (M/z):371.2[ M + H%]+,1H-NMR(600MHz,DMSO-d6)δ9.66(s,1H),8.74(s,1H),8.12(d,J＝7.5,1H),7.61(d,J＝8.4Hz,2H),7.54(d,J＝8.3Hz,2H),7.45(d,J＝8.4Hz,2H),7.19-7.14(m,3H),6.78(d,J＝7.9Hz,1H),6.73-6.65(m,2H),6.48(s,1H),4.40(dd,J＝10.8,11.1Hz,1H),3.13(dd,J＝16.2,3.6Hz,1H),2.56(dd,J＝16.2,3.7Hz,1H),2.25(s,3H,)。
Example 9:
preparation of 2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (4-nitrophenyl) ] semicarbazone (I05)
2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (4-nitrophenyl) was prepared starting from intermediate D1 and 4- (4-nitro) phenylsemicarbazone, according to the procedure for the preparation of Compound I01]Semicarbazide (I05): white solid, yield 50.3%, LC-MS (M/z):402.4[ M + H%]+,1H-NMR(600MHz,DMSO-d6)δ9.67(s,1H),8.89(s,1H),8.13(d,J＝7.7Hz,1H),7.73-7.62(m,2H),7.59(d,J＝8.4Hz,2H),7.45(d,J＝8.4Hz,2H),7.16-7.07(m,3H),6.79(d,J＝8.0Hz,1H),6.72-6.62(m,2H),6.49(s,1H),4.42(dd,J＝10.8,3.9Hz,1H),3.10(dd,J＝16.3,3.6Hz,1H),2.57(dd,J＝16.3,10.9Hz,1H)。
Example 10:
preparation of 2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (4-trifluoromethylphenyl) ] semicarbazide (I06)
2-phenyl-2, 3-dihydro-4 (1H) -quinolinone ketal [4- (4-trifluoromethylphenyl) can be prepared from intermediate D1 and 4- (4-trifluoromethyl) phenylsemicarbazone, according to the preparation method of the compound I01]Semicarbazide (I06): white solid, yield 47.1%, LC-MS (M/z):425.2[ M + H]+,1H-NMR(600MHz,DMSO-d6)δ9.67(s,1H),8.89(s,1H),8.13(d,J＝7.7Hz,1H),7.81-7.66(m,2H),7.61(m,2H),7.53-7.41(m,2H),7.21-7.14(m,3H),6.80(d,J＝8.2Hz,1H),6.69-6.63(m,2H),6.53(s,1H),4.48(dd,J＝10.4,3.1Hz,1H),3.22(dd,J＝16.4,4.2Hz,1H),2.53(dd,J＝16.6,8.8Hz,1H)。
Example 11:
preparation of 2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (4-methoxyphenyl) ] semicarbazone (I07)
2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (4-methoxyphenyl) was prepared from intermediate D1 and 4- (4-methoxy) phenylsemicarbazone, according to the preparation method of Compound I01]Semicarbazide (I07): white solid, yield 55.3%, LC-MS (M/z):387.5[ M + H%]+,1H-NMR(600MHz,DMSO-d6)δ9.69(s,1H),8.77(s,1H),8.11(d,J＝7.6,1H),7.66-7.60(m,2H),7.58-7.51(m,2H),7.45(d,J＝8.4Hz,2H),7.22-7.14(m,3H),6.78(d,J＝8.2Hz,1H),6.69-6.61(m,2H),6.44(s,1H),4.43(dd,J＝10.8,11.1Hz,1H),3.78(s,3H),3.13(dd,J＝16.2,3.6Hz,1H),2.56(dd,J＝16.2,3.7Hz,1H)。
Example 12:
preparation of 2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dichlorophenyl) ] semicarbazone (I08)
2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dichlorophenyl) was prepared from intermediate D1 and 4- (2, 4-dichlorophenyl) semicarbazide by the method of preparation of Compound I01]Semicarbazide (I08): white solid, yield 58.3%, LC-MS (M/z):485.3[ M + H]+,1H-NMR(600MHz,DMSO-d6)δ9.92(s,1H),9.17(s,1H),8.14(d,J＝7.8Hz,1H),7.86-7.79(m,2H),7.62-7.57(m,2H),7.45(d,J＝8.4Hz,2H),7.19(m,2H),7.12(dd,J＝8.4,1.5Hz,1H),6.81(dd,J＝8.4,0.8Hz,1H),6.73-6.67(m,1H),6.56(s,1H),4.47(dd,J＝10.8,3.6Hz,1H),3.12(dd,J＝3.4Hz,1H),2.57(dd,J＝16.2,11.2Hz,1H)。
Example 13:
preparation of 2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dimethylphenyl) ] semicarbazone (I09)
2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dimethylphenyl) was prepared from intermediate D1 and 4- (2, 4-dimethylphenyl) semicarbazide, according to the preparation method of Compound I01]Semicarbazide (I09): white solid, yield 61.7%, LC-MS (M/z):425.1[ M + H]+,1H-NMR(600MHz,DMSO-d6)δ9.89(s,1H),8.58(s,1H),7.99-7.96(m,1H),7.67(s,1H),7.62-7.58(m,2H),7.46(m,2H),7.22-7.12(m,3H),6.84(m,2H),6.69-6.65(m,1H),6.53(s,1H),4.47(dd,J＝11.2,4.2Hz,1H),3.17(dd,J＝16.8,3.6Hz,1H),2.55(dd,J＝16.4,11.1Hz,1H),2.27(s,6H)。
Example 14:
preparation of 2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (3, 5-dichlorophenyl) ] semicarbazone (I10)
2-phenyl is prepared by taking intermediate D1 and 4- (3, 5-dichlorophenyl) semicarbazide as raw materials according to the preparation method of compound I01-2, 3-dihydro-4 (1H) -quinolinone [4- (3, 5-dichlorophenyl)]Semicarbazide (I10): white solid, yield 54.3%, LC-MS (M/z):485.1[ M + H]+,1H-NMR(600MHz,DMSO-d6)δ9.87(s,1H),9.21(s,1H),8.18(d,J＝7.5Hz,1H),7.86(d,J＝1.7Hz,2H),7.68-7.58(m,2H),7.47(m,2H),7.21(t,J＝1.9Hz,1H),7.18(m,2H),6.77(dd,J＝8.2,0.8Hz,1H),6.74-6.61(m,1H),6.55(s,1H),4.47(dd,J＝10.9,3.8Hz,1H),3.13(dd,J＝3.6Hz,1H),2.56(dd,J＝16.4,11.0Hz,1H)。
Example 15:
preparation of 2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (3, 4-dimethylphenyl) ] semicarbazone (I11)
2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (3, 4-dimethylphenyl) was prepared starting from intermediate D1 and 4- (3, 4-dimethylphenyl) semicarbazide according to the preparation method of compound I01]Semicarbazide (I11): white solid, yield 63.1%, LC-MS (M/z):425.6[ M + H]+,1H-NMR(600MHz,DMSO-d6)δ9.78(s,1H),8.52(s,1H),7.97-7.94(m,1H),7.66(s,1H),7.66-7.51(m,2H),7.51(d,J＝8.6Hz,2H),7.19-7.11(m,2H),6.81-6.74(m,2H),6.71-6.67(m,2H),6.61(s,1H),4.52(dd,J＝11.8,3.4Hz,1H),3.17(dd,J＝16.4,3.3Hz,1H),2.55(dd,J＝16.4,11.1Hz,1H),2.29(d,J＝17.8Hz,6H)。
Example 16:
preparation of 2- (4-bromophenyl) -2, 3-dihydro-4 (1H) -quinolinone (4-phenyl) semicarbazide (I12)
Starting from intermediate D3 and 4-phenylsemicarbazone, with reference to the preparation of compound I01, 2- (4-bromophenyl) -2, 3-dihydro-4 (1H) -quinolinone condensation (4-phenyl) semicarbazide (I12) was prepared: white solid, yield 61.2%, LC-MS (M/z):435.0[ M + H]+,1H-NMR(600MHz,DMSO-d6)δ9.67(s,1H),8.83(s,1H),8.11(d,J＝7.8Hz,1H),7.61(dd,J＝20.6,8.0Hz,4H),7.45(d,J＝8.1Hz,2H),7.29(t,J＝7.7Hz,2H),7.11(t,J＝7.4Hz,1H),7.00(t,J＝7.2Hz,1H),6.79(d,J＝8.0Hz,1H),6.67(t,J＝7.4Hz,1H),6.49(s,1H),4.48-4.38(m,1H),3.11(dd,J＝16.3Hz,3.6,1H),2.57(dd,J＝16.2,3.4Hz,1H)。
