通过FGF401的构效关系研究发现一种新颖的FGFR4选择性抑制剂（英文）

设计并合成了一系列FGF401类似物以研究其FGFR4抑制、抗肿瘤活性及其构效关系.研究发现了N-(5-氰基-4-((2-甲氧基乙基氨基)吡啶-2-基)-7-甲酰基-6-((N-甲基四氢吡喃-4-甲酰胺)甲基-1,2,3,4-四氢-1,8-萘啶-1-甲酰胺(8ac)不仅在酶和细胞学水平上对FGFR4具有强效的的抑制活性,并表现出了出色的选择性.其活性及选择性优于阳性对照FGF401,并且在HCC (hepatocellular carcinoma)动物移植瘤模型中显著抑制肿瘤生长,还引起了肿瘤萎缩.     

新型吡唑联噻吩甲酰胺类衍生物的设计、合成及其抑菌活性研究

琥珀酸脱氢酶抑制剂(SDHI)是一类低毒、高效的杀菌剂,为开发结构新颖、广谱的SDHI杀菌剂,将噻吩环引入吡唑酰胺类杀菌剂的骨架中,设计并合成了24个吡唑联噻吩甲酰胺类衍生物.结构经过~1H NMR、~(13)C NMR和HRMS鉴定,其中N-(4-甲氧基苯基)-4-(1-甲基-1H-吡唑-4-基)噻吩-2-甲酰胺(7i)经过X射线衍射确定其空间结构.通过对6种植物病原真菌离体抑制活性测试,发现在50μg/mL的浓度下,部分化合物对水稻纹枯病菌、小麦赤霉病菌和草莓灰霉病菌有较高的抑制活性.其中化合物N-(4-氟苯乙基)-4-(1-甲基-1H-吡唑-4-基)噻吩-2-甲酰胺(7c)对水稻纹枯病菌的EC_(50)为11.6μmol/L,化合物N-(2-氟苯基)-4-(1-甲基-1H-吡唑-4-基)噻吩-2-甲酰胺(7j)对小麦赤霉病菌的EC_(50)为28.9μmol/L,化合物N-(4-氯苯基)-4-(1-甲基-1H-吡唑-4-基)噻吩-2-甲酰胺(7h)对草莓灰霉病菌的EC_(50)为21.3μmol/L.分子对接结果表明,活性较高的目标化合物与琥珀酸脱氢酶关键氨基酸残基形成较强的相互作用.     

新型2-(1-甲基-1H-吡唑-4-基)嘧啶-4-甲酰胺的设计、合成、杀菌活性及分子对接研究

为寻找结构新颖的嘧啶类杀菌剂,以2-氯嘧啶-4-甲酸、1-甲基-4-吡唑硼酸频哪醇酯、取代苯胺或取代苄胺等为原料,经Suzuki偶联和酰胺化反应合成了13种2-(1-甲基-1H-吡唑-4-基)嘧啶-4-甲酰胺类化合物,其结构经过1H NMR、13CNMR、IR、HRMS鉴定,并利用X射线单晶衍射法确定了N-苄基-2-(1-甲基-1H-吡唑-4-基)嘧啶-4-甲酰胺(4h)的晶体结构.初步测试了目标化合物对3种植物病原菌的杀菌活性,在浓度为100 mg/L时, N-(4-甲基苯基)-2-(1-甲基-1H-吡唑-4-基)嘧啶-4-甲酰胺(4f)和N-(4-氯苄基)-2-(1-甲基-1H-吡唑-4-基)嘧啶-4-甲酰胺(4j)对水稻纹枯菌表现出较高的杀菌活性,抑制率分别为85.3%和79.1%.分子对接研究显示4f可与琥珀酸脱氢酶活性腔内的氨基酸残基形成2个氢键和1个阳离子-π相互作用.     

1,6-二氢-S-四嗪与异氰酸酯催化重排反应的研究

3,6-二甲基-1,6-二氢-S-四嗪与异氰酸酯反应,在N′,N-二甲基苯胺催化下生成N-苯基-3,6-二甲基-1,6-二氢-S四嗪-1-甲酰胺,在4-二甲胺基吡啶(DMAP)催化则生成一类新化合物.与14种不同的取代苯基异氰酸酯反应,生成14种新化合物,产率中等.化合物3i经X射线单晶衍射分析表明其结构为N,N′-双(邻甲苯基)-3,6-二甲基-1,4-二氢-S-四嗪-1,4-二甲酰胺,这表明发生了重排.据¹H NMR测定结果,对反应机理作了初步讨论.14种化合物体外抗癌活性检测表明部分化合物有强的生物活性.     

5-氨基吡唑及5-氨基三唑类成纤维细胞生长因子受体激酶抑制剂的设计合成

成纤维细胞生长因子受体(FGFR)是近年来抗肿瘤靶向治疗药物研发的前沿热点.本研究以Debio1347为先导化合物,依据其与FGFR蛋白的对接结果,设计并合成了11个5-氨基吡唑及5-氨基-1,2,3-三唑类FGFR抑制剂.测定了化合物对受体酪氨酸激酶FGFR2以及FGFR2依赖型胃癌细胞株(SNU16)的体外抑制活性,并对其构效关系进了初步的探讨.其中,1-[5-氨基-1-(2-甲基-1H-苯并[d]咪唑-6-基)-1H-吡唑-4-基]-1-(1H-噻吩并[3,2-b]吡咯-2-基)甲酮(8)与1-[5-氨基-1-(2-甲基-1H-苯并[d]咪唑-6-基)-1H-1,2,3-三唑-4-基]-1-(1H-吲哚-2-基)甲酮(18)在酶水平上表现出了与Debio1347(3.5 nmol·L-1)相近的活性,其IC50值分别为3.3,2.3 nmol·L-1;在细胞水平上,化合物8和18与Debio1347(37.7 nmol·L-1)相比较活性略微降低,其IC50值分别为77.3,155.2 nmol·L-1.     

含酰胺结构的新型2-氨基-4-苯基噻唑类化合物的合成及抗癌和抗菌活性研究（英文）

基于索拉非尼的结构特征设计、合成了一系列含有酰胺结构的新型2-氨基-4-苯基噻唑类化合物.所合成的化合物结构经1H NMR,13C NMR和HRMS表征,并对目标化合物的抗肿瘤和抗菌活性进行了研究.体外抗肿瘤抑制活性结果表明,部分目标化合物显示出较好的活性,特别是N-[3-(2-乙酰氨基噻唑-4-基)苯基]-3-氟苯甲酰胺(4n)对人类结肠癌细胞(HT29)和人肺上皮细胞(A549)细胞株具有显著的抗肿瘤作用,IC50值分别为6.31和7.98μmol·L-1.进一步的研究表明化合物4n可以影响Raf/MEK/ERK信号通路.此外,体外抗菌活性筛选发现,N-[3-(2-乙酰氨基噻唑-4-基)苯基]-3,4-二氯苯甲酰胺(4h)、N-[3-(2-乙酰氨基噻唑-4-基)苯基]-3-氯苯甲酰胺(4i)和N-[3-(2-乙酰氨基噻唑-4-基)苯基]-2,4-二氯苯甲酰胺(4o)对革兰氏阳性菌、革兰氏阴性菌均具有较好抑制作用.     

新型N-[2-((取代苯基)氨基)吡啶-3-基]嘧啶甲酰胺的合成、杀菌活性及分子对接

为寻找新型结构的琥珀酸脱氢酶抑制剂,以高效杀菌剂啶酰菌胺为先导化合物,设计、合成了17种N-[2-((取代苯基)氨基)吡啶-3-基]-4-甲基-2-甲硫基嘧啶-5-甲酰胺(4a～4g)和N-[2-((取代苯基)氨基)吡啶-3-基]-4-甲氧基-2-甲硫基嘧啶-5-甲酰胺(4h～4q),并通过~1H NMR、~(13)C NMR和MALDI-TOF-MS确证了化合物的结构.离体杀菌活性试验表明,在剂量为50μg/mL时, 16种化合物对菌核菌表现出较高的杀菌活性,抑制率在90%以上.一些化合物在此剂量下对灰霉菌显示出中等活性,抑制率为70%～84%.分子对接研究揭示了具有较高活性的化合物,N-[2-((3-氟-4-甲基苯基)氨基)吡啶-3-基]-2-甲硫基-4-甲氧基嘧啶-5-甲酰胺(4p)与琥珀酸脱氢酶(SDH)靶酶氨基酸形成4个氢键和一个阳离子-π相互作用.     