Example 17:
preparation of 2- (4-bromophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-chlorophenyl) ] semicarbazide (I13)
2- (4-bromophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-chlorophenyl) ketal ] was prepared from intermediate D3 and 4- (4-chlorophenyl) semicarbazide by the method described for Compound I01]Semicarbazide (I13): white solid, yield 41.2%, LC-MS (M/z):493.1[ M + Na [ ]]+,1H-NMR(600MHz,DMSO-d6)δ9.67(s,1H),8.89(s,1H),8.13(d,J＝7.7Hz,1H),7.73-7.62(m,2H),7.59(d,J＝8.4Hz,2H),7.45(d,J＝8.4Hz,2H),7.16-7.07(m,3H),6.79(d,J＝8.0Hz,1H),6.7-6.62(m,1H),6.49(s,1H),4.42(dd,J＝10.8,3.9Hz,1H),3.10(dd,J＝16.3,3.6Hz,1H),2.57(dd,J＝16.3,10.9Hz,1H)。
Example 18:
preparation of 2- (4-bromophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-bromophenyl) ] semicarbazide (I14)
Preparation of 2- (4-bromophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-bromophenyl) ketal ] from intermediate D3 and 4- (4-bromophenyl) semicarbazide by the method of preparation of Compound I01]Semicarbazide (I14): white solid, yield 57.1%, LC-MS (M/z):513.1[ M + H%]+,1H-NMR(600MHz,DMSO-d6)δ9.67(s,1H),8.89(s,1H),8.12(d,J＝7.7Hz,1H),7.86-7.82(m,2H),7.67-7.53(m,2H),7.45-7.41(m,2H),7.31-7.22(m,2H),6.91(m,2H),6.81-6.62(m,1H),6.54(s,1H),4.41(dd,J＝10.1,3.6Hz,1H),3.22(dd,J＝16.8,3.2Hz,1H),2.55(dd,J＝16.6,10.8Hz,1H)。
Example 19:
preparation of 2- (4-bromophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-methylphenyl) ] semicarbazide (I15)
2- (4-bromophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-methylphenyl)]Semicarbazide (I15): white solid, yield 63.9%, LC-MS (M/z):449.4[ M + H]+,1H-NMR(600MHz,DMSO-d6)δ9.62(s,1H),8.74(s,1H),8.10(d,J＝7.5Hz,1H),7.59(d,J＝8.4Hz,2H),7.50-7.46(m,2H),7.45(d,J＝8.4Hz,2H),7.1-7.04(m,3H),6.79(d,J＝7.9Hz,1H),6.71-6.63(m,1H),6.48(s,1H),4.42(dd,J＝10.9,11.0Hz,1H),3.10(dd,J＝16.3,3.6Hz,1H),2.56(dd,J＝16.3,3.8Hz,1H),2.25(s,3H)。
Example 20:
preparation of 2- (4-bromophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-nitrophenyl) ] semicarbazide (I16)
2- (4-bromophenyl) -2, 3-dihydro-4 (1H) -quinolinone condensation [4- (4-nitrophenyl) was obtained from intermediate D3 and 4- (4-nitrophenyl) semicarbazide, according to the preparation method of Compound I01]Semicarbazide (I16): white solid, yield 43.7%, LC-MS (M/z):480.1[ M + H]+,1H-NMR(600MHz,DMSO-d6)δ9.65(s,1H),8.89(s,1H),8.16(d,J＝7.7Hz,1H),7.78-7.68(m,2H),7.61(d,J＝8.2Hz,2H),7.45-7.36(m,2H),7.19-7.11(m,3H),6.79(d,J＝8.0Hz,1H),6.74-6.64(m,1H),6.49(s,1H),4.41(dd,J＝10.2,3.8Hz,1H),3.14(dd,J＝16.2,3.6Hz,1H),2.57(dd,J＝16.4,10.8Hz,1H)。
Example 21:
preparation of 2- (4-bromophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-trifluoromethylphenyl) ] semicarbazide (I17)
Preparation of 2- (4-bromophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-trifluoromethylphenyl) ketal ] starting from intermediate D3 and 4- (4-trifluoromethylphenyl) semicarbazide according to the preparation method of Compound I01]Semicarbazide (I17): white solid, yield 45.8%, LC-MS (M/z):503.1[ M + H%]+,1H-NMR(600MHz,DMSO-d6)δ9.67(s,1H),8.86(s,1H),8.16(d,J＝7.7Hz,1H),7.74-7.61(m,2H),7.54(d,J＝8.4Hz,2H),7.42-7.33(m,2H),7.11-7.04(m,3H),6.82(d,J＝8.2Hz,1H),6.74-6.63(m,1H),6.47(s,1H),4.43(dd,J＝10.6,3.6Hz,1H),3.11(dd,J＝16.0,3.8Hz,1H),2.58(dd,J＝16.2,10.6Hz,1H)。
Example 22:
preparation of 2- (4-bromophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-methoxyphenyl) ] semicarbazide (I18)
Preparation of 2- (4-bromophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-methoxyphenyl) with intermediate D3 and 4- (4-methoxyphenyl) semicarbazide starting with the preparation of Compound I01]Semicarbazide (I18): white solid, yield 60.7%, LC-MS (M/z):465.3[ M + H]+,1H-NMR(600MHz,DMSO-d6)δ9.69(s,1H),8.77(s,1H),8.13(d,J＝7.5Hz,1H),7.61-7.56(m,2H),7.51(d,J＝8.2Hz,2H),7.41(d,J＝8.2Hz,2H),7.11-7.01(m,3H),6.81(d,J＝8.1Hz,1H),6.74-6.61(m,1H),6.48(s,1H),4.37(dd,J＝11.4,3.6Hz,1H),3.75(s,3H),3.00(dd,J＝16.2,3.1Hz,1H),2.56(dd,J＝16.4,11.3Hz,1H)。
Example 23:
preparation of 2- (4-bromophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dichlorophenyl) ] semicarbazide (I19)
2- (4-bromophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dichlorophenyl) -2) is prepared from intermediate D3 and 4- (2, 4-dichlorophenyl) semicarbazide by the method for preparing compound I01]Semicarbazide (I19): white solid, yield 45.7%, LC-MS (M/z):503.2[ M + H]+,1H-NMR(600MHz,DMSO-d6)δ9.92(s,1H),9.14(s,1H),8.14(d,J＝7.6Hz,1H),7.86(d,J＝1.8Hz,2H),7.66-7.51(m,2H),7.43-7.35(m,2H),7.19-7.10(m,1H),7.14(dd,J＝8.4,1.6Hz,1H),6.81(dd,J＝8.2,0.7Hz,1H),6.71-6.65(m,1H),6.55(s,1H),4.43(dd,J＝10.9,3.9Hz,1H),3.12(dd,J＝3.4Hz,1H),2.58(dd,J＝16.4,11.0Hz,1H)。
Example 24:
preparation of 2- (4-bromophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dimethylphenyl) ] semicarbazide (I20)
Preparation of 2- (4-bromophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dimethylphenyl) ketal ] from intermediate D3 and 4- (2, 4-dimethylphenyl) semicarbazide by the method of preparation of Compound I01]Semicarbazide (I20): white solid, yield 51.2%, LC-MS (M/z):464.1[ M + H]+,1H-NMR(600MHz,DMSO-d6)δ9.77(s,1H),8.58(s,1H),7.88-7.82(m,2H),7.77-7.64(m,1H),7.60-7.55(m,1H),7.44(d,J＝8.2Hz,2H),7.10-6.96(m,2H),6.72(t,J＝8.2Hz,2H),6.59-6.43(m,1H),6.38(s,1H),4.78(dd,J＝8.6,4.2Hz,1H),3.16(dd,J＝18.1,3.6Hz,1H),2.51(dd,J＝16.2,11.6Hz,1H),2.28(d,J＝18.6Hz,6H)。
Example 25:
preparation of 2- (4-bromophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (3, 5-dichlorophenyl) ] semicarbazide (I21)
2- (4-bromophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (3, 5-dichlorophenyl) -) was prepared from intermediate D3 and 4- (3, 5-dichlorophenyl) semicarbazide by the method described for preparation of Compound I01]Semicarbazide (I21):white solid, yield 53.2%, LC-MS (M/z):503.6[ M + H]+,1H-NMR(600MHz,DMSO-d6)δ9.89(s,1H),9.16(s,1H),8.18(d,J＝7.5Hz,1H),7.86(d,J＝1.7Hz,2H),7.62-7.57(m,2H),7.45(d,J＝8.4Hz,2H),7.19(t,J＝1.9Hz,1H),7.12(m,1H),6.79(dd,J＝8.1,0.7Hz,1H),6.71-6.65(m,1H),6.52(s,1H),4.43(dd,J＝10.9,3.9Hz,1H),3.12(dd,J＝3.4Hz,1H),2.58(dd,J＝16.4,11.0Hz,1H)。
Example 26:
preparation of 2- (4-bromophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (3, 4-dimethylphenyl) ] semicarbazide (I22)
Preparation of 2- (4-bromophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (3, 4-dimethylphenyl) ketal ] from intermediate D3 and 4- (3, 4-dimethylphenyl) semicarbazide by the method of preparation of Compound I01]Semicarbazide (I21): white solid, yield 44.0%, LC-MS (M/z):464.9[ M + H]+,1H-NMR(600MHz,DMSO-d6)δ9.78(s,1H),8.52(s,1H),7.97-7.92(m,1H),7.65(s,1H),7.62-7.58(m,2H),7.46(d,J＝8.4Hz,2H),7.13-7.06(m,2H),6.81(t,J＝7.1Hz,2H),6.68-6.63(m,1H),6.50(s,1H),4.44(dd,J＝11.1,3.9Hz,1H),3.13(dd,J＝16.4,3.3Hz,1H),2.56(dd,J＝16.4,11.1Hz,1H),2.25(d,J＝17.3Hz,6H)。
Example 27:
preparation of 2- (4-methoxyphenyl) -2, 3-dihydro-4 (1H) -quinolinone (4-phenyl) semicarbazide (I45)
Starting from intermediate D6 and the (4-phenyl) semicarbazide, 2- (4-methoxyphenyl) -2, 3-dihydro-4 (1H) -quinolinone condensation (4-phenyl) semicarbazide (I45) was prepared according to the preparation method of compound I01: white solid, yield 39.7%, LC-MS (M/z):387.1[ M + H]+,1H-NMR(600MHz,DMSO-d6)δ9.67(s,1H),8.85(s,1H),8.13(d,J＝7.1Hz,1H),7.65(d,J＝7.0Hz,2H),7.42(d,J＝7.5Hz,2H),7.30(d,J＝6.5Hz,2H),7.11(d,J＝6.5Hz,1H),7.06-6.92(m,3H),6.82(d,J＝7.6Hz,1H),6.68(t,J＝6.5Hz,1H),6.40(s,1H),4.37(d,J＝9.1Hz,1H),3.76(s,3H),3.10(d,J＝15.5Hz,1H),2.64-2.53(m,1H)。
Example 28:
preparation of 2- (4-methoxyphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-chlorophenyl) ] semicarbazone (I46)
2- (4-methoxyphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-chlorophenyl) ketal ] was prepared from intermediate D6 and 4- (4-chlorophenyl) semicarbazide by the method described for Compound I01]Semicarbazide (I46): white solid, yield 45.2%, LC-MS (M/z):421.1[ M + H]+,1H-NMR(600MHz,DMSO-d6)δ10.12(s,1H),9.16(s,1H),8.27(d,J＝8.1Hz,1H),7.89(d,J＝7.7Hz,1H),7.64-7.58(m,2H),7.51-7.43(m,1H),7.46(d,J＝8.3Hz,2H),7.34(m,1H),7.16-7.10(m,1H),7.07-7.01(m,1H),6.82(d,J＝8.1Hz,1H),6.69(t,J＝7.3Hz,1H),6.56(s,1H),4.46(dd,J＝11.0,3.7Hz,1H),3.75(s,3H),3.15(d,J＝17.5Hz,1H),2.59(dd,J＝16.0,11.3Hz,1H)。
Example 29:
preparation of 2- (4-methoxyphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-bromophenyl) ] semicarbazide (I47)
Preparation of 2- (4-methoxyphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-bromophenyl) ketal ] with intermediate D6 and 4- (4-bromophenyl) semicarbazide starting with reference to preparation of Compound I01]Semicarbazide (I47): white solid, yield 50.6%, LC-MS (M/z):465.1[ M + H]+,1H-NMR(600MHz,DMSO-d6)δ9.65(s,1H),8.89(s,1H),8.12(d,J＝7.7Hz,1H),7.69-7.59(m,2H),7.40(d,J＝8.6Hz,2H),7.17-7.05(m,3H),6.95(d,J＝8.7Hz,2H),6.79(d,J＝7.7Hz,1H),6.67-6.62(m,1H),6.38(s,1H),4.35(dd,J＝11.2,3.8Hz,1H),3.75(s,3H),3.07(dd,J＝16.4,3.2Hz,1H),2.54(dd,J＝16.4,11.3Hz,1H)。
Example 30:
preparation of 2- (4-methoxyphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-methylphenyl) ] semicarbazide (I48)
2- (4-methoxyphenyl) -2, 3-dihydro-4 (1H) -quinolinone condensation [4- (4-methylphenyl)]Semicarbazide (I48): white solid, yield 57.1%, LC-MS (M/z):401.2[ M + H]+,1H-NMR(600MHz,DMSO-d6)δ9.60(s,1H),8.74(s,1H),8.09(d,J＝.8Hz,1H),7.50(d,J＝8.2Hz,2H),7.40(d,J＝8.5Hz,2H),7.09(d,J＝8.1Hz,3H),6.95(d,J＝8.5Hz,2H),6.79(d,J＝8.1Hz,1H),6.65(t,J＝7.4Hz,1H),6.37(s,1H),4.35(dd,J＝11.2,3.4Hz,1H),3.75(s,3H),3.07(dd,J＝16.3,3.0Hz,1H),2.54(dd,J＝16.3,11.3Hz,1H),2.25(s,3H)。
Example 31:
preparation of 2- (4-methoxyphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-nitrophenyl) ] semicarbazone (I49)
2- (4-methoxyphenyl) -2, 3-dihydro-4 (1H) -quinolinone condensation [4- (4-nitrophenyl) was obtained starting from intermediate D6 and 4- (4-nitrophenyl) semicarbazide, according to the preparation method of Compound I01]Semicarbazide (I49): white solid, yield 35.9%, LC-MS (M/z):432.2[ M + H%]+,1H-NMR(600MHz,DMSO-d6)δ9.63(s,1H),8.86(s,1H),8.15(d,J＝8.2Hz,1H),7.77-7.69(m,2H),7.43(d,J＝8.4Hz,2H),7.22-7.14(m,3H),6.95-6.87(m,2H),6.79-6.68(m,1H),6.67(d,J＝7.7Hz,1H),6.37(s,1H),4.32(dd,J＝10.1,3.6Hz,1H),3.70(s,6H),3.06(dd,J＝18.1,3.6Hz,1H),2.47(dd,J＝15.2,11.2Hz,1H)。
Example 32:
preparation of 2- (4-methoxyphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-trifluoromethylphenyl) ] semicarbazide (I50)
2- (4-methoxyphenyl) -2, 3-dihydro-4 (1H) -quinolinone condensation [4- (4-trifluoromethylphenyl) was obtained from intermediate D6 and 4- (4-trifluoromethylphenyl) semicarbazide, according to the preparation method of Compound I01]Semicarbazide (I50): white solid, yield 43.6%, LC-MS (M/z):455.2[ M + H]+,1H-NMR(600MHz,DMSO-d6)δ9.76(s,1H),8.84(s,1H),8.19(d,J＝8.1Hz,1H),7.80-7.70(m,2H),7.41(d,J＝8.4Hz,2H),7.26-7.13(m,3H),6.91-6.80(m,2H),6.81-6.74(m,1H),6.62(d,J＝7.8Hz,1H),6.45(s,1H),4.39(dd,J＝10.6,3.4Hz,1H),3.65(s,3H),3.19(dd,J＝16.1,3.2Hz,1H),2.44(dd,J＝15.6,9.8Hz,1H)。
Example 33:
preparation of 2- (4-methoxyphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-methoxyphenyl) ] semicarbazone (I51)