N-取代吡啶基-2-酰基四氢哒嗪-1(2H)-硫代甲酰胺的合成及除草活性

以取代氨基吡啶为原料,经二步反应合成关键中间体——取代吡啶基异硫氰酸酯,再分别与4个制备的取代六氢哒嗪中间体缩合,合成了4个系列共22个新型N-取代吡啶基-2-酰基四氢哒嗪-1(2H)-硫代甲酰胺类化合物8~11.所有目标产物的结构均经过1H NMR,13C NMR和HRMS的确证.初步的除草活性测试表明,部分化合物在375 g·ha-1剂量下,对双子叶杂草苘麻及反枝苋和单子叶杂草马唐具有约100%芽前抑制活性.进一步活性筛选发现,2-[(5-氯吡啶-2-基)硫代氨基甲酰基]四氢哒嗪-1(2H)-甲酸乙酯(9e)在45 g·ha-1剂量下对苘麻的抑制率仍达到95%.     

新型香豆素类衍生物的合成及抗肿瘤活性研究

为了寻找结构新颖、活性较好的抗肿瘤化合物,设计合成了19个未见文献报道的3,4,5-三甲氧基苯基香豆素类化合物,并用核磁共振(NMR)和高分辨质谱(HRMS)等方法对化合物结构进行表征.用四甲基偶氮唑盐(MTT)法评价了该类化合物对人前列腺癌细胞(PC-3)、人食管癌细胞(EC-109)和人胃癌细胞(MGC-803)三种肿瘤细胞的抑制活性.结果显示,N-苄基-2-((4-甲基-2H-色烯-2-酮-7-基)氧基)-N-(3,4,5-三甲氧基苯基)乙酰胺(4a)和N-((5-氯苯并[b]噻吩-3-基)甲基)-2-((4-甲基-2H-色烯-2-酮-7-基)氧基)-N-(3,4,5-三甲氧基苯基)乙酰胺(4n)对三种肿瘤细胞的抑制活性优于阳性对照药5-氟尿嘧啶,其中化合物4n对人前列腺癌细胞(PC-3)的抑制活性最好,其IC_(50)为4.18μmol/L.     

2,3-二氢喹唑啉-4(1H)-酮类化合物的合成研究进展

2,3-二氢喹唑啉-4(1H)-酮是一类重要的含氮稠杂环化合物,具有广泛的药理及生物活性,在药物合成与研发领域有着重要应用价值,因而其合成方法也倍受人们关注.归纳总结了2,3-二氢喹唑啉-4(1H)-酮类化合物的合成研究进展,主要介绍了以邻氨基苯甲酰胺、靛红酸酐、邻硝基苯甲酰胺、邻叠氮基苯甲酰胺、邻溴苯甲酰胺、邻溴苯甲腈、邻氨基苯甲酸、邻氨基苯甲腈、邻氨基N-甲基-N-丙二烯基苯甲酰胺、N-烷基苯胺等为起始原料的2,3-二氢喹唑啉-4(1H)-酮类化合物的合成研究进展概况及其反应机理.最后对该类化合物的合成研究进展进行了总结,并对其发展前景进行了展望.     

Synthesis of new 1,2,3-triazole linked benzimidazole molecules as anti-proliferative agents

One pot click chemistry is used to link triazole and benzimidazole pharmacophore to get N-((1-((1H-benzo[d]imidazol-2-yl)methyl)-1H-1,2,3-triazol-4-yl)methyl)aniline and its derivatives. Flexible linkages in the form of –CH₂–R or –O–R/–N–R were designed during synthesis. All the newly synthesized compounds were characterized by FT-IR and NMR spectroscopy as well as high-resolution mass spectrometry. Selected compounds were screened for in vitro anti-proliferative activity using National Cancer Institute (NCI)-60 human tumor cell line screening program. The most potent structure N-((1-((1H-benzo[d]imidazol-2-yl)methyl)-1H-1,2,3-triazol-4-yl)methyl)-4-chloroaniline 7e showed 40% growth inhibition in renal cancer cell line (UO-31) at 10?µM concentration.     