2- (4-methoxyphenyl) -2, 3-dihydro-4 (1H) -quinolinone condensation [4- (4-methoxyphenyl) was obtained from intermediate D6 and 4- (4-methoxyphenyl) semicarbazide by the method for preparing Compound I01]Semicarbazide (I51): white solid, yield 57.1%, LC-MS (M/z):417.3[ M + H%]+,1H-NMR(600MHz,DMSO-d6)δ9.89(s,1H),8.75(s,1H),8.23(d,J＝8.6Hz,1H),7.74-7.66(m,2H),7.64(d,J＝8.2Hz,2H),7.45(d,J＝8.6Hz,2H),7.21-7.14(m,3H),6.79(d,J＝8.6Hz,1H),6.64-6.59(m,1H),6.51(s,1H),4.32(dd,J＝9.6,2.8Hz,1H),3.77(s,6H),3.06(dd,J＝15.8,3.6Hz,1H),2.53(dd,J＝14.8,11.8Hz,1H)。
Example 34:
preparation of 2- (4-methoxyphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dichlorophenyl) ] semicarbazone (I52)
2- (4-methoxyphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dichlorophenyl) was prepared from intermediate D6 and 4- (2, 4-dichlorophenyl) semicarbazide by the method described for Compound I01]Semicarbazide (I52): white solid, yield 37.3%, LC-MS (M/z):455.3[ M + H]+,1H-NMR(600MHz,DMSO-d6)δ9.88(s,1H),9.09(s,1H),8.10(d,J＝7.2Hz,1H),7.83(d,J＝1.2Hz,2H),7.72-7.66(m,2H),7.54-7.44(m,2H),7.29-7.16(m,1H),7.11(dd,J＝8.2,1.4Hz,1H),6.78(dd,J＝8.6,0.7Hz,1H),6.72-6.61(m,1H),6.59(s,1H),4.44(dd,J＝13.1,3.6Hz,1H),3.71(s,3H),3.08(dd,J＝3.4Hz,1H),2.55(dd,J＝16.4,11.8Hz,1H)。
Example 35:
preparation of 2- (4-methoxyphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dimethylphenyl) ] semicarbazone (I53)
2- (4-methoxyphenyl) -2, 3-dihydro-4 (1H) -quinolinone condensation [4- (2, 4-dimethylphenyl) was obtained from intermediate D6 and 4- (2, 4-dimethylphenyl) semicarbazide by the same method as described for Compound I01]Semicarbazide (I55): white solid, yield 48.9%, LC-MS (M/z):415.4[ M + H]+,1H-NMR(600MHz,DMSO-d6)δ9.97(s,1H),8.61(s,1H),8.15(d,J＝8.2Hz,1H),7.54-7.46(m,2H),7.42-7.36(m,2H),7.21(t,J＝8.2Hz,1H),7.11(d,J＝8.6Hz,1H),6.87(d,J＝8.6Hz,2H),6.71(d,J＝10.2Hz,1H),6.67(t,J＝7.6Hz,1H),6.44(s,1H),4.31(dd,J＝9.8,3.6Hz,1H),3.69(s,3H),3.12(dd,J＝15.8,2.8Hz,1H),2.58-2.52(m,1H),2.16(t,J＝14.8Hz,6H)。
Example 36:
preparation of 2- (4-methoxyphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (3, 5-dichlorophenyl) ] semicarbazone (I54)
2- (4-methoxyphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (3, 5-dichlorophenyl) was prepared from intermediate D6 and 4- (3, 5-dichlorophenyl) semicarbazide by the method described for Compound I01]Semicarbazide (I54): off-white solid, yield 41.8%, LC-MS (M/z):452.9[ M + H]+,1H-NMR(600MHz,DMSO-d6)δ9.87(s,1H,),9.16(s,1H,),8.17(d,J＝7.8Hz,1H),7.86(d,J＝1.2Hz,2H),7.40(d,J＝8.6Hz,2H),7.18(t,J＝1.8Hz,1H),7.16-7.04(m,1H),6.95(d,J＝8.7Hz,2H),6.80(d,J＝7.9Hz,1H),6.72-6.58(m,1H),6.41(s,1H),4.35(dd,J＝11.2,3.8Hz,1H),3.76(s,3H),3.09(dd,J＝16.4,3.2Hz,1H),2.56(dd,J＝16.4,11.4Hz,1H)。
Example 37:
preparation of 2- (4-methoxyphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (3, 4-dimethylphenyl) ] semicarbazone (I55)
2- (4-methoxyphenyl) -2, 3-dihydro-4 (1H) -quinolinone condensation [4- (3, 4-dimethylphenyl) was obtained from intermediate D6 and 4- (3, 4-dimethylphenyl) semicarbazide by the same method as that for Compound I01]Semicarbazide (I55): white solid, yield 50.7%, LC-MS (M/z):415.2[ M + H%]+,1H-NMR(600MHz,DMSO-d6)δ9.57(s,1H),8.65(s,1H),8.08(d,J＝7.8Hz,1H),7.43-7.31(m,4H),7.09(t,J＝7.5Hz,1H),7.03(d,J＝8.1Hz,1H),6.95(d,J＝8.5Hz,2H),6.79(d,J＝8.1Hz,1H),6.65(t,J＝7.4Hz,1H),6.37(s,1H),4.34(dd,J＝11.1,3.3Hz,1H),3.75(s,3H),3.07(dd,J＝16.2,2.8Hz),2.58-2.52(m,1H),2.17(t,J＝15.1Hz,6H)。
Example 38:
preparation of 2- (2-thienyl) -2, 3-dihydro-4 (1H) -quinolinone (4-phenyl) semicarbazide (I123)
Starting from intermediate D9 and 4-phenylsemicarbazone, according to the preparation method of compound I01, 2- (2-thienyl) -2, 3-dihydro-4 (1H) -quinolinone condensation (4-phenyl) semicarbazide (I123) was prepared: off-white solid, yield 43.6%, LC-MS (M/z):363.1[ M + H]+,1H-NMR(600MHz,DMSO-d6)δ9.73(s,1H),8.83(s,1H),8.10(s,1H),7.63(s,2H),7.43(s,1H),7.28(s,2H),7.06(d,J＝65.8Hz,4H),6.79(s,2H),6.65(s,1H),4.77(s,1H),3.09(d,J＝12.4Hz,1H),2.79(s,1H)。
Example 39:
preparation of 2- (2-thienyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-chlorophenyl) ] semicarbazone (I124)
2- (2-thienyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-chlorophenyl) ketal ] was prepared from intermediate D9 and 4- (4-chlorophenyl) semicarbazide by the method described for Compound I01]Semicarbazide (I124): white solid, yield 39.7%, LC-MS (M/z):394.9[ M-H]-,419.1[M+Na]+,1H-NMR(600MHz,DMSO-d6)δ10.20(s,1H),9.16(s,1H),8.28(d,J＝8.0Hz),7.88(d,J＝7.8Hz,1H),7.51-7.43(m,2H),7.39-7.31(m,2H),7.07(t,J＝4.6Hz,1H),7.01(dd,J＝4.8,3.6Hz,1H),6.81-6.76(m,1H),6.73(s,1H),6.69(t,J＝7.4Hz,1H),4.81(dd,J＝9.0,3.9Hz,1H),3.14(dd,J＝16.4,4.0Hz,1H),2.82(dd,J＝15.3,9.1Hz,1H)。
Example 40:
preparation of 2- (2-thienyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-bromophenyl) ] semicarbazide (I125)
Preparation of 2- (2-thienyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-bromophenyl) ketal ] from intermediate D9 and 4- (4-bromophenyl) semicarbazide by the method of preparation of Compound I01]Semicarbazide (I125): white solid, yield 40.1%, LC-MS (M/z):441.3[ M + H]+,464.1[M+Na]+1H-NMR(600MHz,DMSO-d6)δ10.05(s,1H),9.28(s,1H),8.15(d,J＝8.6Hz),7.79(d,J＝8.5Hz,1H),7.66-7.57(m,2H),7.45-7.33(m,2H),7.12(t,J＝4.2Hz,1H),7.01(dd,J＝4.8,3.6Hz,1H),6.83-6.74(m,1H),6.69(s,1H),6.54(t,J＝8.4Hz,1H),4.77(dd,J＝8.6 3.0Hz,1H),3.08(dd,J＝15.2,3.8Hz,1H),2.76(dd,J＝14.2,8.2Hz,1H)。
Example 41:
preparation of 2- (2-thienyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-methylphenyl) ] semicarbazide (I126)