Synthesis and antitumor activity of novel pyridazinone derivatives containing 1,3,4-thiadiazole moiety

Abstract

A series of novel pyridazinone derivatives containing the 1,3,4-thiadiazole moiety were synthesized and characterized by ¹H NMR, 13C NMR, spectroscopies HRMS and IR. Among them, the structure of compound 5c (2-(Tert-butyl)?4-chloro-5-((5-((2-ethylphenyl)amino)?1,3,4-thiadiazol-2-yl)thio)pyridazin-3(2H)-One) was unambiguously confirmed via single crystal X-ray diffraction analysis. The inhibitory activity of all the target compounds against MGC-803 and Bcap-37 was determined by MTT assay, with doxorubicin (the inhibition rates were 95.5?±?0.4% and 95.7?±?1.0% respectively) as a control. The preliminary results showed that the inhibitory activity of compound 5n (2-(Tert-butyl)?4-chloro-5-((5-((3-fluorophenyl)amino)?1,3,4-thiadiazol-2-yl)thio)pyridazin-3(2H)-One) was superior to the others. The inhibition rates of MGC-803 and Bcap-37 cells were 86.3?±?2.2% and 92.3?±?0.6% at a concentration of 10?μmol/L, respectively. The preliminary structure-activity relationship showed that when the 2-position of the benzene ring was substituted by a methyl group, such as compound 5j (2-(Tert-butyl)?4-chloro-5-((5-((2,3-dimethylphenyl)amino)?1,3,4-thiadiazol-2-yl)thio)pyridazin-3(2H)-One), it exhibited good anticancer activity on MGC-803 cells. Besides, introducing fluorine, chlorine, or trifluoromethyl group onto the benzene ring, such as compound 5?m (2-(Tert-butyl)?4-chloro-5-((5-((4-(trifluoromethoxy)phenyl)amino)?1,3,4-thiadiazol-2-yl)thio)pyridazin-3(2H)-One), displayed good anticancer activity on MGC-803 and Bcap-37 cells.     

Three new diterpenes and the biological activity of different extracts of Jasonia montana

Three new diterpenes, namely jasonin-a (1), jasonin-b (2), and jasonin-c (3) were isolated from the aerial parts of Jasonia montana (Asteraceae). Their structures were elucidated on the basis of spectral data as [(1E)-2-((2S)-1,2,5-trimethylbicyclo[3.2.l]octan-8-yl)vinyl] benzene-3-carboxylic acid (1), [3-((2S, 5S)-1,2, 5-trimethylcycloheptanyl)propyl]benzene-3-carboxylic acid (2), and [(1E)-3-((7R)-1,7-dimethy-4-methylenecycloheptanyl)prop-1-enyl] benzene-3-carboxylic acid (3). In addition, the previously reported 5,7,3'-trihydroxy-3,6,4'-trimethoxy flavone designated as centaureidin (4), was also isolated and characterized from this source. The different extracts of the plant were also screened for hypoglycemic, antidiabetic, and antimicrobial activities, wherein the petroleum ether and ethanolic extracts exhibited hypoglycemic and antidiabetic activity, and the petroleum ether and chloroform extracts showed antimicrobial activity.     

Synthesis and in vitro antibacterial activity of new oxoethylthio-1,3,4-oxadiazole derivatives

In the present investigation, a series of 2(4-pyridyl)-5[(aryl/heteroarylamino)-1-oxoethyl]thio-1,3,4-oxadiazole were synthesized using isonicotinohydrazide and substituted aryl/heteroaryl amines using pyridine as solvent. Newly synthesized compounds were tested for their in vitro anti-tubercular activity against Mycobacterium tuberculosis H37Rv using the BACTEC 460 radiometric system. Among the synthesized compounds, compounds 2(4-pyridyl)-5((2-nitrophenylamino)-1-oxoethyl)thio-1,3,4-oxadiazole (5e), 2(4-pyridyl)-5((4-nitrophenylamino)-1-oxoethyl)thio-1,3,4-oxadiazole (5g) and 2(4-pyridyl)-5((2-pyrrolylamino)-1-oxoethyl)thio-1,3,4-oxadiazole (5k) produced highest efficacy and exhibited >90% inhibition at a concentration of 0.0077, 0.0052 and 0.0089 μM, respectively. All the new compounds were pharmacologically evaluated for their in vitro Antimicrobial activity.     