2- (2-thienyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-methylphenyl)]Semicarbazide (I125): white solid, yield 50.3%, LC-MS (M/z):375.0[ M-H]-,399.2[M+Na]+,1H-NMR(600MHz,DMSO-d6)δ9.68(s,1H),8.75(s,1H),8.09(d,J＝7.7Hz,1H),7.51(d,J＝8.4Hz,2H),7.44(dd,J＝5.0,1.1Hz,1H),7.10(dd,J＝10.1,5.9Hz,4H),7.00(dd,J＝5.0,3.5Hz,1H),6.78(d,J＝7.9Hz,1H),6.71-6.60(m,2H),4.77(dd,J＝9.1,4.3Hz,1H),3.08(dd,J＝16.4,4.2Hz,1H),2.78(dd,J＝16.4,9.3Hz,1H),2.25(d,J＝10.4Hz,3H)。
Example 42:
preparation of 2- (2-thienyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-nitrophenyl) ] semicarbazide (I127)
2- (2-thienyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-nitrophenyl) quinolinone-ketal ] was prepared starting from intermediate D9 and 4- (4-nitrophenyl) semicarbazide, according to the preparation method of Compound I01]Semicarbazide (I127): off-white solid, yield 38.1%, LC-MS (M/z):408.4[ M + H]+,1H-NMR(600MHz,DMSO-d6)δ9.74(s,1H),8.90(s,1H),8.12(d,J＝7.9Hz,1H),7.65(dd,J＝8.7,5.0Hz,2H),7.44(d,J＝4.9Hz,1H),7.17-7.06(m,4H),7.00(dd,J＝4.8,3.7Hz,1H),6.78(d,J＝8.1Hz,1H),6.72-6.61(m,2H),4.77(dd,J＝8.8,4.0Hz,1H),3.09(dd,J＝16.4,4.1Hz,1H),2.79(dd,J＝16.4,9.2Hz,1H)。
Example 43:
preparation of 2- (2-thienyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-trifluoromethylphenyl) ] semicarbazide (I128)
2- (2-thienyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-trifluoromethylphenyl) ketal ] was prepared from intermediate D9 and 4- (4-trifluoromethylphenyl) semicarbazide by the method of preparation of Compound I01]Semicarbazide (I128): white solid, yield 40.8%, LC-MS (M/z):431.1[ M + H]+,1H-NMR(600MHz,DMSO-d6)δ9.86(s,1H),8.93(s,1H),8.21(d,J＝8.2Hz,1H),7.84-7.77(m,2H),7.48(d,J＝4.2Hz,1H),7.23-7.14(m,4H),7.00(dd,J＝4.8,3.7Hz,1H),6.78(d,J＝8.1Hz,1H),6.72-6.61(m,2H),4.74(dd,J＝8.2,4.4Hz,1H),3.11(dd,J＝14.8,4.2Hz,1H),2.65(dd,J＝18.1,8.6Hz,1H)。
Example 44:
preparation of 2- (2-thienyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-methoxyphenyl) ] semicarbazide (I129)
Starting from intermediate D9 and 4- (4-methoxyphenyl) semicarbazide, reference is made to the preparation of Compound I01By the method, 2- (2-thienyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-methoxyphenyl) is prepared]Semicarbazide (I129): white solid, yield 53.1%, LC-MS (M/z):375.0[ M-H]-,399.2[M+Na]+,1H-NMR(600MHz,DMSO-d6)δ9.42(s,1H),8.77(s,1H),8.14(d,J＝7.7Hz,1H),7.63(d,J＝8.8Hz,2H),7.56-7.44(m,1H),7.13-7.01(m,4H),6.94(dd,J＝5.8,4.2Hz,1H),6.78-6.67(m,1H),6.61-6.54(m,2H),4.54(dd,J＝9.1,4.3Hz,1H),3.69(s,3H)3.08(dd,J＝16.4,4.2Hz,1H),2.78(dd,J＝16.4,9.3Hz,1H),2.25(d,J＝10.4Hz,3H)。
Example 45:
preparation of 2- (2-thienyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dichlorophenyl) ] semicarbazide (I130)
2- (2-thienyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dichlorophenyl) -quinolinone ] was prepared from intermediate D9 and 4- (2, 4-dichlorophenyl) semicarbazide by the method of preparation of Compound I01]Semicarbazide (I130): white solid, yield 38.4%, LC-MS (M/z):431.2[ M + H]+,1H-NMR(600MHz,DMSO-d6)δ9.88(s,1H,),9.22(s,1H),8.14(d,J＝7.6Hz,1H),7.89-7.78(m,2H),7.64-7.54(m,2H),7.15-7.09(m,2H),7.02(dd,J＝4.8,3.5Hz,1H),6.81(d,J＝8.0Hz,1H),6.58(dd,J＝8.8,3.9Hz,2H),4.72(dd,J＝8.6,4.4Hz,1H),3.16(dd,J＝14.8,4.0Hz,1H),2.80(dd,J＝16.4,9.3Hz,1H)。
Example 46:
preparation of 2- (2-thienyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dimethylphenyl) ] semicarbazone (I131)
2- (2-thienyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dimethylphenyl) ketal is prepared from intermediate D9 and 4- (2, 4-dimethylphenyl) semicarbazide by the method of preparing compound I01]Semicarbazide (I131): white solid, yield 45.7%, LC-MS (M/z):391.2[ M + H]+,1H-NMR(600MHz,DMSO-d6)δ9.88(s,1H),8.62(s,1H),7.87(d,J＝8.2Hz,1H),7.66-7.54(m,1H),7.42(d,J＝5.6Hz,1H),7.17-7.02(m,4H),6.86(t,J＝8.4Hz,3H),6.59(d,J＝7.8Hz,1H),4.74(dd,J＝10.0,4.2Hz,1H),3.08(dd,J＝14.8,4.6Hz,1H),2.78(dd,J＝14.48.6,1H),2.22(d,J＝18.6,6H)。
Example 47:
preparation of 2- (2-thienyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (3, 5-dichlorophenyl) ] semicarbazide (I132)
2- (2-thienyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (3, 5-dichlorophenyl) -quinolinone ] was prepared from intermediate D9 and 4- (3, 5-dichlorophenyl) semicarbazide by the method described in reference to preparation of Compound I01]Semicarbazide (I132): white solid, yield 38.4%, LC-MS (M/z):431.1[ M + H%]+,1H-NMR(600MHz,DMSO-d6)δ9.97(s,1H),9.17(s,1H),8.17(d,J＝7.8Hz,1H),7.87(d,J＝1.4Hz,2H),7.44(dd,J＝5.0,1.1Hz,1H),7.19(t,J＝1.8Hz,1H),7.15-7.09(m,2H),7.00(dd,J＝5.0,3.5Hz,1H),6.79(d,J＝8.0Hz,1H),6.68(dd,J＝11.0,3.9Hz,2H),4.78(dd,J＝9.0,4.1Hz,1H),3.10(dd,J＝16.4,4.1Hz,1H),2.80(dd,J＝16.4,9.3Hz,1H)。
Example 48:
preparation of 2- (2-thienyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (3, 4-dimethylphenyl) ] semicarbazone (I133)
2- (2-thienyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (3, 4-dimethylphenyl) ketal ] was prepared from intermediate D9 and 4- (3, 4-dimethylphenyl) semicarbazide by the method of preparing Compound I01]Semicarbazide (I133), white solid, yield 48.1%, LC-MS (M/z):391.2[ M + H]+,1H-NMR(600MHz,DMSO-d6)δ9.85(s,1H),8.53(s,1H),7.94(d,J＝7.8Hz,1H),7.66(s,1H),7.45(d,J＝4.7Hz,1H),7.15-7.05(m,3H),7.01(dd,J＝4.8,3.6Hz,1H),6.81(t,J＝8.8Hz,3H),6.66(d,J＝7.2Hz,1H),4.78(dd,J＝9.1,3.9Hz,1H),3.12(dd,J＝16.4,4.0Hz,1H),2.78(dd,J＝16.4,9.4Hz,1H),2.25(d,J＝17.6Hz,6H)。
Pharmacological study of the products of the invention
The two-fold dilution method is one of the most common in vitro methods for screening antifungal activity of drugs. Next, the antifungal activity of the 2-aryl-2, 3-dihydro-4 (1H) -quinolinone semicarbazone partial compound of the above formula I according to the present invention was evaluated in vitro.
The experimental method comprises the following steps:
with reference to the 2003 edition published protocols for the spore-forming filamentous fungi drug susceptibility test by the national committee for standardization of clinical laboratories (NCCLS), culture medium for culture and dilution was SDA medium and not RPMI-1640.
Positive control drugs, fluconazole (Fluoconazole), Itraconazole (Itraconazole)
Test strains 7 test fungi were stored and provided in the institute of microbiology, university of shenyang medical science, and were: candida tropicalis (C.t), candida albicans (C.a), Cryptococcus neoformans var. gattii, C.n), Aspergillus fumigatus (A.f), fluconazole-resistant candida albicans 100, 103, and candida albicans SC5314 (fluconazol-resistant c. albicans 100, stain103, stain SC 5314).
Experimental methods and procedures
(1) Preparation of test Compound and control drug dilutions
Carrying out drug sensitivity detection by using a disposable sterile 96-well plate; for each test fungus, RPMI1640 medium without antifungal drug was used as a growth control, which was added to the eleventh well of the 96-well plate. Accurately weighing 12.8mg of each sample to be tested, and sequentially adding dimethyl sulfoxide (0.05mL), Tween 20(5mL) and sterilized distilled water (4.0 mL); adding the mixture into the first hole of a 96-well plate, and sequentially diluting the mixture to the tenth hole in a multiple ratio manner, wherein the twelfth hole is a blank control which is not added with liquid medicine or bacterial suspension and is only added with liquid culture medium. The concentrations of the drug base are respectively 128, 64, 32, 16, 8, 4, 2, 1, 0.5 and 0.25 mug/mL. Control dilution was as above.
(2) Inoculating and culturing
Inoculating activated strain on a slope of a Sabouraud's medium, culturing for 2-3 days at 32 ℃, adding 5mL of sterilized normal saline on the slope, slightly scraping hypha and spores by using an inoculating loop, transferring the hypha and the spores into a 100mL triangular flask filled with glass beads, shaking for 20min to ensure that the hypha is uniformly distributed in the normal saline, filtering, adjusting the absorbance A value of the bacterial suspension to be 0.2-0.5, and diluting 50 times by using the culture medium as an inoculated bacterial suspension.
Culturing, namely standing and incubating the 96-well plate at 35 ℃; and (3) judging the MIC after the rhizopus is cultured for 21-26h, judging the MIC after the cryptococcus neoformans is cultured for 70-74h, and judging the MIC for other coccoid for 46-50 h.
Table 1 determination of antifungal Activity of some of the compounds
Figure BDA0001672662320000251
Figure BDA0001672662320000261
Note: MIC: minimum inhibitory concentration, FC: fluconazole, KCZ: ketoconazole, C.t: candida tropicalis, C.a: candida albicans, A.f: aspergillus fumigatus, C.n: cryptococcus neoformans variation, C.a (statin 100): fluconazole-resistant candida albicans 100, C.a (statin 103): fluconazole-resistant candida albicans 103, C.a (SC 5314): candida albicans SC 5314.

Claims (8)

1. A2-aryl-2, 3-dihydro-4 (1H) -quinolinone semicarbazone derivative shown in formula I and its pharmaceutically acceptable salt
Figure FDA0003130647690000011
Wherein:
R1is H atom, halogen, C1-C4 alkyl, C1-C4 alkoxy, nitro, cyano, halogenated C1-C4 alkyl;
R2,R3is H atom, halogen, cyano, nitro, halogenated C1-C4 alkyl, C1-C4 alkyl, C1-C4 alkoxy; r2，R3May be the same or different;
ar is furyl, thienyl or substituted or unsubstituted phenyl, and the substituent is halogen, cyano, nitro, halogenated C1-C4 alkyl, C1-C4 alkyl, C1-C4 alkoxy.
2. The derivative of claim 1 and pharmaceutically acceptable salts thereof wherein:
R1h atom, halogen, nitro, cyano, trifluoromethyl, methyl, methoxy;
R2,R3h atom, halogen, cyano, nitro, trifluoromethyl, C1-C4 alkyl, C1-C4 alkoxy; r2，R3May be the same or different;
ar ═ furyl, thienyl, phenyl containing 1 to 4 halogen, cyano, nitro, trifluoromethyl, C1 to C4 alkyl, C1 to C4 alkoxy substituents.
3. The derivative of any one of claims 1-2, and pharmaceutically acceptable salts thereof:
R1is H atom, halogen, nitryl, cyano, trifluoromethyl, methyl, methoxyl;
R2,R3is H atom, halogen, nitro, trifluoromethyl, methyl, methoxy, R2，R3May be the same or different;
ar is thienyl, phenyl substituted by 1-4 halogens, cyano, nitro, trifluoromethyl, methyl and methoxy.