Synthesis,characterization and biological properties of novel ON donor bidentate Schiff bases and their copper(II) complexes

Four novel ON donor Schiff bases (E)-3-((4-phenoxyphenylimino)methyl)benzene-1,2-diol (HL₁),(E)-3-((4-(4-biphenyloxy)phenyliminomethyl)benzene-1,2-diol (HL₂), (E)-3-((4-naphthoxyphenylimino)methyl)benzene-1,2-diol (HL₃), (E)-3-((4-(2-naphthoxy)phenylimino)methyl)benzene-1,2-diol (HL₄) and their copper(II) complexes bis((E)-3-((4-phenoxyphenylimino)methyl)benzene-1,2-diol) copper(II) (Cu(L₁)₂) bis((E)-3-((4-(4-biphenyloxy)phenylimino)methyl)benzene-1,2-diol) copper(II) (Cu(L₂)₂), bis((E)-3-((4-naphthoxyphenylimino)methyl)benzene-1,2-diol) copper(II) (Cu(L₃)₂), bis((E)-3-((4-(2-naphthoxy)phenylimino)methyl)benzene-1,2-diol) copper(II) (Cu(L₄)₂) have been synthesized and characterized by spectroscopic (FTIR, NMR, UV–visible) and elemental analysis. The crystal structures of HL₁, HL₂, HL_3, and HL₄ have been determined, which reveal intramolecular N-H?O (HL₁, HL₂, HL_3, and HL₄) hydrogen bonds in the solid state. Keto-amine and enol-imine tautomerism is exhibited by the Schiff bases in solid and solution states. The Schiff bases and their copper(II) complexes have been screened for their biological activities. In antimicrobial assays (antibacterial and antifungal), HL₄ showed promising results against all strains through dual inhibition property while the rest of the compounds showed activity against selective strains. On the other hand, in cytotoxic, DPPH, and inhibition of hydroxyl (OH) free radical-induced DNA damage assays, the results were found significantly correlated with each other, i.e. the ligands HL₁ and HL₂ showed moderate activity while their complexes Cu(L₁)₂ and Cu(L₂)₂ exhibited prominent increase in activity. As the results of these assays are supporting each other, it represents the strong positive correlation and antioxidant nature of investigated compounds.     

Opioid ligands with mixed properties from substituted enantiomeric N-phenethyl-5-phenylmorphans. Synthesis of a micro-agonist delta-antagonist and delta-inverse agonists

Enantiomeric N-phenethyl-m-hydroxyphenylmorphans with various substituents in the ortho, meta or para positions of the aromatic ring in the phenethylamine side-chain (chloro, hydroxy, methoxy, nitro, methyl), as well as a pyridylethyl and a indolylethyl moiety on the nitrogen atom, were synthesized and their binding affinity to the mu-, delta-, and kappa-opioid receptors was examined. The higher affinity ligands were further examined in the [(35)S]GTPgammaS assay to study their function and efficacy. 3-((1R,5S)-(-)-2-(4-Nitrophenethyl)-2-aza-bicyclo[3.3.1]nonan-5-yl)phenol ((-)-) was found to be a mu-agonist and delta-antagonist in that functional assay and was about 50 fold more potent than morphine in vivo. 3-((1R,5S)-(-)-2-(4-Chlorophenethyl)-2-aza-bicyclo[3.3.1]nonan-5-yl)phenol ((-)-) and several other ligands displayed inverse agonist activity at the delta-opioid receptor. The absolute configuration of all of the reported compounds was established by chemical conversion of (-)- to 1R,5S-(-)-.HBr.     

Synthesis,characterization, and antioxidant activity of heterocyclic Schiff bases