4. A derivative selected from the group consisting of:
2-phenyl-2, 3-dihydro-4 (1H) -quinolinone (4-phenyl) semicarbazone
2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (4-chlorophenyl) ] semicarbazone
2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (4-bromophenyl) ] semicarbazide
2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (4-methylphenyl) ] semicarbazone
2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (4-nitrophenyl) ] semicarbazone
2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (4-trifluoromethylphenyl) ] semicarbazone
2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (4-methoxyphenyl) ] semicarbazone
2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dichlorophenyl) ] semicarbazone
2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dimethylphenyl) ] semicarbazone
2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (3, 5-dichlorophenyl) ] semicarbazone
2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (3, 4-dimethylphenyl) ] semicarbazone
2- (4-bromophenyl) -2, 3-dihydro-4 (1H) -quinolinone (4-phenyl) semicarbazide
2- (4-bromophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-chlorophenyl) ] semicarbazide
2- (4-bromophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-bromophenyl) ] semicarbazide
2- (4-bromophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-methylphenyl) ] semicarbazide
2- (4-bromophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-nitrophenyl) ] semicarbazide
2- (4-bromophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-trifluoromethylphenyl) ] semicarbazide
2- (4-bromophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-methoxyphenyl) ] semicarbazide
2- (4-bromophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dichlorophenyl) ] semicarbazide
2- (4-bromophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dimethylphenyl) ] semicarbazide
2- (4-bromophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (3, 5-dichlorophenyl) ] semicarbazide
2- (4-bromophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (3, 4-dimethylphenyl) ] semicarbazide
2- (4-chlorophenyl) -2, 3-dihydro-4 (1H) -quinolinone (4-phenyl) semicarbazone
2- (4-chlorophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-chlorophenyl) ] semicarbazone
2- (4-chlorophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-bromophenyl) ] semicarbazide
2- (4-chlorophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-methylphenyl) ] semicarbazone
2- (4-chlorophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-nitrophenyl) ] semicarbazone
2- (4-chlorophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-trifluoromethylphenyl) ] semicarbazide
2- (4-chlorophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-methoxyphenyl) ] semicarbazone
2- (4-chlorophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dichlorophenyl) ] semicarbazone
2- (4-chlorophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dimethylphenyl) ] semicarbazone
2- (4-chlorophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (3, 5-dichlorophenyl) ] semicarbazone
2- (4-chlorophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (3, 4-dimethylphenyl) ] semicarbazone
2- (4-methylphenyl) -2, 3-dihydro-4 (1H) -quinolinone condensation (4-phenyl) semicarbazide
2- (4-methylphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-chlorophenyl) ] semicarbazone
2- (4-methylphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-bromophenyl) ] semicarbazide
2- (4-methylphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-methylphenyl) ] semicarbazone
2- (4-methylphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-nitrophenyl) ] semicarbazone
2- (4-methylphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-trifluoromethylphenyl) ] semicarbazone
2- (4-methylphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-methoxyphenyl) ] semicarbazone
2- (4-methylphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dichlorophenyl) ] semicarbazone
2- (4-methylphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dimethylphenyl) ] semicarbazone
2- (4-methylphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (3, 5-dichlorophenyl) ] semicarbazone
2- (4-methylphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (3, 4-dimethylphenyl) ] semicarbazone
2- (4-methoxyphenyl) -2, 3-dihydro-4 (1H) -quinolinone condensation (4-phenyl) semicarbazide
2- (4-methoxyphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-chlorophenyl) ] semicarbazone
2- (4-methoxyphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-bromophenyl) ] semicarbazide
2- (4-methoxyphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-methylphenyl) ] semicarbazone
2- (4-methoxyphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dichlorophenyl) ] semicarbazone
2- (4-methoxyphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dimethylphenyl) ] semicarbazone
2- (4-methoxyphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (3, 5-dichlorophenyl) ] semicarbazone
2- (4-methoxyphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (3, 4-dimethylphenyl) ] semicarbazone
2- (2, 4-dichlorophenyl) -2, 3-dihydro-4 (1H) -quinolinone condensation (4-phenyl) semicarbazide
2- (2, 4-dichlorophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-chlorophenyl) ] semicarbazone
2- (2, 4-dichlorophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-bromophenyl) ] semicarbazide
2- (2, 4-dichlorophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-methylphenyl) ] semicarbazide
2- (2, 4-dichlorophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-nitrophenyl) ] semicarbazide
2- (2, 4-dichlorophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-trifluoromethylphenyl) ] semicarbazide
2- (2, 4-dichlorophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-methoxyphenyl) ] semicarbazide
2- (2, 4-dichlorophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dichlorophenyl) ] semicarbazide
2- (2, 4-dichlorophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dimethylphenyl) ] semicarbazone
2- (2, 4-dichlorophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (3, 5-dichlorophenyl) ] semicarbazide
2- (2, 4-dichlorophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (3, 4-dimethylphenyl) ] semicarbazone
2- (2, 4-dimethylphenyl) -2, 3-dihydro-4 (1H) -quinolinone condensation (4-phenyl) semicarbazide
2- (2, 4-dimethylphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-chlorophenyl) ] semicarbazone
2- (2, 4-dimethylphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-bromophenyl) ] semicarbazide
2- (2, 4-dimethylphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-methylphenyl) ] semicarbazide
2- (2, 4-dimethylphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-nitrophenyl) ] semicarbazone
2- (2, 4-dimethylphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-trifluoromethylphenyl) ] semicarbazone
2- (2, 4-dimethylphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-methoxyphenyl) ] semicarbazone
2- (2, 4-dimethylphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dichlorophenyl) ] semicarbazone
2- (2, 4-dimethylphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dimethylphenyl) ] semicarbazone
2- (2, 4-dimethylphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (3, 5-dichlorophenyl) ] semicarbazone
2- (2, 4-dimethylphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (3, 4-dimethylphenyl) ] semicarbazone
6-chloro-2-phenyl-2, 3-dihydro-4 (1H) -quinolinone condensation (4-phenyl) semicarbazide
6-chloro-2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (4-chlorophenyl) ] semicarbazone
6-chloro-2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (4-bromophenyl) ] semicarbazide
6-chloro-2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (4-methylphenyl) ] semicarbazide
6-chloro-2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (4-nitrophenyl) ] semicarbazone
6-chloro-2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (4-trifluoromethylphenyl) ] semicarbazone
6-chloro-2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (4-methoxyphenyl) ] semicarbazone
6-chloro-2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dichlorophenyl) ] semicarbazone
6-chloro-2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dimethylphenyl) ] semicarbazone
6-chloro-2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (3, 5-dichlorophenyl) ] semicarbazone
6-chloro-2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (3, 4-dimethylphenyl) ] semicarbazone
6-chloro-2- (4-chlorophenyl) -2, 3-dihydro-4 (1H) -quinolinone condensation (4-phenyl) semicarbazide
6-chloro-2- (4-chlorophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-chlorophenyl) ] semicarbazone
6-chloro-2- (4-chlorophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-bromophenyl) ] semicarbazide
6-chloro-2- (4-chlorophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-methylphenyl) ] semicarbazide
6-chloro-2- (4-chlorophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-nitrophenyl) ] semicarbazide
6-chloro-2- (4-chlorophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-trifluoromethylphenyl) ] semicarbazide
6-chloro-2- (4-chlorophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-methoxyphenyl) ] semicarbazone
6-chloro-2- (4-chlorophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dichlorophenyl) ] semicarbazone
6-chloro-2- (4-chlorophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dimethylphenyl) ] semicarbazone
6-chloro-2- (4-chlorophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (3, 5-dichlorophenyl) ] semicarbazone
6-chloro-2- (4-chlorophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (3, 4-dimethylphenyl) ] semicarbazone
2- (4-bromophenyl) -6-chloro-2, 3-dihydro-4 (1H) -quinolinone condensation (4-phenyl) semicarbazide
2- (4-bromophenyl) -6-chloro-2, 3-dihydro-4 (1H) -quinolinone [4- (4-chlorophenyl) ] semicarbazide
2- (4-bromophenyl) -6-chloro-2, 3-dihydro-4 (1H) -quinolinone [4- (4-bromophenyl) ] semicarbazide
2- (4-bromophenyl) -6-chloro-2, 3-dihydro-4 (1H) -quinolinone [4- (4-methylphenyl) ] semicarbazide
2- (4-bromophenyl) -6-chloro-2, 3-dihydro-4 (1H) -quinolinone [4- (4-nitrophenyl) ] semicarbazide
2- (4-bromophenyl) -6-chloro-2, 3-dihydro-4 (1H) -quinolinone [4- (4-trifluoromethylphenyl) ] semicarbazide
2- (4-bromophenyl) -6-chloro-2, 3-dihydro-4 (1H) -quinolinone [4- (4-methoxyphenyl) ] semicarbazide