Schiff base derivatives have gained great importance due to revealing a great number of biological properties. Schiff bases were synthesized by treatment of 4-amino-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one ( 1 ) with various aldehydes in methanol at reflux. In addition, diamine was reacted with an aldehyde to yield the corresponding Schiff bases. The structures of synthesized Schiff bases were elucidated by spectroscopic methods such as microanalysis, ¹H-NMR, ¹³C-NMR, and FTIR. Antioxidant activities of synthesized Schiff bases were carried out using different antioxidant assays such as 1,1-diphenyl-2-picryl-hydrazyl free radical (DPPH^•) scavenging, 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical scavenging, and reducing power activity. (E)-4-((1H-indol-3-yl)methyleneamino)-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one ( 3 ), (E)-1,5-dimethyl-4-((2-methyl-1H-indol-3-yl)methyleneamino)-2-phenyl-1H-pyrazol-3(2H)-one ( 5 ), (E)-1,5-dimethyl-2-phenyl-4-(thiophen-2-ylmethyleneamino)-1H-pyrazol-3(2H)-one ( 7 ), (E)-1,5-dimethyl-2-phenyl-4-(quinolin-2-ylmethyleneamino)-1H-pyrazol-3(2H)-one ( 9 ), (1S,2S,N1,N2)-N1,N2-bis((1H-indol-3-yl)methylene)cyclohexane-1,2-diamine ( 11 ), and (1S,2S,N1,N2)-N1,N2-bis((2-methyl-1H-indol-3-yl)methylene)cyclohexane-1,2-diamine ( 12 ) were synthesized in high yields. Compound 5 displayed a good ABTS^•+ activity. Compound 3 revealed the outstanding activity in all assays. Compound 7 has the best-reducing power ability in comparison to other synthesized compounds. Although compounds 5, 11, 12 are new, compounds 3, 7, 9 are known. Due to revealing a good antioxidant activity, the synthesized compounds ( 3, 5, 7 ) have the potential to be used as synthetic antioxidant agents.     

1,3,4-噁二唑和1,3,4-噻二唑衍生物的设计、合成和生物活性研究

为了寻求新型抗肿瘤药物,设计并合成了一系列新型1,3,4-噁二唑和1,3,4-噻二唑衍生物,对这些化合物在人类四种癌细胞:B-16(皮肤黑色素瘤细胞)、PC-3(人前列腺癌细胞)、U87(人原发性胶质母细胞瘤细胞)和A549(人非小细胞肺癌细胞)进行抗肿瘤活性评价.结果显示部分化合物具有较好的抗肿瘤活性,尤其是5-{6-[4-(2-羟基乙基)哌嗪-1-基]-2-甲基嘧啶-4-基氨基}-[1,3,4-噻二唑-2-羧酸(2-甲氧基苯基)酰胺(8b)和5-{6-[4-(2-羟基乙基)哌嗪-1-基]-2-甲基嘧啶-4-基氨基}-[1,3,4-噻二唑-2-羧酸(4-甲氧基苯基)酰胺(8c),对四种癌细胞都显示出较高的抗肿瘤活性,其抑制活性均优于阳性对照达沙替尼.随后对这类化合物抑制肿瘤的可能靶点开展了进一步研究.     

Synthesis and antimicrobial properties of new 2-((4-ethylphenoxy)methyl)benzoylthioureas

New acylthiourea derivatives, 2-((4-ethylphenoxy)methyl)-N-(phenylcarbamothioyl)benzamides, were tested by qualitative and quantitative methods on various bacterial and fungal strains and proved to be active at low concentrations against Gram-positive and Gram-negative bacteria as well as fungi. These compounds were prepared by the reaction of 2-((4-ethylphenoxy)methyl)benzoyl isothiocyanate with various primary aromatic amines, and were characterised by melting point and solubility. The structures were identified by elemental analysis, ¹H and ¹³C NMR, and IR spectral data. The level of antimicrobial activity of the new 2-((4-ethylphenoxy)methyl)benzoylthiourea derivatives was dependent on the type, number and position of the substituent on the phenyl group attached to thiourea nitrogen. The iodine and nitro substituents favoured the antimicrobial activity against the Gram-negative bacterial strains, while the highest inhibitory effect against Gram-positive and fungal strains was exhibited by compounds with electron-donating substituents such as the methyl and ethyl groups.     

Synthesis of novel azabicyclo derivatives containing a thiazole moiety and their biological activity against pine-wood nematodes

Abstract

To explore a new skeleton with nematicidal activity, a series of novel azabicyclo derivatives containing a thiazole moiety were designed, synthesized and evaluated for their nematicidal activities. The bioassay results against pine-wood nematodes (Bursaphelenchus xylophilus) showed that most of the title compounds displayed nematicidal activity at a concentration of 40?mg/L. Especially, the title compounds2-((8-methyl-8-azabicyclo[3.2.1]octan-3-yl)oxy)-4-(4-chlorophenyl)thiazole (7e), 2-((8-methyl-8-azabicyclo[3.2.1]octan-3-yl)thio)-4-phenylthiazole (10a) and 2-((8-methyl-8-azabicyclo [3.2.1]octan-3-yl)thio)-4-(4-chlorophenyl)thiazole (10e) exhibited more than 90% mortality against Bursaphelenchus xylophilus.