2- (4-bromophenyl) -6-chloro-2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dichlorophenyl) ] semicarbazide
2- (4-bromophenyl) -6-chloro-2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dimethylphenyl) ] semicarbazone
2- (4-bromophenyl) -6-chloro-2, 3-dihydro-4 (1H) -quinolinone [4- (3, 5-dichlorophenyl) ] semicarbazide
2- (4-bromophenyl) -6-chloro-2, 3-dihydro-4 (1H) -quinolinone [4- (3, 4-dimethylphenyl) ] semicarbazone
6-chloro-2- (4-methylphenyl) -2, 3-dihydro-4 (1H) -quinolinone condensation (4-phenyl) semicarbazide
6-chloro-2- (4-methylphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-chlorophenyl) ] semicarbazone
6-chloro-2- (4-methylphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-bromophenyl) ] semicarbazide
6-chloro-2- (4-methylphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-methylphenyl) ] semicarbazide
6-chloro-2- (4-methylphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-nitrophenyl) ] semicarbazide
6-chloro-2- (4-methylphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-trifluoromethylphenyl) ] semicarbazide
6-chloro-2- (4-methylphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-methoxyphenyl) ] semicarbazone
6-chloro-2- (4-methylphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dichlorophenyl) ] semicarbazide
6-chloro-2- (4-methylphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dimethylphenyl) ] semicarbazone
6-chloro-2- (4-methylphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (3, 5-dichlorophenyl) ] semicarbazide
6-chloro-2- (4-methylphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (3, 4-dimethylphenyl) ] semicarbazone
6-chloro-2- (4-methoxyphenyl) -2, 3-dihydro-4 (1H) -quinolinone condensation (4-phenyl) semicarbazide
6-chloro-2- (4-methoxyphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-chlorophenyl) ] semicarbazone
6-chloro-2- (4-methoxyphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-bromophenyl) ] semicarbazide
6-chloro-2- (4-methoxyphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-methylphenyl) ] semicarbazide
6-chloro-2- (4-methoxyphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-nitrophenyl) ] semicarbazone
6-chloro-2- (4-methoxyphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-trifluoromethylphenyl) ] semicarbazone
6-chloro-2- (4-methoxyphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-methoxyphenyl) ] semicarbazone
6-chloro-2- (4-methoxyphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dichlorophenyl) ] semicarbazide
6-chloro-2- (4-methoxyphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dimethylphenyl) ] semicarbazone
6-chloro-2- (4-methoxyphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (3, 5-dichlorophenyl) ] semicarbazide
6-chloro-2- (4-methoxyphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (3, 4-dimethylphenyl) ] semicarbazone
6-chloro-2- (2, 4-dichlorophenyl) -2, 3-dihydro-4 (1H) -quinolinone condensation (4-phenyl) semicarbazide
6-chloro-2- (2, 4-dichlorophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-chlorophenyl) ] semicarbazone
6-chloro-2- (2, 4-dichlorophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-bromophenyl) ] semicarbazide
6-chloro-2- (2, 4-dichlorophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-methylphenyl) ] semicarbazide
6-chloro-2- (2, 4-dichlorophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-nitrophenyl) ] semicarbazide
6-chloro-2- (2, 4-dichlorophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-trifluoromethylphenyl) ] semicarbazide
6-chloro-2- (2, 4-dichlorophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-methoxyphenyl) ] semicarbazone
6-chloro-2- (2, 4-dichlorophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dichlorophenyl) ] semicarbazide
6-chloro-2- (2, 4-dichlorophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dimethylphenyl) ] semicarbazone
6-chloro-2- (2, 4-dichlorophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (3, 5-dichlorophenyl) ] semicarbazide
6-chloro-2- (2, 4-dichlorophenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (3, 4-dimethylphenyl) ] semicarbazone
6-chloro-2- (2, 4-dimethylphenyl) -2, 3-dihydro-4 (1H) -quinolinone condensation (4-phenyl) semicarbazide
6-chloro-2- (2, 4-dimethylphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-chlorophenyl) ] semicarbazone
6-chloro-2- (2, 4-dimethylphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-bromophenyl) ] semicarbazide
6-chloro-2- (2, 4-dimethylphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-methylphenyl) ] semicarbazone
6-chloro-2- (2, 4-dimethylphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-nitrophenyl) ] semicarbazone
6-chloro-2- (2, 4-dimethylphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-trifluoromethylphenyl) ] semicarbazone
6-chloro-2- (2, 4-dimethylphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-methoxyphenyl) ] semicarbazone
6-chloro-2- (2, 4-dimethylphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dichlorophenyl) ] semicarbazide
6-chloro-2- (2, 4-dimethylphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dimethylphenyl) ] semicarbazone
6-chloro-2- (2, 4-dimethylphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (3, 5-dichlorophenyl) ] semicarbazide
6-chloro-2- (2, 4-dimethylphenyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (3, 4-dimethylphenyl) ] semicarbazone
6-methyl-2-phenyl-2, 3-dihydro-4 (1H) -quinolinone condensation (4-phenyl) semicarbazide
6-methyl-2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (4-chlorophenyl) ] semicarbazone
6-methyl-2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (4-bromophenyl) ] semicarbazide
6-methyl-2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (4-methylphenyl) ] semicarbazide
6-methyl-2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (4-nitrophenyl) ] semicarbazone
6-methyl-2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (4-trifluoromethylphenyl) ] semicarbazone
6-methyl-2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (4-methoxyphenyl) ] semicarbazone
6-methyl-2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dichlorophenyl) ] semicarbazone
6-methyl-2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dimethylphenyl) ] semicarbazone
6-methyl-2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (3, 5-dichlorophenyl) ] semicarbazone
6-methyl-2-phenyl-2, 3-dihydro-4 (1H) -quinolinone [4- (3, 4-dimethylphenyl) ] semicarbazone
2- (4-chlorophenyl) -6-methyl-2, 3-dihydro-4 (1H) -quinolinone condensation (4-phenyl) semicarbazide
2- (4-chlorophenyl) -6-methyl-2, 3-dihydro-4 (1H) -quinolinone [4- (4-chlorophenyl) ] semicarbazone
2- (4-chlorophenyl) -6-methyl-2, 3-dihydro-4 (1H) -quinolinone [4- (4-bromophenyl) ] semicarbazide
2- (4-chlorophenyl) -6-methyl-2, 3-dihydro-4 (1H) -quinolinone [4- (4-methylphenyl) ] semicarbazide
2- (4-chlorophenyl) -6-methyl-2, 3-dihydro-4 (1H) -quinolinone [4- (4-nitrophenyl) ] semicarbazide
2- (4-chlorophenyl) -6-methyl-2, 3-dihydro-4 (1H) -quinolinone [4- (4-trifluoromethylphenyl) ] semicarbazide
2- (4-chlorophenyl) -6-methyl-2, 3-dihydro-4 (1H) -quinolinone [4- (4-methoxyphenyl) ] semicarbazone
2- (4-chlorophenyl) -6-methyl-2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dichlorophenyl) ] semicarbazide
2- (4-chlorophenyl) -6-methyl-2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dimethylphenyl) ] semicarbazone
2- (4-chlorophenyl) -6-methyl-2, 3-dihydro-4 (1H) -quinolinone [4- (3, 5-dichlorophenyl) ] semicarbazone
2- (4-chlorophenyl) -6-methyl-2, 3-dihydro-4 (1H) -quinolinone [4- (3, 4-dimethylphenyl) ] semicarbazone
2- (2-thienyl) -2, 3-dihydro-4 (1H) -quinolinone (4-phenyl) semicarbazone
2- (2-thienyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-chlorophenyl) ] semicarbazone
2- (2-thienyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-bromophenyl) ] semicarbazide
2- (2-thienyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-methylphenyl) ] semicarbazide
2- (2-thienyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-nitrophenyl) ] semicarbazone
2- (2-thienyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-trifluoromethylphenyl) ] semicarbazide
2- (2-thienyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-methoxyphenyl ] semicarbazide
2- (2-thienyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dichlorophenyl) ] semicarbazone
2- (2-thienyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dimethylphenyl ] semicarbazide
2- (2-thienyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (3, 5-dichlorophenyl) ] semicarbazone
2- (2-thienyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (3, 4-dimethylphenyl) ] semicarbazone
2- (2-furyl) -2, 3-dihydro-4 (1H) -quinolinone condensation (4-phenyl) semicarbazide
2- (2-furyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-chlorophenyl) ] semicarbazone
2- (2-furyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-bromophenyl) ] semicarbazide
2- (2-furyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-methylphenyl) ] semicarbazide
2- (2-furyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-nitrophenyl) ] semicarbazide
2- (2-furyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-trifluoromethylphenyl) ] semicarbazide
2- (2-furyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (4-methoxyphenyl ] semicarbazide
2- (2-furyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dichlorophenyl) ] semicarbazide
2- (2-furyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (2, 4-dimethylphenyl ] semicarbazide
2- (2-furyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (3, 5-dichlorophenyl) ] semicarbazide
2- (2-furyl) -2, 3-dihydro-4 (1H) -quinolinone [4- (3, 4-dimethylphenyl) ] amino.
5. A process for the preparation of derivatives and pharmaceutically acceptable salts thereof as claimed in claim 1, characterized in that: the process is as follows:
Figure FDA0003130647690000081
wherein R is1，R2，R3Ar is as defined in claim 1.
6. A pharmaceutical composition comprising the derivative of any one of claims 1 to 4 and a pharmaceutically acceptable salt thereof as an active ingredient.
7. Use of a derivative according to any one of claims 1 to 4 or a composition according to claim 6 in the manufacture of a medicament for the treatment or prophylaxis of a fungal infection.
8. The use of claim 7, wherein the fungal infection is a post-operative visceral or dermal fungal infection.
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